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+{"text": "Dear Editor, The global incidence and burden of Neonatal Abstinence Syndrome (NAS) are constantly increasing  due to https://www.hcup-us.ahrq.gov)  is the largest hospital-based pediatric database in the United States. It is compiled by the Healthcare Cost and Utilization Project (HCUP) and sponsored by the Agency for Healthcare Research and Quality and their partners . The 20CUP, 2019), we excWe performed Chi-square tests and logistic regressions on SPSS 20 to calculate the risks of ventricular septal defects (VSD), tetralogy of Fallot (TOF), atrial septal defect (Ostium Secundum defect) (ASD), and coarctation of aorta in neonates presenting with NAS. A total of 22145 (weighted) neonatal abstinence syndrome patients were considered suitable for our study. 305  cases of VSD, 26 cases  of tetralogy of Fallot, 1248  cases of ASD, and 47  cases of coarctation of aorta were identified Table 1.The pathophysiology behind the teratogenic effects of opioid on cardiovascular development is still not fully understood. Opioid use during fetal life has shown to impact the migration and development of various systems such as neurons in rat studies and DNA synthesis in fetal cardiac tissues (Walhovd et al., 2009; BroussaThe authors declare no conflict of interest."}
+{"text": "One quarter of the residents in the City of Toronto is comprised of older adults, and this number is expected to continue to grow dramatically over the next few decades. The development of evidence-based interventions to meet the health and social care needs of Toronto\u2019s aging population can be hampered by failing to account for broader implementation considerations that can adversely affect successful uptake. The present initiative provides a case-example of a research and public policy sector partnership that used an implementation approach to co-design an older adult social housing model for low-income older adult groups. Implementation science is the study of the uptake of research evidence into practice. Our team used the Consolidated Framework for Implementation Research (CFIR) to support the planning, implementation and evaluation process of a new social housing model for older adults by: 1) identifying all relevant stakeholders; 2) generating evidence via qualitative interviews/focus groups, a scoping review, secondary data analysis, and an environmental scan; 3) facilitating large scale stakeholder consultation events with older adults, front-line practitioners and other community agencies; 4) supporting the development of an evaluation framework; and 5) providing opportunities for knowledge exchange and transfer across each phase of the initiative. An implementation science approach has augmented the ability of the City of Toronto to optimize the co-creation of housing strategies aimed at improving the overall wellness of vulnerable older adults living in social housing. Further, a number of valuable lessons were learned on how to foster successful research and public policy relationships."}
+{"text": "Integration of health and social services is touted as a key method to address social needs and improve population health. We will share the latest evidence on how Area Agency on Aging (AAA) partnerships with health care entities and other organizations improve health outcomes for older adults, while reducing health care costs. AAAs are community leaders in cross-sectoral partnerships that effectively address social determinants of health for older adults, who account for a substantial share of overall health care spending. Results of a longitudinal study (2008 \u2013 2016) which links data from four waves of the National Surveys of AAAs to data on county-level health outcomes show that AAA\u2013health care partnerships and programs reduced health care utilization and costs. AAA partnerships with hospitals reduced Medicare spending by $136 per beneficiary. AAA involvement in evidence-based health promotion programs decreased potentially avoidable nursing home use by nearly one percentage point (representing a change of 6.5%). Finally, we will describe the prevalence and nature of contracting relationships between community-based organizations and health care entities, based on data from the 2020 CBOs and Health Care Contracting Request for Information, the third national RFI of AAAs, Centers for Independent Living, and other aging and disability community-based organizations."}
+{"text": "A alleleexhibited higher levels of ChAT activity. Considering this is the first study toreport the influence of genetic variability of CHAT locus over ChAT activity inAD patients plasma, it opens a new set of important questions on peripheralcholinergic signaling in AD.The choline acetyltransferase (ChAT) and vesicular acetylcholine transporter(VAChT) are fundamental to neurophysiological functions of the centralcholinergic system. We confirmed and quantified the presence of extracellularChAT protein in human plasma and also characterized ChAT and VAChTpolymorphisms, protein and activity levels in plasma of Alzheimer's diseasepatients  and in cognitively healthy controls . Wefound no significant differences in plasma levels of ChAT activity and proteinbetween AD and EC groups. Although no differences were observed in plasma ChATactivity and protein concentration among ChEI-treated and untreated AD patients,ChAT activity and protein levels variance in plasma were higher among therivastigmine-treated group .Moreover, AD patients homozygous for SNP rs1880676  The central cholinergic system plays a fundamental role in memory and learningmechanisms, and cholinergic deficit in Alzheimer\u2019s disease (AD) generates cognitiveimpairment  refer toCholinergic dysfunction is characterized by severe reduction in the cholinergic enzymecholine acetyltransferase (ChAT), which is one of the key features of the brains ofpatients with AD , predominantly euro descendants). Thesamples were from the Cognitive Dysfunction Ambulatory from Clinical Hospital of theFederal University of Parana (HC-UFPR) and Disorders Clinic Memory and Behavior (ADEMEC)of Curitiba Neurology Institute (INC).The diagnostic criteria for patients with AD followed the NINCDS-ADRDA standards, were alcoholics, had previous history of stroke or lossof memory lapse, unable to perform daily life activities, had persistent complaintsabout memory and depressive symptoms.In the current study, the global cognition was assessed by the Mini-Mental StateExamination tests, MMSE . The patrs3810950, rs733722, and rs1880676 forCHAT) and rs2269338 for theSLC18A3 gene (VAChT). Then we investigated whether these geneticvariants influence ChAT profiles in the plasma samples of this Brazilian cohort, inrelation to education, cognitive performance and the use of cholinesterase inhibitors(ChEIs).We also determined the genetic polymorphism in the cholinergic locus (theGenotyping was performed by TaqMan SNP Genotyping Assays (Applied Biosystems) in a ViiA 7Real-Time PCR System (Thermofisher Scientific). For this, the total genomic DNA wasextracted from peripheral blood by a salting out method  (with moTo determine the levels of ChAT in plasma we performed an integrated enzymeactivity-sandwich ELISA-(Enzyme Linked Immunosorbent Assay) set up as describedpreviously .Nortest package R program was used to test for normality (Shapiro-Wilk test withLilliefors correction) of the variables activity and protein concentration, MMSE andyears of study. After analyzing the distributions, comparisons were made by means of theThe demographic data of the AD patients and the EC are presented in st and 3rd quartiles values of theprotein concentration and activity of ChAT in the plasma samples of AD patients and ECis presented in The median together with 1Unlike the ChAT levels in the brain of patients with AD, the plasma pattern of ChAT isnot known, so this is the first report on ChAT levels and how they differed in the brain and ChAT protein concentrationin plasma (p = 0.79) between patients with and without treatment with CHEIs. However,separating by type of treatment ,althoug,About 70% of the AD patients, included in the current study, were on treatment with theChEIs, which are the main therapeutic option available today. Currently, there is noinformation on how treatment with ChEIs may affect the levels of soluble ChAT in plasma,cerebrospinal fluid or the brain. Therefore, the lack of difference between the plasmaChAT levels among the AD and the controls could be due to an increase in ChAT levels inplasma, possibly induced by treatment with ChEIs. This is because ChEIs are expected toalter ACh homeostasis by inhibiting degradation of ACh by cholinesterases in circulation,. Thus thrs1880676 SNP altersdifferentially the phenotypic profiles of ChAT activity and protein expression in theplasma of the AD patients. This is the first study to report the influence of geneticvariant of the cholinergic locus with the profile of soluble ChAT in plasma. Overall,the findings warrant further studies since identification and understanding of factorsthat may influence the phenotypic profile of ChAT in plasma could be important for theunderstanding of the role of this soluble enzyme in the normal and pathological functionof peripheral cholinergic signaling.In conclusion, we reaffirm the presence of ChAT in human plasma by measuring both proteinand activity of this enzyme in a reasonably large number of samples from patients withAD and the control group. Albeit no difference between plasma levels of ChAT among thegroups were observed, we found that the"}
+{"text": "Grain legumes are nutritionally important components of smallholder farming systems in sub-Saharan Africa and Asia. Unfortunately, limited access to quality seed of improved varieties at affordable prices due to inadequate seed systems has reduced their contribution to improving nutrition and reducing poverty in these regions. This paper analyses four seed systems case studies: chickpea in Ethiopia and Myanmar; cowpea in Nigeria; and tropical grain legumes in Nigeria, Tanzania and Uganda highlighting outcomes, lessons learned, and the enabling factors which supported the successful innovations. All four case studies highlighted at least some of the following outcomes: increased adoption of improved varieties and area planted; increased productivity and income to farmers; improved market access and growth; and significant national economic benefits. Important lessons were learned including the value of small seed packets to reach many farmers; the value of innovative partnerships; capacity building of value chain actors; and continuity and coherence of funding through Tropical Legumes projects II and III and the recently funded Accelerated Varietal Improvement and Seed Delivery of Legumes and Cereals in Africa (AVISA) project. Successful adoption of innovations depends not just on the right technologies but also on the enabling environment. The case studies clearly showed that market demand was correctly identified, establishment of successful partners and institutional linkages overcame constraints in production and delivery of improved seed to smallholders, and fostered conducive policies supported national seed systems. All were integral to seed system viability and sustainability. It is hoped that these examples will provide potential models for future grain legume seed systems efforts. In addition, the analysis identified a number of areas that require further research. Grain legumes are nutritionally important components of smallholder farming systems in much of sub-Saharan Africa and Asia. Their higher protein and micro-nutrient contents enhance diets and their ability to fix nitrogen improves soil health . Good quVarious factors contribute to lack of interest by the formal sector in grain legume seed production in less-developed countries. These include lower seed multiplication rate requiring extra space, labour and effort to move from breeder seed to certified/Quality Declared Seed (QDS) at commercial scale; relatively large seed size \u2013 for every hectare up to 100 kg of seed is needed for some legumes, which has cost implications for the storage and transportation of seed; and seeds of some legumes deteriorate rapidly after harvest, especially if shelled . There aTwenty years ago, a comprehensive study of national seed systems in Eastern and Southern Africa highlighted a number of strategic interventions necessary for the development of grain legume seed systems . These iBox 1.Twelve principles for mainstreaming functional legume seed systems in Eastern Africa.Principle 1: Mainstreaming legume seed systems requires a clear theory of changePrinciple 2: Mainstreaming legume seed systems is supported by a robust policy environment and regional integrationPrinciple 3: Mainstreaming legume seed systems is supported by a strong institutional frameworkPrinciple 4: Mainstreaming legume seed systems begins with tackling the early generation seed (EGS) supply challengePrinciple 5: Mainstreaming legume seed systems requires an integrated approach in tackling the commercial seed class challengePrinciple 6: Mainstreaming legume seed systems requires institutional capacity buildingPrinciple 7: Mainstreaming legume seed systems is linked to the promotion of utilization for improving food and nutrition securityPrinciple 8: Mainstreaming legume seed systems involves market linkages and income securityPrinciple 9: Mainstreaming legume seed systems is linked to the role in agricultural and dietary diversification and resiliencePrinciple 10: Mainstreaming legume seed systems is linked to women and youth empowermentPrinciple 11: Mainstreaming legume seed systems requires multi-stakeholder involvementPrinciple 12: Mainstreaming legume seed systems requires well-defined seed and adoption roadmapsFrom: Several good examples of the promotion of improved grain legume varieties and the establishment of viable seed systems in sub-Saharan Africa and Asia have been achieved by the CGIAR Research Program \u2013 Grain Legumes and Dryland Cereals , 2019, iChickpea breeding efforts in Ethiopia started in the early-1970s, focusing mainly on yield improvement. Over the years, many challenges were identified necessitating concerted efforts in improvement for biotic  and abiotic  stress resistance/tolerance; farmer requirements  and market preferences ; integrated crop management packages that include inputs such as efficient and effective rhizobia inoculants as well as efficient seed and technology delivery systems. Since 2007, the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) through the Tropical Legumes projects  worked closely with partners in Ethiopia including the Ethiopian Institute for Agricultural Research (EIAR), Regional Agricultural Research Institutes, Higher Institutions of Learning, Regional and District Bureaus of Agriculture, Seed Enterprises, the International Centre for Agricultural Research in Dry Areas (ICARDA), Integrated Seed Sector Development (ISSD), the Feed the Future Chickpea Innovation Laboratory and the Alliance for a Green Revolution in Africa (AGRA) among others to address some of these challenges, contributing to the release of 10 improved varieties targeting various agro-ecologies of Ethiopia as well as the promotion of on-the-shelf varieties.During 7 years, adoption of improved chickpea varieties rose from 31\u201380%; the share of chickpea growers rose from 65\u201390%; the area sown to chickpea per farm rose from 0.17\u20130.4 ha; and household welfare was significantly increased . AdoptioThe partnership between the EIAR, the extension services, ICRISAT and other value chain actors including farmers, seed producers, quality control actors and export grain aggregators laid the foundation for building the multi-stakeholder EthioPEA Alliance which was crucial in strengthening the chickpea value chain .https://ethiopia.un.org/sites/default/files/2019-08/GTPII%20%20English%20Translation%20%20Final%20%20June%2021%202016.pdf).A seed production and distribution system was established through seed grower associations and more than 70,000 extension agents were involved in promoting, supporting and sustaining the chickpea seed system. Attracted by early successes, chickpea seed grower associations formed seed companies with additional support from AGRA and ISSD. Local markets for excess seed were accessible and demand from both local and export markets drove increased production. The Government of Ethiopia included chickpea in the 5-year agricultural growth strategy (Growth and Transformation Plan II 2015/16\u20132019/20) and in the Ethiopian Commodity Exchange (ECX) with direct investment from government budgets in crop improvement, seed systems and market development In Myanmar, chickpea is grown in the post-rainy season on residual moisture in Central Dry Zone (CDZ). Sagaing, Mandlay and Magway are the major chickpea growing divisions in the country. The Department of Agriculture Research (DAR) conducts research while the Department of Agriculture (DOA) is responsible for research and development activities on chickpea in collaboration with ICRISAT. During 1975 to 2017, more than 5200 ICRISAT breeding lines and gene bank accessions were shared with the DAR (unpublished data from ICRISAT). Several advanced breeding lines supplied by ICRISAT were found suitable for cultivation in the CDZ and led to release of eight improved Yezin cultivars.The adoption of improved Yezin varieties was rapid during 2004\u201305, covering an area of 82% of the country . Recent Myanmar has witnessed a chickpea revolution in the last two decades. From 1998 to 2018, the chickpea area increased from 101,172 ha to 368,390 ha, and the yield doubled from 668 Kg/ha to 1384 Kg/ha resulting in a total production of 0.54 m tons in 2018 . During The partnership between ICRISAT and the DAR and the DoA lead to the establishment and development of 1343 Village Seed Banks in 495 villages of Central Dry Zone between 2015 and 2018 supported by the ACIAR funded MyPulses project . The extOne of the main drivers of adoption of improved chickpea varieties and the subsequent seed systems development was a strong export market. Of note, the Government of Myanmar has a flexible approach to supporting diverse methods of seed production which facilitates production and distribution. In addition, it is also supportive of export crops such as chickpea.Striga gesnerioides and Alectra vogelii and multiple disease and insect resistance  worked closely with partners in Nigeria to build on progress from previous work. Activities were initiated on the identification of additional sources of resistance to drought and heat as well as previously mentioned biotic stresses by exploiting the germplasm collections  began in early 1970s, focusing mainly on grain yield and pyramiding genes for individual disease and insect resistance. In the early 1980s, focus shifted to cowpea improvement for multiple disease and pest insect resistance, with acceptable seed quality traits . In the 1990s to early 2000s, the focus shifted again to the development of varieties with different maturity periods, growth habit, and suitability for intensive cropping systems as well as to sistance . Of notelections .Through these efforts, improved, high yielding cowpea varieties with different maturity periods, multiple resistances to biotic stresses and drought tolerant were promoted resulting in the release of over 20 improved varieties in Nigeria since the early 1980s. Access to seed and information on improved varieties was fostered. Forty-two percent of the farmers have adopted improved varieties resulting into 26% increase in yields, 14% increase in production costs, 61% increase in net returns per hectare and 5% reduction in poverty incidence, equivalent to 930,000 people moving out of poverty , 2020.The partnerships between IITA, the Institute for Agricultural Research and the University of Agriculture, Makurdi were important for the release of improved cowpea varieties as well as for facilitating smallholder farmers\u2019 access to high quality seed to enhance uptake of the improved varieties. To accelerate cowpea seed production and delivery to smallholder farmers, diverse strategies were used. One of the interventions was the establishment of multi-stakeholder platforms consisting of both public and private partners. These platforms provided linkages among cowpea value chain actors, provided awareness for training and skill enhancement, and enhanced efficiency and effectiveness in technology delivery, development and use. In addition, the platforms served as a critical channel through which farmers conveyed their preferences for traits and other varietal and seed attributes. A wide range of partners were engaged in seed production and dissemination of cowpea across the country. An integrated system was adopted where various actors were engaged in producing different seed classes. .Investment in small seed packets for distribution to farmers raised awareness of as well as promoted improved varieties. Farmers were willing to buy seed of profitable new varieties that met market demands. The Government of Nigeria reclassified cowpea as a priority crop resulting in a nation-wide increase in consumption of cowpea further fostering demand.Scaling-up outputs and outcomes from TL II through TL III achieved more impact and built sustainable seed systems for cowpea in Nigeria. Strengthened seed systems were conducive to increasing the involvement of private seed companies in cowpea which increased from 50 in 2017 to 314 in 2018. Improved grain quality was well-received by both local and export markets and good country-wide market access developed. Nigerian seed laws were revised to allow companies to produce foundation seed for certified seed production. The National Seed Regulation body (NASC) supported seed certification and quality control while the Economic Community of West African States (ECOWAS) supported the movement and sale of cowpea seed between countries.To boost legume seed production and delivery to smallholder farmers, a multi-pronged strategy was used consisting of building partnerships between farmers, seed companies, governmental organizations and extension workers; training seed producers and marketers in technology and best practices through participatory varietal selection and on-farm demonstrations and mobile app-based advisories . The useThe Tropical Legumes (TL) Projects funded by the Bill and Melinda Gates Foundation together with precursor and complementary projects facilitated the development of 304 nutrient dense, climate-smart, farmer- and market-preferred varieties and the production of 397,050 t of certified and quality declared seeds (QDS) . TL III helped to scale out previous projects and seed was planted on about 4.4 million ha by more than 22 million smallholder farmers in the 15 target countries and beyond, producing about 4.9 million t of grain worth US$2.6 billion. In Tanzania, the groundnut area increased from 400\u20131.6 million ha and yields increased from 0.6\u20131.2 t/ha; in Nigeria, yields of cowpea increased from <0.5 to 1.1 t/ha by 2018ICRISAT, IITA and the International Centre for Tropical Agriculture (CIAT) formed partnerships with more than 100 public sector institutions during the course of the projects. The value of innovative partnerships linked to seed producer groups was demonstrated. Improved quality control for production of QDS was conducive to attracting private seed companies to produce grain legume seed. The importance of market preferences to fostering demand was also clarified.Quality seed of improved varieties fed into the multi-pronged strategy building partnerships between farmers, seed companies, governmental organizations and extension workers. Capacity building of seed producers and marketers in technology and best practices through participatory varietal selection as well as on-farm demonstrations and mobile app-based advisories was integral to successful outcomes. Market incentives were created through 55 multi-stakeholder platforms. In the case of Tanzania, the government increased support for legume crops of less interest to the private sector and established the Agricultural Seed Agency (ASA) to support multiplication of early generation seed for foundation seed. The Tanzania Official Seed Certification Institute (TOSCI) support for the production of QDS was a key development, lowering the cost of seed without compromising quality  which funded Tropical Legumes projects I, II and III and has recently funded the AVISA project. However there is still a need for improved integration of donor-funded seed systems projects to enable the development of coherent national seed strategies  while keAlthough significant adoption of improved varieties of legume crops in Africa has been reported due to efforts in seed systems projects, the overall use remains low. Although interest by the private sector is growing, further expansion is compounded by the botanical challenges of the crops besides limited product information, including the technical and market performance of new varieties, a dearth of knowledge of the size and scale of the business opportunity, limited access to early generation seed (EGS) and obscurity about the licensing and regulatory environment. The BMGF\u2019s investment in AVISA consolidates the gains made and lessons learnt from the Tropical Legumes Projects for better scale and efficiency. AVISA will address the private sector constraints by enabling the establishment of a robust system that (i) increases the quantity and quality of performance data substantiating varietal superiority; (ii) boosts the availability of EGS seed by strengthening the technical and business acumen of the public EGS systems through technical, management and business capacity building; (iii) establishes a clear path and handover process from the research system to the private sector; and (iv) enables private sector multipliers to seize opportunities to capitalize on the commercialization of these crops. The project is committed to linking with/aligning around new (some pending) institutional seed systems initiatives of BMGF, USAID and AGRA in these and other AVISA target geographies to achieve donor coherence and potentially greater outcomes than would be possible through independent efforts.AVISA is also committed to gender equity as a guiding principle, considering the critical role women play in choosing legume varieties and seed sources. Women seed entrepreneurs and women-led seed companies will garner special attention for capacity development in seed business and technical areas. To ensure women farmers have equal access to improved seed, gender-responsive demand will be generated through linkages and innovative public-private partnerships and platforms with actors along the commodity value chains and through demonstrations that directly expose women farmers and other value chain actors to the material.In summary, all four case studies created an enabling environment for successful innovations in grain legume seed systems. These case studies clearly show that identifying market demand correctly, working with innovative institutions/models to overcome constraints in production and delivery of improved seed and the existence of conducive policies to support seed systems are integral to their success. This is reinforced by a number of the principles identified by The analysis of these four case studies also identified a number of areas that require further research. Firstly, there is a need to better understand farmer demand for quality seed . MethodoIn spite of the successes shown by these four case studies in the adoption and spread of improved varieties and establishment of viable seed systems resulting in notable increases in productivity, such results can be patchy and restricted to intervention areas where projects are implemented. There is a need for further efforts to exploit available opportunities for achieving larger impacts by enhancing productivity and production of grain legumes . There iIt is somewhat ironic that although the Sustainable Development Goal 2 is to \u2018End hunger, achieve food security and improved nutrition and promote sustainable agriculture\u2019, insufficient attention has been paid to the important role of nutritious grain legumes in this objective. Governments, funders and the international community need to put much more effort into mainstreaming grain legumes in production systems to realize this critical goal."}
+{"text": "Purpose: Now 10 years after the Great Recession of 2018, we examined the impact and long-term health outcomes impacting adults (\u2265 50 years). Methods: Data from the Health and Retirement Survey , was used to examine how changes in financial hardship pre-post the Great Recession of 2008 impacted the likelihood of developing new chronic conditions in 2016. Results: Preliminary results suggest that reduced medication use during the recession was significantly correlated with a higher likelihood of developing arthritis, lung disease, psychological conditions, depression, and greater deterioration of mental and physical health relative to an absence of reduced medication use in 2006 and 2010 (1). Conclusion: These findings underscore the adverse influences of increased financial hardships that impact medication use during recessionary periods on long term health and wellbeing of older adults. They also provide evidence of deleterious effects on health of difficulty paying bills throughout the study period."}
+{"text": "Against the backdrop of mounting calls for the global scaling-up of mental health services \u2013 including quality care and prevention services \u2013 there is very little guidance internationally on strategies for scaling-up such services. Drawing on lessons from scale-up attempts in six low- and middle-income countries (LMICs), and using exemplars from the front-lines in South Africa; we illustrate how health reforms towards people-centred chronic disease management provide enabling policy window opportunities for embedding mental health scale-up strategies into these reforms. Rather than going down the oft-trodden road of vertical funding for scale-up of mental health services, we suggest using the policy window that stresses global policy shifts towards strengthening of comprehensive integrated primary health care systems that are responsive to multimorbid chronic conditions. This is indeed a substantial opportunity to firmly locate mental health within these horizontal health systems strengthening funding agendas. While this approach will promote systems more enabling of scaling up of mental health services, implications for donor funders and researchers alike is the need for increased time commitments, resources and investment in local control. Key innovations/implementation strategies recommended to promote rapid scale-up include task sharing; care that is balanced across levels and different sectoral delivery platforms; the use of digital technologies; and interventions to enhance demand for care  research consortium  provides a useful framework to this end , was insufficient to sustain integration, with the need for system strengthening interventions to enable integration emphasised . Implementing and scaling up of this package is being achieved through a sustained partnership between MhINT researchers and provincial and district Department of Health managers who are intimately involved in implementation strategy formulation along with providing essential bureaucratic facilitation for integrated care to become part of public sector governance and administration.Recent calls for health reforms in LMICs towards horizontal chronic people-centred health systems  supporting the integration of mental health strategic plans into the broader provincial annual performance plans in order to ensure allocation of finances to support the project of integration and facilitate person-centric approach to health service planning; (ii) reviewing and revising mental health data elements available in the clinical health information systems to facilitate improved monitoring of mental health services at primary health care; (iii) supporting the development of standardised operating procedures for mental health screening at PHC level; and (iv) putting in place a national and provincial steering committee to routinely review bottlenecks and innovations in implementation at the meso- and micro-levels see .Fig. 1.et al., At the meso-level, the MhINT programme has had to be responsive to the unique contextual factors that support or hinder the integration of mental health care using CQI strategies and tools to develop innovative solutions for the latter. To overcome the challenge of the integration of mental health into PHC being seen as additional work to existing responsibilities, MhINT aligned its activities with the Integrated Clinical Services Management (ICSM) model of managed care for chronic conditions. This has been done through strengthening the existing PHC process of clinical management and (i) locating mental health screening in the same space where all screening for vital signs are conducted. MhINT further strengthened the screening process by introducing a validated brief mental health (BMH) screening tool and collaboratively developing processes to facilitate referral of patients in need of emergency mental health care or further assessment at PHC; (ii) enhancing clinicians' training on existing clinical decision-making tools for managing chronic diseases [integrated chronic care guidelines called Adult Primary Care (APC)]  inclusion of the MhINT psycho-social intervention training in a pre-service curriculum of auxiliary social workers in KZN who will be based at PHC facilities, so that there is a larger dedicated pool of healthcare workers that can provide psychosocial interventions for CMDs at PHC level; (ii) clinical communication skills have been integrated into the diagnosis and management of mental health problems in the APC guide from outset; (iii) mental health psychoeducation and detection of mental health problems at the community level has been included into the community health worker curriculum from the outset; (iv) the province has adopted the validated BMH screening tool to be used by enrolled nurses in the vital signs station across the province.Importantly, the structures and relationships fostered by MhINT have also been leveraged to strengthen the health system for tuberculosis (TB) patients who are particularly vulnerable to CMDs. Towards this end, a work package of the National Institute for Health Research (NIHR) Global Health Research Unit on Health System Strengthening in Sub-Saharan Africa (ASSET) NIHR,  for streThese lessons from the ground have implications for the way in which we, as the global mental health community, approach scaling up of increased access to mental health care in scarce-resource contexts.et al., et al., et al., In the first instance, they sound a cautionary note to the call for global mental health financing similar to that invested in eradicating HIV and other epidemics (Kleinman et al., Second, the inclusion of dialogical action principles such as the adoption of co-learning and co-design between researchers and communities are important to foster acceptability and sustainability. This requires a recasting of partnerships and collaborations between research institutes, organisations and funding bodies situated in high-income geographies, and researchers, policy-makers and implementers at a local level in LMICs, from expert-driven to emphasising co-learning, support and respect Horner, ; and balet al., Lancet editorial calling for the global mental health community to \u2018transform global health into a movement with mental health\u2019 (Horton, Lastly, global policy shifts, as well as emerging policy shifts in LMICs towards strengthening of comprehensive integrated primary health care systems that are responsive to multimorbid chronic conditions, provide a policy window for the global mental health community to ensure that mental health is firmly integrated within these multimorbidity policy shifts and accompanying implementation strategies from the outset of such reforms. This should assist to address the low priority afforded to mental health in LMICs historically, alleviate the problem of it being seen as an add-on to existing services, improve health outcomes, reduce costs as well as potentially reduce institutional stigma (Thornicroft  Horton, ."}
+{"text": "Neighborhood environments shape the availability of resources for social engagement and social interaction, which are associated with better health outcomes. However, these contextual factors are also considered sources of potential social distress and tension, increasing the risk of subsequent health deficits, including cognitive decline. Our understanding of the linkage between childhood neighborhood environments and cognitive functioning in later life is limited. This study employed three waves of nationally representative data from the China Health and Retirement Longitudinal Study  to investigate the relationship between self-reported neighborhood social cohesion during childhood  and cognitive functioning (Chinese version of TICS). We employed latent growth curve modeling to test hypotheses relating to life course models of childhood conditions and later life cognitive functioning (the long arm of childhood). The results showed that perceptions regarding the willingness of neighbors to help and close-knit neighborhood characteristics during childhood were positively associated with levels of later life cognitive function. Further, growing up in a neighborhood characterized by the willingness of neighbors to help others was negatively associated with the rate of cognitive decline, net of childhood and adulthood covariates. Self-report of neighborhood safety during childhood was unrelated to cognitive function (level and change). These findings underscored the long-term ramifications of childhood conditions as potential risk factors for later-life cognitive health. Social cohesion at the neighborhood level as experienced during childhood may be a protective factor for healthy cognitive aging among older Chinese adults."}
+{"text": "This article investigates the influence of ramped wall velocity and ramped wall temperature on time dependent, magnetohydrodynamic (MHD) natural convection flow of some nanofluids close to an infinitely long vertical plate nested in porous medium. Combination of water as base fluid and three types of nanoparticles named as copper, titanium dioxide and aluminum oxide is taken into account. Impacts of non linear thermal radiation flux and heat injection/consumption are also evaluated. The solutions of principal equations of mass and heat transfer are computed in close form by applying Laplace transform. The physical features of connected parameters are discussed and elucidated with the assistance of graphs. The expressions for Nusselt number and skin friction are also calculated and control of pertinent parameters on both phenomenons is presented in tables. A comparative study is performed for ramped wall and isothermal wall to evaluate the application extent of both boundary conditions. Nanoparticles have the tendency to elevate the thermal conductivity of usual fluids such as water, ethylene glycol and mineral oils. The formation of nanoparticles comprises of carbides, metals and carbon nanotubes. Some practical utilities of nanoparticles these days are such as, vehicles have more lighter weight bumpers, cars have sunscreens which provide resistant to radiations, stronger synthetic bones, several sports balls are more durable and clothes are stain repellent. In addition, in the modern era of nanotechnology, where each object is getting enrich in features and reducing in size, nano-catalysts have significant applications in numerous process like water purification, drugs delivery, bio diesel production, solid rocket propellants and formation of carbon nanotubes2. As reported by Masuda et al.3, nanofluid has higher thermal conductivity due to addition of nanoparticles, but certainly it has different structure depending upon the size and shape of nanoparticles. Das et al.4 presented two to four times enhancement in thermal conductivity of In modern times, nanotechnology is attracting researchers and scientists for its practical utilities in engineering and industrial sciences. Contemporaneously, nanoliquids are involved in heating and cooling processes such as calming down the nuclear reactors, minimizing the temperature of radiators in vehicles, handling the heat generation in computer processes and controlling thermal flows through heat valves. In pharmaceutical industry, diagnoses and treatment of cancer is based on nanoliquid operators which comprise of different radiations. These noteworthy physical attributes of nanofluids and their implications are fascinating scientists and researchers. The term nanofluid is referred to addition of some solid nanoparticles in regular fluid, sometimes known as base fluid. This idea was first introduced by Choi6 and vertical cavities8. From the variety of purposeful applications of these cavities in industrial and environmental sciences, a few are named as thermal insulation, cooling of nuclear fuel, solar collectors and solidification. Hamad et al.9 examined the characteristics of naturally convective flow of nanofluid over a semi-infinite vertical plate in existence of external magnetic field. Das and Jana10 investigated the influence of magnetic field on nanofluid flow over an infinite vertical plate. An exact analysis of mass and heat transfer for MHD slip flow of nanofluids is provided by Turkyilmazoglu11. Sheikholeslami and Ganji12 numerically studied the flow of nanofluid over a permeable surface in rotating system. Hussanan et al.13 examined unsteady flow of some nanofluids over an accelerating wall nested in porous media in presence of magnetic field. Problems associated to modeling of heat and mass transfer flows in porous material are discussed by Amhalhel et al.14. The impact of using porous moving wall for forced MHD laminar flow corresponding to convective boundary conditions was investigated by AbdEl-Gaied et al.15. Wang et al.16 theoretically analyzed the formation of vortex in magnetized superfluids by constructing the exact solutions through similarity transformation. Turkyilmazoglu17 derived analytical solutions for momentum and energy transfer of MHD natural convective nanofluids motion over an instinctive upright wall. Mass transfer in porous stretching surface generating nonlinear MHD flow was reported by Singh et al.18.The study of mass and thermal flows of incompressible, viscous nanofluids is highly significant because of essential applications of such flows in engineering, chemistry and physics. Imposition of external magnetic field and placement of cavities filled with fluid and porous medium affect the flow of electrically insulated fluid in bearings, pumps, MHD motors, and generators. Such cavities can be portioned as horizontal cavities19. The other prime factors which can effectively control the rate of heat transfer are thermal radiation and heat injection/consumption. These factors have variety of practical utilities in food processing, ventilation, heat treatment and air conditioning20. Welding mechanics and thermal engineering deals with addition of heat sources or sinks to free and forced convective MHD flows to optimize the efficiency of cooling and heating processes22. Heat absorption/generation effects for MHD natural convective nanofluid flow over a vertical plate were reported by Chamkha and Aly23. Turkyilmazoglu and Pop24 conducted a theoretical study to analyze the radiation effects on MHD natural convection flow of nanofluids passing a vertical stretching sheet. Sheikholeslami et al.25 operated two phase model to analyze the impacts of heat radiation flux on heat transfer and MHD flow of nanofluids. Li et al.26 proved the global stability of nonlinear equations based ferromagnetic type solitons with the assistance of energy comparison. Influence of heat injection/consumption on nanofluid stagnation point flow was discussed by Soomro et al.27. Hamad and Pop28 studied and discussed the time dependent MHD natural convective nanofluid motion over a permeable flat vertical wall in a revolving frame of reference with constant heat generation. Reddy29 investigated the impacts of thermal radiation and heat generation for a micro-polar fluid flow over a stretching surface. Khan et al.30 inspected heat transfer phenomenon for MHD flow of Casson type nanofluid in presence of heat generation/consumption and thermal radiation. Some identical investigations can be studied in35.The investigation of thermal flow features of transient, MHD natural convective flow of viscous fluids with insertion of solid nanoparticles is extremely valuable due to practicability of such fluids in heat transfer instruments. Nanofluids have wide range of applications in numerous engineering process like advanced nuclear power plants and space aircraft due to convective heat transfer rates and higher thermal conductivity36 for unsteady flow and mass transfer of Newtonian fluid passing an impulsively moving vertical plate. Operating ramped wall temperature and ramped wall velocity is highly significant in various subdivisions of present-day technology and science. For instance, ramped velocity is useful in evaluating the functioning of heart and blood vessels. Diagnoses of cardiovascular deceases, determining treatment and establishing prognosis involve treadmill testing and Ergometry, which operate on the basis of ramped velocity37. Bruce38 reported ramped velocity based analysis which provides the functional tolerance and exercise limitations of cardiac patients. Furthermore, ramped exercise protocols for clinical exercise testing were investigated by Myers and Bellin39.However, all these efforts were made for uniform boundary conditions only, though ramped boundary conditions have enormous significant applications. According to authors\u2019 knowledge there is no single article in literature which deals with simultaneous application of ramped velocity and ramped temperature at wall for unsteady natural convective MHD nanofluid mass and heat transfer. The principal reason behind this shortfall is that resulting mathematical relations are extremely intricate and handling them analytically is sometimes troublesome. The idea of operating ramped wall velocity and ramped wall temperature at the same time was first initiated by Ahmed and Dutta40, Schetz41 and Hayday42. There are numerous methods available in chemical industry for the management of hazard material through thermal screening. To name a few only, e.g., Insulated Exotherm Test (IET), Differential Scanning Calorimeter (DSC), Thermal Screening Units (TSU), Differential Thermal Analysis, The Carius tube apparatus. With existence of these methods, ramped heating is an efficient technique to handle the anticipation of temperature rise under adiabatic conditions. Another significant practicability of time dependent temperature condition was highlighted by Kundu43. He reported that the purpose of destroying cancerous cells can be achieved by thermal therapy since time dependent temperature condition allows to reduce the side effects of this therapy to almost non-existence. Moreover, Kundu43 suggested five dissimilar kinds of Fourier and non-Fourier heating based boundary conditions to optimize the effectiveness of the cancer treatment. Keolyar et al.44 examined unsteady radiative MHD flow of a nanofluid passing a flat plate with controlled temperature condition. Impact of ramped wall temperature boundary condition on convective viscous fluid flow was evaluated by Chandran et al.45. Seth et al.46 further elaborated this analysis of ramed wall temperature by considering the plate nested in porous medium. Narahari et al.47 used ramped wall temperature at boundary to discuss the influence of mass transfer on viscous convective fluid flow passing an infinite vertical plate. Seth et al.50 gave attention to practical features of heat and mass transfer under different physical phenomenons like Hall current, chemical reaction and Darcy\u2019s law for impulsive/accelerating motion of plate subjected to ramped temerature at the boundary. Zin et al.51 provided a comprehensive analysis of considering ramped temperature condition for transient MHD natural convection flow of Jaffery fluid passing over an upright wall. Maqbool et al.52 further extended this study by adding the ramped wall velocity condition at wall and porosity of the medium.The credit of considering non-uniform (ramped or time-dependent) temperature conditions may be awarded to pioneer studies of Malhotra et al.The primary goal of this investigation is to analyze the influence of simultaneous application of ramped wall temperature and ramped wall velocity on unsteady, natural convective flow of water based nanofluids passing an infinite vertical plate nested in porous medium. Along the direction perpendicular to the plate, a uniform magnetic field is imposed in existence of thermal radiative flux and heat injection/consumption. The nanofluids of three types containing water as base fluid along with nanoparticles of Copper (Cu), Titanium dioxide  and  and 6) aThe initial and boundary conditions corresponding to momentum and energy equations are respectively stated as55The expressions for dynamic viscosity 56.Hamilton and Crosser model is applied to effectively anticipate the the thermal conductivity of nanoparticlesw,\u00a0np and nf are associated to the properties of base fluid water, nanoparticles and nanofluid respectively. Moreover it is significant to mention that relations , ,  and 14)14), the elations  are confFrom above expression, it is clear that heat radiation flux is non-linear function of temperature. However, it can be linearized with the assumption that during nanofluid flow, temperature differences are sufficiently small. Expansion of Taylor series of In the light of Eqs.  and 16)16), Eq. Some non-dimensional variables are introduced as followsu for the sake of brevity, we acquire the following dimensionless coupled system of partial differential equationsEmploying above dimensionless terms together with Eqs.  and 14)14) in Eq59 is an efficient tool to derive the solution of present problem, since the numerous traditional techniques such as separation of variables, perturbation method and Homotopy analysis method fail to overcome the complexity of time controlled boundary conditions. Formulation of integral form of Laplace transform pair to evaluate the results of considered model is proposed asLaplace transformationIn current problem, l in Eq. , where \\2, 1, 1, 23)1, 1, 1 and usising Eq.  gives33\\Introducing Eqs.  into 3333 resultThe solution of ordinary differential Eq.  subjecteOperating inverse Laplace transform on Eq.  results The expression for rate of heat transfer (or Nusselt number) at wall is derived asThe gradients involved in Eq.  are provThe skin friction coefficient at wall is computed asd in Eq. \u2013A5)..43\\documThe energy and momentum solutions for isothermal plate temperature and uniform plate velocity take the following form46. In addition, if magnetic parameter 45.The cause of authentication of our current results is achieved, when pure viscous fluid In order to achieve the goal of having comprehensive understanding of physical mechanism of current problem completely, a parametric analysis is performed, and computed solutions are revealed with the assistance of graphs and tables. In this section, solid lines present the solutions of velocity and energy equations with ramped wall velocity and temperature conditions, and similarly dashed lines present solutions under isothermal (constant) wall velocity and temperature conditions. The noteworthy physical attributes of associated parameters such as radiation parameter (Nr), heat injection/consumption parameter (Q), permeability parameter (K), magnetic parameter (M), time  is a significant factor. In Fig.\u00a0entclass1pt{minimaThe prime concern of this investigation is to evaluate the physical effects of application of simultaneous ramped wall velocity and ramped wall temperature condition on unsteady, MHD convection flow of some nanofluids over an infinite vertical plate. The Darcy\u2019s law is applied to encounter the porosity of the medium. In addition, heat injection/consumption and heat radiative flux are also inculcated in the model. It is worth mentioning that simultaneous application of ramped and isothermal wall boundary conditions is physically significant but analytical handling of resulted mathematical expressions is burdensome at the same time. However, in this work, exact solutions are derived by employing the Laplace transform and presented in close form. The impact of associated parameters on dimensionless temperature and velocity solutions are illustrated graphically, meanwhile, the computed results for skin friction (shear stress) and Nusselt number are provided through tables. The solutions for isothermal plate boundary condition and ramped plate boundary condition are also compared.In case of temperature, velocity, shear stress and rate of heat transfer, respective profile behaves in a similar manner for both ramped wall and isothermal wall boundary conditions.Momentum and thermal boundary layers have more thickness in case of isothermal wall in contrast to ramped wall.Nanofluid velocity is a decreasing function of magnetic parameter M and volume fraction Momentum boundary layer thickness increases for increasing values of Grashof number Gr, permeability parameter K and radiation parameter Nr.The temperature of Cu-water is found to be higher but an exactly inverse statement holds for velocity field.Cu-water has higher skin friction at the wall (associated to shear stress).Rate of heat transfer at the wall is found to be higher for The principal investigations of this analysis are concluded asSupplementary Information."}
+{"text": "The present study aims to examine whether duration of sleep moderates the relationship between daily stressor severity and headache severity and test age differences in these associations. We used the second wave of the Midlife in the United States (MIDUS) study and its subproject, the National Study of Daily Experiences . Stress severity was measured based on the respondents\u2019 perception of reported stressors, and headache severity was indicative of subjective rating of the symptom. Multilevel analysis results showed significant interaction effects between concurrent-day stressor severity and duration of sleep. Specifically, stressor severity was associated with more severe headache when people slept for shorter amount of time the same day. There were no differences by age in these associations. These results suggest that shorter-than-usual sleep may aggravate the intensity of headache on stressful days in daily life."}
+{"text": "Journal of Personalized Medicine titled, \u201cEthical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience\u201d identified the common concerns of IRBs in the process of reviewing such studies, and some concerns included the readability of informed consent materials, potential risks to participants, information sharing with family members, options for withdrawal or receiving limited results, and provisions to clear participant questions. Since there is an increase in the number of genomic medicine implementation studies worldwide, the insights provided by this study would assist future researchers in protocol preparation as well as aid project review by IRB members.The development of high-throughput techniques has permitted the accumulation of enormous amounts of genomic information. As increasing numbers of studies aim to utilize individual genomic information for diagnostic, preventive, or therapeutic purposes, Institutional Review Boards (IRBs) have a greater opportunity to review such types of study protocols. An article published in the  Journal of Personalized Medicine titled, \u201cEthical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience\u201d, Fossey et al. examined the Institutional Review Board (IRB) reviews and decision-making processes involved in the eMERGE III study [A huge amount of genomic information is increasingly available due to the advancement of high-throughput techniques . However, numerous barriers have prevented the translation of these data into clinical settings. To identify the optimal methods and practices for the incorporation of genomic information into clinical practice, the National Human Genome Research Institute has sponsored a multicenter consortium called \u201celectronic Medical Records and Genomics\u201d (eMERGE) since 2007 . CurrentAccording to their study , the majStudies seeking to implement the findings of genomic analyses are being increasingly conducted globally. Furthermore, comprehensive genomic information is becoming more readily available, and it is being translated to daily clinical settings. Although the study by Fossey et al. was conducted in the US, the underlying principles and study protocol reviews of EHR-based genomic medicine studies are applicable across the world. The authors identified the common concerns of IRBs in the process of reviewing genome medicine implementation studies. The findings would help future investigators and IRB members handle such projects."}
+{"text": "Malaysia contracted a high number of COVID-19 positive cases among the Southeast Asian countries. Albeit the global COVID-19 pandemic trend is increasing, Malaysia is seeing a decrease on the number of infections, with high recoveries and low mortality rates [As of July 04, 2020, Malaysia recorded 8658 COVID-19 positive cases, with 121 deaths and 8461 recoveries, leaving with only 76 active cases [Measures to contain the outbreak were formulated based on three principal strategies: (1) slowing introduction of global infections; (2) slowing infection of local outbreaks; and (3) executing community mitigation strategies. Travel restrictions for citizens, suspension of immigration facilities to travelers from affected regions, isolation of confirmed cases and quarantine of exposed individuals were imposed to slow introduction of global infections ,5. EntryAn exponential growth of COVID-19 cases was triggered in the second wave  due to a massive cluster gathering within the state of Selangor . Under MWith legislative and non-pharmacological interventions being put into place, the success of compliance was highly correlated with community engagement and support. The implemented interventions were concurrently executed with community mitigation strategies. Key community mitigation measures include: (1) obeying the cancellation or postponements of ad hoc or planned events, sports and religious activities; (2) high compliance on the practice of physical distancing measures and the usage of face mask; (3) reducing flight and public transportation services; (4) self-quarantine at home; (5) changes to crucial essential services like funerals to minimize crowd size and exposure to body fluids; and (6) avoidance of misinformation \u2013 verified and clear information regarding COVID-19 needs to be delivered on-time and consistently to the public to avoid fake news, rumors and panic.Conveying accurate and rapid information on COVID-19 risk factors, transmissibility, clinical features and prevention strategies via social, print or electronic media would enhance community\u2019s understanding of the disease. Consistent daily interaction between the government and the people to digest latest statistical updates and the do\u2019s and don\u2019ts during MCO via Short Messaging Service (SMS) reminders, daily press conference and social media posts had maintained transparency and compliance for successful execution of legislative measures [With declining trend of positive cases, Malaysia executed a relaxed Conditional Movement Control Order (CMCO) that aims to carefully re-open the country\u2019s major economy in phases . MalaysiContact tracing is more critical when individuals with high risk of transmission within detected clusters are difficult to track rapidly. Other vulnerable groups such as migrants or homeless people with poor living conditions compounded with overcrowding have increased susceptibility towards the spread of potential local contagion . The exeLockdowns have unprecedented psychological repercussions to people . To overWe are in the midst of battling the transmission of a pathogen that disrespects national and international borders with many uncertainties. While being the most potent infection to the human population globally, the anticipated hazards and implications are expected to prolong for months to come until appropriate evidenced based treatment modalities and vaccines are discovered. Pending answers to the many puzzles of COVID-19 from the scientific and medical perspective, it is crucial to reckon the importance of executed public health measures in such critical times to disallow an uncontrolled spread and replication of the virus to the human living environment, which would ultimately be difficult to tackle. Malaysia has taken a unique targeted approach in controlling the COVID-19 outbreak."}
+{"text": "Drosophila melanogaster [The Hedgehog signaling pathway was first discovered in 1980 during a large-scale genetic screening seeking to find mutations that affect larval body segment development in the fruit fly, International Journal of Molecular Sciences, entitled \u201cHedgehog Signaling in Organogenesis and the Tumor microenvironment\u201d, thus includes four original articles and five reviews that provide new insights regarding the roles of Hedgehog signaling in organogenesis and the tumor microenvironment.This Special Issue of the Tarulli et al., report on \u201cDiscrete Hedgehog Factor Expression and Action in the Developing Phallus\u201d, and they describe a potential developmental interaction involved in urethral closure that mimics bone differentiation and incorporates discrete Hedgehog activity within the developing phallus and phallic urethra .Takebe et al., examined Gli-CreERT2; tdTomato mice, and they demonstrate that the SHH-Gli1 signaling pathway is involved in intramembranous and endochondral ossification during the fracture healing process .Takabatake et al., describe \u201cThe Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma\u201d, and their findings revealed that (1) autocrine effects of SHH induce cancer invasion and (2) paracrine effects of SHH govern parenchyma\u2013stromal interactions of oral squamous cell carcinoma .El Shahawy et al., propose that \u201cSonic Hedgehog Signaling Is Required for Cyp26 Expression during Embryonic Development\u201d, and they explain that rigidly calibrated Hedgehog and retinoic acid activities are required for normal organogenesis and tissue patterning .Hosoya et al., provide an overview of recent advances related to the role of SHH signaling in tooth development, homeostasis, regeneration, and the regulatory mechanism of stem cell properties in the dental mesenchyme from experiments using tamoxifen administration in iGli1/Tomato mice .Jeng et al., extensively review the recent progress made in the field of \u201cSonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments\u201d, focusing on the combined use of SHH signaling inhibitors and chemotherapy/radiation therapy/immunotherapy targeting cancer stem cells .Hyuga et al., contribute a comprehensive overview of the \u201cHedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial-Mesenchyme Interaction (EMI)\u201d and compare possible similarities and divergences in Hedgehog signaling functions and the interaction of this signaling with other local growth factors between organogenesis and tumorigenesis. They discuss two pertinent research aspects of Hedgehog signaling: (1) the potential signaling crosstalk between Hedgehog and androgen signaling and (2) the effect of Hedgehog signaling between the epithelia and the mesenchyme on the status of the basement membrane with extracellular matrix structures located on the epithelial\u2013mesenchymal interface .Bechtold et al., offer a thorough review of the recent progress made in studies on the roles of Indian Hedgehog signaling in temporomandibular joint (TMJ) formation, and they discuss important findings regarding the involvement of Hedgehog signaling in TMJ development during embryonic and early postnatal stages as well as in the establishment and postnatal maintenance of TMJs, plus the possible involvement of Hedgehog pathways in osteoarthritic conditions .Haraguchi et al., provide a detailed discussion about \u201cRecent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate\u201d, and they review the multiple roles of the Hedgehog pathway in the regulation of growth plate formation and differentiation, as well as longitudinal bone development and skeletal disorders .The Editor hopes that these articles will help readers update their knowledge about the role of Hedgehog signaling in physiology and pathology. The efforts of the authors who contributed their excellent articles to this Special Issue are greatly appreciated."}
+{"text": "The pioneering Age-Friendly University (AFU) initiative, endorsed in 2016 by GSA\u2019s Academy for Gerontology in Higher Education (AGHE), calls for institutions of higher education to respond to shifting demographics and the needs of aging populations through more age-friendly programs, practices, and partnerships. Over 65 institutions in the United States, Canada, European countries, and beyond have joined the network and adopted the 10 AFU principles. Despite the importance and appeal of the AFU initiative, individuals leading age-friendly efforts on their campuses have found that ageism in higher education is a persistent, yet overlooked, factor holding us back from embracing age diversity. This symposium will feature AFU partners who will discuss how ageism presents itself in higher education, along with offering recommendations for breaking it down and promoting greater age inclusivity. Montepare will open the session with an overview of systematic and implicit instances of ageism in higher education. Bowen and colleagues will then discuss results from an AFU Campus Climate Survey that examined the age attitudes of faculty, students, and staff along with their views about that nature of campus age-friendliness. Manoogian will discuss the value of approaching the teaching of age diversity from an intersectionality perspective. Reynolds and Kruger will provide theoretical framing and dissemination models for the GSA online course Ageism First Aid within various AFU and programmatic structures. Andreoletti and June will discuss how creating an age-inclusive AFU Learning Community can raise awareness about ageism across campus as well as in the community where a campus resides. Age-Friendly University (AFU) Interest Group Sponsored Symposium."}
+{"text": "Audiology Research (ISSN 2039-4349) was launched in 2011 and published over the past nine years by PAGEPress Publications [rch ISSN 039-4349 Audiology Research from PAGEPress and perpetuate the legacy of the journal. Audiology Research complements the portfolio of MDPI medical and pharmacology journals very well [Acoustics [We are delighted to take over the publication of ery well , and procoustics .MDPI will publish the second issue of 2020 in this December, and thereafter publish four quarterly issues as of 2021. Audiology Research [We are looking forward to publishing your research work in Research !"}
+{"text": "With rapid population ageing, providing better end-of-life care (EOLC) is becoming a source of social demand and financial pressure for public and private budgets in many countries. This paper uses data from harmonized end-of-life interviews in the HRS family of studies to assesses variation in health care utilization across different income groups and how they differ across different health care systems. Hospital stay did not vary across health care systems, but nursing home stays were lower in countries with either national or statist social health insurance systems. Hospice use was low in all countries, but particularly in national and social health insurance systems. Lower income was associated with greater use of nursing homes in both the private and social health care systems. Low income was also associated with greater use of hospice in national health service, but lower use in social health service."}
+{"text": "Welcome to the first issue of MJR for 2019: it hosts interesting contributions from authors across the Mediterranean area and beyond. In this issue we bring together facets of rheumatology clinical care and aspects of laboratory techniques used in the evaluation and validation of immunological tests.1 discuss how data originating from large population-based databases could contribute to the decision making and improve clinical practice. They comment on the study of Mansour et al.,2 who collected data from a large health provider organization in Israel. The authors look back to the first steps of rheumatology and present how data collection in this field has evolved over the last 150 years.In their editorial, Bragazzi et al.3 discusses the serious problem of cerebrovascular events in patients with Systemic Lupus Erythematosus (SLE). Stroke is the major central nervous system manifestation of SLE: Boumpas and his team, world experts in the field of SLE, provide comprehensive information about the epidemiology, work-up, management and primary prevention of cerebrovascular events in patients with lupus. The role of thrombolysis as a therapeutic intervention in this particular group of patients is also highlighted in the article.A top-quality review article by Nikolopoulos et al.4Systemic sclerosis (SSc)-related interstitial lung disease remains an extremely challenging area in rheumatology with significant advances and numerous ongoing trials investigating regimens with different modes of action, namely conventional and biologic immunosuppressants, anti-fibrotic agents, and cannabinoid receptors. Daoussis & Liossis, who have produced original data of their own in this field, summarise the recent data and provide practical guidance regarding the treatment of this difficult-to-manage subgroup of SSc patients, focusing on mycophenolate mofetil as the cornerstone of treatment for patients with severe pulmonary involvement.6Monogioudi and Zegers from the European Commission Joint Research Centre in Belgium remind us how important, but also how hard, is the process of validation and standardization of autoantibody testing techniques to ensure reliable results and correct diagnosis in autoimmune diseases across different countries and areas. The authors underline the collaboration between the European Commission and scientific organizations in the development of autoantibody assays.5 They underline the importance of physical therapy and rehabilitation, which are at least as important as the various pharmacological interventions.Besides systemic diseases, in daily clinical rheumatology practice we are frequently confronted with syndromes with diffuse or residual musculoskeletal pain requiring a multidisciplinary approach by different medical teams and allied health professionals. Complex regional pain syndrome is a typical difficult-to-treat disease: in this issue Misidou & Papagoras provide an excellent clinical update of this condition with practical tips regarding its overall management.2 In line with previous reports, they demonstrated an increased risk of deep vein thrombosis in RA patients which was associated with high CRP levels. These findings confirm once more the tight link between inflammation and vascular disease and underscore the continuous need for optimal control of RA.The risk of venous thromboembolic events in patients with autoimmune disorders has attracted the interest of rheumatologists over the last years. In the current issue Mansour et al. present a population-based study from the largest health provider in Israel assessing the incidence of deep venous thrombosis and pulmonary embolism in 11,782 rheumatoid arthritis (RA) patients and 57,973 age- and gender-matched controls.7 Interstitial lung fibrosis has been recognized recently as a possible initial manifestation of p-ANCA-associated vasculitis, and such cases could promote awareness amongst rheumatologists and other physicians of this type of pulmonary involvement in this specific subgroup of patients with systemic necrotizing vasculitis.A complex case of an elderly female patient with microscopic polyangiitis and pulmonary fibrosis is presented by Koutsoviti et al.8 and the performance of the Assessment of Spondyloarthritis International Society criteria for the classification of ankylosing spondylitis in a large cohort from a regional centre in Crete.9In our regular research protocol section, we publish in this issue 2 protocols funded by the Greek Rheumatology Society and Professional Association of Rheumatologists after external international peer review. They include a prospective study assessing nailfold capillaroscopy as a prognostic tool for the long-term outcome in SSc patients"}
+{"text": "Purpose: Recent studies report daily fluctuations in stress among family caregivers of older individuals with dementia. Several studies focused on daily stressors or behavioral and psychological symptoms of dementia and use of adult day services. Most previous studies on daily fluctuations of caregivers\u2019 stress have used a daily diary approach. This approach involves creating multiple daily reports, making it possible to examine between-person differences and within-person processes of change. However, only few studies used this approach for family caregivers in Asian countries. Therefore, this study examines the applicability of a daily diary approach for Japanese family caregivers and the effects of formal care services on their stress and depression. Methods: Participants were 13 family caregivers of individuals with dementia using formal care services in a rural area in Japan. They were assessed through self-administered questionnaires including use or nonuse of formal care services, caregiving stressors (DASC-8), depressive symptoms (K-6), and caregiving stress for 7 days. Generalized linear mixed models (GLMM) with data nested within persons were used to examine the effects of formal services on stress and depression. Results: For the GLMM procedure, this study used caregiving stressors and stress variables as fixed effects and participants as random effects. Results indicated that use of formal services significantly lowered caregivers\u2019 stress and depression. Conclusion: The findings demonstrate the applicability of a daily diary approach and the effectiveness of formal services on the stress of Japanese family caregivers."}
+{"text": "The data article investigates the role of coping strategies, psychological and social well-being in the time of stress due to the effects of technology. Increased technology in the life of students introduces complexities, uncertainty, and overload in higher education institutes. This data provides an ideal research scope for examining the effects of coping strategies on social and psychological well-being. The present dataset includes three hundred and one (301) survey questionnaires from university students in Surabaya city, Java Timor province, by using simple random sampling techniques. This article includes information on reliability and factor loadings, as well as results of regression analyses. Specifications table\u2022The data can be used to explain how students use coping strategies  to reduce the stress due to technology overload, complexity, and uncertainty.\u2022The data is important for policy implementation  in higher education in the digital age.\u2022The data is also valuable for designing student's psychological and social activities  on campus.1The data can provide insight into the relations between social and psychological well-being of individuals, and coping strategies against technostress (TS) Evidence for discriminant validity is provided in 2The data were collected during the Spring 2018 semester from university students in Java province using a distributed online questionnaires survey research approach Participants responded to items on a Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree). The questionnaires were taken from the extant literature The measure of technostress TS;  used in The measure of coping strategies Psychological well-being was measured with three items, and measures hopefulness and feeling good about oneself . Social capital was measured with three items and explains cultural awareness and social cohesion with society ."}
+{"text": "Prior research has found that the risk of cognitive decline increases after the death of a spouse. In general, the impact of life transitions is contingent on contextual factors such as socio-demographic characteristics or relationship quality. However, there is limited research on how marital quality before spousal loss and gender influence the association between spousal loss and cognitive change. The current study examines the effects of spousal loss on change in cognitive functioning as well as the moderating effects of pre-loss marital quality and gender. Data from two waves of the Midlife in the United States (MIDUS) study were analyzed . The analytic sample consists of two groups: (1) 179 bereaved adults who were age 54 or older at MIDUS2  and whose spouses died between MIDUS2 and MIDUS3, and (2) 179 non-bereaved adults, matched with the bereaved group on age and gender, who did not experience spousal loss between the two waves. Cognitive function was assessed via BTACT (Brief Telephone Adult Cognition Test) at both waves. Regression results show that both pre-loss marital quality and gender significantly moderate the association between spousal loss and change in cognitive functioning. Specifically, relative to their counterparts, men and those who reported better marital relationships prior to spousal death had a greater risk of cognitive decline after a spouse\u2019s death. The findings suggest the significance of pre-loss marital quality and gender for cognitive changes in widowhood and have implications for the development of efficient interventions"}
+{"text": "A nihilistic approach to the treatment of non-small cell lung cancer (NSCLC) has characterized the predominant attitude of physicians as well as patients during most of my professional career. This attitude has persisted despite therapeutics that have demonstrated efficacy in terms both of quality and quantity of life since at least the early 1990s  of the Eastern Cooperative Oncology Group (ECOG) 4599 trial  were markedly superior  to a similarly treated arm on the prior ECOG trial E1594), which did not have the restrictions on eligibility  ,13. Furt94, whichOverall, the results of this study provide a snapshot of practice that confirms the results of clinical trials but demonstrates how socioeconomic features and physician attitudes strongly influence how these developments are applied. Overcoming these barriers is likely to remain an important challenge.Affiliation of author: Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA."}
+{"text": "In 2018, 382,069 new cases of uterine cancer were registered worldwide and 89,929 deaths from this cancer were reported [For low-grade endometrioid endometrial cancer, the standard treatment is surgery, and when surgery confirms an early stage, surgical treatment is also the only treatment . The staIn the early 1980s, Bokhman [Less than ten years ago, a paper published by The Cancer Genome Atlas (TGCA) Research Network  revealedThe progress achieved in the classification of endometrial cancer with diagnostic algorithms combining immunohistochemical markers and molecular tests has made it possible to better define, for prognostic purposes, the risk groups currently included in the latest European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for the management of endometrial cancer . To idenThe consideration of other immunohistochemical markers, such as L1 Cell Adhesion Molecule (L1CAM), would still be valuable to better classify those cases of endometrial carcinoma that are still considered globally as low risk but have clinically different outcomes .In this Special Issue, we invited experts in the field of endometrial cancer histopathology and immunohistochemistry as well as risk assessment and prognosis to contribute original articles or systematic reviews and meta-analyses reporting recent advances in the role of immunohistochemical markers in stratifying women with endometrial cancer into homogeneous prognostic groups who could benefit from specific individualized therapies."}
+{"text": "Stroke is the leading cause of global mortality and disability. Cerebral edema and intracranial hypertension are common complications of cerebral infarction and the major causes of mortality. The formation of cerebral edema includes three stages , which involve multiple proteins and ion channels. A range of therapeutic agents that successfully target cerebral edema have been developed in animal studies, some of which have been assessed in clinical trials. Herein, we review the mechanisms of cerebral edema and the research progress of anti-edema therapies for use after ischemic stroke. Stroke is the leading cause of death worldwide  and water entering the cells of neurons or astrocytes , aquaporin-4 (AQP4), the Na+-H+ exchanger, and the Na+-Ca2+ exchanger drive this process , the Na+-H+ exchanger, and AQP4  model in rats and in an oxygen and glucose deprivation-reoxygenation model in endothelial cells  reduced the number of immature blood vessels following cerebral edema in a rat MCAO model  is also involved in the formation of cerebral edema  significantly reduced the Na+ concentration and reduced cerebral edema  could reduce the formation of cerebral edema and cerebral infarction volume after cerebral ischemia  regulate the gene expression at the transcriptional level and are promising targets for disease therapy (Carleton et al., via its antioxidant actions (Chaudhary et al., Vasogenic edema is accompanied by BBB destruction. Thus, maintaining BBB integrity is an important outcome measure for anti-edema treatments. Alpha-tocopherol can protect the BBB Cerebral edema following ischemic stroke is associated with a poor prognosis. Unfortunately, there are currently limited specific anti-cerebral edema treatment options available for clinical use. Traditional osmotic therapies are not specific to the molecular mechanism of cerebral edema. Their main role is to reduce intracranial hypertension and relieve mass effects (Stokum et al., A range of therapeutic agents  have beeYZ and XL designed and conceptualized the review. YY drafted and revised the manuscript. YL revised the manuscript. RY and JL retrieved and screened the review. All authors contributed to the manuscript and approved the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Dear Editor,Prevalence and mortality of liver fibrosis continue to grow . For thCurrently, numerous research activities are performed to identify or optimize therapies for chronic liver disease (Trauner et al., 2017; Svinka The authors declare no conflict of interest."}
+{"text": "There is growing interest in the role of \u201cplace\u201d in the provision of long-term services and supports (LTSS) for older adults with disabilities, who receive ~16 billion hours of care per year from family and unpaid caregivers, but information is lacking. Using data from the 2015 National Health and Aging Trends Study (NHATS) linked to census-tract-level information from the American Community Survey, we described the association between caregiving intensity (hours of care received per week) and neighborhood social deprivation among N=2125 community-dwelling older adults with disabilities. Individuals receiving 40 hours or more of help per week had greater levels of functional impairment and dementia, and more often lived in neighborhoods at the highest quartile of social deprivation compared to those receiving fewer than 20 hours of care . Findings have policy implications for targeting LTSS strategies toward addressing inequities in social determinants of health for vulnerable populations."}
+{"text": "The standard for monitoring sedation levels in critically ill patients is intermittent bedside evaluation, and is prone to anchoring bias. Quantitative electroencephalography (qEEG) allows automated processing of recorded brain electrical activity and could be used to continuously monitor level of consciousness in critically ill patients. The majority of qEEG studies have included persons 80 years of age or less, and the qEEG profiles of nonagenarians have been incompletely characterized. Knowledge of the qEEG patterns of patients 90 years and older is essential for appropriate interpretation of such metrics in this population. This retrospective cohort study characterized qEEG profiles of acutely ill nonagenarians. We investigated whether the relationship between qEEG and level of consciousness differed between patients with and without a history of dementia. We included patients 90-100 years old admitted to Vanderbilt University Medical Center who underwent EEG and as part of their clinical care. We compared qEEG features to nursing-defined level of arousal as measured by the Richmond Agitation-Sedation Scale (RASS) in patients with and without history of dementia. Between January and December 2019, 26 nonagenarians underwent EEG for clinical purposes. One study was excluded due to excessive artifact. Of the remaining, 6 (24%) were male and 18 (72%) were Caucasian. Among all patients, RASS decreased with increases in EEG theta variability . This relationship was not significantly modified by history of dementia . Dementia does not impact qEEG features of level of consciousness in nonagenarians."}
+{"text": "Penaeus monodon) in Khulna, Bagerhat and Satkhira districts of Bangladesh. This dataset was developed following two consecutive steps. In the first step, participatory rural appraisal tools were applied to get the conceptual framework for data collection regarding lists of farmers and the variables of the risk factors of WSD. In the second step, sampling of farmers, google featured questionnaire development, and mobile phone-assisted survey were carried out. The total surveyed farms were 233 consisting of 21 and 212 semi-intensive and extensive farms, respectively. The data were collected in the form of continuous, nominal and binary variables disaggregated by saline zones. The dataset contains some basic socio-economic data of shrimp farmers, farm characteristics, environmental attributes and disease history of shrimp farms. The dataset also has GPS coordinates of all the surveyed farms individually which are very useful for spatial analysis. In total, the dataset in MS Excel has 46 variables and attached as the supplementary material with this article.The article presents the summary of a dataset related to the risks factors of white spot disease (WSD) of farmed shrimp ( Specifications TableThe dataset of WSD affected 233 shrimp farmers is disaggregated by their farm characteristics and management practices, and by saline zones in southwest Bangladesh which can be used to conduct comparative studies of the changes in shrimp farming on a temporal scaleThe key strength of the dataset is that it has GPS coordinates of all the individual farms which researchers and policymakers can use for the establishment of farm traceability that Bangladesh shrimp farms lack severelyThe data can be useful for spatial modelling of the impacts of climate change particularly the impact of saline water intrusion on shrimp farming and rural livelihoodsOverall, the data are important for various stakeholders including farmer, policymakers, researchers, scholars, academicians to mitigate the negative impacts of WSD on the entire shrimp farming area of Bangladesh towards sustainable farmingValue of the Data1N\u202f=\u202f233) are given in the summary The dataset has been built in MS Excel format having two sheets. The first sheet (Dataset) is the main dataset of 46 variables and the second one (DataCoding) is about the coding of different nominal and binary data. The short descriptions of the whole dataset N\u202f=\u202f23 are giv2This dataset was developed following two consecutive steps. In the first step, participatory rural appraisal tools such as key informant interview (KII), focus group discussion (FGD) and field observations were conducted to get the conceptual framework for generating lists of farmers and the variables associated with the risk factors of white spot disease (WSD). In the second step, sampling of farmers, google featured questionnaire development, and data collection were carried out by android mobile phone-assisted survey. In the beginning, through extensive literature review particularly reviewing the statistical report published by Fisheries Resource Survey System (FRSS) of the Department of Fisheries (DoF), the major shrimp producing sites were selected in Khulna, Satkhira and Bagerhat districts of Bangladesh . Shrimp shrimp zone\u2019 consisting of high saline, intermediate saline and low saline areas from where comprehensive lists of WSD experienced shrimp farmers were collected from the key informant, local Upazilas (sub-districts) Fisheries Officers of the DoF. The list of shrimp farmers in an individual farming site was cross-checked through FGD with farmers. From each of the farming sites populated with WSSV experienced shrimp farmers , about 30% of farmers each from Khulna (150), Bagerhat (26) and Satkhira (57) in a total of 233 farmers, who experienced WSD in the past years (from 2010 to 2017), were sampled using a simple random sampling technique that made a robust dataset for statistical analyses. The total number of semi-intensive and extensive farms were 21 and 212, respectively (https://goo.gl/forms/ckG1AIf9xMTxtPpf1) and then applied by the trained enumerators to conduct the survey. After the survey, the dataset was downloaded in the computer from the Google in CSV  format and then converted to a MS Excel file.These sites are collectively known as the \u2018ectively . The queThe authors declare that they have no known competing for financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article."}
+{"text": "The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR . The spread of the new coronavirus SARS-CoV-2 is challenging many health and care systems around the globe . Its onsrd European Health Programme in order to systematically review current practices in the health and care sector to see how existing services could be improved [Prior to the outbreak, care authorities from six European countries have joined forces in the VIGOUR project funded under the 3improved . Taking Integration of health and social care is widely advocated as way to improve the management and outcomes for increasing numbers of older, vulnerable people with varying and/or complex health and social care needs 6 with th878121314Against this background, a multi-staged process was developed by the VIGOUR project  to suppoThe experiences gained during the pandemic so far reinforce the care integration approach of the VIGOUR project and encourage to build more connected health and care systems enabling collaboration across care settings and disciplines 18. EffecVIGOUR care authorities detected features gaining a higher importance during the pandemic outbreak, evolving into three major requirements to drive innovation in integrated care under emergency situations within health and care systems. First, the increased need for technology related innovation with regard to COVID-19 was recognized. Major aspects that gained momentum were triage and (remote) pre-triage, tele-consulting and tele-monitoring of COVID-19 positive patients and suspected cases, employment of screening or mobile diagnostic applications, contact tracing and monitoring of hospital and ICU beds availabilities. Second, VIGOUR pilot sites detected the requirement for quarantine related innovation during the pandemic outbreak. Social isolation and quarantine are required to be managed by means of cross-service guidelines for home isolation, by fostering at-home physical activity during quarantine and keeping remote contact with lifestyle coaches. Third, dynamics were also facilitated in the field of care pathway related innovation. A stronger involvement of case managers, personalized care planning efforts for COVID-19 patients, the development of dedicated integrated care processes and clinical pathways for patients and suspected cases and an enhancement of advanced care planning in long-term care represent underlying mechanisms anticipated.Figure Reflecting upon the VIGOUR progress so far, some preliminary lessons learned can be drawn on how envisaged care integration approaches of the pilot sites were shaped within the course of the pandemic.Not surprisingly, eHealth and digitalization in their various characteristics represent a valuable tool for facilitating integrated care processes also during the COVID-19 pandemic. The COVID-19 experiences that the VIGOUR partners have been able to make so far have made particularly clear the potential generally provided by digital technologies for the provision of person-centred and coordinated integrated care. However, the availability of practical and safe applications is crucial . Still, Social isolation was discovered as hotspot, as on the one hand, it has proven to be a necessity to avoid transmission of the COVID-19 infection and on the other hand, isolation may lead to deeper psychological and mental health issues, especially for older, vulnerable citizens 22. LiterAdditionally, the role of primary health care in regards to the development of an integrated care system has received prompt attention by VIGOUR partners and is on line with the World Health Organization (WHO) Anniversary Meeting in Astana .The pandemic has brought to fragmentation and gaps in our social and health care systems and has accelerated the need for integration and coordination of health and social care. In order to achieve better integration, a realistic perspective is moving forward given the complexity and variety of culture and socio-political dependant variables. The framework within VIGOUR project partners takes into consideration the fact \u201cthat one model does not fit all\u201d. Thus, the insights and various models developed during the project will assist the exploration, development and implementation of different care integration approaches in distinct systems across Europe  as well The onset of COVID-19 constitutes a critical issue and forces health care systems not to just provide acute care opportunities for COVID-19 patients, but also to rethink and redesign care pathways. The VIGOUR project approach seems robust to influences evoked by the pandemic and flexible enough to take advantage of integrated care initiatives available on pilot level and adopt them to specific needs emerging in pandemic times. eHealth, quarantine management and integrated clinical management of COVID-19 patients and suspected cases evolved into promising aspects, leading health and social care systems towards a more integrated care approach. Further information on this topic may be expected from VIGOUR by fall 2021."}
+{"text": "Aging is a physiological and dynamic process enduring time, which is influenced by various underlying mechanisms occurring within the biological, psychological and social spheres. We investigated biopsychosocial determinants of subsequent health and mortality in the English Longitudinal Study of Ageing (ELSA) (Steptoe). Cognitive impairment and dementia, particularly Alzheimer\u2019s disease (AD), represent significant challenges to individuals, families and healthcare. We found an indication of socioeconomic differentials influencing the mediating biological and psychological pathways in relation to subsequent cognitive health, which was ascertained with a latent g factor across various cognitive domains in the Harmonised Cognitive Assessment Protocol in ELSA (Cadar). We also identified an interplay between socioeconomic markers and genetic factors influencing the time of dementia and Alzheimer\u2019s disease (AD) diagnosis in individuals from the English Longitudinal Study of Ageing, particularly in those with a polygenetic predisposition to AD (Ajnakina). Within the same cohort, we found that participants who transitioned into a single household due to divorce or bereavement had a higher risk of mortality (Abell). The adverse health outcomes associated with loneliness are well documented, but less is known in terms of hospitalization and accessing health care. In the Healthy Ageing in Scotland (HAGIS), we found an increased hospitalization for older individuals reporting higher loneliness (Douglas); and various loneliness patterns in relation to age, gender, marital status and socioeconomic status in participants from first wave of the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (Neville). Our findings highlight the imperative need for policy interventions and tailored strategies."}
+{"text": "This individual symposium abstract will focus another evidence-based approach to mental health treatment and in older adults, the collaborative care model. Collaborative care is a consultation-based approach in primary care that has been described with multiple clinical trials, with significant benefit for access and treatment. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) using the collaborative care model found that those older adults receiving the intervention had a higher utilization of mental health treatment (psychotherapy and/or antidepressant treatment) and had a 2.2 times greater decline in suicidal ideation over 24 months. The authors will describe the utility of using the collaborative care model on the identification of suicidal ideation and subsequent mental health treatment for older adults. The authors will also share about challenges and successes related to collaborative care implementation in healthcare settings for older adults, and relevant policy and financing components for the model."}
+{"text": "Interprofessional research pertaining to LGBTQ older adult cultural sensitivity training for social workers and nurses is often missing in the empirical literature. Members of the LGBTQ communities become increasingly vulnerable to health disparities as they age and treating clients with respect and dignity is at the forefront of this study. Students and faculty engaged in an interprofessional simulation project with older members of the LGBTQ community to learn health knowledge and applied assessment and brief intervention skills. Quantitative findings  indicated increased student health knowledge. Reflection and qualitative findings are included with four primary themes: (a) bias of health care providers, (b) access to quality care, (c) specific health care needs, and (d) health risks of LGBTQ older adults. Specific emphasis is given to reflection and insight of the older lesbian participants about access to care, recognition of significant relationships, and marriage equality."}
+{"text": "The unique capability of embryonic stem cells (ESCs) to maintain and adjust the equilibrium between self-renewal and multi-lineage cellular differentiation contributes indispensably to the integrity of all developmental processes, leading to the advent of an organism in its adult form. The ESC fate decision to favor self-renewal or differentiation into specific cellular lineages largely depends on transcriptome modulations through gene expression regulations. Chromatin remodeling complexes play instrumental roles to promote chromatin structural changes resulting in gene expression changes that are key to the ESC fate choices governing the equilibrium between pluripotency and differentiation. BAF (Brg/Brahma-associated factors) or mammalian SWI/SNF complexes employ energy generated by ATP hydrolysis to change chromatin states, thereby governing the accessibility of transcriptional regulators that ultimately affect transcriptome and cell fate. Interestingly, the requirement of BAF complex in self-renewal and differentiation of ESCs has been recently shown by genetic studies through gene expression modulations of various BAF components in ESCs, although the precise molecular mechanisms by which BAF complex influences ESC fate choice remain largely underexplored. This review surveys these recent progresses of BAF complex on ESC functions, with a focus on its role of conditioning the pluripotency and differentiation balance of ESCs. A discussion of the mechanistic bases underlying the genetic requirements for BAF in ESC biology as well as the outcomes of its interplays with key transcription factors or other chromatin remodelers in ESCs will be highlighted. Second, they have the capacity to differentiate into every cell type of the body. For decades, the mechanism underlying the self-renewal and pluripotency of ESCs has been the focus of intensive research in the field of stem cell biology.Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocyst-stage embryos  on the maintenance of ESCs and their pluripotency, among which OCT4, SOX2, and NANOG form a core transcriptional regulatory circuit   complex, the mammalian homolog of the SWI/SNF complex, is one of four ATP-dependent chromatin remodeling complex families known in mammals   complex is required for the regulation of the ESC transcriptome, therefore controlling the self-renewal and differentiation of ESCs , reduced colony-forming capability, and downregulated expressions of Nanog and Klf4, indicating that BRD9 has an important role in maintaining the na\u00efve pluripotent state of ESCs . Depletion of In summary, esBAF complex is crucial for the maintenance of ESCs, with distinct effects from the deletion of different subunits. The knockout of different subunits of esBAF leads to defects of ES differentiations to different lineages, though the precise molecular mechanisms underlying the different phenotypes upon the deletion of different subunits need further investigations.Nanog, Oct4, and Sox2 as well as a variety of other factors governs the maintenance of pluripotency in ESCs -depleted ESCs, leading to the downregulation of Stat3 target genes  (Gatchalian et al., esBAF also regulates gene expression in ESCs (Ho et al., Drosophila followed by the observation of male flies with ectopic sex combs (Margueron and Reinberg, The PcG family has first been discovered in Tbx3 expression is critical to the proper differentiation of ESCs to mesoendoderm. The other PRC2 subunit EZH2 also opposes DPF2-dependent differentiation through a distinct mechanism involving Nanog repression (Zhang et al., The cooperative function of BAF complex with PRC2 in ESCs has been revealed (Ho et al., Dpf2 only affects about 8% of BRG1 binding sites on the genome (Zhang et al., Inactivation of different subunit of BAF complex differentially affects the expression of pluripotency TFs . FurtherDpf2 does not change the level of H3K27ac around DPF2-bound lineage markers during differentiation of ESCs. Consistently, overexpression of Dpf2 in ESCs does not lead to the upregulation of endo- and mesodermal markers, supporting an idea that BAF complex regulates ESC differentiation indirectly (Zhang et al., Tbx3 is a pluripotency TF, and the downregulation of its expression impairs ESC self-renewal (Ivanova et al., Tbx3 also plays key roles on ESC differentiation. Deregulation of its expression impairs the differentiation of ESCs (Lu et al., Dpf2 participates in the self-renewal and differentiation of ESCs via precisely regulating Tbx3 expression in both ESCs and differentiating cells (Zhang et al., Nanog represses expression of differentiation marker genes and maintains the self-renewal of ESCs (Niwa, Dpf2 regulates the expression of Nanog with PRC2 subunit Ezh2, thereby controlling the proper differentiation of ESCs (Zhang et al., BAF complex regulates both the maintenance and differentiation of ESCs (Ho and Crabtree, Cs Niwa, . Dpf2 reOct4 expression, which provides another example to demonstrate how BAF complex controls the balance between pluripotency and differentiation (You et al., Baf47 in ESCs indicates that more studies are required to clarify the discrepancy (Sakakura et al., BAF47 controls the differentiation of ESCs via regulating BAF complex is functionally important for the self-renewal and differentiation of ESCs. Knockout of different subunits of BAF complex changes the expression of different pluripotency TFs and impairs the differentiation of ESCs differently. Thus, it is of particular importance to explore how BAF complex regulates the balance between the maintenance of identity of ESCs and their differentiation to three germ layers. We have outlined studies that described functions of specific subunits of various BAF complexes in ESCs. Moreover, our recent study demonstrates an attractive mechanism that distinct BAF subunit controls the integrity of only a part of BAF complex on the genome, and therefore, its deletion only affects the binding of a part of BAF complex, which directly changes the expression of distinct pluripotency TFs in both ESCs and differentiating cells with other TFs and chromatin modifiers (Zhang et al., YY, XC, and WZ conceived the study and wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Older adults are discriminated against at different social levels- called ageism and the people living with dementia (PlwD) not only face ageism due to being elder but also encounter prejudices, negative attitudes and discrimination because they live with dementia. The purpose of this review is to highlight the different conceptual and methodological approaches used and the groups being investigated as well as the findings from studies in the combined research field of ageism and dementia. Five scientific databases were used within a timeframe between 2009 and 2018. A total number of 98 articles  were included and analyzed based on (i) the conceptual frameworks, (ii) methodological approaches, (iii) groups studied, and (iv) findings. The result emerged six themes (i) stereotypes and attitudes in the general population; (ii) stereotypes and attitudes of themselves; (iii) stereotypes and attitudes among staff; (iv) stereotypes and attitudes as part of culture; (v) stereotypes and attitudes of family members; and (vi) miscellaneous. The principal findings identified lower education, lack of knowledge and less information about dementia as the main contributing factors to manifest stereotypes, attitudes, and ageism in society toward PlwD that leads to stigma. Moreover, this review found few studies were based on explicit conceptual frameworks but rather on descriptive understandings of relations between attitudes. There is a domination of the quantitative approach where the target populations were mostly from Western regions. The review suggests that a more conceptually coherent approach would allow for a better cumulative building of knowledge."}
+{"text": "Despite the well-established need to measure and address the growing issue of disparities among older minority populations, little is known about the prevalence and correlates of disability, morbidity, and mortality among older US Pacific Islander adults. This paper discusses culturally appropriate approaches for conducting evidence-based research on a representative probability sample of older Native Hawaiian and Pacific Islander adults interviewed as part of the Pacific Islander Health Study and Native Hawaiian and Pacific Islander National Health Interview Survey. Important strategies that increase response rates and respondent participation when engaging this multi-ethnic and culturally diverse special population in research are highlighted. The model describes successful methodologies that combine CBPR approaches of community engagement with more traditional survey design methods. The findings from this work emphasizes the importance of representative data on hard-to-survey populations to illustrate granular differences in health outcomes within underrepresented populations that are not reflected in national health surveys."}
+{"text": "Prior research has indicated that religiosity may buffer against the deleterious effects of caregiving. However, research is lacking in examining the role of religiosity and caregiving intensity in the context of caregiver wellbeing and mortality. Data come from the Health and Retirement Study (2004-2014 waves) and consisted of spousal caregivers and noncaregivers . Pearlin\u2019s Stress Process Model (1990) informed this study to analyze how religiosity impacts caregiver self-rated health and mortality by comparing the intensity of provided care among spousal caregivers and spousal noncaregivers. This study used two indicators to measure religiosity: 1) the importance of religion in life and 2) frequency of attending religious services. Bivariate probit model was used to model the impact of caregiving intensity and religiosity on self-rated health and all-cause mortality. After controlling for sociodemographic and health covariates, results showed that only the importance of religion in life predicted a better self-rated health among high intense spouse caregivers defined by providing >=14 hours of care per week. Findings suggest religiosity may buffer the adverse effect of caregiving stress on health for high intense spousal caregivers. Development and maintenance of religiosity may enhance positive aspects of caregiving and decrease caregiver burden."}
+{"text": "Arthropods of medical and veterinary importance live alongside people, our livestock and pets, and wildlife, creating a pathway for zoonotic pathogens to jump between reservoir hosts and accidental hosts. These pests and parasites at a minimum are the sources of general annoyance to people and animals. Some serve as vectors which inflict further damage by transmitting pathogens that cause disease and negative changes in body condition or physiology to hosts. In addition to biological impacts, pests of livestock can cause billions of dollars in economic damage . FurtherStudies of these organisms and how to reduce their impacts on animal and human welfare began \u2018in the field\u2019, in the natural or synanthropic habitat occupied by the pest. However, the field techniques to trap, study, or manipulate pests of medical and veterinary importance have not been described as thoroughly as molecular and \u2018-omics\u2019 methods. Many field techniques are not fully detailed in manuscripts but are instead housed with the developer and not shared publicly. Some of these techniques and procedures may be lost over time, as a result of developer attrition . Thus, we present herein a collection that provides protocols, procedures, and techniques for many important field components of pest research and includes studies of common pests of humans and animals, as well as some lesser-studied organisms.The use of recommended field techniques and protocols provides consistency across studies and allows for comparisons of data even across different geographies. A collection of such protocols and techniques serves as a reference point for students and other scientists across many institutions  who are beginning research on pests of medical and veterinary importance. Many of the papers in this collection also provide considerations and potential pitfalls that researchers should be aware of before, during, and after data collection, which will expedite the research study overall. The goal is to preserve and catalog protocols to be shared with generations of future medical and veterinary entomologists.The papers in the special collection include:Oral and Topical Insecticide Response Bioassays and Associated Statistical Analyses Used Commonly in Veterinary and Medical Entomology Labarrus pseudolividus (Coleoptera: Scarabaeidae) and Onthophagus taurus (Coleoptera: Scarabaeidae) Using Flotation and Sieve-Separation Methodology  Beauveria bassiana Culturing and Harvesting for Bioassays With House Flies (se Flies Peromyscus leucopus (Rodentia: Cricetidae) and Peromyscus maniculatus for Vector and Vector-Borne Pathogen Surveillance and Ecology  Collecting and Monitoring for Northern Fowl Mite (Acari: Macronyssidae) and Poultry Red Mite (Acari: Dermanyssidae) in Poultry Systems Collection and Rearing of Container Mosquitoes and a 24-h Addition to the CDC Bottle Bioassay Lipoptena Nitzsch, 1818 and Neolipoptena Bequaert, 1942) and Ticks (Acari: Ixodidae) From Hunter-Harvested Deer and Other Cervids (Collecting Deer Keds (Diptera: Hippoboscidae:  Cervids Trapping White-Tailed Deer (Artiodactyla: Cervidae) in Suburbia for Study of Tick\u2013Host Interaction A Beginner\u2019s Guide to Collecting Questing Hard Ticks (Acari: Ixodidae): A Standardized Tick Dragging Protocol .Lipoptena Nitzsch, 1818 and Neolipoptena Bequaert, 1942)  General Considerations for On-Animal Ectoparasiticidal Product Evaluations Using Visual and Digital Imagery to Quantify Horn Fly (Diptera: Muscidae) Densities Methods for Surveying Stable Fly Populations Sarcoptes scabiei Density in Skin Biopsies (A Tissue Digestion Protocol for Measuring Biopsies A Simple, Inexpensive Method for Mark-Recapture of Ixodid Ticks"}
+{"text": "Background: Positive and effective staff\u2013resident interactions are imperative to adequately assess and meet the needs of cognitively impaired residents in nursing homes and optimize their quality of life. Purpose: The purpose of this study was to quantify, describe, and analyze the interaction between staff and cognitively impaired residents in nursing homes, using the Quality of Interaction Schedule (QuIS). Specifically, the following aims were addressed\u2014 Aim 1: To quantify and describe the quality of interactions between staff and cognitively impaired residents in nursing homes. Aim 2: To analyze whether the quality of staff\u2013resident interactions vary by resident cognitive status (moderate vs severe) and interaction characteristics . Method: This descriptive analysis utilized baseline data from the first 2 cohorts in a randomized clinical trial including 341 residents from 35 nursing homes. Results: Five hundred fifty-six staff\u2013resident interactions were evaluated; majority were positive  and the remaining were either neutral  or negative . The quality of interactions varied by interaction location, interpersonal distance, and resident participation. Conclusion: This study provides some current descriptive information about the quality of staff-resident interactions in nursing homes and the interaction characteristics that might impact these interactions. Future research should focus on decreasing the negative/neutral interactions and explore staff characteristics  and facility factors  that might influence the quality of interactions."}
+{"text": "To further understand social, cultural, and personal predictors of oral health outcomes, this study addressed the relationship between acculturation and subsequent oral health problems and tested the moderating role of neighborhood disorder in such a relationship among older Chinese Americans. The working sample included 2,706 foreign-born community-dwelling older Chinese Americans aged 60 years or older who participated in the Population Study of Chinese Elderly in Chicago at the baseline and the first follow-up. Stepwise Poisson regression using lagged dependent variable was conducted. Behavioral acculturation was protective against subsequent oral health problems. Residence in Chinatown was associated with an increase in the risk of subsequent oral health problems. The relationship between behavioral acculturation and subsequent oral health problems varied by levels of neighborhood disorder. To reduce oral health-related disease burdens, it is important to consider the role of acculturation and the neighborhood on subsequent oral health problems in practice and policy. Part of a symposium sponsored by the Oral Health Interest Group."}
+{"text": "Chronic pain and cognitive decline are common age-related conditions affecting a large segment of older populations. Little is known about the pathway of cognitive functioning during the course of pain management in older adults. The current study aimed to examine the association between chronic body pain management and cognitive function over time among Chinese older adults. A total of 792 respondents aged 60 and above from urban and rural households in 28 provinces, 150 counties/districts, and 450 communities were selected from the China Health and Retirement Longitudinal Study (2013\u20132015). Cognitive function was measured in three domains: episodic memory, mental status, and global cognitive function. Difference-indifferences approach and mixed-effects linear regression models were employed to assess the association between chronic body pain management and cognitive function over time. Scores of mental status were found to decline slower by 0.49 unit  in respondents who received pain management using analgesics, complementary and alternative medicine, or both from 2013 to 2015 after controlling for basic demographic and health confounders. Chronic pain management was associated with slower decline in domain-specific cognitive function, mental status over time. Findings of the study may contribute to understanding the mechanism of change in diverse cognitive abilities attributable to pain symptoms. More research is needed to elucidate the mediating effect of pain on cognitive decline, which could lead to testing of the impact of pain management on cognitive function among older population in both clinical and community settings."}
+{"text": "Gerontology educators continually innovated over multiple decades to create a field characterized by its diversity of programs with a variety of structures to meet a wide range of educational experiences. This paper explores the rich history of how innovations emerged and shares insights on how these grand ideas became broadly accepted practice. Since early 1970\u2019s 6 distinct innovations emerge with sticking power, including convergence upon a core intellectual foundation; support of interdisciplinary education; offering internships or practicums; integration of gerontological training with opportunities provided by community/organizational partners, research affiliates, and alumni to foster applied learning experiences in research, policy, and practice; and, development of leadership across and among generations through the Emerging Scholar & Professional Organization (ESPO)."}
+{"text": "The fifth speaker is Dr. Kali Thomas. Dr. Thomas will discuss her experience working in partnership with government and non-profit organizational stakeholders to conduct aging research that informs policy and practice. Dr. Thomas is an Associate Professor at the Brown School of Public Health and research health science specialist at the Providence VA Medical Center, where her research focuses on identifying ways to improve the quality of life of older adults needing long-term services and supports (LTSS) through applied health services research."}
+{"text": "The aim of this article is to promote the use of knowledge visualization frameworks in the creation and transfer of complex public health knowledge. The accessibility to healthy food items is an example of complex public health knowledge. The United States Department of Agriculture Food Access Research Atlas (FARA) dataset contains 147 variables for 72,864 census tracts and includes 16 food accessibility variables with binary values (0 or 1). Using four-digit and 16-digit binary patterns, we have developed data analytical procedures to group the 72,684 U.S. census tracts into eight and forty groups respectively. This value-added FARA dataset facilitated the design and production of interactive knowledge visualizations that have a collective purpose of knowledge transfer and specific functions including new insights on food accessibility and obesity rates in the United States. The knowledge visualizations of the binary patterns could serve as an integrated explanation and prediction system to help answer why and what-if questions on food accessibility, nutritional inequality and nutrition therapy for diabetic care at varying geographic units. In conclusion, the approach of knowledge visualizations could inform coordinated multi-level decision making for improving food accessibility and reducing chronic diseases in locations defined by patterns of food access measures.  In the context of a community-based food system, research on food access is in the dimensions of availability, accessibility, affordability, acceptability, and accommodation ,2,3. In In the knowledge visualization process, visual representations are designed to communicate experiences, insights and potentially complex knowledge . The groWe focus in this research article on pattern discovery from public health-relevant datasets. The methods for knowledge transfer facilitate effective communication of complex analytic results and uptake of relevant information for policy and priority considerations . KnowledThe visualization types in knowledge visualization are sketch, diagram, image, map, object, interactive visualization and story . Our priThe USDA Economic Research Service (ERS) Food Access Research Atlas dataset is currently the most comprehensive food environment classification at the census tract geographic entity in the United States . We viewThe USDA FARA dataset May 2017 update) (referred to here as the FARA dataset) consist of 72,864 census tracts and 147 variables including new variables on total census tract counts of subpopulations . The USD update  were constructed to respectively describe the status of food access measures and the food desert measures. The inclusion of these binary number patterns as fields in the FARA dataset can expand the type of data analytics techniques  that researchers can apply to further understand the interactions of food access measures in communities. Binary datasets represent a compact and simple way to store data about the relationships between a group of objects and their possible properties .Access to food that is healthy and nutritious is a factor that influences the prevalence of obesity ,26,27. OThe availability of data on adult obesity rates for 2620 census tracts in the Commonwealth of Pennsylvania provided an example dataset to coordinate the knowledge between food accessibility and obesity rates in census tracts of the United States. We expected that a subgroup defined by a pattern of food access measures would contain census tracts with a range of adult obesity rates. Thus, our second research objective was to design and implement knowledge visualizations of census tract subgroups with the same pattern of food access measures but significantly different obesity rates. The subgroups of census tracts could be the basis for research on factors in the food access dimensions that influence differential obesity rates between census tracts of identical patterns of food access measures.The materials and methods reported in this article build on our prior research approaches using visual analytics techniques and technologies ,32,33,34The design and implementation of interactive views of datasets were performed in software for visual analytics following guidelines on (1) interaction design for complex cognitive activities ,36,37; Data Source for Constructing Food Access Patterns for Census Tracts in the United States.(2)Construction of Food Access Patterns using Variables with Binary Values (0 or 1).(3)Design and Implementation of Interactive Visualizations as Solutions for Grouping Census Tracts by Food Access Patterns.(4)Comparison of Obesity Rates in Census Tracts.The remaining description of the materials and methods section is: The datasets associated with the United States Department of Agriculture\u2019s (USDA) Food Access Research Atlas (FARA) were the data sources for constructing the patterns of food access measures for census tracts in the United States . A spreaThe Variable Lookup worksheet has three columns  with a header row and 147 rows of records. The Food Access Research Atlas worksheet has entries in 147 columns and 72,865 rows including a header row. This multivariate dataset has the Census Tract identifier (an 11-digit numeric) as the unique identifier for each record. The variables are categorized as (1) general tract characteristics, (2) low-access and distance measures, (3) vehicle availability, (4) group quarters, (5) low-income and low-access measures, and low access by population subgroups ; Arizona ; Minnesota [St. Louis]; New Mexico [San Miguel]; Oregon [Klamath]; South Dakota [Bennett]; Texas [Uvalde]; Utah [San Juan]; and Washington [Clallam]. The dashboard  integratIn We observed 4654 census tracts designated as low-income low-access (LILA) and were described by six patterns: 0111110111100111 (1 census tract), 1011110111111001 (2 census tracts), 1111111111111001 (13 census tracts), 0011111111100111 (60 census tracts), 0011110111100111 (139 census tracts), and 1011111111111001 (4439 census tracts). The urban census tracts described by binary number 1111111111111001 are in counties located in Alabama, Arizona, Connecticut, Indiana, Maryland, Michigan, Nevada, New York, North Carolina, Ohio, Oklahoma and Texas .We designed a bar plot view to compare the three general tract characteristics (population (2010), median family income, and poverty rate) for the group of 13 census tracts with food access pattern 1111111111111001 . The estAccording to the Food Access Research Atlas documentation, a low-access tract at 20 miles is a rural tract with at least 500 people, or 33 percent of the population, living more than 20 miles from the nearest supermarket, supercenter or large grocery store. Six food access patterns that define low-access tract at 20 miles and their census tract counts are 0111110111100111 (1 census tract); 0100000011100111 (3 census tracts); 0000001011100111 (7 census tracts); 0011111111100111 (60 census tracts); 0011110111100111 (139 census tracts); and 0000000011100111 (178 census tracts). We constructed a geographic map view to display the counties where low-access tract at 20 miles are located . Of the We assigned binary numbers describing food access patterns to 2620 census tracts in a dataset of estimates of obesity rates in adults (2006\u20132010) for 3121 census tracts in Pennsylvania. A box-and-whisker plot design represents data on LILA Patterns, food access patterns, region and 2006 to 2010 estimates of obesity rates . In FiguThe length of the whisker of the box-and-whisker plot (box plot) gives insights on the distribution of the estimated adult obesity rates for census tracts with the same food access pattern. The color of the census tracts encodes regional locations. The upper outlier and lower outlier values provide a guide to the identification of census tracts with significant differences in obesity rates. For example, census tract 42003140100 in Allegheny County (Southwest Pennsylvania) is compared to census tract 42081000800 in Lycoming County . The visualization also provides a motivation to seek details on the reason(s) for the differences in the obesity rates. The box plot in The aim of this article is to promote the use of knowledge visualization frameworks in the creation and transfer of complex public health knowledge. We are developing a series of knowledge visualizations, which represent new knowledge and communicates complex data analytic results on the 18 May 2017 version of the Food Access Research Atlas (FARA) dataset. We recognized that datasets and visual representations from public health-relevant datasets must provide explanation (why) and prediction (what-if) to support priority setting and evaluation work of health system decision makers . Thus, oWe then integrated the valued-added FARA dataset with a dataset on the 2006 to 2010 estimates of adult obesity rates in 2680 census tracts of the 67 counties of the Commonwealth of Pennsylvania. A value added to the obesity data is a regional context . The dataset from Pennsylvania presents a use case for the knowledge visualizations produced . From a Based on our findings, we propose that knowledge visualization resources developed with public health-relevant datasets could be designed as integrated explanation and prediction system for public health research and practice. A major implication of our research is to inform decision making for improving food accessibility and reducing obesity rates in the United States ,49. The We have designed and implemented the knowledge visualizations for explanation and prediction in health systems decision making to follow guidelines on the functions ; and design principles of knowledge visualization ,16. AddiOur first research objective was to design and implement knowledge visualizations that communicate census tracts in the FARA dataset as subgroups defined by binary numbers. Thus, we have developed a knowledge visualization (that combines an enclosure table and a bar plot) for attention and new insights on the distribution of the absence (0) or presence (1) of the 16 FARA food access measures (variables) in the 72,684 census tract dataset . The couIn We observed 388 census tracts described as low-access tract at 20 miles. Several factors predispose residents of rural areas in the United States to a higher risk of chronic diseases such as obesity compared to residents of urban areas ,59. AddiAccording to the conceptual framework of the food environment, the inputs to the food environment are from production, storage, transformation and transportation of food . The fooOf the 72,864 census tracts in the FARA dataset, 41,994 census tracts are low-income tracts (digit 8 of the 16 digit food access pattern) . We obseThe knowledge visualizations in The limitations and strengths of secondary data analysis could affect the results of our research . The objOur focus on interactive visualization makes it necessary for the use of online access see . We haveThe aim of this article is to promote the use of knowledge visualization frameworks in creation and transfer of complex public health knowledge. Datasets of national public health relevance such as the Food Access Research Atlas (FARA) present opportunities for interactive data visualization techniques of cognitive, social and emotional benefits. We have designed and implemented knowledge visualizations that have the collective purpose of knowledge transfer and specific functions of attention, recall, elaboration, motivation, coordination, and motivation. The knowledge visualizations communicate knowledge on food access patterns and obesity rates age geographic levels of regional, county, and census tracts. This multi-level approach could inform coordinated multi-level decision making for improving food accessibility and reducing chronic diseases in locations defined by food access measures."}
+{"text": "Objectives:This study aimed to investigate the mediating roles of coping styles and stroke knowledge between social support and uncertainty in illness among patients with primary stroke in China. Methods:The total of 204 Chinese primary stroke patients recruited using convenience sampling were asked to answer Mishel Uncertainty in Illness Scale for Adult(MUIS-A), Stroke Knowledge Questionnaire(SKQ), Social Support Rating Scale(SSRS), and Medical Coping Modes Questionnaires (MCMQ). Demographics characteristics of the patients were presented using descriptive statistics. We reported the relationship between the study variables using Pearson\u2019s Correlation Coefficients. We performed structural equation modeling to estimate the mediator effect of coping styles and stroke knowledge between social support and uncertainty in illness.Results: The results showed that 92% of patients with primary stroke had moderate above level of uncertainty in illness, with a mean score 75.04 (SD=9.61).Uncertainty was positively associated with coping styles , and negatively associated with social support and stroke knowledge .The structural equation model indicated that the coping styles and stroke knowledge respectively acted as mediator role between social support and uncertainty in illness.Conclusions:Most patients with primary stroke present moderate above level of uncertainty in illness. stroke knowledge and coping styles were important mediating factors in the pathway between coping styles and uncertainty in illness. Our findings suggest the provision of stroke knowledge and training of coping styles for patients with primary stroke could alleviate their uncertainty in illness."}
+{"text": "This data article is about bats observed from fragmented forest understories interspaced by agricultural plantations, utility corridors, and man-made structures within rural areas of Setiu (Bukit Kesing Forest Reserve and Ladang Tayor TDM) and Hulu Terengganu  that are situated in Terengganu state, Peninsular Malaysia. Surveys were conducted from October 2018 until January 2019. These bats were captured using harp traps and mist nets that were set 30 m apart across flyways, streams, rivers and less cluttered trees in the 50 m transect zones (identified at each site). All animals captured were distinguished by morphology and released at the same location it was caught. The data comprise of 15 species of bats from four family groups, namely Hipposideridae, Pteropodidae, Rhinolophidae and Vespertilionidae. The data were interpreted into weight-forearm length (W-FA) to inform about bats Body Condition Index (-0.25 to 0.25). Specifications table\u2022Data on abundance and distribution of bats are beneficial for the scientific community to understand diversity patterns and spatial distribution of bats species within their habitat which is important for interpreting ecological processes as bats such as pollinator of orchard and agricultural plantation crops, dispersal agent of seeds, and natural biological control predator of insect pests.\u2022Data on bat species from different guilds is necessary for scientific community to investigate the effects of monoculture agriculture on abundance, diversity, and foraging behaviour of frugivorous bats.\u2022Sex and life stage\u00a0data will allow scientific community to determine key reproductive features such as timing of reproductive activity, and to determine seasonal patterns in body masses of adult males and females in relation to energetic costs of different stages of the life cycle.\u2022Body condition index that indicate individual fitness of bats could be extended towards predicting reproductive traits and survival of bats, resource acquisition and allocation, nutritional status, immune-competence and stress.\u2022Data on different methods of sampling bats can give an opportunity to scientific community to assess the variation among species of bats in their susceptibility to traps.\u2022Comparative abundance of bats in fragmented and non-fragmented habitats, scientific community can explore further about the variety of bats present in agricultural, rural s, inhabited and forested areas and examine the effects of landscape changes on bats. Such information is important and useful for the authorities for planning and implementation of species conservation and management.1The dataset in this article is constructed using field survey results that indicate abundance of bats in fragmented forests within Terengganu state with all captured bats were identified, and enumerated. 2Our field team visited two districts Setiu (Bukit Kesing Forest Reserve and Ladang Tayor TDM) and Hulu Terengganu  between October 2018 and January 2019. We sampled each site for seven days (six nights). We used four-bank harp traps, which we set up about 1 m above the ground level and mist nets with the help of two poles to support the net following"}
+{"text": "The development of health and social services should be based on a thorough needs assessment with all stakeholders, followed by ongoing monitoring of implementation and subsequent short and long term outcomes. Relying on four different service models, this symposium reviews their evaluation processes and summarizes the main lessons learned, in order to inform future efforts. Wyman and colleagues outline efforts to develop culturally-sensitive dementia care services for American Indian and Alaska Native older adults and caregivers using qualitative interviews and community-based participatory research methods. Findings offer guidance for culturally-tailored implementation of services. Shepherd-Banigan et al. report on a quantitative needs assessment of over 1,500 caregivers of older Veterans enrolled in Veterans Administration healthcare. Providing care to individuals with co-morbid conditions predicted higher levels of distress and burden among caregivers, pointing to likely benefit from additional caregiver-focused support programs. The paper by Gum and co-authors moves to assessment of outcomes by examining mortality and other outcomes among older adults screened by an Area Agency on Aging and either receiving or waiting for services. Finally, the paper by Ayalon and Shinan-Altman use service evaluation to demonstrate the importance of needs assessment and the gap between the vision of service developers and real life constraints. The included papers discuss the value of various methodologies, illustrating the important role that assessment and evaluation play in service development and implementation for older adults and caregivers."}
+{"text": "Technology holds great potential to support those aging with and into disability. Research and development efforts in the aging space (aging into disability) have traditionally focused on improving health conditions, whereas those in the disability space (aging with disability) have primarily focused on supporting activity and participation. Bridging these perspectives and approaches adds rich context to guide the development and evaluation of technology interventions. Examples of technology interventions that support activity and participation and thereby improve health outcomes for adults aging with mobility disabilities show the need for bridging. The Telewellness research study used videoconferencing to deliver an evidence-based tai chi intervention to small groups. The Digital Assistant study explored the potential of the Amazon Echo to support controlling the home environment, engaging in physical activity, interacting with others, and managing health. Both projects offer credence to the value of supporting adults aging-in-place with wide range of capabilities and limitations. Part of a symposium sponsored by the Lifelong Disabilities Interest Group."}
+{"text": "Mycobacterium bovis and Mycobacterium tuberculosis are the most common causes of TB in animals and humans, respectively. Integral to TB control strategies are the communities affected by this epidemic. Tuberculosis awareness by the community is an effective TB control strategy as education empowers people to make informed choices with regard to mitigating TB risk factors in their daily lives. We conducted a knowledge, attitude and perceptions survey in Mnisi pastoral community in South Africa using a semi-structured questionnaire to evaluate the level of bovine TB (bTB) awareness, and provided informed feedback to the community on the outcome of the study. Although participants were aware of TB, the knowledge of the zoonotic potential of bTB and about susceptible hosts was limited. The study findings showed knowledge gaps regarding common risk factors, including coughing while herding cattle, unsupervised/uninspected communal slaughter and improper disposal of infected meat. In contrast, it was noted that the majority of participants discarded meat with visible lesions and consumed pasteurised milk; thus, the risk of TB transmission via the ingestion route is low. Tuberculosis knowledge gaps were evident in the community, and public health and veterinary authorities need to improve relationships with stakeholders and implement awareness programmes that use a one health approach.Tuberculosis (TB) is a global health concern of zoonotic importance, and  Mycobacterium bovis is the causal agent of bovine tuberculosis (bTB), an infectious and chronic disease in animals and humans  pandemic , with approximately 12 832 cattle and 15 diptanks  (N): 552 farmers; hypothesised % frequency of outcome factor in the population (p): 50% \u00b15; confidence limits as % of 100(absolute \u00b1%)(d): 5%; design effect (for cluster surveys-DEFF): 1. Using proportional representations, 127 farmers were recruited for questionnaire administration (minimum of 20 and maximum of 30 farmers per diptank\u2019s catchment area). All questions were prepared in English and translated into Xitsonga, the lingua franca of the community. Data were captured, filtered and analysed for descriptive statistics using Microsoft ExcelThe project was approved by the University of Pretoria Animal Ethics Committee (AEC) (certificate number v116-16) and the Faculty of Health Sciences Research Ethics Committee (certificate number 374/2016). Informed consent was obtained from all the participants who were briefed about their right to withdraw from the study if they wished so and guaranteed confidentiality.A total of 110 participants completed questionnaire . ApproxiM. bovis   Musoke . The reaThe respondents suggested to improve veterinary services through the provision of more facilities and extensive repairs of current infrastructure. Certain individuals displayed a clear disconnect and some level of mistrust between the community and veterinary services. Such opinions or perceptions include top-down approach to policy formulation or implementation, veterinary officials sometimes carry out procedures on livestock without explaining the basis and purpose of the procedures to owners and lack of adequate feedback from earlier studies conducted in the community. In Britain, breakdown in relationships between the state authorities and farmers was linked with differential farmer attitudes and views to most effective scientifically based interventions and the practicality of state recommendations on bTB (Cowie et al."}
+{"text": "The pioneering Age-Friendly University (AFU) initiative, endorsed in 2016 by GSA\u2019s Academy for Gerontology in Higher Education (AGHE), calls for institutions of higher education to respond to shifting demographics and the needs and interests of our aging populations through more age-friendly programs, practices, and partnerships. This symposium will focus on AFU Principle 9 that advocates for engaging actively with an institution\u2019s retired community. Appreciating the diversity of ways in which this principle can be put into practice, participants will discuss the various ways their AFU campuses have built connections with members of their local communities of retired adults. Montepare (Lasell University) will discuss the living and learning model of the institution\u2019s affiliated-retirement community (Lasell Village) that coordinates engagement in 450 credit hours of educational activity as a benefit of residency. Berman (Ithaca College) will discuss the Gerontology Institute\u2019s longstanding relationship with the Longview senior living community and how intergenerational educational and social experiences serve as enriching activities for students, faculty, and residents. Elfenbein (University of North Georgia) will discuss campus collaboration with The Wisdom Project, a community organization of adults 55+ interested in using their skills and talents to benefit their community through action and advocacy projects. Wenrick (Drexel University) will discuss Writers Room, a university-community literary arts program, and their intergenerational co-living initiative, creating a network of homeowners and student tenants whose shared interest in writing and storytelling forms the foundation for meaningful cohabitation."}
+{"text": "Background: Jingyin granule is one of the widely used traditional Chinese medicine mixture composed of multiple herbs in the treatment of respiratory system diseases. The mechanism of its therapeutic effects has still been obscure. The aim of this study is to use the network pharmacology approach for identification of the main active ingredients of Jingyin granule against COVID-19 targets and to explore their therapeutic mechanism.Material and Method: In this study, the ingredients of Jingyin granule were evaluated by the usage of Traditional Chinese Medicine Systems Pharmacology Database and Traditional Chinese Medicine Integrated Database, and the interactions between potential gene targets and ingredients were identified using the SwissTargetPrediction database. Meanwhile the possible efficient targets COVID-19 acts on were identified via Online Mendelian Inheritance in Man database, DisGeNET database and GeneCards database. In addition, functions, components and pathways were identified by Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein interaction, ingredients-targets network was established.Results: Our findings showed that numerous ingredients of Jingyin granule could act on COVID-19 with 88 target genes. GO enrichment analysis, KEGG pathway analysis, and protein-protein interaction network revealed that these targets were interrelated with regulation of immune function, directly targeting disease genes.Conclusions: Jingyin granule could be utilized to exert systematic pharmacological effects. Jingyin granule could directly target the major genes, and also regulate the immune system, acting as oblique disease treatment. Early in December 2019, an atypical pneumonia became epidemic in Wuhan, China In the treatment of COVID-19, the combination of Chinese and western medicine has achieved good clinical efficacy in China Jingyin granule has been used in Shuguang hospital affiliated to Shanghai University of traditional Chinese medicine for more than 40 years for lung-wind-heat cold, acute bronchitis and acute pneumonia. It is safe and effective for the respiratory diseases of wind-heat syndrome with fever, aversion to cold, sore throat and cough as the main symptoms. It has also won numerous battles against the epidemic such as SARS, human influenza A (H1N1) infection. Jingyin granule can be utilized as a mixture of valuable chemical probes for the investigation of complex biological processes and identification of potential therapeutic target genes or molecules. However, the particular molecular mechanisms exploring how Jingyin granule takes effects are rarely studied.Network computational methods are now utilized not only in structure-based drug design and pharmaceutical development, but also in better comprehending the mechanism of how an ingredient of compounds act at the molecular biology level and in this way to discover the therapeutic effect. Nevertheless, because of the prodigious amount, it is impractical to experimentally screen all possible interactions between ingredients of compounds and target proteins. Therefore, computational modelling and network approaches are considered to be notably theoretical methods which can also accurately identify potential drug-target interactions in order to provide evidence for basic experimental studies In this study, the pharmacological effects and machanisms of Jingyin granule were elucidated systematically by using computational methods. First, the ingredients of Jingyin granule was evaluated by the usage of the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) TCMSP database and TCMID database are resources of system pharmacology for the Chinese medicines or relavant compounds which are both informative about identified ingredients of herbs. TCMSP database also provide detail information of the ingredients, include characters of absorption, distribution, metabolism, and excretion (ADME).Among all the ADME properties, oral bioavailability (OB) and drug likeness (DL) are the foremost features of orally medicines because of their vital roles in assessing the velocity and percentage of the oral drug absorbed and reaching the systemic circulation. In this study, each herb of Jingyin granule was searched to find out identified ingredients in both databases, and all identified ingredients were searched in TCMSP database to screen potential druggable ingredients following the criteria: 1) OB \u2265 30%; 2) DL \u2265 0.18 Because of the similarity and homology of SARS-COV-2, MERS-COV and SARS-COV, target genes of diseases caused by these three viruses were searched and screened by GeneCard database, OMIM database and DisGeNET database. All the search results are merged, and reduplicate targets are removed to acquire all the potential target of the diseases. Target genes of ingredients were searched and screened by SwissTargetPrediction database. Jingyin granule matched the target prediction results of effective ingredients with the searched results of diseases related target genes and intersection targets were collected as the relevant potential targets of Jingyin granule for the treatment of COVID-19, which might be the potential therapeutic target set.http://www.genome.ad.jp/kegg/) database is a common database which provides annotation and visualization of pathways to identify relevant genes with similar functions.GO analysis is widely used for genes and gene products annotating, including molecular functions (MF), biological processes (BP), and cellular components (CC). The Kyoto Encyclopedia of Genes and Genomes  has been validated as a mediator and regulator of inflammatory responses and microbial products or proinflammatory cytokines which could induce the expression of NOS2 in a large number of inflammatory and tissue cells In summary, Jingyin granule is an active compound of herbs or a superb mixture of ingredients that could be further studied to discover a multiple target medicine with anti-infection effects. By using bioinformatic methods, this study provides a novel insight into the investigation of Jingyin granule, one of the widely used traditional Chinese medicine and offers an overview of its application in future clinical application."}
+{"text": "In the present paper, Mohosen et al.  reviewed(HLA) polymorphisms. Growing attempts are necessary to adopt emerging prophylactic and therapeutic vaccines for the prevention and control of major infectious and noninfectious diseases."}
+{"text": "Several sets of proteins exist in eukaryotic cells wherein accurately localized in appropriate cellular locations containing plasma membrane, cytoplasm, nucleus and different membrane-enclosed organelles. Each protein is involved in distinct biochemical processes within the normal cell; therefore, the correct subcellular localization of protein is vital; as it provides the physiological context for protein function. However, protein mislocalization described as changing the appropriate subcellular localization of protein, was reported as a key feature of many proteins in a variety of human cancers The mechanisms by which subcellular mislocalization is arising in cancer are various and deeply reviewed by Wang and Li The aberrant subcellular position of proteins in cancer tissues has been investigated broadly by antibody-based strategies including Immunohistochemistry (IHC). The major localization of sortilin on cell surface of ovarian carcinoma tissues rather than the main resident in ER-Golgi compartment of normal tissues was detected using IHC technique The property of malignant cells in differently subcellular localization of proteins might be recruited as an intelligent strategy for detection of malignant but not normal cells in clinical diagnostic and prognostic applications In conclusion, the subscellular mislocalization of proteins is a frequent event in cancers defined as an accessory approach for proliferation, survival and invasion of tumors. However, targeting and trapping proteins in specific cellular compartments has been conceptualized as a promising approach for diagnostic, prognostic and therapeutic clinical use."}
+{"text": "Loss of balance and risk of falls is a major problem in older persons. Literature shows increasing use of yoga practices and dance therapy across Indian oldage homes and day care centres to improve balance and reduce risk of falls in older persons. Aim of this study is to evaluate the effects of dance therapy with focus on therapeutic movements derived from Indian classical dances on balance and risk of falls in older adults of Day Care Centres in Calcutta Metropolitan Institute of Gerontology, under Ministry of Social Justice and Empowerment, Govt. of India. Total of 24 older adults across 2 day care centres participated in the study attending dance therapy sessions for 3 months. All of them self reported problems of balance and repeated falls alongwith difficulties in performing Activities of Daily Living. Twenty one of them were females and 3 males. The mean age of the participants was 75.5 years. Limits of Stabililty (LOS) was used to measure balance and pre tests and post tests were performed. Results showed that the Limits of Stability were significantly higher (17.5%) in older persons after participating in the dance therapy sessions. This study supports that dance therapy using movements derived from Indian classical dance forms can support older persons to function with reduced risk of falls, improved balance, safely carry out mobility tasks and perform better Activities of Daily Living . Further studies can show how dance therapy can facilitate healthy ageing and influence State policies on healthy ageing."}
+{"text": "Alzheimer\u2019s and related dementias (ADRD) disproportionately affect the African American community. Brain donation, a crucial part of translational research, is less common among African American research participants compared to White research participants at Alzheimer\u2019s Disease Research Centers (ADRCs) across the US. Existing literature suggests three categories of contributory factors for African Americans: concerns and misconceptions about brain research and brain donation; religious beliefs; and the role of the family. Existing knowledge of community interventions is limited. We conducted seven focus groups, stratified by brain donation intent and cognitive status, to capture the perspectives of African American research participants. Qualitative content analysis reveal the following contributory themes: personal connection to memory loss or dementia; altruism; spirituality/religion; historical and current racism in health care and research; trauma and objectification; trust; representation; understanding the purpose and process of brain donation; and fluidity in decision-making. Future research will explore trauma-informed and culturally responsive interventions. Part of a symposium sponsored by the Alzheimer\u2019s Disease Research Interest Group."}
+{"text": "To the Editor,Neurological prognosis is one of the great concerns for the survivors of cardiopulmonary resuscitation. Ai and colleagues demonstrated that the higher mean arterial pressure (MAP), as far as below 100\u2009mmHg, was associated with better neurological function among the survivors of cardiopulmonary resuscitation.The timing of MAP measurement might be unclear. Their findings would further improve when the authors identify the most appropriate timing of MAP measurement: for example, on admission to intensive care unit (ICU), on discharge from ICU, or the average of whole ICU stay. Association between MAP and imaging analyses at serial time points might also more clarify the impact of MAP on neurological function.The authors found the association between MAP and neurological function,The authors stated that the cessation of blood flow during a cardiac arrest results in the formation of microvascular thrombosis that impairs the cerebral vascular autonomic regulation system.Teruhiko Imamura receives grant support from JSPS KAKENHI: JP20K17143."}
+{"text": "In the original article, the Ethics Statement was incomplete as it only included the name of one of the institutions. The corrected statement appears below.The studies involving human participants were reviewed and approved by Ethic committee Istituto Ortopedico Rizzoli IRCCS, Regina Elena National Cancer Institute IRCCS, Bambino Ges\u00f9 Children's Hospital IRCCS and by the proper institutional review boards of the CRO Aviano IRCCS National Cancer Institute, Veneto Institute of Oncology (IOV) IRCCS, University of Padua, Candiolo Cancer Institute FPO-IRCCS, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Meldola IRCCS, Istituto Nazionale dei Tumori di Milano Fondazione IRCCS. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."}
+{"text": "Dear colleagues and friends,The year 2019 is almost at an end, and our Polymer Analysis section has experienced another fruitful year of high-quality Special Issues and scientific papers devoted to different topics of polymer analysis.In particular, some of them thoroughly investigated new insights on flame retardance of biopolymer composites , polyurFurthermore, special attention was devoted to the design, preparation, and characterization of polymer micro- and nanocomposites containing modified graphene oxide (Octadecylamine-Grafted Graphene Oxide Helps the Dispersion of Carbon Nanotubes in Ethylene Vinyl Acetate ), hydrotSignificant developments were also achieved in the characterization of crystallization phenomena taking place in polymers and polymer composites (How Chain Intermixing Dictates the Polymorphism of PVDF in Poly(vinylidene fluoride)/Polymethylmethacrylate Binary System during Recrystallization: A Comparative Study on Core\u2013Shell Particles and Latex Blend ; DevelopFinally, a very challenging and up-to-date paper assessed the suitability of additive manufacturing ) for tissue engineering applications .Polymers. I would remind all of you that 15 Special Issues are still open and ready to receive your valuable manuscripts.All these few examples clearly witness the activity in the Polymer Analysis section of I hope that in 2020 the Polymer Analysis section will continue to grow and expand with the help of all the Editorial Board, the Editorial Staff, and (last but not least) all the readers and authors!"}
+{"text": "Field Canals Improvement Projects is an important sustainable project to save fresh water in our world. Machine learning and artificial intelligence (AI) needs sufficient dataset size to model and predict the cost and duration of Field Canals Improvement Projects. Therefore, this data paper presents dataset includes the key parameters of such project to be used for analyzing and modelling project cost and duration. The data were acquired based on questionnaire survey and collecting historical cases of Field Canals Improvement Projects. The data consists of the following features: area served, total length of PVC pipe line, number of irrigation values, construction year, geographical zone, cost of FCIP, and duration of FCIP construction. The data can be applied to compare and evaluate the performance of machine learning algorithms for predicting cost and duration. Specifications Table\u2022The data explains the key cost drivers of Field Canals Improvement Projects (FCIPs).\u2022The dataset is important for irrigation authorities and stakeholders such as contractors, engineers and decision makers to estimate the conceptual cost of FCIPs based on financial and feasibility perspectives.\u2022The data objective is developing a reliable parametric cost or duration estimation model at the conceptual phase for Field Canals Improvement Projects (FCIPs).\u2022The data can be applied to compare and evaluate the performance of machine learning algorithms for predicting cost and duration.\u2022Data can be used as a benchmark data to assess the accuracy of other novel frameworks or models against the developed models in the previous studies \u2022The data can be conducted to applied advanced computational theories and algorithms such as fuzzy-genetic model and deep learning algorithms.1Construction cost estimation can be applied for several projects such as Irrigation 2Questionnaire survey and collecting historical cases of Field Canals Improvement Projects have been conducted to collect the data using Delphi rounds as Developing a reliable parametric cost estimation model consists of two main stages: key cost drivers identification and machine learning model development As shown in Secondly, a comprehensive tool for parametric cost or duration estimation can be developed using ML algorithms such as multiple regression analysis and the optimum neural network model. The data objective is developing a reliable parametric cost estimation model before the construction of FCIPs. Therefore, a total of 1276 FCIPs of constructed projects are collected to build up the proposed model. This data can be used for executing the most common artificial intelligence (AI) techniques which are conducted for cost modeling such as fuzzy logic (FL) model, artificial neural networks (ANNs), regression model, case-based reasoning (CBR), hybrid models, and evolutionary computing (EC) such as genetic algorithm (GA)[1] as showed in"}
+{"text": "Medical Bionics or neuroprostheses are active implantable devices designed to: (i) provide therapeutic intervention, sensory feedback or motor function via electrical stimulation of nerves or muscles following trauma or disease; and/or (ii) record the electrical activity from nerve or muscle to detect disease states, enable the voluntary control of devices such as prosthetic limbs or provide closed-loop feedback to modulate neural prostheses.There have been many bionic devices approved for clinical use; the modern neurotechnology industry is dominated by five major commercial applications including: (i) auditory prostheses that provide auditory cues for severe and profoundly deaf; (ii) spinal cord stimulation (SCS) for treatment of chronic back pain; (iii) vagal nerve stimulation for the control of epilepsy and treatment of depression; (iv) deep brain stimulation (DBS) for motor control in Parkinson's disease (PD) and essential tremor, and (v) sacral root stimulation for improved bladder and bowel function. These devices have had a dramatic impact on the quality of life of millions of people around the world and have generated an industry worth US$12.0 billion by 2020 [New neuroprostheses are being developed at an astonishing rate, with successful technologies nurtured under a multidisciplinary environment in order to deliver both safe and effective devices. These technologies are, by necessity, built on advances in engineering, electronics, materials science, electrochemistry, battery technology, neuroscience, clinical and surgical practice, and improved rehabilitation techniques.The aim of this Special Issue is to bring together eight examples of technological development that hold promise in future clinical application.Leccardi and Ghezzi review the potential use of organic materials in neuroprostheses with specific emphasis on their use at the electrode/neural interface. These polymers offer both mechanical and electrochemical advantages over the use of metal electrodes and can be relatively simply introduced into existing manufacturing techniques. Richardson and colleagues review the advantages and limitations of optical stimulation of neural tissue. Direct optical stimulation via infrared light or through the use of optogenetics, have the potential to achieve higher precision of neural activation compared with electrical stimulation. Kosta, Loizos and Lazzi present a computational investigation of improved stimulus waveforms for application in retinal prostheses. They describe a class of asymmetric biphasic pulses that can generate precise ganglion cell firing patterns with up to 55% lower current requirements compared to traditional current pulses. McDermott and Sinclair review the application and benefit of adaptive DBS in PD by automatically adjusting each patient's stimulation settings in response to their ever-changing needs. A biomarker that estimates the severity of motor impairment and is linked to an adaptive control algorithm to optimises the stimulation is presented. Parker, Karantonis and Single describe the closed-loop control of SCSs used to maintain a predetermined level of neural recruitment, and propose a hypothesis to explain the difference in efficacy between open-and closed-loop operational modes. This work provides a rational basis for directing clinical research and improving SCSs. Kilgore and colleagues review the optimal architecture of multi-function neuroprostheses for spinal cord injury with particular emphasis on powering strategies. They describe the significant advantages associated with a wired multipoint implant technology with a centralized power supply. Steadman and Grill describe novel SCS techniques to restore bladder control in spinal cord injury. While SCS provides a clear pathway to sustainable commercial availability and clinical impact, further research, directed at effective stimulation parameters and the appropriate timing and location of stimulation, is required. Finally, Parker and Dietz report on the potential application of SCS to reduce spasticity associated with cerebral palsy. Reviewing the small number of clinical reports using this approach, the authors propose a mechanism of action based on current understanding of SCS and provide techniques that enable improved tuning of these devices for more substantial relief from symptoms.In closing I would like to thank Professor Christopher James (Editor-in-Chief), Dr Helen Dyball (Executive Editor), and all contributing authors for their generous support of this Special Issue."}
+{"text": "Using data from three waves  of the National Health and Aging Trends Study (NHATS) linked to the National Study of Caregiving (NSOC), we identified family caregivers of those with advanced dementia and compared caregiving strain among those with zero, <20, and 20+ hours/week paid care. Family caregivers of those who received 20+ hours (26% of the sample) reported less caregiver strain  and less frequently reported having more to do than they could handle  or not having enough time for themselves . The association persisted in a multivariable model. These results support the conceptualization of dynamic and potentially multidirectional relationships between paid and family caregivers and suggest that paid caregivers impact both those receiving care and their families."}
+{"text": "Identifying individuals at clinical high risk (CHR) for psychosis leverages a critical window of opportunity for prevention and early intervention. The characterization of effective detection and therapeutic strategies for this population represents one of the most unmet needs of contemporary psychiatry. The purpose of this Research Topic is to reflect on the similarities and differences in clinical, cognitive, biological, cultural and social aspects of CHR samples from different cultures and countries. This topic issue presents 3 perspectives, 1 study protocol, 4 reviews, and 4 original research articles which span the field of CHR research in different countries and offer insightful directions for future study and comprehensive practical suggestions in improving the efficacy in early intervention.Schiffman et al., argue that the current \u201cone-size-fits-all\u201d approach of CHR identification does not fully reflect individual differences, particularly in context, ethnicity, race, culture, and development. They propose practical strategies for improving the accuracy of CHR identifications within and across different cultural settings. A culturally specific example, by Parabiaghi et al., describes the implementation of early detection and treatment of severe mental illness in youth across multiple regions of Italy. Promoting local community coalitions and an emphasis on accessibility, their broad preventive approach identified a group of 15\u201324 year olds enriched for CHR status. Finally, Kennedy et al., discuss what is needed from a public health perspective to extend systematic screening for early psychotic symptoms to general practice clinics.All three perspective pieces speak to the degree to which current CHR methods are identifying and serving the actual target population. Mahmood et al., describe a specific protocol to test a novel intervention in an underserved Latino CHR population in two different languages (Spanish and English) and countries (the United States and Mexico). This efficacy pilot is comparing Compensatory Cognitive Training (CCT) with recreational therapy (RT) to target cognitive and functional outcomes. Trials that extend the inclusiveness of the population served and real-life outcomes measured have important implications for the relevance of CHR efforts to public health.Oliver et al. review the limitations of current structured interviews for identifying CHR and propose to address them with a Psychosis Polyrisk Score (PPS) prototype based on non-genetic risk factors, including social context. In a conceptual but non-systematic review furthering attention to sampling biases, Fusar-Poli et al., illustrate risk detection models targeting three different populations: secondary mental health care, primary care, and the community . From their review of the evidence, the authors argue for the international advancement of CHR detection through complementary approaches. Transdiagnostic individualized risk calculators must be tested and implemented in primary and secondary care and digital and/or sequential screening in community samples. The final review on this topic extends the literature covered to include the prediction of outcomes in individuals identified using established structured interviews of CHR. Based on a meta-analysis of the largest sample of individualized data , their model achieved only moderate prognostic value. They argue that the high level of heterogeneity in samples worldwide limits the clinical value of any one predictive model.Improving the detection of CHR-P individuals is the topic of three reviews. Fusar-Poli, on behalf of the Healthy London Partnership, reviews the evidence for established integrated and youth-friendly mental health services. In spite of the lack of robust controlled trials on their impact, early intervention for psychosis services may provide a paradigm to lead further reform.Finally, since the 0 to 25 years is a vulnerable developmental period during which children and young people experience many psychosocial and neurobiological changes, Won et al., explores the characteristics and patterns of emotional recognition deficits in 495 patients with early psychosis. Their results show the correlation between symptom severity and the extent of emotional recognition deficits for different emotions. Examining the clinical characterization of schizotypy dimensions in a largely adolescent student sample  from northern Spain, Fonseca-Pedrero et al., estimates a multidimensional psychosis liability network, a dynamic and complex system of risk and protective factors.Two original research studies investigate clinical and behavioral characteristics of early psychosis in culturally diverse samples. A study from the Korean Early Psychosis Cohort by Liu et al., investigates the resting-state functional connectivity of the alpha rhythm measured by electroencephalography (EEG) to test a hypothesis of abnormal functional connectivity. Both early psychosis groups (first-episode schizophrenia and CHR) show an increased degree of connectivity compared with healthy controls, especially in the left occipital lobe area which is higher in the CHR group than in the first-episode schizophrenia group. Bonoldi et al., examine the relationship between basic self-disturbances and alterations in cortical midline structure volume measured by magnetic resonance imaging (MRI). They find that the higher level of basic self-disturbances in CHR individuals appear to be related to reductions in anterior cingulate volume.Two other studies target the biological correlates of CHR syndromes and symptoms. Taken together, the high-quality contributions gathered in this Research Topic highlight both the promise and limitations of extant research for identifying, understanding, and helping CHR individuals across different cultures and countries. Several important and exciting efforts have been completed or are in progress, but much work still remains to be done. These articles provide international research collaborators with the key insights to further improve the tools and methods for identifying CHR individuals, and for developing effective interventions as well.TZ, JW, and KW have contributed intellectual content and have contributed to the actual writing of the editorial.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Preferences for Everyday Living Inventory (PELI) was mandated as a pay for performance indicator by the Ohio Department of Medicaid in 2015. This study explored the impacts of PELI implementation on regulatory outcomes in 2017.The level of PELI implementation from n=551 Ohio nursing home providers between 2015 and 2017 were linked with Centers for Medicare and Medicaid Services Nursing Home Compare data. Fixed effects panel regression analyses assessed the effects of time-varying PELI implementation on 2015-2017 regulatory outcomes that could be correlated with quality of life including fines, substantiated complaints, health scores, deficiency counts and deficiency scores.Results show a significant increase in substantiated complaints among providers that were slow adopters of the PELI. Overall, the extent of PELI implementation was not associated with regulatory outcomes.The use of the PELI may not impact substantiated complaints suggesting further research is needed to identify person-centered outcomes of interest. Part of a symposium sponsored by the Research in Quality of Care Interest Group."}
+{"text": "For several decades, the history of interdisciplinary education and the development of AGHE initiatives have been closely linked. The need to educate colleagues on methods and benefits of interdisciplinary/ interprofessional cooperation toward service and research of aging has never waned. In this presentation we (a) highlight how AGHE has performed as a potent incubator for progress in this area and (b) use a few examples to illustrate how notable resulting efforts have improved geriatric care. For example, early and significant infusion of federal funds for gerontology training programs supported multi-disciplinary university-based centers, the Veterans Health Administration created interprofessional geriatric training programs, foundations such as John A. Hartford and Josiah Macy founded team training and interprofessional education programs, and the Health Resources and Services Administration funded Geriatric Education Centers and Geriatric Workforce Enhancement Programs. Efforts to advance interdisciplinary/interprofessional education have been fruitful and AGHE\u2019s role as an incubator continues to evolve."}
+{"text": "Perceived control is an important psychological resource for middle-aged and older adults. Aging in place may help foster feelings of control and autonomy, yet many community-dwelling older adults must rely on others for physical assistance. Little is known about psychological reactions to receiving this support. This study investigated how receiving home care from different sources was associated with two facets of perceived control (mastery and perceived constraints) among adults with varying levels of physical disability. Data was drawn from the 2012 and 2014 waves of the Health and Retirement Study. Community-dwelling adults aged 50 years and older receiving help for at least one activity of daily living (ADL) impairment (N = 884) reported their relationship to each respective caregiver , level of ADL impairment, and ratings of perceived control. Ordinary least squares (OLS) regression was used to examine the association between type of support and perceived control and the moderating effect of physical disability on that relationship. Receiving formal or a combination of formal and informal support was related to perceptions of greater control over one\u2019s life, but only in terms of mastery. The level of one\u2019s ADL impairment did not have a moderating effect on the relationship between support type and perceived control. Findings suggested that the type of instrumental support adults receive in their home has implications for specific facets of perceived control. Those receiving formal or mixed support had perceptions of greater mastery than those only receiving informal support."}
+{"text": "Objectives: To examine whether caregiver (CG) depression predicts subsequent occurrence of elder abuse and whether change in the severity how care-recipient change in the severity of care recipient (CR) neuropsychiatric symptoms influence this association. Methods: Using two-year longitudinal data, we analyzed a consecutive sample of 800 Chinese family CGs and their CRs with dementia recruited from the geriatric and neurological departments of three Grade-A hospitals in People\u2019s Republic of China (PRC). All the participatory dyads were assessed between September 2015 and February 2016 and followed for two years. Results: CG depression at baseline predicted the subsequent occurrence of physical and psychological abuse and CG neglect. However, change in the severity of CR neuropsychiatric symptoms altered these relationships. Specifically, while unchanged and increased CR neuropsychiatric symptoms heightened the positive effect of CG depression on subsequent abuse, decreased CR neuropsychiatric symptoms protected older adults from abuse by a depressed CG. Conclusion: This study showed the differential impact of CG depression on subsequent occurrence of elder abuse depending on the change in the severity of neuropsychiatric symptoms related to the CRs. The present findings provide important insights to the design of a systematic and integrative intervention protocol for elder abuse that simultaneously focuses on treating CG depression and CR neuropsychiatric symptoms."}
+{"text": "Despite the widespread use of antiretroviral therapy, HIV-associated neurocognitive disorder (HAND) continues to be one of the most common central nervous system complications of human immunodeficiency virus type 1 (HIV-1). The severity and prevalence of HAND underscores the need for safe, effective therapies to mitigate or eliminate the impacts of the disorder to improve the quality of life of individuals living with HAND. The current study conducted a systematic review of the literature regarding experimental studies of clinical therapeutic interventions for HAND. An electronic search of four databases  initially returned 4,280 articles, 31 of which met the inclusion criteria for this study. Articles were selected for inclusion based on several criteria, including the use of a clinical experimental study design and measurement of neuropsychological performance. A large number of studies were excluded due to utilizing observational or cross-sectional designs, relevance, or for otherwise not meeting inclusion criteria. The results of this review revealed 31 articles that investigated both pharmaceutical and cognitive therapies for HAND. Pharmaceutical interventions range from common antiretroviral therapies to novel drug classes with various mechanisms of action. Importantly, this review revealed a number of limitations present in the greater body of HAND research including inconsistencies among methods of diagnosis of HAND and study design, which ultimately make comparisons across studies difficult. This review presents the current evidence that exists regarding therapies for HAND and broadly discusses trends, limitations, and gaps in the literature."}
+{"text": "The Conference was focused on the discussion of the research on gene pools of the world\u2019s nations, ancient DNA analysis, possibilities of judicial genetics, population-genetic database development, biobanks, and new genomics technologies. It was a unique event referred to as the 100th anniversary of the first human population study in 1919.Human population genetics has more than hundred year history. Modern next-gen sequencing technologies, genotyping and bioinformatics extended the research boundaries raising new genetics problems. This special issue of BMC Genetics presents the selected works studies discussed at the \u201cCentenary of Human Population Genetics\u201d conference in Moscow in May 2019, organized on the base of Moscow State University (http://conf.bionet.nsc.ru/sbb2019/en/). The SBB School series on bioinformatics is organized annually since 2008 by the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences and Novosibirsk State University [This journal special issue contains materials on human genetics and genomics presented at the conference in Moscow and SBB-2019 (Systems Biology and Bioinformatics - 2019) School in Novosibirsk in 2019 (iversity .https://bgrssb.icgbio.ru/2020) multiconference with genetics sessions [The SBB Schools in Novosibirsk are satellite events for BGRS\\SB (Bioinformatics of Genome Regulation and Structure \\ Systems Biology)  is a development gene which is likely to affect optic disk area by altering the expression of the associated genes via long-range interactions. Role of gene regulatory regions in the human genome were discussed in [GFI1 repressor gene expression, which might be the cause of increased optic disk area characteristic of the East Asian populations.Work by Vladimir Babenko and colleagues  . We invite our readers worldwide to attend the systems biology meetings in Russia - Digital Medicine Forum and MGNGS-2020  event postponed to 2021 (http://ngs.med-gen.ru/mgngs20/).We aim to support international exchanges and education in the form of international conferences and schools for young scientists on bioinformatics, genetics and systems biology  (https:/"}
+{"text": "This presentation discusses the importance of using digital technologies on reducing mental health disparities among older adults from diverse backgrounds. This talk primarily focuses on the role of ethnicity, socioeconomic status and geography. First, the speaker presents the current status of digital technology use among older adults and how different levels of digital technology use affect mental health disparities by ethnicity, SES, and place of residence. Second, the speaker introduces a recently funded government project on developing an IoT-based home system (Internet of Things) to screen mild cognitive function for Korean older adults. Lastly, the speaker discusses potential implications, as well as directions for future research on using digital technologies to reduce mental health disparities among diverse populations."}
+{"text": "Since the escalation of coronavirus disease 2019 (COVID-19) pandemic, over a billion people across the world have faced restrictions due to varying degrees of confinement, and in the absence of a vaccine against SARS-CoV-2, massive public health interventions have been implemented to contain the outbreak. The lockdown set up in many countries to combat the COVID-19 epidemic entails unprecedented disruption of lives and work, determining specific risks related to mental and physical health in the general population, especially among those who stopped working during the current outbreak .The World Health Organization (WHO) classified physical inactivity as the fourth leading risk factor accounting for 6% of global mortality, following hypertension (13%), smoking (9%) and diabetes (6%). The relationship between physical inactivity and obesity trends was quite evident since 1953 when the London Busmen Study showed that bus drivers who mainly sat during work presented with larger waist circumferences, higher levels of adiposity and increased risk of coronary events than bus conductors, who walked the aisles and climbed the stairs of double-decker buses .Physical inactivity levels are rising in many countries with significant implications for the prevalence of non-communicable diseases and the general health of the population worldwide. The WHO recommends that adults accumulate at least 150 min of moderate to vigorous-intensity physical activity (MVPA) or 75 min of vigorous-intensity physical activity (VPA) throughout the week, cumulated in bouts lasting \u226510 min. This volume of physical activity (PA) is associated with a lower risk of cardiovascular (CV) morbidity and mortality and a number of other healthcare benefits (Recent evidence suggests that sedentary behavior (SB) is independently associated with traditional CV risk factors and increased CV morbidity and global mortality, regardless of PA volume . SB is dThus, physical inactivity and SB should be considered as separate entities with their unique determinants and health consequences, but with synergistic harmful effects on CV health .While containing the spreading of the contagion as quickly as possible is the urgent public health priority, there have been few public health guidelines for the public as to what people can or should do in terms of maintaining their daily exercise or PA routines , 10. SafWHO just released guidance intended for people in self-quarantine without any symptoms or diagnosis of acute respiratory illness, containing a set of practical advice on how to stay active and reduce SB while at home. WHO further highlights how standard recommendations of 150 min of MVPA or 75 min of VPA per week, or a combination of both, can still be achieved even at home, with no special equipment and with limited space.There is a robust health rationale for staying active at home in the current precarious environment, for all age groups. The following are general recommendations, unless otherwise specified.Specific recommendations and tips for children, adults, and elderly are further detailed in While recognizing the importance of confinement policies set up to contain COVID-19 pandemic, we firmly recommend the relevance of home-based programs for disruption physical inactivity and sedentary behavior as a critical behavioral strategy for the prevention of global health and consequences of psychosocial stress during the current lockdown.FR and PI drafted the manuscript. All co-authors provided critical revision for important intellectual content.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Questionnaire-based binary indicators of sleep sufficiency and sleep quality in each cohort were assessed with respect to objectively measured green space exposures adjusting for age, sex, and maternal education. Models were augmented with proxy measures of traffic noise and two-way interaction terms to test for effect modification. Cross-tabulations illustrated little convincing evidence of association between green space and insufficient sleep or poor sleep quality in either sample, except for insufficient sleep among 10 year old participants in Germany. These null findings were replicated in adjusted models. The proxy for traffic noise was associated with poor quality sleep in 15 year old participants in Germany, but no convincing evidence of modified association with green space was observed.Increasing evidence suggests adults living in greener areas tend to have more favourable sleep-related outcomes, but children and adolescents are under-researched. We hypothesised that children and adolescents living in greener areas would have better quality and more sufficient levels of sleep on average, especially within the context of high traffic noise exposure. These hypotheses were tested using multilevel logistic regressions fitted on samples from the nationally representative Longitudinal Study of Australian Children (10\u201311 years old,  Accumulating evidence suggests that poor quality and insufficient sleep in adults may increase the risks for depression , obesityInterventions across multiple levels beyond the individual , are needed to improve levels of quality and sufficient sleep at the population-level . BuildinPsychological benefits of nearby green space may help to restore depleted cognitive capacities and relieve periods of chronic stress . In turnBetter sleep-related outcomes were found to be associated with greater exposures to nearby green space in a recent systematic review of seven cross-sectional studies and five intervention studies . These pTo build on this seminal work, more research is needed on green space and sleep focussed on child and adolescent populations with objectively measured exposure data. This work would also ideally involve an accounting of age-related differences in sleep-related outcomes that are known to occur across childhood and adolescence .Accordingly, the objective of this study was to examine associations between nearby green space and multiple measures of sleep in child and adolescent samples living in different countries\u2014Australia and Germany\u2014sites of previous studies linking nearby green space with favourable child and adolescent mental health outcomes e.g., ,41). Two. Two41])\u201cGerman Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development\u201d (GINIplus), and the \u201cInfluence of life-style factors on the development of the immune system and allergies in East and West Germany\u201d (LISA). The Australian Government Department of Social Services and the ethical committee from the University of Wollongong (HREC 2019/015) approved the data analysis from the LSAC study. For the GINIplus and LISA studies, the ethical approval was given by the Bavarian Board of Physicians, the University of Leipzig, and the Board of Physicians of North Rhine-Westphalia.Data were drawn from samples aged 10\u201311 years old and 14\u201315 years old from cohort studies in Australia   and Germn = 4169) and 2014 (n = 3537) waves of the kindergarten cohort of the LSAC. Participants in the LSAC had been originally recruited in 2004 at ages 4\u20135 years from postcodes distributed across Australia (79.4% baseline response rate). Sampling drew from the Medicare enrolment database and a spatially clustered design was used to ensure coverage across all states and territories )Indirect contrasts in results from two well-recognised cohorts in two countries with broadly comparable outcome, confounders, and objectively measured exposure measures is a strength within the context of a literature replete with single-setting studies. By integrating results from multiple settings and data sources, this affords opportunities for triangulation to strengthen potentially causal inferences. A priori declaration of assumptions in the form of a directed acyclic graph is also important for justifying which variables were adjusted in our regression models. Other strengths included the relatively large sample sizes and balanced sex ratios in both cohorts.In conclusion, children and adolescents in greener areas did not have higher odds of getting sufficient amounts of, or good quality sleep. These null findings were consistent, regardless of traffic noise exposure. This runs counter to increasing evidence suggesting that green space in cities could support better sleep outcomes in adults ,37 and o"}
+{"text": "Despite frequent recognition of disparities in cognitive functioning between White and non-White older adults, the pathways or mechanisms through which race affects cognitive functioning have yet to be elucidated. The research questions addressed in this paper are: 1) Is there a relationship between racial minority status and cognitive functioning in middle and later life? 2) To what extent do social resources  mediate the relationship between racial minority status and cognitive functioning? 3) Finally, drawing on intersectionality theory, if social resources do mediate the relationship between racial minority status and cognitive functioning, to what extent is this mediation effect moderated by the interaction of gender and Socioeconomic Status (SES)? Using cross-sectional data drawn from the Canadian Longitudinal Study on Aging (CLSA) with a sample of over 50,000 Canadians (2010-15) aged 45 to 85 years, multivariate regression analyses  assess the mediating effect of social resources on the relationship between racial minority status and cognitive functioning. Controlling for age, gender and other relevant determinants, preliminary results reveal that racial disparities in cognitive functioning  exist in Canada and that this relationship is partially mediated by some indicators of social resources . Our findings suggest the need for interventions targeted at increasing social resources for racial minority groups to cope with the risk of developing cognitive impairment in later life."}
+{"text": "Repairing DNA damage is one of the most important functions of the \u2018housekeeping\u2019 proteins, as DNA molecules are constantly subject to different kinds of damage. An important mechanism of DNA repair is the mismatch repair system (MMR). In eukaryotes, it is more complex than it is in bacteria or Archaea due to an inflated number of paralogues produced as a result of an extensive process of gene duplication and further specialization upon the evolution of the first eukaryotes, including an important part of the meiotic machinery. Recently, the discovery and sequencing of Asgard Archaea allowed us to revisit the MMR system evolution with the addition of new data from a group that is closely related to the eukaryotic ancestor. This new analysis provided evidence for a complex evolutionary history of eukaryotic MMR: an archaeal origin for the nuclear MMR system in eukaryotes, with subsequent acquisitions of other MMR systems from organelles.The online version of this article (10.1007/s00239-020-09979-5) contains supplementary material, which is available to authorized users.  The archaeal ancestor in turn, probably acquired the mutS laterally from a bacterial group very long ago, before the evolution of the first eukaryotes , Arabidopsis (green plants), Saccharomyces (Fungi), Dictyostelium (Amoebozoa) and Monocercomonoides (a flagellated protist assumed to be early branching among eukaryotes).A strategic sampling of Saccharomyces, Arabidopsis or Homo. They were used as a starting point. Different eukaryotic paralogues were aligned with 100 iterations of MAFFT (Katoh and Standley hmmbuild (Eddy ), which was employed to build both MutS and MutL profiles used in the searches. Profiles were employed by HMMER tool hmmsearch (hmm 358 kb)(trim 68 kb)(contree 11 kb)(txt 11 kb)(trim 152 kb)(contree 11 kb)(trim 102 kb)Below is the link to the electronic supplementary material."}
+{"text": "The objective of the Symposium is to make progress in understanding the causes and mechanisms of health-related disparities in Alzheimer\u2019s disease, related dementias and other prominent age-related diseases. Topics will cover a range of academic and administrative topics including: i) partitioning analysis of disparities and time trends in Alzheimer\u2019s Disease and Related Dementia; ii) a structural model approach to ethnic disparities in dementia and its assessment; iii) traumatic brain injury and dementia in the Medicare population: differences in genotype and phenotype-related risk between veteran and non-veteran subsets; iv) geographic disparities in county-level prevalence of Alzheimer\u2019s disease across the United States; and v) the role of comorbidities in the geographic disparities of AD/ADRD mortality. A focus will be made on evaluating patterns of race/ethnicity and geographic health disparities as well as changes in time trends in AD/ADRD prevalence and mortality; identifying the causes and describing the mechanisms of these respective processes, and demonstrating how they can be identified in studies using established administrative data resources such as Medicare claims databases; and demonstrating how innovative analytic approaches such as partitioning analyses, structural model approaches, and methods of latent data analyses can be used in conjunction with empirical and regression approaches to uncover previously overlooked or understudied aspects in this area of research. Analyses of such increasingly available large health datasets provides an opportunity to obtain nationally representative results based on individual-level measures that reflect the real care-related and epidemiological processes generating disparities and time trends in AD/ADRD health outcomes."}
+{"text": "Myxacorys almedinensis and two other cyanobacteria were isolated from the limestone walls of the Old Cathedral of Coimbra, Portugal (UNESCO World Heritage Site). The high-quality genome sequences presented here will be essential for characterization purposes and description of the novel taxa.The recently described species  Myxacorys almedinensis and two other cyanobacteria were isolated from the limestone walls of the Old Cathedral of Coimbra, Portugal (UNESCO World Heritage Site). The high-quality genome sequences presented here will be essential for characterization purposes and description of the novel taxa.The recently described species  Epilithic and endolithic cyanobacteria are known to cause severe esthetic and physicochemical alterations to stone substrata \u20133. Due t\u2013Myxacorys almedinensis coi00094076  has been recently described (Nostoc sp. B (2019) and Synechococcales cyanobacterium C are currently being performed. In this article, we present the high-quality draft genome sequences of three isolated strains that were retrieved from the limestone walls of the Old Cathedral of Coimbra. The samples were collected by scraping off green/dark-green biofilms with the help of a sterile scalpel. The cyanobacterial strains were isolated from liquid BG11 enrichment cultures (\u22122 s\u22121) until they had developed enough biomass for DNA extraction (During an experimental survey aimed at fully characterizing the community of microalgae and cyanobacteria of the Old Cathedral of Coimbra, Portugal, three novel cyanobacterial taxa were isolated . The strcultures  by meanstraction  with deftraction  with deftraction  with defPRJNA596374. This submission encompasses both the raw data and assembled data.The data from this whole-genome sequencing project have been submitted to NCBI under the accession number"}
+{"text": "This study is among the first to investigate whether and how socioeconomic inequalities in the receipt of formal and/or informal care by disabled older adults vary across long-term care (LTC) systems. We link data from the SHARE survey with LTC system indicators for 136 regions in 12 European countries in 2015. Using multinomial multilevel models with cross-level interactions, we test whether and how income and wealth gradients in the receipt of only informal, only formal, and mixed care vary with the number of beds in residential LTC facilities across regions. We find pro-rich inequalities in the receipt of formal and mixed care only in regions with low or intermediate numbers of LTC beds, and no inequalities in regions with greater availability of residential beds. Our findings suggest that the presence of extensive formal LTC services may lead to a fairer distribution of formal and mixed care use across socioeconomic groups."}
+{"text": "Comparative microbial genomics analysis by high-throughput whole-genome sequencing (WGS) offers exquisite resolution for epidemiological investigations of infectious disease. This approach has revolutionized outbreak detection and monitoring of transmission dynamics of infectious agents and antimicrobial resistance across humans, animals, and environment. The objective of this Research Topic was to assemble articles on genomic epidemiological approaches to identify sources and mechanisms of transmission of infection and antimicrobial resistance. Leading experts discuss advances in fine-tuning the WGS laboratory workflows and bioinformatics for analyzing viral, bacterial, and protozoan genomic data as well as best available WGS data sharing and vizualization tools for infectious disease surveillance and control. The Research Topic consists of 13 articles on public health applications of comparative genomics of key human and zoonotic pathogens, including Original research, Reviews, Systematic Review and Curriculum, instruction, and pedagogy reports.Theys et al. review cutting-edge phylodynamic analysis tools and visualization solutions for translating these data into information for disease control decisions by public health and health policy professionals. They discuss bioinformatics platform use for temporal and spatial visualization through examples for tracking viral disease dissemination across populations and monitoring viral evolution and adaptation.The ongoing COVID-19 pandemic underlines the crucial need for open access to advanced viral infectious disease surveillance systems that integrate genomic and epidemiological data on epidemic pathogens in real-time. Hendriksen et al. describe the value of bacterial genomics for monitoring the global threat of antimicrobial resistance by efficient and rapid identification of genetic determinants of drug resistance. They review the operational characteristics, functionalities, strengths, and limitations of bioinformatics tools and knowledge bases accessible online for these purposes. They offer their expert perspective for standardization of analytical pipelines and database validation for more robust genomic-enhanced antimicrobial resistance surveillance.Ribeiro Duarte et al. report on their e-learning and crowdsourcing pedagogic experience to explore expectations and opinions as well as educate academic, public health, and food safety professionals on the potential of microbial metagenomics in surveillance of pathogens and antimicrobial resistance. They ran a blended training exercise followed by massive open online interactive course to disseminate metagenomics knowledge and skills to a global audience of research and surveillance experts and gather their opinions. A majority of participants expected a slow transition to metagenomics for surveillance and food safety risk assessment subject to further harmonization of experimental protocols and interpretation of results.. Clostridioides (Clostridium) difficile is an important enteric pathogen in the healthcare setting where it causes both sporadic and epidemic infections with substantial morbi-mortality. It is increasingly frequent as a community-acquired pathogen although infection sources remain elusive. In a mini-review, Janezic and Rupnik summarize the WGS-based typing schemes for C. difficile and compare the merits of single nucleodide variant typing and core genome multilocus sequence typing (cgMLST) methods for surveillance and cluster investigations. They highlight how WGS-based studies help elucidating the global population structure of C. difficile, mapping the intercontinental spread of epidemic lineages, resolving relapses, and reinfections in recurrent disease and evaluating the effect of disease prevention measures. Knight and Riley review the diverse ecological reservoirs of C. difficile from a One-Health perspective. Micro-evolutionary studies are revealing how the open pan-genome of several successful zoonotic lineages that have adapted to different ecological niches. This foster their global spread between food animals and farm environment to humans under the selective pressure of antimicrobial use in livestock and human medicine.The value of next-generation sequencing technologies for surveillance and study was reviewed for several human pathogensvan der Werf and K\u00f6dm\u00f6n report on a systematic review of three international tuberculosis outbreak investigations that were supported by WGS-based typing. WGS data analysis from different sequencing platforms used the SNV mapping approach with diverse bioinformatics tools. WGS analysis was helpful in supporting evidence from epidemiological data for delineating outbreak-related-cases and excluding unrelated ones. Further standardization of WGS methodology and data sharing procedures is desirable for tuberculosis control.Morris et al. assess the state-of-the-art genome sequencing methods for Cryptosporidium species identification and genotyping in the public health setting. Technical hurdles relate to genomic DNA extraction, sequencing depth, and assembly. Biological complexity is challenging due to sexual recombination of the parasite and multiplicity of infection in humans and animals. While WGS is not yet feasible for routine genotyping, the increasing volume of Cryptosporidium genome data available from diverse hosts and geographical sources is helping design novel genotyping markers and better understand its population diversity and virulence variation.Seth-Smith and Egli have examined current evidence on high-resolution typing of Corynebacterium diphtheriae using WGS for surveillance of this re-emerged pathogen in low incidence settings and describe international networks supporting this new approach to the control of diphtheria. The authors review the phylogeny of this diverse species and explain how the timing of disease can be inferred from WGS data. They argue that de-centralized sequencing strategies with redundancy in sequencing capacities, followed by data exchange, may be a valuable future option, especially as WGS becomes more available and portable.Chattaway et al. describe the transformational impact of WGS on reference microbiology practice and public health laboratory surveillance for Salmonella. They document experience from Public Health England and review challenges of implementing WGS as a routine country-wide reference laboratory service. Their experience started in 2014 and led to the radical transformation of public health practice based on the integrated and cross-disciplinary analysis and decision-making. The authors explain how this transformation led to improved accuracy of results, reduced turn-around times of reports and better recognition and monitoring of smaller and geographically dispersed outbreaks of common Salmonella serovars and outbreaks of prolonged duration. They outline the PHE approaches to the bioinformatics pipelines, detection of antimicrobial resistance in foodborne bacteria and integrated analysis of data. The authors also remind us about the essentiality of inter-agency sharing and comparisons of microbiological, epidemiological, and food chain analyses for effective food safety and control.Several contributions to this Research Topic have focused the attention on the added value of genomic surveillance for controlling foodborne diseases. Gerner-Smidt et al. from the US Centers of Disease Control and Prevention who presented compelling evidence for the One Health approach to foodborne surveillance. They argue that such an approach takes public health surveillance to the next level as many foodborne outbreaks ultimately originate from animal or environmental sources. The authors illustrate the power of this approach in helping to successfully solve several persistent community outbreaks, including polyclonal listeriosis associated with contaminated ice cream, multidrug resistant Salmonella Heidelberg linked to contaminated chicken, an outbreak caused by six serotypes of Salmonella associated with consumption of an imported herbal supplement, and multidrug resistant Campylobacter linked to contact with puppies sold by a specific pet store chain. Such outbreaks are significantly more complex than typical point source outbreaks and might be difficult to solve using traditional epidemiological approaches. This paper presents examples of how WGS surveillance enables flexible outbreak case definitions and efficient epidemiological traceback.These messages are reinforced and expanded by Pietzka et al. demonstrates the potential of genome sequencing in identifying sources of outbreaks of listeriosis. The authors utilized a core genome MLST scheme based on 1,701 target genes to type over six thousand isolates of Listeria monocytogenes from human and food associated sources. The typing results helped to identify a community outbreak in eastern Austria and trace back the source of the outbreak to one meat-processing company. The whole-genome sequence based typing yielded better accuracy and higher discriminatory power than pulsed-field gel electrophoresis as well as higher laboratory throughput at a lower cost. These findings are of particulars relevance to public health microbiologists as the growing proportion of elderly citizens drives up listeriosis notifications across many countries in the EU and Northern America.An insightful report from the Austrian Agency for Health and Food Safety led by Seth-Smith et al. aim to improve our understanding of whole genome sequencing protocols employed for laboratory surveillance. The authors evaluated three popular library preparation protocols based on enzymatic fragmentation which are fast and require minimal amounts of genomic DNA. They provided in-depth analysis of WGS results obtained from libraries prepared by Nextera XT (Illumina), Nextera Flex (Illumina), and QIAseq FX (Qiagen) protocols using a set of 12 reference strains representing pathogenic bacteria with different DNA guanine-cytosine (GC) content. The results suggest that Nextera Flex and Qiaseq FX are less sensitive than Nextera XT to variable GC content. Interestingly, more alleles were detected in the cgMLST analysis with these two best library preparation protocols, producing better discrimination of closely related genomes. Furthermore, these protocols achieved a more complete representation of accessory genes and ensured the detection of every antibiotic resistance gene from short read data with coverage of 50 or higher.We hope both public health professionals and clinicians will find this issue useful for their practice. The editorial team thanks external reviewers for their constructive criticism and hopes that this issue of Frontiers in Public Health will assist healthcare professionals and scientists involved in translational research and genomics-informed public health laboratory surveillance and will be of interest to everyone who is passionate about international efforts to control communicable diseases.MS and VS jointly drafted and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Background: In 2014 the World Health Organization (WHO) warned of an emerging world-wide crisis of antibiotic-resistant microorganisms. In response, government and professional organizations recommended that health care systems adopt antimicrobial stewardship programs (ASPs). In the United States, the Centers for Medicare Services (CMS) mandated antimicrobial stewardship in the hospital inpatient setting. Effective 1 January 2020, the Joint Commission required ambulatory centers that prescribe antibiotics, such as wound centers, to institute an ASP. Chronic wounds often remain open for months, during which time patients may receive multiple courses of antibiotics and numerous antimicrobial topical treatments. The wound clinician plays an integral role in reducing antimicrobial resistance in the outpatient setting: antibiotics prescribed for skin and soft tissue infections are among the most common in an outpatient setting. One of the most challenging aspects of antimicrobial stewardship in treating chronic wounds is the inaccuracy of bacterial and infection diagnosis. Methods: Joint Commission lists five elements of performance (EP): (1) identifying an antimicrobial stewardship leader; (2) establishing an annual antimicrobial stewardship goal; (3) implementing evidence-based practice guidelines related to the antimicrobial stewardship goal; (4) providing clinical staff with educational resources related to the antimicrobial stewardship goal; and (5) collecting, analyzing, and reporting data related to the antimicrobial stewardship goal. This article focuses on choosing and implementing an evidence-based ASP goal for 2020. Discussion: Clinical trials have demonstrated the ability of fluorescence imaging (MLiX) to detect clinically significant levels of bacteria in chronic wounds. Combined with clinical examination of signs and symptoms of infection, the MLiX procedure improves the clinician\u2019s ability to diagnose infection and can guide antimicrobial use. In order to satisfy the elements of performance, the MLiX procedure was incorporated into the annual ASP goal for several wound care centers. Clinicians were educated on the fluorescence imaging device and guidelines were instituted. Collection of antimicrobial utilization data is underway. The world-wide emergence of antibiotic-resistant bacteria endangers the efficacy of antibiotics and increases the morbidity and mortality associated with infectious diseases ,2,3. In The outpatient wound care center features prominently in the development of antimicrobial resistance for several reasons: antibiotic prescriptions written in the outpatient setting are most commonly for skin and soft tissue infections; the typical wound is open for more than three months, during which time the patient may receive repeated courses of antibiotics and topical antimicrobials; and uninfected wounds with excessive inflammation are often misdiagnosed and treated as infected ,9. More S. aureus) to fluoresce red while Pseudomonas aeruginosa uniquely fluorescence cyan and tissue fluoresces green . In. In18]. This manuscript proposes a straightforward evidence-based method to establish an ASP in the outpatient wound care center, using point-of -care fluorescence imaging to visualize high bacterial load. Data on topical antimicrobial and antibiotic use will be collected from advanced wound care centers across the United States. The pandemic has delayed implementation; however, antimicrobial stewardship will soon become part of standard wound center reporting. The ultimate goal is for wound care centers to share this information. The cumulative data on antimicrobial use will improve patient care and inform future ASP interventions."}
+{"text": "Objective: This study aims to analyze how older adults express themselves sexually. For this purpose, a qualitative research was carried out, which analyzes their perspectives at a cross-national level. Methods: Four hundred and ninety five older participants aged 65 to 98 years, were interviewed. Participants were of three different nationalities and lived in the community. All the interviews went through the process of verbatim transcription and subsequent content analysis. Results: Results of content analysis produced nine themes: Tender and care ; altruism and gratitude ; attractiveness ; positive communication ; sexual activity ; good health and physical condition ; supportive relationship ; eroticism ; and feeling active and alive . Conclusions: This study stressed different ways on expressing sexuality in old age and underlined the importance of tender and care and eroticism for older adults who are sexually active. Keywords: Content analysis; older adults; qualitative study; sexual expression."}
+{"text": "The United States spends $50 billion each year on 2.8 million injuries and 800,000 hospitalizations older adults (age 65 years and older) incur as the result of falls. Chronic use of central nervous system (CNS)-active medications, such as opioid and/or benzodiazepine (BZD) medications, increases the risk of falls and falls-related injuries in this older adult population. This Centers for Disease Control and Prevention (CDC)-funded randomized control trial uses electronic health record (EHR) data from primary care outpatient clinics to identify older adult patients at risk for falls due to chronic opioid or BZD use. The primary program aim is to test the efficacy of a targeted consultant pharmacist service to reduce the dose burden of these medications in the targeted population. Impact of this intervention on the risk of falls in this population will also be assessed. Licensed clinical pharmacists will review at-risk patients\u2019 medical records weekly and make recommendations through the EHR to primary care providers for opioid or BZD dose adjustments, alternate medications, and/or adjunctive therapies to support deprescribing for approximately 1265 patients in the first two cohorts of intervention clinics. One thousand three hundred eighty four patients in the control clinics will receive usual care. Outcome measures will include reduction or discontinuation of opioids and BZDs and falls risk reduction as measured by the Stop Elderly Accidents, Death and Injuries (STEADI) Questionnaire. Primary care provider adoption of pharmacists\u2019 recommendations and satisfaction with the consult service will also be reported."}
+{"text": "Unpaid and paid care in the home are closely intertwined, but a lack of outside supervision and support often forces family and non-family caregivers to negotiate care tasks and boundaries alone, leading to role conflict and role ambiguity. This analysis drew on two qualitative studies of home health aides  to explore 1) aides\u2019 perception of their caretaking role; 2) aides\u2019 experiences co-producing care with family members; and 3) factors affecting these relationships. Data were analyzed through grounded theory and discourse analysis. We identified three relationship dynamics between aides and family members: independent, where aides and families provided care separately; competitive, where aides and families struggled over control of care tasks; and carative, where aides considered family part of the unit of care. We propose strategies for employer agencies to better support paid and unpaid caregivers in negotiating boundaries and co-producing care."}
+{"text": "In a similar vein, we previously examined the impact of posterior left atrial wall isolation on the restoration of sinus rhythm.2 Our examination of 57 patients with persistent or high-burden paroxysmal atrial fibrillation  reconfirmed the difficulty in obtaining acute electrical isolation of the posterior LA  and failed to prove a statistical benefit regarding the treatment of recurrent arrhythmias. We have, however, seen the favorable resolution of atrial fibrillation in our convergent patients who demonstrated elimination of posterior left atrial signal during the procedure.3The report by Nagarakanti et al.1 present and the procedural success of the Cox maze procedure lend convincing support for the isolation of the left atrial free wall in patients with advanced atrial fibrillation. The creation of contiguous, transmural ablation lines that electrically isolate the left atrium and pulmonary veins acutely and chronically is likely to improve procedural outcomes. The Epi/Endo Ablation for Treatment of Persistent Atrial Fibrillation (CONVERGE) trial (NCT01984346), which aims to study the treatment of symptomatic persistent AF patients who are refractory or intolerant to at least one class I or class III antiarrhythmic drug via the use of the EPi-Sense\u00ae-AF Guided Coagulation System with VisiTrax\u00ae , has almost completed enrollment and is expected to provide additional insight regarding this question.The embryological and fibrotic considerations Nagarakanti et al."}
+{"text": "Despite the current pressure to reduce state and federal spending, policymakers must find ways to address the challenges of a growing population of older adults with complex health care problems. There is an increased need for the health professions workforce to have collaborative care skills and geriatric clinical competencies. Therefore, programs like the Geriatric Workforce Enhancement Program (GWEP) and the Geriatric Academic Career Awards (GACA) are important in strengthening the workforce and supporting policy development that addresses increased demands on the health care system. In 2019, the Bureau of Health Professions, under the Health Resources and Services Administration, provided 48 GWEP awards and 26 GACA awards in 37 states and 2 territories. These programs play an important advocacy role to improve on and expand geriatric education. This symposium provides an overview of these programs and their role in advancing geriatric care and in shaping policy."}
+{"text": "Global environmental and energy issues are the two major challenges of the 21st century. Climate change and the energy crisis have urgently called for the establishment of sustainable and innovative solutions to tackle these issues. Among the many established strategies, the emergence of functional nanocomposites as potential tools to address environmental and energy-related issues has attracted wide attention in both laboratory research and industry applications. The synergistic effects concertedly contributed by a broad range of nanomaterials and their host materials have rendered unprecedented advantages over the conventionally used materials. With the astonishing chemical and physical properties exhibited by various nanocomposites, their potentials have been unlocked in many practical applications. Nanocomposites are also particularly interesting in offering sustainable solutions to curb global challenges related to environmental issues and energy shortages.This Special Issue, themed \u201cNanocomposites for Environmental and Energy Applications\u201d, gathers material scientists and engineers working in this realm to look into various aspects associated to the development of the state-of-the-art nanocomposites dedicated for environmental and energy applications. A collection of research articles and reviews, with special attentions focused on the synthesis, design, optimization and applications of novel nanocomposites has been compiled in this Special Issue. The nine contributions (seven research articles and two reviews), look into the recent advancement and future trends related to the development of nanocomposites.4 and reduced graphene oxide (rGO) [4 and rGO of different dimensions  were synthesized and coupled to form a heterojunction semiconductor. It was observed that 2D\u20132D chemical coupling of BiVO4 and rGO exhibited the highest visible light activated photocatalytic activity toward the degradation of acetaminophen. The findings highlighted the importance of dimensional factors in the design of heterojunction photocatalysts. Lee et al. prepared mesoporous-rich activated polymer-based hard carbon to be used as electrodes in electrical double-layer capacitors [3/carbon composite microspheres on a large scale [3 nanocrystals were evenly distributed within the amorphous carbon matrix. The resultant MoO3/carbon composite microspheres achieved higher Li-ion storage compared to MoO3 owing to their greater high structural stability and electrical conductivity.Carbon-based nanocomposites are an important class of functional nanomaterials for the remediation of environmental issues and the development of energy-related devices. Sun et al. engineered the dimensional interface of nanocomposite composed of BiVOde (rGO) . BiVO4 a2) into the 3D crossed region of stacked plasmonic Ag nanowires to enhance the photocatalytic activities [2 interface rendered efficient hot electron transfer. The synergistic effects endowed the hybrid material with high photocatalytic performance across the ultraviolet and visible light spectral regions.The removal of heavy metals from wastewater using through adsorption and electrochemistry approaches has been investigated. Tan et al. reported an enhanced sludge treatment to remove Cu (II) ions followed by the application of the copper-doped porous materials as supercapacitor electrode materials . The imptivities . In thisThe two review articles compiled in this Special Issue were contributed by Subramaniam et al.  and Tu eThe diverse contributions from these nine articles have witnessed the roles and importance of nanocomposites for environmental and energy applications. The versatilities of nanocomposites in addressing pollution and energy shortage issues have been evidenced. These contributions have addressed some of the important fundamental questions and shed light on the better understanding of the natures of the newly developed nanocomposite materials. It is hoped that this Special Issue could provide some useful guidelines for the future development of nanocomposites for environmental and energy applications."}
+{"text": "Fear of falling is a known predictor for decreased health-related quality of life (QoL) in older adults, including among high risk frail community-dwelling older adults with multiple comorbidities including depression. The study aimed to examine the sequential explanatory roles of frailty and depressive symptoms in the relationship between fear of falling (FoF) and QoL in a program for all-inclusive care for the elderly (PACE). This was a retrospective single cohort study that included 84 older adults in a PACE program located in the Northeastern United States. Participants were cognitively intact older adults \u226555 years . FoF was assessed with the Falls Efficacy Scale-International; frailty was measured with the Edmonton Frail Scale; QoL was measured with the Short Form 12v2 which includes both physical and mental domains. Using the Process Macro (model 6) in SPSS, path models were constructed hypothesizing frailty and depressive symptoms as serial mediators of the relationship between FoF and QoL while controlling for race, gender, age and comorbidities. Frailty and depressive symptoms serially mediated the FoF and mental QoL relationship . Serial mediation effects of frailty and depressive symptoms were not replicated for the association between FoF and physical QoL . Understanding the roles of frailty and depressive symptoms in explaining the association between FoF and mental health-related QoL can delineate targeted areas for intervention development not typically considered when attempting to reduce the influence of FoF on QoL in older adults."}
+{"text": "Allosteric regulation is a common mechanism employed by complex biomolecular systems for regulation of activity and adaptability in the cellular environment, serving as an effective molecular tool for cellular communication. As an intrinsic but elusive property, allostery is a ubiquitous phenomenon where binding or disturbing of a distal site in a protein can functionally control its activity and is considered as the \u201csecond secret of life.\u201d The fundamental biological importance and complexity of these processes require a multi-faceted platform of synergistically integrated approaches for prediction and characterization of allosteric functional states, atomistic reconstruction of allosteric regulatory mechanisms and discovery of allosteric modulators. The unifying theme and overarching goal of allosteric regulation studies in recent years have been integration between emerging experiment and computational approaches and technologies to advance quantitative characterization of allosteric mechanisms in proteins. Despite significant advances, the quantitative characterization and reliable prediction of functional allosteric states, interactions, and mechanisms continue to present highly challenging problems in the field. In this review, we discuss simulation-based multiscale approaches, experiment-informed Markovian models, and network modeling of allostery and information-theoretical approaches that can describe the thermodynamics and hierarchy allosteric states and the molecular basis of allosteric mechanisms. The wealth of structural and functional information along with diversity and complexity of allosteric mechanisms in therapeutically important protein families have provided a well-suited platform for development of data-driven research strategies. Data-centric integration of chemistry, biology and computer science using artificial intelligence technologies has gained a significant momentum and at the forefront of many cross-disciplinary efforts. We discuss new developments in the machine learning field and the emergence of deep learning and deep reinforcement learning applications in modeling of molecular mechanisms and allosteric proteins. The experiment-guided integrated approaches empowered by recent advances in multiscale modeling, network science, and machine learning can lead to more reliable prediction of allosteric regulatory mechanisms and discovery of allosteric modulators for therapeutically important protein targets. Allosteric regulation is an efficient and robust mechanism for molecular communication and signaling in the cell employed by proteins for regulation of activity and adaptability during processes of signal transduction, catalysis, and gene regulation  allosteric sites sporadically appear during conformational transitions of a protein in the presence of a bound ligand. These hidden allosteric sites are invisible in crystal structures and can be detected due to the stabilization of the low-populated, higher-energy conformation by certain compounds. Even with the advanced sampling techniques and enormous computer power that is now available, the experimental validation and confirmation of allosteric states represents the key component to ensure robust quantitative modeling and analysis of allosteric mechanisms.NMR spectroscopy is a powerful method for studying protein dynamics and allosteric mechanisms by probing multiple time scales and detecting residue-specific conformational changes associated with ligand binding  simulation method has been shown as effective tool to perturb protein dynamics and assess both conformational and dynamical redistributions in allosteric systems  of Hsp90 is important for dimerization of the chaperone and contains a second nucleotide binding site  relying on the robust function approximations and representation properties of deep neural networks has provided us with new tools to automatically find compact low-dimensional representations (features) of high-dimensional data  is to produce fully autonomous agents that interact with their environments to learn optimal behavior, improving over time through trial and error. An important mathematical framework for experience-driven autonomous learning through interactions with the environment is reinforcement learning (RL)  which are at the core of RL methods and Markovian modeling of allosteric states in proteins. Several methods adopted RL-based conceptualization to develop MDP algorithms for conformational mapping of the protein landscapes and detection of functional allosteric states. REinforcement learning based Adaptive samPling (REAP) algorithm has shown a considerable promise by adopting RL principles in which an agent  takes actions in an environment  to maximize a reward function  models, most notably variational autoencoder (VAE) (Gomez-Bombarelli et al., A systematic interdisciplinary effort is needed to leverage the burgeoning knowledge about allosterically regulated proteins in the development of experiment-informed data-oriented computational tools for prediction of allosteric mechanisms and allosteric drug discovery. The main advantage of experiment-informed Markovian modeling is the ability of this technique to adequately describe hierarchy of allosteric states and the molecular basis of allosteric mechanisms. Using a combination of NMR-guided simulations and MSM approach, we can determine structural and dynamic patterns of conformational ensembles and identify functional allosteric states that are hidden in the conformational ensembles. The critical challenges of these methodologies for modeling allosteric regulation phenomenon is selecting a set of experimentally-informed collective variables defined by the intrinsic dynamics to provide the optimal projection of the landscape into functional allosteric states. In this context, the newly emerging information-theoretical flow approaches and modeling of entropy transfer in proteins can represent viable complementary tools for adequate reconstruction of functional conformational landscapes in proteins. The proposed integration of biomolecular simulations and NMR experiments with machine learning into a comprehensive research platform is expected to produce a toolkit of approaches for prediction of allosteric states and mapping of allosteric mechanisms.Network algorithms, information-theoretical approaches and DL models may be time-consuming and require a systematic exploration and engineering of features and neural net architectures with a constant and evolving feedback from NMR experiments to validate and confirm predictions. Several different ML architectures can be further explored to address potential efficiency and convergence problems including transfer learning, imitation learning, episodic control and dueling networks. To achieve synergies and robust integration of emerging technologies for predicting allosteric regulation mechanisms, a new open science infrastructure development is required which implies extensive sharing of experimental and computational data, software and knowledge across many discipline. Through integrative studies of allosteric mechanisms empowered by biophysical and data science approaches we can expand the toolkit of to dissect and interrogate allosteric mechanisms and functions in the therapeutically important protein families.The growing body of computational and experimental studies has shown that integration of data-driven biophysical and ML approaches can bring about new drug discovery paradigms, opening up unexplored venues for further scientific innovation and unique biological insights. The integration of computational and NMR approaches into a novel research platform that explores experiment-informed physical simulations, Markov state modeling, information-theoretical formalism of dynamic allosteric networks under the unified umbrella of machine learning will key to dissect molecular rules of allosteric regulation. The innovative cross-disciplinary approaches that expand the knowledge, resources and tools for studies of allosteric regulation can promote a broader usage of new technologies to understand and exploit allosteric phenomenon through the lens of chemical biology, material science, synthetic biology and bioengineering. By developing an open science infrastructure for machine learning studies of allosteric regulation and validating computational approaches using integrative studies of allosteric mechanisms, the scientific community can expand the toolkit of approaches and chemical probes for dissecting and interrogation allosteric mechanisms in many therapeutically important proteins. The development of community-accessible tools that uniquely leverage the existing experimental and simulation knowledgebase to enable interrogation of the allosteric functions can provide much needed impetus to further experimental technologies and enable steady progress.GV, PT, and GH conceived and designed the research, analyzed the results, and wrote the manuscript. GV, SA, PT, and GH performed the research. GV wrote the final version of the manuscript and supervised the project. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Maintaining healthy behaviors has been linked to positive emotional and physical health outcomes. Older adults are at a greater risk for functional decline and can benefit from the protective effects of health behaviors. The purpose of this symposium is to present and highlight: (1) innovative research linking health behaviors and health outcomes among older adults, and (2) work of emerging scholars in the Behavioral and Social Sciences (BSS) section. The papers highlight findings from descriptive studies and randomized trials testing behavioral health interventions. O\u2019Brien and Hess describe patterns of engagement in health-promoting activities and highlight mediating and moderator factors. Fausto and colleagues report on physical activity and cognitive health benefits of a multi-level intervention focused on heart and brain health for older African American residents of public and subsidized housing. Still and colleagues assess the efficacy of a multi-component technology-based intervention on hypertension self-management in African American older adults. Nehrkorn-Bailey and colleagues report on the pilot testing of AgingPLUS, an intervention targeting attitudinal and motivational barriers to physical activity and highlight improvements in grip strength and blood pressure. Lastly, Wierenga and colleagues test an emotion regulation intervention following a cardiac event and highlight the intervention\u2019s potential efficacy in improving mental health and physical activity. These papers underscore the importance of promoting healthy behaviors in older adults and the need for large-scale interventions that support healthy aging. As discussant, Atienza will assess the strengths and limitations of these papers, and consider how emerging scholars can contribute to the field."}
+{"text": "Cognitive aging research is gaining societal and practical importance because of population aging. Current research is focused on describing age differences and age-related changes in cognitive performance, understanding potential causes underlying these differences and changes, and identifying factors that promote maintenance of cognitive functioning in old age. The goal of this research group is to showcase new developments in research studying age differences in cognitive performance and longitudinal cognitive change in the second half of life. H\u00fcl\u00fcr et al. examine associations between midlife occupational factors and trajectories of cognitive change using data from the German Interdisciplinary Longitudinal Study of Adult Development and Aging (ILSE). Luo et al. use 12-year longitudinal data from 499 older participants in ILSE to study bidirectional associations between social relationships and cognitive performance. Small et al. examine the correspondence between objective and subjective cognitive performance, and measures of fatigue and depressed mood in experience sampling data from breast cancer survivors. Haas et al. compare laboratory and at-home online assessments of cognitive status and prospective memory over the adult lifespan and evaluate the quality of self-administered tests. The discussion by Elizabeth Stine-Morrow will focus on how these approaches contribute to our understanding of processes of cognitive aging and how they can be utilized to promote maintenance of cognitive functioning in old age."}
+{"text": "Clustered regularly interspaced short palindromic repeats associated protein nuclease 9 (CRISPR-Cas9) technology offers novel approaches to precisely, cost-effectively, and user-friendly edit genomes for a wide array of applications and across multiple disciplines. This methodology can be leveraged to underpin host-virus interactions, elucidate viral gene functions, and to develop recombinant vaccines. The successful utilization of CRISPR/Cas9 in editing viral genomes has paved the way of developing novel and multiplex viral vectored poultry vaccines. Furthermore, CRISPR/Cas9 can be exploited to rectify major limitations of conventional approaches including reversion to virulent form, recombination with field viruses and transgene, and genome instability. This review provides comprehensive analysis of the potential of CRISPR/Cas9 genome editing technique in understanding avian virus-host interactions and developing novel poultry vaccines. Finally, we discuss the simplest and practical aspects of genome editing approaches in generating multivalent recombinant poultry vaccines that conform simultaneous protection against major avian diseases. Poultry offers a major food source worldwide and continues to expand to satisfy the rising demands of the global population Speedy, . HoweverAdvances in pathogens biology and recombinant DNA technology are setting foundations in providing novel approaches to overcome the problems encountered with conventional vaccines design , nuclease-mediated , and recombinase-mediated (using Cre recombinase)  when being inactivated can induce protection against WNV-induced cell death    and unique short 4 (US4) genes from the ILTV genome and replaced with GFP reporter gene and F gene of NDV, respectively using NHEJ-CRISPR/Cas9 system to construct a bivalent vaccine candidate against two major avian respiratory viruses (ILTV and NDV). Thus, we concluded that the transgene insertion into the ILTV genome using CRISPR/Cas9 and subsequent excision of marker genes with Cre\u2013Lox system is an effective approach to stably express genes without causing any detrimental effect for the viral vaccine vector replication  is one of the most important avian viral pathogens causing major economic losses globally  causes substantial economic losses in the poultry industry while a persistent pandemic danger is posed by the occasional transmission of these viruses to humans  in a chromosomal location specified by the guide RNA  approach has been utilized to generate HVT-AIV bivalent vaccine and the selection of recombinant HVT-HA was done through the development of a precise, easy, and quick erythrocyte adsorption assay instead of using traditional approaches   is a lymphoproliferative disease of chicken primarily controlled by vaccination since 1969  and can be transmitted through infected birds and fomites  is a respiratory disease affecting the poultry industry and has a economic impact worldwide , Herpesvirus, Adenovirus, and Baculovirus are the most commonly used DNA viruses for the development of recombinant viral vectors Brun, , while AAdvances in next generation sequencing platforms have enabled the sequencing of species entire genome and viruses's genome. The National Center for Biotechnology Information (NCBI) dedicated a web-based portal for the collection of virus sequences and datasets  Genzel, . On the in silico design for the gRNA to target the viral genome; (2) construction and assembly of the Cas9 and sgRNA expression vector system and (3) construction of the antigen and selectable markers expression cassette and assembly to the donor plasmid. The Cas9 endonuclease precision is dependent on single guide RNA (sRNA) complementary to the target sequence. In designing the sgRNA, primary considerations are the PAM region specific for S. pyogenes Cas9 recognition which is 5\u2032-NGG and the on/off-target activity. Various web-based and local programs have been developed to identify possible PAM region and target sequences, as well as provide a predictive value that ranks the gRNAs based on on-target and off-target activities. Using CRISPR/Cas9 technology in the development of recombinant viral vectors requires understanding the following: (1) https://www.addgene.org/crispr/) provides a wide array of CRISPR plasmids and resources.Cas9 enzyme and gRNA need to be expressed in the cells for the efficient CRISPR/Cas9 technology. Various plasmid expression systems are available to use CRISPR in eukaryotic cells. To select the plasmid expression system, some precautions should be considered such as Cas9 enzyme and gRNA expression promoter, plasmid backbone components including selectable markers (antibiotic or flourophore) and appropriate plasmid delivery method. Addgene   protein separation from the mixture through SDS-PAGE, (2) transfer of separated protein into a solid support such as nitrocellulose membrane, and (3) detection of the protein through binding to appropriate antibodies  error-prone and HDR (homology-directed reparation pathway) high fidelity. Due to its high degree of reliability, the main focus of most studies is on the HDR application for vaccine production. Our research investigated the fast generation of recombinant vaccines by both HDR and NHEJ based CRISPR/Cas9 systems. The CRISPR/Cas9 system is a gene-editing technology, which has been recently developed and has shown to be beneficial in gene modification and provides an alternative rapid development of recombinant vaccines based on HDR and NHEJ systems.For multiple antigen insertion within the viral vector, the selection of an appropriate selectable marker is challenging especially with the use of fluorescent markers. The application of Cre/lox system to subsequently excise the fluorescent marker within the recombinant viral vector has been implemented and provided an answer to the challenge of selection of multiple antigen inserts and removal of the selectable marker for vaccine licensing. Development of a strategy for a single donor plasmid approach that carries multiple antigens will make a meaningful impact to the field. This is an important area of continuous study for the production of vaccines.Further, while majority of the CRISPR/Cas9 studies focus on the improvement of its specificity and efficiency, it is also important to address the biosafety implications of the on and off target effects of the system. Biosafety studies should be carried out to study on and off-target effects and their possible unintended mutations on the host cells and the potential interaction with the virus. Outcomes of these studies will be beneficial in the proper utilization of CRISPR/Cas9 tool in the advancement of viral vector construction. Taken together, the CRISPR/Cas9 system provides a significant advancement in various areas in avian virology specially in vaccine development. Together with the improvement in modern technology, next-generation sequencing and artificial intelligence, CRISPR/Cas9 system will continue to improve and ultimately its limitations will be addressed and solved.MM conceived the idea, has edited and reviewed the manuscript. JV and MR have written the manuscript. All authors approved the manuscript for submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The growing prevalence of functional impairment is a serious concern due to its relation to decreased quality of life in later life. Guided by the social convoy model and the stress process model, the present study investigated whether psychological resilience, particularly optimism and mastery moderated an association between functional impairment and subsequent depressive symptoms in later life. This study used data derived from two population-based national studies in the United States: 2012 and 2016 waves of the Health and Retirement Study  and 2004 and 2013 waves of the Midlife in the United States . Ordinary least squares regression was used to estimate the impact of optimism and mastery, respectively, on the associations between functional impairment (baseline measure at wave(t-1), changes over the study period from wave(t-1) to wave(t)) on subsequent changes in depressive symptoms. Across both studies, we found that having and developing functional impairment are related to increased number of depressive symptoms. Optimism independently predicted decreased depressive symptoms over the study periods and buffered the negative effects of functional impairment on depressive symptoms across the two studies. Specifically, the mitigating effects of optimism on depressive symptoms were greater for those with more numbers of functional limitations. The findings suggest that psychological resilience plays a key role in decreasing depressive symptoms, especially for midlife and older adults with functional impairment. The results also demonstrate the importance of examining both optimism and mastery when investigating psychological resilience and emotional well-being in older adults."}
+{"text": "Health and Demographic Surveillance Systems Within the Child Health and Mortality Prevention Surveillance Network. Clin Infect Dis 2019; the Child Health and Mortality Prevention Surveillance (CHAMPS) Methods Consortium was inadvertently omitted from the author byline.The article has been corrected, and the publisher regrets this error."}
+{"text": "The accumulation of blood proteins and cells on extracorporeal membrane oxygenation (ECMO) circuits has been proposed as a contributing factor to the coagulopathic state of many patients. This systematic review aims to summarize and discuss the existing knowledge of blood components binding to the ECMO circuits in human patients. A systematic review was conducted using the Medline, PubMed and Embase databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven studies were included in this review. Three studies identified a leukocyte adhesion, three studies observed von Willebrand factor accumulation and four studies identified bound platelets on the surface of the circuits. Other identified components included fibrin, albumin, hemoglobin, erythrocytes, progenitor cells, fibronectin and IgG. This systematic review demonstrates the limited state of knowledge when it comes to adsorption to the ECMO circuits in humans. Most of the studies lacked insight or detail into the mechanisms of binding and the interactions between different components bound to the ECMO circuits. Further research is required to comprehensively characterize surface adsorption to ECMO circuits in humans and to define the specific mechanisms of binding, enabling improvements that increase biocompatibility between the blood-circuit interface in this important clinical setting. Extracorporeal membrane oxygenation (ECMO) is a modified form of cardiopulmonary bypass (CPB), which provides cardiac and/or respiratory support for critically ill patients. ECMO is associated with a high incidence of bleeding and thrombotic events, which may contribute to morbidity and mortality. For example, in one large study , 38% of One of the primary causes hypothesized to initiate a coagulopathic state in ECMO patients is the increased contact of blood components with the artificial ECMO circuit. Blood circulates within an ECMO circuit under different hemodynamic conditions to the patients\u2019 body, altering the shear stress experienced during flow  and actiThis systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines .We searched Medline, Embase and PubMed indexed online databases for studies published from January 1985 to December 2019. The specific search terms used for each database search are detailed in Inclusion criteria: (I) ECMO circuit, (II) deposit composition or binding assessed, (III) blood components (cells or proteins) analyzed, (IV) English language and (V) human study.Exclusion criteria: (I) CPB or other non-ECMO extracorporeal circulation, (II) deposit volume rather than composition assessed, (III) binding of administered drugs analyzed, (IV) study did not investigate deposit composition in the context of ECMO circuit surface and (V) conference abstract.The included studies were reviewed by VI and PM, with disagreement resolved by discussion. Data extracted included study design, study length, patient age group, ECMO duration and mode, sample types, analysis technique/s and outcomes of any confirmed identification of bound blood components to the ECMO circuits from each study. The risk of bias assessment of each included study was performed in accordance with the Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) quality assessment tool . All of n = 565) excluded for not fulfilling the inclusion parameters. Many of the excluded articles were either conducted in the setting of cardiopulmonary bypass circuits (CPB) or in the context of ECMO but focusing on aspects such as the outcomes of anticoagulation strategies or assessing the feasibility of different ECMO circuit designs rather than specifically investigating surface adsorption on ECMO surfaces. Sixteen studies were reviewed for the full text screening with nine studies excluded for either only investigating drug binding to the circuit (n = 2), for not analyzing the surface deposition in the context of ECMO circuits (n = 2), for being animal studies (n = 1) or for being conference abstracts (n = 4). We identified 581 unique studies using our systematic search strategy. Papers were initially screened on their titles and abstracts with the majority of studies , which offered minimal information beyond the presence of particular components ,16,17. AThough the remaining four studies utilized immunofluorescent microscopy and SEM for direct visualization of the ECMO adsorption ,12,14,15Four of the seven studies analyzed adhesion during adult ECMO support with only a single neonatal case explored. The findings of these studies are therefore limited to adult ECMO patients and may not translate to pediatric or neonatal patients especially in the context of Developmental Hemostasis. The studies also limit their analysis exclusively to components binding in the membrane oxygenators and do not investigate other circuits such as tubing or pumps, which are known to also accumulate deposits in animal model studies ,8. FurthThe binding of blood cells and proteins to ECMO surfaces is likely associated with ECMO complications responsible for high morbidity including thrombosis and bleeding. The current state of knowledge on blood component adsorption to ECMO circuits in humans is limited to a small selection of studies. Several proteins and cells were identified involving ECMO adsorption by either protein identification through sample elution or direct microscopy visualization but none of these extensively characterized the root cause of adherence with the sample restricted to the membrane oxygenator only. Hence, there is a need for future studies. SEM, TEM, confocal microscopy, SWATH-MS and Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) could be first applied to characterize the different blood components (soluble and cellular elements) involved in the surface adherence during ECMO support and how they interact with the circuit and with each other. In addition, the association between the circuit adsorption and patient demographics, the pathway onto ECMO, the duration of ECMO, clinical events  and therapies such as blood product administration during an ECMO run should be investigated. Once we understand this key knowledge and insight into the mechanism of initiation of the ECMO circuit binding and thrombus formation, we can progress to design circuits that may reduce bleeding and clotting complications during ECMO and improve clinical outcomes on ECMO."}
+{"text": "Social services for older adults are instrumental in addressing vulnerabilities associated with aging. Yet, practitioners report needing expanded geriatric knowledge and enhanced supervision. Agency-based supervision is essential to skilled practice and staff retention, directly impacting the quality of services delivered by the teams they support. The Supervisory Leaders in Aging (SLA) program of the National Association of Social Workers (NASW) was designed to strengthen supervision of the social service workforce. The SLA program, adopted in four states , trained 134 MSW supervisors who support 1,200 social service staff, aimed at enhancing the well-being of 264,000 clients annually. This paper reports newly available final outcomes data from the 3-year implementation study of SLA. Trainees self-rated use of relevant supervisory best-practices was measured with novel 30-item instrument which captured frequency in use of supervisory best practices. The measure was administered prior to the first session and at three and twelve months after the final session. Comparisons of ratings across time periods demonstrate a range of positive and significant increases at the end of program workshops  and after one year . Supervisory best practices were maintained by those who already engaged in these behaviors, and participants who previously underutilized best practices adopted and maintained these behaviors as a result of the workshops. Implications of this tested model for enhancing workforce capacity will be discussed, including variation of impacts by supervisor characteristics and retention of learning gains over time."}
+{"text": "The San Diego Imperial Geriatric Education Center is comprised of a robust partnership between two academic institutions, two County Area Agencies on Aging, three Federally Qualified Health Centers (FQHCs), three Programs of All-Inclusive Care for the Elderly (PACE), and several local community organizations providing older adult services across two large, diverse counties. Guiding the implementation of Age-Friendly and Dementia-Friendly Healthcare at our partner FQHC and PACE sites, and a large academic institution, has allowed us to review the similarities and unique qualities of each organization. We identified a common theme that providers would benefit from improved awareness and access to community resources  support services), regardless of the specific health care system. The value of academic and community partnerships and the development of an infrastructure for information sharing and linking resources will be highlighted during this symposium presentation."}
+{"text": "Over the past twenty years, total debt for Americans ages 70 and over has increased more relative to all other ages group- by 543% according to the Federal Reserve Bank of New York (2019). Higher rates of debt among older adults have been attributed to a range of factors including expanded access to consumer credit, the capability for people to borrow from 401(k) plans, increases in costs of living, and limited financial literacy, among others. Related research of adults nearing retirement age who carry debt points to delayed retirement timing, lower levels of retirement savings, and higher risk and rates of bankruptcy. This symposium introduces timely investigations of retirement planning and economic security among older adults with debt. The first presentation will provide an overview of the impact of financial hardship on health among older adults in the United States over a recent ten-year period. The second presentation will focus on over-indebtedness among pre-retirees. The third presentation will examine the role of safety net services and borrowing from retirement plans among older adults with debt, particularly among older adults of color. The fourth and final presentation will focus on student loan debt as a hurdle to near-term and long-term financial security for older women in particular. A discussant will comment on how, together, the aforementioned papers contribute to our understanding of economic wellbeing and retirement preparedness in this era of increasing longevity. The session will integrate policy and programming implications for gerontological professionals."}
+{"text": "The aim of this research is to identify the impacts of material resources such as income, assets, housing and living standards on quality of life, health status and social relations. Amartya Sen\u2019s capabilities approach has formed the conceptual basis of the theoretical framework. This paper will report on the results of co-created research with older M\u0101ori in New Zealand aged 50 years and older. Objective measures of income, wealth, housing and living standards are compared with a range of scales including overall wellbeing and subjective health status and co-created scales of indigenous loneliness. The results demonstrate significant relationships between material resources and quality of life, health status and other social relations indicators. They quantify the impact material resources have on key indicators of social relations and social exclusion which enables informed and targeted policy interventions for social inclusion."}
+{"text": "The response to the outbreak which would have halted wider spread to neighboring countries failed. Hence, high risk districts in Uganda initiated preparedness activities in the wake of a possible inflow of cases. This study was therefore designed to identify, describe and assess surveillance activities and preparedness in the Kasese, Ntoroko and Bundibugyo districts of Uganda.the study employed the mixed method approach. The qualitative arm involved the use of participant observation to describe surveillance activities that were carried out as part of the ebola preparedness surveillance in the high-risk districts. The quantitative arm included assessment of 102 health facilities on ebola virus disease preparedness with a WHO standard checklist hosted on the Open Data Kit software. Descriptive statistics were performed using STATA (version 14).the study showed that high risk districts employed numerous interlocking public health emergency activities which included readiness assessment, risk mapping and temperature-based screening for ebola at points of entry. Most health workers (91.18%) could correctly state the case definition of ebola although only 56.86% of them were trained on ebola surveillance.health worker knowledge on ebola virus disease case definition was high but training and logistics were inadequate. Continuous efforts are required to sustain health workers knowledge on ebola surveillance through trainings and supportive supervision whiles addressing gaps in the operation of ebola screening posts. Ebola virus disease perhaps is one of the greatest public health threat in recent times having caused over fifteen outbreaks in eleven countries since 2011 with the deadliest of which occurred in some countries across West Africa . As at mPreparedness in infectious disease control depends on many factors such as robust disease surveillance systems, reliable health information, prevention, diagnostic, and treatment services, financing, and strong political commitment and skilled health professionals, who should be valued and protected everywhere, to act as the first line of defense of individual health security . The WorStudy design: observational and descriptive studies on systems put in place to ensure adequate preparedness for ebola virus diseases in the wake of possible spillover from the Democratic Republic of Congo to Rwenzori region of Uganda. The study used both qualitative and quantitative approach to describe surveillance activities/procedure that were carried as part of the preparedness and also assessed health facilities with respect to knowledge of staff on EVD, logistics and Standard Operating Procedures (SOPs) availability and also Alert reporting.Study site description: the Rwenzori region of Uganda is located within the western part of the country. It is made up by districts around the Mountain Rwenzori which stretches through the region into the Democratic Republic of Congo (DRC). Five districts in the region were classified as high-risk district for ebola due to their proximity form the ongoing outbreak. These districts are Kaborole, Bundidugyo, Ntoroko, Kasese and Buyangabu.Study population: the qualitive aspect of the study observed activities and individuals within selected districts for EVD preparedness activities including individuals who cross into those districts from DRC for the purpose of healthcare, trade and other social and economic activity with emphasis on health care professional with various agencies engaged in surveillance activities during preparedness phase for ebola. The quantitative aspect assessed health facilities preparedness within the study area.Exclusion and inclusion criteria: although five high-risk districts form part of the Rwenzori region, districts without Points of Entry (PoE) or borders directly with DRC were excluded from the study. The study therefore focused on Kasese, Ntoroko and Bundibugyo only.Sampling and sample size: all health facilities within the districts were assessed. Data drawn from the ODK server for the period of August 2018 to May 2019 showed that, 93 health facility based EVD assessments were performed in the Kasese district, 32 in Bundibugyo and 29 in Ntoroko district. It was observed that some health facilities were assessed repeatedly at difference times within the period of study. The study ignored earlier assessments that were done in case facility had more than one entry. The most recent assessment for a health facility was used for the analysis since it is the true state of the facility prior to exiting of preparedness to response phase. The most recent assessment in each health facility in the districts were 77 for Kasese, 15 for Bundibugyo and 10 for Ntoroko district, making a total of 102 for the study.Data collection procedure: mixed method approach was used to collect data. The qualitative arm involved participant observation (observations made by researchers on the field during the period of preparedness documented by way of reports and field notes). The observations with regard to surveillance activities were scripted with reference to reports and personal notes on an observational checklist. The individual scripts of the researchers on surveillance were then merged. The quantitative arm includes the use of available data captured with the Open Data Kit (ODK) on alerts, health facilities preparedness and Points of Entry\u00b4s (PoEs) screening data. The health facility assessment was done with health facility EVD preparedness assessment checklist. A standard tool by the World Health Organization hosted on Open Data Kit (ODK).Data analysis: data saved on the ODK server was extracted and exported in excel format. The data was cleaned and checked for accuracy and completeness and then imported to STATA (STATA 14) for analysis and presentation in charts and graphs. Descriptive statistics were performed with STATA (STATA 14) which involved cross-tabulations to show proportions of indicators/variables. Key indicators of EVD preparedness assessed were availability of EVD SOPs, training of health facility Surveillance Focal Persons on EVD surveillance and knowledge on EVD case definition, evidence of active search for EVD. The qualitative analysis was achieved by the principal investigator reading the narrative on the observational checklist scripted by the individual researchers. Thematic concepts in ebola surveillance as observed by researchers were coded and aggregated in categories by combining like information. The combined findings on the surveillance procedure in high-risk districts were agreed upon by all the researchers.Ethical considerations: permission was obtained from the appropriate authorities including the World Health Organization Country Office and the Ministry of Health in order to access and use available data/records. The activities described and data analyzed were part of the preparedness interventions of the Ministry of Health of Uganda/World Health Organization Country Office respond to possible influx of ebola from the Democratic Republic of Congo. We did not use any confidential data and did not disclose any unauthorized names in our report.Ebola preparedness surveillance activities in the Rwenzori region of Uganda: the EVD preparedness in the Rwenzori region combined various public health emergency strategies and activities under the coordination of District Ebola Task Force (DETF). Two subgroups within the DETF spearheaded surveillance activities in the districts. The teams were the surveillance subcommittee and the Rapid Respond Team (RRT). Below were the findings with regard to surveillance procedure or activities that were undertaken in the absence of a confirmed case.Readiness assessment: the initial activity was a readiness assessment by a national team deployed by the Ministry of Health. The team from the national level used the World Health Organization\u00b4s EVD readiness assessment tool to examine the level of readiness of the high-risk districts to detect and manage ebola cases in the event of any inflow. The team also supported the districts to identify actions to be performed to ensure operational readiness including the establishment of the district ebola task force. The readiness assessment found the following surveillance gaps in the districts. Lack hotline in place for reporting of cases, inadequate case investigation forms and standard case definitions and inadequate training in EVD surveillance.Risk mapping: the risk mapping majorly focused on Uganda - Democratic Republic of Congo border population movements, reasons for their movements, border crossing points and major destinations in either countries. The risk mapping identified points of entry. The points of entry were further classified based on the average number of individuals who crosses on daily basis and nearness to a corresponding community in the Democratic Republic of Congo in which cases are occurring. The outcome of the risk mapping aided prioritization of activities.Screening at points of entry (PoEs): screening facilities were set up at points of entry. Trained volunteers mount these facilities and ensures individuals entering Uganda washes their hands with 0.05% chlorinated water, dip their foots in 0.5% chlorinated water and temperature checked with infra-red thermometers within reasonable distance. Individuals with temperatures of 38\u00b0C and above were detained for about thirty minutes for verification of the high temperature. Detained individuals with high temperatures were considered as alerts case. The volunteers at the screening facilities then informs the rapid response team for assistant. The team upon reaching the site conducts further enquiries and transfer the patient to the Ebola Treatment Unit (ETU) for investigations and management. The screening facilities were organized in four units, the hand washing, temperature checking, data recording and case holding zones. Not all identified crossing points were conducting screening due to inadequate logistics and manpower. Some crossing points were seen to pose less threat according to the risk mapping. Capacity building for ebola detection and active search: formal training and Health facility-based capacity building in ebola detection were used. Training on ebola surveillance and contact tracing for health facility heads and surveillance focal persons. The training equipped participants on case definition of ebola and order of reporting identified cases. The district surveillance teams conducted health facility-based capacity building of health workers on identification of ebola and the appropriate measures to implement when a case is detected.Community based ebola surveillance and sensitization: another surveillance activity identified was active search for ebola cases in communities. The focus of the community visit was the Village Health Teams (VHTs), Community Development Officers (CDOs), Political and Opinion leaders. They were sensitized on the disease and asked for the presence of any case in the community. Follow ups were conducted whenever a case was reported. Organize groups, markets and schools were also sensitized and EVD posters with hotlines for reporting suspected cases were also distributed. The district surveillance teams exchange contacts with VHTs and community leaders for easy information sharing and response to alerts.Alert response and case investigation: there were four (4) main sources of alerts. Alerts which came from the points of entry screening, health facilities, rumours  and VHTs and community leaders. The Rapid Response Team (RRT) which is composed of surveillance and case management personnel were deployed to the locations when an alert was given. The RRT assess the alert case including travel and exposure history from the health facility, screening point or community. Cases that met the case definitions were transported to the Ebola Treatment Units (ETU) for case-based investigation. During the preparedness phase, a total of 77 alerts were investigated and geocoded using ODK. Preparedness of health facilities prior to confirming of ebola in Uganda: from The August 2018 ebola outbreak, the tenth to hit Democratic Republic of Congo (DRC) turns out to be second largest outbreak of ebola in public health history. The response to the outbreak which would have halted wider spread to neighboring countries failed  but UganEbola preparedness surveillance activities in the Rwenzori region of Uganda: readiness assessment being the foremost activity was needful since it helped to identify gaps in the high-risk districts. The World Health Organization (WHO) standard tool; ebola virus disease consolidated preparedness checklist [hecklist  gave a shecklist . With mohecklist . Both seTraining is a way of equipping professionals with needed skills to handle a situation . SelectePreparedness of health facilities prior to Kasese outbreak in Uganda: from et al. in their study on strengthening healthcare workforce capacity during and post ebola outbreaks in Liberia showed that training improves the knowledge and confidence of health staff. Improve knowledge and confidence significantly leads to reduction in health care workers infection and reduction response time to subsequent public health events [et al. in the Bundibugyo district showed that slightly over 51% community had knowledge about EVD [et al. in their study \u201cManaging ebola from rural to urban slum settings: experiences from Uganda\u201d reveal that community leadership and mobilization was very important in early case detection and isolations well as contact tracing and public education [h events . Despitebout EVD . About 8bout EVD . Okware ducation .Whereas there were no confirmed cases of ebola in the Rwenzori region of Uganda, high risk districts implemented varied public health surveillance interventions similar to surveillance activities in outbreak settings. The prompt identification and swift response to the ebola outbreak in June 2019 in the Kasese district could be associated with high health workers knowledge on case definition and detection of ebola. That notwithstanding, several gaps existed in the operations of temperature-based screening points for ebola which must addressed. Health facilities played a major role in identification of alerts amidst inadequate training and resources such EVD surveillance guideline. Continuous efforts are recommended to sustain health workers knowledge on EVD surveillance through trainings and supportive supervision whiles addressing gaps in the operation of ebola screening posts.With the recent less difficulty in travelling and trade, geographical distance is no longer a major hindrance in transmission of infectious diseases such ebola;The outbreak in DRC posed a huge challenge to the health security of neighboring countries including Uganda considering the possibility of geographical spread;Ebola preparedness surveillance involves non-contact temperate based screening at points of entry (PoEs).Health worker knowledge on EVD case definition was high in the high-risk districts which was key in the prompt identification of the Kasese outbreak;Thirty point thirty-nine percent (30.39%) of health facilities were having ebola virus disease standard operating procedure guideline;Eighty eight percent (88%) of health facilities had poster or information, education and communication materials on ebola surveillance at vantage points to educate health facility users."}
+{"text": "Many potyvirus species are among the most economically-significant plant viruses as they cause substantial yield losses to crop plants globally. Investigating their infectious cycles and host\u2013potyvirus interactions is therefore essential for the development of anti-viral strategies and resistant cultivars. The thirteen original articles included in the Special Issue on \u201cThe Complexity of the Potyviral Interaction Network\u201d shed light on the current state of potyvirus research in three main areas: (i) complex interactions between multifunctional potyviral proteins and antiviral or proviral host factors; (ii) molecular and physiological responses of the plant to potyvirus infection; and (iii) potyvirus evolution and phylogeny.The review of Shen et al.  illustraIn an additional four articles, the molecular responses of crops to potyvirus infection are analyzed through high-throughput transcriptomics approaches. Different pathosystems that yield different outcomes in potyviral infection are analyzed, which include antagonism or synergism induced in papaya by mixed-infection of papaya ringspot potyvirus and papaya mosaic potexvirus , tomato Finally, two complementary articles on potyvirus phylogeny complete the contributions to this Special Issue. The study of Moury and Desbiez  describeCollectively, the papers in this Special Issue exemplify the diversity of studies focused on this major plant virus group. We wish to express our sincere thanks to all authors who contributed to the Special Issue \u201cThe Complexity of the Potyviral Interaction Network\u201d and our gratitude to the reviewers who vetted the contributions."}
+{"text": "The Virginia Geriatric Education Center (VGEC)\u2019s Geriatrics Workforce Enhancement Program (GWEP) partners with two programs, Senior Strong at Eastern Virginia Medical School in Norfolk, VA and the Richmond Health and Wellness Program at Virginia Commonwealth University in Richmond VA to support their age-friendly initiatives. These programs enhance primary care for an older population experiencing adverse social determinants of health by providing screening around the 4Ms pillars of age-friendly healthcare and connecting participants with healthcare and community-based organizations. These programs offer a rich learning environment for interprofessional students. The VGEC GWEP strengthens these programs by developing faculty and student training in collaboration with the programs and facilitating program participation in the GWEP-CC Age-Friendly Action Community to develop and refine age-friendly practice workflows, referral pathways and documentation."}
+{"text": "Through a collaborative agreement with the Administration for Community Living, Memory Care Home Solutions translated the evidence-based program (EBP) Care of Persons with Dementia in their Environments (COPE) into community practice as a covered benefit through Medicare and commercial health insurance for people living with dementia. While many studies have demonstrated the efficacy of family-centered behavioral interventions for this population, few of these interventions have been translated from academic studies into successful community practice. This session will describe the process of translating an EBP into community practice utilizing social work and occupational therapy interventionists with a diverse population of people living in both urban and rural areas of Missouri and Illinois, including modifications required and lessons learned in rural service delivery. Attendees will gain an understanding of the translation process, differential treatment outcomes for people living with dementia and care partners and Medicare billing mechanisms for sustainability."}
+{"text": "The NIA Edward R. Roybal Centers for Translational Research in the Behavioral and Social Sciences of Aging aim to translate and integrate basic behavioral and social research findings into principle-driven interventions aimed at innovatively improving both the lives of older people and the capacity of institutions to adapt to societal aging. Newly funded Centers focus on interventions to promote caregiving mastery, integrate the use of technology in care support to improve assessments and interventions in care provision, develop behavioral interventions to reduce isolation and promote social connectedness in caregivers, promote health in racial/ethnic minorities, and apply insights from data science and behavioral economics to improve palliative care delivery and long-term support facilities for persons with dementia and their caregivers. Center leaders will present an overview of their cutting-edge, early-stage research projects based on the NIH Stage model conceptual framework and discuss implications for improving care of caregivers and patients."}
+{"text": "The profilins (PRFs) are low-molecular weight, cytosolic proteins made up of 129\u2013133 amino acids and tightly control cell-cytoskeleton architecture mainly through actin polymerization  reveal that the purifying selection is primarily responsible for the evolutionary stability of PRF genes. In addition, the segmental and tandem duplication events are also prominent for their structural/functional divergences among lineages , Mesozoic (252 MYA) and Cenozoic (66 MYA) life forms. Thus, PRFs are the notable outcome of the continuous evolution under natural selection   consists of 134 amino acids and 11 amino acids long PAINRs (AIQEKGTPGMR) present at 64, 78\u201379, 81, 89, 94, 114\u2013116, 120, 124 amino acid positions  compared to the vegetative and floral tissues  gene in tobacco results in the hyperactivation of apical meristem, early flowering and a relative increase in the flower number per plant  and ARP6 genes are upregulated in the vegetative and floral tissues of PRF transgenics. These results establish a novel and systematic functional relationship between trans-PRF gene expression and early flower primordium initiation in PRF trasngenics  the initiation of healthy floral buds, normal stamen and pollen production, and flower growth. Floral organ development is severely defected in PRF silencing lines with shortened staminal tube coverage and filament duration, reduced stamen number, indehiscence of anthers, abrupt and uncoordinated increase in the style duration, and irregular seed shape . Increased accumulation of ROS may cause cellular damages mainly through the degradation of lipids, proteins and nucleic acids  staining of the target tissues  in tobacco. The molecular basis of such enhanced emergence of shoot-initial on the edges of explants is directly linked to the relative transcription of CLAVATA1 (CLV1) and WUSCHEL (WUS) genes/trans-factors that alter proportionally with the magnitude of organogenesis in PRF-overexpression lines. The CLV1 and WUS genes are involved in the activation of essential signal transduction pathways required for the activation and formation of shoot primordial during in vitro organogenesis (PRF genes have a direct role in the organogenesis process in vitro which can further be exploited for the improvement of agronomic traits in many crop species.A prerequisite to the successful ogenesis  (Pandey ogenesis . TherefoDP and BC conceptualized the research and outlines of the article and discussed all results and wrote the manuscript. DP performed all lab experiments cited in the article. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "This symposium addresses issues surrounding Alzheimer\u2019s disease and related dementia (ADRD) across multiple racial/ethnic minority groups, including African Americans, Latinos, and Arab Americans. Using US national data, Kindratt and colleagues challenge the universality of the healthy migrant effect by comparing patterns of cognitive disability across US- and foreign-born Arab Americans. Arab Americans represent an increasingly visible ethnic minority group whose unique history has the potential to clarify knowledge about sociocultural influences on ADRD. Also using US national data, Garcia and colleagues examine within-group heterogeneity among Latinos. They conclude that the number of years and proportion of life spent with and without subjective cognitive impairment differ as a function of ancestry and nativity. Using data from two local communities, Diminich and colleagues investigate mechanisms underlying ADRD risk among Latinos by considering both stress responding and plasma-based AD biomarkers as predictors of Latino cognitive health. Lee and colleagues focus on social relationships and cognitive aging in a diverse, national cohort. They suggest that the quality of social support from social network members may uniquely affect the cognitive functioning of African Americans older adults. Finally, Cerise Elliott from the National Institute on Aging (NIA) will offer perspectives on how racial/ethnic minority group focused research can advance NIA\u2019s goals related to understanding and eliminating ADRD inequalities. In total, this symposium highlights the need to disaggregate racial/ethnic groups, as well as the importance of incorporating both individual and contextual factors in order to fully understand patterns of ADRD risk and resilience."}
+{"text": "The labour market activity of older workers and their ability and disposition to maintain it depend on institutional conditions, age norms, labour demand and shifting overall economic conditions. The paper discusses exclusion and inequality in later working life from a European comparative perspective and emphasises shifts in late work and retirement patterns as well as later-life outcomes in Sweden and Poland. An emphasis is on changing institutional conditions on the national and branch level. Gendered risks for economic exclusion and later life precarity are stressed. Analyses for the two countries are contrasted with Germany and the UK. The analyses are part of the research program \u2018Exclusion and Inequality in Late Working Life: Evidence for Policy Innovation Towards Inclusive Extended Work and Sustainable Working Conditions in Sweden and Europe \u2013 EIWO\u2019 (2019-24). Analyses use data from SHARE and EU-SILC and address older workers of age 60 and older in Sweden, Poland, German and the UK. They find increasingly heterogeneous preretirement and transition patterns, new gender gaps and increasing risks of economic exclusion in retirement. Situations differ between countries with the prolongation of late working life in Sweden having a mostly positive effect on gender inequalities with low education and specific migrant groups as an exception. Poland is specific case due to unequally low retirement age for woman (60) and for men (65) with consequently large structural gender differences and increases in the process of increasing labour force participation of older workers and increasingly gendered risks for old-age economic exclusion."}
+{"text": "These data can be useful for the prediction of the long-term waterproof performance of water-swelling materials and provide reference for material selection. The data presented herein was used for the article, titled \u201cLaboratory evaluation of long-term sealing behaviors of two water-swelling materials for shield tunnel gasket\u201d This article provides comprehensive experimental data of two water-swelling materials, water swelling rubber (WSR) and water-swelling polyurethane (WSP). Swelling tests, Dynamic Mechanical Analyzer (DMA) and Scanning Electron Microscope (SEM) were performed. Sealing properties of WSR and WSP were characterized by the data of swelling ratios (S Specifications Table\u2022The comprehensive data can be used for prediction of the long-term waterproof performance of WSR and WSP\u2022Waterproof materials, mechanical property\u2022The data of swelling test are valuable for understanding the long-term swelling behaviors of WSR and WSP\u2022The data about storage moduli provides accurate comparison of WSR and WSP, demonstrating the potential application of DMA to measure the dynamic mechanical properties for low strength material\u2022The data provides reference for material selection of WSR and WSP1a and Sw), storage moduli (E\u2019) and SEM images, which is used to access the sealing capacity of water swelling rubber (WSR) and water-swelling polyurethane (WSP). a and Sw) of specimens, respectively. The data consists of swelling ratio  and SEM were performed with different compression loads and saline environments. The saline environments in this experiment consists of distilled water, artificial seawater and condensed artificial seawater with double ion concentration. The configuration of artificial seawater can be found in Garcia et al. 2.2a) and free swelling ratio (Sw) In this data article, the axial swelling ratio (Sa with time of the WSR and WSP specimen under different compression load.w) with time of the WSR and WSP specimen in different saline environments.The storage moduli E\u2019 (kPa), which is typically related to Young's modulus SEM images present micro-crack morphology of WSR and WSP, which is helpful for the assessment of damage characteristics under long-term compression or immersion in different solutions"}
+{"text": "Gerontology education and the goal of \u201cgeriatric competence\u201d are considered invaluable within the field but barriers exist in communicating ideas and training needs across areas of specialization. The main challenge of higher education institutions throughout the world is to develop professionals capable of understanding and responding to the current issues of diverse aging populations. The specific focus of the presentation will be the examination of aging education \u201cthemes\u201d within and across different conference sections\u2019 presentations in GSA conference proceedings across the last six years. Specifically, this presentation will review the outcomes of qualitative content analyses from several GSA conferences\u2019 research presentations regarding the role of education across different disciplines in the gerontology field. Thematic analysis of several past years GSA conference programs of 2013 through 2019 yielded some of the following education-related themes (sample): theme #1: community education for clients, practitioners and applied service providers, theme #2: intergenerational educational mentoring/programming among researchers and practitioners in the field, and theme #3: professional knowledge updating for geriatric professionals. The implications for increasing emphasis on ongoing geriatric education for all professionals in the field and those they serve  will be discussed. This presentation offers insights regarding trends in educational issues within the field as well as the unique valuation of gerontology education within different areas of field specialization. The importance of examining different areas of specialization exists because different aging-related disciplines can share knowledge and resources in providing an integrated array of educational and training options."}
+{"text": "This study investigates the psychometric properties of the mobile cognitive app performance platform (mCAPP), designed to detect memory changes associated with preclinical Alzheimer\u2019s Disease (AD). The mCAPP memory task includes learning and matching hidden card pairs and incorporates increasing memory load, pattern separation features, and spatial memory. Participants included 30 older adults with normal cognition. They completed the mCAPP, paper and pencil neuropsychological tests and a subset completed a high-resolution structural MRI. The majority of participants found the difficulty level of the mCAPP game to be \u201cjust right\u201d. Accuracy on the mCAPP correlated with performance on memory and executive measures, while speed of performance on the mCAPP correlated with performance on attention and executive function measures. Longer trial duration correlated with measures of the parahippocampal cortex. The relationship of mCAPP variables with molecular biomarkers, at-home and burst testing, and development of additional cognitive measures will also be discussed."}
+{"text": "Escherichia coli using virulence factor gene deletion and engineered vaccine vectors based on probiotics. We also describe methods for the detection of pathogenic bacterial strains in eco-environmental headspace and aerosols, as well as samples of animal and human breath, based on the composition of volatile organic compounds and fatty acid methyl esters. We explain how the introduction of these low-cost biotechnologies and protocols will provide the opportunity to enhance co-operation between networks of resistance surveillance programs and integrated routine workflows of veterinary and clinical public health microbiology laboratories.The application of next-generation molecular, biochemical and immunological methods for developing new vaccines, antimicrobial compounds, probiotics and prebiotics for zoonotic infection control has been fundamental to the understanding and preservation of the symbiotic relationship between animals and humans. With increasing rates of antibiotic use, resistant bacterial infections have become more difficult to diagnose, treat, and eradicate, thereby elevating the importance of surveillance and prevention programs. Effective surveillance relies on the availability of rapid, cost-effective methods to monitor pathogenic bacterial isolates. In this opinion article, we summarize the results of some research program initiatives for the improvement of live vaccines against avian enterotoxigenic  Campylobacter spp., Staphylococcus spp., Salmonella spp., Clostridium perfringens type A, Enterococcus faecalis, and Escherichia coli  is an open platform that displays a taxonomic framework classifier based on FAME composition and bacterial 16S rRNA gene sequences [The fatty acid composition of bacterial species is genetically conserved . When esequences . Thus, wGlobal environmental changes and ecosystem impairments have contributed to the dissemination of bacterial pathogens from animals to humans and vice-versa. Despite progress in some countries, effective and coordinated strategies, such as antimicrobial stewardship and One Health strategy, for the containment of misuse of antimicrobials and the spread of antibiotic-resistant microorganisms have not been globally implemented . The EurThe next generation of live bacterial strains and engineered probiotics based on lactic acid bacteria and yeast as vaccine delivery vectors offer many attractive advantages over traditional recombinant vaccines. Rapid diagnostic methods for bacterial infections and airborne disease outbreaks in farm animals and communities are constant challenges faced by hospitals and health institutions in developing countries. Antibiotic stewardship programs are a key component in preventing the spread of antibiotic resistance in all healthcare facilities and across the world. Non-invasive and fast diagnostic tools based on breath biopsy hold great promise in identifying animal and human pathogens. The implementation and use of chromatography and mass spectrometry methods and chemical sensors in the clinical laboratory for determination of VOCs and FAMEs have immense potential in the development of biomarkers for the early diagnosis of infectious diseases. Finally, the application of these innovative methods will provide quantitative insights into the contribution of microbiota to farm animal growth and enable future studies on the interacting roles of diet and gut microbiome on animal physiology and health."}
+{"text": "Objective: While about 75% of people with ADRD receive care informally by their family members, relatively little is known about the effect of the quality of caregiving on maintaining carerecipient\u2019s health and financial burden of out-of-pocket (OOP) healthcare costs. The goal of this study is to examine the quality of caregiving on the out-of-pocket healthcare costs among ADRD patients and if caregiving prevents deterioration of physical health of carerecipients. Data and Sample: We used a nationally representative sample of people diagnosed with ADRD from the Aging Demographic and Memory Study, subsample of the Health and Retirement Study. The study sample includes carerecipients whose caregivers participated in the survey (N=261). Outcome measures: Primary outcomes were deterioration of carerecipients\u2019 health  and annual OOP healthcare costs. The quality of caregiving is captured by if caregiving made them feel good, feel useful and fee closer to carerecipients. More than 70% caregivers reported that caregiving make them feel good or useful. About 60% of carerecipients\u2019 physical health was maintained, and average out-of-pocket costs was $3,701/year . Multivariable logit for binary health outcome and OLS regression for OOP cost were estimated. Results: The likelihood of health deterioration was significantly lower for carerecipients whose caregivers reported that caregiving made them feel useful  and lower OOP remained significantly associated with presence of usefulness of caregiving . Positive feeling of caregiving is independently associated with lower OOP cost and deterioration of physical health among ADRD patients."}
+{"text": "In spite of their elevated presence in the laboratories, women are still underrepresented in the top ranks of the scientific careers, including biomedical disciplines. This Research Topic offered a platform to promote the work of women scientists across the field of Signaling. Studies from researchers from Australia, Spain, United States and France have addressed a variety of issues that keep in common signaling alterations and human diseases.Merechar et al. describe a new tool to test if gain-of-function Pik3ca mutations can cause vascular malformation syndromes. Expression of the most common post-zygotic activating mutation of Pik3ca in mice neural crest and related embryonic lineages allow the authors investigate the consequences of this mutation. Outcomes included macrocephaly, cleft secondary palate and more subtle skull anomalies. These murine phenotypes may aid discovery of new candidate human PRDs affecting craniofacial and vascular smooth muscle development as well as the reciprocal paracrine signaling mechanisms leading to tissue overgrowth.Inappropriate activation of the PI3K signaling pathway lies at the core of most human cancers. Missense mutations of the PIK3CA oncogene are also found in affected tissues of a distinct set of congenital tumors and malformations collectively termed PIK3CA-related disorders (PRDs). Chatterjee and Sing review the current understanding of EVs in retinal (patho) physiology including disease-associated EV alterations in specific retinal diseases. Identifying different sub-populations of EVs in the retina in normal versus diseased condition(s), understanding the consequence of cell-specific EV cargo  as well as understanding the mechanism behind the packaging of this cargo for retinal homeostasis would help to understand the mechanisms leading to retinal disease. The identification and characterization of cell specific EVs in body fluids like plasma, serum, VH, and aqueous humor in healthy subjects versus patients with retinal degenerative diseases will also be instrumental in development of biomarkers.Extracellular vesicles (EVs) secreted by cells have important functions in cellular homeostasis and cell-cell communication. Evolutionarily conserved from prokaryotes to eukaryotic cells, EVs play an important role in autocrine, paracrine, and endocrine signaling. Alterations in these mechanisms are implicated in multiple human disorders including prominent retinal degenerative diseases, like age related macular degeneration (AMD) and diabetic retinopathy (DR). Rinc\u00f3n-Ortega et al. use the follicular epithelium (FE) of the Drosophila ovary as a model system to study the role of cell-ECM interactions in stem cell proliferation and differentiation during development. Their studies point to a role for the integrin-mediated cell-BM interactions in the control of epithelial cell division and subsequent differentiation.Signaling by integrins is crucial for normal epithelial tissue growth and development, and continues to be critical for tissue homeostasis and regeneration throughout life. Defects in the correct control of stem cells proliferation and differentiation can lead to abnormal tissue and is a hallmark of cancer. Weerasinghe et al. Review bone-associated signaling pathways and the direct impact of antipsychotics on different receptors present in bone cells.An important aspect of signaling studies is that of investigate the potential effect side effects of medical treatments. Between 2005 and 2014, the prescription rate of antipsychotic use overall has increased in 10 out of 16 countries, and its use is associated with a number of side effects. A growing body of evidence suggests diminished bone mineral density (BMD) and increased fracture risk associated to antipsychotics."}
+{"text": "The current scientific literature has increased our understanding of how medication could be beneficial for patients with eating disorders (EDs) on a molecular, functional, and behavioural level. Based on theoretical considerations about neurotransmitters, hormones and neural circuits, possible drug targets for the treatment of EDs may include signal molecules and receptors of the self-regulatory system such as serotonin, norepinephrine and glutamate; the hedonic system including opioids, cannabinoids and dopamine; and the hypothalamic homeostatic system including histamine, ghrelin, leptin, and insulin.The currently approved pharmacological treatments for EDs are limited to fluoxetine for bulimia nervosa (BN) and - in some countries \u2013 lisdexamfetamine (LDX) for binge eating disorder (BED). Topiramate might be an additional option for people with BN and BED.There are no approved pharmacological options for anorexia nervosa (AN), even though study results for olanzapine and dronabinol are promising. Psilocybin, ketamine, and metreleptin have recently been considered and tried in AN.Case reports and studies regarding the drug treatment of the new DSM-5 EDs include the use of mirtazapine for avoidant restrictive food intake disorder (ARFID); fluoxetine for pica; and levosulpiride and baclofen for rumination disorder.This talk is based on a comprehensive review of the scientific literature regarding the pharmacological treatment for EDs and will include a preview of the 2023 update of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders.None Declared"}
+{"text": "Recent evidences suggest that situations of abandonment, neglect and abuse are risks factores for onset of psychopatology in adulthood. This association occus in that traumatic events in the early stages of development and may trigger severe and disabling psychiatric disorders in adults.The presente study aimed to evaluate the associations between the occurence and severity of chidhood trauma and the development of psychiatric disorders in hospitalized teenagers of the Hospital Psychiatric Vida Londrina/Pr.The sample was consisted of 14 psychiatric patients, evaluated for severity of psychiatric symtoms by the Back Scale for Suicid Ideation (BSI); Beck Depression Inventory (BDI); Beck Anxiety Inventory (BAI); Back Hopelessness Scale (HAD) and the Barratt Impulsiveness Scale (BIS-11).In the sample studie, 84% of the teenegers reports that they had some type of childhood trauma. The results indicate that traumas are associated mainly with the development of mood disorders and also with increasin severity of psychiatric symptoms, specially the depressive symptoms, hopelessness, suicidal ideation and impulsivity. Teenagers with emocional neglect, emocional abuse and physical neglect demonstrated having five times more risk of personality disorder. Individuals who suffered physical abuse; sexual abuse and physical neglect presentes at three times more risk of commiting suicid attemps.These data demonstrate the relevance of trauma childhood as a trigger for psychiatric symptoms.None Declared"}
+{"text": "Cellular neurophysiology is the study of the electrical and chemical activity of neurons, the basic structural and operational units of the nervous system. The history of this field can be traced back to the nineteenth century when scientists first began measuring the electrical activity of nerve cells. Early research focused on understanding the elementary properties of neurons, such as the action potential and synaptic transmission. Subsequent advances in technology allowed for more detailed studies of neural physiology and connectivity, membrane biophysics, and neuronal structure. Today, by studying the functioning of individual neurons and the mechanisms that underlie their electrical and chemical signaling, scientists can gain a deeper understanding of the physiology of the nervous system and how it is disrupted in diverse neurological or psychiatric disorders. This Research Topic assembles contributions  that highlight several contemporary experimental techniques and methods used to study fundamental questions in cellular neurophysiology.Qi et al. combined injections of multiple retrograde tracers into mouse forelimb and hindlimb muscles with 3DISCO tissue clearing to image the entire spinal cord without sectioning. The authors thus determined the three-dimensional distribution of motor neurons innervating different branches of the brachial plexus. The data could help to better understand the structural and functional connections between motor neurons and muscle fibers and improve the diagnosis and therapy of motor neuron and peripheral nerve diseases.An understanding of the spatial distribution of motor neurons, their efferent fibers, and neuromuscular targets are essential to the study of motor coordination, motor neuron impairment, and nerve repair  enhances neuronal excitability through non-canonical activin receptor signaling, which led to the suppression of a standing G protein-gated inwardly rectifying K+ (GIRK) current. This study provides a molecular mechanism linking EE to enhanced GIRK current and increased firing, potentially explaining the beneficial effects of EE on cognitive performance and affective behavior.Activin A serves as a neuroprotective factor and has been implicated in cognitive function  allow controlling neuronal activity with single-cell precision  in the nasal epithelium  via up/down-states as the surrogate of sleep activity ex vivo. Their results show that SWOs potentiate both excitatory and inhibitory spontaneous synaptic strength in neurons and establish an effective method to study the effects of SWOs on individual neurons ex vivo.Sleep profoundly affects brain functions and promotes the consolidation of procedural and emotional memories (Diekelmann and Born, Hanson and Wester review recent methods to target and manipulate defined neuron types in vivo to dissect their role in native neural circuits. They describe the development and use of transgenic mice and/or AAVs for cell type targeting, recently identified genetic enhancers, and intersectional fate and circuit mapping tools. The utility of genetically encoded voltage indicators and CRISPR-based genetic manipulations are described that allow for interrogation of circuit function with cell-type specificity. This timely review highlights powerful new genetic tools that can help us better understand how cortical microcircuits develop and function in health and disease.Neuronal circuits consist of diverse excitatory and inhibitory neurons. Recent work has classified previously underappreciated cell types based on unique morphological, electrophysiological, and transcriptional signatures (Zeng and Sanes, Hu et al. established a new method for identifying protein complexes and post-translational modifications in cultured hippocampal neurons. They combine lentiviral protein expression with tandem affinity purification followed by mass spectrometry to investigate neuronal KV4.2 potassium channel complexes. This approach offers a new way to identify protein-protein interactions and explain neuronal signaling mechanisms that may be involved in the pathophysiology of neurological diseases.Protein complexes are a cornerstone of cell biological processes (Marsh and Teichmann, The submissions to this Research Topic covered a wide range of neurophysiology methods and applications, including imaging techniques, electrophysiology, and genetic manipulations . ContinuAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."}
+{"text": "Asthma still poses a substantial and unacceptable health and economic burden. The National Asthma Education and Prevention Program (NAEPP) guidelines for the management of asthma continue to evolve based on emerging clinical data, improving the understanding of asthma and approaches to its management.To examine the clinical implications of current NAEPP guidelines for the diagnosis and treatment of asthma and the potential impact of the proposed 2007 guidelines update on asthma management. To examine the role of managed care organizations in fostering evidence-based asthma management.Current NAEPP guidelines recognize symptom control as the chief therapeutic target in the management of asthma. The proposed update to NAEPP guidelines places greater emphasis on symptom control by expanding its definition to not only include measures of impairment but also the risk for deteriorating pulmonary function, asthma exacerbations, and controller medication side effects. Although inhaled corticosteroids remain central to achieving long-term asthma control in both current and proposed guidelines, the latter offers greater treatment flexibility and recognizes combination therapy as a preferred choice for achieving control in many patients with moderate persistent asthma. Managed care organizations, primarily using disease management programs, provide impetus for the widespread adoption of evidence based asthma treatment guidelines.Widespread adoption of evidence-based asthma management programs offers the opportunity for achieving and maintaining asthma control."}
+{"text": "Mental health problems increase the risk for long-term sick leaves, early transitions to disability pensions and unstable career paths. Individual Placement and Support (IPS) is an evidence-based program integrated into psychiatric care aiming to support individuals with serious mental illness in finding employment. One key element in the implementation of the program is that the program is adequately integrated into the psychiatric care. However, knowledge on implementation challenges as well as best practices experienced by the practitioners, especially from the perspective of professionals in psychiatric care, is limited.The Finnish Individual Placement and Support Evaluation Study (2020-2023) aims at investigating the implementation, feasibility as well as perceived benefits and outcomes of IPS program. The present study focuses on experiences on implementation of the program in the psychiatric care.Both quantitative and qualitative data from different stakeholders have been and will be collected. The data collection will be finished at the end of 2022. For the present study, data among professionals (psychiatric nurses and psychiatrists) in the psychiatric care has been and will be collected using questionnaires (n=58) and individual interviews (n=17). Among IPS employment specialist delivering the program, the data have been / will be collected using focus group interviews  and workshops.The preliminary findings of the study show that the key elements in successful implementation of the IPS program into the psychiatric care are sufficient information about the program among professionals in the psychiatric care, adequate flow of information between IPS employment specialists and psychiatric care (including regular meetings) and facilities promoting the co-operation . Majority of professionals in psychiatric care reported that the client-related communication with the IPS employment specialist had been active (81%) and adequate (76%).Successful implementation and integration of the IPS program into psychiatric care requires seamless cooperation and communication between mental health professionals and IPS employment specialists, especially in cases when the IPS employment specialists do not have access to patient information due to confidentiality legislation.None Declared"}
+{"text": "The Doctor of Nursing Practice (DNP) project collection is a group of approximately 120 DNP projects archived between 2017 and 2022 in Health Sciences Research Commons (HSRC), the health sciences institutional repository (IR) for the George Washington University. Our project focused on expanding avenues for the dissemination of DNP projects beyond our Digital Commons IR by integrating this content into the library's instances of Ex Libris Alma and Primo VE. By utilizing the Ex Libris Repository type import profile rather than the OAI-PMH feed, we identified enhanced opportunities for content discovery while likewise retaining better control over individual item records. The George Washington University (GW) is an R1 research institution located in Washington D.C. and the Himmelfarb Health Sciences Library is one of several GW libraries. Himmelfarb has maintained an instance of Digital Commons (Health Sciences Research Commons [Although the rise of search engines has led to the diminishing role of discovery services within academic libraries , the libThe content integration project focused on three phases\u2013extracting relevant metadata from the Digital Commons IR, adding content to library services platform and discovery system, and assessing usage. The project team began by exploring the Ex Libris documentation on Managing Import Profiles  and ultiIn the fall of 2021, the project team successfully batch added 89 bibliography records to the Himmelfarb instances of Alma and Primo VE using the Repository type import profile and the templated spreadsheet. Librarians have also created a DNP project Special Collection in Primo VE ["}
+{"text": "Depression is the leading cause of disability worldwide and low and middle-income countries (LMICs) carry over 80% of this disease burden. Attempts have been made to address depression in LMICs, with improvements in the home environment and maternal knowledge. However paternal depression is a neglected and under-researched area. Since maternal depression is associated with depression in fathers there is a need for partner inclusive parenting programs to address parental mental health and improve child outcomes.To evaluate the clinical and cost effectiveness of partner inclusive Learning through play plus (LTP+) intervention in reducing depression in fathers and mothers.To evaluate the effectiveness of LTP + intervention in improving child outcomes.To conduct process evaluation and identify challenges in transition to scale up of the intervention across Karachi, Pakistan from the perspective of fathers, mothers, and other stakeholders.This is a cluster randomised controlled (cRCT) trial of partner inclusive group parenting program called (Learning Through Play (LTP+) across 18 towns in the city of Karachi. Over 5000 parents (fathers and partners) will participate in the study with a capacity building component of training 4000 Community Health Workers across Pakistan.This large cRCT will confirm the clinical and cost-effectiveness of LTP+ in reducing depression in parents and improving child outcomes along with the barriers and facilitators to implement the LTP+ group parenting program and the possibilities to roll out the innovation at national level through engagement with policy makers.Addressing depression in parents is hugely important because of its adverse effects both for child and parents. This low-cost group parenting program will help in scaling up the innovation across health services in Pakistan and other LMICs.None Declared"}
+{"text": "Obesity and overweight attributed to poor nutrition and a lack of physical activity increasingly become a serious problem among women of reproductive age . PregnanAs recommended by the World Health Organization (WHO) and the Royal College of Obstetricians and Gynecologists (RCOG), sedentary time should be reduced and a weekly minimum of 150 min of aerobic physical activity of moderate intensity is needed for pregnant women . In a syPrevious studies have explored the impact and safety of different varieties of sports in pregnant women, either using a virtual program or via on-site supervision ,6. GenerThe short- and long-term influence of pregnancy physical activity on maternal and offspring health have always been a heated topic in this area. Previous systematic reviews and meta-analyses supported a positive effect of physical activity for preventing the onset of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP) and excessive gestational weight gain ,8,9. MorThe safety of physical activity during pregnancy possibly worries mothers most when they have a lack of knowledge regarding the fact that exercise is necessary and beneficial both for them and their child. Thus, it is of great importance to educate women pre-pregnancy or in the early pregnancy stages on the advantages of gestational exercise, especially women who received ART. Women should also be warned about the absolute and relative contraindications to physical activity such as severe cardiac or respiratory diseases in advance. An individualized strategy tailored by professional physicians taking into consideration personal motivation and resistance is recommended for improving adherence to physical activity throughout pregnancy . In conclusion, physical activity during pregnancy has great potential to improve maternal and offspring health in different ways. Future clinical studies of higher quality, especially prospective RCTs of larger populations, are warranted for further exploration of more efficient exercises to guide clinical practices."}
+{"text": "Deceased organ donation consists of both donation after circulatory death (CD) and donation after brain death (BD) . The majTo reduce transplant waiting lists, the use of marginal liver grafts could expand the pool of available organs by using deceased donors. Marginal livers can be classified into two different categories: those with a higher risk of impaired function , and grafts carrying the risk of infection or malignancy for the recipient  . This toThere is an urgent demand for therapeutic, surgical, and technological strategies to alleviate the detrimental effects of BD and CD on liver grafts, improve the tolerance of marginal livers to ischemia/reperfusion (I/R) injury, and address regenerative failure in partial hepatectomies and liver transplants . DespiteThere is also an unmet need for swift and non-invasive methods to assess the degree of steatosis and the presence of liver pathologies in donors, as these factors significantly impact transplantation prognosis. The establishment of novel approaches in liver transplantation and hepatic resections requires such tools.This Research Topic encompasses a range of contributions, including basic, translational, and clinical research, original studies, reviews, systematic reviews, brief research reports, case reports, and mini-reviews, focusing on the mentioned areas.Ning et al.). Other results shown in this issue identify and summarize the existing evidence regarding enhanced recovery after surgery (ERAS) failure and related risk factors after hepatic surgery. This systematic review and meta-analysis concluded that the frequently identified risk factors for ERAS failure after hepatic surgery are linked to operative and anesthesia factors, with major resection being a crucial aspect. Nevertheless, the authors highlight the necessity of performing more randomized controlled trials with standardized evaluation frameworks for ERAS programs . On the other hand, a review presented on the current topic discusses and shows the new advances made to detect the early signs of sterile inflammation and the extent of this damage as well as potential therapeutic options. This process named sterile inflammation is of clinical relevance in the context of liver surgery because it is the immune response associated with DAMPS released during cell death . Finally, the last manuscript in the collection elucidates on the prevalence of systemic circulating tumor cells (CTCs) before and after the resection of HCC and detects differences in CTCs between open liver resection (OPEN) and laparoscopic liver resection (LAP) cohorts. In comparison to conventional OPEN technology, LAP technology can augment the quantity of epithelial, mixed, and mesenchymal circulating tumor cells (CTCs). The study concluded that there was an increase in the total number of CTCs within the LAP group . This special topic consists of different manuscripts reporting new data about potential clinical applications in the field of major liver surgeries. The editors believe that they are of clinical and scientific relevance and further research in this direction is crucial for improving the clinical outcomes of liver transplantation and partial hepatectomy.The articles published on this topic show advances in the field of major liver surgeries as partial hepatectomies or liver transplantation, which could be of scientific and clinical interest. The first investigation presented in this issue is a case report that indicates the efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in patients with hepatocarcinoma (HCC) who underwent immunotherapy previously for the first time, which may be an alternative salvage option for HCC therapy (MM-C: Writing\u2014original draft. AT: Writing\u2014review & editing. CP: Writing\u2014review & editing."}
+{"text": "Anhedonia is a transdiagnostic psychopathological phenomenon, which is assessed as \u00abcore\u00bb for several diseases, first of all - schizophrenic and affective spectrum disorders. The problem of clinical features differentiation and identification of anhedonia\u2019s neurobiological mechanisms in the structure of the affective and schizophrenic spectrum disorders is still topical and far from being resolved.The aim of the study was comparative research of the relationship between the features of neurocognitive functioning and the manifestations of anhedonia among patients with disorders of the schizophrenic and affective spectra.The sample consisted of 40 patients, 17 patients with schizophrenic spectrum disorders and 23 patients with affective spectrum disorders were examined. We used next psychometric techniques to research anhedonia: Revised Social Anhedonia Scale (RSAS), The Temporal Experience of Pleasure Scale (TEPS), Physical Anhedonia Scale (PAS). We used following methods to study neuropsychological features: Dynamic praxis; Color interference test; Arithmetic Tasks; Plot picture; Number of skips and impulsive errors; Reverse and straight rows; Verbal fluency; Number of repetitions; Rey-Osterritz figure.Patients with schizophrenia spectrum disorders show lower scores of pleasure anticipation ability and ability to experience pleasure in the social sphere. Neuropsychological indicators of prefrontal cortex dysfunction demonstrate a positive relationship (p = 0.035) with the severity of social anhedonia and a negative relationship with the ability to anticipate pleasure. Thalamus and forehead dysfunction indicators mainly show a negative relationship with the ability to directly experience pleasure. Indicators of dysfunction of the parietal, occipital and temporal lobes have single connections with different parameters of anhedonia.Manifestations of different parameters of anhedonia demonstrate their heterogeneity among patients with schizophrenic and affective spectrum disorders. Patients with schizophrenic spectrum disorders have greater difficulty with anticipation of pleasure and the ability to experience pleasure in the social sphere. The ability to anticipate pleasure is more strongly related to prefrontal brain function, whereas the ability to experience pleasure directly is related to subcortical brain function.None Declared"}
+{"text": "Detailed information about the impact of bacterial antimicrobial resistance (AMR) on Lower Respiratory Tract and other thorax Infections (LRTIs) is currently unavailable. It is important to have precise data on bacterial AMR to develop effective programs and policies for controlling AMR and to use antibiotics prudently for optimal treatment of LRTI patients. The primary objective of this research is to present extensive estimates of the mortality due to \"bacterial pathogens\" and its \"AMR\" of LRTIs in the United States in 2019.Mortality data associated with bacterial antimicrobial resistance and lower respiratory tract infection (LRTI) pathogens were acquired from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) in 2019.In United States, there were 88089 deaths  due to bacterial pathogens in LRIT in 2019. Highest number of deaths observed due to Staphylococcus aureus (34.04%), followed by Streptococcus pneumoniae (18.30%), Pseudomonas aeruginosa (12.48%) in LRTI in 2019. There were 10984 deaths attributed to and 46482 deaths associated with bacterial AMR in LRTI in 2019.Bacterial pathogens causing LRTIs are a significant cause of mortality in the United States. Moreover, antimicrobial resistance (AMR) among these pathogens has become a growing concern, exacerbating the burden of LRTI-related deaths. The implementation of such measures, along with the promotion of antimicrobial stewardship, can help to mitigate the impact of LRTI-associated deaths and preserve the effectiveness of available antimicrobial agents for the future.All Authors: No reported disclosures"}
+{"text": "Recent studies suggest oral antibiotics can be a non-inferior alternative to intravenous antibiotics for treating bone and joint infections. In this study, we aimed to investigate whether insurance type affects the choice of antibiotic treatment routes and whether the route of antibiotic treatment influences the delivery of home health services.We conducted a retrospective chart review of non-bacteremic patients who underwent amputations for forefoot osteomyelitis with residual signs of infection on proximal bone cultures and were discharged home from the hospital. Of 461 patients scheduled for hospital follow-up visits for bone and joint infections in our community practice infectious diseases clinic from January 2019 to December 2022, 40 met the inclusion criteria. Results were analyzed with multivariable logistic regression, selecting models with the lowest Akaike Information Criterion.The placement of PICC lines decreased significantly over time , mirroring national trends favoring increased oral antibiotic use. After controlling for the year of treatment, we observed a trend towards patients with Medicaid insurance more frequently receiving IV antibiotics . We found no evidence that the antibiotic administration route led to differences in the delivery of home health services at the time of discharge (p = 0.99).PICC Placement Percentage by Year and InsurancePercentage of PICC line Placement by year in patients with and without Medicaid Insurance during hospital encounterPICC Placement Frequency by Insurance and Home NursingFrequency of PICC placement in patients during hospital encounters based on (A) if a patient has Medicaid insurance and (B) if home nursing is ordered at dischargeOrganisms Cultured by YearFrequency of organisms cultured on proximal bone cultures by year of studyOur findings suggest a trend towards patients with Medicaid insurance more frequently receiving IV antibiotics, despite the higher direct and indirect costs. It remains unclear whether this trend is due to differences in the severity of infections or microbiological resistance patterns. Future studies should assess the interaction of psychosocial and microbiological factors in influencing shared decisions regarding the route of antibiotic treatment outside of clinical trial settings.Organisms Cultured by Antibiotic Route, Insurance Type, and Home Nursing OrdersFrequency of PICC line placement (A), Insurance coverage (B), and ordered for home nursing at discharge (C) by organisms cultured from proximal bone marginsAll Authors: No reported disclosures"}
+{"text": "Bipolar disorder (BD) is a chronic and recurrent mental condition characterized by mood fluctuations between hypomania or mania and depression, with high level of burden and mortality rates . Subsyndromal mood symptoms, including residual depression, mania and/or anxiety, are major risk factors for episodic relapses after mood stabilisation . A psychological protective mechanism against the occurrence of these maladaptative mood symptoms is dispositional mindfulness (DM). DM refers to paying purposeful attention to present moment experiences with a curious, non-judgmental and accepting attitude . DM has been barely assessed in BD and there is very little evidence on the relationship between DM, residual mood symptoms and quality of lifeTo explore associations between DM, residual mood symptoms and quality of life in individuals with BDAfter informed consent, a total of 94 adults  with diagnosis of BD according to DSM-5 criteria, in full or partial remission,were recruited from the Bipolar and Depressive Disorders Unit at the Hospital Clinic of Barcelona. The ethical committee approved this study. Dispositional mindfulness was assessed using the Mindfulness Attention Awareness Scale (MAAS).The presence of residual depressive symptoms was assessed with the Hamilton Depression Rating Scale (HDRS), residual mania symptoms were assessed with the Young Mania Rating Scale(YMRS), and anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale (HAM-A). The subjective quality of life was assessed with the Quality of Life in Bipolar Disorder Questionnaire (QoL-BD). Pearson correlations were carried out and the level of significance was set at p<0.05DM was negatively related to residual depressive symptoms  and to anxiety symptoms , and positively related to quality of life , but not related to residual manic symptoms in BDOur preliminary data suggest that BD patients with higher levels of DM may experience less depressive and anxiety subsyndromal symptoms and perceived higher quality of life. No associations were detected regarding mania symptoms. These findings support the use of mindfulness training as an adjunct therapy to pharmacotherapy to reduce residual mood symptoms and improve quality of life in patients with BDNone Declared"}
+{"text": "To outline some of the causes of medication errors and recommend ways that managed care pharmacy organizations and managed care pharmacists can prevent some of these errors through practitioner and patient education.Patient safety has become a major concern since the November 1999 release of the Institute of Medicine (IOM) report, To Err Is Human. Errors involving prescription medications are responsible for up to 7,000 American deaths per year and the financial costs of drug-related morbidity and mortality may cost nearly $77 billion a year. The Institute for Safe Medication Practices (ISMP) collects and analyzes voluntary confidential medication error reports and makes recommendations on the prevention of these errors. This article uses the expertise of ISMP in medication error prevention to make recommendations on educational programs for patients and managed care and community pharmacists to reduce medication errors in the outpatient (community) setting. These educational areas focus on patient education, compliance, and health care literacy.Managed care pharmacy is well positioned to affect change in the health care system. Through information dissemination and education, managed care pharmacists should play a more active role in medication error-reduction activities by improving the patient education process and in assisting the pharmacy community in its goal of improving patient safety."}
+{"text": "Synaptic plasticity defined as the ability of neurons to modify their synaptic strength and connectivity as a function of activity, has long been postulated to mediate experience-dependent remodeling of neural circuits that ultimately underlies memory formation at various timescales. Since the discovery of hippocampal long-term potentiation (LTP), considerable progress has been made in our understanding of structural and mechanistic bases of different forms of synaptic plasticity that drive behavioral adaptation to the changing environment but also may confer our vulnerability or resilience to brain and behavioral pathology in response to adverse environmental factors, aging, and different types of trauma and insult across development /NO/ soluble guanylate cyclase (sGC) signaling, leading to enhanced frequency and amplitude of excitatory postsynaptic currents. This finding provides an additional structural plasticity mechanism underlying LTP expression.Structural plasticity of synapses correlates with changes in synaptic strength. For example, activation of NMDA receptors results in long-term enhancement of both dendritic spine size and synaptic strength  is a form of inherited intellectual disability caused by the loss-of-function mutations in the FMR1 gene. Key synaptic phenotypes in the FXS include exaggerated long-term synaptic depression (LTD) and impaired homeostatic synaptic plasticity, as well as altered spine density and morphology  stimulation in the intact brain of behaving animals. They made the interesting observation that LTP can be induced not only at the ipsilateral PP-CA3 synapses where the presynaptic input received direct stimulation, but also at secondary downstream synapses such as CA3 to contralateral CA1 synapses, thus corroborating previous reports demonstrating polysynaptic \u201cpropagation\u201d of LTP at synapses directly downstream of the stimulated ones . The cross-modal plasticity increases the capabilities and performance of spared modalities in the affected individual that is dependent on the remaining senses in their everyday life  model of ELA, which causes fragmented and unpredictable maternal care and neglect of pups  suggest that exposure to severe stress and adverse experiences during sensitive early developmental periods confer considerable risk for vulnerability to substance use disorder, depressive and anxiety phenotypes by triggering/altering synaptic plasticity in brain regions and neural circuits that are critical for cognitive functioning, mood regulation and motivated behavior  receptor activation (Palmer et al., The collection in this Research Topic serves as a vignette of the current efforts in the field of synaptic plasticity. These discoveries will continue to deepen our understanding of normal and pathological synaptic plasticity and we hope they fuel enthusiasm for future synaptic-based research on causal mechanistic links between structural and functional synaptic plasticity within brain circuits and networks influencing learning, reward and motivated behaviors in health and disease.FN, KL, and LC equally contributed to writing the article and approved the submitted version. All authors contributed to the article and approved the submitted version."}
+{"text": "Cellular reprogramming is the process whereby one cell type can be converted to another, this includes directed differentiation, induced pluripotency and transdifferentiation. Understanding the mechanisms underlying normal cell and tissue development has provided insight to how these cell-type conversions arise and enabled the development of potential autologous cell-replacement therapies.The goal of this Research Topic was to highlight novel and promising advances in the field of cellular reprogramming and differentiation that have potential utility in the design and development of cell replacement therapies. The Research Topic includes four articles that shed light on different aspects of regenerative medicine and cellular reprogramming, including kidney development and disease, osteoblast development, degenerative conditions and novel therapeutic targets for cardiovascular disease. These studies provide valuable insights into the underlying mechanisms of these processes and present potential avenues for future research and clinical applications.Moretto Rodrigues et al. investigated the role of triiodothyronine (T3) in proliferation, differentiation and maintenance of osteoblasts. Using osteoblast-like cells differentiated from human adipose-derived mesenchymal stem cells, the authors show that T3 adversely affected osteoblast development by hindering crucial signaling pathways involved in bone metabolism. This study highlights the need for further research to elucidate the mechanisms of T3 action and its potential implications the pathophysiology of bone disease.The brief research report by Kuang et al. For each disease, the authors highlight recent progress in the production of functional cell types and provide an overview of the starting cell types, factors and methods used in cellular reprogramming approaches. By discussing the underlying mechanisms of reprogramming and presenting recent progress in diverse functional cell types, the authors lay the foundation for future investigations and highlight the potential general principles governing reprogramming.The latest advances into the potential of directed differentiation and transdifferentiation for cell-based therapies for the treatment of diverse diseases, including type I diabetes, myocardial infarction, neurodegenerative diseases and liver fibrosis, were reviewed by Safi et al. provide a comprehensive review on the development of kidney organoids derived from human pluripotent stem cells (hPSCs). These organoids provide a platform for studying kidney morphogenesis, renal differentiation and disease modelling. The authors describe the interplay of developmental pathways and discuss how CRISPR/Cas9 technology has enabled the recapitulation and correction of cellular phenotypes associated with renal disease. The limitations of kidney organoid technology are acknowledged, and the potential for bioengineering solutions to enhance standardization is discussed.Barungi et al. Currently, surgical intervention for cardiovascular disease relies on coronary artery bypass grafting or stent placement. However, immune responses and restenosis (a re-thickening of the vessel following surgery) frequently thwart these approaches. The authors highlight the capacity of harnessing technological advances, such as electrospinning and bioprinting, to generate cellularized vascular tissue engineered vascular grafts. Key aspects in the production of such grafts are discussed, including cell sources, and coating with therapeutically designed nanoparticles designed to improve biocompatibility.The merits and pitfalls of current interventions for cardiovascular disease were debated by The findings presented in these articles highlight the ongoing efforts in the scientific community and point towards promising future directions for biomedical research and clinical applications. By expanding our knowledge in these areas, researchers can pave the way for improved diagnostics, treatments, and regenerative medicine approaches."}
+{"text": "Neurodegenerative diseases (ND) have caused a wide range of distress and social problems in the aging population and affect millions of people worldwide . Among tvia regulating ubiquitin proteasomal system (UPS) (via HDAC6 inhibition (via chaperone-mediated autophagy (CMA) . PRO-Br particularly reduced insoluble pathogenic pTau clumps and enhanced memory functions in AD mouse models . Protopine-derivative PRO-Br prompted CMA for the clearance of pTau and inhibited the function of HDAC6 to enhance the expression of molecular chaperones and lysosomal biogenesis.Over the years, Traditional Chinese Medicine (TCM) has been in practiced in East Asia for the treatment of neurological disorders like AD and PD using herbal formulations  and phytem (UPS) . Among thibition . ChemicaSelvarasu et al.). Overexpression of KIF5B significantly increased tau hyperphosphorylation, aggregation, and memory impairment in AD models suggesting that KIF5B is important for tau stability. Conclusively, their results found that KIF5B is an essential protein in modulating the tau firmness in microtubules and reducing the tau aggregates accumulation in AD and other tauopathies. One more research article evaluated the functions of differentially expressed genes (DEGs) and intestinal microbiota regarding the occurrence and causatives of post-stroke depression (PSD), which is one of the most common NDs . In this study, the authors identified metabolic pathways causing stroke and PSD via enrichment analysis, and constructed a global metabolic network to study the disease progression and the prevention of PSD. Based on transcriptomics, 16S rDNA sequencing and non-targeted metabolomics patient data, the authors found the causative microbial flora and impaired DEGs which can induce depression by impacting the metabolism of PSD patients. Collectively, using advanced technology, this study has found new therapeutic targets for the impediment of PSD and therapy for PSD patients with concluding evidence. An additional interesting study revealed that SIRT6 is an essential target for the neurological severity in Friedreich ataxia (FRDA), a recessive ND . Patients with FRDA were subject to DNA analysis to find the targets proteins which are contributory to the symptoms of FRDA and its severity. It was revealed that patients with cytosine variants of SIRT6 had less severe neurological symptoms and visual dysfunction when compared with the common thymine SIRT6 variant patients. In conclusion, the authors found that transcriptomic changes in the SIRT6 variant function may be causative of the neurological symptoms of FRDA patients, and a deep constructive analysis remains a requirement for clinical trials.In another submitted article, the authors found that knockdown of kinesin I heavy chain KIF5B reduces tau hyperphosphorylation and aggregation in AD models with tauopathies (The research articles published in this Research Topic demonstrate the advancement in studies pertaining to NDs, utilizing state-of-the-art technologies and strategies with effective tools for molecular therapeutic research. These research articles may provide a foundation for future research ideas and may enable the development of therapeutic targets with translational potential in ND research. In conclusion, this Research Topic is noteworthy in its contribution to the advancement of diagnostics and therapeutics of NDs."}
+{"text": "The recovery of cells after tissue and organ injury is a complex process. To understand the underlying molecular biological mechanisms, more detailed insights into the cellular processes of repair and regeneration are urgently needed. Based on this knowledge, this Special Issue focuses on current in vitro systems exploring repair and regeneration mechanisms. Experimental research approaches to investigate the mechanisms involved and laboratory methods to establish and optimise models for tissue and organ repair and regeneration, as well as theoretical modelling and computational models, but also review papers are included here. Eleven articles are published in the Special Issue, which deals with various tissue and organ regeneration questions or the modelling or summary of the research models used in this process.Shyam et al. comprehensively summarise various methods involved in developing 3D cell culture systems, emphasising the differences between 2D and 3D systems and methods involved in recapitulating the organ-specific 3D microenvironment . They alTwo original works use in vitro models of mesenchymal stromal/stem cells (MSCs) to investigate regenerative purposes. Barbon and coworkers use an in vitro conditioning regimen of MSCs towards the endothelial lineage to stimulate coagulation factor VIII production . The bacIn addition, two other in vitro studies use epithelial cell systems to investigate their differentiation or their involvement in inflammatory processes. Primary alveolar epithelial cells\u2019 main limitation is the difficulty of maintaining the type II phenotype in culture. Marhuenda and coworkers show that culturing primary alveolar epithelial cells on lung extracellular matrix-derived hydrogels facilitated the prolonged culturing of these cells and enhanced the preservation of the type II phenotype . Baer anSteyn-Ross and coworkers describe the ex vivo quantification of tissue oxygen consumption by measuring oxygen partial pressure as a function of probe depth using thin slices of cortical brain tissue . The autFinally, this Special Issue contains two publications addressing issues using in vivo models. Azam and coworkers investigated the prevention of neuroinflammation in vitro and in vivo using an herbal extract and purified dioscin . The in"}
+{"text": "Diarrhoea remains the major cause of morbidity and mortality of children under five years in Africa. Several studies have shown that inadequate and unsafe water, lack of sanitation, and poor hygiene practices are complex issues for different pathogens and accountable for the occurrence of diarrhoea diseases. We assessed the combined effect of household\u2019s source of drinking water and type of toilet facility and residential wellbeing on the incidence of childhood diarrhoea in 33 Sub-Saharan Africa countries while accounting for relevant compositional and contextual factors.The 2010\u20132019 datasets from the Demographic and Health Surveys were drawn for analyses. The outcome variable used in this study was the incidence of childhood diarrhoea. Three negative log-log generalized linear regression models were then sequentially fitted to the data to examine the joint effect of household water and sanitation practices on child diarrhoea. The results were presented using crude odds ratios (CORs) and adjusted odds ratios (AORs) at 95% confidence intervals (CIs). Using ArcGIS software, maps were design to unveil the spatial distribution of key variables.Approximately 16% of the 307,741 mothers interviewed reported an incidence of diarrhoea disease among children under-five years in their households. The results showed that a household depending on an unimproved source of drinking water and with an unimproved type of toilet facility was not significantly associated with childhood diarrhoea. However, those with improved drinking water but an unimproved type of toilet facility had higher odds of reporting childhood diarrhoea  compared to those in households with both improved source of drinking water and type of toilet facility. Across the geographical regions, Eastern  and Central Africa  were more likely to experience child diarrhoea.Water and sanitation practices such as the source of drinking water and toilet facility, and geographic region had significant effects on childhood diarrhoea in sub-Saharan Africax. The findings suggest the need for multi-sectoral actions that recognise the geo-spatial and temporal characteristics identified in the study through regional to national policies. Water and sanitation community-based interventions that seek to improve equitable access to safe water and sanitation in the sub-region should be intensified. Access to safe drinking water, sanitation facilities and proper hygiene is fundamental to the maintenance of good health and wellbeing. Improving access to safe water, adequate sanitation and proper hygiene are on the frontline of efforts to achieve the anticipated 2030 Sustainable Development Goals 3 and 6 . HoweverA recent report from the United Nations Inter-agency Group for Child Mortality Estimation (UN-IGME) indicates that 6.3 million children and young adolescents died in 2017 alone  aims to share relevant and action-oriented information and motivate program specialists to work with communication specialists in preparing strategic communication. Similarly, BCC should be incorporated into health education for teenage mothers, to instil behaviour change for effective hygiene practices that will help protect children from disease pathogens.This study examined the joint effect of water and sanitation practices on childhood diarrhoea in sub-Saharan Africa. The current reported prevalence (16%) is still high. Water and sanitation practices and geographical region within SSA all contribute significantly to childhood diarrhoea. These findings require multi-sectoral actions that recognise the geo-spatial and temporal characteristics identified, through regional to national policies. Water and sanitation community-based interventions that seek to improve equitable access to safe water and sanitation in the sub-region must be intensified. Moreover, interdisciplinary research aimed at comparing existing interventions  using longitudinal designs to assess their effectiveness over time would help policy re-alignment and also pave the way for new strategies.S1 Fig(JPG)Click here for additional data file."}
+{"text": "Rashid et al.).Microglia are a type of immune cells found in the retina that play a crucial role in maintaining retinal homeostasis, protecting against injury, and responding to disease . In a heWang et\u00a0al.). These strategies include depleting microglia with chemicals or radiation, reprogramming microglia using homeostatic signals or other small molecules, and inhibiting the downstream effects of microglia, such as by blocking cytokine activity or phagocytosis. The paper discusses the use of genetic and pharmacological methods for depleting microglia in animal models and provides details on various small molecules, such as CSF1R inhibitors . The paper highlights the poor phagocytic capacity of resident retinal microglia in clearing cellular and myelin debris, which is a major contributor to the formation of growth-inhibitory myelin debris and a glial scar that inhibit RGC axon regeneration and visual function recovery in patients with traumatic optic neuropathy. The review also discusses the impact of intraocular inflammation and chronic neuroinflammation on secondary tissue damage and visual function recovery after ONC. The potential therapeutic strategies target the controlled activation of retinal microglia to foster neuroprotection and nerve repair.Continuing with the problem of microglia contribution to neuroinflammation and its impact on retinal ganglion cell survival, the second review paper focuses on the role of resident retinal microglia in facilitating Wallerian degeneration and subsequent axon regeneration after optic nerve crush (ONC) injury as well as their production of pro-inflammatory cytokines, chemokines, and reactive oxygen species that have neurotoxic effects on retinal ganglion cells (RGCs)  in retinal vein occlusion (RVO) using en-face optical coherence tomography (OCT). These infiltrating cells are likely to consist of retinal microglia and inflitrating macrophages (MLCs). The research involved 36 patients with RVO, and the MLCs were binarized and quantified using a semiautomated method. The results showed that the morphology of MLCs in RVO eyes appeared larger and plumper, and the density of MLCs was significantly higher in the affected region than in the unaffected region. The study suggests that the increased density and changes in morphology characterized by OCT may indicate generalized activation and aggregation of MLCs in RVO. The role of MLCs in the clinical consequences of retinal diseases is a growing interest. The study presents a novel in vivo imaging method to visualize individual MLCs on the inner limiting membrane of the human retina using clinical en face OCT.In the more clinical research contribution, Puthenparampil et\u00a0al.). In this, the authors investigated the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing-remitting MS (RRMS) patients at clinical onset. They found that HRF count in the ganglion cell layer (GCL) was associated with certain cytokines and that CSF concentrations of certain cytokines were also associated with global cortical thickness. HRF count in the inner nuclear layer (INL) correlated with different cytokines, and the CXCL-13/CXCL-2 ratio was strongly associated with HRF count and cortical lesion volume. The authors suggest that the association of HRF with cytokines confirms their microglial origin and indicates they may be useful as markers of activated microglia. OCT with a single linear scan through the macula proved an effective method for in vivo evaluation of activated microglia in the retina.The final manuscript in the collection is the original research investigating retinal hyper-reflecting foci (HRF) in the OCT images in the retina of multiple sclerosis (MS) patients that may represent clusters of activated and proliferating microglia (In conclusion, studying microglia in the retina is an area of active research. The contributions in this Research Topic highlight new and innovative methods for investigating these immune cells. The review papers shed light on the potential of targeting microglia to treat degenerative eye diseases and to foster neuroprotection and nerve repair. The original research contributions provided valuable insights into the molecular profile of human retinal microglia, the clinical features of macrophage-like cells in retinal vein occlusion, and the use of retinal hyper-reflecting foci as markers of activated microglia in MS. Overall, the findings presented in this special issue enhance our understanding of microglia biology in the retina and pave the way for new therapeutic approaches for retinal diseases.The editorial was written by AL and K-SC and revised by AL, both authors reviewed and accepted the final version of the manuscript."}
+{"text": "The Canadian Real-world Evidence for Value of Cancer Drugs  collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug\u2019s perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health\u2019s Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations. The rapid pace of cancer drug development over the past decade has led to new challenges for health care spending, particularly in publicly funded health care systems . In CanaThe Canadian Real-world Evidence for Value in Cancer Drugs  Collaboration was created to develop a framework to generate and use RWE to support cancer drug funding decisions . CanREVaGiven the potentially large number of uncertainties that may be addressed through RWE analyses, there is a need to assess and prioritize RWE questions that are relevant and feasible for public payers when making drug-funding decisions. Multi-criteria decision analysis (MCDA) is an approach that can be used to support complex decision-making by allowing the assessment of multiple different viewpoints across a broad range of stakeholders . ThroughThe development of the MCDA rating tool was led by an expert in MCDA application (FD) and developed in collaboration with the Planning and Drug Selection WG. The methods used to inform our development process have been applied successfully in numerous health care settings in Canada and are in accordance with the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Good Practices Guidelines ,14. On tIn consultation with an expert in MCDA development (FD), a set of draft criteria to assess and prioritize potential RWE questions was conceptualized. This set included 10 criteria categorized into two groups. Group A assessed the importance of the proposed RWE question or uncertainty identified during assessment of drug funding recommendations and Group B assessed the likelihood of finding an answer to the RWE question or resolving the identified uncertainty . As recoNext, the WG developed performance measures unique to each criterion. The performance measures encompass either quantitative or qualitative metrics to assess the RWE question. For instance, assessment of the drug\u2019s perceived incremental benefit is quantitative based upon reported clinical outcomes  of the therapy of interest as observed in either clinical trial evidence or through indirect comparisons. Alternatively, a qualitative assessment by expert opinion is required to assess the relevance of the proposed RWE question .Rating scales allow for scoring of the developed performance measures . A uniquWeights were developed for each criterion in the MCDA rating tool to incorporate the relative importance of each criterion in the assessment of a proposed RWE study. The process of weighting the criteria involved multi-disciplinary stakeholder engagement to ensure the preferences of relevant end-users were elicited and incorporated . Note thConsistent with other applications of MCDA in health care, an additive model is used to calculate aggregate scores and thus was adopted for our rating tool . ApplicaROS-1 rearrangement?\u201d, and (b) \u201cWhat is the real-world comparative effectiveness of nivolumab in patients with classical Hodgkin\u2019s Lymphoma with evidence of disease progression following autologous stem cell transplantation and brentuximab vedotin, as compared to standard single-agent chemotherapy or pembrolizumab immunotherapy?\u201d Following each pilot test, qualitative feedback was elicited from participants through the use of surveys and roundtable discussions, to assess the overall usability of the MCDA rating tool and its applicability in assessing the value of potential RWE projects. Following development of the initial MCDA rating tool , two pilot tests were performed in June and December 2020 to evaluate the usability of the tool in assessing and prioritizing proposed RWE projects. Each pilot test was conducted with a group of multi-disciplinary participants made up of clinical experts, methodologists, and various health policy experts. During the pilot tests, five participants were provided a mock RWE study proposal and were asked to individually rate the proposal using the MCDA rating tool. The two mock RWE proposals were: (a) \u201cWhat is the real-world comparative effectiveness of first-line crizotinib, as compared to platinum-based chemotherapy for patients with metastatic non-small cell lung cancer that harbors a Through this process, participants consistently reported that the MCDA rating tool was easy to use. Participants felt that the MCDA rating criteria assessed all relevant attributes needed to understand the importance and feasibility of RWE proposals. Consensus on criterion rating was consistently achieved through discussion. Instances of initial discordant results often occurred when users reported uncertainty in their rating of specific criteria, most commonly with criterion 1 , criterion 4 (relevance of uncertainty), criterion 7 (data) and criterion 9 (methodology). However, by engaging a multi-disciplinary committee of experts, members were able to share pertinent expertise and unique perspectives to address each criterion in the MCDA rating tool which contributed to meaningful discussion and helped to achieve consensus. There was agreement that future committees should continue to include clinical experts, methodologists and decision-makers involved in Canadian drug funding decisions. We also identified several other critical stakeholders to be included in future iterations, such as a bioethicists and patient representatives. Additionally, many users also noted overlap in their interpretation of criterion 3 (impact of uncertainty) and criterion 4 (relevance of uncertainty). Through careful consideration of this feedback, it was felt that criterion 3 was assessing a similar attribute as criterion 4. Therefore, to avoid redundancy in the rating tool, criterion 3 was removed. Similarly, many users noted overlap in their assessment and rating of criterion 8 (expertise) and criterion 9 (methodology) prompting merging of these two criteria to avoid redundancy. The modified MCDA rating tool inclusive of seven criteria can be found in Through a stepwise, iterative process, CanREValue\u2019s Planning and Drug Selection WG has created and validated a MCDA rating tool that can be used to assess the value and support the prioritization of proposed RWE studies intended to reduce uncertainties in Canadian cancer drug funding recommendations. As the number of cancer drugs in the public drug funding pipeline continues to grow, use of the MCDA rating tool is expected to support a process that identifies the most pertinent and relevant post-market RWE studies. A notable limitation of the current MCDA rating tool is the reliance on expert opinions to measure performance for many of the criteria. To mitigate this, as our validation testing shows, effective use of the MCDA rating tool into decision-making for utilization of RWE in drug funding recommendations will require multi-disciplinary committees, with all relevant clinical, health policy and methodology experts included, to adequately apply the MCDA rating tool and minimize any potential uncertainty with generated scores. Additionally, the quantitative measures used to evaluate the magnitude of uncertainty in survival estimates and/or estimates of cost-effectiveness  may be imprecise given their derivation from consensus opinion among the WG . HoweverFuture directions for the CanREValue\u2019s Planning and Drug Selection WG include ongoing engagement with stakeholders in the cancer drug funding pathway to identify opportunities for application of the MCDA rating tool and to discuss implementation strategies. This includes a recent partnership with the Canadian Agency for Drugs and Technology in Health (CADTH) Provincial Advisory Group (PAG) to gain important insight into how this tool could be used to identify potential RWE studies during initial drug funding deliberations, as well, to promote ongoing discussions of how planned RWE studies may be used to support initial drug funding recommendations."}
+{"text": "The blood-brain barrier (BBB) is a crucial physiological structure that plays a vital role in maintaining the integrity and homeostasis of the brain. It acts as a highly selective semipermeable border, formed by capillary endothelial cells, tight junctions, astrocytic end-feet, and pericytes embedded in the basement membrane, to regulate the passage of substances between the blood and the brain. The development of visualization systems using advanced imaging techniques offers new opportunities to study BBB dynamics and its contribution to neurological disorders including Alzheimer's disease and related dementias. These advancements have the potential to improve our understanding of the disease mechanisms, aid in early diagnosis, and guide the development of novel therapeutic strategies.ex vivo or in vivo BBB imaging to better characterize properties of diseased tissues; (3) Potential applications of BBB imaging techniques in Alzheimer's disease and related dementias; (4) Analysis of BBB functions using advanced imaging techniques in the whole brain or specific brain regions between patients and healthy controls to find biomarkers for neurodegenerative diseases or try to explain their pathogenesis; and (5) Applications of BBB imaging in studying pathological processes of brain diseases that contribute to disease classification and early diagnosis.The purpose of this Research Topic was to encourage the proposal of advanced methodologies related to BBB imaging techniques and their applications to BBB related diseases. The current researchers have enthusiastically been developing visualization systems of BBB dynamics using advanced magnetic resonance imaging and molecular imaging techniques: (1) Novel methods that facilitate the progress of BBB imaging techniques; (2) High-resolution and high-field Moyaert et al., they overviewed the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging modalities for evaluating BBB function and integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? They highlighted the need for further advancements in imaging techniques, including validation, standardization, and the development of cost-effective methods. By addressing these challenges, BBB imaging has the potential to become a valuable clinical tool in both resource-limited and well-resourced settings.In a comprehensive and well-written review, by Uchida et al. summarized the recent developments in BBB imaging using advanced MRI techniques in the context of Alzheimer's disease and related dementias. They described the histories and principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies with a detailed comparison between them. In addition, they addressed the challenges of BBB imaging techniques and suggested future directions to develop clinically useful imaging biomarkers for Alzheimer's disease and related dementias.Another comprehensive review article by Lee and Funk reviewed the structural and functional changes in the BBB that occurred during the Alzheimer's pathogenesis in terms of neuroinflammation. They emphasized the importance in discerning the trajectory of BBB breakdown, aided by improving BBB imaging technologies. These advancements can help identify specific microstructural changes within the neurovascular unit and shed light on the mechanisms underlying BBB breakdown in Alzheimer's disease and related dementias.Neuroinflammation has been known to play a significant role in the pathogenesis of these conditions, and BBB dysfunction is closely linked to the inflammatory processes in the brain. Zhukov et al. investigated the BBB function and neurovascular coupling in a specific model of amyloidopathy called the 5xFAD mouse model. Using in vivo two-photon microscopy in the superficial cortical layers and ex vivo imaging across brain regions, the authors examined the BBB function and neurovascular coupling at the level of individual brain vessels in adult female 5xFAD mice leading to a better understanding of Alzheimer's pathophysiology and the development of novel therapeutic strategies.The study conducted by Jullienne et al. underwent in vivo positron emission tomography (PET) imaging with 18F-Fluorodeoxyglucose to assess regional glucose metabolism. They highlighted a potential mismatch between metabolic demand and vascular delivery of nutrients in the 5xFAD mouse model. This mismatch between metabolic demand and vascular supply may contribute to the progressive cognitive deficits observed in the 5xFAD mouse model. Understanding the complex interplay between vascular dysfunction and metabolic alterations might be crucial for unraveling the mechanisms underlying Alzheimer's disease and developing effective therapeutic strategies.Using both male and female 5xFAD mice, Overall, the collective findings presented in these manuscripts have advanced our knowledge of the BBB physiology and its implications in Alzheimer's disease and related dementias. They provide a foundation for future research and open new avenues for the development of interventions and imaging biomarkers in the field of neurodegenerative diseases.YU wrote the editorial. All authors read and approved the final editorial."}
+{"text": "In the published article, there was an error in the Funding statement. [grant no. . The correct statement appears below:Acknowledgments\u201cThis research work was funded by the Institutional Fund projects under grant no. (IFPIP:1866-141-1443). The authors gratefully acknowledge technical and financial support provided by the Ministry of Education and King Abdulaziz University (KAU), Deanship of Scientific Research (DSR), Jeddah, Saudi Arabia.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."}
+{"text": "The Cancer-associated fibroblasts (CAF) are abundant cell types, present in stromal that are found in stromal pockets of solid tumors. Under normal physiological conditions, fibroblasts exist as quiescent and less migratory cell types with limited synthetic and metabolic activities . HoweverCAFs are highly versatile and plastic populations with both molecular and functional heterogeneity . CAFs haComprehensive analysis of CAFs using single cell genomics and transcriptomics may shed light on molecular and functional heterogeneity of CAFs. Recent single cell transcriptomics identified several subsets of CAFs depending on types of tumors and position within tumors. However, the study of the conservation of these populations across the species and tissue of origin can elucidate commonalities that may have therapeutic potential. In addition, comprehensive dissecting of the signaling pathways responsible for instigating CAF-mediated tumor progression may facilitate the targeting tumor promoting cues and sparing the inhibitory cues for increasing the efficacy of cancer therapies."}
+{"text": "More than one billion people live in informal settlements under precarious conditions. Urban planning is considered an important instrument to mitigate compromised living conditions in informal settlements. However, limited studies have investigated the long-term impact of urban planning in contexts with limited capacity to enforce building and planning regulations. The purpose of this study is to assess the long-term impact of urban planning on the development of sustainable urban form in contexts characterized by unregulated urban development.The study conducted geospatial surveys of three urban areas in Maputo, Mozambique covering adjacent planned and unplanned settlements that were established more than 40 years ago and subsequently developed with limited enforcement of building and planning regulations. High-resolution maps were produced and six urban form metrics were computed for the planned and unplanned areas respectively, providing the basis for quantitative and qualitative comparative analysis.Although the study found signs of street encroachment and appropriation of the public space in the planned areas, the study found higher levels of built densities, higher proportions of public space, and higher average street widths in all planned areas compared to the respective neighboring unplanned areas. Furthermore, the statistical analysis consistently showed large effect sizes (Cohen\u2019s d > 0.8) of urban planning on indicators of compact city development and access conditions.The results underscore that planning of street fabrics and plot layouts can enhance compact city development, improve transportation conditions, and increase the feasibility of investments in infrastructure in contexts with limited capacity to administer the urban growth. Over one billion people reside in informal settlements characterized by lack of state recognition, contested rights to the land, and non-compliance with building and planning regulations . InformaSeveral aspects of the sub-standard living conditions commonly found in informal settlements are linked to spatial factors such as inadequate accessibility, high levels of building coverage, and limited public space , 12. As A number of studies have emphasized suitable policy measures to support the development of sustainable urban form of informal settlements in sub-Saharan Africa. These strategies include early establishment of planned urban structures, in situ upgrading of established informal settlements, and state recognition of the land occupation , 19\u201320. In the context of Maputo, Mozambique, previous research reported four distinct categories of informal settlements in Maputo: (1) formally planned areas recognized by the state, (2) unplanned areas lacking state recognition, (3) planned areas lacking state recognition, (4) unplanned areas recognized by the state . NotablyTo answer the question, the study analyzed the urban form characteristics of adjacent planned and unplanned settlements in Maputo which were established more than 40 years ago and subsequently developed with limited enforcement of building and planning regulations. These areas were surveyed using UAVs (drones) and GPS trackers for production of high-resolution geo-referenced orthophotos which were manually delineated and used for computation of urban form metrics. The study employed an analysis of quantitative urban form metrics extracted from the geospatial surveys along with a qualitative investigation of the respective planned and unplanned urban fabrics based on visual inspection of the manually delineated maps.Although the analysis does not provide insights into the socioeconomic and cultural dimensions of the development of the neighborhoods, it highlights the spatial outcome of these processes . DocumenThe study relies on (1) high-resolution geospatial surveys of case study areas covering adjacent planned and unplanned informal settlements; (2) manual delineation of buildings, streets, and trees; (3) computation of urban form metrics of the planned and unplanned informal settlements; (4) quantitative analysis the urban form metrics and qualitative analysis of the manually delineated maps.Mozambique is a low-income country located in southeast Africa and Maputo is the capital as well as social, economic, and cultural center of the nation. Since Independence, most of the urban growth of Maputo has been accommodated through proliferation of informal settlements and the majority of the population in the city resides in the informal housing sector . The stuThe sample areas were largely established in the period after Mozambique gained independence from Portugal during which the population of Maputo grew rapidly. However, although no academic sources exist on the planned area in Maxaquene A, it was established prior to independence as can be observed in historical aerial photos. The planned areas in Maxaquene D and Polana Cani\u00e7o A included in the study were established as a part of the Urbanization Project of Maxaquene and Polana Cani\u00e7o (1977\u20131979) developed by the National Directorate of Housing and funded by the United Nations . As a padistrito) and neighborhood (bairro) levels using a standardized form for conducting fieldwork obtained from the Faculty of Architecture and Physical Planning, Eduardo Mondlane University  to obtain authorization to capture aerial photographs of the sample areas. The detailed geospatial surveys of all planned and unplanned sample areas were conducted in June and July 2019, using a drone (UAV) for systematic collection of high-resolution photometric data. Utilizing Pix4D photogrammetry software, the aerial photos (photometric data) were processed to generate geo-referenced orthophotos, Digital Surface Models (DSM), and digital 3D models of each of the examined areas . The deeas (see ). These Buildings, streets, and trees were manually delineated based on the GPS traces, detailed orthophotos, DSMs, and 3d model. More specifically, the boundaries of all buildings were traced on the basis of the orthophoto. Each floor of multi-story buildings was delineated and annotated based on building heights and identification of each floor based on the DSMs and the 3d models. The street network and the public space were identified based on the GPS traces and orthophotos enabling delineation of the boundaries of all blocks. Trees were delineated with circles corresponding to the canopy observed in the orthophotos. The outputs, including orthophotos and manually delineated maps of each of the planned and unplanned sample areas are presented in Figs The manually delineated maps enabled automatic extraction of the total area of buildings , private space (blocks), and tree canopy cover. In addition, the number of blocks along with the total length of both the street network and the building perimeters were automatically computed and extracted from AutoCAD. The total public space area was calculated by subtracting the total private space area from the total area of each sample area. These data were used to compute six indicators of urban form, including Floor Area Ratio (FAR), Public Space Ratio (PSR), Average Block Size (ABS), Surface Area to Volume ratio (SAV), Average Street Width (ASW), and Urban Tree canopy Cover (UTC).These indicators were selected because of their respective importance in relation to scholarly discussions on urban form and sustainable transformation of informal settlements. Urban density measures such as FAR and SAV where included because compact city development is widely acknowledged for its beneficial effects on economic development, enhanced mobility, and reduced costs of infrastructure and service delivery . This isThe following section presents a concise overview of the six urban form indicators utilized in this study: Floor Area Ratio (FAR) is a metric used to measure the intensity of land use and building density. FAR is defined as the ratio of the total building floor area to the total land area [and area . FAR canPublic Space Ratio (PSR) is a metric used to measure the proportion of the public space relative to the total sample area. The public space is defined as areas of a neighborhood which the public has legal access to, such as streets, sidewalks, and parks . PSR is Average Block Size (ABS) is a metric highlighting the scale of the urban fabric. A block consists of private space surrounded by public space . ABS is Surface Area to Volume ratio (SAV) is a metric highlighting the compactness of the built environment. SAV is defined as the total building surface area divided by the volume of all buildings . The calAverage Street Width (ASW) is a metric highlighting the access conditions. ASW is defined as the total area of the public space divided by the total length of the street network .Urban Tree canopy Cover (UTC) is a metric highlighting the density of trees. UTC is defined as the total ground area covered by the crowns of trees divided by the total sample area , 38.Each of these six metrics were computed for each planned and unplanned sample area providing the basis for the quantitative analysis of the urban form of the adjacent planned and unplanned informal settlements. Mean values and standard deviation across all planned and all unplanned sample area were computed for each indicator. Effect sizes (Cohen\u2019s d) were computed to provide standardized representations of the magnitude of differences on selected indicators between planned and unplanned areas. Effect sizes were interpreted based on established thresholds: values around 0.2 indicate a small effect size, around 0.5 indicate a moderate effect size, and around 0.8 or higher indicate a large effect size . Photos The qualitative analysis relied on visual inspection of the manually delineated maps . This apThe six indicators of urban form computed for each settlement under examination are summarized in The statistical analysis documents large effect sizes (Cohen\u2019s d > 0.8) of urban planning on five out of six indicators of urban form. The largest effect size was observed on SAV (Cohen\u2019s d = 3.2), indicative of a consistently more compact built environment and more optimized land use efficiency of construction across the planned urban areas. Similarly, a large effect size on FAR was observed (Cohen\u2019s d = 1.7), indicative of a consistently denser built environment across the planned sample areas. Notably, large effect sizes were also observed concerning PSR (Cohen\u2019s d = 2.8) and ASW (Cohen\u2019s d = 1.9), indicative of the consistently improved access conditions and larger proportion of public space found across all planed areas. A large effect size was furthermore observed concerning AWB (Cohen\u2019s d = 1.2), indicative of a consistently higher level of pedestrian porosity across the planned sample areas. A moderate effect size was observed regarding UTC, indicative of lower vegetation density in planned urban areas.The qualitative analysis of the urban fabrics highlights variations in street widths within planned areas indicative of gradual encroachment upon the street space see . FurtherThe study analyzed the urban form of adjacent planned and unplanned settlements in Maputo, Mozambique that were established more than 40 years ago and subsequently development with limited enforcement of building and planning regulations. The purpose of the study was to document the spatial impact of urban planning in contexts characterized by limited enforcement of building and planning regulations. The findings consistently reveal notable qualitative and quantitative differences across the planned and unplanned areas that have critical implications for infrastructure provision, accessibility, and livelihood. Notably, all of the examined planned areas are characterized by higher levels of built density, more compact urban form, higher proportions of public space, and higher average street widths compared to the respective adjacent unplanned areas. Notably, the statistical analysis consistently showed large effect sizes of urban planning on indicators of compact city development (FAR and SAV) as well as accessibility and pedestrian porosity , while showing a moderate effect size on vegetation density (UTC). The qualitative analysis furthermore, documented variations in street widths and inconsistencies of the street network geometry, indicative of street encroachment and appropriation of the public space.The study found that the proportion of public space and the average street widths were higher across all three planned areas compared to all three unplanned areas. More specifically, the proportion of public space was on average 27% higher in the planned areas while the average street width was 20% higher. In addition, the average block size was generally larger and dead-end pathways more common in unplanned areas. Notably, large effect sizes (Cohen\u2019s d = 1.2\u20132.8) of urban planning were consistently found across indicators of the public space, including proportion (PSR), access conditions (ASW), and pedestrian porosity (ABS). The differences notably imply that the planned areas feature near-universal car access facilitated adequate street widths, while the unplanned areas exhibit limited car access attributable to constrained road networks. According to UN-Habitat, street space should cover at least 30% of the land area in a neighborhood to support adequate mobility systems . HoweverThe study consistently found more compact urban form  in the planned settlements compared to the respective neighboring unplanned settlements. Furthermore, large effect sizes (Cohen\u2019s d 1.7\u20133.2) were observed for FAR and SAV. This suggests that the planned areas are characterized by fewer, more compact and larger buildings or that the buildings are more conjoined while the unplanned areas are characterized by smaller and more scattered buildings. In addition, the qualitative assessment of the maps underscores that buildings in the planned areas are more aligned with the streets. These findings indicate that the planned areas are characterized by more optimized land use efficiency. Compact city development can accommodate a higher population density, that result in shorter commuting distances, reducing time and resource consumption on transportation , 44. HigThe study found a higher average urban tree canopy cover in the unplanned areas along with a moderate effect of urban planning on UTC (Cohen\u2019s d = 0.5). Lack of trees can lead to increasing surface urban heat island effect compromising local micro-climate  and linkWhile the study found higher levels of built density, higher proportions of public space, and larger average street widths in all planned sample areas compared to the adjacent unplanned areas, the study also found some variations in these data across the three planned areas. The qualitative assessment of the urban fabric highlighted that the urban fabric of the planned area in Maxaquene A is characterized by irregularities which are likely the result of residents appropriating entire streets. Furthermore, small variations in street widths and shifts in extensions of plots and buildings into the street space observed at local level across all examined planned areas underpin that small-scale appropriation of the public space through street encroachment is a common practice. As critical differences in such practices are both observed qualitatively and quantitatively across the sample areas, this is indicative of different local administrative practices in the planned informal settlements. More specifically, street encroachment and wider appropriation of the public space is accepted to a varying degree, underscoring the importance of local administrations in informal settlements in administering the urban development.A number of questions arises on the background of the analysis for future research to investigate. What explains the higher levels of built density and more compact urban form in the planned areas? Why are the planned areas characterized by lower tree canopy cover? Are the higher levels of built density observed in the planned areas the outcome of smaller plots and higher density of households? Do households with higher socioeconomic status who can afford to construct larger houses seek to live in planned areas because of better access conditions for cars? Is the more compact urban form in the planned areas an outcome of the simpler plot geometry which is more optimized for efficient configuration of buildings? However, as the study does not document the sociocultural dynamics that account for the differences observed between the planned and unplanned areas , it is uThe formation of street-systems and plot boundaries are essential for the long-term urban development as they typically remain unchanged through successive generations of society . AccordiInformal housing in Maputo is characterized by simple rectangular building layouts optimized for standardized construction materials . The simThe study investigated the impact of urban planning in contexts with limited capacity to enforce building and planning regulation based on analysis of planned and unplanned sample areas in peri-urban Maputo, Mozambique established more than 40 years ago. The study found higher levels of built density, more compact urban form, higher proportions of public space, and higher average street widths in all of the examined planned areas compared to the adjacent respective unplanned areas. In addition, the study showed large effect sizes of urban planning on indicators compact city development as well as pedestrian and vehicular accessibility. The study thus demonstrates that a basic level of urban planning can have a long-term impact on the urban form of informal settlements despite limited enforcement of urban regulation. The study highlights that urban planning can enhance compact city development and improve access conditions in informal settlements. This may increase the cost-efficiency of investments in infrastructure and increase the impact of such investments. Accordingly, the study suggests that a basic level of urban planning can support sustainable urban development in rapidly urbanizing contexts with limited institutional capacity.S1 Fileopenaerialmap.org.Manually delineated features of the urban environments of all sample areas used in the study. The high-resolution orthophotos are available via (DWG)Click here for additional data file.S2 FileMandatory form about ethical aspects of conducting research in a global context.(DOCX)Click here for additional data file."}
+{"text": "Moreover, the multi-scale feature of the model allows for multi-scale system engineering analysis of decarbonising heating, including system-informed heating technology design, identifying optimal operational setups at the consumer end, and assessing trade-offs between consumer investment in heating technologies and infrastructure requirements in different heat decarbonisation pathways.This paper presents the HEGIT  model for optimal infrastructure planning for decarbonising heating in buildings. HEGIT is an optimisation model based on Mixed Integer Linear Programming. The model co-optimises the integrated operation and capacity expansion planning of electricity and gas grids as well as heating technologies on the consumer side while maintaining the security of supply and subject to different environmental, operational and system-wide constraints. The three main features of the HEGIT model are: Planning periods [year]Type of biomass [-]Days of each year [day]Type of gas boilers Heating demand categoryType of heat pump Technologies in the electricity grid, Electricity generating technologies the use biomass as fuel, Conventional electricity generating technologies, Electricity generating technologies, Electricity generating technologies the use Methane as fuel, Variable renewable technologies, Electricity storage technologies in the electricity grid, Gas production/storage technologies Hydrogen production technologies that use biomass as fuel, biomethane production technologies Hydrogen production technologies supplied by the electricity grid, Hydrogen production technologies that use fossil fuels as fuel, Linepack storage, Hydrogen production technologies that use methane as fuel, Hydrogen production technologies, Renewable hydrogen production technologies, Hydrogen storage technologies, Underground hydrogen storage, All the heating technologies at the consumer side Alternative low carbon energy vectors Energy vectors that will not be replaced, Energy vectors that will be replaced, Time periods [hour]Energy vectors used for heating, All the technologies, All the generation technologies in electricity and gas grids, All the technologies in electricity and gas grids, All the storage technologies in electricity and gas grids, Number of available units of technology step width planning years [year]Weighted average temperature increase required at consumer-side [\u00b0C]Demand reduction by energy efficiency improvement for energy vector Gas boiler efficiencyEfficiency of generation technologies Conversion efficiency for each energy vector Round trip efficiency of storage unit Density of water [Availability factor of technology Number of new built units of technology Build rate of technology Specific heating capacity of water [Cost of decommissioning gas grid [\u00a3Cost of avoided Maximum available capacity for each salt cavern formation in the UK [Capital expenditure of technology Carbon intensity of the energy vector Capacity margin [%\u00a0Coefficient of performance for heat pump type Total annual cost of biomass required in year Carbon price floor in year Price of imported electricity [\u00a3/Carbon price floor in year Total annual biomass demand in year Demand for biomethane [Regular annual electricity demand projection at year Annual electricity demand projection for EV at year Demand for primary energy vector Total electricity demand [Demand for gas from boiler Total annual demand for hydrogen at year Demand for natural gas [Discount factor in year Normalised demand profile for regular electricity [-]Normalised demand profile for EV charging [-]Normalised demand profile for heating in buildings [-]Minimum down time requirements of technology Emission target for heating in buildings at year Total investment on fuel switching over the planning horizon [\u00a3]The maximum injection rate to each underground storage unit [The maximum discharging rate from each underground storage unit [Average heating demand from each household in year Natural gas import in year Injection rate to salt caverns as % of working gasInstallation cost share for heating heating technology Industrial and other demand sources for natural gas in year Maximun linepack state of charge per unit of demand [Minimum linepack state of charge per unit of demand [Lifetime of technology Lifetime of available units of technology Water inflow to the tank integrated with heating technology Water outflow from tank integrated with heating technology Hot water stored in the tank integrated with heating technology Maximum available biomass of type Maintenance cost for heating technology Number of units of technology Nominal capacity of technology Nominal thermal capacity of heat pump installed in year Storage capacity of underground gas storage technologies Gas network losses [\u00a3]Network reinforcement factor for transmission and distribution networksNumber of units of storage technology Operating margin requirement in the gas gridOperational costs of technology Total operational costs in year Fixed operational costs of technology Start-up costs of technology Electricity demand for gas storage in year Electricity demand for hydrogen production in year Electricity demand from backup heater in year Electricity generation from technology Hydrogen production from technology Electricity to heat pump Domestic production of natural gas at year Electricity to demand from technology Hydrogen to demand from generation technology Electricity to storage technology Peak electricity load in year Peak load of hydrogen demand in year Cost of biomass type Price of imported electricity [\u00a3/Electricity to grid-level storage from technology Hydrogen input to storage technology Hydrogen to storage from generation technology Heat output from backup heater integrated with heating technology Heat demand supplied by energy vector Heating demand supplied by alternative low carbon energy vectors Heat output from the thermal storage tank for each heating technology Heat delivered by energy vector Reserve capacity provided by technology Maximum ramp down rate of technology Minimum days of reserve requirement [day]Absolute reserve margin [%\u00a0Maximum ramp up rate of technology Minimum storage inventory level of underground storage-cushion gas [%\u00a0Effective state of charge of technology Inventory level in storage technology Maximum storage inventory level [%\u00a0Minimum storage inventory level [% Electricity from storage to demand from technology Hydrogen to demand from storage technology Electricity system emission target in year Minimum system inertia demand [Hydrogen from underground storage units to Linepack [Supply margin requirement in the gas gridReserve capacity provided by technology Hydrogen from storage unit Supply of biomass type Shanon Weiner Diversity IndexAir temperature [\u00b0C]Soil temperature [\u00b0C]Features of technology Features of technology Losses in transmission network [%]Total system cost [\u00a3]Total system emission [Total system emission at year Number of units of technology Unit cost of gas boiler Unmet Hydrogen demand-gas shedding [Unmet electricity demand-load shedding [Minimum up time requirements of technology Hot water cylinder storage capacity integrated with technology Value of Lost electricity load [\u00a3/Value of Lost heat Load [\u00a3/Number of units of technology Withdrawal rate from salt caverns as % of working gasRepresentative day weighting factor [-]Annual weighting factor [-]Dynamic reserve for wind electricity generation [%\u00a0Number of units of technology Emission rate of biomethane production from anaerobic digestion [Specifications tableEnergy system models are integrated frameworks that provide quantitative insights into alternative energy systems. They provide structured stories about future developments through scenario analysis and based on an organised exploration of data and assumptions . Whole eAchieving climate change mitigation targets will require decarbonisation efforts across all sectors of the economy, particularly the energy sector. Decarbonising heating in buildings is central to this energy transition challenge. Heat is one of the largest energy-consuming sectors and a major source of emissions in many countries with a cold climate. The scale of the heat challenge differs significantly from state to state depending on various factors, such as climate conditions, building stock, energy prices, the heating technology portfolio mix in buildings and the current structure of the energy system in a country. There is a wide range of options for decarbonising heating, with different pathways leading to very different energy systems. Modelling the future heat system is complex, and an effective representation of different heat decarbonisation pathways requires capturing the interactions across many domains, including buildings, heating systems, the electricity sector, and the existing fuel supply infrastructure such as the gas and electricity grids .This paper presents the HEGIT  model for optimal infrastructure planning for decarbonising heating in buildings. HEGIT is a multi-scale integrated electricity and gas systems\u2019 unit commitment, economic dispatch and capacity expansion planning optimisation model based on Mixed Integer Linear Programming (MILP). The model is designed to investigate the coordinated transition of electricity and gas grids and assess the impacts of different policies and decisions for decarbonising heating in buildings on the operation and long-term investment planning of these networks. HEGIT is implemented in GAMS and uses CPLEX as the mixed integer linear programming solver. The model co-optimises the short-term operations and long-term investment planning of electricity and gas grids as well as the individual heating technologies in buildings while ensuring the security of supply and subject to different environmental, operational and system-wide constraints. The main outputs of the model are the portfolio mix and cost-optimal operation schedule of heating technologies in buildings, the cost-optimal dispatch schedules, the optimal technology mix and the evolution over the planning horizon for both gas and electricity grids. Such a coordinated approach is crucial for understanding the interaction between major components of the system, exploring cross-system solutions and identifying trade-offs between infrastructure requirements and investments in heating technologies at the consumer side for decarbonising heating. It also provides insights into the necessary levels of deployment of different options, the likely levels of investment required, key periods when strategic decisions need to be made, and the system-wide impacts of different choices .\u2022It incorporates an integrated unit commitment and capacity expansion planning problem for coordinated operation and long-term investment planning of the electricity and gas grids. This enables the model to assess different scenarios regarding the future of the gas grid and its role in providing low-carbon heating, quantify the system-wide implications of different pathways for decarbonising heating in buildings, identify the most efficient and effective use of available resources and technologies, identify strategies for maximising synergies between system planning goals and minimise trade-offs and provide technical evidence for policy making.\u2022It incorporates the flexible operation of heating technologies and demand response in coordinated planning of gas and electricity grids for decarbonising heating. This will allow the user to conduct simultaneous multi-scale system analysis for system flexibility planning and assess the potential benefits of access to a wider set of flexibility options through demand side management, and coordinate the planning of heating and electricity decarbonisation in order to avoid expansive stop-gap measures and long-term lock-in.\u2022It incorporates a multi-scale techno-economic representation of design features of heating technologies into whole energy system modelling and capacity planning .Fig. 3MuTo have a more accurate representation of heating technologies\u2019 cost and performance, such as variations in heat pump performance with outside temperature, and to study the impacts of different heat pump designs features on the operation and planning of the electricity grid, we soft-linked HEGIT with the thermodynamic and component-costing models developed by Olympios et\u00a0al.  that capModels are usually tailored for a specific application or research question, which determines their complexity, modelling scope, and temporal and spatial resolutions Modelling scope. The \u2018whole system\u2019 scope includes all major gas and electric flows, detailed representations of technologies (including their flexibility attributes) for electricity generation and supply, gas production and supply, as well as decentralised heating generation technologies in buildings. Therefore, the model captures the interaction between electricity and gas grids and the heating in buildings through the conversion of energy vectors to each other and emission exchange/offsetting. Long-term capacity planning. HEGIT considers pathways from 2020 to 2050 by taking into account long-term trends in energy technologies, electricity and heating demands, fuel prices and carbon tax. The model considers annual time steps of 5 years over the planning horizon. The end of the planning horizon in the model can be modified based on the application and research questions.Temporal factors. The energy system design is strongly influenced by temporal variations in demand and supply as well as peak levels of demand, especially as more variable renewable energy sources are integrated into the system. HEGIT accounts for seasonal and diurnal changes in demand and supply and explores the trade-offs between various ways to manage peak demand . HEGIT has an adjustable temporal resolution. In order to reduce computational expenses, and because the full hourly version of the model takes a long time to solve, representative time steps can be used to reflect seasonal and diurnal variations in demand and supply. In our analysis, we use 13 representative days (12 representative days and one peak day), each with 24 consecutive hours. To identify the representative days for our analysis, we used k-means clustering with an energy-preserving approachSpatial factors. Geographic resolution is another important aspect to consider when designing energy systems, especially as distributed renewable resources are added to the system. the current version of the model represents a country as a single node, and the geographical distribution of resources and demand is not taken into account.Input data. Large-scale bottom-up models typically require extensive data sets, which leads to a compromise between a highly disaggregated and detailed model on the one hand and data availability and model complexity on the other hand. The current version of HEGIT takes four types of data, as shown in \u2022Temporal data: This includes demand profiles for heating and electricity, renewable energy sources availability, air and ground temperatures, and imported electricity prices.\u2022Technology data: This data includes capital investment, fixed operating costs, variable operating costs, and start-up costs, as well as the flexbility attributes and performance parameters such as economic lifetime, emission rate, efficiency, minimum safe operating level, uptime, downtime, ramp rates, inertia provision, and reserve provision for different technologies.\u2022System data: This includes resource price projections, resource availability data, discount rates, carbon tax projections, population data, number of households, emission budgets, as well as electricity and gas grids operating constraints.\u2022Heating technology data: This includes market cost and performance data on different domestic heating technologies, cost and performance data for various heat exchangers and compressors, thermodynamic parameters and specifications for different working fluids.\u2022We used a central planner perspective, and our results do not take into account consumers\u2019 preferences for heating technologies.\u2022Heating demand is population-adjusted, and detailed segmentation of housing stock is not considered in this version of the model.\u2022The regular electricity demand and the additional electricity demand from electrifying other sectors (such as transportation) are exogenously considered.\u2022Uncertainties in the input parameters are not considered, and the model is deterministic.\u2022A perfect market and perfect foresight over the planning horizon (2020\u20132050) is assumed.\u2022Energy efficiency improvements in buildings are assumed to be independent of the heating technology and vice versa.\u2022It is assumed that fuel switching occurs only if demand for heating is supplied by the direct burning of fossil fuels.\u2022To ensure the grid security for capacity planning and to take into account extreme events such as sustained periods of low wind and the risks from renewable sources\u2019 intermittency; we assume that renewable sources will not be available on the peak day.The other key assumptions considered in the model are:As shown in 2a is the balance between heating demand (both space heating and hot water) v in the existing system l that replace the energy vector v, The key constraint on the demand side in each planning year factor \u03bb . Eq.\u00a0(4)The system is limited to only relying on electricity and gas grids and energy efficiency measures to decarbonise heat. Other options, such as solar thermal and heat networks, were not considered in our study since assessing the value of these distributed options requires a finer spatial resolution and regional energy system modelling. Furthermore, we assume that fuel switching occurs only if demand for heating is supplied by the direct burning of fossil fuels in individuation heating technologies in buildings. Consequently, if demand is already supplied by biomass, electricity or renewable sources, fuel switching does not occur .(5)qlc with electric backup, ground-source heat pump (GSHP) with electric backup, hybrid air-source heat pumps with natural gas boilers, hybrid air-source heat pumps with hydrogen boilers, and hydrogen boilers.The main constraints for heating technologies are the heat demand balance as indicated in hp at each time step t and day c is constrained by the coefficient of performance (COP) of the heat pump at that time step and its installed capacity (The output from each heat pump unit type capacity .(11)COP is calculated based on the boiler\u2019s efficiency, which is assumed to be the same for both hydrogen and gas boilers With respect to heat pumps, we use the empirical cost and performance equations\u00a0from the integrated heat pump thermodynamic and component-costing model (discussed in Section\u00a0\u201cIntroduction\u201d and This part reviews the integrated capacity expansion planning and unit commitment optimisation problem in HEGIT that has been developed for modelling the coordinated operation and investment planning of the gas and electricity grids.Gas flow model nonlinearity (introduced by Weymouth gas equation) significantly impacts the computational time of the gas network models System-wide constraints. We assume that two different types of gases can be injected into the gas grid: methane and hydrogen. The main uses of methane in the electricity and heating sectors are for gas-fired power plants, hydrogen production using methane reforming, the direct use of methane in gas boilers in buildings and other demand from other sectors such as industry  and SM coefficient) Gas production plants operation:Hydrogen production units\u2019 output can be used to meet demand or to charge storage units, including linepack . SWDI is a quantitative measure that reflects the diversity of the members of a set and is widely used in long-term energy planning and security of supply studies. Higher index values indicate a more diverse mix [erse mix . Accordierse mix . EquatioPooya Hoseinpoori: Conceptualization, Methodology, Software, Formal analysis, Validation, Data curation, Visualization, Writing \u2013 original draft. Jeremy Woods: Supervision, Writing \u2013 review & editing. Nilay Shah: Supervision, Methodology, Writing \u2013 review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."}
+{"text": "Past research examining the relationship between psychosis and criminality has typically focused on chronic schizophrenia and violence. However, contact with the criminal justice system is not constrained to the most unwell or most violent. The present study is novel as it examines the different clinical stages of psychosis, from the at-risk mental states (ARMS)/Ultra-High Risk (UHR) to the early and chronic psychotic illness phase, across the entire spectrum of criminal offending.The main study objective is to establish the prevalence of the clinical stages of psychosis among adults entering custody and to examine the sociodemographic and forensic characteristics associated with the different stages of psychosis. A further aim is to examine whether psychosis-spectrum prisoners differ from non-psychotic prison controls across these characteristics.Participants consist of unselected 291 adult male and female prisoners entering the largest maximum security reception centres in New South Wales (NSW), Australia. They completed a range of semi-structured questionnaires and adapted mental health screening measures. The Comprehensive Assessment of At Risk Mental States  was used to ascertain whether participants met the Ultra High Risk (UHR), First Episode of Psychosis (FEP) or Established Psychosis (EP) criteria.p = 0.035). Among prisoners with a psychosis-spectrum illness (n = 121), the prevalence of UHR was 24%, First Episode Psychosis (FEP) was 6% and established psychosis was 11%. Compared to controls, psychosis spectrum prisoners were found to have higher levels of social disadvantage, psychiatric comorbidities and multiple incarceration episodes. However, psychosis was not associated with a greater risk of violent offending. Implications on the complex illness burden associated with psychosis and the need for early identification and intervention across forensic mental health services will be further discussed.Participants were 34.25 years old (SD = 10.69) on average and men were significantly older than women (This study is novel as it examines the full spectrum of psychotic illness across the entire spectrum of criminal offending. The findings support the notion that risk of criminal justice contact and complex illness burden exist across the different clinical stages of psychosis, from the UHR to the early FEP and chronic psychosis stages, for both violent and non-violent offending. Early intervention services must consider how to more effectively identify and intervene to reduce the risk of criminal justice system contact among mentally ill individuals.None Declared"}
+{"text": "Drs. Crownover and Curtiss published separate editorials that made reference to our article on health care utilization among patients with asthma who were treated with inhaled corticosteroids (ICSs) in combination with either montelukast (MON) or salmeterol (SAL). The subject of Crownover's editorial is application of the PP-ICONS tool to skim research articles to quickly evaluate new publications. The Curtiss editorial more broadly discusses asthma disease management. Both the Crownover and Curtiss editorials reference the NAEPP guidelines for diagnosis and management of asthma. Curtiss states that leukotriene modifiers (LMs) are recommended for only one category of patient, those in Step 3 with moderate persistent asthma. In fact, LMs are listed in the guidelines as alternative treatment for both mild persistent and moderate persistent asthma for infants and young children (aged 5 years and younger) and for adults and children older than 5 years."}
+{"text": "Eliminating adolescent HIV in high-burden African countries depends on the success of implementing evidence-based interventions to reduce transmission and improve treatment outcomes. The Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) takes a collaborative approach to addressing key challenges and identifying and developing new areas of investigation to advance the adolescent HIV agenda. This special supplement represents the collective learning of the Alliance related to implementation science in the context of the adolescent HIV continuum of care from multiple African countries. Specifically, this series describes the current academic landscape of adolescent HIV and implementation science, such as the methodological use and utility of implementation measures and frameworks; addresses timely topics such as the use of innovative technologies for study adaptations in the context of the global COVID-19 pandemic; and explores opportunities to enhance adolescent-responsive approaches to HIV prevention and treatment using implementation science. In 2021, 160,000 children under five years old were newly infected with HIV \u20138. This AIDS & Behavior special supplement provides insight into evidence generated by the Fogarty International Center\u2019s Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA). AHISA has adopted a solutions-driven, collaborative approach for adolescent HIV implementation research to address key challenges and identify and develop new areas of investigation in advancing the adolescent HIV agenda [This V agenda . AHISA iV agenda . It usesIn this supplement, AHISA members present IS research findings related to the adolescent HIV continuum of care from multiple African countries. More specifically, articles in this series: (1) present data on components of the adolescent HIV continuum of care, including access to and utilization of testing and treatment and optimized integrated health services; (2) address timely topics such as the use of innovative technologies for study adaptations in the context of the global COVID-19 pandemic; (3) describe the current academic landscape of adolescent HIV and IS, such as the methodological use and utility of implementation measures and frameworks; and (4) explore opportunities to enhance adolescent-responsive approaches to HIV prevention and treatment using IS.In their broad scoping review, Vorkoper et al.  examine Subramanian and colleagues  reviewedAtujuna et al.  provide Several articles addressed timely topics, such as, innovations used in adapting research and practice in the context of the global COVID-19 pandemic. Lowenthal et al.  and AhmeInnovative technologies are also vital to adolescent research and programming and are featured in the supplement. Despite an increase in the use of mHealth interventions in health research in low- and middle-income countries (LMICs), there is a paucity of studies evaluating their implementation in the context of adolescent HIV. Goldstein et al.  conducteA number of articles explored opportunities for IS to enhance adolescent-responsive approaches. These included best practices in adolescent engagement, tailoring programs, and peer support , 19, 20 Tahlil et al.  and NelsMental health is a critical driver of adolescent HIV outcomes . The anaAIDS & Behavior supplement lays the groundwork for the application of IS in adolescent HIV research in high-burden countries. It provides data and first-hand lessons from ongoing and recently-completed studies. The information and research agenda presented establishes evidence and resources for practical approaches to support global adolescent health initiatives, such as the PEPFAR DREAMS, the Global Fund\u2019s Strategic Investment in Adolescent Girls and Young Women, the World Health Organization\u2019s Global Accelerated Action for the Health of Adolescents, Africa REACH and UNAIDS. Data and lessons learned shared in these articles will aid in identifying and addressing impediments to reducing HIV incidence and related mortality among adolescents. It also catalyzes and underpins the need for rigorous adolescent HIV-related implementation research to ultimately ensure global elimination of HIV in adolescents and young people.This"}
+{"text": "Cai et al.; Li et al.; Liu, Han et al.; Yang B. et al.). It has become increasingly clear that the gut microbiome is influenced by a variety of factors, including the host genome, nutrient metabolism, habitat environment, and seasonal dynamics . Of particular note is the growing interest in the relationship between host behavior and gut microbiota, as studies have demonstrated that host behavioral processes are shaped by the microbiome and represent important predictors of similarities and differences in the composition of the gut microbial communities  The putative gut microbiome transmission in the wild animal social groups: the quality and quantity level of gut microbiome transmission, (2) The potential reciprocal connections between an animal's social behavior and its gut microbiome: the convergent pattern among different animals, (3) The function of the transmitted microbiome in wild animals, (4) How the microbiomes can affect host behavior, (5) The evolutionary perspective on the relationship between social behavior and the gut microbiome. The Research Topic currently includes 17 original research articles and one review article.Zhang J. et al. found the importance of maternal fecal microbiota for rapid colonization of the gut microbiota of calves (yak and cattle) at different weeks after birth, and they determined that early establishment of the gut microbiota in the calves was facilitated mainly by maternal fecal microbial transmission. Moreover, social behavior can also promote horizontal transmission of gut microbiota among different species in a shared environment. Zhang T. et al., for instance, discovered that social interactions between goats and pigs in the same pen promoted greater homogenization of both rumen and cecum microbiomes.Typically, mammals lack gastrointestinal microbes before birth, requiring each generation to undergo a reassembly of the gut microbiota .The relationship between host social behavior and the microbiome is reciprocal. Social interactions can influence the gut microbial composition, whilst in turn, the gut microbiome can regulate host behavior  population, the bacteria beneficial to host health  were more abundant in the gut of sociability individuals, whereas certain potentially pathogenic bacteria  were more abundant in fewer sociability individuals. Overall, these results highlight the critical link between host health and social behavior-gut microbiome composition.Social interactions can enhance the transmission of the social microbiome in social animals, which can fundamentally affect the costs and benefits of group living (Majolo et al., The relevance, interaction, and importance of host social behavior and the gut microbiome have been reconfirmed in the most recent study on this topic. However, these recent developments simultaneously present us with new inquiries and challenges. It has been demonstrated that intestinal mucosa-associated fungi can influence social behavior by modulating neuroimmune in mice (Leonardi et al., Moreover, with the growing number of studies in recent years that have unveiled the mechanisms linking the brain-gut axis to host immune diseases, it has further been evidenced that the brain-gut axis significantly influences host behavior. In particular, the researchers have identified and formulated a more specific microbiota-gut-behavior axis to highlight the critical role in regulating social behavior (Ntranos and Casaccia, The crucial role of maternal vertical transmission of gut microbiota in the early development and lifelong maintenance of the host gut microbiome has been extensively supported by numerous clinical trial results (Vandenplas et al., Despite the initial understanding of the interactions between social behavior and the gut microbiome, the reasons and timing of their relationship, as well as the intergenerational heritability and continuity of social behavior shaping gut microbiome, are still largely unknown (Moeller et al., The author confirms being the sole contributor of this work and has approved it for publication."}
+{"text": "Transgender women (TGW) in Malaysia experience unique social and interpersonal challenges that contribute to their risk of acquiring HIV and sexually transmitted infections (STIs). The study aimed to understand the experiences of this vulnerable population, barriers and enablers of safe sexual practices relating to oral transmission of STIs.Participants were recruited through a snow-balling method of sampling with the help of TGW community advocates. Theories of Health Belief Model and Andersen\u2019s Behaviour Model of health services use were used to devise the interview guide. Semi-structured in-depth interviews and Focus group discussion with participants gave insights into the needs of the community.  The data obtained was transcribed, coded and subjected to thematic analysis using the constructs of the Information, Motivation and Behavioural skills (IMB) theory. Results are presented as n (%) or median .Participant characteristics are outlined in table 1. The major themes that emerged through qualitative analysis are highlighted . The results identified gaps in awareness of oral transmission of STIs among TGW and lack of condom use during oral sex. Self-medication / non-professional treatments and lack of utilization of dental services was a concern.The importance of social support in positively influencing health promotion as well as improving health care and dental care utilization was highlighted. The areas of concern identified through this qualitative research will inform the design and development of an educational intervention aimed at addressing these concerns and providing support. Developing a customised, culturally sensitive, peer reviewed educational intervention that will be delivered through a widely popular social media platform is proposed.All Authors: No reported disclosures"}
+{"text": "In the framework of the EU-Erasmus+, the European Alliance for Sport and Mental Health (EASMH) project has been funded, aiming to promote the improvement of good clinical practice for sport-based psychosocial interventions throughout Europe. A specific training programme tailoring professional sport coaches has been developed in order to improve their skills in engaging and involving patients with severe mental disorders in sport-based rehabilitation activities.to evaluate the perceived quality and utility of the EASMH training programme by sport coaches from different European countries .As part of the EASMH project, the University of Campania \u201cL. Vanvitelli\u201d has coordinated the development of training materials for professional sport coaches. The training programme has been tested in a pilot training programme. An ad-hoc questionnaire has been developed and administered at the end of the training, during a meeting held in Brussels in July 2022.The EASMH training programme consists of six modules, dealing with the following topics: definition of mental health/mental disorders; classification systems; essential clinical features of severe mental disorders; personal and social burden associated with severe mental disorders; how to build a therapeutic relationship with a patient with severe mental disorders; verbal and non-verbal communication; evaluation of patient\u2019s preference in selecting sport activities; definition of a personalized plan; motivational interview/problem-solving strategy. A total of eight professional coaches involved in different sport coming from Italy, Romania, United Kingdom and Finland participated in the entire training, consisting of six 4hr training modules. Seven out the eight coaches compiled the questionnaire. The overall feedback has been extremely positive. Overall, coaches have judged the modules as very clear, useful and of high standing. Each question has been rated with an average of 4.35 related to the overall content.The present survey confirms that a short online training programme focused on professional sport coaches is well received by participants and can provide them with useful information on how to engage patients with severe mental disorders. The next step of the EASMH project foresees the implementation of several local pilot actions with the active involvement of patients with severe mental disorders.None Declared"}
+{"text": "Editorial on the Research TopicEmerging trends in global women\u2019s health\u2014sex and gender differences in diseaseOver the years, the discussion surrounding the implications of sex characteristics and gender dimensions on health outcomes has shifted from a fringe topic to a central concern in scientific research. Global health trends and the COVID-19 pandemic have underlined the significance of understanding the differential impacts of diseases across genders. This Research Topic brings together a collection of papers exploring the various dimensions of women's health, highlighting sex and gender disparities in disease manifestation and outcomes.Ferretti et al. tap into the realm of behavioural patterns by exploring the evolving trends of smoking prevalence in women across 191 countries from 1990 to 2019. Their finding that smoking habits are not universally convergent but cluster in specific \u201cclubs\u201d provides a lens to understand regional variations in smoking habits of women. Intriguingly, the role of economic factors, especially cigarette affordability, emerges as a significant determinant of these smoking trends, shedding light on the interconnectedness of socioeconomic policies and smoking behaviours among women.In their brief investigation, Rao. Their mini-review sheds light on the urgency of understanding how biological sex characteristics, such as an XX-sex chromosomal karyotype and menopausal transition, influence viral reservoir characteristics and immune responses in cis-women. They report that sex-specific differences in HIV-1 may hinder the development of a scalable cure for women living with HIV-1 (WLHIV). The authors call for comprehensive HIV-1 cure research that ensures sufficient representation of WLHIV and the systematic inclusion of sex stratification in data reporting of drug responses and viral reservoir locations and consideration of sex differences in clinical trial endpoints.The enduring challenge of Human Immunodeficiency Virus type-1 (HIV-1), especially its disproportionate impact on women, is brought into focus by Hallam et al. provide an insightful perspective on the trajectory of sex and gender research (SGR) in health and draws attention towards skill development of early- and middle-career researchers (EMCRs). Their recommendation includes three pivotal dimensions that can potentially improve future SGR practices: synergizing the objectives of SGR with the responsibility of addressing systemic biases, expanding SGR to include intersectional approaches and elevate the importance of \u201cnull findings\u201d. The authors underscore that concerted efforts on these avenues can indeed pave the way for tangible advancements in reducing health disparities on a global scale.Busl\u00f3n et al. bring attention to the intersections of technology and sex- and gender related biases, notably in the burgeoning field of Artificial Intelligence (AI) in health. Their concerted effort to spotlight sex and gender biases in AI research echoes the global call to champion diversity and inclusivity in technological advancements. In their brief report, they offer key recommendations from the Bioinfo4women (B4W) program to facilitate the inclusion of sex and gender perspectives in AI and health research.In a brief research report, Hoffmann et al. Their qualitative exploration underscores the unique challenges faced by highly educated women working in global health in different European counties during the pandemic, from amplified domestic responsibilities to shifts in professional demands. The silver lining, perhaps, is the potential of women-centric networks like Women in Global Health (WGH) in fortifying resilience and fostering collaboration during crises.Lastly, the ramifications of the COVID-19 pandemic on gender dynamics form the focus of the original study by Taken together, these papers provide a panoramic view of different initiatives addressing global women's health and illuminating the multi-faceted challenges and opportunities that lie ahead. It is our hope that this Research Topic sparks renewed interest and ignites collaborative efforts in addressing the health inequities that persist across genders. The journey towards a more equitable healthcare landscape requires persistent inquiry, and these papers offer knowledgeable examples for the incorporation of sex and gender considerations into global health research. We anticipate that health researchers, regardless of their niche, will glean actionable insights for their own work from these contributions."}
+{"text": "Transcriptome and proteomic analysis during the embryonic development of temporomandibular joint in miniature pigs revealed the key regulatory genes and proteins for condylar ossification during embryonic development. This research finding could provide a basis for the pathogenesis of temporomandibular joint, tissue engineering, and regenerative medicine.The cover image is based on the article \u2018Transcriptomic and proteomic studies of condylar ossification of the temporomandibular joint in porcine embryos\u2019(Doi:"}
+{"text": "In December 2014, the International Committee for Monitoring AssistedReproductive Technology under the umbrella of the World Health Organizationconvened an expert meeting to re-examine, update and expand the infertilityglossary previously published in 2009. Thus, the International Glossary ofInfertility and Fertility Care was developed and published in 2017simultaneously in Fertility and Sterility and Human Reproduction. In thisarticle, we present the glossary translated into Spanish, obtained afterevaluation by Argentinian experts in the field of assisted reproductivetechnologies, reviewed by Dr. Zegers-Hochschild and approved by the board of theArgentinian Society of Reproductive Medicine (SAMeR). The translation of theglossary to Spanish will facilitate communication between professionalsresponsible for the practice of ART in Spanish-speaking communities. Moreover,it will lend support to promote better understanding as well as safer and bettercare for Spanish-speaking minorities and those experiencing cross-borderreproductive care. The International Committee Monitoring Assisted Reproductive Technologies (ICMART) is anindependent, international non-profit organization that has taken a leading role in thedevelopment, collection and dissemination of worldwide data on assisted reproductivetechnology (ART). Regional and national registries, such as the European Society ofHuman Reproduction and Embryology (ESHRE), the Society for Assisted ReproductiveTechnology (SART) and the Latin American Network of Assisted Reproduction (REDLARA),report their results to ICMART. Thus, in an effort to synchronize the reporting, ICMARTin collaboration with the World Health Organization (WHO) compiled a standard set ofdefinitions on ART published in 2006 , Dutch . Since nThe International Glossary of Infertility and Fertility Care, 2017 is ultimately theresult of a work led by ICMART together with a worldwide consortium of internationalorganizations related to reproductive health: the American Society for ReproductiveMedicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE), theInternational Federation of Fertility Societies (IFFS), March of Dimes (MOD), theAfrican Fertility Society (AFS), the Groupe Interafricain d\u2019Etude de Recherche etd\u2019Application sur la Fertilit\u00e9 (GIERAF), the Asian Pacific Initiative onReproduction (ASPIRE), the Middle East Fertility Society (MEFS), the Latin AmericanNetwork of Assisted Reproduction (REDLARA), the International Federation of Gynecologyand Obstetrics (FIGO). It was agreed with the corresponding editors to have the glossarypublished simultaneously in the journals Fertility and Sterility (The current article contains a translation into Spanish of the 283 terms and definitionsdescribed in the ICMART 2017 glossary (Zegers-We believe this Spanish version of the glossary will standardize and facilitatecommunication in the practice of ART not only in Spanish-speaking countries but also incountries where Spanish-speaking communities are visibly present. The Spanishtranslation of the glossary may be advantageous to Spanish-speaking minorities since itmay attenuate language barriers, which are well recognized to have a negative impact onthe quality of patients\u2019 care ("}
+{"text": "Editorial on the Research TopicLifestyle and vascular ageingVascular ageing is a lifelong process, and cardiovascular diseases are the result of genetic predisposition, fetal programming, and environmental factors . IndividLares-Villasenor et al.). More time playing video games, a surrogate of sedentary behavior, was not associated with higher blood glucose levels. However, higher socioeconomic status and higher healthy eating index were associated with lower blood glucose levels. These observations demonstrate an association between lifestyle behavior and cardiovascular risk exposure already in young children. Further evidence suggests that the improvement of cardiovascular risk factors in pediatric populations via lifestyle modifications may lead to a more favorable vascular phenotype in adulthood, thus reducing the likelihood of cardiovascular events . This study highlights the pressing need for more projects creating trajectories of vascular biomarkers to understand the impact of lifestyle-based risk factor modification on vascular ageing.It is beyond doubt that high cardiorespiratory fitness and regular physical activity exert beneficial effects on cardiovascular risk factors  and alsoDe Sousa et al.). The authors showed that higher levels of cardiorespiratory fitness but not of moderate-to-vigorous physical activity were associated with better vascular health phenotypes in 82 older individuals (mean age 67\u2009\u00b1\u20095 years). This study highlights the protective effect of high cardiorespiratory fitness levels on vascular health and contributes to the important message that cardiorespiratory fitness is a strong predictor of end-organ damage and mortality . The authors emphasize the need to customize such strategies based on cultural peculiarities in the respective country.Over the past 30 years, the important role of lifestyle behaviors for the individual course of vascular ageing has become very clear. However, the worldwide incidence of physical inactivity, sedentary behavior, and unhealthy diet keeps increasing , 8. ThisKubiak et al.) evaluated the role of the advanced nurse practitioner in the care of patients with peripheral artery disease in France. By consulting the patient after hospital discharge at home, the advanced nurse practitioner ensures clinical assessment, nursing supervision, adverse event screening, and renewing of drug prescriptions. This concept extends in-hospital patient care into the home-based environment and is in line with the current policy of the P4 medical approach to individual care  the understanding of the mechanisms underlying the effects of lifestyle on individual vascular ageing, (b) the identification and application of novel and established biomarkers that sensitively monitor vascular lifetime trajectories with and without treatment, and (c) both population-wide and individual medical programs for an effective implementation of healthy lifestyle behaviors."}
+{"text": "The kynurenine pathway of tryptophan catabolism has come into the spotlight of schizophrenia research since its catabolites exert neuroactive effects. A strong body of evidence suggests that kynurenic acid, a catabolite of kynurenine pathway, acts as the only endogenous NMDA receptor antagonist leading to the weakening of circuits in layer III of dorsolateral prefrontal cortex of schizophrenia patients. Studies exploring the levels of kynurenic acid and other metabolites of tryptophan in peripheral blood did not yield any definite conclusions.Primary objective of this study was to assess differences in concentrations of key constituents of kynurenic pathway in blood plasma \u2013 tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) between schizophrenia patients (SCZ) and healthy controls (HC). Secondary objective was to explore correlations between these concentrations and clinical characteristics.In our two-centre prospective case-control study we measured plasma concentrations of TRP, KYN and KYNA in 36 healthy controls (HC) and 38 schizophrenia (SCZ) patients during acute exacerbation and remission and explored the correlations with clinical parameters using PANSS scale. The patients were matched with HC by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.TRP concentrations were significantly higher in HC than in SCZ patients in acute phase  and remission , while SCZ patients in acute phase had significantly higher TRP levels than in remission . Levels of KYNA and KYN were significantly lower in SCZ patients than in HC both in acute phase and remission, all with high statistical significance . There was no statistically significant difference between acute phase and remission neither for KYN , nor for KYNA . There was no correlation of plasma levels of TRP, KYN and KYNA with total PANSS score, PANSS positive scale score, PANSS negative scale score and PANSS general psychopathology scores, both in acute phase and remission . Also, there was no correlation between plasma levels of TRP, KYN and KYNA in SCZ patients in remission with improvements measured with PANSS scale .Although there are concerns about the value of measurement of metabolites of kynurenine pathway in the peripheral blood, our data suggest that significantly decreased levels of KYN and KYNA could suggest that disrupted TRP degradation in SCZ patients may be reflected in the peripheral blood as well. Further studies of peripheral levels of kynurenine pathway metabolites on larger samples should also explore effects of antipsychotic therapy, but also their correlation with other clinical parameters such as neurocognition.None Declared"}
+{"text": "Pregnancy interval may have various impacts on psychiatric and psychologic disorders of the offspring.This systematic review aimed to assess the relationship of short and long inter-pregnancy intervals (IPIs) with the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).We performed a systematic search on electronic databases including Pubmed, Web of Science, Scopus, and Embase. We included observational studies that evaluated the association between IPIs and the risk of ASD and ADHD. Two reviewers independently screened and then extracted data on study characteristics, IPIs/ birth intervals, and outcome measures. The methodological quality of the included studies was evaluated following the Joanna Briggs Institute (JBI) critical appraisal checklist.At the final step, 19 out of 161 studies were included in our systematic review. Among them, 16 and 5 studies assessed the association between IPI and the risk of ASD and ADHD, respectively. In 9 studies, findings supported the association between short intervals and an increased risk of ASD. In addition, 7 studies reported significant association between both short and long intervals and an increased risk of ASD. Moreover, 3 studies demonstrated an association between short intervals and ADHD risk, while long birth interval was merely assessed in 2 studies with conflicting results.This systematic review strongly confirmed the association of short and long birth intervals with ASD and ADHD. Future studies should investigate the mechanisms underlying these associations and the possible modifiers to decrease the risk of such disorders.None Declared"}
+{"text": "Therapeutic Drug Monitoring (TDM), i.e. the measurement of blood levels of antipsychotics, is a well-established clinical routine tool in the treatment with antipsychotics including clozapine. Nevertheless, worldwide there are different utilisation cultures and trends with use of TDM varying from regular to very limited. In order to assess attitudes regarding the use and utility of therapeutic drug monitoring in psychiatry trainees and young psychiatrists, the EPA ECPC Task Force on Communication and Publications is performing an online survey consisting of 12 questions previously validated in a british context to gather data on TDM attitudes, practices, and clinical setting.Apart from capturing early career psychiatrists\u2019 current practices and perspectives regarding antipsychotic TDM the goal of this project is to identify predictive factors for future use of therapeutic drug monitoring (TDM). Here we present the preliminary results of our currently ongoing survey.G. Schoretsanitis Consultant of: HLS Therapeutics and ThermoFisher"}
+{"text": "While a growing corpus of literature regarding the stress suffered by caretakers for people living with dementia (PLWD) already exists, very little data is available regarding this subject among Romanian caretakers.This cross-sectional study aims to compensate for this by assessing a small (N=72) sample of caretakers through the use of self-reporting questionnaires for subjective feelings of stress and burden.Responders filled and online survey containing miscellaneous socio-demographic questions and the Kingston Caregiver Stress Scale (KCSS) along with the Caregiver Health Assessment Self Questionnaire (CHASQ). Results were collected and analysed in SPSS for subsequent correlations.The majority (77%) of caretakers are women and 86% of responders are offering their care at home, emphasizing pervasive gender roles and lack of availability or accessibility of social services for the PLWD in Romanian society. Three thirds of caregivers were children of PLDW. More than half of responders (51%) had KCSS scores that suggested severe stress while less than 9% related only mild stress. Most responders (52%) related social aspects of their lives as most affected by their caregiver status.While in line with most other findings and limited in scope and means by its methodology, this study offers a quick snapshot on the subjective levels of stress affecting caretakers of Romanian PLWD and can lead towards further points of inquiry on the matter in the Romanian population.None Declared"}
+{"text": "In the published article, there was an error in (A) Correlation analysis of HBV-HCC immune pathway related genes and hub genes by using GSE55092. (B) Correlation analysis of HCV-HCC immune pathway related genes and hub genes by using GSE69715. Red was positively correlated and blue was negatively correlated. The size of the circle represented the magnitude of correlation, and the cross indicated no correlationExpression correlation analysis of hub genes and Immune related genes The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."}
+{"text": "There has been an increased focus on the practices associated with dissemination for the translation of research to clinical practice and ultimately, policy. Simultaneously, there has been attention placed on the role of the clinical research workforce in supporting optimal dissemination efforts for impact and societal benefit. Curriculums focused on education opportunities for dissemination for translational scientists have been under-reported. The Translational Science Benefits Model (TSBM) is a framework that has been developed to support assessment of clinical and translational research outcomes that measure impact  beyond traditional citations in academic journals/bibliometric activities. The TSBM framework outlines more than 30 different facets of impact and can provide a basis for operationalizing broad impacts of research for translational and clinical scientists. Engagement science offers methods and modalities to work with individual stakeholders, and collaborators in a team science model, and engagement with external scholars and society. This article will describe the use of the TSBM framework and engagement science strategies to develop a translational dissemination framework with novel components for evaluation of dissemination and implementation activities. We propose using the translational dissemination framework to guide the development of an educational curriculum for the clinical research workforce. We outline the educational domains and proposed evaluation criteria essential in implementing this innovative translational dissemination educational content for the clinical and translational research workforce. Shelton et al., 2022). D&I approaches have epistemological underpinnings of pragmatism, supporting the understanding of the essential nature of the underlying complexity of people, communities, and systems in disseminating, adopting, and sustaining interventions within real-world settings and contexts (For nearly 20\u00a0years the fields of dissemination and implementation (D&I) have developed within the translational sciences domain to extend basic, clinical, and public health research findings to practice to achieve improved health outcomes for both individuals and populations . D&I worcontexts . Previoucontexts .Unlike more specialized scientific or clinical disciplines, D&I activities and research span numerous scientific fields, methodological approaches, and health research settings across the translational spectrum from bench research to society . When NoMehta et al., 2021). CTSAs fund translational research infrastructures in over sixty academic medical research centers and enable multidisciplinary investigators to 1) facilitate translational research and training across the translational continuum ; 2) provide training to facilitate workforce development, and 3) develop, demonstrate, and disseminate effective research tools and solutions to overcome translational roadblocks .D&I sciences have been embraced as critical concepts within the lifecycle of translational researcher . While fThe end goal of D&I integration is to ultimately improve the quality and impact of translational research to improve the health of individuals and communities . To thisPrevious scholars have developed core D&I domains for education and integration, particularly for use within the CTSA context and environment  We propoLuke et al., 2018) The purpose of TSBM was to broadly define scientific activities that lead to downstream impact in areas of clinical/medical, public health, economic/innovation, and policy/legislative impacts and advances . The TSBM benefits were identified using Delphi process with the ultimate goal of two phases of translation - the first being more traditional dissemination of research results through manuscripts and conferences for a scientific audience, and the second phase including dissemination to a broader audience which includes clinicians, policymakers, health advocates, communities, and funders  was developed in 2018 by interdisciplinary translational scientists at Washington University in St. Louis  The purp funders .Engagement science has been introduced as a central process representing specific methodologies related to translational sciences and D&I . EngagemNovel frameworks are needed to support translational dissemination in a manner that is equity-oriented, or working to reduce the power imbalances represented by research participants, illness-oriented communities, historically marginalized groups, and/or geographic communities . The cliWe are in the process of expanding our D&I core at the hub integrated Translational Health Research Institute of Virginia (iTHRIV), an NIH-NCATS funded CTSA Hub. Our current educational activities seek to introduce key translational dissemination concepts while also developing an environment to interact with other scientists and research staff interested in D&I engagement . Future work involves extending the curriculum offerings and continually assessing uptake and reach. These learning activities are intended to be delivered in an online environment with opportunities for real-time engagement with multiple sessions to allow for full concept engagement. The various curriculum activities are meant to take place over the course of a calendar year (August through late July).[can be quantified through bibliometric analyses]\u2022 Use theories and methods of multiple disciplines in developing integrated research frameworks [can be assessed through collaborative contributions of team members on a research study protocol]\u2022 Integrate concepts and methods from multiple disciplines in designing interdisciplinary research protocols can be quantified by assessing the educational background and department affiliation of members of the research team]\u2022 Investigate hypotheses through interdisciplinary research [[can be quantified by assessing agency and disciplinary breadth of grant funding applications submitted]\u2022 Draft funding proposals/grants for interdisciplinary research programs [can be assessed through bibliometric analysis and network analysis of authorship]\u2022 Disseminate interdisciplinary research results both within and outside the discipline - including both journals and conference presentations [can be assessed through bibliometric analysis and network analysis of authorship]\u2022 Author publications with scholars from other disciplines Metrics for uptake, reach, and adoption are central to the ongoing evaluation process. Gonzales and colleagues previously developed competencies for translational researchers engaged in D&I sciences including the following .\u2022 Use thLuke et al., 2018). Shea and colleagues also extend D&I domains and competencies by adding elements incorporated through the engagement sciences such as the centering of community engagement and contextual learning within the evaluation components , outcomes, dissemination plans, observation of formal and informal processes of decision making]\u2022 Ability to organize the partnership in a way that facilitates collective decision-making and the ability to adapt to the needs of the community through the research process \u2022 Assessment of communication effectiveness \u2022 Assessment of equitable distribution of resources and credit \u2022 Sustainability of partnership The D&I evaluation competencies that  proposedmponents  These evmponents .\u2022 Level [can be assessed through analysis of written curriculum documentation and video transcripts]\u2022 Racism must be recognized as a fundamental driver of healthcare inequities [can be assessed through engagement science domains]\u2022 Multisector partnerships [can be assessed through engagement science domains]\u2022 Active engagement of community members [can be assessed through engagement science domains]\u2022 Contextual understanding of healthcare delivery and impact on communities We posit extending these evaluation components by including measures associated with:[can be assessed through frequency and modality of results return]\u2022 Community-engaged results return of research findings  [can be assessed through analysis of curriculum documentation and eventual practices]\u2022 Economic assessments that include distributional cost effectiveness and assessments of equity impacts [can be assessed through representation of outcome measures and team science nature of the proposal using methods that focus on end-user experience]\u2022 Centering of impact of interventions on patients, families, clinicians, and other end-users \u2022 Use of open science practices \u2022 Use of public-engaged non-traditional dissemination strategies [can be assessed through network analysis of multidisciplinary approaches used over time and expansion of team across projects]\u2022 Sustained team science collaboration Further engagement with our own stakeholders is needed to co-design and finalize collaborative evaluation frameworks for equity-oriented translational dissemination that include the CTSA D&I, community engagement, and research workforce core groups, as well as the training programs (K and T Scholars). An optimal framework for translational D&I evaluation includes wide ranging products of dissemination incorporated within the TSBM framework, an orientation that centers health equity, along with methodological approaches and contextual learning supported through the engagement sciences. Expanding the core competencies through integration with TSBM products of impact and components of the translational dissemination framework will be the product of future work of our CTSA.Translational scholars have thoughtfully outlined the central importance and requirements of D&I components within national CTSA development . At our"}
+{"text": "Neural activities as reflected in brain oscillations are the \u201cbuilding blocks\u201d of neurocognitive functions  provides a comprehensive framework for understanding how different cognitive functions are formed through the synchronization of neuronal oscillations  is another widely accepted theory that explains how phase synchronization of brain oscillations facilitates communication and information transmission between different brain regions Fries, . While nIn general, the brain is considered an orchestra hall, during which we see purposeful coordination between brain oscillations  and functional magnetic resonance imaging (fMRI) as an effective method for characterizing the roles of brain oscillations in terms of both network topology and the neurophysiological mechanisms. The authors also provide a comprehensive review of research findings related to the involvement of brain oscillations in various cognitive functions  and neurocognitive disorders .In this Research Topic, Moenne-Loccoz et al. investigated the association between neural oscillatory activity in the motor cortex and striatum and varying degrees of motor activity under normal and parkinsonian conditions, and demonstrated the modulatory effects of local field potential (LFP) oscillations on the dopamine level in rats . Changes in broad-band oscillatory activities of cortico-basal ganglia networks (including changes in the relative power of low- and high-frequency bands) were correlated to ongoing motions, reflecting that these oscillatory patterns are modulated by the neural motor control system.Moghadam et al. developed a computational model of navigation focusing on mutual interactions between the hippocampus (HPC) and medial prefrontal cortex (mPFC). Results of the model simulations indicated that changes in the frequency characteristics of neuronal oscillations can impair the recall and retrieval of required information in navigation, leading to spatial disorientation in Alzheimer's patients.Soleimani et al. demonstrated that transcranial direct current stimulation (tDCS) can modulate large-scale neural connectivity. In a study investigating the neural circuitry underlying methamphetamine use disorder, the authors found that bilateral tDCS can increase cortical excitability in the executive control network (ECN) and ventral attention network (VAN) networks while having opposite effects on the default mode network (DMN). This research highlights the potential for externally induced stimulation methods like tDCS to modulate brain oscillations.As mentioned before, CTC is a theory that emphasizes the role of brain oscillations in connecting and communicating between neural networks. Ebrahimzadeh, Fayaz et al. have demonstrated the utility of machine learning approach for classifying patients with major depression disorder (MDD) who responded to repetitive transcranial magnetic stimulation (rTMS) treatment from the non-responders using resting state EEG data. K-nearest neighbor (KNN), support vector machine (SVM), and multilayer perceptron (MLP) algorithms classified the responders vs. non-responders using relevant features extracted from the EEG time series. The strongest discriminative indicators were EEG beta power, the sum of bispectrum diagonal elements in delta and beta bands, and correlation dimension. This study suggests that EEG assessments have the potential to predict the effectiveness of rTMS as a treatment for patients with MDD.Finally, Why the exact frequencies in our brains matter\u201d .Building on the previous Research Topic on \u201cAs an increasing number of studies investigate the contribution of brain oscillations to neurocognitive control systems, the articles featured in this Research Topic demonstrate the value of using neural oscillations to investigate both healthy and pathological brain states as well as to assess treatment outcomes of neuromodulation methods such as rTMS. We believe that brain oscillatory measures will continue to serve as critical non-invasive tools for comprehensively understanding neurocognitive systems, given their high sensitivity and accuracy.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."}
+{"text": "Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which primarily causes a symmetric polyarthritis. Clinical manifestations of the disease include joint pain, stiffness, and swelling. Unless treated, this debilitating disease can progress into long-term disability. Medications for RA include synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic agents. The rapid expansion of new RA drugs into the market has led to a need for health care practitioners to understand the effectiveness of each medication and the indications of use including when to initiate and stop therapies. Clinical assessment tools, including biomarkers used to indicate RA and the progression of the disease, have been proven effective for making a diagnosis and determining effective treatment regimens. Disease activity scales are also useful for guiding diagnoses and monitoring patients to assess treatment effectiveness.To review the various clinical assessment tools that have been designed to confirm an early diagnosis of RA, measure disease progression, and assist in determining the most optimal treatment regimens for patients with RA.The diagnosis of RA combines the patient history of joint pain and stiffness and the physical examination documentation of symmetric polyarticular joint swelling (synovitis). Laboratory tests including radiographs and blood tests for biomarkers can provide useful information to confirm the diagnosis of RA. Various autoantibodies have been reported in the blood of RA patients, but only the rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have been incorporated as diagnostic measures in routine clinical practice. Monitoring and assessment instruments for RA include the Disease Activity Score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Although these clinical assessment tools have limitations, health care providers can use them as measures of disease progression and to assist in planning treatment strategies to modify disease activity and improve the quality of life for the patient."}
+{"text": "The Affordable Care Act (ACA) is driving the evolution of reimbursement from a fee-for-service model to an outcomes-based system. Accountable care organizations (ACOs) are 1 component of this evolution, and 1 of their charges is to reduce hospital readmission rates for key diagnoses such as congestive heart failure (CHF) and other cardiovascular comorbidities. Lack of patient follow-up and adherence are 2 major causes of readmission. Providing strong medication management is 1 of the common factors in successful readmission programs. We discuss here how electronic solutions might strengthen these medication management programs.To explore the key issues and strategies that affect the use of electronic medication reconciliation processes and to identify the role the Academy of Managed Care Pharmacy (AMCP) can play in spearheading the adoption of electronic solutions.This was a descriptive analysis of the medication reconciliation process and the factors that promote or limit the application of electronic solutions to medication reconciliation and transitions of care processes. AMCP convened a panel of managed care, hospital, community, ACO, and medication therapy management pharmacists; technology vendors; and other health care stakeholders with an expertise or interest in transitions of care.In the last few years, there has been considerable uptake of electronic solutions to the admission medication reconciliation process, largely due to increasing penetration of vendors using sophisticated medication history tools. The current electronic solutions to the admission medication reconciliation record are remarkably similar in content. Some pilots for electronic solutions to discharge medication reconciliation are emerging.The focus group recommended specific programs AMCP can pursue to increase the adoption of electronic solutions for medication reconciliation. One important aspect to address is developing a business case that documents the return on investment (ROI) for electronic solutions. Besides electronic efficiencies, the ROI needs to include hospital readmission penalties, loss of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) incentives, avoidance of duplicative efforts, and payer costs for readmissions. Managed care pharmacy needs to be engaged in assessing its incentives for promoting electronic solutions."}
+{"text": "Drug induced liver injury (DILI) occurs in patients exposed to drugs at recommended doses that leads to idiosyncratic DILI and provides an excellent human model with well described clinical features, liver injury pattern, and diagnostic criteria, based on patients assessed for causality using RUCAM  as original method of 1993 or its update of 2016. Overall, 81,856 RUCAM based DILI cases have been published until mid of 2020, allowing now for an analysis of mechanistic issues of the disease. From selected DILI cases with verified diagnosis by using RUCAM, direct evidence was provided for the involvement of the innate and adapted immune system as well as genetic HLA (Human Leucocyte Antigen) genotypes. Direct evidence for a role of hepatic immune systems was substantiated by (1) the detection of anti-CYP (Cytochrome P450) isoforms in the plasma of affected patients, in line with the observation that 65% of the drugs most implicated in DILI are metabolized by a range of CYP isoforms, (2) the DIAIH (drug induced autoimmune hepatitis), a subgroup of idiosyncratic DILI, which is characterized by high RUCAM causality gradings and the detection of plasma antibodies such as positive serum anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), rarely also anti-mitochondrial antibodies (AMA), (3) the effective treatment with glucocorticoids in part of an unselected RUCAM based DILI group, and (4) its rare association with the immune-triggered Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) caused by a small group of drugs. Direct evidence of a genetic basis of idiosyncratic DILI was shown by the association of several HLA genotypes for DILI caused by selected drugs. Finally, animal models of idiosyncratic DILI mimicking human immune and genetic features are not available and further search likely will be unsuccessful. In essence and based on cases of DILI with verified diagnosis using RUCAM for causality evaluation, there is now substantial direct evidence that immune mechanisms and genetics can account for idiosyncratic DILI by many but not all implicated drugs, which may help understand the mechanistic background of the disease and contribute to new approaches of therapy and prevention. Amanita phalloides .,54.53,54Tienilic acid is now off the market, which explains the rarity of case reports on its potential to cause autoimmune DILI and the missing listing among the drugs most involved in DILI  53,54].,54.53,54Immunological aspects of idiosyncratic DILI have attracted much interest among clinical physicians and theoretical scientists, who presented their views mostly as narrative proposals in multiple publications ,70,129. Direct evidence for a role of the hepatic immune system in cohorts of specific idiosyncratic DILI caused by selected drugs was provided by cases with verified causality using RUCAM to ensure that the DILI was not attributed to alternative causes commonly observed in DILI cohorts . For insDirect evidence for an involvement of the immune system in idiosyncratic DILI was also provided by its rare association with the immune-triggered Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) caused by a small group of drugs . CausaliDirect evidence for a role of the innate and adaptive immune system in idiosyncratic DILI with RUCAM based verification of the diagnosis is increasingly observed. The initiation of an immune response requires activation of antigen presenting cells (APCs) by molecules such as danger-associated molecular pattern molecules (DAMPs) . Direct Finally, direct evidence of an immune involvement in an idiosyncratic DILI was recently provided in a highly appreciated prospective study in humans by urine metabolomics and microbiome analyses, which revealed the mechanism of DILI caused by anti-tuberculosis drugs with verified diagnosis, as assessed for causality using the updated RUCAM .Gaps are obvious in a few areas of the hepatic immune system related to idiosyncratic DILI. More specifically, clear initial mechanistic immune-based clues triggering the idiosyncratic liver injury are poorly understood, speculative, and not based on evidence. In this context, there is also uncertainty how inflammatory mediators interact with parenchymal and non-parenchymal cells of the liver and how immunological processes affect the liver histology, function and integrity of liver mitochondria and bile salt export pumps (BSEP) . There aThere is increasing awareness that the human model of idiosyncratic DILI rather than any animal model is ideal and appropriate to search for mechanistic clues leading to this specific disease , provideIdiosyncratic DILI is a classical human disease of the liver, well defined by clinical features reported in 81,566 cases with verified diagnosis by using RUCAM to establish causality. Data derived from the current mechanistic analysis help understand pathogenetic principles of the hepatic immune systems leading to DILI and may contribute to search for new therapeutic approaches urgently needed for DILI patients, providing therefore substantial advantages for future biomedical applications. With respect to genetic data retrieved from RUCAM based DILI reports, there is increasing awareness that genetic variation represents a risk factor for the development of DILI, which will require a more critical consideration by the physician before initiation of a treatment with a new drug. New challenges emerged from this analysis because a portion of this disease is not related to these pathways, illustrating its inhomogeneity and explaining the variability of treatment efficacy attempted by various therapeutic approaches. Using the perfect RUCAM based DILI cohort further studies are now needed to close the gaps of mechanistic features among the large DILI group with different immunological and genetic background susceptible to liver injury caused by more than 1000 drugs. To study this, using cohorts consisting of patients with RUCAM based DILI are the optimal approach whereas animal models are not the ideal tool due to lack of mimicking individual inherited characteristic features of affected humans."}
+{"text": "While there is some research that shows personal and psychological factors to be linked to disease-avoidant behaviour and attitudes in the time of Covid-19, this research is however mixed and inconsistent .In this study we clarify whether demographic and psychological factors specifically predict vaccination willingness and attitudes using Machine learning of a global survey sample from 137 countries (N = 24 000).Random forest machine learning algorithm was used to identify the strongest predictors of vaccination willingness and attitudes, while regression trees were developed to identify individuals at greater risk for anti-vaccination attitudes.Conspiratorial thinking and lack of trust in experts were associated with vaccination attitudes and willingness.The findings underscore the role of conspiratorial beliefs in shaping the uptake of non-pharmacological and pharmacological novel pandemic protective measures.None Declared"}
+{"text": "Asci et al.]. By providing non-invasive and cost-effective tools, voice analysis based on artificial intelligence holds significant potential to revolutionize the clinical management of neurologic disorders manifesting in voice abnormalities, as well as in a telemedicine scenario.Voice is a complex biological phenomenon resulting from the highly integrated and coordinated activation of the phonatory, respiratory and articulatory apparatus achieved by the nervous system. Voice is currently receiving growing interest among researchers working in the field of neurology. The neuronal basis of voice is indeed a fascinating area of research that explores the intricate neural networks involved in the production of vocalizations and is currently termed the phonological loop. Besides the complexity of brain networks contributing to vocalization, the acoustic analysis of voice is also characterized by high-dimensional data based on an exponential number of features. Accordingly, conventional voice analysis has recently received a relevant boost from more advanced approaches based on artificial intelligence and machine learning algorithms. By rapidly processing vast amounts of data, artificial intelligence can identify subtle patterns and anomalies that might be overlooked by human observers, leading to faster and more precise classifications. Indeed, recent studies have demonstrated that machine-learning algorithms significantly improve the accuracy of the objective classification of voice samples in humans [\u20134; Asci Voice Analysis in Healthy Subjects and Patients with Neurologic Disorders is an updated collection of research in the field. The first set of studies included in the Research Topic has investigated voice abnormalities in people with Parkinson's disease (PD) and other movement disorders. Two studies have confirmed and further expanded previous findings supporting the robustness and native language-independent accuracy of conventional as well as automated voice analysis based on artificial intelligence in people with PD . The observations strongly support the reliable use of voice analysis in people with different native languages  and stuttering , supporting the utility of objective voice analysis in the overall clinical management of various neurologic conditions.The present Research Topic entitled anguages . Moreovepairment . A finalIn conclusion, the research articles included in the present Research Topic further support the clinical utility of objective voice analysis in people with Parkinson's disease and other neurologic disorders. Voice analysis presents an evolving and promising non-invasive and cost-effective tool to complement traditional assessments, potentially leading to earlier diagnoses and improved outcomes for patients with various neurologic conditions , 7. HoweAS: Writing\u2014review and editing. GC: Writing\u2014review and editing. PG-V: Writing\u2014review and editing. GS: Writing\u2014review and editing."}
+{"text": "Corrigendum to: Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective .This corrigendum corrects funding information to: This project was partly supported by Gazi University Scientific Research Projects Coordination Unit (BAP) (project code: 01/2019-38). The authors would like to thank Gazi University for funding this project. The authors sincerely apologize for the error and confirm that this correction does not change the conclusion of the article."}
+{"text": "Background: High flow therapy (HFT) has been demonstrated to be a safe and effective noninvasive respiratory support technique for the treatment of pre-term infants in neonatal intensive care.Objectives: Our objective was to develop a quantitative framework based on available evidence to estimate the economic impact of adoption of a HFT respiratory support strategy compared to current standard of care.Methods: Model parameters were derived from a recent study comparing respiratory modality utilization between five US-based neonatal intensive care units (NICUs) adopting a HFT strategy and a larger pool of NICUs in the Vermont-Oxford Network (VON), and from single center experience. We computed the total cost difference between the respiratory support strategies based on published cost data. Parameter uncertainty was tested in sensitivity analyses.Results: The constructed model projected expected cost savings of $2,317 for the HFT strategy for the base case. Results were sensitive to length of HFT use, length of CMV, cost of HFT, and length of nCPAP support.Conclusions: Adoption of a HFT strategy appears to be associated with meaningful savings in total NICU episode of care costs, primarily because of reductions in the time of conventional mechanical ventilation. Further research is warranted to substantiate these findings."}
+{"text": "Total hip and knee arthroplasty for end stage arthritis are among the most cost-effective interventions available in all of medicine. Success of hip and knee arthroplasties is not universal and approximately one in ten patients are not satisfied with their arthroplasty and 10 to 34% of patients have an unfavourable long term pain outcome. The aim of this edition of Arthroplasty was to identify factors associated with: (1) poor joint specific outcome, (2) poor health related quality of life outcome and (3) dissatisfaction following total hip and knee arthroplasty.The scope was deliberately broad to identify factors (known and unknown) that influence outcome of total hip and knee arthroplasty, and of 40 submissions, eight were selected for this special edition after peer review.Many of the included studies reported subjective\u00a0patient reported outcome measures as their key outcomes but other objective measures such as muscle mass, timed Up-and-Go test, kneeling ability and postoperative pain are also featured. Some studies involved a focus on early rehabilitation after surgery (ERAS) principles and how to optimise pre-rehabilitation and reduce length of hospital stay readmission and reoperation. The effect of metal allergy and drain usage on outcomes is also explored. A variety of methodologies have been used including one randomised control trial, some machine learning and three systematic reviews investigating the effect of metal allergy on outcomes, associations with postoperative pain and the effect of patella resurfacing.This special edition has advanced our knowledge of factors influencing to the outcome of hip and knee arthroplasty but has also identified several areas of research that need to be addressed to improve the outcomes of our patients. Total hip and knee arthroplasty for end stage arthritis are among the most cost-effective interventions available in all of medicine . The \u201csuArthroplasty was to identify factors associated with: (1) poor joint specific outcome, (2) poor health related quality of life outcome and (3) dissatisfaction following THA and KA. The scope was deliberately broad to identify factors (known and unknown) that influence outcome of THA and KA, and of 40 submissions, eight were selected for this special edition after peer review  [The aim of this edition of ct 2023) \u201312. Manyct 2023) \u201310 but oct 2023) , timed Uct 2023) , kneelinct 2023)  and reduct 2023) , 9, 10 rct 2023)  and reopct 2023)  and draict 2023)  and threct 2023) , associaThe association of ipsilateral hip abductors muscle mass and gait following THA was assessed by Yasuda et al.  in a cohMarch et al.  investigClement et al.  performePeacock et al.  undertooMaliarov et al.  conductePostoperative pain is estimated to effect approximately 23% of patients after THA. Zhang et al.  conducteA risk prediction model for 30-day readmission after KA was developed by Gould et al.  using maShah et al.  under toThis special edition has advanced our knowledge of factors influencing to the outcome of hip and knee arthroplasty but has also identified several areas of research that need to be addressed to improve the outcomes of our patients."}
+{"text": "The WHO Special Initiative for Mental Health, aiming to establish accessible and affordable mental healthcare, reported insights into the challenges faced by participating countries, including the Philippines.,,The enactment of the Philippine Mental Health Act in 2018 signaled a step towards a comprehensive mental health framework.,WHO also introduced the Consolidated Framework for Implementation Research.In the Philippines, the internal setting of the WHO Framework can refer to the partnership of WHO, the Department of Health, and the Philippine Council for Mental Health (PCMH), an agency entrusted with formulating mental health policies and services.kapwa.,,The external setting of the WHO framework encompasses the complex environment influencing interventions. Filipino culture offers valuable resources to enhance Filipinos' mental well-being and social support, encompassing tight-knit community structures and Filipino psychology concepts, such as Ensuring the quality of personnel who lead community-based interventions in mental health system development is vital.Multi-stakeholder participatory engagement process is crucial for mental health system transformation in the Philippines.RA has previously received funding from the WHO and UNICEF for mental health projects within the Philippines."}
+{"text": "Dr. Pereira-Sanchez will draw upon his experience of use of various major social media platforms for professional networking and collaboration in international psychiatry and global mental health. These platforms offer opportunities to connect with colleagues worldwide individually and in groups and open avenues for peer support, research and advocacy. Specific examples the speaker will bring from his own experience include the World Network of Psychiatric Trainees and the Global Mental Health Think Tank, both of which gather hundreds of colleagues across continents.None Declared"}
+{"text": "The hemispheric lateralization of memory has largely been informed through the study of patients with temporal lobe epilepsy originating from medial temporal sources (mTLE). The material-specific model of memory relies on the basic framework that the left temporal lobe mediates verbal memories, while the right temporal lobe mediates non-verbal memories. Over the years, this model has been refined, and even challenged, as our understanding of the material-specific memory deficits in mTLE has been further elaborated in the neuropsychological and neuroimaging literature. The first goal of this mini-review is to highlight the major findings in the mTLE literature that have advanced and expanded our understanding of material-specific memory deficits in mTLE. Second, we will review how functional neuroimaging patterns of material-specific hemispheric lateralization in mTLE are being translated into the innovative clinical application of preoperative fMRI memory mapping. Temporal lobe epilepsy (TLE) is the most common form of localization-related epilepsy in adults, accounting for approximately 60% of cases   fMRI has been gaining momentum in clinical practice as a means to estimate the risk for memory decline following ATLR in mTLE. The foundation for clinical fMRI mapping is based on the patterns of material-specific findings discussed above, as well as patterns of neuroplasticity and reorganization and their relationship to outcome measures. While there are still methodological and even material-specific challenges (Jansen et al., Neuroimaging studies in mTLE have revealed functionally asymmetric patterns of activation within MTL structures contralateral to the seizure foci during material-specific encoding (Golby et al., Predictive studies of memory outcomes following ATLR have generally relied on two perspectives to guide decision making (Chelune et al., The functional adequacy model is supported by findings that demonstrate mTLE patients with better preoperative memory functioning are at greater risk for significant memory declines, than patients with low average or poor preoperative memory functioning (Chelune et al., less verbal memory decline after ATLR (Bonelli et al., The functional reserve hypothesis has received less support; however, recent neuroimaging work has found evidence for a more nuanced understanding of the functional reserve hypothesis based on anterior and posterior divisions of the MTL (Bonelli et al., The underlying focal pathology and surgical management of mTLE has informed much of our understanding about the material-specific lateralization of memory function. As research methodologies and cognitive theories have been developed, their application to the study of memory deficits in mTLE has refined and even challenged the model of material-specificity. Within the verbal domain, recent work has highlighted the importance of accounting for language adequacy and pre-existing semantic associations. The association between non-verbal deficits and right mTLE has been less consistent than the link between verbal memory and left mTLE, but tasks such as object-location binding have demonstrated promise. Finally, mTLE patients demonstrate aberrant lateralization of activation patterns on functional neuroimaging studies during material-specific memory tasks. These patterns are now being investigated as potential tools for clinical mapping to estimate post-operative memory outcomes following ATLRs.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "This invention introduces an innovative modality for malaria vector control that combines both effectiveness and efficiency with the highest levels of human safety and environment friendliness.larvae of Anopheles gambiae, Culex pipiens and Aedes aegypti. In this context, the accumulated photoactive compound (photosensitizer) in the larvae body induces, upon sunlight exposure, an oxidation stress that results in organism death. The obtained results reveal that SAFE is highly effective as it ensures up to 100% mortality of mosquitoes larvae. The effectiveness of SAFE accumulation in the larvae bodies was qualitatively and quantitatively investigated using the Confocal Laser Scanning Microscopy (CLSM) technique. The active ingredient of SAFE (chlorophyll derivative) exhibit several advantages: they are low cost, natural products extracted from green plants and endorsed by the Food and Drug Administration (FDA) as food additives. In addition, they are used in very low concentrations (\u00b5M), can be easily applied in the field by being dissolved in an aquatic environment and most importantly they are highly effective.The Novality of this (PCT) patent lies in developing a new ecologically safe modality using a natural plant extract (chlorophyll derivatives) and mosquito larvae attractant as sunlight active photo-larvicide for outdoors control of the"}
+{"text": "Thyroid cancer is the most common endocrine malignancy and its incidence has increased considerably over the past few decades . This ReThe articles gathered here reflect a particular interest in the genetic and epigenetic factors that could affect the thyroid cancer cell and its microenvironment. In particular, this topic will present preclinical and clinical research addressing the following issues: (i) identification of specific molecular patterns of thyroid tumorigenesis and tumor microenvironment, which could suggest new directions in pharmacotherapy research; (ii) discovery of new biomarkers to predict response or resistance to drug treatment, facilitating targeted cancer therapies and patient follow-up after treatment; (iii) discovery of environmental risk factors that might affect PTC development; and (iv) evaluation of preclinical models of human thyroid cancers with regard to their suitability for testing new drugs and molecule-targeted agents and for studies of targetable mechanisms of oncogenesis, malignant progression, and metastatic disease.Specific areas of investigation in this topic include the following as they relate to thyroid cancer: epidemiology and clinical research; epigenetics in thyroid; personalized medicine in thyroid; the tumor microenvironment; novel applications of bioinformatics in human thyroid cancer cell lines; molecular characterization of thyroid tumors; and use of diagnostic and prognostic biomarkers.Currently no successful treatment is available for advanced thyroid cancer, including poorly differentiated (PDTC), anaplastic/undifferentiated (ATC), and metastatic recurrent/persistent differentiated PTC that is not responsive to radio-iodine therapy.V600E mutation), tumor suppressors , and translocations , have clarified molecular mechanisms underlying the pathogenesis of thyroid cancer. However, correlations between each biomarker and prognosis/outcome have not yet been determined in a broad cohort of patients with metastatic thyroid cancer. Currently, BRAFV600E is the most frequent genetic hallmark of PTC and has been highlighted as a prognostic biomarker to improve risk stratification of patients with PTC, including low risk PTC  non-cellular components   regulatory T cell (Treg) frequency in primary PTC correlates with more aggressive disease  could offer an additional approach to the treatment of patients with these types of cancers. Targeting other cell types in the microenvironment instead of, or in addition to, the BRAF"}
+{"text": "Combined assessment of wall motion from cine imaging and perfusion defects from first-pass perfusion (FPP) imaging has been shown to have a high diagnostic performance for detection of acute ischemia. In this setting, a single ungated CMR scan capable of simultaneously capturing perfusion deficits and wall motion abnormality can be useful for rapid diagnosis of ongoing acute ischemia. We propose an accelerated FPP technique with ungated continuous acquisition capable of generating cardiac-phase resolved FPP images thereby enabling concurrent imaging of wall motion and perfusion deficits.FPP imaging without magnetization preparation using a steady state acquisition has been described before  and seenThe top row of Fig. We have demonstrated, for the first time, the feasibility and effectiveness of ungated cardiac-phase resolved (cine) FPP imaging for concurrent imaging of myocardial wall motion and perfusion in an animal model with flow-limiting stenosis. The presented method may improve the feasibility of detecting acute myocardial ischemia using CMR because of its reduced scan time (single scan for both cine and FPP) and reduced complexity (no cardiac gating). It may also enhance the accuracy and speed of diagnosis by virtue of concurrent (inherently fused) imaging of wall motion and FPP. The presented results demonstrate that the method is capable of imaging at high HRs with high spatial and sufficient temporal resolution. While the current method is limited to imaging a single slice during a breathhold, it can potentially be extended to 3D through spatio-temporal acceleration.Grant sponsors: American Heart Association Postdoctoral Fellowship Award 11POST7390063; National Institutes of Health grants nos. NHLBI HL38698, HL091989."}
+{"text": "A complete description of the relative spatiotemporal pressure gradients which drive blood flow has been a central goal of hemodynamics research over six decades. We have previously described a novel computational method for the in vivo estimation of these relative pressure gradients in the human cardiovascular system based on 4D flow Cardiovascular Magnetic Resonance (CMR) datasets (reference 1). We now describe the application of this method to allow a comprehensive assessment of the spatiotemporal distribution of relative pressure in the human aorta, based on 4D flow CMR datasets, in both healthy subjects, and in patients with established aortic disease. We have extended the approach by isolating, and individually analysing, the three major components of relative pressure, providing unique insights into the nature and timing of intra-aortic relative pressure changes.Six subjects underwent time-resolved, phase contrast CMR with 3-directional velocity encoding (4D flow) at 3 Tesla. Three were healthy volunteers and three were patients with established aortic disease . Spatiotemporal pressure maps were computed from the CMR flow fields using a finite-element implementation of the pressure Poisson equations. Using this formulation, the individual components of pressure were separated as time-varying inertial (\"unsteady\"), spatially-varying inertial ( \"convective\") and viscous component Figure .Aortic pressure differences are mainly caused by the unsteady effects (15mmHg at instant of peak acceleration), followed by the convective and a small viscous contribution (3.14mmHg and 0.2mmHg respectively at instant of peak velocity). Visualisation of relative pressure maps allowed identification of well-localised abrupt changes in pressure identified in each of the diseased cases. These regions of abrupt pressure difference were explained by either differences in aortic geometry, such as the presence of an aneurysm, a pseudo-coarctation, or the inlet of a dissection, or by complex flow features, such as vortical flow, particularly in the case of convective component of pressure  comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust , the British Heart Foundation , the Oxford NIHR Biomedical Research Centre , and the Oxfordshire Health Services Research Funds . Stefan Neubauer and Nic Smith acknowledge support from the BHF Centres of Research Excellence at Oxford and Kings College London respectively."}
+{"text": "Next-generation sequencing (NGS) is quickly replacing other methods for determining expression profiling of RNA as well as single-nucleotide variations within the genomes of both model organisms and human samples. At the Boston facility of Merck Research Laboratories, we concentrate on preparation and sequencing of samples where the research needs cannot be met by commercial venders. These unmet needs may be due to either availability of up-to-date protocols or to deadline constraints. In addition to validating and developing new library-construction and sequencing protocols, we also evaluate commercial vendors in consideration for future outsourcing. One of these current projects is an evaluation of transcriptome sequencing and profiling of formalin fixed paraffin embedded (FFPE) samples from Merck's current and past clinical studies. FFPE samples are readily available and easily stored but create difficulties in NGS analysis due to the low quality of the purified nucleic acids. Here, we compare techniques for transcriptome sequencing to microarray profiling of RNA purified from FFPE tissues as well as their mirrored fresh frozen counterparts."}
+{"text": "Aberrant expression of antigen presentation machinery (APM) has been closely associated with more aggressive tumors and may inhibit the therapeutic response to T-cell based immunotherapies. Furthermore, the selective pressure of immunotherapies may select for resistant clones that down regulate expression of APM as means of therapeutic resistance. This report characterizes a microfluidic assay for the screening and serial assessment of APM in circulating tumor cells (CTCs) from patients with advanced renal cell carcinoma and prostate cancer. Cell surface expression of MHC class I is identified in both renal cell and prostate cancer CTCs. Gene expression analysis for components of APM in CTCs is also validated using quantitative RT-PCR. The results of these studies suggest a unique CTC biomarker that may serve as a predictive and pharmacodynamic biomarker for use in clinical trials with T-cell based immunotherapies. Future studies will focus on the development of assays for markers of resistance to checkpoint inhibitors and expression of tumor associated antigens."}
+{"text": "The destruction of the hip joints with the development of osteonecrosis (ON) - a common complication and a leading cause of functional impairment in patients with systemic onset juvenile idiopathic arthritis (soJIA).A detailed study of the character of local disturbances and the structure of femoral heads (FH) in soJIA according to the comprehensive radiologic and morphological studies.Four patients with similar clinical and demographic characteristics , underwent total hip replacement (5 hip joints), because of ON of the FH. Changes in the FH were investigated using a specially designed protocol with the use of radiologic , computed tomography (CT), magnetic resonance imaging (MRI)) and morphological techniques.Ro-, CT revealed pronounced joint space narrowing, the picture of osteonecrosis with FH deformation, realignment of bone structure, erosions. Zones with significant restructuring of the bone (detected by CT) and enhanced heterogeneous MRI signal  were characterized by diverse damage in cartilaginous and bone tissues at morphologic examination .The results show that in patients soJIA with destructive hip damage similar changes of FH, interpreted by the radiological methods as ON, are characterized by a variety of histological disorders. Further in-depth comprehensive study of bone structure, damaged by ON of the FH will promote understanding of the pathogenetic nature of this complication."}
+{"text": "Globally, dengue has become one of the most alarming infectious diseases and its resurgence reflects the failure of traditional reductionistic disciplinary approach. Because neither an effective vaccine nor an effective vector control program is available for dengue prevention and control, a Community-Based Approach (CBA) to vector control and individual behavior change has been implemented in many countries. However, by and large, the CBA has failed as it ignored local community members\u2019 basic needs and perspectives in these processes. By challenging reductionist notions, this research will delineate the mental maps of local urban residents of the City of Dhaka, Bangladesh concerning dengue transmission and methods of dengue prevention and control.This study involved focus group discussion in 3 wards of Dhaka City Corporation, semi-structured interview of 30 stakeholders representatives; 900 ward/community members (300 from each ward); 18 policy- and/or decision makers  and community members\u2019 mental map construction of 24 ward representatives (supplemented by 300 ward members).This study revealed the lack of intersectoral coordination between local and national institutions dealing with disease and household sanitation, and highlights the difficulties in avoiding dengue vectors in urban areas with irregular water supply, poor sanitation services, and finally the location of large and small construction zones all over the city.The conclusion emphasizes the importance of the knowledge about the daily problems faced by the community members and partnership needed in all sectors to address water supply problem and disease surveillance systems."}
+{"text": "We present a prototype framework for exploring hypotheses about the neuroanatomical structures and connectivity in the cerebellar cortex at various levels of granularity, based on experimental data and hypotheses from the scientific literature . As illuThe core assumptions of the framework are: 1) connectivity rules are specified as probability distributions for overlapping volumes of objects of different categories; 2) synapse locations are randomly generated from the distribution associated with an overlapping volume 3) the volumes that represent dendritic trees have regions of uniform synaptic density.We use the NineML language for declarative descriptions of integrate-and-fire neuronal dynamics, and we have built two extensions to NineML to describe conductance-based neuronal spiking mechanisms and geometric connectivity. The NineML Conductance language is an extension of NineML for describing Ohmic and GHK currents based on the Hodgkin-Huxley formalisms or Markov chains. The NineML BREP language is an extension of NineML for constructive 3D boundary representation , and pro"}
+{"text": "The Nur transcription factors Nur77 , Nurr1 (NR4A2), and Nor-1 (NR4A3) are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal (HPA) axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction. The transcription factors Nur77  -responsive element (NBRE) (A/TAAAGGTCA)  and ventral tegmental area (VTA) in basal conditions  discharge corticotropin-releasing factor (CRF) that in turn increases both the secretion of adrenocorticotrophin hormone (ACTH) and the transcription of its precursor, the proopiomelanocortin (POMC) gene, in the anterior pituitary. ACTH stimulates the release of glucocorticoids (GCs) and the transcription of genes encoding several steroidogenic enzymes in the adrenal gland. GCs exert diverse effects on target tissues to mobilize energy for the body to deal with the stressor, and also exert a negative feedback through the inhibition of the synthesis and secretion of CRF and POMC  axis Figure . The eviA complex signaling cascade involving Nur factors is required for POMC regulation. The group of Eduardo Arzt (Kovalovsky et al., Less is known about the role of Nur factors regulating CRF in the PVN. While Nurr1 is expressed constitutively in the PVN (Saucedo-Cardenas and Conneely, In addition to its crucial role in the activation of the HPA axis, CRF functions as a neurotransmitter/neuromodulator coordinating extra-hypothalamic aspects of the stress response (Aguilera, Repeated immobilization stress and chronic mild stress induce CRF expression in the BNST (Stout et al., The motivation/reward circuit has its roots in dopamine neurons located in the VTA, which send afferences to the NAc, BNST, septum, amygdala, and PFC. Acute administration of drugs of abuse, which increase dopamine release (Di Chiara and Imperato, The development of compulsive running, associated with a high risk of addictive behavior, correlates with lower Nur77 and Nor1 expression in several nuclei of the motivation/reward circuit, in the addiction-prone Lewis rat strain compared with the less-addiction prone Fisher rats which do not develop compulsive running (Werme et al., It has been proposed that the persistent behavioral and cognitive effects of chronic intake of drugs of abuse depend on new programs of gene expression triggered by immediate-early genes. Tolerance and sensitization of Nur factors expression in nuclei of the motivation/reward and stress brain circuits suggest that these early genes play a signaling role in the plastic changes underlying long-term adaptations. Studies in cocaine abusers showed a reduction of Nurr1 expression in SN neurons (Nielsen et al., Opposing to a tolerance effect observed for Nurr1; Nur77 seems to adapt to dopamine changes and its levels are still inducible after chronic drug intake. For instance, it has been shown that Nur77 expression increases in the frontal cortex of rats after 10 days of cocaine self-administration (Freeman et al., Chronic stress also triggers tolerance and sensitization of Nur factors expression. In the PVN, it has been shown that Nur77 is no longer induced after chronic stress stimuli (Umemoto et al., Chronic stress plays a primary role in the origin of several brain pathologies such as anxiety and depression (McCormick and Green, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Resting state MRI (rsMRI), based on fluctuations in blood oxygenation level dependent (BOLD) signals, serves as a powerful tool to map networks of \u201cfunctional connectivity\u201d in the brain even in the absence of task activation or stimulation. The most popular analysis techniques for resting state networks involve region of interest (ROI) correlations or Independent Component Analysis (ICA) approaches where the networks are assumed to be undirected and static over the course of the several minute long scan. Recent studies by Majeed  and ChanWavelets have been used extensively in the analysis of neurological BOLD signals, most commonly, however in task-induced studies with few examples in rsMRI studies. Here we utilize wavelet features of voxel time series, which are clustered using an agglomerative clustering method. The DWT, an algorithm based on subband coding provides a fast computation of the wavelet transform, as in the multiresolution analysis (MRA) algorithm defined by Mallat . A varie"}
+{"text": "Although these languages enable software interoperability and therefore model reuse and reproducibility, they lack semantic information that would facilitate efficient model sharing and retrieval.The diversity of modeling approaches in computational neuroscience makes model sharing, retrieval, reuse and reproducibility difficult and even sometimes impossible. To address this problem, standardized languages have been developed by and for the community, such as NeuroML, PyNN 22 and NinIn the context of the INCF Multi-Scale Modeling (MSM) program, we have developed an ontology to annotate spiking network models described with NineML and other structured model description languages. Ontologies are formal models of knowledge in a particular domain and composed of classes that represent concepts defining the field as well as the logical relations that link these concepts together . These chttp://bioportal.bioontology.org/ontologies/3003).We are proposing the first version of the Computational Neuroscience Ontology or CNO. This ontology is composed of 207 classes representing general concepts related to computational neuroscience organized in a hierarchy of concepts. CNO is currently available on Bioportal (http://www.neuinfo.org). Integration with this large federation of neuroscience ontologies has two main advantages: (1) it allows the linking of models with biological information, creating a bridge between computational and experimental knowledge bases; (2) as ontology development is an iterative process that relies on inputs from the community, NIF has developed NeuroLex (http://neurolex.org), an effective collaborative platform, available for community inputs on the content in CNO.The design of CNO follows some of the recommendations of the Open Biological and Biomedical Ontologies (OBO) community and is compatible with the ontologies developed and maintained within the Neuroscience Information Framework (NIF, http://wwWith the further development of CNO based on inputs from the community, we hope CNO will provide a useful framework to federate digital resources in the field of computational neuroscience."}
+{"text": "A multicentre practice assessment study on peripheral intravenous catheters (PVC) utilization was carried out in 920 healthcare facilities (HCF) in France in 2010. Breaches in practices were observed particularly for insertion and maintenance of PVC.The objective was to evaluate the impact of the study practices on implementation of corrective measures.All HCF in Northern France participating in the practices study were requested by electronic way to answer an on-line questionnaire with the following items: protocol of care , organization and practices , change of material or products .Overall, 125 HCF of 280 participating in the practices study responded to the questionnaire (45%). They were mainly public hospitals and private clinics (89%). Actualization of care protocols (81%), traceability (59%), and training programs on the insertion and maintenance of the PVC (54%) were the most frequent reported corrective actions. One third of HCF modified disinfectant product or PVC type according to standard recommendations.This study showed that direct observation of clinical practices could have a significant impact on safety and quality of PVC use and may reduce infectious risk.None declared."}
+{"text": "The development of successful pharmacotherapeutics for the treatment of alcoholism is predicated upon understanding the biological action of alcohol. A limitation of the alcohol research field has been examining the effects of alcohol only and ignoring the multiple biological active metabolites of alcohol. The concept that alcohol is a \u201cpro-drug\u201d is not new. Alcohol is readily metabolized to acetaldehyde within the brain. Acetaldehyde is a highly reactive compound that forms a number of condensation products, including salsolinol and iso-salsolinol . Recent experiments have established that numerous metabolites of alcohol have direct CNS action, and could, in part or whole, mediate the reinforcing actions of alcohol within the mesolimbic dopamine system. The mesolimbic dopamine system originates in the ventral tegmental area (VTA) and projects to forebrain regions that include the nucleus accumbens (Acb) and the medial prefrontal cortex (mPFC) and is thought to be the neurocircuitry governing the rewarding properties of drugs of abuse. Within this neurocircuitry there is convincing evidence that; (1) biologically active metabolites of alcohol can directly or indirectly increase the activity of VTA dopamine neurons, (2) alcohol and alcohol metabolites are reinforcing within the mesolimbic dopamine system, (3) inhibiting the alcohol metabolic pathway inhibits the biological consequences of alcohol exposure, (4) alcohol consumption can be reduced by inhibiting/attenuating the alcohol metabolic pathway in the mesolimbic dopamine system, (5) alcohol metabolites can alter neurochemical levels within the mesolimbic dopamine system, and (6) alcohol interacts with alcohol metabolites to enhance the actions of both compounds. The data indicate that there is a positive relationship between alcohol and alcohol metabolites in regulating the biological consequences of consuming alcohol and the potential of alcohol use escalating to alcoholism. Alcoholism and alcohol (EtOH) abuse is a global burden. Alcoholism is estimated to be responsible for 3.8% of all global deaths, and cost associated with treatment equivalent to 1% of gross national product of high- and medium-income countries . The drug disulfuram (tetraethylthiuramdisulphide), which has been approved for the treatment of alcoholism, exacerbates the aversive symptoms of ACD by inhibiting the metabolism of ACD thereby encouraging individuals to abstain from EtOH consumption. The mechanisms of action behind disulfuram treatment were discovered serendipitously. In the early 20th century, a report emerged describing individuals who worked in a metal manufacturing plant experiencing transitory aversive symptoms  following the consumption of alcoholic beverages Koelsch, . Such sySoon thereafter, two researchers, Erik Jacobsen and Jens Hald, began examining tetraethylthiuramdisulphide (disulfuram) as a possible treatment for intestinal worms. Utilizing themselves as test subjects, both men reported experiencing several aversive symptoms following EtOH consumption  and aldehyde dehydrogenase (ALDH) enzymes  within the blood brain barrier it was widely accepted that very little ACD could commute into the brain from the periphery Hunt, . Additio2O2) scavenging compounds ebselen and alpha lipoic acid inhibit the formation of ACD through their reduction in the catalase-H2O2 reaction and subsequent formation of Compound I  inhibit catalase activity, thereby decreasing ACD formation within the brain, and have been shown to alter EtOH related behaviors. For instance, both sodium azide and triazole significantly altered EtOH-induced locomotor activity when infused into the arcuate nucleus of the hypothalamus  was peripherally administered to the University of Chile Bibulous (UChB) alcohol preferring rat line and resulted in significantly higher ACD blood levels while also significantly reducing EtOH consumption  administration of ACD acted to increase the consumption of and preference for EtOH in rodents  is the most extensively studied byproduct of ACD in relation to EtOH-use disorders and studies aimed at examining the underlying contribution of SAL to the reinforcing properties of EtOH are still in full swing. The While the effect of SAL administration on EtOH intake received considerably less attention than that of ACD, early endeavors found that centrally ICV administered SAL caused animals to exhibit an increase in both their consumption of and preference for , the dissemination of the underlying mechanisms of ACD and SAL at the neurobiological level has gained significant traction over the past three decades. The advent of a number of novel techniques  has allowed researchers to more thoroughly evaluate the neurobiological actions of drugs of abuse including EtOH and its metabolites. Research to date suggests that the neurobiological actions of EtOH and EtOH metabolites overlap to ultimately affect the development/expression of EtOH-use disorders. This section will present an overview of preclinical research focused on the neurobiological mechanisms within the brain reward pathway that have been identified to play a key role in the rewarding/reinforcing properties of EtOH, ACD, and the THIQs.3; Lovinger and Zhou, A) and glycine  channels  as a key mediator of the rewarding/reinforcing properties of virtually every major drug of abuse including EtOH  blocked the ICSA of EtOH, ACD, and SAL into the pVTA  rats  would readily self-adminster EtOH directly into the VTA exhibiting a U-shaped dose response curve with 100 mg % being the most effective concentration . An early study employed such a paradigm to examine the down-stream effects of microinjections of THP into the VTA on DA efflux within the core (AcbC) and the AcbSh reporting that a 13.6 \u03bcM microinfusion of THP increased DA efflux in the AcbC (94%) whereas the same dose decreased DA efflux in the AcbSh  completely abolished ICSA responding for SAL.The findings from the microinjection/microdialysis study by Deehan et al.  extend o3 receptors in the reinforcing properties of EtOH and SAL but not ACD. The compound ICS 250,390 (a 5-HT3 receptor antagonist) selectively prevents the ICSA of both EtOH and SAL but does not affect the ICSA of ACD  in the neurobiological actions of EtOH, ACD, and SAL within the MCL. Naltrexone, a general opioid antagonist with an affinity for all three opioid receptors , has been approved by the FDA for use in the treatment of alcohol use disorders (Johnson and Ait-Daoud, 1 antagonist; Peana et al., Both ACD and SAL possess locomotor stimulating properties within the VTA and much like EtOH, the activation of locomotor activity has been reported to be dependent on MOR activation (Sanchez-Catalan et al., The action of EtOH within the CNS is extremely complex yet the current body of literature has outlined a significant role for ACD and SAL in the modulation of the behavioral and neurological effects of EtOH. It has been shown that EtOH can act directly within the VTA to stimulate DA neurons (Gessa et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Introduction by guest editors Nina Marano  and MargSalmonella Newport)  (6).The World Health Organization has defined zoonoses as those diseases and infections naturally transmitted between nonhuman vertebrate animals and humans  and a myriad of human behavioral risk factors  for these diseases.The artwork featured on the cover of this December issue emphasizes the theme of humans living in harmony with animals. We hope this theme issue promotes greater awareness among our readers of the strong link between human and animal health and underscores the importance of establishing new partnerships between human and animal health, agricultural, natural resource, environmental, and other sectors to truly achieve a \"Peaceable Kingdom.\""}
+{"text": "Dear Editor,I read with interest the recent publication by Pattanshetty and Gaude on the role of chest physiotherapy for the prevention of ventilator-associated pneumonia (VAP). This ranPattanshetty and Gaude report on the clinical evolution of the clinical pulmonary infection score (CPIS) after intubation and mechanical ventilation, as a surrogate measure of VAP. The authors, however, did not formally report an actual VAP rate CPIS > 6) for the study. The CPIS has limited sensitivity and specificity and hence may not be the most suitable measure to estimate VAP. Chest ph for the et al. should be Choi et al.). The authors also neglected to report on the microbiological results of the sputum samples, which would have provided a more valid and specific diagnosis of VAP.[The authors should have investigated the impact of other known risk factors associated with VAP such as chronic obstructive pulmonary disease chronic obstructive pulmonary disease (COPD), airway intubation, mechanical ventilation time, intracranial monitoring, airway re-intubation, use of positive end expiratory pressure (PEEP), steroid use, tracheostomy, reduced conscious state and admission acute physiology and chronic health evaluation (APACHE) II score. Considers of VAP."}
+{"text": "Arabidopsis thaliana is accompanied by radical changes in cell wall structure and chemistry, but analysis of the underlying mechanisms and identification of the genes that are involved has been hampered by difficulties in accurately sampling discrete developmental states along the developing stem.Plant cell walls are complex dynamic structures that play a vital role in coordinating the directional growth of plant tissues. The rapid elongation of the inflorescence stem in the model plant By creating stem growth kinematic profiles for individual expanding Arabidopsis stems we have been able to harvest and pool developmentally-matched tissue samples, and to use these for comparative analysis of global transcript profiles at four distinct phases of stem growth: the period of elongation rate increase, the point of maximum growth rate, the point of stem growth cessation and the fully matured stem. The resulting profiles identify numerous genes whose expression is affected as the stem tissues pass through these defined growth transitions, including both novel loci and genes identified in earlier studies. Of particular note is the preponderance of highly active genes associated with secondary cell wall deposition in the region of stem growth cessation, and of genes associated with defence and stress responses in the fully mature stem.The use of growth kinematic profiling to create tissue samples that are accurately positioned along the expansion growth continuum of Arabidopsis inflorescence stems establishes a new standard for transcript profiling analyses of such tissues. The resulting expression profiles identify a substantial number of genes whose expression is correlated for the first time with rapid cell wall extension and subsequent fortification, and thus provide an important new resource for plant biologists interested in gene discovery related to plant biomass accumulation. Directional (anisotropic) cell wall expansion is an integral part of most plant developmental processes, where it facilitates the structural changes necessary for proper cell and organ morphogenesis. The initial expansive growth phase, which requires both addition of new extracellular polymers and remodeling of existing components in the primary cell walls, is often succeeded by cell wall thickening and rigidification processes to create secondary cell walls that enhance the structural integrity of the organ, but also curtail further wall extension. These sequential processes require a high degree of dynamic, context-specific coordination of cell wall building, reconstruction and fortification in order to harness the underlying driving force of turgor pressure in a spatially-defined manner . Consin vitro cultured Zinnia mesophyll cells  clusters of genes displaying stage-specific expression. Top 10 most significant over-represented GO terms appearing more than once in the gene list are shown ranked according to p-value (<0.05). Only GO terms with two or more genes in the input set and showing enrichment compared to the background frequency (in the full genome) are reported (number of genes indicated in brackets). Score indicates the fraction of input genes annotated with the GO term. 'Term occurrences' column indicates the number of co-occurrences of each GO term in the AtCoeCis results among all expression categories (left-most column).Click here for file"}
+{"text": "The investigations of A Fedorovska and L Nazarchuk (1995 to 2000) showed the necessity to introduce specific antigens of G class for the treatment of sepsis in immunodeficiency patients. We refer newborns to such patients. Effective treatment of sepsis in newborns and children of a young age group is impossible without evaluation of immunocompetent systems.Bioven mono when extracting anti-staphylococcus, anti-proteus and anti-pseudomonas antibodies in 150 newborns with postoperative and bone and joint sepsis. This immunoglobulin has international certification. During the last 10 years the main problem for treatment of postoperative sepsis in newborns is the treatment of pseudomonade infection. Regarding that traditional preparations have an insignificant titer of anti-pseudomonade antibodies, we used new anti-pseudomonade immunoglobulin received from specific plasma for 37 newborns and children under 1 year old. There were 20 patients having sepsis with esophageal atresia, two patients with angiocardiogenic sepsis, five with laryngotracheostenosis, five with bone and joint sepsis, and five after polytrauma with injury of pelvis bones and urinary bladder. In these 37 patients we used a new method for introduction of immunoglobulin in combination with fresh frozen plasma (patented).We successfully used intravenous normal human immunoglobulin Bioven in combination with antibacterial therapy allowed treatment of up to 90% of infants with severe sepsis. The use of new anti-pseudomonade immunoglobulin allowed recovery of the susceptibility of pathogenic flora to antibiotics after triple introduction of specific immunoglobulin, to raise phagocytal response and thus to gain positive results in 35 patients.Use of The experience of immune system correction in newborns with postoperative and bone and joint sepsis allow one to consider this method a leading one in clinic practice. The use of specific immune preparations increases complementary activity of blood and antibiotic susceptibility of pathogenic microflora."}
+{"text": "New recommendations from task force criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) include regional right ventricle (RV) akinesia or dyskinesia or dyssynchronous RV contraction associated to RV dilatation or RV dysfunction evaluated by magnetic resonance imaging (MRI) as major diagnostic criteria. However the frequent presentation of ventricular arrhythmias during the acquisition of MRI results in significant limitations in the evaluation of these images.Lidocaine has been used clinically in the suppression of ventricular arrhythmias. Objetctive: we used lidocaine to attempt ventricular arrhythmias suppression during MRI acquisition in order to improve the quality images to assessment of function and focal segmental contractility of RV in the evaluation of patients with ARVC/D suspected.We included 20 patients with ARVC/D suspected submitted to MRI presenting frequent ventricular arrhythmias (mostly ventricular bigeminy and trigeminy) during the acquisition of MRI. First we performed the Stead State Free Precession (SSFP) to RV evaluation in the presence of ventricular arrhythmias and after we administrated 1mg/kg of intravenous lidocaine in 30s and repeated the SSFP images to RV re-evaluation.Before and after the administration of lidocaine we registered the frequency of ventricular arrhythmias and analyze the image quality of global and regional RV function in .We observed significant reduction of ventricular arrhythmias on subsequent five minutes after administration of lidocaine with suppression of bigeminy and trigeminy in 75%. We observed significant better quality of images in 80%. Moreover none relevant side effect due lidocaine was observed.In evaluation of ARVC/D by MRI, the use of lidocaine can improve the image quality in patients presenting ventricular arrhythmias during the acquisition of exam.None."}
+{"text": "The National Rural Health Mission (NRHM) provides flexi-fund  to states and districts for paying for urgent but discreet expenses pertaining to maintenance of health infrastructure and provision of services at district, block and village level.Decisions on use of such fund is to be made locally through various bodies/committees at district, block and village levels such as District Health Societies (DHS), Rogi Kalyan Samitis (RKS), Panchayati Raj Institutions (PRIs), Village Health and Sanitation Committees (VHSC) and village level health and Integrated Child Development Services (ICDS). Various policy documents and guidelines are available on use of flexi-fund.Primarily, this fund is meant to ensure that health institutions at all the levels for healthcare services have readily available fund to overcome any bottlenecks that arise in the delivery of public health services. Amount of the flexi-find at various levels of healthcare services has been fixed Table .As per the financial monitoring reports available from the state government, the utilisation of AMGs at primary health centres and community health centres level has remained around 50% in years 2008-09 and 2009-10. Utilisation of untied fund at health sub-centre level has been about 30% during the same years. Utilisation of untied fund at the village level by VHSCs has remained low.We conducted this study to identify factors that impede or facilitate utilisation of flexi-fund at district and sub-district level. We aimed to use the findings of this study to developed revised operational guidelines on use of flexi-fund for consideration by state government.We reviewed relevant literature and used lessons from our work (using problem-solving approach) with health services to understand issues affecting underutilisation of flexi-fund in Jharkhand.We observed that late release of fund and lack of clarity on decision-making processes as well as operational guidelines in regard to utilisation of flexi-fund were barriers to effective utilisation of flexi-fund. Other issues included poorly defined auditing as well as supervision/monitoring systems and lack of orientation to fund managers.Our findings suggest that existing guidelines for use of flexi-fund need revision in order to make them comprehensible and useful for fund managers and users. Any revisions in programme guidelines/implementation should be followed up to assess the appropriateness and effectiveness of revisions.There is need to build capacity of fund managers especially as many of the staff appointed as fund managers are dealing with fund management first time. There is need to strengthen monitoring and evaluation systems. Despite political and socio-economic variations across the country, there is tremendous scope for adapting existing best practices from other states."}
+{"text": "Banasik and Suchecka express their discontent with our recent review on the (in-)direct neurotoxic effects of parent and hydroxylated (OH-) polybrominated diphenyl ethers (PBDEs) on the (developing) nervous system . Their min vivo, ex vivo, and in vitro studies reporting both structural and functional effects  exposure to PBDEs induces adverse neurotoxic effects is widely supported by numerous  effects . For som effects . In shor effects . HoweverCritical remarks can be found throughout our review , but thein vivo investigation of  neurotoxicity. Differences exist in the selection of investigated end points and also in methodologies for the investigation of a specific end point, as reviewed for effects on motor activity by brominated flame retardants  neurotoxicity studies would be very useful, it was beyond the scope of our review (Nonetheless, Banasik and Suchecka raise an important issue: the existence of differences in experimental designs for tardants . These dr review ."}
+{"text": "This paper investigates the steady hydromagnetic three-dimensional boundary layer flow of Maxwell fluid over a bidirectional stretching surface. Both cases of prescribed surface temperature (PST) and prescribed surface heat flux (PHF) are considered. Computations are made for the velocities and temperatures. Results are plotted and analyzed for PST and PHF cases. Convergence analysis is presented for the velocities and temperatures. Comparison of PST and PHF cases is given and examined. Interest of recent researchers in analysis of boundary layer flows over a continuously moving surface with prescribed surface temperature or heat flux has increased substantially during the last few decades. These flows have abundant applications in many metallurgical and industrial processes. Specific examples of such industrial and technological processes include wire-drawing, glass-fiber and paper production, the extrusion of polymer sheets, the cooling of a metallic plate in a cooling bath, drawing of plastic films etc. Such situations occur in the class of flow problems relevant to the polymer extrusion in which the flow is generated by stretching of plastic surface A large number of industrial fluids like polymers, soaps, molten plastics, sugar solutions pulps, apple sauce, drilling muds etc. behave as the non-Newtonian fluids The main theme of present analysis is to discuss the steady three-dimensional boundary layer flow of Maxwell fluid over a bidirectional stretching surface subject to prescribed surface temperature and prescribed surface heat flux. The effects of applied magnetic field are also included in this analysis. To our knowledge, not much is known about flows induced by a bidirectional stretching surface. Wang Consider three-dimensional magnetohydrodynamic (MHD) boundary layer flow of an incompressible Maxwell fluid. The flow is induced by bidirectional stretching surface Prescribed surface heat flux (PHF)Here Following In this section, we solve the problem consisting of Eqs. (24)\u2013(27) with boundary conditions in Eq. (28) by HAM. For that the initial guesses and auxiliary linear operators are taken as follows:At zeroth order, the problems satisfyIn above expressions, It should be pointed out that when The general solutions are arranged as followsIt is well known fact that the homotopy analysis method has a great freedom to choose the auxiliary parameters The results are displayed graphically to see the effects of In this study, the three-dimensional MHD flow of Maxwell fluid generated by bidirectional stretching surface is investigated for two cases of prescribed surface temperature (PST) and prescribed surface heat flux (PHF). The effects of applied magnetic field Effects of Deborah number Both Increase in ratio parameter Temperature for An increase in heat generation/absorption parameter enhances the temperatures Our series solutions have an excellent agreement with the previous results in limiting cases."}
+{"text": "Eurygaster spp. and Aelia spp.) on the composition of wheat gluten proteins and its influence on flour technological quality were investigated in the present study. Wheat samples of six wheat varieties, collected from two localities in northern Serbia, were characterized by significantly different level of wheat bug infestation. Composition of wheat gluten proteins was determined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE), while the selected parameters of technological quality were determined according to standard and modified empirical rheological methods . The surface morphology of the selected samples was viewed using scanning electron microscopy (SEM). Wheat from wheat bug-infested locality regardless of the variety had deteriorated technological quality expressed with higher Farinograph softening degree, lower or immeasurable Extensograph energy, and Alveograph deformation energy. The most important changes in the gluten proteins composition of bug-infested wheat were related to gliadin subunits with molecular weights below 75\u2009kDa, which consequently caused deterioration of uniaxial and biaxial extensibility and dough softening during mixing.The effects of wheat bug infestation ( Eurygaster spp. and Aelia spp.) have been the regular members of entomofauna of small grains in Serbia. In this regard, in years characterized by shorter and milder winter, sudden transitions from low to high daily temperatures, and/or occasional local occurrence of heat stresses in May and June, the critical number of insects is exceeded . Th. Th21]. The microstructure of kernel endosperm  reflecteWheat bug infestation affected decrease in Gluten Index values significantly determined by both standard and modified Gluten Index methods indicating the change in the composition of gluten complex. The proteolytic process degraded gluten towards creation of higher number of both glutenin and gliadin bands, but the most expressed change was related to gliadins of molecular weights below 75\u2009kDa. The change in the number of bands and amount of gliadin and glutenin fractions affected the technological quality of selected wheat varieties, altering uniaxial and biaxial extensional properties as well as dough mixing properties."}
+{"text": "The study was conducted to determine the correlations between serum concentration of selected macro- and microelements, namely: magnesium (Mg), copper (Cu), zinc (Zn), arsenic (As), calcium (Ca), cadmium (Cd) chromium (Cr) and selenium (Se) with increased or decreased predisposition to breast and ovarian cancer.The subjects selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland . Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria  to achieve the maximum of similarity between them.All the elements were quantitatively measured simultaneously in diluted serum samples by inductively coupled plasma mass spectrometry (ICP-MS) using mass spectrometer  in standard mode  and in DRC mode  with methane as a reaction gas, for removing polyatomic interferences in measurement.Statistically significant differences have been found for arsenic and zinc. In case of arsenic, individuals classified in the second and fourth quartile had a significantly higher risk of breast or ovarian cancer than those in the first quartile. In case of zinc a significantly lower risk of breast or ovarian cancer was observed among individuals classified in the second quartile. The data are shown in Table Apart from the influence of single elements some interactions from combinations of arsenic, magnesium, cadmium, zinc and calcium with selenium were also analyzed. The combinations with statistically significant differences between quartiles in the disease risk are shown in Table"}
+{"text": "The EPMA Journal following its transfer to BioMed Central two years after publication of the first article in the journal.Changing long-held beliefs is never easy. As a consequence of the accumulating clinical data and knowledge about the epidemiology and pathological mechanisms of the most frequent causes of morbidity and mortality, we are currently reconsidering our view of the origins and progression of cardiovascular, oncologic and neurodegenerative diseases. Optimistic versus pessimistic prognosis for healthcare sector depends much on diagnostic, preventive and treatment approaches, which healthcare systems will preferably adopt in the near future. PPPM offers great promise for the future practice of medicine. We are pleased to announce this first open access volume of  The EPMA Journal.Predictive, preventive and personalized medicine (PPPM) offers great promise for the future practice of medicine. Essential components of this approach include well-organized population screening protocols utilizing novel diagnostic biomarkers of disease states, targeted prevention of common human pathologies, optimal treatment planning and personalized medicine thereby resulting in a substantial improvement in the quality of life. This approach also offers the advantage of delivering care at potentially reduced costs to the population at large, thereby addressing social and ethical issues related to access to and affordability of healthcare. A broad distribution and a routine clinical utilization of advanced technological approaches could enable a significant portion of the population to reach and exceed 100 years of age yet remaining vibrant and in excellent physical and mental health as actively contributing members of society. One of the central issues discussed is the screening for predisposition of healthy individuals to potential pathologies later in life. The groups at risk identified within the general population can be given a fair chance of a focused diagnosis with multidisciplinary expertise and well-timed preventive measures. The reliability of the blood-tests proposed, potential application to clinical routines, enormous economic and social impacts of the new generation of molecular- and nanotechnology-based diagnostic approaches - are all discussed in As a consequence of the accumulating clinical data and knowledge about the epidemiology and pathological mechanisms of the most frequent causes of morbidity and mortality, we are currently reconsidering our view of the origins and progression of cardiovascular, oncologic and neurodegenerative diseases. The majority of these pathologies are of chronic nature: they progress from precursor lesions over one or even several decades of life until a diagnosis is made that is often too late for effective therapeutic intervention. An excellent example is the epidemic scale of diabetes mellitus type 2 witnessed in the European Union. In most industrialized countries and countries with large populations, the permanently growing cohort of people with diabetes creates a serious healthcare problem and dramatic health economic burden. Estimates for diabetes prevalence in the years 2030 is half a billion patients worldwide Figure .Furthermore, the contemporary onset of the dominant type 2 diabetes has already been observed in subpopulations of teenagers [The EPMA Journal provides highly professional multidisciplinary insights into current \"disease care\" versus desirable \"healthcare\" mechanisms to promote the paradigm change from delayed interventional \"disease care\" to PPPM as the medicine of the future [Our message is that new guidelines should create the robust juristic and economic platform for advanced medical services utilizing the cost-effective models of risk assessment followed by tailored treatments focused on the precursor stages of chronic disease . The EPMe future .versus pessimistic prognosis in future developments of the healthcare sector depends much on diagnostic, preventive and treatment approaches which healthcare will hopefully adopt in the near future [The EPMA Journal promotes this \"three-dimensional\" vision in medical approaches, namely as outlined in [Figure Optimistic r future . Withoutn Figure .The EPMA Journal that are highly appreciated by readers, namely:There are some features of a paper design specific for the articles published with \u2022 Highly informative content that provides an overview of corresponding topics, including related multi- and inter-disciplinary aspects in a reader-friendly manner that makes articles particularly useful for professionals working in allied medical fields and non-medical braches.\u2022 A reasonable combination of at least two aspects of the PPPM-concept; such as: predictive diagnostics followed by treatment design tailored to the patient; or innovative approach for population screening combined with concomitant recommendations for targeted prevention and individually created treatment algorithms.status quo (currents achievements & problems) overview followed by outlook for future trends and prognosis of developments\u2022 Discussion of the \u2022 A clear message in each publication supplied with a well-formulated PPPM-related title, a correspondingly structured abstract and conclusions including expert recommendations in the field\u2022 Smart paper-design characterized by reader-friendly subheadings of paragraphs for ease of navigationstatus quo and perspectives, text and illustrative materials\u2022 A good balance between clinical aspects and technological solutions, The EPMA Journal Award\" for distinguished articles presented at the regular EPMA world congresses.\u2022 Overall excellent scientific and technological level of publications that undergo an additional evaluation by the Editorial Board (more than 50 experts from more than 30 countries worldwide) for consideration in \"The EPMA Journal is for everyone: on reading the journal, readers can learn a new philosophy in medicine, novel trends in healthcare and biomedical education. The journal provides important information for individuals of various professional and scientific backgrounds. Professionals can consider the general concept of multidisciplinary approaches and learn the mindset of related medical areas and other scientific branches. A partial list of those who will especially benefit from the information provided in the journal is as follows:\u2022 professionals in conventional and molecular diagnostics, biomedicine, biotechnologies, ethics and economics, and the healthcare industry\u2022 universities, research units, private and public hospitals\u2022 patients and their family members\u2022 international associations with healthcare-oriented scientific, research and public health-related activities/responsibilities\u2022 political organizations and authorities active in the healthcare sectorThe EPMA Journal are created according to the principle of the informational pyramid turned upside-down: highly specific topics that individual professional groups work on (the pyramid-tip) are brought into more generalized scientific context and, further, correlated with concrete tasks to be performed in the healthcare sector. Consequently, PPPM-related aspects potentially interesting for corresponding border areas and giving an overview of other scientific branches. An example is provided in [Figure To reach the maximum educational impact, the review articles in n Figure . The autThe mission of the European Coordinator in this field of PPPM is performed by the European Association for Predictive, Preventive and Personalized Medicine. The concepts of innovative European and international projects, which EPMA represents for further consideration at the EU Commission, the European Parliament, NIH/NCI are elaborated upon by the consortium of the world-leading professionals (not restricted to Europe).The EPMA Mission and Objectives in the field of predictive, preventive and personalized medicine have been introduced to UNO Figure . The parThe EPMA Journal, the Association creates a professional forum to discuss most effective technologies and innovative approaches of predictive, preventive and personalized medicine.Practical application of innovative technologies in favour of predictive diagnostics, targeted preventive measures and personalized patient treatment in European healthcare and in global scale is the central idea of the Association. Through"}
+{"text": "The aim of this study was to investigate the effectiveness of the application of antimicrobial copper alloys (Cu +) in a Neonatal Intensive Care Unit (NICU) in relation to the reduction of microbial flora.+, using dry and wet method technique.At a Level III Neonatal Intensive Care Unit of a pediatric hospital, with the capacity of twenty-six (26) incubators, antimicrobial copper (Cu +) was implemented on touch surfaces and objects. The copper alloy contains Cu 63% - Zn 37% (Lead Low). Microbiological cultures were taken in three different time periods, before and after the application of CuIn the above NICU, the reduction of microbial flora after the implementation of the antimicrobial copper (Cu +) on the selected surfaces and objects was statistically significant  and was recorded at 90%. The pathogens isolated at high rates (CFU / ml) prior to copper implementation were as follows: Klebsiella spp., Staph. Epidermidis, Staph. Aureus, Enterococcus spp.This study highlights the positive impact of antimicrobial copper (Cu +) and demonstrates that copper implemented surfaces and objects are effective in neutralizing bacteria, which are responsible for Health Care Acquired Infections in the nosocomial environment (HCAIs).The innovative implementation of antimicrobial copper in the NICU and the significant reduction of microbial flora heralds the reduction of antimicrobial drugs use, and a possible reduction of hospital acquired infections and hospitalization time.None declared."}
+{"text": "Whilst evidence based innovations exist for helping to address Health Care Associated Infections (HCAIs), the uptake and implementation of these is highly variable and in some cases very slow. We aimed to investigate organisational innovation adoption decisions and implementation processes in the context of Infection Prevention and Control (IPC). Here we focus on the implications of stakeholder involvement during these processes.We sampled NHS trusts in England, which were winners of the Department of Health 'HCAI Technology Innovation Award 2009'. By analysing data from over 100 semi-structured qualitative interviews with clinical and non-clinical staff at all levels, we looked at technology selection decisions and implementation processes.Stakeholder involvement varied across the trusts with decisions highly exclusive to the IPC team, to highly inclusive of wider trust members. The context, including previous experience, and logistical factors influenced the level of stakeholder engagement. The method and timing of stakeholder involvement impacted on: the nature of innovations considered, innovations selected, success of the implementation of innovations. Cases of non-adoption and discontinued technologies are presented for important learning. Cases of successful implementation are presented in context of the adopting hospital. A model of potential benefits to \u2018successful\u2019 innovation adoption and implementation is presented.Key stakeholder involvement can lead to innovation adoption decisions compatible with structural and cultural contexts. There are potential synergies through stakeholder engagement across the two phases of decision making and implementation. Our model has useful application as a strategic and operational toolkit for IPC.None declared."}
+{"text": "Zheng classification study based on infrared thermal imaging technology has not been reported before. To detect the relative temperature of viscera and bowels of different syndromes patients with pulmonary disease and to summarize the characteristics of different Zheng classifications, the infrared thermal imaging technology was used in the clinical trial. The results showed that the infrared thermal images characteristics of different Zheng classifications of pulmonary disease were distinctly different. The influence on viscera and bowels was deeper in phlegm-heat obstructing lung syndrome group than in cold-phlegm obstructing lung syndrome group. It is helpful to diagnose Zheng classification and to improve the diagnosis rate by analyzing the infrared thermal images of patients. The application of infrared thermal imaging technology provided objective measures for medical diagnosis and treatment in the field of Zheng studies and provided a new methodology for Zheng classification. Infrared thermal imaging technology is a noninvasive imaging procedure used to record the thermal patterns using infrared camera. It is widely applied in the field of biomedicine. It is believed that infrared thermal imaging cameras can potentially be used to detect subjects with fever, the cardinal symptom of SARS, and avian influenza . And it 72 healthy volunteers (group A) were enrolled from community resident in Dongcheng District of Beijing. 111 patients with pulmonary disease including chronic obstructive pulmonary disease, bronchial asthma, and chronic bronchitis were derived from the outpatient of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine. Among these patients, 35 cases were diagnosed cold-phlegm obstructing lung syndrome (Group B) and 76 cases were diagnosed phlegm-heat obstructing the lung syndrome (Group C). The clinical trial was approved by the Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine. The gender and age distribution was shown in Tables practical internal medicine and chronic obstructive pulmonary disease treatment guidelines (2007 revision) was written by chronic obstructive pulmonary disease study group of Chinese Society of Respiratory Diseases [Reference to the lines 200 revisionBronchial asthma prevention and treatment guidelines was revised by Asthma study group of Chinese Society of Respiratory Diseases on November 7, 2002 [Reference to the  7, 2002 .Chronic bronchitis clinical diagnosis and the efficacy criteria was revised by National Clinical Professional meeting of chronic bronchitis in 1979 [Reference to the Chinese internal medicine and TCM Zheng Diagnosis and efficacy standard [TCM terms [Reference to the standard  and TCM CM terms .Primary symptoms include (1) cough or (and) dyspnea; (2) yellow sticky sputum.Associated symptoms include (1) vexation, (2) abdominal distention and fullness, (3) dry mouth and thirst and like drinking cold, (4) fever but without aversion to cold, (5) yellow urine, (6) dyschezia, (7) red tongue, (8) yellow or yellow with greasy tongue fur, and (9) slippery and rapid pulse.Primary symptoms: (1) cough or (and) dyspnea (2) white sputum.Associated symptoms include (1) oppression in the chest, (2) fear of cold and cold extremities, (3) pale tongue, (4) white with lubricating tongue fur, (5) string-like with tight pulse.Patient with primary symptoms and two associated symptoms can be diagnosed.In line with the diagnosis criteria of chronic obstructive pulmonary disease or bronchial asthma or chronic bronchitis.In line with the diagnosis criteria of phlegm-heat obstructing the lung syndrome or cold-phlegm obstructing lung syndrome.46 to 75 years old.Without skin diseases or skin allergies or skin surface damage.Patients in stable condition can coordinate with the researchers to completed the trial independently.Signed informed consent.ATIR-M301 medical infrared thermal imager  was used in this clinical trial. The scanning room temperature was controlled at 24 \u00b1 2\u00b0C and the humidity was 65%\u201370%. In order to make the surface temperature balanced, the healthy volunteer or patients exposed completely the body and stood quietly in the scanning room for 15 minutes to adapt to the environmental temperature before being checked. The anteroposterior images were scanned and saved to be analyzed. Medical thermography analysis software was used to detect and analyze the relative temperature of viscera and bowels of healthy people and patients with different Zheng of pulmonary diseases. The relative temperature was measured in the region that viscera and bowels project.\u03c72 test was used to analyze the enumeration data. One-way ANOVA was used to analyze the data between the normal and different Zheng classification groups. q test and LSD method were used for the paired comparisons, with P < 0.05 denoted as significant.The trial showed that in the normal group and in the cold-phlegm obstructing lung syndrome group, as well as in the phlegm-heat obstructing lung syndrome group, the maximum temperature of viscera and bowels was taken in the lung region, followed by the lower temperature in both the descending colon and the ascending colon regions; see Figures The results showed that the temperature characteristics of viscera and bowels were different in different Zheng classifications of pulmonary diseases. Compared with normal group, the relative temperature of lung, descending colon, ascending colon, small intestine, and stomach significantly increased in the phlegm-heat obstructing lung syndrome group, and there was a statistical difference. While compared with normal group, the relative temperature of lung and descending colon was significantly increased in the cold-phlegm obstructing lung syndrome group, and there was a statistical difference, but the relative temperature of ascending colon, small intestine, and stomach was not significantly different. Compared with cold-phlegm obstructing lung syndrome group, the relative temperature of lung and small intestine significantly increased in phlegm-heat obstructing lung syndrome group, and there was a statistical difference. See Tables Syndrome differentiation is one of the important guidance and principles in the clinic of traditional Chinese medicine. Zheng classification is the basis of syndrome differentiation, and it is a method to distinguish between the health and disease by correlation of all four examinations. The research on Zheng classification is one of the cut-in points on integration of traditional Chinese and Western medicine . It is aEpidemiological studies have shown that the main leading causes of death in China urban population in 2002-2003 were cancer and heart diseases, respectively; the death due to respiratory diseases accounted for 15.63% of the total mortality year round. In 2006, the death due to respiratory diseases was in the fourth place . The fouCompared with previous Zheng classification study, the infrared thermal imaging technology was used in this trial. The two opposing Zheng classification including cold and heat of pulmonary disease were studied to distinguish the characteristics by infrared thermal imaging.Infrared thermal imaging technology is a functional imaging technique. The body temperature can be continuously traced objectively and accurately by medical infrared imaging at any point and two-dimensional temperature field. Infrared thermal imaging provides visual and diversified information of body temperature distribution marked with different colors to the clinicians. It provided an important way for disease diagnosis by analyzing the heat map and the difference of surface temperature . In manyZheng classification study based on infrared thermal imaging technology has not been reported before. Our previous studies showed that under physiological conditions, the relative temperature of viscera and bowels was regulated by a special rule and the relative temperature in descending order was ordered as follows: lung > descending colon > ascending colon > liver > stomach > kidney > small intestine . In thisPairing of the viscera and bowels is an important theory, which provides guidance to traditional Chinese medicine (TCM) clinical practice. The investigation has been the focus of research on the basic theory of TCM [the lung and large intestine are exteriorly-interiorly related. The application of infrared thermal imaging technology provided objective method for medical diagnosis and treatment in the field of Zheng studies and provided a new methodology for Zheng classification.y of TCM . The resIn the clinic, the traditional Chinese medicine Zheng classification of pulmonary diseases presented diversity. Experienced Chinese medicine practitioners usually make syndrome differentiation by four examinations obtained. But some Zheng classification diagnosed by some doctors were still not clear; they directly reduced the efficacy of treatment and even aggravated the patient's illness. In the clinic, Zheng classification diagnostic tools were lacking at present. The infrared thermal images characteristics of different Zheng classifications of pulmonary disease were distinctly different. The influence on viscera and bowels was deeper in phlegm-heat obstructing lung syndrome group than in cold-phlegm obstructing lung syndrome group. The viscera and bowels relative temperature of patients with different Zheng classification of pulmonary diseases was different. The trial indicated that it is helpful to diagnose Zheng classification and to improve the diagnosis rate by analyzing the infrared thermal images of patients.The infrared thermal images characteristics of different Zheng classifications of pulmonary disease were distinctly different. The influence on viscera and bowels was deeper in phlegm-heat obstructing lung syndrome group than in cold-phlegm obstructing lung syndrome group. It is helpful to diagnose Zheng classification and to improve the diagnosis rate by analyzing the infrared thermal images of patients. The application of infrared thermal imaging technology provided objective measure for medical diagnosis and treatment in the field of Zheng studies and provided a new methodology for Zheng classification."}
+{"text": "Multilevel significant atherosclerotic disease involving the carotid bifurcation and the proximal ipsilateral common carotid or brachiocephalic arteries presents an uncommon and difficult management problem. Axial (aortocarotid bypass) or extra-anatomic procedures  and variations in the performance of thromboendarterectomies are all possibilities in treatment of tandem brachiocephalic arteries stenosis. Although extra-anatomic procedures have excellent patency (90% at 5 years) and durability and avoid the morbidity of median sternotomy, they are usually performed in patients with significant cardiovascular comorbidities who may be detrimentally affected because of the use of general anesthesia and the possible need of prosthetic devices and multiple incisions. The desire to avoid the need for intrathoracic and extra-anatomic reconstructions has fostered the use of transluminal angioplasty and primary stenting of the supra-aortic vessels. Combined or hybrid carotid procedures can offer an easier solution to a sometimes difficult technical problem.The aim of this study was to review the existing literature on such hybrid procedures. An electronic search of the pertinent literature was undertaken.Grego et al. treated 16 patients with CEA and retrograde angioplasty and stenting for tandem lesions. The procedure was successful in 14, and there was no neurologic morbidity or mortality at 30 days. At 1-year follow-up, all treated vessels were patent and patients were free of focal cerebrovascular symptoms We have demonstrated that CEA combined with proximal stenting seems a simple and convenient alternative to conventional surgery for symptomatic multilevel disease of the extra-cranial vessels. We suggest this procedures will become the treatment of choice for this subset of patients."}
+{"text": "Mutation impact extraction is a hitherto unaccomplished task in state of the art mutation extraction systems. Protein mutations and their impacts on protein properties are hidden in scientific literature, making them poorly accessible for protein engineers and inaccessible for phenotype-prediction systems that currently depend on manually curated genomic variation databases.We present the first rule-based approach for the extraction of mutation impacts on protein properties, categorizing their directionality as positive, negative or neutral. Furthermore protein and mutation mentions are grounded to their respective UniProtKB IDs and selected protein properties, namely protein functions to concepts found in the Gene Ontology. The extracted entities are populated to an OWL-DL Mutation Impact ontology facilitating complex querying for mutation impacts using SPARQL. We illustrate retrieval of proteins and mutant sequences for a given direction of impact on specific protein properties. Moreover we provide programmatic access to the data through semantic web services using the SADI (Semantic Automated Discovery and Integration) framework.We address the problem of access to legacy mutation data in unstructured form through the creation of novel mutation impact extraction methods which are evaluated on a corpus of full-text articles on haloalkane dehalogenases, tagged by domain experts. Our approaches show state of the art levels of precision and recall for Mutation Grounding and respectable level of precision but lower recall for the task of Mutant-Impact relation extraction. The system is deployed using text mining and semantic web technologies with the goal of publishing to a broad spectrum of consumers. MuteXt by  albeit dependent on semi-automatic processing of information from databases or text mining pipelines.We believe these issues can be addressed by developing methods for co-reference resolution of mutation mentions and by improving mutation extraction and grounding algorithms, as well as extending gazetteers containing words describing directionality. Textual descriptions of kinetic variables could also be used as an extension to our current abbreviation-centric method and therefore improve recall of Mutant-Impact relation extraction. Finally, the special cases where the impact is a total loss of function can be handled by a new set of rules connecting terms describing enzymes/mutants and terms describing inactivity. Until now the tools for the extraction of mutation mentions from text have been considered appropriate for augmenting the manual curation of mutation databases, providing candidate protein point-mutation impact suggestions , de novofully automated mutation impact extraction from unstructured text has a respectable level of precision of 0.86, albeit with moderate recall. Although further testing of these grounding and impact extraction algorithms on a larger corpus of documents from open access journals is required, using such platforms it will become possible to assess the range of impacts that have been investigated though mutational analysis of target protein sequences and the outcomes of these investigations. This will give researchers insight into the type and scale of improvements that have been made to enzymes using existing mutagenesis approaches. Moreover, cross referencing of these improvements with the methodologies used to generate the mutations will provide further guidance to scientists in deciding on strategies for further enzyme improvement, e.g. site directed mutagenesis versus directed evolution. Beyond the summarization of such information for trend analyses, extracted and grounded mutation impact annotations will also aid protein engineers when reviewing 3D visualizations of protein structures, as described by [The dedicated infrastructure we have developed for ribed by . Finallyribed by , so thatThe challenges we addressed, namely extraction and publication of mutation impacts, required the development and deployment of advanced solutions leveraging named entity recognition, grounding techniques, knowledge representation for mutation impacts as well as the setup and registration of semantic web services. The major innovations were to: design novel impact grounding techniques and to couple this with existing approaches for mutation grounding to protein sequences; exploit the utility of the SADI framework to expose the grounding and relation detection algorithms as semantic web services. Once operational these services are readily findable and easy to integrate with existing semantic web services in the SADI registry. This combination provides enhanced access to legacy information using a contemporary publishing medium.GATE: General Architecture for Text Engineering; MuNPEx: Multi-lingual Noun Phrase Extractor; JAPE: Java Annotation Patterns Engine; MGDB: Mutation Grounding Database; OWL: Web Ontology Language; SWRL: Semantic Web Rule Language; SADI: Semantic Automated Discovery and Integration; RDF: Resource Description Framework; SPARQL: SPARQL Protocol and RDF Query Language; SWS: Semantic Web Service; SHARE: Semantic Health and Research Environment; COSMIC: Catalogue Of Somatic Mutations In Cancer;The authors declare that they have no competing interests.JBL developed the rules for grounding of mutations and protein properties, contributed to the ontology design and corpora annotation. NN contributed to the pipeline design and corpora preparation. RW participated in coordinating the work and contributed to the ontology design. AR developed the web based deployment and wrote the corresponding section. AK contributed to the methods for relation scoring. CJOB led the work coordination and study design. All authors contributed to the manuscript."}
+{"text": "Additional insight can be gleaned via controlled human exposure studies  and toxicologic studies using animal models of disease. The authors of the current study integrated these various lines of evidence to determine whether there was coherence of associations across the scientific disciplines. They also assessed the biological plausibility of specific characteristics identified in epidemiologic studies as potentially conferring susceptibility to PM-related health effects.The authors focused on the collective evidence evaluated in the most recent science review of the PM National Ambient Air Quality Standards and also built upon the evidence presented in previous reviews. The studies examined the health effects primarily due to both short- and long-term exposures to the fine and/or coarse fractions of PM.Overall, the characteristics of populations most associated with increased susceptibility to PM-related health effects included 1) life stage, specifically children and older adults; 2) preexisting cardiovascular and respiratory diseases; 3) specific genetic polymorphisms; and 4) low socioeconomic status, as measured by educational attainment and income. The authors found more limited evidence suggesting an increase in PM-related health effects in individuals with diabetes, chronic obstructive pulmonary disease, and increased body mass index. Potentially increased risks of PM-related health effects by sex and race/ethnicity also were indicated, although these associations were not consistent across health effects, PM size fractions, or, in some instances, study locations.The authors concede they are unable to clearly state the overall strength of the evidence for some characteristics of potentially susceptible populations due to inconsistent evidence across epidemiologic studies as well as lack of information from experimental studies regarding biologically plausible mechanisms.However, the novel integrative approach used to identify characteristics of populations potentially susceptible to PM may be a valuable assessment tool for other air pollutants. The authors also propose a comprehensive definition of \u201csusceptibility\u201d to encompass all populations potentially at increased risk of adverse health effects as a consequence of exposure. Use of such a standardized definition could help reverse inconsistencies in terminology within the epidemiologic literature that may have complicated the identification of high-risk populations to date."}
+{"text": "AbstractThekaryotype, C-banding, and nucleoar organizer regions (NORs) of eight specimens ofKonya wild sheepfrom Turkey were examined. The complement included six large metacentric autosomes, 46 acrocentric autosomes of decreasing size, a medium-sized acrocentric X chromosome, and a small bi-armed Y chromosome . G-banding allowed reliable identification of all the chromosome pairs and the pairing of homologous elements. All the autosomes possessed distinct centromeric or pericentromeric C-positive bands. The X chromosome had a pericentromeric C-positive band, and the Y chromosome was entirely C-heterochromatic. The NORs were located in the terminal regions of the long arms of three metacentric and two acrocentric autosomes. The karyotype of the Konya wild sheep and its banding patterns are quite similar to chromosome complement reported in domestic sheep and European mouflon. Ovis  is rather complicated and there are different opinions in respect of the number of species and the actual species borders ; Ovis ophion Blyth, 1841] introduced to various parts of Europe are generally evaluated as feral populations of ancient domestic stocks  and argali sheep [Ovis ammon ] ] . In a suOvis orientalis has generally been used, although some authors use the name Ovis aries for both wild species and its domestic descendants  or Ovis gmelinii anatolica  have the same diploid number of 54 chromosomes as the domestic sheep. In the Iranian populations of urial sheep the diploid number of 58 chromosomes was recorded, and hybrid zones with polymorphic karyotype were found in the areas of contact with Ovis orientalis (Ovis nivicola Eschscholtz, 1929, and 2n=54 in both the American species (PageBreakChromosome research has contributed significantly to understanding of the evolutionary divergence among sheep taxa, and different chromosome numbers were found in individual geographic populations. The European mouflon and wild sheep from western Palaearctic (ientalis . The arg species . The chr species .The karyotype of the Konya wild sheep was studied by We examined eight specimens of Konya wild sheep including four females and four males. All the studied animals originated from Bozda\u011f in the Konya province, Turkey . ChromosThe karyotype contained 54 chromosomes  includinThe obtained karyotypic data confirm possible close relationships between the Konya wild sheep and domestic sheep. The diploid number of chromosomes and their morphology expressed in the number of chromosomal arms and the proportion of the metacentric and acrocentric autosomes are the same in both complements. The detailed structure of banded chromosomes of the Konya wild sheep appears quite similar in comparison with the standard chromosomal complement of the domestic sheep cf. . The G-bPageBreakPageBreak.A considerable degree of similarity can also be demonstrated by comparison of our results with previously reported differentially stained chromosomes of various wild sheep taxa . Banding"}
+{"text": "Deficits of contralesional space awareness (neglect and extinction) often follow right hemisphere damage and are typically attributed to the disruption of neurocognitive mechanisms subserving orienting of attention in space (Driver and Vuilleumier, The studies collected in the present Research Topic cover both spatial and non-spatial aspects of neglect and extinction. With respect to the anatomical basis of these disorders two studies use a meta-analytic approach based on anatomical likelihood estimation to investigate the heterogeneous nature of the neuroanatomical underpinnings of neglect. Molenberghs et al.  found sp"}
+{"text": "ARDS is characterized by increased pulmonary capillary permeability secondary to diffuse alveolar inflammation and injury. Common risk factors can be classified into two groups: extrapulmonary causes (indirect etiologies: ARDSexp) or pulmonary causes (direct etiologies: ARDSp). There are few quantitative methods to distinguish between the differences in these two ARDS categories.A subanalysis of the trial by the PiCCO Pulmonary Edema Study  in 23 ICUs of academic tertiary referral hospitals in Japan. All consecutive adult patients requiring mechanical ventilation with the diagnosis of ARDS were monitored by the transpulmonary thermodilution technique system  for 3 days: day 0, day 1 and day 2. The pulmonary vascular permeability index (PVPI), extravascular lung water index and intrathoracic blood volume index were measured concurrently. Three experts retrospectively determined the pathophysiological mechanism causing ARDS by patient history, clinical presentation, chest computed tomography and radiography. Patients were classified into two groups: patients with ARDS triggered by ARDSexp and ARDSp.During the study period from March 2009 to August 2011, a total of 173 patients were assessed including 56 ARDSexp patients and 117 ARDSp patients, with the most common cause of ARDSexp secondary to sepsis (71%) and of ARDSp pneumonia (80%). The measurement of PVPI was significantly elevated in the ARDSp group on all days. There were no significant differences in mortality at 28 days, mechanical ventilation days, and hospital length-of-stay between the two groups, while the ARDSexp group seemed to be associated with prolonged mechanical ventilation days and hospital length-of-stay.This study suggests the existence of several differences in pathogenetic pathways and the degree of pulmonary permeability between patients with ARDSexp and ARDSp. We therefore believe that using the PVPI may provide us with timely quantitative information to make clinical decisions."}
+{"text": "The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been shown to play an important role in a number of cognitive functions including arousal, working memory, and attention. However, despite a wealth of behavioral and anatomical data, understanding how cholinergic synapses modulate cortical function has been limited by the inability to selectively activate cholinergic axons. Now, with the development of optogenetic tools and cell-type specific Cre-driver mouse lines, it has become possible to stimulate cholinergic axons from the basal forebrain (BF) and probe cholinergic synapses in the cortex for the first time. Here we review recent work studying the cell-type specificity of nicotinic signaling in the cortex, synaptic mechanisms mediating cholinergic transmission, and the potential functional role of nicotinic modulation. Cholinergic axons from the basal forebrain (BF) innervate the entire cortex and are the main source of cortical acetylcholine   the patterns of activity in cortically projecting cholinergic axons during behavior; (2) the functional roles of nAChR-expressing cortical neurons and their subsequent modulation by endogenously released ACh; and (3) the respective impact of fast and slow nicotinic modulation on cortical circuits. The recent proliferation of Cre-driver lines has allowed investigators to begin to probe the function of various classes of cortical cells, including some cell-types known to express nAChRs. However, further work is needed to uncover how the function of these cortical neurons is modulated by activation/silencing of cholinergic fibers and blockade of specific receptor subtypes. Given the well-established role for nicotinic signaling in numerous neuropsychiatric diseases, a better understanding of the mechanisms underlying nicotinic modulation of cortical activity holds promise for the development of more effective therapeutic interventions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The purpose of this longitudinal outcome study was to determine the effectiveness of the Integrative Health Clinic and Program (IHCP) and to perform a subgroup analysis investigating patient benefit. The IHCP is the first organized integrative health clinical service within the Veterans Affairs Health Care System utilizing research based Complementary and Alternative Medicine (CAM), mind-body skills, and conventional treatments based on a health promotion and wellness model for the bio-psychosocial management of chronic non-malignant pain and stress related depression, anxiety, and symptoms of PTSD.A post hoc quasi experimental design was used combined with subgroup analysis to determine who benefited the most from the program. Data were collected at intake and up to four follow-up visits over a two year time period. Hierarchical Linear Modeling (HLM) was used for the statistical analysis and the outcome measures included: Health Related Quality of Life (SF-36), the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Comparisons included mental health subgroups and chronic nonmalignant pain subgroups.The mental health subgroups with the greatest improvement, seen at 6 months, were found in the high anxiety group (Cohen\u2019s d=.52), the high depression group (Cohen\u2019s d=.46), and the PTSD group (Cohen\u2019s d=.41). The chronic pain group with the greatest improvement at 6 months was the Chronic Non Spinal Pain group  with a decrease in depression and anxiety and improvement in health related quality of life at six months\u2019 follow-up ; the benefit persisted over 24 months.This study provides evidence that the VA Integrative Health Clinic offers an effective reduction in pain-related psychopathology  and may improve some aspects of health related quality of life through use of nonpharmacological therapies, mind body skills and complementary and alternative Medicine."}
+{"text": "This type of analysis of AIDS related lymphomas (ARLs) has been limited because of their rarity, heterogeneity and lack of frozen tissue for analysis, with the largest studies including 25 cases . To overcome this limitation, we employed a \u00ae), with modification of the cDNA and quality control (QC) steps. The following cases of ARL with confirmed diagnosis and sufficient RNA were used for evaluation in duplicate: Weill Cornell Medical College in New York, USA (36 cases), the AIDS Malignancy Consortium (AMC) (24 cases), University of Siena, Italy (20 cases), Italy (21 cases), Tata Memorial Hospital in Mumbai, India (35 cases), University of Ibadan, Nigeria (1 case). Non-AIDS lymphomas were included as controls (15 cases from India and 13 cases from Weill Cornell). A 1mm diameter core was obtained from each block and RNA extracted. Tissue microarrays were also prepared of the available specimens, and characterization of viral status and lymphoma subtype were determined by immunohistochemistry and in situ hybridization for Epstein-Barr encoded RNA (EBER). Fluorescent in situ hybridization (FISH) was used to evaluate for genomic deletions in A20, and translocations of cMYC, BCL-2 and BCL-6.We performed expression profiling from FFPE samples of AIDS related lymphoma for using DASL (IlluminaGene expression profiling of 126 cases was initially performed using DASL. Quality control assessment and data analysis revealed poor predictive ability of the QC method and poor quality of the cDNA resulting in data variability and lack of reproducibility. Therefore, we developed alternative methodologies for cDNA preparation and assessment of quality of the RNA, resulting in more than double the number of genes detected and good reproducibility in the majority of the samples. Analysis of gene expression profiling of 116 cases of ARL and 28 matched non-AIDS lymphomas will be presented.We have developed methods that allow gene expression analysis of large numbers of ARLs, which will pave the way of determining whether subtype specific signatures resemble those of lymphomas in immunocompetent individuals, and eventually if these have clinical implications."}
+{"text": "For high dose rate SPE proton radiation, the threshold value for retching was 75 cGy, and for ferret vomiting, it was 1 Gy.A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animals exposed to space flight stressors combined with the types of radiation expected during an SPE. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations: gamma rays or electrons). All animal studies described have been approved by the University of PA IACUC. Some conclusions from recent CARR investigations are as follows: (i) the relative biological effectiveness (RBE) values for SPE-like protons compared with standard reference radiations (gammas or electrons) for white blood cells (WBCs) vary greatly between mice, ferrets and pigs, with the RBE values being greater in ferrets than those in mice, and considerably greater in pigs compared with those in ferrets or mice . This trend for the data suggests that the RBE values for WBCs in humans could be considerably greater than those observed in small mammals, and SPE proton radiation may be far more hazardous to humans than previously estimated from small animal studies. (ii) Very low doses of SPE proton radiation (25 cGy) increase blood clotting times in ferrets, and the low SPE-like dose rate has more severe effects than high dose rate radiation [3]. (iii) Results from pig and ferret studies suggest that disseminated intravascular coagulation is a major cause of death at doses near the LD"}
+{"text": "Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world. Incidence is particularly high in much of Southeast Asia, where hyperendemic transmission plagues both urban and rural populations. However, endemicity has not been established in some areas with climates that may not support year-round viral transmission. An understanding of how dengue viruses (DENV) enter these environments and whether the viruses persist in inapparent local transmission cycles is central to understanding how dengue emerges in areas at the margins of endemic transmission. Dengue is highly endemic in tropical southern Vietnam, while increasingly large seasonal epidemics have occurred in northern Viet Nam over the last decade. We have investigated the spread of DENV-1 throughout Vietnam to determine the routes by which the virus enters northern and central regions of the country. Phylogeographic analysis of 1,765 envelope (E) gene sequences from Southeast Asia revealed frequent movement of DENV between neighboring human populations and strong local clustering of viral lineages. Long-distance migration of DENV between human population centers also occurred regularly and on short time-scales, indicating human-mediated viral invasion into northern Vietnam. Human populations in southern Vietnam were found to be the primary source of DENV circulating throughout the country, while central and northern Vietnam acted as sink populations, likely due to reduced connectedness to other populations in the case of the central regions and to the influence of temperature variability on DENV replication and vector survival and competence in the north. Finally, phylogeographic analyses suggested that viral movement follows a gravity model and indicates that population immunity and physical and economic connections between populations may play important roles in shaping patterns of DENV transmission. Reports from sub-tropical regions of the world suggest a growing risk of introduction and establishment of dengue viruses (DENV) in new locales. Recent dengue epidemics in northern Viet Nam present an opportunity to study how DENV invades and spreads in these environments. The proximity of this region to tropical areas experiencing year-round endemic DENV transmission makes it an ideal site for studying the effects of human population movement and climate on DENV emergence. We performed a phylogenetic analysis using DENV-1 envelope gene sequences from Southeast Asia. We show that DENV are regularly imported into northern and central Viet Nam from southern Vietnam, and that increasingly large seasonal epidemics in the north are caused by newly introduced viruses each year. While tropical Vietnam maintains localized virus populations for multiple years, cool winter temperatures in sub-tropical northern Viet Nam may reduce mosquito populations and virus replication to levels that are not conducive to year-round DENV transmission. Finally, we found that the dispersal of DENV across the region is well-described using human movement and immunity data, and believe that increased epidemiological, entomological, and virological surveillance are needed to understand the processes by which endemic DENV transmission becomes established in new populations. Flaviviridae), within which considerable genetic diversity is present on both global and local scales Dengue viruses (DENV) are single-stranded, positive-sense, mosquito-borne RNA viruses  of DENV-1 envelope gene sequences collected from Vietnamese hospitals and studies across Southeast Asia, where Genotype I has been the dominant circulating DENV-1 lineage since at least 1980. With these data, we investigated the movement of this lineage into Viet Nam and addressed the following questions: (i) Does highly endemic southern Viet Nam act as a source population for DENV circulating in other parts of the country? (ii) Do DENV populations persist over multiple seasons in central and northern Viet Nam? (iii) What factors determine the patterns of dispersal of DENV lineages to new environments across Viet Nam and within Southeast Asia?Dengue viruses were recovered from suspected dengue patients presenting to hospitals across Viet Nam as part of routine diagnostic serology. The envelope (E) genes of 60 isolates recovered from north and central Viet Nam and one from southern Viet Nam were sequenced as described previously DENV-1 E gene sequences from northern and central Viet Nam were combined with full-length DENV-1 E gene sequences catalogued in GenBank to comprise all DENV-1 sequences from across Asia for which the year and country of sampling were known. Nucleotide alignments of 1765 full-length DENV-1 E gene sequences (1485 nt), including the 80 isolates from northern and central Viet Nam, were manually constructed using Se-AL To investigate the routes of invasion of DENV-1 into northern and central Viet Nam, the geographic areas of Viet Nam were categorized using (i) a \u2018Local geographic model\u2019 \u2013 categorized by government-defined regions , and by country outside of Viet Nam , and (ii) a \u2018Regional geographic model\u2019 \u2013 categorized by larger regions  and elsewhere by country as in the previous scheme. We inferred rates of viral migration between locations using an asymmetric model of discrete diffusion across Southeast Asia and within Viet Nam To account for potential sampling biases in space and time, posterior distributions were also estimated as above for ten data sets that were subsampled randomly, with replacement, to include no more than 50 sequences per region  for each of the ten major geographic regions in the data set  and for ten data sets that were subsampled such that no more than five samples per year were chosen randomly from each of the locations indicated above (205 sequences). In addition, six major clades containing northern and central Vietnamese isolates were identified in trees inferred from the full data set and were analyzed individually using the asymmetric discrete diffusion model to assess potential differences in the spatial and temporal patterns of diffusion among them, to identify routes of invasion into northern and central Viet Nam, and to determine whether lineages were maintained over multiple years in these newly sampled populations.To test hypotheses related to viral dispersal and establishment, we set rate priors to specific values to construct a series of (asymmetric) phylogeographic models that might reflect the epidemiology and dispersal of DENV in Viet Nam. These models were analyzed using both the full and subsampled data sets for the Regional and Local geographic models. These models were: (i) a geographic diffusion model that assumes equal rates of viral migration between all regions of interest , (ii) a model based on the physical distance separating the populations in question using the inverse of the Euclidian distance between the centroids of the largest cities in each region , (iii) a population size-based model, utilizing the census population estimate of the largest city from which sequences were collected in each region as representative of the influence of that region in attracting migration from other locations  Model priors were normalized (mean one and unit variance) and incorporated into asymmetric matrices that allow for directional rates to vary between individual location pairs. A posterior simulation-based analogue Akaike's information criterion through MCMC (AICM) was implemented using likelihoods specific to the geographic model priors, and marginal log likelihood estimates for each model were compared to determine the best fit model to the data in hand Sequencing of de-identified viruses collected in this study was undertaken under Human Research Ethics Approval 0700000910 from the Queensland University of Technology. Viruses collected at The National Hospital of Tropical Diseases in Hanoi, Viet Nam were from patients enrolled in a study approved by the scientific and ethical committees at the National Hospital of Tropical Diseases and The Oxford University Tropical Research Ethics Committee(OXTREC) We determined the E gene sequences of DENV-1 isolates collected from 81 Vietnamese dengue patients and combined these with Southeast Asian DENV-1 E gene sequences collected between 1997 and 2009. The full data set included 46 sequences from northern Viet Nam (1998\u20132009), 34 sequences from central Viet Nam (2004\u20132009), and 461 sequences from southern Viet Nam (2003\u20132008), and 70, 63, and 31 envelope gene sequences from Thailand (1997\u20132007), Cambodia (2000\u20132008), and Singapore (2003\u20132008), respectively. All viruses were collected subsequent to a clade replacement event that occurred within the DENV-1 population in Thailand in the mid-1990s that has been attributed to enhanced transmission capacity within the vector Thailand, Cambodia, and Viet Nam all experienced the co-circulation and maintenance of multiple lineages for several years and importation of novel viruses from other countries . Our phyA minimum of eight distinct lineages of DENV-1 Genotype 1 entered Viet Nam between 1990 and 2007 and persisted until at least 2007\u20132009. While all viral diversity captured within the country was represented in samples from the south, viral populations in the northern and central regions were less diverse. Nearly all viruses isolated from northern and central Viet Nam clustered within the diversity of the south with the exception of viruses isolated in northern Viet Nam prior to 2003 and a single divergent virus collected in the Central Highlands in 2004 ; notably, very few sequences were available from southern Viet Nam during this time period . While strong support was found for a Cambodian origin of most Vietnamese lineages, Clades 7 and 2 may have been introduced from Singapore (or elsewhere in maritime Southeast Asia) and Thailand, respectively. Clade 7 contained two examples of importation of novel lineages of the maritime Southeast Asian clade into northern Viet Nam followed by localized, short-term transmission during a single year and apparent fade-out with the onset of winter , when teA previous analysis of DENV-1 within southern Viet Nam indicated that Clade 2 became established there in 2002 Of six viral lineages involved in transmission within the central and northern regions of Viet Nam, five showed invasion and dispersal throughout the country and frequent movement between areas of interest. To investigate the spread of DENV-1 genotype 1 within Viet Nam, we estimated Markov Jump counts between locations across the full phylogeny and in subsampled data sets, and analyzed specific viral clades to investigate fine-scale spatial and temporal patterns of dispersal. Using the Regional asymmetric phylogeographic migration model, we determined that southern Viet Nam was the likely source for Vietnamese viruses in Clades 1, 4, 5, and 6 and for Clade 2 viruses isolated after 2002 . No suppThe Mekong Delta and Southeast regions also acted as secondary centers of viral diversity within the country. The Mekong Delta region is the inferred entry site of Clade 1 into Viet Nam. Long-term transmission of these viruses as well as sub-lineages in Clades 2 and 4 also occurred in the Mekong Delta. However, viruses only disseminated from this region into areas with which it shares borders, namely Ho Chi Minh City and the Southeast . The MekTo determine whether distinct viral populations persisted in northern and central Viet Nam over multiple seasons, we investigated the timing of invasion and establishment of novel viral sub-lineages  and the potential co-circulation of distinct lineages in these areas. Viral invasion and establishment were detected in northern Viet Nam in 1990, 2004, 2008, and 2009, and in central Viet Nam in 2003, 2006, and 2008. Except in Clade 2, these data suggest that invading lineages in northern Viet Nam did not persist in the region over multiple dengue seasons .The times to most recent common ancestry (TMRCAs) of viral clusters in northern Viet Nam suggested that viruses are imported to the region throughout the year, although most invasion events occurred in the middle of the year via viral migration from the south (Ho Chi Minh City and the Southeast). This period coincides with seasonal increases in the number of dengue cases throughout the country and in Hanoi In contrast to the north, DENV from six central Vietnamese transmission clusters  suggested that seasonal invasion in this region occurred during the \u2018dengue season\u2019 in the second half of the year , with unTo determine how viral transmission routes within Southeast Asia were influenced by population and geographic factors, we compared the fit of a variety of phylogeographic models related to human population size, distance, and DENV transmission intensities to the spatially- and temporally-related E gene sequence data. Although slightly different results were obtained for the Local and Regional models , Table 3This study documents the dispersal of DENV-1 to populations across Viet Nam and provides evidence that viral populations are regularly introduced into northern Viet Nam from external populations but do not establish endemic cycles of transmission. Strong clustering at all spatial scales indicated that the viral diversity present in a given area is determined primarily by local gene flow. Frequent movement between neighboring locations under the Local geographic model may reflect a combination of human movement and vector dispersal in the movement of DENV between human populations in close proximity, as observed at smaller geographic scales Aedes aegyptiA. aegypti mosquitoes. In contrast, strains of DENV introduced into central Viet Nam establish cycles of transmission extending over multiple years.Our results also show that the DENV population in sub-tropical northern Viet Nam is characterized by regular seasonal invasions of lineages from the highly endemic south, with no detectable persistence into the following dengue season. Regardless of the time of year in which invasion occurred, our phylogenetic data suggest that invading lineages experience severe seasonal bottlenecks and regular fade-out in northern Viet Nam at the end of each year, when temperatures in much of the north drop below those considered optimal for survival of the vector and efficient transmission of the virus by Clade 2 represents one possible exception to the observations above. Our analysis suggests that this lineage entered through the north and became established in the North Central Coast, where it may have persisted for over a decade prior to its invasion and establishment in the south. Although the possibility of long-term transmission in northern Viet Nam cannot be excluded, the lack of contemporaneous sequence data from the south and the distant relationships between these basal sequences result in a lack of resolution at this early time point and thus low support for an inferred ancestral location of the lineage. Additionally, a number of other sequences sampled from early time points in the north (Clade 4) also fall at basal positions in the phylogeny, although generally within the diversity of southern Viet Nam. Thus, the relationships among these northern sequences do not necessarily indicate their persistence. Instead, they may represent multiple importations from DENV populations in the south in the 1990s that experienced a significant bottleneck in the early 2000s, prior to the entry and rapid establishment of Clades 1, 4, 5, and 6. If the processes of DENV invasion in Viet Nam were similar to those observed at more recent time points when sampling was conducted across the country, we would expect that these northern sequences would fall into southern lineages that circulated prior to the bulk of our sampling. However, the lack of any signature of intermediate diversity suggesting the presence of this lineage in the highly sampled south prior to 2002 makes it difficult to test this hypothesis.Among the more recently sampled sequences, there are a number of interesting patterns of viral dispersal within Viet Nam. Ho Chi Minh City and the Mekong Delta experience high transmission intensities and were highly sampled relative to the other populations . PreviouPrevious studies in southern Viet Nam have suggested that viruses move through the area along somewhat predictable human migration routes based on estimates of physical and economic connectedness Although we believe that REf calculations in part integrate issues related to vector biology, reflecting a lower force of infection in Singapore (where aggressive vector control efforts may limit transmission) and in northern Viet Nam (where winter temperatures likely limit vector density and competence), the lack of models that explicitly integrate vector biology is a weakness of this analysis. The availability of data on vector densities and species in the locations considered is limited, and the spatial and temporal scales of these analyses do not easily lend themselves to explicit consideration of vector dynamics in our models. As analytical methods and the scale of viral sampling improve, the use of phylogeographic methods that model the impact of factors such as vector density and vector competence on the dynamics of DENV in locations where such data are systematically collected may offer greater insight into the processes that mediate viral migration and establishment in new regions. Additionally, a better understanding of true human movements in the region  may allow us to further elucidate the relative roles of human movement, vector species and competence, and population immunity in the dispersal and persistence of DENV in these environments.Phylogeographic inference may be strongly affected by uneven sampling in space and time Given recent increases in DENV incidence in northern Viet Nam and its geographic position at the margins of endemic transmission, additional sampling in this area is clearly warranted. Figure S1Inferred patterns of migration of DENV-1 across Viet Nam. The number of arrows corresponds to the number of inferred migration events resulting in successful establishment of transmission in the recipient population with branch-specific Markov Jump probability \u22650.85.(EPS)Click here for additional data file.Table S1Geographic distribution of DENV-1 sequences collected in Viet Nam from 1998 to 2009. QUT indicates viruses collected and sequenced using the Queensland University of Technology protocol. OUCRU Hanoi and OUCRU HCMC indicate collected and sequenced using the protocols of the respective Oxford University Clinical Research Unit.(DOCX)Click here for additional data file.Table S2Viral migration patterns in subsampled data sets. The number of viral introductions is represented by Markov Jump counts  intervals). All significant Markov Jump counts are shown.(DOCX)Click here for additional data file."}
+{"text": "Formation of infectious HIV-1 particles involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids following proteolytic disassembly of the Gag shell. Maturation is essential for viral infectivity; it is required for full activity of viral enzymes, for virus uncoating and for efficient membrane fusion. Morphological maturation involves dramatic rearrangements in the interior of the virus, but also leads to coordinated clustering of the low number of Env trimers on the virion surface. Env incorporation is dependent on specific regions in Gag and the C-terminal tail of Env, but appears to be mediated by formation of Env patches larger than the actual assembly site. Here, we will discuss aspects of Gag-dependent Env recruitment and morphological alterations during virion maturation."}
+{"text": "Quantification of historical sociological processes have recently gainedattention among theoreticians in the effort of providing a solid theoreticalunderstanding of the behaviors and regularities present in socio-politicaldynamics. Here we present a reliability theory of polity processes with emphaseson individual political dynamics of African countries. We found that thestructural properties of polity failure rates successfully capture the risk ofpolitical vulnerability and instabilities in which Beginning with the Berlin Conference in 1884 \u2013 leading to the colonialdespotism, to the National Conference of 1989 in Benin \u2013 marking the beginningof the democratic renewal, Africa continues to experience various patterns ofpolitical-economic regulations, mostly shifting away from autocratic regimes andtoward more open governance. The continent has seen an increasing number ofincomplete transitions to democracy, resulting in a high vulnerability to outbreaksof conflict Political processes within Africa have been characterized by waves of politicalinstabilities, economic under-performances and other social factors with more thanhalf of the sub-Saharan countries having experienced some forms of state-formationand/or post-independence civil conflicts since 1960, making the continent a testbedfor exploring the determinants of political instabilities and state failures. As aresult, we have seen an upsurge of literature addressing the causes of civil warsand political unrests. Understanding the causes and consequences of these civilconflicts have been a focus for most of the recent social science research, inparticular sociological, political and economic inquiries with in-depth studieshighlighting the role of economic under-development and economic grievances inshaping risks of conflicts as illustrated by the works of Auvinen The model described herein links the levels of democracy, polity durations andproperties associated with the risk of regime failure. To quantify the relationshipbetween the polity duration and regime type, we use the polity score from the PolityIV data set Aggregating polity levels, we found that the average polity durations for highlyautocratic and institutionally consistent democratic regimes are longer than theanocratic ones  of the countries with bathtub-shapefailure rates have extreme to serious level of state fragility index  of the countries with this propertyhave high to serious state fragility index. Monotonically increasing polity hazardhas the largest number of countries with more than eighty-seven percents(87.50%) having high to serious state fragility index  followed by a longer constant failurethan other countries within this cliometric space of shape parameters Click here for additional data file."}
+{"text": "The gut is the most extensive organ innervated by the vagus nerve; it is also the primary site of innate immunity in the newborn. Here we review the mechanisms of possible neuroimmunological brain-gut interactions involved in the induction and control of antenatal intestinal inflammatory response and priming. We propose a neuroimmunological framework to (1) study the long-term effects of perinatal intestinal response to infection and (2) to uncover new targets for preventive and therapeutic intervention.Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease that affects the intestine and may result in necrosis, systemic sepsis and multisystem organ failure. NEC affects 5\u201310% of all infants with birth weight \u2264 1500 g or gestational age less than 30 weeks. Chorioamnionitis (CA) is the main manifestation of pathological inflammation in the fetus and is strong associated with NEC. CA affects 20% of full-term pregnancies and upto 60% of preterm pregnancies and, notably, is often an occult finding. Intrauterine exposure to inflammatory stimuli may switch innate immunity cells such as macrophages to a reactive phenotype (\u201cpriming\u201d). Confronted with renewed inflammatory stimuli during labour or postnatally, such sensitized cells can sustain a chronic or exaggerated production of proinflammatory cytokines associated with NEC (two-hit hypothesis). Via the cholinergic anti-inflammatory pathway, a neurally mediated innate anti-inflammatory mechanism, higher levels of vagal activity are associated with lower systemic levels of proinflammatory cytokines. This effect is mediated by the  In this review we summarize the emerging understanding of the mechanisms of necrotizing enterocolitis  controls the phosphorylation/dephosphorylation of the myosin light chains in the villus enterocytes and surface colonocytes   for lipopolysaccharide (LPS) recognition) or by proinflammatory cytokines  is defined as the arrangement of neurons and supporting cells throughout the gastrointestinal tract, from the esophagus to the anus  and anti-inflammatory (IL-10) processes. If even small anomalies occurred in any of the components of the system , the inflammatory response would be amplified and would result in intestinal injury. Such anomalies may occur secondary to immaturity in preterm babies.The premature gastrointestinal tract has increased permeability, low levels of protective mucus and secretory immunoglobuline A, higher risk of bacterial overgrowth caused by dysmotility due to ENS immaturity and decreased regenerative capabilities Neu, . UncontrFurthermore immunomodulatory nutrients such as glutamine, arginine, nucleotides, omega-3 polyunsaturated fatty acids and lactoferrin are provided with enteral nutrition and prevent diseases such as NEC. Difficulties with enteral feeding in the first weeks of life predispose premature infants to sepsis and NEC  plays a predominant role in complex coordinated control of multiple vitally important physiological subsystems in the organism and is part of the neuroimmunological response to pathogens via CAP  was confirmed in innate immune cells such as macrophages (reviewed in Tracey, CAP has been implicated in the regulation of the inflammatory reflex in adult organisms including humans Tracey, . CAP is Vagal nerve activity in basal conditions provides inhibitory input that dampens innate immune response (Haensel et al., Under resting conditions, the inflammatory reflex helps establish the set point for the magnitude of the innate immune response to molecules arising from infection, injury or ischemia. Vagus nerve output maintains homeostasis by limiting proinflammatory response to the healthy, protective and non-toxic range  Figure . However\u03b17nAChR, the magnitude of the proinflammatory cytokine response and the extent of tissue damage increase during infection, haemorrhagic shock and stroke (Guarini et al., \u03b1 amounts and the shock response to endotoxemia has widespread implications. It is a previously unrecognized, direct and rapid endogenous mechanism that can suppress the lethal effects of biological toxins. The CAP has much shorter response times than humoral anti-inflammatory pathways. Electrical stimulation of the vagus nerve or administration of \u03b17nAChR agonists reduces the magnitude of proinflammatory cytokine production by 50\u201375% but does not eliminate cytokine activity (Borovikova et al., Numerous factors can experimentally or clinically impair the CAP, each resulting in an exaggerated innate immune response. For instance, in animal models with vagotomy or deficient in locus minoris resistentiae of incipient NEC would be decreased or normalized.Adult clinical data indicate that loss of inhibition from the CAP unleashes innate immunity, produces higher levels of proinflammatory mediators, and exacerbates damage to the organism (Lindgren et al., As vagal nerve stimulation stimulates CAP activity without causing immunosuppression (Borovikova et al., In a murine model of postoperative ileus, the anti-inflammatory effect of intracerebroventricular injection of semapimod was abolished in the presence of vagotomy (The et al., \u03b17nAChR agonists to act on macrophages; or centrally using intracerebroventricular injections of semapimod (The et al., The optimal choice of vagal nerve stimulation parameters in order to activate the CAP for therapeutic purposes remains challenging. Although the literature provides a spectrum of possibilities, further studies are needed. Huston et al., Intrauterine infection leads to macrophage activation in LPS-induced chorioamnionitis in fetal sheep and in a rat model of postnatal sepsis. Intrauterine infection may prime innate immune cells for subsequent exacerbated response and increase intestinal permeability. However, the effects of CAP on this process have not been elucidated. The existence of CAP in adult mammals, including humans, is by now well established. CAP may play an important role in fetal and perinatal development by serving as a neuroimmunological network for \u201cinternal surveillance\u201d linking the CNS and the vagus nerve to modulate systemic and intestinal inflammation. The presence of such a brain-gut network and its significance for perinatal health have not yet been fully studied. Further research on the physiology and pathophysiology of fetal and perinatal neuroimmunological interactions may open new avenues for diagnosis of fetuses at risk of intestinal injury, such that appropriate preventive or therapeutic interventions may be taken. Specifically, fetal CAP activation is likely to suppress the adverse effects of macrophage activation thus decreasing antenatal and perinatal intestinal injury. New pharmacologic targets or validated non-invasive methods of vagus nerve stimulation for manipulating the inflammatory response in compromised fetuses may emerge to improve perinatal and postnatal outcome."}
+{"text": "FOXP3+ regulatory T cells (Treg) are critical in maintaining self tolerance and are therefore considered important targets for the treatment of autoimmune disease. However, environmental factors at the site of autoimmune inflammation, such as enhanced costimulatory potential of antigen presenting cells (APC) and increased proinflammatory cytokine production, can negatively affect Treg function, thereby limiting effectiveness of these Treg targeted approaches.Here we studied the phenotype of APC present at the site of inflammation in patients with Juvenile Idiopathic Arthritis (JIA) and investigated whether these cells can interfere with Treg mediated suppression.Mononuclear cells were isolated from peripheral blood (PB) of healthy controls (HC) and from paired PB and synovial fluid (SF) of JIA patients. The phenotype of APC was analysed using flow cytometry. In vitro suppression assays were performed to study T cell activation and Treg mediated suppression in the presence of SF and PB derived APC.Monocytes from the site of inflammation displayed a more pro-inflammatory phenotype, with significantly increased costimulatory molecule expression, compared to monocytes from PB. In line with this pro-inflammatory phenotype, SF APC induced enhanced proliferation of effector cells and decreased suppression of effector cell proliferation in the presence of Treg.APC from the site of inflammation have an enhanced stimulatory capacity that interferes with Treg mediated suppression. Therefore, this increased stimulatory potential should be targeted as well, in order for a Treg enhancing approach to be fully effective in the treatment of autoimmune inflammation."}
+{"text": "We have previously shown that uncertainty is a core theme in living and coping with food allergy. Uncertainty about labelling may result in anxiety/avoidant behaviour or frustration/risky behaviours. We aimed to evaluate understanding and acceptance of defined thresholds and risk stratification in parents and teens.Under the aegis of FARRP, we carried out focus groups with parents of children and teens with food allergy (N30), teens with food allergy (N20), and clinicians. Data was analysed using grounded theory.The analysis revealed 4 main themes : 'The reality of living with risk'; 'maintaining a balance'; 'feeling Informed and in control of risk management'; 'communicating thresholds'. Current risk hazard approaches reinforce uncertainty and that consumers and clinicians want a 'new' way of risk assessment and management.The themes will form a basis for further discussion with parents, children, teens and adults living with food allergy, and the health professionals who diagnose and advise them. Consumer engagement can ensure communication tools and methods are valid and relevant to both majority groups and sub-groups."}
+{"text": "Live kidney transplantation (LKT) is underutilized, particularly among ethnic/racial minorities. The effectiveness of culturally sensitive educational and behavioral interventions to encourage patients' early, shared  and informed consideration of LKT and ameliorate disparities in consideration of LKT is unknown.We report the protocol of the Talking About Live Kidney Donation (TALK) Study, a two-phase study utilizing qualitative and quantitative research methods to design and test culturally sensitive interventions to improve patients' shared and informed consideration of LKT. Study Phase 1 involved the evidence-based development of culturally sensitive written and audiovisual educational materials as well as a social worker intervention to encourage patients' engagement in shared and informed consideration of LKT. In Study Phase 2, we are currently conducting a randomized controlled trial in which participants with progressing chronic kidney disease receive: 1) usual care by their nephrologists, 2) usual care plus the educational materials, or 3) usual care plus the educational materials and the social worker intervention. The primary outcome of the randomized controlled trial will include patients' self-reported rates of consideration of LKT . We will also assess differences in rates of consideration of LKT among African Americans and non-African Americans.The TALK Study rigorously developed and is currently testing the effectiveness of culturally sensitive interventions to improve patients' and families' consideration of LKT. Results from TALK will provide needed evidence on ways to enhance consideration of this optimal treatment for patients with end stage renal disease.NCT00932334ClinicalTrials.gov number,  Living related kidney transplantation (LKT) represents an optimal strategy for the treatment of patients with end stage renal disease (ESRD), offering recipients substantially improved length and quality of life when compared to patients receiving dialysis . HoweverLittle is known about effective strategies for improving patients' and families' early consideration of LKT. Consideration of LKT prior to patients' development of ESRD could provide time for both recipients and potential donors (often family members) to fully consider the risks and benefits of LKT, enhancing the probability that their decisions regarding pursuit of LKT align with their personal values. Early consideration of LKT may be particularly important in facilitating and preparing for pre-emptive  LKT-- which is associated with the most superior clinical outcomes . DespitePatients who have not yet progressed to ESRD may have unique barriers to considering LKT, including their lack of awareness of the severity of their kidney disease  and low We describe the protocol for a two phase study in which we 1) developed culturally sensitive educational and behavioral interventions to improve patients' early, shared, and informed consideration of LKT and 2) are currently testing the effectiveness of these interventions to improve patients' consideration of LKT in a randomized controlled trial.The Talking about Live Kidney Donation (TALK) study is a two-phase study to design and test the effectiveness of culturally sensitive behavioral and educational interventions on patients' early, shared, and informed consideration of LKT. In Phase 1, we developed culturally sensitive interventions and we developed and piloted data collection tools. In Phase 2, we are currently conducting a randomized controlled trial to assess the effectiveness of interventions to improve patients' shared and informed consideration of LKT. The Johns Hopkins School of Medicine Institutional Review Board has approved all study procedures.Interventions were developed on the basis of evidence obtained through (1) a review of published scientific literature informing barriers to patients' pursuit of LKT among minorities and non-minorities as well as a review of lay publications  produced by patient advocacy organizations and government agencies to educate patients on LKT -16, and The educational booklet and video were developed by a team of experts, including a transplant nephrologist, a transplant surgeon, a transplant social worker, a general internist, a behavioral psychologist, experts in developing interventions to address health disparities, experts in creating health literacy sensitive educational materials, and patient advocates from the National Kidney Foundation of Maryland. Educational materials provide complimentary information to encourage patient and families' shared and informed consideration of LKT, including: 1) information about eligibility for LKT, 2) the clinical evaluation required for LKT, 3) the donor selection process, 4) surgical procedures for transplantation and donation, 5), and concerns brought forth about these factors  identified through the structured group interviews .Both the booklet and the video are designed to be reviewed by patients and their families. The booklet is designed to be read at a fourth to sixth grade reading level and to be sensitive to persons with limited health literacy . It alsoWe have developed a family-based social worker intervention founded on well-established Social Construction-based Family Problem Solving Theory, -20 to adDuring the intervention, a social worker engages potential LKT recipients in one-on-one meetings and, if potential recipients desire, also engages potential recipients and their families in a follow-up family meeting. In one-on-one meetings with potential recipients, the social worker probes to assess specific factors potential recipients perceive inhibit them from progressing through behaviors necessary to achieve LKT . In follow-up meetings with families, the social worker probes to assess specific concerns or barriers family members perceive might inhibit them from pursuing LKT . The social worker also probes to assess the extent to which previous family discussions about patients' CKD have occurred, the results of those discussions, whether families have discussed living LKT with patients' physicians, and barriers families perceive for an open discussion about living kidney donation/transplantation with patients' physicians. The social worker's assessments of factors primarily affecting potential recipients' decision-making at the time of the intervention will guide their development of individualized culturally sensitive intervention plans based on the perceived needs of the potential recipient. Thus, goals of patient and family meetings will be based on which factors are felt to be most prominent for each individual potential recipient and their family. The social worker is also available to patients and families for the provision of information regarding LKT as well as for limited facilitation of further family communication. Social workers employed in the intervention have been trained in techniques for brief individual/family therapy by a behavioral psychologist with experience with problem solving interventions. Social workers have also been trained in effective cross-cultural communication and negotiation utilizing the model for education in cultural competence developed by the American Association of Medical Colleges .We are currently conducting a randomized controlled trial to assess the incremental effectiveness of educational materials and the social worker intervention on improving patients' and families' engagement in shared and informed consideration of LKT.2), those whom the physicians believe are potentially eligible for kidney transplantation based on the following criteria: age 18 to 70; no evidence of cancer within 2 years prior to recruitment date; no evidence of stage IV congestive heart failure; no evidence of end-stage liver disease; no evidence of unstable coronary artery disease; no evidence of pulmonary hypertension; no evidence of severe peripheral vascular disease; no history of HIV; no chronic (debilitating) infections; and no prior kidney transplant.We are targeting patients with advanced, progressive chronic kidney disease who have not yet initiated dialysis therapy and their family members for participation. Patients are recruited from five academically affiliated and community-based nephrology practices in the Baltimore, MD metropolitan region, which we have selected to provide an ethnically and socioeconomically diverse population of participants. To identify potential participants with kidney disease, we ask nephrologists from participating practices to identify from their patients with National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) Stages 4 or 5  CKD  placed in practice waiting rooms and examination rooms. The brochures provide a description of the study goals, participant eligibility criteria, and the contact phone number and e-mail for the coordinating center. We actively identify potentially eligible participants by screening nephrology practices' administrative  month follow up telephone assessment, we ask all patient participants (regardless of intervention assignment) to identify a family member they feel they would involve in an important medical consideration, such as the consideration to pursue LKT to participate in a telephone questionnaire. We offer patient participants two options for contacting family members: 1) patient participants may contact family members or friends themselves and invite them to contact the study coordinating center, or 2) patient participants may let family members or friends know that they have provided their family members' contact information to the study and that the coordinating center will contact the family member. We recruit family members using a prepared telephone script and oral consent process.For patient participants randomized to receive the social worker intervention (see intervention groups below), we ask participants to invite family members to a follow-up visit with the social worker. Prior to attending the follow up social worker session, we contact family members via telephone to obtain their consent for participating in the study using a prepared telephone script and oral consent process. Some participants bring additional family members, friends, or other non-relatives to visits beyond those consented. We therefore also obtain written consent from family members or friends attending social worker meetings.Using blind and secure allocation by computer, we randomly assign participants to one of three intervention arms: 1) control group ; 2) video and booklet intervention only (\"TALK Program\"); and 3) video, booklet plus social worker intervention (\"TALK Plus Program\"). Randomization is blocked by recruitment site to ensure equal allocation within each site.Participants randomly assigned to receive Usual Care proceed with their usual clinical care with their nephrologists as already routinely implemented by their physicians. Since all patient participants have stage 4 CKD at the time of recruitment, many have already had some discussions of options for renal replacement therapy with their physicians (including LKT). Many practices from which patient participants are recruited routinely refer patients to \"pre-dialysis education\" group sessions led by dialysis social workers and nurses to discuss the process of preparation for dialysis and transplantation.Patient participants randomly assigned to receive the TALK Program receive the culturally sensitive educational booklet and video at the time of enrollment. We provide participants the option of reviewing these materials on their own or with study staff in their homes or at a public location of their choice. Study staff members also encourage patient participants to share the materials with their family members or friends. Participants randomly assigned to receive the TALK-Plus Program receive the culturally sensitive educational booklet and video at the time of enrollment in a similar fashion with a similar approach to the TALK Plus assignment. In addition, participants in this group are invited to participate in an initial 60-minute counseling session with a licensed social worker experienced in working with patients and families undergoing evaluation for transplant surgery followed by a second 60-minute session with the social worker and their families, if patient participants desire. All participant meetings are audio-recorded and later transcribed verbatim, excluding names of participants for analysis of participant meeting content.All patient participants enrolled in the study are assessed using structured interviews administered by telephone at baseline, 1 month, 3 months, and 6 months following recruitment and enrollment in the study.The primary outcome is change in participants' consideration of LKT over time. This outcome is measured as participants' movement through 12 possible behavioral 'stages' reflecting their completion of key steps toward considering LKT, including (1) preparation for and/or execution of patient-family discussions about LKT; (2) preparation for and/or execution of patient-physician discussions about LKT; (3) preparation for and/or completion of evaluation for LKT; (4) completion of the LKT recipient evaluation, and (5) identification of a potential live kidney donor. To assess these behaviors, we ask participants a series of questions to which they can answer 'yes' or 'no' . We categorize participants into one of the 12 stages based on their answers. Once we have categorized the participants, we also assess potential barriers to consideration of LKT, including the barriers to discussions with family and providers about LKT .  access to and sources of information about LKT; (2) barriers to obtaining information on LKT; 3) prior discussions with health care providers about LKT; (4) perceived satisfaction and patient-centeredness of their relationship with their nephrologist; (5) preferred role in decision-making about LKT; (6) beliefs about the benefits of LKT; (7) knowledge and interest regarding LKT; (8) concerns about the risks of LKT to themselves and to donors; (9) family structure and relationships; (10) depression and social support; (11) religiosity/spirituality; (12) financial stress, (13) health literacy, and (14) sociodemographic characteristics. (Table  prior diPatient participants' family members are assessed once after patient participants' 1-month assessments and once after patient participants' 3-month assessment via structured interviews administered via telephone. Assessments include family members': (1) access to and sources of information regarding LKT ; (2) knowledge about LKT; (3) presence and quality of family discussions about LKT.For participants randomized to receive social worker meetings (TALK Plus Program) social workers document potential barriers to LKT elucidated by patients and families, and assess immediate outcomes of patient/family discussions, including: (1) whether patients and families arrived at consensus regarding mutual patient/family solutions, (2) presence (or lack thereof) of plans agreed upon by patients and families to discuss LKT with patients' physicians, and (3) presence (or lack thereof) of plans agreed upon by patients and families to pursue evaluation for LKT.Randomly assigned intervention group  will be the main independent variable for intent-to-treat analysis . The co-Our main analysis will assess the proportion of participants in each randomized group that has moved one additional step 'forward' in consideration of LKT over study follow up. We are not aware of other studies assessing this outcome among patients and families who have not yet initiated dialysis therapies. We conservatively assume that approximately 30% of our participants, who have not yet initiated dialysis, will consider LKT as a treatment option under usual care at follow up ,24,25. ADespite the success of LKT as a treatment strategy for ESRD, improvements in utilization have been largely stagnant in recent years, and ethnic/racial disparities in utilization of LKT persist ,27. AlthThe TALK study represents one of the first efforts to explicitly design culturally sensitive interventions to improve African American' and non-African Americans' early consideration of LKT. Prior studies of educational interventions among patients with progressive chronic kidney disease have not assessed the effect of early education on patients' or their families' consideration of LKT and have not examined whether interventions narrow ethnic/race differences in consideration of treatments among United States patients ,30. A reOur efforts to identify both shared and differing concerns about pursuing LKT among minority and non-minority patients and families represent a novel strategy for developing culturally sensitive interventions to improve consideration of LKT and could enhance interventions' effectiveness. If effective, interventions could serve as a model for future programs seeking to provide resources to support ethnic/racial minority and non-minority patients' and families' early and informed decisions about LKT. Our collection of information on factors contributing to interventions' success (e.g. the patient-physician relationship and family members' perspectives on the process of considering LKT in discussions) will provide additional valuable insight into the mechanisms through which interventions may act as well as ways in which interventions might be further tailored to optimize their effectiveness.In summary, the TALK study has rigorously developed and is currently testing the effectiveness of culturally sensitive educational and behavioral interventions to improve patients' and families' early and informed consideration of LKT. Results from TALK will provide needed evidence regarding ways to enhance consideration of this optimal treatment strategy among African American and non-African American patients and families.LKT: Live Kidney Transplantation; ESRD: End-Stage Renal Disease; TALK: Talking About Living Kidney Donation.The authors declare that they have no competing interests.LEB conceived, designed, and conducted the study and drafted the manuscript. FHB contributed to the conception, design, and conduct of the study and the drafting of the manuscript. EK contributed to the conception, design, and conduct of the study and the drafting of the manuscript. JKM contributed to the conception, design, and conduct of the study and the drafting of the manuscript. RM contributed to the conception, design, and conduct of the study. BB contributed to the conception, design, and conduct of the study. MS contributed to the conception, design, and conduct of the study and the drafting of the manuscript. KEE contributed to the conception, design, and conduct of the study and the drafting of the manuscript. PE contributed to the conception, design, and conduct of the study and the drafting of the manuscript. MU contributed to the conception, design, and conduct of the study and the drafting of the manuscript. ND contributed to the drafting of the manuscript. NRP contributed to the conception, design, and conduct of the study and the drafting of the manuscript. All authors approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/12/34/prepub"}
+{"text": "Fibrinolytic shutdown plays a pivotalrole in the pathogenesis of multiple organ dysfunction syndrome (MODS) in disseminated intravascular coagulation (DIC). We tested the hypothesis that the levels of thrombin activatable fibrinolysis inhibitor (TAFI) are not sufficient to overcome fibrinolytic shutdown, thus contributing to MODS and the poor prognosis in sepsis-induced DIC.Fifty patients with sepsis, severe sepsis, or septic shock were enrolled in the study. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC criteria. The overt DIC scores based on the International Society on Thrombosis and Haemostasis (ISTH) were also calculated. On the day of sepsis diagnosis (day 1), and days 3 and 5, we measured TAFI, soluble fibrin, and global coagulation and fibrinolysis markers.The JAAM DIC scores on day 1 and maximum JAAM DIC scores were independent predictors of patient death and MODS, respectively. The JAAM DIC patients, especially those who simultaneously met the ISTH overt DIC criteria, showed lower TAFI antigen levels and activity, and higher levels of soluble fibrin in comparison with non-DIC patients. There were differences in the levels of soluble fibrin and TAFI activity between the patients with and without MODS. The findings of stepwise logistic regression and multiple regression analyses suggested that low TAFI activity is an independent predictor of patient death and MODS. A multiple regression analysis also indicated that soluble fibrin negatively correlated with the TAFI activity in DIC patients.Thrombin activation results in the consumption of TAFI. Low TAFI activity is involved in the pathogenesis of DIC-induced MODS and poor prognosis."}
+{"text": "In essence, Toxicogenomics was defined as any study that investigates the response of a genome to hazardous substances by means of (1) genomic-scale mRNA expression analyses (Transcriptomics), (2) cell and tissue wide protein expression techniques (Proteomics), or (3) cell and tissue wide metabolite profiling (Metabolomics). These \u201comic\u201d datasets typically require intricate in silico analyses (Bioinformatics) to integrate the results and by doing so provide insights into mechanistic toxicology and biomarkers of exposure.In October 2004, the Organisation for Economic Co-operation and Development (OECD) and the International Programme on Chemical Safety (IPCS) organized a workshop in Kyoto Japan to outline the fundamental aspects and future directions of the then emerging science of \u201cToxicogenomics.\u201d The output of this three-day meeting was summarized in the Report of the OECD/IPCS workshop on Toxicogenomics  the yeast system, which focusses on genome-wide responses to chemical stressors linked to Environmental Health, Pharmacology, and Biotechnology (dos Santos et al., By spanning a wide taxonomic breadth, this encyclopaedic coverage results in a collection of unique approaches, tools and technologies, which are currently defined by the availability and feasibility for each organism to study the genomics of xenobiotic or stress biology. We anticipate that this information will not only foster cross-phyla awareness, but also expand the horizon of Toxicogenomics. We hope you enjoy this eclectic mix of papers."}
+{"text": "This article reports an analysis of microRNA expression on tissues collected in peak lactation (90 day postpartum) and late lactation (210 day postpartum). The experiments reported in this article are related to and originate from the same animals as those described in our previous publication below:Identification and characterization of microRNA in the dairy goat (Capra hircus) mammary gland by Solexa deep-sequencing technology.Ji Z, Wang G, Xie Z, Zhang C, Wang J.Mol Biol Rep. 2012 Oct;39(10):9361-71.The Molecular Biology Reports article focused on the analysis of miRNA expression on goat tissues collected in early lactation (20 day postpartum). The publication in Molecular Biology Reports should have been cited in the PLOS ONE article and the authors apologize for this omission.In addition, in the light of the previous publication in Molecular Biology Reports, the following claims outlined in the PLOS ONE article regarding the originality of the global miRNA expression profile analysis in Capra hircus are inaccurate:Abstract: 'This study provided the first global of the microRNA in Capra hircus and expanded the repertoire of microRNAs'Introduction 'In this study, we provided the first global of the miRNA expression profiles (miRNome) in Capra hircus and expanded the repertoire of miRNAs.'Conclusions 'The present study is the first to examine the goat mammary gland miRNA expression profile'"}
+{"text": "Since 2000 several outbreaks of acute HCV infections have been reported among HIV-positive patients. The majority of AHC infections have been observed in Europe and have been almost exclusively limited to men who have sex with men. The epidemic is still ongoing, has been recognized in several large HIV-cohorts and recent outbreaks have also been reported from Australia and the USA. Risk factors for sexual transmission in HIV-infected patients appear to be concurrent sexual transmitted diseases such as syphilis or lymphogranuloma venereum or rough sexual practices, both thought to disrupt mucosal integrity and facilitate permucosal infection. Non-injecting drug use has also been more frequently found among HIV-positive patients with AHC compared to HIV-positive without history of AHC. While tremendous efforts have been undertaken to better understand the epidemic, the natural history and pathogenesis of AHC, and to develop concepts on diagnosis and management of AHC in HIV-infected patients there is still a lack of guidance informing us how to best manage our patients.As data from clinical trials and cohort studies has become available, evidence-based guidelines are timely to permit the best management of these patients. To address this issue, the European AIDS Treatment Network (NEAT) invited members of the European AIDS Clinical Society (EACS) hepatitis group, the European Association for the Study of the Liver (EASL), the European Study Group on Viral Hepatitis (ESGVH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European AIDS Treatment group (EATG) and other experts to attend a consensus conference on acute HCV infection in HIV-infected individuals in Paris, France, on May 21st, 2010. On behalf of the consensus panel this presentation will report on the consensus statements developed."}
+{"text": "Following mounting evidence for the value of qualitative research; trials are increasingly adopting mixed method approaches. Reviews suggest that whilst qualitative methods are being utilised within trials, methodological gaps, failure to integrate findings and variation in quality are ongoing issues. Clinical Trials Units (CTUs) have been established within the UK to \"support, high quality, efficient, effective and sustainable clinical trials research\". It is common practice for CTUs to provide statistical, quality assurance and health economics support but the formalisation of qualitative support is limited.To address this within Wales, the QUalitative Enquiry Supporting Trials (QUEST) unit has been set up as the qualitative arm of the West Wales Organisation for Rigorous Trials in Health (WWORTH). Funded by the National Institute of Social Care and Health Research (NISCHR), QUEST aims to; provide qualitative support and resources to trial development and management groups and to ensure high quality, qualitative research becomes and integral part of clinical trials within Wales.QUEST is collaborating with a number of trial groups. The Hughes Abdominal Repair Technique (HART) Trial; a surgical technique feasibility trial, provides an example of how QUEST has achieved the integration of qualitative methods within the overall trial design. Qualitative methods have been used to inform trial necessity, investigate patient and health professional views and the development of a condition specific Patient Reported Outcome Measure (PROMS).The development of the qualitative arm of a clinical trials unit in Wales has led to increased implementation, appropriateness and quality of qualitative methods within trials."}
+{"text": "It is understood that toe walking involves the absence or limitation of heel strike in the contact phase of the gait cycle. When there is no medical cause of the gait pattern, a diagnosis of idiopathic toe walking (ITW) is made. Although there has been limited research into the pathophysiology of ITW, there has been an increasing number of references proposing that this gait pattern may be linked to sensory processing dysfunction (SPD). The purpose of this study was to investigate and profile 30 children with an ITW gait compared to 30 peers with a typical gait, using both qualitative and quantitative data.Participants were assessed using the: (i) Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), (ii) The Sensory Profile, (iii) Sensory Integration and Praxis test (SIPT), (iv) Vibration Perception Threshold (VPT) and (v) interview with parents about social factors of toe walkingResults of testing 33 children thus far have determined children with an ITW gait have lower vibration perception thresholds, a preponderance to be left handedness, and notable differences in sensory seeking and modulation scores as measured by the Sensory Profile. The BOT-2 scores found children who toe walked scored overall lower in the composite scores for fine motor and balance tasks; however, they generally scored above average in the strength sub-test. SIPT results found a significant different in post-rotary nystagmus. Parents discussed excitement and anxiousness as being factors that triggered ITW.These early results support the theory that the children who had an ITW gait differ in vestibular and tactile processing from the children who had a typical gait. The identification of these differences may assist allied health practitioners understand the gait pattern development and to plan more effective treatment methods."}
+{"text": "Improving the health of women of reproductive age extends beyond focusing on pregnancy and birth outcomes. Approaching women's health from a life course perspective offers an opportunity to reduce overall and pregnancy-related illnesses and deaths and to eliminate disparities through enhanced health promotion and disease prevention .www.cdc.gov/reproductivehealth) indicate shifts in the proportion of maternal deaths from traditional direct causes of maternal deaths  toward more chronic conditions, particularly cardiovascular diseases , articles by Farr et al  provides an opportunity to further extend clinical guidance for women's reproductive and wellness health screening through the Affordable Care Act. These recommendations provide no-cost coverage for 1) an annual well-woman preventive health visit, including preconception care, and additional visits depending on a woman's health status, needs, and other risk factors; 2) an array of contraceptives approved by the Food and Drug Administration; 3) human papillomavirus testing as part of cervical cancer screening; 4) annual counseling for sexually transmitted infections and screening for human immunodeficiency virus in sexually active women; 5) screening for gestational diabetes in pregnant women; and 6) comprehensive support and counseling for breastfeeding.The US Department of Health and Human Services adoption of the Institute of Medicine's recommendations of preventive services for women , an annual survey of women with a recent live birth, provides coverage of nearly 80% of births nationwide and monitors not only trends in certain chronic diseases  but also trends in key risk behaviors underlying many chronic diseases . PRAMS data on preconception and interconception care indicators can help programs anticipate prevention needs . Surveillance of state health policies  can also be evaluated with PRAMS data to examine their effect on health outcomes before, during, and after pregnancy.CDC's Pregnancy Risk Assessment Monitoring System (PRAMS) .Through existing funding initiatives and new funding opportunities from the Affordable Care Act, approaches for broad public health interventions can improve the health of women of reproductive age by supporting activities that address social policies, systems, and practices that improve population health. A public health approach to chronic disease prevention through community-based prevention efforts can help address health promotion among women of reproductive age."}
+{"text": "Multiple funding organizations and a grant were incorrectly omitted from the Funding Statement. The following should be read with the Funding Statement:\"The Natural Protected Areas National Commission of Mexico (SEMARNAT/CONANP) provided personnel, biological station facilities, boats, fuel and conventional tags during the early stages of the work (2003-2009). Those stages also were supported in part by a Mexico Small Grants Program funded by the UNDP/Global Environment Facility, as provided by the Mexican NGO SER de Quintana Roo A.C. The authors sincerely regret this omission.\"In addition, the following Acknowledgments were incorrectly omitted from the Acknowledgments Statement:\"The authors were remiss in acknowledging the assistance and leadership of Francisco Remolina Suarez, Jaime Gonzalez Cano and Jose Juan Perez Ramirez of the Natural Protected Areas National Commission of Mexico in helping to launch and coordinate this collaborative study.\""}
+{"text": "Scientific and regulatory disagreements and debates routinely arise during the determination of which specific environmental agents are of concern and at what exposure levels. Such debates are common during the development of human health assessments by the U.S. Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS). Indeed, IRIS has been the subject of several congressional hearings and National Academy reviews  preciselIn \u201cInstruments for Assessing Risk of Bias and Other Methodological Criteria of Published Animal Studies: A Systematic Review,\u201d In the clinical field, objective and transparent evidence-based systematic review methods have been used for several decades. These methods have been empirically tested and refined over time for evaluating scientific evidence to assess the effectiveness and potential risks of medical interventions . Such stIn their paper,"}
+{"text": "Alzheimer disease (AD) and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function. Alzheimer's disease (AD) is a devastating neurological disorder characterized by progressive deterioration of brain structure and function  but also AD  maintains CBF relatively constant in the face of changes in arterial pressure Lassen, . In partCBF decreases with advancing age and is lower in patients with AD compared with age-matched healthy individuals   which cross the blood-brain barrier (BBB) and stimulate neurogenesis and angiogenesis (Trejo et al., Regular aerobic exercise ameliorates endothelial dysfunction and central arterial stiffness (Seals et al., AD and cerebrovascular disease often coexist in the aging brain. Traditional view that AD and VaD are two divergent clinical entities with few or no overlap between their pathologies is challenged by an accumulating body of evidence indicating a close association between vascular disease and the risk of AD development. More recently, physiological studies also have demonstrated that vascular dysregulation of CBF elevate the risk of both cerebrovascular disease and AD. Specifically, presence of central arterial stiffness and endothelial dysfunction elevates the risk of pressure pulsatility or flow-related damage to brain structure and function. Further study of these modifiable risk factors through pharmacological or non-pharmacological approaches is likely to be important for developing an effective prevention or treatment for AD. In particular, further mechanistic study of the effect of regular aerobic exercise on arterial aging, brain perfusion and structure may provide new insights into how to prevent or slow the age-related cognitive decline, AD, and other age-related cerebrovascular diseases.Takashi Tarumi drafted the manuscript. Rong Zhang revised the manuscript critically for important intellectual content. Rong Zhang and Takashi Tarumi approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "There is growing evidence that foot problems and inappropriate footwear impair balance and increase the risk of falls in older people. These risk factors are potentially amenable by podiatric intervention, although this is yet to be evaluated in a clinical trial. This presentation reports on the first randomised controlled trial of a multifaceted podiatry intervention designed to improve balance and prevent falls in older people.We randomly allocated 305 community-dwelling people aged over 65 years with foot pain and an increased risk of falling to a control or intervention group. Both groups received routine podiatry care. The intervention group also received a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear was inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures were the number of fallers/multiple fallers and the falls rate, recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline included the Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index (MFDPI), the Falls Efficacy Scale International, foot and ankle strength and range of motion (ROM), and balance and functional tests.There was a significant reduction in falls rate in the intervention group compared to the control group  but no significant differences between the groups in the proportion of fallers/multiple fallers. There were also significant improvements in secondary outcome measures of the SF-12 physical subscale, the MFPDI function subscale, and several measures of foot and ankle strength and ROM, balance and functional ability in the intervention group compared to the control group.In older people with foot pain and an elevated risk of falling, a multifaceted podiatry intervention reduces the rate of falls by 36% and improves several aspects of foot and ankle strength, ROM, balance and functional ability suggesting that podiatry has a valuable role to play in preventing falls in older people."}
+{"text": "The use of osteopathic manipulative treatment (OMT) in preterm infants has been documented and results from previous studies suggest the association between OMT and length of stay (LOS) reduction, as well as significant improvement in several clinical outcomes. The aim of the present study is to show the effect of OMT on LOS and daily weight gain in a sample of premature infants.Randomized controlled trial on preterm newborns admitted in a single NICU between 2008-2009. N=101 subjects free of medical complications and with gestational age >28 and < 38 weeks were enrolled and randomized into two groups: study group (N=47) and control group (N=54). All subjects received routine pediatric care and OMT was performed to the study group for the entire period of hospitalization. Endpoints of the study included differences in LOS and daily weight gain. Statistical analyses were based on univariate tests and multivariate linear regression.Univariate statistical analysis showed no significant imbalances among treated and control groups in terms of main characteristics measured at admission. At the end of follow-up, OMT was significantly associated with LOS (days)  and with daily weight gain (grams) . After adjusting for all potential confounders, multivariate analysis showed a significant association between OMT and LOS reduction . OMT was not independently associated with any change in daily weight gain.The present study suggests that OMT plays an important role in the management of preterm infants hospitalization."}
+{"text": "The temporal and spatial resolution of cardiac magnetic resonance (CMR) imaging allows precise tracking of the left ventricle (LV) atrioventricular junction (AVJ) throughout the cardiac cycle. Similar to tissue Doppler imaging in echocardiography, AVJ motion assessed by CMR reflects diastolic LV function. A prior study by our group demonstrated significant differences in the displacement and velocity of the AVJ during diastole in patients with heart failure with preserved ejection fraction compared to normal hearts. In the current study we hypothesized that diastolic left ventricular function defined by AVJ motion is abnormal in patients with hypertrophic cardiomyopathy (HCM), a group known to have altered LV relaxation properties.We retrospectively identified 24 patients with known or suspected HCM and normal ejection fractions who underwent CMR as part of their clinical assessment and 14 normal control subjects. The longitudinal motion of the lateral and septal AVJs was tracked at 25 times through the cardiac cycle using the 4-chamber cine CMR view . The baseline position of the AVJ was defined at end diastole and its longitudinal displacement was measured relative to a reference line drawn between the LV apex and the midpoint of the mitral annnulus. The displacement of the AVJ in relation to its starting position at end diastole was normalized by LV length. Based on the resulting plots of AVJ position versus time in the cardiac cycle (see figure below) five motion variables were calculated: maximum longitudinal displacement (MD) of the AVJ, maximum velocity during early diastole (MVED), velocity at half-maximal displacement during early diastole (VHMDED), slope of the best fit line of displacement in diastasis (VDS), and the ratio of VDS/MVED. Data obtained in HCM patients were compared to normal control subjects using the Student t-test.Means and standard deviations were calculated for each of the AVJ motion variables  for the septal (S) and lateral walls (LW) of HCM patients and normal control subjects. Lateral and septal AVJ data were directly compared to the corresponding walls in patients and controls. We found highly statistically significant differences in MD and the four CMR correlates of diastolic LV function  in patients with HCM compared to normal controls, as noted in the table below.Novel CMR correlates of diastolic left ventricular function are markedly abnormal in patients with HCM. Measured at the AVJ, patients with HCM had significantly less maximal displacements, slower velocities during early diastolic filling, and higher velocities during diastasis compared to normal control subjects. The evaluation of AVJ motion by CMR may provide a new method to assess diastolic function.NIH 1R21HL108218-01."}
+{"text": "Objectives of IOL: We have two primary objectives: (i) To conduct world premier research in radiation sciences by collaborating with distinguished scientists from leading research institutes in the world. (ii) To promote further internationalization at NIRS by active research collaboration with foreign scientists.Brief history: IOL started at the end of 2008 and its first term ended in March 2011after 2 years and four months. Drs Hirohiko Tsujii and Ohtsura Niwa were very instrumental in the establishment of IOL. The first term IOL has three unit leaders and three distinguished scientists: These are Yukio Uchihori for the Space Radiation Research unit working with Professor Tom Hei from Columbia University (USA), Takeshi Murakami for the Particle Therapy Model Research unit working with Professor Anders Brahme from Karolinska Institute (Sweden) and Ryuichi Okayasu for the Particle Radiation Molecular biology unit working with Professor Penny Jeggo, University of Sussex (UK). Dr Tsujii was named as Director of the first-term IOL. These three units scored \u2018excellent\u2019 for overall evaluation for their accomplishment by the international review committee organized in 2010. Many workshops were held by these IOL units and helped further the internationalization of NIRS.Current IOL: In April 2011, the second-term IOL began and will complete in March 2014. As for the first-term IOL, each unit was selected by a special committee organized within NIRS. The structure of the second-term IOL is shown in Fig.\u00a0Conclusion: NIRS IOL significantly contributed to the internationalization of NIRS and is serving as a good model for international scientific collaboration."}
+{"text": "During elimination of medical consequences of various emergencies the issues concerning victims' mass evacuation to a specialized hospital base are constantly brought up. The physicians of the Central Airmobile Rescue Service of EMERCOM of Russia and the specialists of Kazan Helicopter Plant 'Zarechye' developed two types of modules. The Medical Airplane Module (MMS) is used for medical evacuation of four victims aboard Ilyushin 76 aircraft. The Medical Helicopter Module (MMV) is used for medical evacuation of two victims aboard an MI 8 helicopter. MMS and MMV advantages are: mobility - the possibility of installation in various aircraft cabins types; and versatility - the possibility of any required equipment installation for the treatment of victims with various trauma severity, safe fixation of medical equipment straight on the module, equipment operation off-line as well as using the aircraft power supply network.From December 2008 until now 28 medical evacuations were carried out using MMS aboard Iluyshin 76 aircraft: traffic accident victims, terrorism act victims and manmade catastrophes. In total, 198 patients were evacuated (including 12 children), 55 victims with artificial lung ventilation (ALV). Medical evacuation of severely injured children and adults from regional hospitals to Moscow specialized hospitals in order to provide efficient and modern medical aid was carried out using MMV. In total, 27 patients were evacuated (including five children), five patients with ALV. The majority of victims were in severe and extremely severe conditions with associated multisystem trauma. Closed craniocerebral injury was observed in 75% of victims with mass affection of locomotor apparatus, mine and explosion trauma, gunshot wounds, burn shock and burn disease. Constant monitoring, oxygen therapy, ALV, analgesia and sedation, intensive and anti-shock care as well as wound dressing were carried out in flight. The victims' general condition was evaluated according to the Glasgow Coma Scale, APACHE II and SOFA scales.MMS and MMV application in case of mass evacuation in flight ensures spare victims' transportation, total monitoring and treatment continuity. It enables one to carry out anesthetic and resuscitation treatment, intensive care, monitoring and treatment of all the victims.The quality of mass medical evacuation of extremely injured victims has considerably improved and the time of transportation from emergency area to specialized hospitals to render them efficient medical aid has reduced."}
+{"text": "Resveratrol, a polyphenol mainly present in grapes and red wine, demonstrated interesting biomedical properties for its cardioprotective action due to inhibition of the oxidation of low-density lipoprotein (LDL) and of platelet aggregation, inhibitory effects on cancer promotion and propagation and anti-inflammatory activities. These potential therapeutic and prophylactic applications are limited by the low bioavailability caused by its physical properties. Additionally, resveratrol has low water solubility and stability making its clinical success a formidable technological and medical challenge. The aim of this work is to present results of improvement of solubility of resveratrol through micellar and liposomal incorporation.Solubilization of resveratrol in six different bile acid solutions (cholic acid and its keto derivates) was investigated after 18 hours of mixing 2 mg of resveratrol in 2 ml of bile acid solutions in pH 7 buffer at room temperature. Liposome preparations containing pure resveratrol, resveratrol with vitamin C and resveratrol with vitamin E were prepared using the thin film hydration method. Resveratrol content was analyzed using HPLC with UV/DAD detection.The analysis of solubilization of resveratrol showed that keto derivatives of cholic acid have greater ability to solubilize resveratrol than cholic acid, and that this efficiency increases with the number of keto groups present in bile acid. The most effective acid for the solubilization of resveratrol was 3,7,12-triketocholic acid. Also, it has been shown that the efficiency of incorporation of resveratrol in liposomes increases with the amount of added resveratrol during preparation and the presence of vitamin C or E in the formulation, and that these preparations have satisfactory characteristics.Experiments carried out in this study provide useful information for potential development of different dietary and pharmaceutical resveratrol products."}
+{"text": "Humanitarian relief agencies use scales to assess levels of critical food shortage to efficiently target and allocate food to the neediest. These scales are often labor-intensive. A lesser used approach is assessing gathering and consumption of wild food plants. This gathering per se is not a reliable signal of emerging food stress. However, the gathering and consumption of some specific plant species could be considered markers of food shortage, as it indicates that people are compelled to eat very poor or even health-threatening food.We used the traffic light metaphor to indicate normal (green), alarmingly low (amber) and fully depleted (red) food supplies and identified these conditions for Konso (Ethiopia) on the basis of wild food plants (WFPs), crop parts  and crop residues (CRs) being gathered and consumed. Plant specimens were collected for expert identification and deposition in the National Herbarium. Two hundred twenty individual households free-listed WFPs, CPs, and CRs gathered and consumed during times of food stress. Through focus group discussions, the species list from the free-listing that was further enriched through key informants interviews and own field observations was categorized into species used for green, amber and red conditions.Dobera glabra (Forssk.) Juss. ex Poir. and inkutayata, parts of 17 crops with 21 food items conventionally not used as food , ten crop residues (for example bran from various crops) and one recycled food item (tata).The study identified 113 WFPs (120 products/food items) whose gathering and consumption reflect the three traffic light metaphors: red, amber and green. We identified 25 food items for the red, 30 food items for the amber and 65 food items for the green metaphor. We also obtained reliable information on 21 different products/food items (from 17 crops) normally not consumed as food, reflecting the red or amber metaphor and 10 crop residues (from various crops), plus one recycled stuff which are used as emergency foods in the study area clearly indicating the severity of food stress (red metaphor) households are dealing with. Our traffic light metaphor proved useful to identify and closely monitor the types of WFPs, CPs, and CRs collected and consumed and their time of collection by subsistence households in rural settings. Examples of plant material only consumed under severe food stress included WFPs with health-threatening features like We have complemented the conventional seasonal food security assessment tool used by humanitarian partners by providing an easy, cheap tool to scale food stress encountered by subsistence farmers. In cognizance of environmental, socio-cultural differences in Ethiopia and other parts of the globe, we recommend analogous studies in other parts of Ethiopia and elsewhere in the world where recurrent food stress also occurs and where communities intensively use WFPs, CPs, and CRs to cope with food stress. Humanitarian agencies delivering relief resources use combined intensity (severity) and magnitude (impact of the crisis) scales to assess famine and grade levels of critical food shortage. They do so in order to target and most efficiently allocate the ever-limited relief resources to the neediest. Very early assessment scales, designed to mitigate the crisis and prevent its deterioration, included the Indian Famine Codes devised in the 1880s and the Codes of Kenya developed for the northern region (Turkana communities), which coded three subsequent famine warnings or measurement levels of food insecurity: 1) near-scarcity, 2) scarcity, and 3) famine when eaten without extended processing. Gathering and consumption of these wild food plants is viewed as a clear indication of extreme severity of the food stress. Therefore, we strongly recommend that the use of human health threatening foodstuffs be included in the CSI in the enumeration of consumption-related coping strategies for monitoring food security status.karsata (Dobera glabra (Forssk.) Juss. ex Poir.) is envisaged to be the best indicator of critical food stress (red metaphor) in Konso and also in Hamar district[We have complemented the conventional seasonal food security assessments used by humanitarian partners  by providing an easy, cheap approach to scale food stress encountered by subsistence farmers. We recommend analogous studies in other parts of Ethiopia where recurrent food stress also occurs and where communities intensively use crop residues and wild food plants to cope with food stress. The consumption of district,6,8.CP: Crop part; CR: Crop residue; CSI: Coping Strategies Index; FA: Farmers\u2019 Association; WFP: Wild food plants.The authors declare they have no competing interests.DLO, PCS and LLP conceptualised and designed the research. DLO identified the study topic and the study area based on his local food security and ethnobotanical experience in the study area through his extensive food security monitoring in the country. EK supported the study in providing technical guidance in the collection, identification and nomenclature of plant specimens and facilitated depositing of the specimens in the National Herbarium of Addis Ababa University. KK provided a field guide and served as a translator and mediator between the local community, local officials and the study team, thus helping the study team in the daily field activities. DLO, PCS, EK and KK contributed to data collection and data verification. All authors contributed to the writing of the manuscript.Dechassa Lemessa Ocho is an agronomist by profession and has worked as food security researcher and expert for more than 20 years, including more than 15 years with government, international non-governmental organizations and the UN OCHA (Office for the Coordination of Humanitarian Affairs), both at national and international level, in Africa, Asia and the USA and has done extensive research on food security and the occurrence of wild food plants in different parts of Ethiopia, including Konso. He worked with the UN in New York, USA, as a Food Security Officer for the Horn of Africa, including Ethiopia and is currently working for South Sudan UN OCHA.Paul C Struik  and LLP  jointly supervise research on wild food plants in Africa and Asia, PCS focusing on methodological and ecological aspects and LLP focusing on anthropological aspects and socio-cultural methodological aspects.Ensermu Kelbesa  has specific expertise in botany and occurrence of wild food plants in Ethiopia and especially in the Konso region. He has conducted and supervised several ethnobotanical studies in Ethiopia.Koshana Kolo is an academically trained agriculturalist originating from the study community and is currently doing his M.Sc. studies in Ethiopia on WFPs in Konso as the current study helped him initiate his interest in the same subject while he was supporting our field work and he wanted to make use of his extensive knowledge of the local situations in Konso."}
+{"text": "Stroke is one of the most common diseases in China, especially ischemic stroke. Although there are significant advances in treatment of stroke in Western medicine, traditional Chinese medicine also plays an important role in treatment of patients suffering from acute ischemic stroke in China. One Chinese herbal formulation named Qingkailing solution is derived from an ancient formulation of Angongniuhuangwang and has been documented to reduce ischemic injury of the brain. However, due to significant side effects associated with Qingkailing solution, we reconstituted components of Qingkailing solution and formed a new solution named JZQKL. In the study, we are investigating the effect of different concentrations of JZQKL on ischemia induced brain injury.Mice were employed to induce ischemia injury of brain by middle cerebral artery occlusion (MCAO). JZQKL solution was injected into mice through the tail vein at different times  and at different doses . Twenty-four hours after MCAO, neurological function and brain infarction were examined and cell apoptosis at the hippocampus and prefrontal cortex were evaluated by TUNEL, western blot and ROS.After examining the effect of different concentrations of JZQKL on neurological function and brain infarction, we identified that there was a good correlation between concentrations and improvement of neurological function. With a concentration of 3ml/kg, time dependent experiments were conducted. Improvement of neurological function and reduction of infarction gradually decreased with delay of administration of JZQKL. Moreover, JZQKL reduced apoptosis of neurons in the hippocampus and prefrontal cortex as documented by reduction of caspase-3 expression, eIF2a phosphorylation and caspase-12 activation. JZQKL also decreased oxygen-reactive species (ROS) in the brain.Early administration of JZQKL significantly prevented ischemic induced brain injury and its mechanism might be related to an anti-oxidative effect and/or attenuation of apoptosis in the brain."}
+{"text": "Methods for interpreting verbal autopsy (VA) that have been validated fall into two major categories: 1) physician-certified verbal autopsy (PCVA), the commonly-used method in which one or more physicians ascertain causes of death based on their clinical judgment; and 2) computerized coding of verbal autopsy (CCVA), in which causes of death are derived using predefined criteria. Decision rules for CCVA can be expert opinion-based or data driven. The accuracy of these VA interpretation methods varies depending on causes of death per se, while the effect of misclassification error in VA on the estimates of cause-specific mortality fractions (CSMF) depends on the distribution of causes of death. The importance of acknowledging the effects of misclassification of causes of death by VA has been highlighted by the recent controversial estimates of malaria mortality in India [ physicia computerThe gold standard diagnosis of cause of death (COD) for assessing the validity of VA has been the COD derived from hospital medical records. The main limitations of using hospital-based CODs as the gold standard are: (1) The accuracy of medical records-based COD is debatable, even though some studies have refined the diagnosis with expert review of hospital records; and (2) the composition and distribution of hospital CODs may not be representative of deaths occurring in the community. In addition, if diagnostic algorithms for CCVA are developed from subsets of validation study datasets, their external validity may be compromised. Nevertheless, hospital diagnosis of COD based on defined clinical and laboratory criteria are the only useful gold standard available at present for validating VAs.The validity of InterVA has not previously been tested against a gold standard diagnosis. The reliability of InterVA has been determined by examining the concordance of CSMFs estimated by InterVA and PCVA. Given that the accuracy of PCVA is questionable, estimating concordance between causes of death derived by PCVA and InterVA as a measure of validity needs to be interpreted with caution.Measures used to assess the validity of VA include sensitivity, specificity, positive predictive value, and absolute (absolute error) or relative (relative error) difference between CSMF estimated by VA and true CSMF in the validation data. Sensitivity and specificity that measure accuracy at the individual level vary substantially between causes of death across different VA interpretation methods. The absolute and relative errors of CSMF measure the accuracy of VA at the population level. The variability of the absolute error in CSMF appears to be reasonable for most CODs because often the number of false positive and false negative diagnoses balance out. However, the relative error in CSMF tends to be exaggerated, especially if the CSMF is low.Murray and colleagues in this series recommend determining the validity of VAs using cause-specific and average chance-corrected concordance across causes for single cause assignment methods, as well as for one to k causes across causes for individual multiple cause assignment methods . For estFlaxman et al  have dev"}
+{"text": "It is a privilege, pleasure, and honour to present this special issue to the international scientific community. The editorial board is confident that it is a truly good publication; as the papers published in this issue cover a broad spectrum of topics on plant biotechnology, that could be of wide interest. This special issue received 20 papers, of which 2 papers were withdrawn and 4 were rejected . The guest editorial board of this issue would like to mention that the published papers in this special issue contain one paper on molecular and genetic diversity from China that studied 115 sugarcane genotypes based on five genomic simple sequence repeat marker (gSSR) loci and 88 polymorphic alleles of loci as detected by capillary electrophoresis. The results indicated large intrapopulation genetic variation compared with interpopulation variation. The knowledge obtained in this study should be useful for future breeding programs. One paper discusses the problem of mantled fruits as a result of somaclonal variation in oil palm plantlets regenerated via tissue culture. The molecular aspects of the occurrence possibly due to gene repression such as DNA methylation, histone methylation, and histone deacetylation are discussed. This paper described the total protein polymorphism profiles of somaclonal variants of oil palm and the effects of histone deacetylation on this phenomenon.One paper presents cytogenetic study of Papaver species that introduced a new concept by developing ice cold water instead of bromonaphthalene for chromosome studies.Origanum acutidens (Hand.-Mazz.) Ietswaart using stem node explants; use of tissue culture techniques for producing virus-free plant in garlic; adventitious shoot regeneration from leaf explant of aquatic plant Hygrophila polysperma (Roxb.) T. Anderson); secondary somatic embryogenesis in Hovenia dulcis Thunb.; effects of IAA, IBA, NAA, and GA3 on rooting and morphological features of Melissa officinalis L. stem cuttings; comparison of different methods for separation of haploid embryo induced through irradiated pollen and their economic analysis in melon (Cucumis melo var. inodorus); and comparative studies on cellular behaviour of carnation (Dianthus caryophyllus Linn. Cv. Grenadin) grown in vivo and in vitro for early detection of somaclonal variations and the influence of 1-triacontanol on the growth, flowering, and quality of potted Bougainvillea glabra var. \u201cElizabeth Angus\u201d under natural conditions. Still in another paper published in this issue, there is important information about \u201cAnnotation of differentially expressed genes in the somatic embryogenesis of Musa and their location in the banana genome.\" The important information about TDFs sequences opens new possibilities for an in-depth study on molecular and biochemical research pertaining to zygotic and somatic embryogenesis in Musa species.The papers on plant cell and tissue culture include a review on genetic transformation in citrus; micropropagation of http://www.hindawi.com/journals/tswj/psi/biotechnology/). The journal is indexed in many important international databases including Science Citation Index Expanded, Zoological Record, and BIOSIS Previews. These highly esteemed papers are easily available in the form of open access papers at the website of the journal ("}
+{"text": "Simultaneous dislocation of both interphalangeal (IP) joints of same finger is a highly uncommon finding. And dislocation of metacarpophalangeal (MCP) joint along with interphalangeal joints of thumb are reported in literatures if, scarcely. Here we are reporting the three cases, comprising of double dislocation of IP joints in little finger in two patients and simultaneous MCP and IP joint dislocation in thumb in another third patients as a perusal of rare entity from the northern India. First case of double dislocation in a finger was documented in 1874 by Bartel  during cricket playing and reveled that mechanism of injury was hyperextention type. He presented to emergency department within two hours after injury. Radio graphically dorsal dislocation of both interphalangeal joints of little finger in dominant hand was confirmed. We used ring block anaesthesia and reduced by giving longitudinal traction and pressure over base of caudal phalanx. First done at distal and then at proximal interphalangeal joint and immobilized in intrinsic plus position for three weeks and then physiotherapy done. Second one presented (in January 2006) to us after seven days of trauma in his little finger. He was laborer by occupation, and injured during fall on the ground by keeping his right hand on the edge of wall for protecting himself. On radiography there was undisplaced condyler fracture of proximal phalanx along with dorsal dislocation of both interphalangeal joints. Close reduction tried for two times but failed then open reduction and Kirschner wire fixation done and immobilized  and 2. Our third case (in march 2011) of dislocation of MCP and IP joints of left thumb was present in twenty five year soccer player, who got injured during playing and visited to emergency department immediately. It was dorsal dislocation of both joints along with minor intraarticular fracture of base of distal phalanx . ReductiAfter one year of trauma in all cases of IP joints dislocation, there was residual swelling in distal interphalangeal joint. Flexion movement was within normal limit at proximal and distal interphalangeal joints but extension lag of 15-degree was present at distal interphalangeal joints. In thumb dislocation the arc of motion was from 10-degree hyperextension to 60-degree flexion at IP joint and at MCP joint from zero degree to 30-degree flexion. All patients were gone through ethical consideration, and informed consent. Clinical variables were measured clinical and radiological.Review literature of Anderson et al. and study of Hutchison et al., and along with case report of Jahangiri SA et al. are the endorsements of rareness of this injury -4. In te"}
+{"text": "To the Editor: Although transmission between co-feeding vector ticks may perpetuate particular tick-borne viruses, this mode of transmission plays no role in the epizootiology of Lyme disease spirochetes   is some two orders of magnitude less efficient than sequential transmission between ticks feeding on persistently infected reservoir rodents (85.4%). The two studies that relied on natural infestation densities and refrained from using artificial feeding capsules conclusively demonstrated that transmission of Lyme disease spirochetes between ticks feeding simultaneously and in close proximity contributes little to the perpetuation of this pathogen, either in North America or in Europe ("}
+{"text": "Adult neural stem cells (NSCs) are perceived as a homogeneous population of cells that divide infrequently and are capable of multi-lineage differentiation. However, recent data revealed that independent stem cell lineages act in parallel to maintain neurogenesis and provide a cellular source for tissue repair. In addition, even within the same lineage, the stem and progenitor cells are strikingly heterogeneous including NSCs that are dormant or mitotically active. We will discuss these different NSC populations and activity states with relation to their role in neurogenesis and regeneration but also how these different stem cells respond to aging. NSCs depend on Notch signaling for their maintenance. While Notch-dependence is a common feature among NSC populations, we will discuss how differences in Notch signaling might contribute to adult NSC heterogeneity. Understanding the fate of multiple NSC populations with distinct functions has implications for the mechanisms of aging and regeneration. Neural stem cells (NSCs) remain neurogenic during postnatal life within two regions of the mammalian brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the wall of the lateral ventricles. The discovery of adult neurogenesis in mammals opened new avenues for research in regenerative medicine, with a goal of manipulating endogenous NSCs for brain repair (Gage and Temple, One such gap, and a field of active research, relates to the presence of heterogeneous subpopulations of NSCs within the same neurogenic niche (Alvarez-Buylla et al., Work from the 90's and early 2000's discovered the sequential developmental stages that cells undergo during lineage progression within the adult neurogenic niches (Alvarez-Buylla et al., The ability of adult NSCs to survive antimitotic drug treatment and regenerate the neurogenic lineage suggested that they rarely divide (Doetsch et al., in vivo. Lineage tracing approaches with inducible-cre/flp technologies and intersectional analyses combining promoters of cell-cycle marker genes with NSC marker genes may be useful to this end.Discrimination of quiescent from activated NSC populations and niche astrocytes has proven difficult, but progress has been made toward this end in recent years (Pastrana et al., Heterogeneity in the adult neurogenic lineage is not restricted to NSCs. In the SVZ, a proportion of Ascl1+ IPs expresses radial glia markers whereas others do not (Pastrana et al., in vitro (Suh et al., in vivo (Suh et al., in vivo (Alvarez-Buylla et al., in vitro passage and heterotopic transplantation (Merkle et al., in vivo suggest that the local environment plays a role in regional specification of adult NSCs (Ihrie et al., Adult NSCs are capable of multi-lineage differentiation and able to clonally generate multiple neural lineages under appropriate conditions Hes/Hey family is fundamental for maintaining NSCs in an undifferentiated state, suppressing the expression of proneural genes including Ascl1 (Louvi and Artavanis-Tsakonas, Hes5 expression in particular distinguish NSCs from IPs in the developing and adult brain (Basak and Taylor, Hes5 is expressed in both dividing and dormant adult NSCs, Notch is unlikely to be the only key to NSC heterogeneity (Lugert et al., in vitro (Guentchev and McKay, Hes genes is sustained or oscillatory in adult NSCs, and the available tools are not adequate to address this issue in vivo. However, oscillatory expression of Notch targets together with low refractory expression of Ascl1 in adult NSCs that are in the cell-cycle would be compatible with data showing that the Ascl1::CreER locus can be used to lineage trace a subpopulation of neurogenic NSCs in vivo (Kim et al., Hes1 and therefore modulate its oscillatory expression (Bai et al., Hes genes are persistently expressed at high levels in quiescent NSCs.Notch signaling is a key mediator of NSC maintenance in the developing and adult brains (Ables et al., Hes5::CreER transgenic mice demonstrated that NSCs with active canonical Notch signaling generate multiple neuron subtypes in the OB (Giachino et al., Another possible scenario to explain the multifaceted functions of Notch in adult NSCs would be that distinct pathway components are differentially engaged in Notch signaling activity in different cell subpopulations. It has been proposed that Notch1 is required to maintain the active adult NSC pool but is dispensable during quiescence (Ables et al., Hes family genes, with cohorts of radial glia cells expressing either Hes1 or Hes5, or both (Basak and Taylor, Her/Hes family genes correlate with the proliferation rate of NSCs and progenitors in the adult zebrafish (Chapouton et al., Hes5-expressing NSCs in the adult mouse SVZ, whereas most quiescent NSCs express Hes5 but not BLBP (Giachino et al., Not only the activity of Notch paralogues, but also combinations of different Notch target genes in NSC subpopulations may be a source of heterogeneity. NSCs in the developing neural tube of the mouse are heterogeneous based on their expression of The adult mammalian neurogenic niches show a remarkable capacity for self-repair and remodeling in response to lesion (Doetsch et al., One cause of reduced neurogenesis during aging is the impairment of the NSC compartment. An open question is whether this impairment reflects depletion or increased quiescence of NSCs (Hattiangady and Shetty, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "For the subset of most confident predictions the achieved accuracy can reach as high as 95%. Fragmental analysis of the chemical structures was applied to better understand the origin of AHR binding affinity. Analysis confirms several chemical scaffolds of halogenated aromatic hydrocarbons (HAHs) and polycyclic aromatic hydrocarbons (PAHs) as activators of the AHR. The high accuracy of in silico techniques in modeling the in vitro assay results endorses QSAR as a promising technique in predictive toxicology.The Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that, normally inactive, upon activation responds to exogenous and endogenous chemicals with the induction/repression of expression of large battery of genes. This induces diverse biological and toxic effects in a wide range of tissue. To evaluate the structural characteristics of small molecules responsible for AHR binding and toxicity, cross-validated qualitative QSAR models were developed using the free tool OCHEM ("}
+{"text": "Transcranial current stimulation (TCS) is a promising method of non-invasive brain stimulation to modulate cortical network dynamics. Preliminary studies have demonstrated the ability of TCS to enhance cognition and reduce symptoms in both neurological and psychiatric illnesses. Despite the encouraging results of these studies, the mechanisms by which TCS and endogenous network dynamics interact remain poorly understood. Here, we propose that the development of the next generation of TCS paradigms with increased efficacy requires such mechanistic understanding of how weak electric fields (EFs) imposed by TCS interact with the nonlinear dynamics of large-scale cortical networks. We highlight key recent advances in the study of the interaction dynamics between TCS and cortical network activity. In particular, we illustrate an interdisciplinary approach that bridges neurobiology and electrical engineering. We discuss the use of (1) hybrid biological-electronic experimental approaches to disentangle feedback interactions; (2) large-scale computer simulations for the study of weak global perturbations imposed by TCS; and (3) optogenetic manipulations informed by dynamic systems theory to probe network dynamics. Together, we here provide the foundation for the use of rational design for the development of the next generation of TCS neurotherapeutics. Modulating cortical network dynamics with transcranial current stimulation (TCS) has shown promise as a treatment of neurological and psychiatric illnesses , a direct demonstration of a causal role of endogenous EFs in shaping cortical network dynamics has lacked. In particular, the open questions are: (1) if naturalistic EF waveforms have similar effects on network dynamics; (2) if the interaction dynamics differ between feed-forward and feedback application of EFs  requires mechanistic insight into the functional role of endogenous EFs that have been historically discounted as an epiphenomenon of cortical oscillations. Despite a number of studies s Figure  that levm Figure  demonstrm Figure , a depolin vivo models has provided further support for the efficacy of such stimulation paradigms  when the stimulation frequency was between 40 and 50 Hz (Carlen et al., in vitro networks of cultured neurons may also be entrained with optogenetic stimulation (Pina-Crespo et al., In vivo cortical networks are nonlinear systems that exhibit ongoing rhythmic activity. Due to this nonlinearity, the response to TCS will likely be different based on the current state of activity. We here propose that interaction dynamics of TCS and endogenous activity can be studied with optogenetic stimulation to induce in vivo-like activity patterns. For example, a slow oscillation can be entrained using optogenetic stimulation in vitro and EF can be applied while the resulting modulation of activity by TCS is measured using whole-cell patch clamp, multiunit, or LFP recordings (Figure Optogenetics is typically used to activate specific neural pathways, which allows examination of the underlying circuitry involved in different behaviors (Miesenbock and Kevrekidis, s Figure .in vitro animal experiments do not consider the complexity of delivering EFs to the brain through multiple layers of tissue and bone. Furthermore, targeting of specific cortical locations is difficult in gyrencephalic brains due to the different neuronal orientation across gyri and sulci. Since the effect of EFs on the membrane voltage depends on the relative orientation of the field to the somato-dendritic axis of neurons (Tranchina and Nicholson, The above discussed approaches enable fundamental insights into how active cortical networks respond to stimulation. In particular, the application of modern neuroscience tools provides the unique opportunity to understand how non-invasive brain stimulation with EFs can modulate cortical oscillations that are impaired in a broad range of disorders of the central nervous system, such as schizophrenia (Uhlhaas and Singer, in vivo and in vitro studies that leverage optogenetic stimulation to first entrain network activity which allows the targeted study of these interaction dynamics. Together, these interdisciplinary approaches will provide a foundation for the rational design of TCS.Rational design of TCS requires an understanding of the interaction between endogenous EF and network activity and the interaction between network activity and stimulation EFs. Hybrid systems have both established the role of endogenous EFs and resulted in successful control of network activity. Recent studies with large-scale computer models have begun to mechanistically elucidate the interaction dynamics between endogenous network activity and EF stimulation. We further propose The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "According to epidemiological studies, about 2-4% of the population in industrialized countries suffer from food allergies. The symptoms can range from minor skin rash to life threatening anaphylaxis and at present no effective therapy is available. Strict avoidance of the offending food is therefore mandatory for allergic individuals. Nut allergens are regarded highly problematic, because of the severe course of disease and the potential of cross-contamination during food processing. Due to a lack of sensitive and specific detection methods there are no certain threshold values.Another important aspect is the impact of food processing on structure and allergenicity of nut proteins. Processing like roasting or extrusion can lead to reactions of allergens with other food ingredients and thereby change solubility, conformation and digestibility.Allergens from hazelnut, peanut, pistachio and walnut were extracted and digested by trypsin. The resulting peptides were analyzed by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Protein identification was performed via peptide fragment fingerprinting (PFF) of designated marker proteins and database search.in vitro model simulating gastric and duodenal digestion. Several hazelnut cultivars were characterized by two-dimensional polyacrylamid gel electrophoresis (2D-PAGE).Furthermore allergens were processed on the one hand by thermal treatment in presence of sugars and on the other hand by extrusion cooking together with maize. Structural and functional consequences of allergen modification were analyzed via electrophoretic techniques and mass spectrometry. The stability of hazelnut proteins against gastrointestinal degradation was tested by use of an A mass spectrometric method for the detection of nut allergens was developed successfully. Additional matrix experiments showed that the analysis of allergens in chocolate and muesli is also possible. Food processing led to protein aggregation, Maillard products and changes in digestibility. The characterization of several hazelnut cultivars showed minor differences in protein content and composition.According to the results food processing has a strong impact on structure and digestibility of allergens. In addition, different nut cultivars show a certain degree of protein heterogeneity. All of this should be considered for the choice of suitable marker proteins for development of a detection method.None declared."}
+{"text": "Molecular structure is eminently modular and expresses complexity at different levels of molecular organization ToDs and ToPs are derived from non-parametric models of genomic abundance that are free from problems of homology in the alignments of sequences and structures ToDs and ToPs are not affected by the serious problem raised by Maddison  of chara(3)ToDs are highly imbalanced and do not follow the uniform (Yule) and random speciation models Taxon sampling represents a problem in phylogenetic analysis that impacts accuracy and phylogenetic error The troublesome task of solving the problem of orthology and paralogy in sequence analysis Evolutionary processes such as convergent evolution and horizontal gene transfer (HGT) can confound phylogenetic analysis leading to erratic interpretations when dealing with molecular sequence data. However, the effect of these processes on molecular structure appears to be very limited Gough, . Even th(7)Pro with proline generally harbor three domains with ages that span two billion years (Gy) of evolution ToDs and ToPs are appropriately based on a historical analysis of molecular units of evolution, function, and structure, the protein domains Mutation saturation destroys phylogenetic signal in sequences, a serious problem affecting the validity of deep phylogenetic inference Finally, the most fundamental principle of phylogenetic analysis, character independence, states that each character must serve as an independent hypothesis of evolution (Kluge and Farris, ToDs, ToFs, and ToPs are however relatively new to the arsenal of evolutionary bioinformatic approaches and have not been widely used. They are also subject to limitations in structural and functional assignments and the computational demands of sequence-profile or more sensitive profile-profile comparisons [see Nasir et al.  for furt"}
+{"text": "We previously the tested the hypothesize of epigenetic involvement in FMF, mainly based on the occurrence of FMF in patients without mutations and decreased MEFV transcripts in leukocyte samples independent from mutations. Our study showed that higher methylation level of MEFV second exon CpG island in FMF patients compared to healthy controls  patients.student-T test analyses.DNA was isolated from venous blood of age-gender matched FMF (N=20) and JRA (N=17) patients in attack-free period, who are diagnosed and followed up at Istanbul University, Cerrahpasa Medical Faculty, Department of Pediatric Rheumatology. The parents of children were informed and consent forms were fulfilled. Methylation levels were calculated according to the protocol of OneStep qMethyl Kit (Zymo), which is a real-time PCR procedure based on methylation specific restriction enzyme digestion. The methylation levels were compared between groups using First intron and part of the second exon methylation level of MEFV gene were analyzed in both FMF and JRA groups and there was no significant difference between two groups.In this preliminary study we have observed similar MEFV intron 1 and part of exon 2 methylation levels between FMF and JRA patients. In combination with previous studies pointing MEFV involvement in other inflammatory disorders such as JRA and BS, our findings may further support the importance of MEFV in inflammatory pathway and possibly not only through genetic mechanisms but also by means of epigenetic regulations.None declared"}
+{"text": "The connection-set algebra (CSA) ,2 is a nThe CSA is expressive enough to describe a wide range of connectivities and can serve as a concise notation for network structure in scientific writing. CSA implementations allow for scalable and efficient representation of connectivity in parallel neuronal network simulators and could even allow for avoiding explicit representation of connections in computer memory. The expressiveness of CSA makes prototyping of network structure easy.Here, a Python implementation  of the c"}
+{"text": "With the advent of new Multi-Electrode Arrays techniques (MEA), the simultaneous recording of the activity up to hundreds of neurons over a dense configuration supplies today a critical database to unravel the role of specific neural assemblies. Thus, the analysis of spike trains obtained from in vivo or in vitro experimental data requires suitable statistical models and computational tools.The EnaS software [7], developed by our team, offers new computational methods of spike train statistics, based on Gibbs distributions  and taking into account time constraints in neural networks (such as memory effects). It also offers several statistical model choices, some of these models already used in the community (such GLM  and the EnaS allows large scale simulation thanks to our recent study  (hundred"}
+{"text": "Dear Editor,The coincidence risk of autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC) in the absence of viral hepatitis is extremely low and most of the previous reports have been isolated case reports . Meanwhi"}
+{"text": "In an experimental study on the changes in descending drive during muscle fatigue, Semmler et al.  investigIn this commentary, I will first revisited the reasons for investigating IMC and CMC. These measures have the potential to provide key insights into the composition of descending drive Farmer,  and invoCMC and IMC can provide important insights into the diverging projects underlying motor coordination. A major open questions in motor control is how the central nervous system (CNS) controls the redundant degrees of freedom of the musculoskeletal system  into corticospinal drive (Heitmann et al., New techniques may reduce some of these peripheral effects on CMC and IMC, e.g., high-pass filtering EMG before rectification may diminish the effect of EMG signal cancellation (Boonstra and Breakspear, In sum, whilst the concerns expressed by Heroux and Gandevia  regardin"}
+{"text": "Chronic lung diseases affect a significant portion of the population, and the incidences of chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF) are increasing. COPD is the fourth leading cause of death in the USA and the incidence of IPF has doubled over the past decade. Identification of novel transcripts and transcript isoforms  associated with these diseases may help us better understand their molecular pathogenesis, and identify both novel disease-specific biomarkers and therapeutic targets.Using lung tissue sections from the NHLBI Lung Tissue Research Consortium, we sequenced the mRNA  from 145 lung tissue samples that were subsequently split into an initial training cohort of 89 samples and an independent filtering set of 56 samples. Genome-guided transcriptome reconstruction using Cufflinks was performed on the training and independent filtering set. A final conservatively filtered assembly was created by requiring complete overlap of all transcripts present for a gene in the two assemblies. Next, the algorithm MISO was used to quantify isoform proportions for known and novel transcripts found in each gene. These were modeled as a function of the disease state, isoform and the interaction between disease state and isoform to identify disease-associated differentially spliced genes.P<0.01) compared with control. Three of these candidate genes were DE in both diseases. Several examples of disease-associated differential splicing were also identified. These new disease-associated isoforms are being further investigated to identify their biological function and relevance to COPD and IPF.The filtered transcriptome assembly (overlap set) is more similar to known genes (based on comparisons with Ensembl) than the initial training and independent filtering set. A set of 38 novel gene candidates were selected based on gene structure parameters computed from Ensembl annotation. Differential expression (DE) analysis was performed, and five of the candidate genes were DE in emphysema and eight in IPF (RNA-Seq of a large number of lung tissue samples has allowed us to identify novel disease-associated genes and alternative splicing patterns that may contribute to our understanding of the pathogenesis of IPF and COPD."}
+{"text": "Structural magnetic resonance imaging (MRI) studies of Alzheimer\u2019s disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases directional diffusion  damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI."}
+{"text": "We compared the DebugIT control capabilities to the process and results provided by the French surveillance system of infectious disease (Institut de Veille Sanitaire (InVS)) and the antimicrobial resistance surveillance study of the Paul-Ehrlich-Society (PEG).An important limitation of existing large-scale surveillance systems of infectious diseases is that they use mostly manual data collection processes and therefore usually deliver trends on an annual basis. The DebugIT project, funded by the 7InVS currently controls every year multidrug resistant bacteria in 930 French healthcare facilities and Nosocomial Infection in 176 Intensive Care Units. PEG collects 240 isolates from each of 20-30 microbiology laboratories every three years. The DebugIT platform provides a scalable solution for executing real-time clinical queries over European data repositories about antibiotic resistance and antibiotic consumption.Despite different methods for aggregating data and calculate incidence rates and antibiotic consumption , the trends observed by national surveillance programs are similar to those reported retrospectively by the DebugIt platform. The detailed comparison is still ongoing.The use by European surveillance networks of platforms such as DebugIT platform is likely to enhance their ability for real-time identification of new trends in antibiotic resistance and/or antibiotic consumption. An interesting perspective is to connect DebugIT endpoints to general practitioner electronic medical records or private laboratory information systems in order to extend the surveillance to the community.None declared."}
+{"text": "Studies concerning the mechanism of DNA replication and repair have advanced our understanding of the stable transmission through multiple cell cycles of a faithful genetic material. Recent work has shed light on possible means to ensure the stable transmission of information beyond just DNA and the concept of epigenetic inheritance has emerged. Considering chromatin-based information, key candidates have arisen as epigenetic marks including DNA and histone modifications, histone variants, non-histone chromatin proteins, nuclear RNA as well as higher-order chromatin organization. Thus, understanding the dynamics and stability of these marks following disruptive events during replication and repair and throughout the cell cycle becomes of critical importance for the maintenance of any given chromatin state.We will present our most recent work on this topic, considering mostly histone variant dynamics during the cell-cycle and in response to DNA damage."}
+{"text": "The CoLaus study is a large population based cross sectional study in over 6000 subjects aged 35-75 years living in Lausanne, Switzerland. Its main goals are to obtain information on (1)The prevalence of cardiovascular risk factors and diseases in the population of Lausanne, (2)New biologic and genetic determinants of isolated and clusters of cardiovascular risk factors.oC and all Caucasian subjects were genotyped with database in Lausanne.Recruitment was done from 2003 to 2006 to obtain a representative sample of subjects. The participation rate was 42%. The participants were extensively phenotyped by administering a questionnaire on personal and family history of cardiovascular risk factors & personal medical history, a basic physical exam for cardiovascular risk factors, mental status examination and biological markers in blood and urine. Plasma, serum, whole blood and urine were stored at -80Starting in 2004, over 3600 CoLaus participants underwent an extensive psychiatric phenotypization (PsyCoLaus). This extensive phenotype should allow us to better understand the known association between cardiovascular diseases and mental health.In May 2009 follow-up of the entire CoLaus population was started to prospectively assess the association between cardiovascular diseases, cardiovascular risk factors and mental disorders. Data were collected to know the course of the conditions related to cardiovascular diseases or mental disorders observed at baseline, the incidence of such conditions during the follow-up and the evaluation of candidate variables which could be either mediators of a causal relationship or shared factors underlying the association between mental disorders and cardiovascular diseases.Several sub-studies were also started like:(1)AngioLaus \u2013 a case control study in which 500 participants underwent detailed cardiovascular pheno-typing including intima-media thickness in the carotid arteries, pulse-wave velocity, central arterial pressure and endothelial function before and during reactive hyperaemia.(2)HERCULES - to study the prevalence of hypertension using 24-hour ambulatory blood pressure measurement, to assess renal function using 24-hour urine collection  and to expand understanding of genetic variants associated with hypertension and renal function within the CoLaus study.(3)OsteoLaus - to compare risk models to discriminate osteoporotic fractures, to better understand the association of osteoporosis, cardiovascular diseases & mental health and to determine the genetic determinants of osteoporosis.(4)HypnoLaus - to determine the prevalence of sleep disorders in the general population, to assess the genetic basis of sleep and its disorders and for better characterization of a potential link between cardiovascular disease risk factors and mental health.Each subject had reversible anonymised unique identification barcode and samples in the bio-bank were identified with barcodes. The data are stored in an Oracle database updated with Epi-data software. A scientific advisory board consisting of external scientists evaluate the progression of the project. The participant motivation is being sustained with regular newsletters and interactive website. The project had received funding from GlaxoSmithKline initially and is currently supported by the Swiss National Science Foundation. There have been over 100 publications with more than 3000 citations so far from the project."}
+{"text": "The most common causes of long-term failure of the Oxford medial unicompartmental knee arthoplasty (UKR) are the development of lateral compartment osteoarthritis, and component loosening and infection.The Lyon Schuss view (an anteroposterior weight-bearing radiograph taken with the knee in 20\u201330 degrees flexion) offers greater accuracy in determining moderate to severe loss of joint space compared with the standard weight-bearing view with the knee fully extendedWe recommend the Lyon Schuss view as a primary investigation for painful UKR as it instantly establishes the most common cause of failure instantly. The Lyon Schuss view also eliminates the risk of radiation exposure to staff and inconsistency of the applied force associated with stress views."}
+{"text": "Chiropractic care is covered under Medicare, but the scope of services is restricted. The Demonstration of Expanded Coverage of Chiropractic Services under Medicare projected that expanded services would cost Medicare up to $1.15 billion annually. The potential expansion of chiropractic services under Medicare remains controversial. Advocates for expansion cite clinical effectiveness and high patient satisfaction, while critics point to compliance issues and projected cost increases.Seven reports from the US Department of Health and Human Services and the results of two focused Medline queries were reviewed for evidence related to the provision of chiropractic care under Medicare. The literature review summarized the findings of government reports and peer-reviewed publications, and explored the pros and cons of expanded services.Three problem areas pose barriers to expansion of chiropractic services under Medicare: (1) putative provision of maintenance (wellness) care in apparent violation of Medicare practice guidelines; (2) inadequate clinical documentation; and (3) projected increased costs associated with expanded services. However, maintenance care is poorly defined, and evidence for its clinical effectiveness is not without promise, although its cost-effectiveness is unknown. Inadequate clinical documentation, although not justifiable, may be connected to disparities in Medicare documentation requirements and reimbursement. The analysis of budget neutrality of the demonstration project may have been subject to bias due to selection of unrepresentative demonstration sites. No causal relationship was established between expanded services under the demonstration and the observed differences in total Medicare costs.Research on costs and clinical outcomes associated with maintenance care is needed. Any unjustifiable disparities in coverage and payments under Medicare should be corrected. Chiropractic physicians must assume responsibility for correcting deficiencies in compliance and documentation. A policy decision on the expansion of chiropractic services under Medicare should consider the results of a re-evaluation of the demonstration, which is currently underway."}
+{"text": "Unstable shoe designs should support the muscle activity and promise the treatment of leg, back and foot problems. According to manufacturers, they should activate additional muscles and reduce joint reaction forces. Goal of this study is to investigate the effect of an unstable shoe design to gait patterns of healthy volunteers and by the means of inverse dynamic multi-body simulation.Seven subjects  familiar with unstable shoes performed five trials of level walking in three testing conditions . As an unstable shoe the Anti-Step (Chung-Shi) was chosen. Kinematic and kinetic data was acquired with a motion capturing system (Vicon) and two forceplates (AMTI). The inverse dynamics model of the lower extremity consists of nine rigid bodies which are connected with idealized joints and a set of all relevant muscles.Comparing walking speed while walking barefoot or with stable and unstable shoe designs, the volunteers walked significantly slower in the barefoot case (p<.003). Preliminary multi body-simulation data was analysed for four out of seven volunteers. Peak joint reaction forces were reduced by 29% when comparing conventional with unstable shoes Figure . The timThe simulation reveals muscle activation patterns that indicate instability along the inversion/eversion axis of the ankle, which is also found in the literature . The add"}
+{"text": "Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD). Acute mental stress can activate the sympathetic-adrenal-medullary (SAM) axis, eliciting the release of catecholamines (NE and EPI) resulting in the elevation of heart rate (HR) and blood pressure (BP). Combined stress  can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations . Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system  reactivity and enhanced cardiovascular efficiency  in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD. Chronic psychological stress is a risk factor for cardiovascular disease (CVD). In addition, acute psychological stress is asssociated with factors that explain the development of atherosclerosis; endothelial dysfunction, inflammatory reactivity and oxidative stress. The American Psychological Association has provided evidence that 20% of Americans report extreme stress and 80% report that their stress levels have increased over the past year . Additionally, over the past 5 years, 60% of Americans have attempted to reduce their stress, with just 7% reporting success in reducing stress . Examinations of acute responses to psychological stress provide insight into the potential mechanisms that may explain the relationship of psychological stress to CVD. Greater understanding can also provide support for considering therapeutic alternatives that may alleviate the ill effects of stress.This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. Important to our understanding of the development of CVD is how the benefits of physical activity in attenuating the cardiovascular stress response  may also support a reduction in the incidence of stroke and myocardial infarction. Finally, in light of the high prevalence of overweight and obesity  and hypothalamic pituitary adrenal (HPA) axes, and the parasympathetic (PNS) and sympathetic nervous system (SNS) pathways in the body. Acute psychological stress has been shown to elicit increases in the secretion of epinephrine (EPI) and norepinephrine (NE) from the SA axis  met criteria for depression and reported posttraumatic stress disorder symptoms, respectively , hydrogen peroxide (H2O2), and hydroxyl radical (OH\u2212)] , leading to oxidative stress ] Sies, . In heal)] Sies, . When RO)] Sies, . FurtherResearch has previously shown that psychological stress may contribute to the development of atherosclerosis by eliciting an elevation in ROS, which can further induce oxidative DNA damage  and interleukin-6 (IL-6) Ross, . NotablyEpidemiological evidence consistently shows that the benefits of physical activity and fitness on physiological and psychological health. One of the purported benefits associated with aerobic fitness is the attenuation of the cardiovascular response during psychological stress and recovery  was found in patients with coronary heart disease following aerobic exercise training  at rest and in conjunction with resistance exercise has become an increasingly attractive method in which to examine cardiovascular reactivity. BFR training has been shown to increase muscle strength and hypertrophy by restricting blood flow proximal to the exercising muscle resulting in blood pooling and a restriction of venous return  following exercise  and depression, and these stress related disorders have been found to lead to an increased risk of CVD and mortality  via activation of nuclear factor-kappa B (Bouloumie et al., Another potential mechanism to explain stress-induced endothelial dysfunction in obesity is the interactions of leptin with oxidative stress and inflammation. Leptin, an adipocyte-derived hormone, plays an important role in metabolism, adiposity, and vascular inflammation, and has been implicated in the development of coronary heart disease (Wannamethee et al., The studies that have been conducted examining the effect of physical activity on cardiovascular reactivity and CVD generally support Dienstbier's physiological toughness hypothesis Furthermore, aerobic exercise training has been shown to defend against ROS-induced lipid peroxidation and to decrease the occurrence of ROS-associated diseases such as CVDs and Alzheimer disease (Mattson and Wan, Finally, the interaction of obesity and psychological stress on the development of CVD is not fully understood. Future examination of the mechanisms contributing to endothelial dysfunction and the links between obesity, psychological stress and CVD will undoubtedly lead to the development of more specific and effective strategies, such as physical activity training, to address the ill effects of stress on CVD.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Widespread urbanization over the next 20 years has the potential to drastically change the risk of malaria within Africa. The burden of the disease, its management, risk factors and appropriateness of targeted intervention across varied urban environments in Africa remain largely undefined. This paper presents a combined historical and contemporary review of the clinical burden of malaria within one of Africa's largest urban settlements, Nairobi, Kenya.A review of historical reported malaria case burdens since 1911 within Nairobi was undertaken using archived government and city council reports. Contemporary information on out-patient case burdens due to malaria were assembled from the National Health Management and Information System (HMIS). Finally, an audit of 22 randomly selected health facilities within Nairobi was undertaken covering 12 months 2009-2010. The audit included interviews with health workers, and a checklist of commodities and guidelines necessary to diagnose, treat and record malaria.From the 1930's through to the mid-1960's malaria incidence declined coincidental with rapid population growth. During this period malaria notification and prevention were a priority for the city council. From 2001-2008 reporting systems for malaria were inadequate to define the extent or distribution of malaria risk within Nairobi. A more detailed facility review suggests, however that malaria remains a common diagnosis  and where laboratories (n = 15) exist slide positivity rates are on average 15%. Information on the quality of diagnosis, slide reading and whether those reported as positive were imported infections was not established. The facilities and health workers included in this study were not universally prepared to treat malaria according to national guidelines or identify foci of risks due to shortages of national first-line drugs, inadequate record keeping and a view among some health workers (17%) that slide negative patients could still have malaria.Combined with historical evidence there is a strong suggestion that very low risks of locally acquired malaria exist today within Nairobi's city limits and this requires further investigation. To be prepared for effective prevention and case-management of malaria among a diverse, mobile population in Nairobi requires a major paradigm shift and investment in improved quality of malaria diagnosis and case management, health system strengthening and case reporting. The intensity of malaria transmission in urban settlements of Africa is often considerably lower than the immediate peri-urban and rural surrounds -7 and drAfrica is expected to experience rapid rates of urbanization with 54% of Africans living in urban areas by 2030 . This haPlasmodium falciparum sporozoite stage in the salivary glands of the mosquito vector; however windows of transmission potential do exist within an average year and vary between years. The temperature limiting effects of transmission in Nairobi have largely underpinned the recent controversy on the likelihood of transmission of malaria within Nairobi and whether clinical malaria can be acquired within the city limits . Studies of human infection prevalence among communities in the early 1980's [P. falciparum infection prevalence between 2 and 14%. The specific identification of locally acquired versus imported infections has not been established and no study has identified sporozoite positive adult vectors in the city since the 1920s [The possibility of locally acquired malaria infections in Nairobi remains a moot issue. y 1980's  and schoy 1980's  from loche 1920s . As suchhe 1920s  though aDZ and RWS have received honoraria from Novartis Pharma for presenting and chairing, respectively, at their national malaria control programme best practice workshops in Africa. All other authors declare no competing interests.SAM and RWS designed the study. SAM undertook the data collection and record reviews and wrote the first draft of the manuscript. EAO, AMN and DZ provide scientific guidance at the design stage and in the analysis of the primary data. EJ and SAO provided help and stewardship in collecting the facility level data. All authors contributed to the writing and completion of the final manuscript."}
+{"text": "Dear Sir:Your publication of the assessment of Zambia's National Malaria Control Program by Elizabeth Chizema-Kaweshia and othersBetween 2005 and 2008, Zambia applied Integrated Vector Management to malaria prevention and control. The results showed measurable improvements in the successful prevention and advancement of malaria control in Zambia. However, the authors did not acknowledge achievements and compare lessons learned from other African countries recording similar success with malaria control programs. There is a lack of data regarding capacity building for health communication among indigenous people in Zambia."}
+{"text": "Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphoshatemia and inappropriately elevated serum parathyroid hormone (PTH) level due to end-organ resistance of biological activity of parathyroid hormone. It is due to epigenetic change at the GNAS locus and is divided into types Ia, Ib, Ic and II. We hereby describe the first reported case of pseudohypoparathyroidism type Ib Hong Kong."}
+{"text": "The present study, therefore, was undertaken to examine the influence of histamine H1-receptor antagonist on mast cells activation by using an in vitro cell culture technique and fexofenadine hydrochloride (FEX).Allergic rhinitis is well known to be accompanied by inflammatory responses in the nasal wall and lumen including predominant infiltration of eosinophils, T cells and mast cells. With the discovery of IgE as the link between allergen exposure and mediator release, mast cells established their role as effector cells in the development and maintenance of allergic diseases. However, the influence of histamine HSpleen cells obtained from BALB/c mice were cultured for 3 weeks in the presence of FEX, and the number of mast cells was counted with alcian blue. We also examined the influence of FEX on mast cells activation. Cultured mast cells were sensitized with OVA-specific IgE and these sensitized cells were stimulated with OVA in the presence of FEX for 4 hours. The levels of tumor necrosis factor (TNF)-\u03b1, vascular endothelial growth factor (VEGF) and keratinocyte-derived chemokine (KC) were examined by ELISA.FEX could not suppress mast cell growth from progenitor cells in spleen cell suspension, even when 500 ng/ml of the agent was added to cell cultures. On the other hand, treatment of mast cells with FEX caused suppression of factor production from mast cells by antigenic stimulation. The minimum concentration of the agent that caused significant suppression was 200 ng/ml.The present results strongly suggest that FEX exerts inhibitory effects on mast activation and results in favorable modification of clinical status of pollinosis patients."}
+{"text": "This presentation will focus on the variations in SBIRT program activities and work flow by three performance site types: (1) Emergency Departments; (2) Inpatient Hospitals; and (3) Outpatient Clinics. Descriptions of the service providers involved in the various SBIRT service components are presented.The Substance Abuse and Mental Health Services Administration (SAMHSA) sponsored a cross-site evaluation of the grantees of their Screening, brief intervention, and referral to treatment (SBIRT) program for alcohol and other drugs funded in 2008. As part of this evaluation, the cross-site evaluation team was tasked with understanding the implementation and service delivery protocols and work flow processes related to SBIRT service delivery. SBIRT programs have been implemented in a variety of different settings and performance sites, and each has adjusted the flow of SBIRT services to meet the needs of the particular settingFindings were based primarily on observations of program delivery and reviews of grantee-provided data sources , were supplemented with the qualitative analyses of semi-structured interviews with key SBIRT staff. Data extraction techniques were used to review the grantee-provided data sources. Qualitative analyses were conducted using ATLAS.ti software to examine relevant code combinations regarding SBIRT service delivery components and service provider characteristics..The synthesis of the grantee based document review data and qualitative analyses of semi-structured interview data will be presented. Work flow charts will be developed by performance site type depicting the most common work flow elements with variations in separate boxes. Commonalities and variations in SBIRT work flow processes will be discussed in this presentation.Based on the \u201ctypical\u201d SBIRT work flow processes, recommendations for initial program development will be discussed for those seeking to establish SBIRT services within various settings and performance sites"}
+{"text": "After two decades of research, the neurosciences have come a long way from accepting that neural stem/progenitor cells (NSPCs) generate new neurons in the adult mammalian hippocampus to unraveling the functional role of adult-born neurons in cognition and emotional control. The finding that new neurons are born and become integrated into a mature circuitry throughout life has challenged and subsequently reshaped our understanding of neural plasticity in the adult mammalian brain. It is now widely accepted that neurogenesis in the adult central nervous system occurs in multiple brain regions within the rodent brain, including the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG). Since the discovery of ongoing neurogenesis in the adult brain, the field has been addressing questions regarding the cellular identity of adult NSPCs, the molecular pathways regulating maturation and integration of newborn neurons into preexisting circuitries, and how new neurons contribute to adult brain function. Technological advances over the last two decades such as targeted modulation (loss- and gain-of-function) of adult neurogenesis and refinements in behavioral testing paradigms have enabled us to begin addressing these questions directly. Here we give a brief overview of old and new studies examining the function of adult hippocampal neurogenesis (AHN) in the context of evolving technology, which has exponentially expanded our understanding of the neurogenic process in the adult mammalian brain.Early on, the field went through a phase of correlating levels of AHN with performance in behavioral tests of hippocampus-dependent learning and memory, and affective behavior. Manipulations that increase AHN such as environmental enrichment, physical activity, and also treatment with certain antidepressants were found to enhance performance in spatial navigation tasks  and in tests of anxiety-related behaviors  , resulting in substantially enhanced levels of AHN  enhances discrimination between similar contexts in a contextual fear-conditioning task (Sahay et al., Significant advances in conditional gene targeting allowing the generation of transgenic mice and virus-based approaches enabled the selective targeting of adult hippocampal NSPCs and their neuronal progeny, and revealed not only the molecular pathways important for the different stages of neurogenesis, but also specific behavioral correlates of altered AHN (Saxe et al., Recent reports also support a role for AHN in emotional control and affective behavior. These studies benefitted not only from novel methods to ablate AHN, but also refinements in testing paradigms for specific aspects of emotion-related behaviors (Samuels and Hen, how exactly newborn neurons shape the DG circuitry and mediate DG-dependent pattern separation. A large number of open questions remain: how are individual patterns represented in the DG (Deng et al., Accumulating evidence over the last years has clearly demonstrated a role for AHN in hippocampus-dependent cognition and emotional control. However, it is currently unclear Be that as it may, the finding that the adult mammalian brain continuously generates new neurons throughout life has contributed significantly to our understanding of brain functioning and recent technological advances provide further impetus for studying the function of AHN in health and disease."}
+{"text": "Dear Editor,Chronic hepatitis C virus (HCV) infection is the major cause of liver disease related to high morbidity and mortality in hemophilic patients who needs regular blood product administration. AlthoughThe article titled; Distribution of hepatitis C virus genotypes in Iranian patients with congenital bleeding disorders, revealed the genotype distribution of HCV in Iranian hemophilic patients. In this This work has enriched the data of genotype distribution in different areas. Nevertheless, genotype is an important parameter used in selecting an antiviral therapy and genotyping and subtyping of HCV is relevant to the epidemiology of HCV, I believe this article may give some suggestive help in clinical management against chronic HCV infection."}
+{"text": "To document and assess cross-facility differences in the planning, implementation and current characteristics of chiropractic services in VA.Observational comparative case study approach using data collected via semi-structured key stakeholder interviews and abstracted from policy documents and other material. Six VA facilities delivering chiropractic services on-station were studied. Transcripts and documents were coded and analyzed via directed content analysis.One hundred and sixteen stakeholder interviews and 75 source documents were analyzed. The six chiropractic programs varied in terms of methods and patterns of patient access , chiropractor appointment type , level and nature of the clinic\u2019s integration with other clinical programs and services , and other features. Non-DC clinicians expressed diverse views on the appropriateness of chiropractic services, yet most were favorable. These clinicians displayed limited knowledge of the current evidence on managing non-operative spinal conditions and the components of chiropractic case management, however. VA facility staff identified professional and interpersonal attributes of the DC clinicians as important facilitators of clinic status and integration. Chiropractors varied in their professional attributes and self-perceived degree of successful integration. Other variations in planning, implementation and clinic features were identified.VA facilities varied in the manner in which they planned and implemented new chiropractic care programs and in the features of the clinics as established. The findings from this study and may offer policy and practice leaders important insights into effective strategies for managing new clinical program implementation. This study provides a framework for studying the introduction of new clinical services to VA and other healthcare systems."}
+{"text": "The use of radiation in the medical practice has evolved since its beginning and 30% to 50% of medical decisions are affected by radiologic examinations.23The European Commission (EC) and National Radiation Protection Board (NRPB) have been collected some guidelines about radiation protection in dentistry.4This cross-sectional questionnaire-based study was conducted between September 2008 and February 2009. A questionnaire was conducted regarding EC and NRPB recommendations about radiation protection in dental radiography. The radiology departments of all dental school of Iran (18 schools) surveyed in this study.Agreement of the results with some recommendations of EC and NRPB are shown in The findings about radiation protection principles observance in dental radiography point to a slightly better situation than those mentioned by former similar studies in Iran.The current survey emphasizes on the need for further consideration of radiation protection principles, especially on the field of quality control and quality assurance programs, in dental schools of Iran. If quality control and quality assurance problems are corrected, the situation can be improved."}
+{"text": "Dear Sir:The success of the malaria control efforts occurring in Zambia6Furthermore, we agree that improving communication is an enabling factor for success. This is important both centrally to coordinate planning among malaria control partners and peripherally to improve the uptake of interventions in communities and households. The Zambia National Malaria Control Program (ZNMCP) coordinated centrally through the Ministry of Health's National Malaria Control Center has developed a vibrant system of national technical working groups across all the major strategic areas of the malaria program. This is arguably one approach to communication capacity building among those managing national malaria control activities. These groups bring together management and implementing staff within the Ministry of Health and partners and encourage dialogue for a coordinated approach. This approach also encourages collective continuity for strategic priorities in an environment where funding flows and dedicated staffing can be intermittent.At community level, the ZNMCP supports strategic community leader engagement through focused trainings on malaria, malaria interventions, and the importance of leveraging their leadership positions to control the disease. The ZNMCP also targets focused malaria control messages toward \u201cend-users,\u201d those communities and populations at risk of malaria. These messages include the importance of using interventions, recognizing the symptoms of malaria, getting tested and knowing the test results, and seeking treatment early if infected. These messages are channeled through what we believe are the most effective methods of communicating to populations at risk of malaria and include interpersonal communication, through local health workers, community leaders and community advocates, and mass media channels, especially community radio. Influencing these channels of communication is developing local-level capacity to engage in malaria control activities and contributes to local-level success in malaria control."}
+{"text": "Complementary and alternative medicine (CAM) is subject to heated debates and prejudices. Studies show that CAM is widely used by psychiatric patients, usually without the guidance of a therapist and without the use of a solid working method, leading to potential health risks. How can we use CAM alongside conventional psychiatry in an outpatient psychiatric clinic in a judicious and professional way?By searching through scientific and legal articles and discussion in focus groups a scientific model was formulated based on (1) patients\u2019 needs and wishes; (2) respect for their freedom of choice; (3) a mix of western medicine and CAM that are safe and effective; (4) protection against quackery and abuse; (5) Dutch law, the jurisprudence of the Medical Disciplinary Tribunal and the rules of the Dutch Association of Medical Practitioners (KNMG) and (6) scientific evidence.In the Centre for Integrative Psychiatry (CIP) of Lentis in the Netherlands some carefully selected CAM are offered under strict conditions, alongside conventional treatments. Because of the controversy and the potential health risks, Lentis designed a protocol which is presented. A clinical vignette is used to illustrate how this applies to daily practise.The Dutch CAM protocol provides a working method for the judicious use of CAM alongside conventional psychiatry in an outpatient psychiatric clinic."}
+{"text": "The success of national malaria control strategies is increasingly recognised to be limited by the capacity of the health system to deliver interventions at the required levels of coverage and quality . It is cWe systematically reviewed the sequential process of and barriers to, malaria case management through primary health care in sub-Saharan Africa. We thus developed community effectiveness and decision tree models to case management in the public sector. Articles published since the rollout of ACTs were used to obtain a range of estimates for malaria management steps. Parameters were sampled from between these ranges of estimates and used to inform the two models. We then explored scenarios of lifting different case management barriers.The decision analysis model more accurately reflected reported levels of appropriate management of fever  in the public sector (>60% attendees), compared with a systems effectiveness approach (<2%). Scenarios of perfect case management steps all improved correct fever management using both models, except in the case of perfect ACT stock; a decision tree approach predicted a 12% reduction in correct management of all cases compared with a 63% increase with the community effectiveness approach.Using the decision-tree model, increases in availability and rapid diagnostic tests (RDTs) improved overall management of fever upto 65% of all attendees, and reduced overtreatment of NMFI with unnecessary antimalarials by over 35%, but did not substantially improve appropriate treatment rates of malaria cases. The greatest impact on the proportion of malaria cases correctly treated resulted from improving ACT stock (over 65% increase from baseline), even without increased RDT use. Under conditions of perfect availability and use of RDTs, test adherence and drug availability appropriate treatment rates rose to over 85%.The relationship between improving delivery through health systems and resulting impact on health outcomes of infectious diseases is not straightforward, however simple decision analysis models can provide insight into which aspects of delivering care are most likely to impact on care quality and treatment effectiveness. Unlike the community-effectiveness framework, the decision-tree approach accounts for clinical (non-RDT guided) treatment of malaria, under-diagnosis of malaria and unnecessary antimalarial use in NMFI cases, which are all of policy interest impacting on health outcomes and ongoing transmission. Further work into the amenability of health systems to change is required to explore the most cost-effective targets in expanding the delivery of antimalarials."}
+{"text": "The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioral repertoires at the core of affective disorders and ADHD. Behavioral adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o) and its modulation of M1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signaling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial, recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behavior and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone. A number of features, such as genetic vulnerability factors, high degree of overlapping comorbidity, cortisol impaired hippocampal function as a result of trauma, cognitive deficits and response to SSRIs are shared by the spectrum of mood and anxiety disordersIf the hippocampal theta rhythm is associated with increased activity within monoaminergic projection neurons and is the putative basis for encoding of declarative memories within the neocortex, what is the evidence for limbic or paralimbic activation of the cholinergic basal forebrain? Is there a physiological index of implicit affective processes, including the formation of prepotent behavioral repertoires that are predicated on muscarinic signaling?There are some limited tracing studies looking at afferent cortical input to the basal forebrain and the nucleus Basalis of Meynert, in particular. One of the most prominent inputs is the anterior agranular insula , in other words a self-selecting mechanism. Convergence of signaling recruits glutamatergic receptors including those of NMDA and the motivational modulation mediated by mesolimbic dopamine systems. For example D3 dopamine receptor does interact with NMDAR and increases Akt phophorylation  levels induce dysphoric symptoms, particularly in those so predisposed  in a 64 year-old woman with chronic intermittent depression on maintenance electroconvulsive treatment (ECT)  and LHb inhibit firing of a serotonergic raphe cells through GABAergic interneurons  induced disruptions of prepulse inhibition (PPI) in humans and in rat models  may result from exposure to extreme stressors such as childhood physical and sexual abuse and military combat. Complaints of cognitive disturbances especially memory and concentration are commonly reported. Objective deficits in declarative memory, verbal recall in particular, have corroborated this impression  is marked by emotional dysregulation, impulsivity together with instability in interpersonal relationships. It is often attributed to early adversity or abuse and associated with insecure parental attachment, although these factors are neither necessary nor sufficient. Subconsciously motivated outbursts of anger are automatically triggered by the presence of appropriate cues , a potent 5-HT2A/2C agonist, may have some positive mnemonic effects for the specific type of amnesia in patients with focal hippocampal damage. The literature provides some anecdotal instances of psychotomimetic efficacy in the treatment of mood disorder and in particular OCD (Zghoul and Blier, The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "To the Editor: West Nile Virus (WNV) is rapidly spreading in the Western Hemisphere , which includes Saint Louis encephalitis virus (SLEV) (in North and South America), Japanese encephalitis virus (Asia), and Murray Valley encephalitis virus  . None ofThese serologic data should be considered indirect evidence of WNV activity in Colombia. We encourage Colombian human and animal health authorities to enhance surveillance for human, equine, and avian disease attributable to WNV. Efforts are needed to isolate the virus or detect specific viral RNA to confirm this finding and to identify vectors and vertebrate hosts involved in WNV transmission in Colombia."}
+{"text": "Publishing research in open access (OA) journals ensures free and permanent unrestricted online access to peer-reviewed articles , and incHaving had success in biomedical and physics publishing, support continues to grow for open access in chemistry, in particular amongst the cheminformatics community. The range of benefits for authors and institutions makes open access a viable and effective publishing model for chemistry research.This poster provides an overview of the benefits of open access, and compares the OA model to traditional subscription journal publishing."}
+{"text": "The evaluated parameters were: the importance of patients' admission , microbial flora's record in the ICU before and after the implementation of CuDuring December 2010 and March 2011 and respectively during December 2011 and March 2012 comparative results showed statistically significant reduction on the microbial flora (CFU / ml) by 95% and the use of antimicrobial medicine (per day per patient) by 30%  as well as patients hospitalization time and cost.The innovative implementation of antimicrobial copper in ICUs contributed to their microbial flora significant reduction and antimicrobial drugs use reduction with the apparent positive effect (decrease) in both patients hospitalization time and cost. Under the present circumstances of economic crisis, survey results are of highest importance and value.None declared"}
+{"text": "Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in both men and women in developed nations. Gender and population differences in the prevalence, presentation and prognosis of CVD, as well as in the role of traditional risk factors in determining its risk have been increasingly recognized. Thus, multi-ethnic studies are necessary to fully understand the basis for optimal prevention and management of CVD.Cardiovascular imaging is a well-validated form of non-invasive diagnostic and prognostic testing. Coronary artery calcium (CAC), carotid intima-media thickness (IMT), and elevated left ventricular (LV) mass and geometry as assessed by cardiac magnetic resonance (CMR) offer highly specific phenotype data on the extend of CVD. Due to their high sensitivity, these modalities are increasing used to characterize CVD risk in clinically asymptomatic individuals. Noninvasive imaging of the heart and blood vessels has the potential to replace invasive angiography for the evaluation of ischemic and nonischemic cardiomyopathy. Computed Tomography (CT) angiography allows coronary vessels to be accurately assessed for stenosis. Magnetic resonance imaging (MRI) at 1.5 Tesla and 3 Tesla offers superior evaluation of myocardial structure, function and perfusion, as well as atherosclerotic plaque and tissue composition. In summary, new imaging techniques for the heart and blood vessels offer the potential for advanced tools for patient diagnosis. The application of advanced cardiac CT and MRI to study numbers of patients is underway in epidemiologic studies to help understand risk factor effects and genetic relationships ."}
+{"text": "Little is known about how to tailor implementation of mental health services in low- and middle-income countries (LMICs) to the diverse settings encountered within and between countries. In this paper we compare the baseline context, challenges and opportunities in districts in five LMICs  participating in the PRogramme for Improving Mental health carE (PRIME). The purpose was to inform development and implementation of a comprehensive district plan to integrate mental health into primary care.A situation analysis tool was developed for the study, drawing on existing tools and expert consensus. Cross-sectional information obtained was largely in the public domain in all five districts.The PRIME study districts face substantial contextual and health system challenges many of which are common across sites. Reliable information on existing treatment coverage for mental disorders was unavailable. Particularly in the low-income countries, many health service organisational requirements for mental health care were absent, including specialist mental health professionals to support the service and reliable supplies of medication. Across all sites, community mental health literacy was low and there were no models of multi-sectoral working or collaborations with traditional or religious healers. Nonetheless health system opportunities were apparent. In each district there was potential to apply existing models of care for tuberculosis and HIV or non-communicable disorders, which have established mechanisms for detection of drop-out from care, outreach and adherence support. The extensive networks of community-based health workers and volunteers in most districts provide further opportunities to expand mental health care.The low level of baseline health system preparedness across sites underlines that interventions at the levels of health care organisation, health facility and community will all be essential for sustainable delivery of quality mental health care integrated into primary care. The unmet need for mental health care is high in most low- and middle-income countries (LMICs) The decades of experience with attempts to integrate mental health care into PHC in LMICs have highlighted the challenges faced on the ground, particularly with respect to sustainability The Programme for Improvement of Mental health carE (PRIME) is operating in five LMICs  to provide evidence to support the implementation and scale-up of mental health care in primary care and maternal health care settings We conducted a systematic baseline situation analysis in each of the five PRIME study sites, to describe the country-specific and cross-country factors relevant to development and implementation of a district-level mental health care plan. In this paper, we present an analysis of common issues faced by the differently resourced PRIME country districts in order to highlight the challenges and opportunities for integrating mental health into primary care across settings.The PRIME program has been described elsewhere The PRIME countries were selected intentionally to represent diverse settings that would give information about the range of approaches needed to implement mental health care. See A cross-sectional situation analysis largely relying upon information available in the public domain and supplemented by contact with key officials and service heads.http://www.prime.uct.ac.za/index.php/research/tools.html). Existing methods and tools for appraising mental health systems and services in LMICs did not meet the needs of PRIME either due to reliance on primary research For the purposes of the PRIME project, we developed a new situation analysis tool  covered environmental, population, economic, health  and social indicators.Section I : national and local political support for mental health care, including budgets, policies, plans, legislation and welfare benefits, and details of the specialist mental health workforce at national level.Section II : prevalence of MNS disorders, numbers receiving care and estimated treatment coverage.Section III : general health services, including the available cadres of health professionals at each level in the system, specialist mental health services, with particular reference to elements of specialist mental health care needed to support PHC-based mental health care and delivery of the mhGAP packages Section IV : sociocultural aspects, relevant non-health sector organisations and awareness-raising activities.Section V : health information systems, and monitoring and evaluation of services.Section VI  predominated. Only in Dr KK district (South Africa) were MNS disorders among the top ten reasons for out-patient attendance. The burden of HIV was high in Dr KK district (South Africa)  and Kamuli (Uganda)  but was a much lower health priority in the other countries . Other notable public health issues burdening existing health services were outbreaks of dengue fever in Chitwan , undernutrition and reproductive health issues in Sodo (Ethiopia) and emerging NCDs in Kamuli (Uganda).The health system infrastructure varied across the PRIME districts, including the definition and scope of primary health care. See Pre-service training of PHC workers in mental health care was limited to a few hours or days in all districts except Dr KK district (South Africa) where it formed a substantial percentage of the training time (20%). No in-service training had been conducted in Sodo (Ethiopia) or Chitwan  districts. In Kamuli (Uganda), Sehore (India) and Dr KK district (South Africa), in-service training was sporadic and not comprehensive in terms of personnel.The full range of psychotropic medication recommended by the WHO, and included within the essential drug lists of all PRIME countries, was only available in PHC services in Dr KK district (South Africa). In Sodo (Ethiopia) and Sehore (India) districts, psychotropic medication was limited to antiepileptic medication and benzodiazepines (anxiolytic medication). In the low-income country sites the supply of psychotropic medications was considered to be unreliable. All districts except Sodo (Ethiopia) provided free access to medication at the PHC level, including psychotropic medication when available. In Sodo (Ethiopia) medication costs were mostly borne by patients and their families on an out-of-pocket basis. Primary care-based, non-physician health workers who had received appropriate training were permitted to prescribe psychotropic medication in all districts except Sehore (India), but not permitted officially to diagnose or treat mental disorders independently except in Kamuli (Uganda) See In-patient psychiatric care was unavailable in Sodo (Ethiopia) and Kamuli (Uganda) districts. Public sector services for people with alcohol disorders were only available in Chitwan  and Dr KK district (South Africa).Public sector psychological therapies were absent in the low-income country districts  and were limited to a small number of clinical psychologists and general counsellors in the middle-income country districts (in India and South Africa), although provision from NGOs and the private sector was better in these settings. Facility-based mental health rehabilitation services were only available in Dr KK district (South Africa).There was evidence of very limited delivery of mental health care in PHC settings across the country sites. In the Dr KK district (South Africa) PHC workers provided follow-up clinical care for people with chronic and severe mental health problems, including continuing the prescription of medication, psycho-education and some counselling. In the other country sites, when present, PHC activities were largely limited to identification of people with severe mental disorders and direct referral to specialist mental health services without any treatment intervention. For epilepsy, there was evidence of more active intervention within PHC, with initiation of prescribing of antiepileptic medication in Sehore (India) and Chitwan  and continuation of antiepileptic medication initiated by specialists in Sodo (Ethiopia). Interventions for depression and other common mental disorders in PHC were extremely limited across sites. Evidence-based psychological therapies  were not available in any of the PHC facilities in the PRIME districts except for DR KK district (South Africa) where problem solving and behaviour activation therapy was available from one psychologist.Information on treatment coverage for the PRIME priority MNS disorders was difficult to access and not generally considered to be reliable. Epidemiological estimates of community prevalence of the priority MNS disorders were available for the district neighbouring Sodo in Ethiopia See Most of the service organisation components considered important to support delivery of mental health care in PHC were absent from most districts. Specifically, there were no PHC worker training manuals, screening tools or guidelines for interventions for MNS disorders, mechanisms to register people with severe mental disorders and detect drop-out from care, supervision systems or monitoring and evaluation systems for mental health care in Sodo (Ethiopia), Kamuli (Uganda), Sehore (India) or Chitwan .Nonetheless, all districts had relevant models of PHC for chronic communicable disorders, specifically tuberculosis (TB) in all districts and HIV in most districts. Service characteristics for these conditions included adherence support and outreach for patients lost to follow-up. Disability payments were, in principle, available for people with severe mental disorders in Sehore (India), Chitwan  and Dr KK district (South Africa) but absent from the Ethiopian and Ugandan sites, although low levels of awareness of entitlement in Chitwan  meant that few eligible people benefitted in practice.The interface between mental health specialists and PHC was mostly limited to paper referrals from PHC to specialist care, except in Dr KK district (South Africa) where back-referrals from specialist care to PHC and face-to-face meetings with mental health specialists, including provision of supervision, were reported.See Stigma towards, and abuse of, persons with MNS disorders was noted in all PRIME districts, with research evidence from Ethiopia In Sehore (India), Sodo (Ethiopia) and Dr KK district (South Africa), paid community health workers formed a reasonably robust interface between facility-based PHC services and the community. Volunteer health workers were also present in most of the districts. In none of the sites were these community health workers engaged in mental health care.NGOs, faith-based organisations and community-based organisations were present in all districts, but were only working with persons with mental disorders in Kamuli (Uganda) and Dr KK district (South Africa), and with persons with substance use disorders in Chitwan  and Sehore (India). Self-help groups relating to MNS disorders were only present in Dr KK district (South Africa) for alcohol use disorders and in Kamuli (Uganda) for people with all types of mental disorders. Only in the Kamuli (Uganda) district was a community organisation working to improve the livelihoods of persons with MNS disorders The PRIME situation analysis tool provided systematic information on the context , the existing structures and systems to support integration of mental health care into PHC, and the challenges and potential opportunities in the five country sites. The PRIME study districts face substantial contextual and health system challenges in developing and implementing mental health care plans that will be able to deliver adequate services for people with priority MNS disorders in primary care. Although many difficulties were more pronounced in the low-income country settings, common challenges and opportunities were seen across the range of PRIME countries.A previous situation analysis A limitation of the PRIME study approach was that the situation analysis may not have given a fully accurate picture of the situation on the ground; for example, potentially under-estimating the numbers of people with MNS disorders already receiving care in PHC due to poor information systems. We attempted to overcome this limitation by triangulating sources of data and contacting key service co-ordinators and planners to provide clarification where possible. An additional limitation was that the PRIME situation analyses necessarily focused on readily measurable health system structures and, in the absence of previously published reports, were unable to give an in-depth understanding of attitudinal factors, for example, acceptability to PHC workers of task sharing mental health care. This will be addressed in other qualitative formative research, being conducted by the PRIME study Across all PRIME country districts, competing public health priorities, financial constraints and high levels of poverty and social deprivation are enormous challenges to the delivery of mental health care and define the context in which policy-makers and planners need to be engaged. Limited levels of community awareness and high levels of stigma and abuse also emerged as cross-country challenges requiring intervention in order to improve demand for services, retention in services and support for people with MNS disorders. Health system structures and systems to support mental health care were also largely absent; dedicated service co-ordinators and budget, reliable supplies of medications, decision-support tools for clinicians, and monitoring and evaluation mechanisms will all need to be introduced as part of a comprehensive and workable mental health care plan.Three other challenges seen across country sites will now be considered in greater depth: deficient information systems, lack of specialist mental health professionals and the feasibility of psychosocial care.Comprehensive information about treatment coverage for MNS disorders was lacking across all sites. Being able to track changes in treatment coverage for priority MNS disorders is essential for monitoring the impact of initiatives to implement and scale-up mental health care. Health system interventions to improve the recording and reporting of service utilisation are, therefore, needed alongside interventions to train PHC workers to deliver mental health care. Further research is needed to identify optimal service utilisation indicators for mental health care integrated into PHC in LMICs. The situation analysis also revealed the absence of information on the equitable distribution of treatment coverage; for example, for women, the poor and those living in rural areas. Poverty is an established determinant of MNS disorders, as well as a consequence of mental ill-health, meaning that persons with MNS disorders are often to be found amongst the poorest in society The scarcity of specialist mental health workers to support the delivery of mental health care by PHC workers was evident across all sites, except in some sub-districts of the Dr KK district (South Africa) that were relatively well resourced but still unable to meet the need. The acute shortage of mental health professionals across LMICs is well documented Going beyond the absolute numbers of mental health professionals, there is also the challenge of non-availability of a multi-disciplinary workforce trained to provide psychosocial care. Public sector psychologists, social workers, counsellors and support workers were in short supply. The evidence-based psychosocial interventions advocated within the mhGAP intervention guide may not be deliverable on the ground if appropriately skilled health personnel are not available to deliver and supervise such care. PHC nurses and community-based health workers have been shown to be able to provide effective circumscribed psychosocial interventions in LMIC settings A clear opportunity identified within each of the PRIME districts was the presence of existing services for chronic disorders. Depression and alcohol use disorders, in particular, have been shown to be highly prevalent in people with chronic infectious and non-communicable disorders The low level of baseline health system preparedness across sites underlines that interventions at the levels of health care organisation, health facility and community will all be essential for sustainable delivery of quality mental health care integrated into primary care. Such a multi-faceted approach will be evaluated in the implementation of the PRIME mental health plans.Table S1Data sources for the PRIME situation analysis.(DOC)Click here for additional data file."}
+{"text": "There is a rapidly growing body of evidence that production of microvesicles (MVs) is a universal feature of cellular life. MVs can incorporate microRNA (miRNA), mRNA, mtDNA, DNA and retrotransposons, camouflage viruses/viral components from immune surveillance, and transfer cargo between cells. These properties make MVs an essential player in intercellular communication. Increasing evidence supports the notion that MVs can also act as long-distance vehicles for RNA molecules and participate in metabolic synchronization and reprogramming eukaryotic cells including stem and germinal cells. MV ability to carry on DNA and their general distribution makes them attractive candidates for horizontal gene transfer, particularly between multi-cellular organisms and their parasites; this suggests important implications for the co-evolution of parasites and their hosts. In this review, we provide current understanding of the roles played by MVs in intracellular pathogens and parasitic infections. We also discuss the possible role of MVs in co-infection and host shifting. Production of membrane-enclosed microvesicles (MVs) is a universal feature of cellular life and has been demonstrated for organisms as diverse as Proteobacteria, Archaea, plants, and animals   in subsequent life cycle stages , and participate in delivery of virulence factors and regulation of parasite virulence   (manuscript in preparation). Figures P. falciparum short (119 amino acids) PEXEL (Plasmodium export element)-negative ring-exported protein 2 (Rex2) and the H. sapiens Rac1 and Rac2 proteins, providing one example of possible molecular mimicry and parasite-human HGT in parasitic invasion  , but also with plants and protozoa  the ability to transfer nucleic acids, including DNA; (2) the capability of MVs to protect and deliver genetic information to different organs, including reproductive organs in the case of multi-cellular organisms; and (3) the ability to transfer cargo to alien cells and tissues (in the case of parasites). Regev-Rudzki et al.  recentlyMVs are emerging as critical players in HGT including small non-coding RNAs. Major challenges in the field of extracellular vesicle research include (1) development of new comprehensive methods for their isolation and characterization, and (2) isolation of pure populations of specific MVs. Improved understanding of the mechanisms involved in vesicle shuttling of genetic information and proteins is crucial in order for new diagnostic and therapeutic strategies to be designed and implemented.Dissemination of parasite components with MVs provides (1) a unique advantage in protection against host-mediated immune responses and nucleases from blood and other body fluids, (2) the possibility of reaching distant regions and evading immune attacks due to their small size (<1 \u03bcm), and (3) the capability of transferring genetic information long-distance\u2014this may lead to direct participation of pathogenic components in the regulation of gene expression in the different host cells and metabolism synchronization between host and parasite, as well as HGT. This may contribute to further co-adaptation and co-evolution of the parasite and its host. Remarkably, MV exchange may happen similarly in dramatically different animal host cells, as well as in simple multicellular organisms. This can lead to broader host ranges and an increase in the virulence of certain parasites.Our present knowledge of MVs derived from parasites comes from studies involving limited numbers of parasites and hosts. In the future our understanding of how parasite-host exchange of regulatory molecules and genetic information happens may change, especially when taking into account interactions between multiple parasitic species within the same host organism.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD. Physical activity improves endothelial function both in healthy subjects and in patients with cardiovascular disease (CVD) (Volaklis et al., de novo engineered VEGF mimicking peptide, known as QK, acts in the same biological way of VEGF, improving capillary formation both in vitro and in vivo (Santulli et al., In 1997 Asahara and colleagues first isolated and characterized putative EPCs from human peripheral blood, and established their ability to form clusters of round cells on fibronectin-coated dishes (Asahara et al., in vitro and in vivo (Galasso et al., Physical activity is a potent inductor of EPCs mobilization from the BM niche and promotes homing of these cells to sites of ischemia (Leosco et al., In human setting of stable CAD, it was demonstrated that both 28 days of moderate exercise training and 12 weeks of running protocols led to reduced EPCs apoptosis and increased circulating EPCs levels (Laufs et al., EPCs have been hypothesized to realize a compensatory increase in patients with mild to moderate HF, in order to reduce vascular damage of impaired heart (Valgimigli et al., Additional studies confirmed that aerobic physical exercise exerted beneficial effects on EPCs number and activity also in patients with PAD. Indeed, it was analyzed the mobilization of EPCs, after 4 weeks of daily aerobic exercise, in three randomized controlled studies, including PAD patients, PAD patients after successful revascularization, and stable CAD patients, and the results showed a significant increase in EPCs blood count, in particular in PAD patients subgroup (Sandri et al., Improvement of EPCs number and pro-angiogenic activity represents an innovative target to counteract negative effect of aging and CVD. Several researches show that physical activity, performed as part of an exercise-training program, results in a significant increase in circulating EPCs levels and function. Accordingly, significant improvement of endothelial function has been demonstrated in patients with CVD who experienced exercise training. Indeed, EPCs mediated neovascularization could represent a useful way to get a therapeutic revascularization of ischemic areas in patients with endothelial dysfunction and high cardiovascular risk (Isner and Asahara, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "This paper presents a study which holistically examined the innovation processes experienced by the Republic of Kiribati in their adoption of a comprehensive IPCP innovation package.A case study methodology was used to explore IPCP adoption. Data sources and analysis included: 1) Chronological and thematic analysis of IPCP documentation and assessments performed by local staff and external agencies/consultants, and 2) semi-structured interviews with local key informants and external agencies  with thematic analysis. Analysis was informed by the Diffusion of Innovations for Organisations framework.agenda-setting: preparations for severe acute respiratory syndrome (SARS) in 2003 stimulated the identification of organisational IPCP deficits, and 2) matching: IPCP deficits were identified and the decision to adopt an IPCP innovation package was made. Implementation included three stages: a) redefining/restructuring: identification of the components of an IPCP and how they best fit with the local health structure, b) clarifying: integration of IPCP into the health services and defining an infection control role within the nursing division and, c) routinising: the IPCP became an ongoing element in health service delivery.Identification of the two key activities of the innovation process for organisations, initiation and implementation (of the IPCP) was achieved. The initiation activity included two stages: 1) The adoption of the IPCP followed the classic Diffusion of Innovations Process for Organisations. This process can serve as an IPCP adoption model in other low- and middle-income healthcare settings.None declared."}
+{"text": "Obesity is a metabolic disorder developed by overnutrition and a major cause for insulin resistance and cardiovascular events. Since adipose tissue is one of the major sites for the synthesis and secretion of cytokines, enlarged adipose tissue in obese condition alters inflammatory state leading to pathophysiological conditions such as type 2 diabetes and increased cardiovascular risk. A plausible theory for development of metabolic dysregulation is that obesity increases secretion of inflammatory cytokines from adipose tissue and causes a chronic inflammation in the whole body. Additionally accumulation of lipids in non-adipose tissues elevates the cellular levels of bioactive lipids that inhibit the signaling pathways implicated in metabolic regulation together with activated inflammatory response. Recent findings suggest that obesity-induced inflammatory response leads to modulation of sphingolipid metabolism and these bioactive lipids may function as mediators for increased risk of metabolic dysfunction. Importantly, elucidation of mechanism regarding sphingolipid metabolism and inflammatory disease will provide crucial information to development of new therapeutic strategies for the treatment of obesity-induced pathological inflammation. Obesity is an outcome of overnutrition, less exercise, and sedentary lifestyle. Outcomes of obesity include cardiovascular disease (CVD), diabetes, and hyperlipidemia and contribute to increased mortality and morbidity after myocardial infarction and related complications in diabetic compared with non-diabetic patients  in adipocytes in response to overnutrition and releasing these stored lipids during fasting. However, the notion that adipose tissue produces and releases various cytokines, termed \u201cadipokines,\u201d represents this is an active inflammatory organ. The fact that adipose tissue is an active inflammatory organ was initiated from the findings that adipose tissue has increased expression of tumor necrosis factor-\u03b1 (TNF\u03b1) in obese human compared with lean individuals  act as signaling molecules regulating various physiological events such as cell proliferation, apoptosis, and inflammation  followed by a series of reactions involving the enzymes 3-ketosphinganine reductase, ceramide synthase (CerS), dihydroceramide desaturase (DES). Another pathway to produce ceramide is through hydrolysis of sphingomyelin (SM) by acid or neutral sphingomyelinase (SMase)  had improved insulin sensitivity and dexamethasone-induced insulin resistance was prevented  is increased in the obese mice and the lack of JNK showed improved glucose metabolism   also have increased cardiac ceramide and heart failure markers  is a major modulator to maintain vascular function (Steinberg et al., Obesity manifests in developed countries and contributes to the prevalence of insulin resistance and cardiovascular risk. As a result, obesity-induced inflammation had placed the adipose tissue at the center of inflammation-related pathophysiology. When storage capacity of adipose tissue exceeds its limit for fat deposition, spillage of FFA and adipokines alters inflammatory states in various tissues causing etiology of type 2 diabetes and vascular disease Figure . Due to The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Measurement of toe and ankle blood pressure is used to evaluate the peripheral arterial status of patients, yet the pre-test rest period is inconsistent in published studies and among practitioners, and could affect results. The aim of this systematic review was to evaluate all research that has investigated the effect of different periods of pre-test rest on toe and ankle systolic blood pressure.MEDLINE (from 1946), EMBASE (from 1947), CINAHL (from 1937), and Cochrane Central Register of Controlled Trials (CENTRAL) (from 1800) were searched up to April 2012. No language or publication restrictions were applied. Eighty-eight content experts and researchers in the field were contacted by email to assist in the identification of published, unpublished, and ongoing studies. Studies evaluating the effect of two or more pre-test rest durations on toe or ankle systolic blood pressure were eligible for inclusion. No restrictions were placed on participant characteristics or the method of blood pressure measurement. Outcomes included toe or ankle systolic blood pressure and adverse effects. Abstracts were independently assessed by two reviewers for potential inclusion.1658 abstracts were identified by electronic searching. Thirty three of the 88 content experts and researchers in the field replied, identifying five potentially relevant studies. No studies were eligible for inclusion.There is no evidence of the effect of different periods of pre-test rest duration on toe and ankle systolic blood pressure measurements. Rigorous trials evaluating the effect of different durations of pre-test rest are required to direct clinical practice and research."}
+{"text": "Violaceae) so far examined, and in a few species of the coffee family (Rubiaceae).Cyclotides are disulfide-rich miniproteins with the unique structural features of a circular backbone and knotted arrangement of three conserved disulfide bonds. These features make them exceptionally stable and they have applications as plant defense  agents and stable drug frameworks. So far they have been found mainly in two plant families, including in every species of the violet family (We optimized the cyclotide screening protocol using MALDI-TOF/TOF and two dimensional nano LC-MS/MS followed by manual and automated peptide sequence assignments. Biological analysis was carried out by collagen uterine contractility assays and pharmacological data were generated by competitive displacement binding and functional GPCR luciferase assays.Oldenlandia affinis as an uterotonic agent, we have tested and identified cyclotides with oxytocin-like activity and identified the oxytocin receptor, as representative member of the GPCR family, as a molecular target of cyclotides.Using the rapid cyclotide discovery workflow, we analyzed >300 flowering plant species and confirmed the presence of cyclotides in several plant families. On the basis of the phylogeny of cyclotide-bearing plants and the analysis of precursor gene sequences, we have refined the current hypothesis of the evolution of circular plant peptides. Based on the traditional usage of the plant Cyclotides are interesting targets for pharmaceutical applications due to their unique structural framework, their bioactivities and sequence diversity. Based on their predicted number of tens of thousands, which potentially makes them one of the largest protein families within the plant kingdom, they constitute an immense combinatorial library of natural peptides, which is accessible for drug discovery."}
+{"text": "This is the results of Trivandrum Oral Cancer Screening study (TOCS) initiated in 1996 and the Trivandrum Breast Cancer Screening study (TBCS) initiated in 2006. The objective of TOC study is to evaluate the efficacy of oral cancer screening by visual inspection of the oral cavity in detecting early stages of oral cancer and in reducing mortality. Control and intervention groups have been followed up for over 16 years. Visual screening for oral cancer was found to have acceptable sensitivity and specificity, associated with detection in early stages, associated with 34% reduction in oral cancer mortality, highly cost-effective and can be readily integrated into routine care.The TBCS study had the objective of evaluating the efficacy of breast cancer screening to reduce incidence of advanced breast cancer, increase survival and reduce mortality due to breast cancer. The intervention group received health education, regular clinical breast examination and early access to diagnostic procedures. Early stage cases, node negative cases and those who underwent conservative surgery were more among the intervention group."}
+{"text": "Digital breast tomosynthesis (DBT) has the potential to improve the accuracy of standard digital mammography (DM) . The TOMIntervention Women who consent to participate in the trial undergo standard two-view DM and DBT imaging of both breasts. Images are acquired in a single examination under the same degree of breast compression on a commercially available (Hologic) digital mammography system.Women (47 to 73 years old) recalled for further assessment after routine breast screening and women <50 years with a family history of breast cancer, attending annual mammographic screening. The primary outcome measure is the relative sensitivity and specificity of DM and DBT in the detection of early-stage cancers and subtle lesions, particularly in women with dense breasts. This will be evaluated in a retrospective reading study where readers at each centre conduct blinded independent reviews of anonymised DM, or DBT, or DM and DBT images of cases from other centres.The trial set-up has involved lengthy and complex legal negotiation with collaborating sites, the equipment manufacturer and the grant-awarding body. Designated readers from each centre have completed tomosynthesis training and recruitment has commenced.It should be noted that the negotiation of contracts and commercial agreements adds a considerable time burden to the set-up phase of multicentre trials."}
+{"text": "Hereditary non-polyposis colorectal cancer (HNPCC) is a hereditary cancer syndrome in which confirmed carriers of a gene mutation are at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing the decision-making of confirmed HNPCC carriers post-genetic testing about screening and disease management.The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of genetic counselling and DNA testing for HNPCC on individuals in high risk families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n=23) were subjected to re-analysis for the purpose of identifying key barriers to and/or facilitators of effective screening and disease management.Thematic analysis identified personal, health care provider and health care system as the dominant barriers to and facilitators of screening and disease management. Person-centered barriers/facilitators included (1) risk perceptions and decision-making and, (2) enduring screening/disease management. Provider barriers/facilitators were defined in terms of participant perceptions of physician awareness of the family history of HNPCC, knowledge of the disease and recommended screening/treatment protocols, and clinical management skills. The health care system barriers/facilitators were defined in terms of continuity of care and coordination of services among different providers.Individuals at high risk for HPNCC-related cancers often encounter multiple barriers to and facilitators of screening and disease management that go beyond the individual and family to the provider and health care system levels. The current organization and implementation of health care services for clients who are at high genetic risk of developing cancer is inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by health care providers with knowledge of inherited cancer, is necessary to maintain optimal health in these families."}
+{"text": "The optimal functioning of obstetric anesthesia circuit is a key element in the effectiveness of a hospital with a maternity activity since more than 80% of parturients benefits.To analyze dangerous situations that may prevent obstetric anesthesia circuit to ensure anesthetic management of the parturient in optimum safety conditions of care.Based on the functional analysis, the preliminary risk analysis (PRA) is constructed in five steps: cutting functional circuit obstetric anesthesia, identification of dangerous events, hierarchy of feared events, ranking functions, establishment of recommendations to reduce or accept the risk.2 and 88 to criticality C3. They must be action and risk control management of the residual risk for 24 of them. The main causes are related to preventable medical risk , managerial risk  and organizational risk . They are generally human error related to: patient characteristics , the incompleteness of medical records , the lack of protocol or protocols inadequate (obstetric anesthesia protocols), the failure of safety barriers (consultations and pre-anesthetic visit) and the difficulty of coordination exacerbated by local architecture and buildings.The RPA has identified 93 hazardous situations and 178 scenarios which 266 criticality scenarios to criticality CThe use of this tool for risk management from industry can develop an approach to improving patient safety in obstetric anesthesia.None declared."}
+{"text": "Begomovirus, family Geminiviridae) that infect sweet potato (Ipomoea batatas) around the world are known as sweepoviruses. Because sweet potato plants are vegetatively propagated, the accumulation of viruses can become a major constraint for root production. Mixed infections of sweepovirus species and strains can lead to recombination, which may contribute to the generation of new recombinant sweepoviruses.Monopartite begomoviruses . Co-infections and extensive recombination events were identified in Brazilian sweepoviruses. Analysis of the recombination breakpoints detected within the sweepovirus dataset revealed that most recombination events occurred in the intergenic region (IR) and in the middle of the C1 open reading frame (ORF).This study reports the full genome sequence of 34 sweepoviruses sampled from a sweet potato germplasm bank and commercial fields in Brazil. These sequences were compared with others from public nucleotide sequence databases to provide a comprehensive overview of the genetic diversity and patterns of genetic exchange in sweepoviruses isolated from Brazil, as well as to review the classification and nomenclature of sweepoviruses in accordance with the current guidelines proposed by the The genetic diversity of sweepoviruses was considerably greater than previously described in Brazil. Moreover, recombination analysis revealed that a genomic exchange is responsible for the emergence of sweepovirus species and strains and provided valuable new information for understanding the diversity and evolution of sweepoviruses. Ipomoea batatas, family Convolvulaceae) is one of the most important subsistence crops in developing countries and the third most important root crop after potato (Solanum tuberosum) and cassava (Manihot esculenta)  and corresponding iteron-related domains in the 5\u2032-terminal regions of the Rep gene (Rep IRD) of sweepoviruses. Presumed iteron and Rep IRD sequences are colored as follows, blue for the IYVV, SPLCV-ES and SPLCV-IT group; pink for SPLCV-US[Lou:24]; and green for SPLCESV. The three different Rep IRDs present in this study are shown in bold.Click here for fileSweepovirus information: Complete names and color representations of the pairwise sequence identity percentages  of the complete genome sequences of sweepovirus isolates reported here and those available in the public sequence databases. The isolates present in this study are shown in bold.Click here for file"}
+{"text": "Authors describe diagnostic dilemma of differentiating pyelonephritis with lymphomatous involvement of kidney in a known case of lymphoma. FDG uptake pattern was non-discriminatory and pyelonephritis diagnosed retrospectively on follow up study. Authors emphasize the importance of recognition of features and subtle clues of infection evident on CT component of PET-CT. Kidneys being the physiological route of excretion of F18-FDG pose significant problem while interpreting its involvement by focal or diffuse hypermetabolic lesions like malignancies and inflammatory processes. Physiological pelvicalyceal activity can be dealt with the help of intravenous diuretics, oral hydration, and delayed imaging. It is known that lesions of lymphoma with renal involvement are FDG avid and early identification of this pathology causing ARF is crucial for recovery of kidney function.1 To diffe"}
+{"text": "The 11th annual conference of The Australia & New Zealand Academy for Eating Disorders was held on 23-24 August 2013 at the Mercure Pullman Hotel Melbourne. 71 Oral papers and 11 Posters were presented following review of the Scientific Committee chaired by Professor Susan Paxton and Dr Beth Shelton and are published in this supplement. Over 400 delegates attended the conference.The Politics of the body and the body politic and Dr Joe Proietto; Why is it so difficult to maintain weight loss: is this failure related to binge eating disorder and bulimia nervosa? The conference also involved two Plenaries, I-Tools & the internet  and Interventions for the overweight client (Sue Byrne and Leah Brennan) as well as a case panel discussion featuring Susie Orbach, Anthea Fursland and Carolyn Costin.Keynote talks were by Dr Susie Orbach; Seven pre-conference workshops focussed on medical, nursing dietetic and psychological approaches to eating disorders. Susie Orbach\u2019s workshop addressed the interpersonal history and psychology of the body. Jennifer Gaudiani presented insightful and highly rated workshops on medical issues at both introductory and advanced levels. Andrew Wallis and Linsey Atkins provided insight into Family-based Therapy clinical practice."}
+{"text": "Alexander Tsai discusses a new research study by Karen Devries and colleagues, and comments on the possible impact on public health of the study's insights regarding the relationship between intimate partner violence and mental health.Please see later in the article for the Editors' Summary PLOS Medicine:This Perspective discusses the following new study published in doi:10.1371/journal.pmed.1001439Devries KM, Mak J, Bacchus L, Child J, Falder G, et al. (2013) Intimate Partner Violence and Incident Depressive Symptoms and Suicide Attempts: A Systematic Review of Longitudinal Studies. PLoS Med 10(5): e1001439. Karen Devries and colleagues conduct a systematic review of longitudinal studies to evaluate the direction of association between symptoms of depression and intimate partner violence.Declaration on the Elimination of Violence against Women, the global burden of violence against women still remains alarmingly high PLOS Medicine brings us one step closer toward understanding the mental health liabilities associated with violence against women. The public health impact of their contribution is substantial, given the lack of resources devoted to the prevention and treatment of mental disorders worldwide Steven Pinker Their article is not the first to summarize the impacts of various forms of violence and abuse against women on mental health Notably, Karen Devries and colleagues So what do these findings suggest for clinical practice, programming, or policies to prevent violence against women? If depression is causally related to violence, one might consider evidence-based collaborative care management of depression This particular gap in the literature redirects our attention to more systemic determinants of the excess burden of violence and depression among women. The simplified conceptual model depicted in A reduced form of this model might not be obtainable, but at the very least this model suggests that: (a) violence against women may have direct adverse effects on mental health, as suggested by Karen Devries and colleagues With regard to the conceptual model depicted in It would be imprudent to suggest that Rose's \u201chigh-risk\u201d strategy"}
+{"text": "A funding organization was incorrectly omitted from the Funding Statement. The Funding Statement should read: \"Funding support by the Bill and Melinda Gates Foundation (Disease Control Priorities 3 project). The employers of the authors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\""}
+{"text": "Acinetobacter baumannii was isolated sensitive only to polymyxin-E in the sample of tracheal secretions. An exchange of antimicrobial therapy was made, but the patient developed refractory shock and died.A 69-year-old woman underwent elective surgical repair of an abdominal aortic aneurysm. Intraoperative lesions were intestinal and splenic, requiring performing segmental bowel resection and splenectomy. By hemodynamic instability the patient was maintained on mechanical ventilation in norepinephrine and was transferred to the ICU. After 3 days she had fever, tachycardia, hypotension and anuria, with output fetid and purulent secretion by the tracheal tube. Chest X-ray showed opacity in the right lung; cultures were collected and cefepime initiated empirically for treatment of ventilator-associated pneumonia. We report the case of a patient with septic shock.Despite the upgrading of intensive therapies with the presence of increasingly prepared professionals and all of the technological and scientific developments that occurred in the last 10 years, sepsis remains a major challenge for contemporary medicine. Mortality rates may vary from 20 to 80%. Several factors contribute to this high mortality rate, such as the growing population of patients aged over 65 years with various chronic diseases, the most frequent use of invasive procedures, increased demand for immunocompromised patients and the development of nosocomial microorganism infections increasingly resistant to antimicrobial agents. Besides the pathophysiology, evidence substantiated that early intervention reduces mortality in severe sepsis and thus several ICUs have sought to improve the quality of clinical management of septic patients. In 2002, the Medical Society of Intensive American (SCCM) and European (ESICM) together with the International Sepsis Forum initiated the Surviving Sepsis Campaign (SSC). The SSC initiative was based on six strategies, including: implement surveillance sepsis; improve the early diagnosis and safety; establish protocols for treatment and early intervention; create programs continuing professional education; proposed therapy post-ICU; and develop global standards for intensive care.The emergence of antimicrobial-resistant microorganisms is a growing problem worldwide and this complicates the choice of empirical antimicrobials and can compromise the evolutionary outcome of patients."}
+{"text": "Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from  Plastics are widely used in modern life, and their unbound chemicals bisphenol A (BPA) and phthalates can leach out into the surrounding environment. BPA and phthalates have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and adverse health effects . BPA is i.e., specific for hemi-methylated sequences). DNMT2 may be involved in embryonic stem cells and potential RNA methylation. DNMT3A and DNMT3B are involved in active de novo DNA methylation at CpG sites. The early developmental period is thought to be the most susceptible to epigenetic insults because the DNA synthesis rate is high, and the elaborate DNA methylation patterning and chromatin organization required for normal tissue development is established at this time [Epigenetics is the study of heritable changes in gene expression occurring without changes in DNA sequence. Epigenetic mechanisms include DNA methylation, histone modifications , and expression of non-coding RNAs (including microRNAs). In mammals, DNA methylation patterns are established during embryogenesis through the coopearation of DNA methyltransferases (DNMTs) and associated proteins. DNMT1 is responsible for the maintenance of methylation patterns throughout DNA replication . The phenotypic alterations observed in male offspring rats exposed to DBP/BBP/MBP during the perinatal period had remarkable similarities with common human reproductive disorders, including cryptorchidism, hypospadias and low sperm counts [The impacts of phthalate exposure on human health have also been extensively reviewed and reported by the National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction . There im counts . The antm counts .Biomonitoring of BPA through human blood and/or urine testing may underestimate the total body burden of this potential toxicant. Sweat analysis should be considered as an additional method for monitoring bioaccumulation of BPA in humans. Induced sweating appears to be a potential method for elimination of BPA .In the Comparative Toxicogenomics Database , BPA andBisphenol A (BPA) and phthalates (DEHP/MEHP and DBP/BBP/MBP) are epigenetically toxic . The epiin utero and neonatal exposure to low doses of bisphenol A (BPA) and/or phthalates (DEHP/MEHP and BBP/DBP/MBP) may cause DNA hypermethylation/hypomethylation at CpG islands near gene promoter regions, histone modifications , and expression of non-coding RNAs, including microRNAs. These epigenetic marks can induce up/down alterations in gene expression that may persist throughout a lifetime. These permanent changes will result in adverse health effects such as neural and immune disorders, infertility, and late-onset complex diseases (cancers and diabetes). The transient exposure to BPA and phthalates of gestating female rats was further shown to be a transgenerationally differential DNA methylation of the F3 generation.The Exposure to endocrine disrupting chemicals such as BPA and phthalates is of particular concern in the context of development. Neonatal exposure of rats to BPA resulted in an increased incidence of prostate intraepithelial neoplasia, and the prostate tissues showed consistent methylation changes. For example, the phosphodiesterase type 4 variant 4 (Pde4d4) gene of the rat was found to have hypomethylation in the regulatory CpG island and an elevated expression in the adult prostate ,31. NeonHoxa10 gene in mouse in utero exposure model [in utero BPA treatment increased the expression of the developmental homeobox gene Hoxa10 in the uterus of female offspring at two weeks of age. This change in gene expression was associated with significant demethylation of specific CpG sites in both promoter and intron of the Hoxa10 gene. Genome-wide effects of BPA on DNA methylation in brain tissue have also been investigated. Maternal exposure to BPA was associated with either hypo- or hyper-methylation of the promoter-associated CpG islands in several loci in the fetal mouse brain [LAMP3) gene and repress the expression of LAMP3 gene [BPA has been shown to alter the methylation status of the re model . The in se brain . Gene-spMP3 gene .EZH2) level in human breast cancer MCF7 cells and mammary glands of six-week-old mice exposed to BPA in utero [in intro and in vivo, these changes were accomplished by an increase in histone H3 trimethylation at lysine 27, which is the main histone modification catalyzed by EZH2 and is typically associated with gene expression [BPA effects on histone modifications were found to increase expression of the histone methyltransferase Enhancer of Zeste Homolog 2 (in utero . Both inpression .Concerning microRNAs (miRNAs), BPA exposure of human placental cell lines has been shown to alter miRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. This resulted in both slower proliferation rate and higher sensitivity to the DNA damaging agent bleomycin . A mouseESR1 mRNA expression by BBP is related to aberrant DNA methylation in the promoter region of the receptor gene [INSL3) expression and testosterone production [As to phthalates, treatment of human breast cancer MCF7 cells with BBP led to the demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered tor gene . Maternaoduction .Molecular mechanisms that underlie the long-lasting effects of BPA and phthalates continue to be elucidated, and they likely involve disruption of epigenetic programming of gene expression during development. It will be important to determine whether epigenetic markers in more accessible tissues correlate with epigenetic markers in target tissues. Many studies strongly imply that exposures to endocrine-disrupting chemicals (EDCs) may have cumulative adverse effects on future generations, and that these effects could be mediated through epigenetic mechanisms .Finally, the transient exposure to a plastic mixture  of gestating female rats during the period of embryonic sex determination was shown to promote early-onset female puberty transgenerationally (F3 generation) and decrease the pool size of ovarian primordial follicles. Spermatogenic cell apoptosis was also affected transgenerationally, and differential DNA methylation of the F3 generation sperm promoter regions was found in all exposed lineage males .The hypomethylation of the mouse Agouti gene caused by exposure to BPA can be prevented by maternal dietary supplementation with a source of methyl group . HoweverThe growing evidence indicates that epigenetics holds substantial potential for developing biological markers to predict which chemicals would put exposed subjects at risk and which individuals would be more susceptible to developing disease. It is still important to note that the mechanisms by which environmental toxicants modulate the epigenetic landscape of individual cells are yet to be elucidated in order to better understand the biology of epigenetic alterations and the health effects of toxic exposures on these disease-associated epigenetic alterations. Better defined mechanisms will lead to better prediction of the toxic potential of environmental chemicals such as BPA and phthalates and allow for more targeted and appropriate disease prevention strategies.in vitro models must be considered. In this context, human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis [In human studies, the use of laboratory methods with enhanced precision, sensitivity and coverage will be required, so that epigenetic changes can be detected as early as possible and well ahead of disease diagnosis. New technologies available now allow for global analysis of epigenetic alterations and these may provide insight into the extent and patterns of alterations between human normal and diseased tissues. Appropriate ogenesis ,46."}
+{"text": "MGD maintains a comprehensive catalog of genes, functional RNAs and other genome features as well as heritable phenotypes and quantitative trait loci. The genome feature catalog is generated by the integration of computational and manual genome annotations generated by NCBI, Ensembl and Vega/HAVANA. MGD curates and maintains the comprehensive listing of functional annotations for mouse genes using the Gene Ontology, and MGD curates and integrates comprehensive phenotype annotations including associations of mouse models with human diseases. Recent improvements include integration of the latest mouse genome build (GRCm38), improved access to comparative and functional annotations for mouse genes with expanded representation of comparative vertebrate genomes and new loads of phenotype data from high-throughput phenotyping projects. All MGD resources are freely available to the research community.The Mouse Genome Database (MGD) ( The Mouse Genome Database (MGD) is the community model organism database resource for the laboratory mouse, a premier animal model for the study of genetic and genomic systems relevant to human biology and disease. Initially designed and implemented in 1994 to track genetic mapping data and to report on and describe mouse mutant phenotypes, MGD has grown to be the recognized authority for knowledge about mouse genes and as a comprehensive data integration site and repository for mouse genetic, genomic and phenotypic data derived from primary literature as well as from major data providers .The central mission of the MGD is to support the translation of information from experimental mouse models to uncover the genetic basis of human diseases. As a highly curated and comprehensive model organism database, MGD provides web and programmatic access to a complete catalog of mouse genes and genome features including genomic sequence and variant information. MGD curates and maintains the comprehensive listing of functional annotations for mouse genes using Gene Ontology (GO) terms and contributes to the development of the GO content and structure . Finallyhttp://www.informatics.jax.org). The MGI system includes the Gene Expression Database (MGD is a core component of an extensive set of genome informatics resources that collectively comprise the Mouse Genome Informatics (MGI) resource , improved access to comparative and functional annotations for mouse genes and new uploads of phenotype data from the Sanger Institute Mouse Genetics Program  and the ftp://ftp.informatics.jax.org/pub/mgigff/) to support the use of these data in bioinformatics applications.MGD maintains a comprehensive catalog of genes, functional RNAs and other genome features as well as heritable phenotypes and quantitative trait loci (QTL). As described previously , the MGDSingle nucleotide polymorphism (SNP) data in MGD were updated to NCBI dbSNP Build 137. With this update, all of the SNP and structural variation data from deep sequencing of 17 inbred strains of mice (Serpina1a (MGI:891971), where phylogenetic analysis shows five mouse genes and one human gene in the same orthology class  provides data through PMID 7811286 to assert through evidence code Inferred from Sequence Orthology that mouse Bmp4 has inferred molecular function \u2018BMP receptor binding\u2019 (GO:0070700)].Following the revision of the MGD representation of vertebrate orthology, the GO team at MGD implemented new rules for loading of Inferred from Sequence Orthology annotations from other vertebrate species. These annotations are only generated when the contributing annotation is derived from experimental results in the specific organism This article provides the general citation for use of the MGD resource. Please use the following format for citation when referencing data sets specific to the MGD component of the MGI resource: MGD, MGI, The Jackson Laboratory, Bar Harbor, Maine (URL:"}
+{"text": "This article aims to offer, on the basis of Coherence theory, the epistemological proposition that mutually supportive evidence from multiple systematic reviews may successfully refute radical, philosophical scepticism.A case study including seven systematic reviews is presented with the objective of refuting radical philosophical scepticism towards the belief that glass-ionomer cements (GIC) are beneficial in tooth caries therapy. The case study illustrates how principles of logical and empirical coherence may be applied as evidence in support of specific beliefs in healthcare.The results show that radical scepticism may epistemologically be refuted on the basis of logical and empirical coherence. For success, several systematic reviews covering interconnected beliefs are needed. In praxis, these systematic reviews would also need to be of high quality and its conclusions based on reviewed high quality trials.A refutation of radical philosophical scepticism to clinical evidence may be achieved, if and only if such evidence is based on the logical and empirical coherence of multiple systematic review results. Practical application also requires focus on the quality of the systematic reviews and reviewed trials. Object - Subject distinction and asks whether the objective world is subjectively knowable at all. It has been proposed that the real (objective) world and our (subjective) perception of the real world are not the same. Descartes (1641) argued that all that we can know of the real world is tainted by our senses and abilities of understanding [Ding an sich (German: The thing in itself) and the knowable Erscheinung (German: Phenomenon) [Epistemology is described as the branch of philosophy that concerns itself with questions regarding human knowledge . One parstanding . Kant (1nomenon) . Postmodcartes 161 argued nomenon) , and cogcartes 161 argued All these examples -6 share However, the described distinction between the real (objective) world and (subjective) perception of the real world -6 has alIn accordance with the Agrippean argument, evidence elicited from single systematic reviews as proof in clinical practice is vulnerable to radical scepticism. An example is the argument that population-based research  and subsequently appraised through systematic reviews) cannot be applicable to the treatment of individual patients . The valThe aim of this article is to offer the epistemological proposition that, with reference to the Coherence theory and illustrated by one case study, evidence from multiple systematic reviews, if mutually supportive  may be able in principle and on philosophical ground to terminate the infinite regress of proof and thus refute the Agrippean argument against it. This article further aims to highlight some aspects concerning the translation of such proposition from philosophical grounds into health care praxis.The key to refuting the Agrippean argument is to terminate the infinite regression of proof. The radical sceptic rejects refusal of further proof and circular reference to proof, preventing formation of a successful refutation. A possible epistemological solution to this problem is to assert that not just one single belief but many, are expressed in a thesis. Such beliefs do not exist independently from each other but form a system or web of mutually supporting beliefs that justify each other. This line of argument against radical scepticism has been called the Coherence theory -16. The In order to show how the above principles of Coherence theory may be applied in support of specific beliefs in healthcare, a case study including seven systematic reviews -23, all The specific objective of this case study was to illustrate, as example, the refutation of radical scepticism towards the belief that GICs are beneficial in tooth caries therapy on the basis of logical and empirical coherence, and included the following steps:(i) Conducting and publication of systematic review articles addressing different review questions concerning the main belief regarding clinical benefits of GICs in tooth caries therapy;(ii) Extraction of 'web'components, separated by common categories, that are contained in the systematic reviews;(iii) Construction of a 'web-of-beliefs' frame from the extracted components;(iv) Setting of conditions that need to be in place in the constructed 'web-of-beliefs' in order for it to be considered coherent;(v) Discussion about whether the specific information provided by the systematic reviews fulfils the conditions for (a) logical coherence and (b) empirical coherence.The format of systematic reviews of trials was chosen above other forms of scientific investigation , as these are considered to provide the most comprehensive answers to clinical questions, with the least possible systematic error . All sysOf the seven systematic reviews, three included conventional GIC (C-GIC) ,18,22 anThe strength of systematic review evidence relies on (i) the quality of trials reviewed and (ii) the quality of the systematic review itself. The AMSTAR (Assessment of Multiple SysTemAtic Reviews) tool -26 was uThe use of the AMSTAR tool does not establish whether systematic reviews judged the quality of trials according to whether or not bias was successfully prevented. Selection bias, besides e.g. detection/performance-, attrition- or publication bias, is one of the most important types of bias in clinical trials and effectively diverts trial results away from the truth, even in absence of any other types of bias risk . Therefon); Control material (Cn); Treatment type (TNn) and Outcome measure (OMn). Details about the specific components per category are shown in Table All beliefs investigated by the seven systematic reviews: belief related to GICs remineralising effect (Belief 1), caries-preventive effect Belief 2), restoration survival (Belief 3), are mutual to the main belief regarding GIC's benefit in caries therapy. All systematic reviews contained the component categories: Test material  Tooth remineralisation (OM1) is conceptually closer related to absence of carious tooth lesions (OM2) than to lesion presence;(ii) Absence of carious tooth lesions (OM2) on restoration margins is conceptually closer related to tooth restoration survival (OM3) than to failure.In biological/clinical terms, these tautologies are oversimplified, as the process of the caries disease is rather complex. However, within the philosophical context of this case study, these tautologies mean that the higher the tooth remineralisation effect, the less the occurrence of carious tooth lesions is expected to be and the less the occurrence of lesions on restoration margins, the higher the survival of tooth restorations is expected to be.Coherence of clinical evidence  will mean that the following conditions are fulfilled, within the framework of this case study:1) associated with test materials (Tn) is at least not lower than with control materials (Cn), regardless of the type of treatment (TNn);(i) The remineralisation effect (OM2) associated with test materials (Tn) is at least not lower than with control materials (Cn), regardless of the type of treatment (TNn);(ii) Absence of carious tooth lesions (OM3) associated with test materials (Tn) is at least not lower than with control materials (Cn), for tooth restoration as treatment type (TN1);(iii) Tooth restoration survival (OM1 and 2) regardless of type of treatment (TNn) and outcome measure (OMn);(iv) There are no differences in the clinical outcomes between the different versions of the test materials (T1 or 2) in comparison to different control materials (Cn), (under condition of same type of treatment (TNn) and outcome measure (OMn);(v) There is no difference between the clinical outcomes of the same version of the test material (Tn) in comparison to the same control material  (under condition of same type of treatment (TNn) and outcome measure (OMn).(vi) There is no difference between the clinical outcomes of the different version of test material  the higher the tooth remineralisation effect, the less the occurrence of carious tooth lesions and (ii) the less the occurrence of carious tooth lesions on restoration margins, the higher will be the occurrence of the survival of tooth restorations, were adopted. Tautology is a philosophical term that describes a statement that is true in every circumstance, thus forming a necessary truth . This neThe evidence provided by the seven systematic reviews complies with all set conditions for coherence of evidence Table . No non-In line with the Coherence theory, the logical and empirical coherence presented in this case study may be regarded as sufficient to terminate the infinite regression of proof imposed by radical scepticism. This means that radical philosophical scepticism towards the clinical benefit of GIC regarding caries may be successfully refuted in epistemological terms. However, it is important to note that such epistemological proposition can only be translated successfully into practice if and only if no general scepticism concerning the validity of the underlying empirical evidence arises. In the presented case study, empirical evidence is provided by seven systematic reviews. Systematic reviews are regarded as providing the highest form of evidence to healthcare questions . NonetheRadical, philosophical scepticism towards the benefit of clinical procedures in healthcare may epistemologically be refuted on the basis of logical and empirical coherence. Such coherence indicates causality in the real (objective) world - in this example GIC related to caries-therapeutic benefit - that exists independently of (subjective) perceptions or scepticism. Empirical coherence is provided from clinical evidence. Such evidence is acquired through clinical trials and subsequently synthesised by (quantitative) systematic reviews. A single systematic review covering one topic may be insufficient for refuting the Agrippean argument. For this, several systematic reviews covering interconnected beliefs may be needed. It is stressed that a successful application of such epistemological proposition into practice regarding refutation of radical, philosophical scepticism towards the benefit of a particular clinical procedure is possible only if these systematic reviews are of high quality and the quality of reviewed clinical trials is high enough to withstand general scepticism concerning trial validity.SM developed the concept and outline and wrote this paper.The author contributes to the conduct and publication of systematic reviews concerned with topics related to Minimum Intervention (MI) in dentistry."}
+{"text": "The construction of medical information is important to improve the hospital medical care capability, the management decision-making level of health and the hospital operational efficiency. The construction of medical information system of the first Affiliated Hospital of Zhejiang University was begun in 1980s. Nowadays the comprehensive hospital information services and management platform have been established, centering on electronic medical records and clinical pathway. The establishment and use of these information systems played an important role in improving the degree of patient satisfaction, enhancing hospital efficiency and healthcare quality, protecting the safety of healthcare, and reducing healthcare costs.Through the construction of clinical data repository (CDR) centering on electronic medical records, the integrated medical information system has been established in our hospital. At present, CDR has integrated the clinical diagnosis and treatment system,such as the electronic medical records system of inpatient and outpatient, nurse information system(NIS), laboratory information system (LIS), radiology information system (RIS), picture archiving and communication(PACS), ultrasonic information system (UIS), pathology information system(PIS), anesthesia management system, the remote medical network service platform, and the hospital outpatient and emergency registration system, outpatient appointment service system for disease diagnosis and treatment, physical equipment management system, cost management system, financial analysis system and the construction of hospital portal website.The outpatient appointment rate of experts was more than 79%. The utilization ratio of hospital electronic medical records was almost 100%. The good quality medical record rate was over 98%. And overall efficiency of writing medical record was improved by 52.54%. The defect-free medical record rate was over 90%. The average hospital day was reduced by 7.8%. The 94 types of the clinical pathways were developed and applied in 24 departments. The remote medical network service platform was established with 90 hospitals.The establishment and application of hospital information systems improve hospital services and management standards, and ultimately improve the quality of medical services, reduce the medical errors, ensure the medical safety, and reduce healthcare costs."}
+{"text": "Endomyocardial biopsy (EMB) represents the gold-standard for the assessment of myocardial inflammation in the context of suspected myocarditis. Recently, several studies have reported an encouraging diagnostic performance of cardiac magnetic resonance imaging (MRI) for the assessment of myocardial inflammation/myocarditis. However, the comparison of MRI results to clinical data only and the use of preselected patient populations are important limitations of the majority of these reports.We sought to define the diagnostic performance of MRI for the assessment of myocardial inflammation and necrosis as compared to EMB in an unselected cohort of consecutive patients with suspected acute and chronic myocarditis.132 consecutive patients with suspected acute or chronic myocarditis were included in this prospective trial. Patients had to fulfill indications for CMR imaging in suspected myocarditis according to a published consensus report (\u201cJACC White Paper\u201d).All patients underwent left ventricular EMB, cardiac catheterization for exclusion of coronary artery disease, and MRI on a 1.5 Tesla scanner . Imaging protocols included T2-weighted imaging for calculation of the edema ratio (ER), T1-weighted imaging before and after contrast agent administration for calculation of the global relative enhancement (gRE) and assessment of late enhancement (LE) for detection of myocardial necrosis, scarring or fibrosis. Assessment and interpretation ER, gRE, and LE were performed according to the JACC White myocarditis consensus paper. MRI imaging results were considered to be consistent with the diagnosis of myocarditis if 2 out of 3  of the MRI criteria were positive.Patients were divided into 2 groups according to duration of symptoms: patients with presumed acute myocarditis  and those with presumed chronic myocarditis (symptoms > 14 days).The diagnostic performance including sensitivity, specificity and accuracy for the individual imaging techniques is summarized in Table The results of our study underline the usefulness of MRI for assessment of myocardial inflammation/myocarditis in patients with suspected acute myocarditis. In contrast, with the current criteria, techniques and sequences, the diagnostic performance of MRI in patients with suspected chronic myocardial inflammation/myocarditis might be not sufficient to guide clinical management."}
+{"text": "The microscopic findings in tissues from both sites mainly consisted of haemorrhages; oedema; flocculent, granular or/and hyalinised segmentary degeneration; contraction band necrosis; and discoid degeneration or fragmentation of myofibres. We propose that skeletal muscle histopathology provides evidence of ante-mortem injuries even if the sample was taken elsewhere in the carcass and not only within or adjacent to the sharp trauma site and despite the advanced decomposition of some of the carcasses. This method helps to establish the diagnosis of ship strike as the cause of death.Ship strikes are a major issue for the conservation of may cetacean species. Certain gross and microscopic criteria have been previously reported for establishing a diagnosis of death due to ship strikes in these animals. However, some ship-strike injuries may be masked by advanced carcass decomposition and may be undetectable due to restricted access to the animals. In this report we describe histopathological muscular findings in 13 cetaceans with sharp trauma from ship strikes as the cause of death. Skeletal muscle samples were taken from the incision site and from the main locomotor muscle, the  Ship strikes in cetaceans are a major, worldwide conservation concern Several publications have established various criteria for serious injury and mortality caused by ship strikes in cetaceans and pinnipeds, which include the following: one or several cuts, proven ante-mortem bone fracture(s), and haematoma(s) and/or haemorrhage(s) Skeletal muscle histopathological findings have been correlated with episodes of stress in a report on capture myopathy in stranded cetaceans longissimus dorsi, even if this latter muscle was not directly affected by the sharp trauma.In this study, we designed a new muscle-based protocol for diagnosing acute sharp trauma in lethally ship-struck stranded cetaceans, which includes the histopathological findings in the muscle at the site of collision and in the Balaenoptera physalus) (3), short-beaked common dolphin (Delphinus delphis) (10), Risso\u2019s dolphin (Grampus griseus) (3), short-finned pilot whale  (12), north Atlantic bottlenose whale (Hyperoodon ampullatus) (1), pygmy sperm whale (Kogia breviceps) (12), Fraser\u2019s dolphin (Lagenodelphis hosei) (2), Sowerby\u2019s beaked whale (Mesoplodon bidens) (1), Blainville\u2019s beaked whale (Mesoplodon densirostris) (3), Gervais\u2019 beaked whale (Mesoplodon europaeus) (6), harbour porpoise (Phocoena phocoena) (1), sperm whale  (13), false Killer Whale (Pseudorca crassidens) (1), striped dolphin  (25), Atlantic spotted dolphin  (23), spinner dolphin (Stenella longirostris) (2), rough-toothed dolphin (Steno bredanensis) (3), bottlenose dolphin (Tursiops truncatus) (13), and Cuvier\u2019s beaked whale (Ziphius cavirostris) (19).Skeletal muscle from 153 small and large odontocetes and mysticetes of 19 different species of cetaceans that were stranded on the Canary Islands were examined. The animals were of both sexes and ranged in age from neonatal to adult according to biological and morphometric parameters in situ (on a beach or coast), or when the animals could be moved, in an alternate location suitable for necropsy. The required permission for the management of stranded cetaceans anywhere within the Canarian archipelago was issued by the environmental department of the Canary Islands\u2019 Government. No experiments were performed on live animals because our work was based on dead stranded cetaceans, and the field studies did not involve endangered or protected species. The nutritional status of each animal was established morphologically with reference to anatomical parameters such as the presence of certain prominent bones, the dorso-axial muscular mass, and the absence or limited presence of fat, taking account of the species and the age of the animal. Using these parameters, we classified their nutritional status as good-moderate, moderate-poor, or emaciated. The carcass decomposition code was established according to Geraci and Lounsbury longissimus dorsi muscle immediately lateral to the dorsal fin longissimus dorsi is part of the epaxial musculature, which lies along both sides of the vertebral column and is involved primarily in cetacean locomotion, powering the upstroke The skeletal muscle samples were collected during the necropsies, following standard protocols Heart muscle samples were routinely collected during standardized necropsies, whenever possible, and included both left and right atrioventricular walls and valves Skeletal muscle samples from all of the 153 stranded cetaceans were mounted on a tongue depressor (fixed at both ends by pins) with the myofibres oriented lengthwise and immersed in 4% neutral-buffered formalin for 24\u201348 hours. The same methodology was applied to all of the skeletal muscle samples, in which transversely and longitudinally oriented muscle samples were carved and routinely processed, embedded in paraffin, serially sectioned and stained with haematoxylin and eosin (HE), as well as with periodic acid-Schiff (PAS) with and without amylase digestion, phosphotungstic acid haematoxylin (PTAH), and the Von Kossa stain for specific components longissimus dorsi muscle from all of the cases and the area surrounding the incision(s) in those animals with gross evidence of a ship strike.The muscle examinations included a macroscopic evaluation of the muscle mass and a histologic examination of the muscle samples which comprised the All of the sections were examined in a blind manner by three veterinary pathologists and were evaluated for the following histological features: signs of degeneration/necrosis; intramyofibral inclusions/deposits and vacuoles; intramyofibral pigment deposits; chronic myopathic changes ; cytoarchitectural alterations (ring fibres); areas of inflammation and the presence of intramuscular parasites. The combination of the histopathological findings and the data concerning the age and the cause of death All hearts taken from the stranded cetaceans were analyzed in the same manner. Gross and histolopathologic examination of heart samples included the external observation of the right and left atria and ventricles, aorta, pulmonary valve, as well as the mitral and tricuspid valves; and the microscopic study of each of the heart layers  longissimus dorsi were only appreciable at the microscopic level, and all of the lethally struck animals showed microscopic musculoskeletal lesional changes of variable severity, even if this muscle had not been directly affected by the sharp trauma.Thirteen of 153 animals (8.5%) were diagnosed to have died from a ship collision . These alongissimus dorsi samples of the lethally struck animals showed severe acute diffuse degenerative changes or extensive multifocal degenerative changes, even though this muscle was not directly affected by the sharp injury longissimRegarding the other 140 animals with a cause of death other than a collision with a ship, discoid degeneration was not observed in any of the skeletal muscle samples from the examined specimens, including those of the same species with a similar age range . Acute degenerative changes with morphological features similar to those described for acute sharp ship strikes were observed in live stranded cetaceans that died very shortly after stranding (n\u200a=\u200a16); however, the severity and tissue distribution pattern differed between these two groups, being more severe and diffuse (extending to the connective tissue) in the ship-struck animals. Further, different myofibre were affected: type II in ship-struck animals, compared to type I in live stranded animals.Stenella frontalis and the striped dolphin Stenella coeruleoalbaLethal ship-strikes detected in the Canarian archipelago involve a variety of cetacean species The gross lesions associated with ship collision are generally found in the areas surrounding the incision(s) and involve the skin and related soft tissues, although some bone breakage may have occurred longissimus dorsi, even when the epaxial muscles were not directly affected by the sharp injury. The microscopic findings in the muscle of this group of animals mainly consisted of oedema, acute to peracute degenerative changes , contraction-band necrosis, discoid degeneration, fragmentation and disorganisation of the internal structure, and a minimal inflammatory reaction. These features are very similar but not identical to those described in live stranded cetaceans which were related to the stress of stranding and handling All of the lethally struck animals displayed microscopic lesions in the longissimus dorsi muscle and cardiac muscles suggests that they may be affected by a common mechanism In our study, contraction-band necrosis was observed in the skeletal muscle samples from 5 of the animals, which included all three of the calves in this study. Because stress may have a psychological component that can be influenced by experience, it may be expected to vary among individuals of the same species Segmental myonecrosis, in the form of hyalinisation, granulation and/or flocculation of the sarcoplasm and fragmentation and disorganization of myofibres, has been described in a variety of myopathies that involved ischemic damage of the muscle Discoid degeneration was observed in the skeletal muscle of the 61.5% of cetaceans (n\u200a=\u200a8) that died by acute ship strikes. This type of necrosis was not observed in the cetaceans with myopathies associated with other etiologies in our study longissimus dorsi) and not only within or adjacent to the site of the sharp trauma. It is well known that histopathology of wound margins and muscles can often provide insight into ante-mortem/peri-mortem vs. post-mortem injury In previous studies, some troubles have been described related to a conclusive diagnosis of ship strike in cetaceans and pinnipeds: advanced carcass decomposition; difficult access to the carcass; and/or peracute death. Based on our results, despite the advanced decomposition of some of the carcasses, swollen hyalinised and discoid fragmentation of myofibres were still evident in the samples, making this lesion a valuable diagnostic finding in those cases in which a definitive diagnosis of ship strike is difficult to establish. Our study also showed that histopathology of skeletal muscle provides evidence of stress/hypoxia-related injuries even if the sample is taken elsewhere in the carcass (Systematic muscle sampling should be included as a part of the necropsy protocol for stranded cetaceans, with special emphasis in the cases in which ship strikes are suspected.The combined histopathological skeletal muscle findings described here can serve as an additional criterion for differentiating ship collision from other causes of death in these animals, when other evidence of the former is present."}
+{"text": "Mammals exhibit daily anticipatory activity to cycles of food availability. Studies on such food anticipatory activity (FAA) have been conducted mainly in nocturnal rodents. They have identified FAA as the behavioral output of a food entrained oscillator (FEO), separate of the known light entrained oscillator (LEO) located in the suprachiasmatic nucleus (SCN) of hypothalamus. Here we briefly review the main characteristics of FAA. Also, we present results on four topics of food anticipation: (1) possible input signals to FEO, (2) FEO substrate, (3) the importance of canonical clock genes for FAA, and (4) potential practical applications of scheduled feeding. This mini review is intended to introduce the subject of food entrainment to those unfamiliar with it but also present them with relevant new findings on the issue. Circadian rhythms are \u224824 h oscillations in several domains  for mammals; however, a range of non-photic signals is capable of entraining circadian rhythms. Cyclic food availability is one of them. Its effect on circadian rhythms has been mostly studied in rodents, but lagomorphs, marsupials, carnivores, and primates also entrain to scheduled food availability  is its principal component  mechanisms to entrain the FEO  in anterior hippocampal continuation and the septohippocampal nucleus (AH/SHi), paraventricular nucleus of the thalamus (PVT) and DMH in rats. They also found that neuronal activation in parabrachial nucleus (PB) and nucleus of solitary tract (NTS) occurred only during feeding time. Recently, another structure, the cerebellum, was implicated in the regulation of food anticipatory rhythms  and PB in the brainstem exhibit similar neuronal activation in the two conditions: (1) when mice are anticipating food during the feeding schedule and (2) when mice are no more anticipating food on ad lib condition. These data indicate persistent activation of these areas after termination of the feeding schedule and in the absence of FAA. The authors say that: \u201c\u2026 after a return to ad libitum conditions ONLY the regions that are necessary for timekeeping would remain preferentially activated\u201d  of the FEO instead of discrete, and this alternative has been discussed more frequently in recent years (Mendoza et al., Scheduled feeding has a broaden effect on brain activation. We believe that recent findings on neuronal activation are especially relevant for identification of structures comprising the FEO. These studies may be expanded by investigating the pattern of activation during the complete development of FAA and during food deprivation tests, in which FAA re-emerges.Scheduled feeding also appears to act on disrupted circadian rhythm and health markers Figure . Such efThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The contributions included in this research topic encompass the entire bandwidth of known phloem functions with emphasis on the diversity in structures and functions.Research over the past 20 years has revealed new functions of the phloem beyond resource allocation to a system that combines distribution and messaging (Thompson and van Bel, Differentiation and development of vascular cells is complex and not well understood. Vascular development partly depends on environmental cues that have also impacted the evolution of vascular systems and phloem transport mechanisms. A novel phylogenetic approach to identify genes involved in vascular development (Martinez-Navarro et al., Arabidopsis ecotypes (Adams et al., Ample attention has been paid to the structural diversity, particularly in the phloem-loading zone, where environmental changes have unbuffered, and profound effects. The impact of diverse environmental conditions on leaf structure and carbohydrate processing is demonstrated with in situ measurement of sucrose uptake parameters (Hafke et al., Carbohydrate processing may be more homogeneous in transport phloem (Slewinski et al., Long-distance signaling via the phloem can be accomplished by a variety of physiological mechanisms. Electrical signaling along sieve tubes affects both the physiology of distant leaves as well as photosynthate release/retrieval (Fromm et al., RNA-species are most likely translocated as complexes with RNA-binding proteins (Pallas and Gomez, The phloem contains attractants and repellents for animal pathogens. Present work indicates that sterols serve as attractants (Behmer et al., As with other research fields, phloem research reveals an ever receding horizon with undreamed possibilities. This topic shows the amazingly diverse ability of plants to cope with an infinite number of environmental challenges by virtue of the vascular tissues."}
+{"text": "Work during the past few decades has provided a good understanding of alterations that occur in viruses when they interact with host cells. This is generally possible because of the relative simplicity of virus systems, as compared to the more complex cellular systems. There has also been advancement made in delineating host genomic responses to virus infection because of the availability of gene arrays for diverse organisms. However, work that seeks to equally comprehend host responses to virus infection at the protein level (proteomics) has lagged behind because of technical challenges and the great complexity of the cellular proteome.This series consists of six review articles, three original research papers and a single commentary that all focus on current research activities in the field of proteomics of virus-infected host cells, all designed to begin to fill these important gaps in our knowledge. The articles span quantitative proteomic analyses of host protein alterations induced upon virus infection of a range of host cells: archaeal, insect, and various animal systems. Several articles present results and reviews of new discovery-based functional assays to assess broad enzymatic groups within these experimental systems to complement the quantitative proteomics assays.The review article by Enrique Santamaria and co-workers provides an overview of mass spectrometry (MS)-based proteomics and how this method has been useful for delineating some of the interactions between herpes simplex virus type 1 (HSV-1) and the host cells , with an emphasis on interactions between the virus and T cells  to study virus-host interactions (Shahiduzzaman and Coombs, The review by Monteiro and co-workers discusses some of the applications of proteomic analyses of baculoviruses (Monteiro et al., Most of the original research and review articles presented above focus on individual virus-host model systems. The final review article by Zheng and colleagues provides a holistic overview of current approaches being undertaken to better define and functionally validate responses elicited within the host proteome by virus infection (Zheng et al., In the first of three original research papers within this volume, Jiang and colleagues label HeLa cells with either normal isotopic amino acids or heavy forms of arginine and lysine in the SILAC approach (Jiang et al., The research article by Milev and co-workers describes characterization of Staufen 1, a host protein that binds double-stranded RNA and that is associated with HIV-derived ribonucleoprotein complexes (Milev et al., The final article by Maaty and colleagues provides a global analysis of host responses to virus infection in an archaeal system (Maaty et al., In summary, these articles present overviews and ongoing original research in one of the \u201cfrontier\u201d areas of virology\u2014a better understanding of the complexity of various host omic responses to virus infection, with some examples of proteomic and functional genomic approaches."}
+{"text": "Sequences of neuronal activity patterns can be stored in networks of binary neurons with binary synapses. We investigate different forms of inhibition and their effect on such sequence memory, extending on a mean field approach . There iWe further analyzed the effect of nonoptimal replay conditions: The replay performance degrades gracefully with the network exhibiting transient memory replay before falling into a state of silence or non memory-related activity. The regions of stable replay calculated from the mean field model were verified in cellular simulations."}
+{"text": "Primary immune deficiencies are a heterogeneous group of inherited disorders in which dysfunctions of the immune system cause an enhanced susceptibility to infections. Their frequency is higher in Tunisia and the Maghreb as compared to European and North American countries. Indeed, our population is characterized by a high frequency of consanguineous marriages and this may account for the higher incidence of autosomal recessive primary immune deficiencies observed.During the last fifteen years, we have been able as a reference center in Tunisia to establish the diagnosis of primary immunodeficiency in 397 patients including 12 patients from Algeria and Libya. The immunological investigation including phenotypic analysis of peripheral blood cells, lymphocyte proliferation assays, phagocytic cells functions and measurement of immunoglobulins as well as complement allowed us to classify these cases in combined immune deficiencies (27%), predominantly antibody deficiencies (23%), phagocytic cells defects (23%), complement deficiencies (1%), other well-defined syndromes (24%) and other immunodeficiencies (2%). The study of the molecular basis of these diseases in our settings as compared to other European, North American and Asian studies shows a high incidence of autosomal recessive diseases including Ataxia-telangiectasia, Bare Lymphocyte syndrome, Mendelian susceptibility to mycobacteria and Leukocyte adhesion deficiency. Moreover, we have observed a higher frequency of autosomal recessive forms of classically X-linked immune deficiencies such as autosomal recessive agammaglobulinemia and chronic granulomatous disease. A founder effect in our population with a single gene mutation accounting for most cases has been observed for several of these primary immune deficiencies.The establishment of an accurate diagnosis allowed the appropriate treatment of these patients according to the cellular and molecular basis of the disease by bone marrow transplantation, substitutive immunoglobulin therapy, IFNg therapy...etc. The genetic study was aimed: first, to allow an appropriate genetic counselling and a prenatal diagnosis in these consanguineous affected families; second, to help unravelling the immune system functioning since these particularly rare autosomal forms of immune deficiencies offer a unique physiopathological model to study specific host defense pathways in humans."}
+{"text": "Frontiers in Molecular Neuroscience is to provide an overview of the approaches in this area of research, and to present new applications in molecular imaging of ions and remote activation of receptors, ionic channels and synaptic networks. The issue contains experimental and methodological papers as well as review articles dealing with molecular tools for investigation and modulation of neuronal function. It can be divided into two main sections: (i) genetically encoded probes for non-invasive monitoring of ions and ATP; and (ii) optogenetic and optopharmacologic tools for control of neuronal activity with light.Photochromic switches and genetically encoded biosensors have become powerful tools for monitoring and modulating the activity of neurons and neuronal networks. Our understanding of the mechanisms underlying the development and functioning of the nervous system has greatly advanced in recent years thanks to advancements in these effective molecular and genetic tools. The idea of this Special Research Issue of \u2212]i). A sensor with improved sensitivity to chloride, called Cl-Sensor  in different cell types  or cellular compartments  (Akerboom et al., Two papers illustrate the use of genetically encoded probes to analyse physiologically important ions or molecules in different cellular compartments (Surin et al., The last article in the first section (Brondi et al., The second section of this Special Research Issue presents optogenetic tools and photoswitches for the optical control of neuronal activity. A method for studying neuronal plasticity following long-term neuronal stimulation using Channelrhodopsin-2 and monitoring by multi-electrode arrays is presented by Lignani et al. . OptogenThe fields of optopharmacology and optochemical genetics are reviewed by Sandoz and Levitz  and MourThe issue concludes with two articles that are focused on the approaches and techniques to analyse Cl-selective receptor-operated channels. Lynagh and Lynch  used a vWe are grateful to all authors and reviewers for their efforts in providing an excellent overview of these rapidly expanding fields."}
+{"text": "Environmental and occupational risk factors contribute to nearly 40% of the national burden of disease in India , with ai10), sulfur dioxide, and nitrogen dioxide concentrations across 341 CPCB stations in 125 cities and towns and mortality/morbidity data from many municipalities and hospitals\u2014multicity, multipollutant studies of short-term health effects are increasingly feasible. Although such studies alone will not provide the breadth of evidence needed to estimate the burden of chronic, as well as acute, health outcomes, it may be possible to extrapolate long-term risks based on short-term effects, which appear to be similar to those in other countries with more complete data.Levels of ambient air pollution uniformly exceed the recently revised WHO air quality guideline (AQG) levels  across mAccording to the Indian National Census of 2001 , 75% of Indian households use solid fuels (primarily firewood and cow dung), including up to 90% of households in some rural areas. An estimated 400,000 deaths from acute lower respiratory infections (ALRI) in children < 5 years of age and 34,000 deaths from chronic obstructive pulmonary disease (COPD) in women are attributed annually to indoor air pollution  reduce ambiguities in effect estimates; b) optimize health impact/climate cobenefit information for risk communication across rural and urban (or even developed and developing country) settings; c) add momentum for intervention efforts; d) increase efficiency of environmental epidemiology research; and e) jointly inform policy in the environment, health, and energy sectors. With emerging implications of emissions from both outdoor and indoor sources for climate change and health, such integration would also facilitate national efforts for emission reduction  has established a Centre for Advanced Research in Environmental Health that will focus on air pollution and examine a range of exposures and outcomes in a rural\u2013urban pregnant mother\u2013child cohort and an adult endovascular disease cohort. Land-use regression modeling and select gene\u2013environment related end points are also being examined in a nested subsample. In addition, the center will engage in capacity building to address human resource needs by developing training modules for different categories of professionals.With high receptivity among research and funding agencies within and outside India and an increasing base of local research capacities in air pollution, India provides fertile grounds for global research partnerships that can facilitate the launch of strategic epidemiological studies to promote the timely application of international research and accelerate progress toward achieving universal access to clean air. ICMR initiatives to develop collaborative projects on interventions related to household solid fuel combustion under the ongoing Indo-US program on Environmental and Occupational Health reflect first steps toward achieving this goal."}
+{"text": "The identification and quantification of plant hormones in plant tissues are necessary for physiological studies of their metabolism and mode of action. The major problem associated with plant hormone analysis is that the amount of phytohormones present endogenously in plant tissues is very low, usually in the range of fmol to pmol/g fresh weight.TM UPLC,Waters) was coupled to triple quadrupole mass spectrometer  equipped with an electrospray interface (ESI) and the unique performance of collision cell \u2013 ScanWaveTM. The mass spectrometric conditions were optimized for each analyte and quantification was obtained by multiple reaction monitoring (MRM) of precursors and the appropriate product ions.Homogenization and extraction with organic solvents was done in one microcentrifuge tube and accelerated by crushing the plant material in a vibration mill. The extracts from minute amounts of fresh plant material were immediately purified using a solid-phase extraction in combination with ion-exchange and/or immunoaffinity purification. A fast chromatography technique, the ultra performance liquid chromatography MS/MS technology can be used for fast and sensitive quantitative analysis showing reproducibility in the plant hormones profiling in different tree extracts."}
+{"text": "The influence of the autonomic nervous system (ANS) on triggering and perpetuation of atrial fibrillation (AF) is well established. Ganglionated plexi (GP) ablation achieves autonomic denervation by affecting both the parasympathetic and sympathetic components of the ANS. An anatomic approach for GP ablation at relevant atrial sites appears to be safe, and improves the results of PV isolation in patients with paroxysmal and persistent AF. GP ablation can be accomplished endocardially or epicardially, ie, during the maze procedure or thoracoscopic approaches. Further experience is needed to assess the clinical value of this promising technique. The influence of the autonomic nervous system (ANS) on the triggering and perpetuation of atrial fibrillation (AF) is well established. Variations of the autonomic tone have been associated with paroxysms of AF and both sympathetic and parasympathetic activation may be proarrhythmic by shortening of atrial refractoriness.-3 Vagal In the electrophysiology laboratory and the operating theater, identification of major GP has been mainly accomplished through high-frequency stimulation (HFS) and induction of vagal responses in the atria.,20 HFS iIsolated GP ablation has been employed for both paroxysmal and persistent AF with variable success. In paroxysmal AF, arrhythmia-free survival within the first year after the procedure ranged between 26 to 77%.-26 SucceAddition of GP ablation to the conventional Maze procedure has produced improved outcomes with success rates 83-93% over the following year.-33 AlthoThoracoscopic approaches combine PV isolation with selective GP ablation, with or without ligament of Marshall ablation or left atrial appendage amputation.-38 The rAblation-induced atrial or ventricular proarrhythmia has been reported with both endocardial and epicardial (thoracoscopic) approaches.,39-40 AnGP ablation appears to be a safe and efficacious method to improve PV isolation in patients with AF, and has been used in the electrophysiology laboratory, and during the maze procedure or thoracoscopic approaches. However"}
+{"text": "The presence of correlated neuronal activity as such is not surprising, but rather a natural consequence of network connectivity and dynamics, in particular direct synaptic connections and shared local and non-local presynaptic sources . The intA theoretical understanding of correlations requires the representation of (1) the recurrent connectivity and (2) external and internal sources of temporally varying or fluctuating signals. Such a theory is currently lacking. In particular it is still unclear how the recently found mechanism of active decorrelation , explain"}
+{"text": "The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a background of normal or subnormal iron levels . We aimed at clearing local siderosis from aberrant labile metal that promotes oxidative damage, without interfering with essential local functions or with hematological iron-associated properties. For this purpose we introduced a conservative mode of iron chelation of dual activity, one based on scavenging labile metal but also redeploying it to cell acceptors or to physiological transferrin. The \u201cscavenging and redeployment\u201d mode of action was designed both for correcting aberrant iron distribution and also for minimizing/preventing systemic loss of chelated metal. We first examine cell models that recapitulate iron maldistribution and associated dysfunctions identified with Friedreich ataxia and Parkinson's disease and use them to explore the ability of the double-acting agent deferiprone, an orally active chelator, to mediate iron scavenging and redeployment and thereby causing functional improvement. We subsequently evaluate the concept in translational models of disease and finally assess its therapeutic potential in prospective double-blind pilot clinical trials. We claim that any chelator applied to diseases of regional siderosis, cardiac, neuronal or endocrine ought to preserve both systemic and regional iron levels. The proposed deferiprone-based therapy has provided a paradigm for treating regional types of siderosis without affecting hematological parameters and systemic functions. Iron homeostasis relies on the orchestration of a network of systemic and cellular mechanisms for the acquisition, internal distribution and use of iron  the chemical forms and concentrations of the NTBI/LPI, (ii) the LPI's membrane agencies and entry routes in particular cells; (iii) the cell's ability to handle \u201csurplus\u201d iron by sequestering it within \u201csafe\u201d ferritin sanctuaries and (iv) the cell's enzymatic and non-enzymatic means of counteracting the metal-catalyzed formation of reactive oxygen species (ROSs) involved in oxidative damage spin relaxation methods  retrospectively for its correlation with cardiac iron measured in tissue biopsies and (ii) prospectively for its correlation with impaired cardiac function  and (ii) a metabolic decline in cell iron-dependent activities   or saccharide .Unlike hemosiderosis , regional siderosis mostly results from a disruption in cell homeostasis that causes iron to be abnormally distributed in certain cell types or specific organs   the drug's good safety profile in the treatment of hemosiderosis  dissipating large iron agglomerates  were performed in adolescent patients with FRDA . This activation is achieved by an intrinsic  activation factor  that is only present or active in the target region  by chelating excess metal and excreting it via urinary and/or biliary-fecal routes  chelation, which relies on pro-chelating agents that are enzymatically converted into active chelators in various brain areas and act locally as metal-detoxifying agents  Although several novel, brain-targeted pro-chelators have already displayed neuroprotective and neurorestorative properties in preclinical models of neurodegeneration, , whereas Apopharma provided the compound deferiprone and instructions on its use. Zvi Ioav Cabantchik was supported by the A&M Della Pergola Chair in Life Sciences, served on the Scientific Advisory Board of Novartis ESB, received in the past research grants from NIH, EEC (5 and 6 framework), Israel Science Foundation, AFIRNE (Paris), Novartis, Shire and Apopharma  and is presently a consultant for Aferrix, Ltd and Hinoman, Ltd, Israel. David Devos served on the Scientific Advisory Board for Novartis and Aguettant and has received PHRC grants from the French Ministry of Health and research funding from the ARSLA charity and honoraria from pharmaceutical companies for consultancy and lectures. Arnold Munnich is the head of the Pediatric Genetic Unit at Hospital Necker, Paris France. He has served as an advisor to Sanofi Genzyme until May 2013. He has presently no other appointment with commercial entities. Moussa B. Youdim receives Royalties from Teva Pharmaceutical Co. Israel and is Chief Scientific Officer co-owner and shareholder of Abital Pharma Pipeline Ltd, Israel, and of Avraham Pharmaceutical Co. Israel."}
+{"text": "PrPres may accumulate in lymphoreticular system tumors of asymptomatic persons with vCJD. The statistical power of estimates of vCJD prevalence might be increased by expanding screening to include samples of lymphoreticular neoplasms.We report protease-resistant prion protein (PrP The prevalence of preclinical and subclinical vCJD in the United Kingdom and other European countries is still unknown. To date, all tested vCJD patients have shown an accumulation of misfolded protease-resistant protein  female mice closely related to the SJL/J strain, which develops spontaneous B-cell lymphomas at >8 months of age ,. The remres was extracted from brains by using high-speed centrifugation, from spleens by using methanol precipitation according to previously described methods  or 6D11 as previously described  was similar to that seen in the human (lane 1) and mouse (lane 2) brains. Among the control mice, PrPres was not detected in the brain and spleen of any animal or in neoplastic tissues of the single affected animal  tests, Hilton and colleagues  when compared to mice with the longest survival time (>380 days). On the basis of our findings, we propose that screening of lymph node tissues from persons with reactive and neoplastic conditions and patients with various cancers with metastases in lymphoreticular organs could provide additional information, especially regarding older persons, on the prevalence of vCJD in the United Kingdom and other European countries.Our observation of the widespread presence of PrP"}
+{"text": "We examine the environmental, climatic and geographical controls on tropical ostracod distribution in the marine Ordovician of North America.bicornis graptolite biozone, analyses of the entire dataset suggest that these provinces remain distinct throughout the Sandbian interval. Differences in species composition between the provinces appear to have been controlled by changes in physical parameters  related to water depth and latitude and a possible regional geographic barrier, and these differences persist into the Katian and possibly the Hirnantian. Local environmental parameters, perhaps operating at the microhabitat scale, may have been significant in driving local speciation events from ancestor species in each region.Analysis of the inter-regional distribution patterns of Ordovician Laurentian ostracods, focussing particularly on the diverse Late Ordovician Sandbian (ca 461 to 456 Ma) faunas, demonstrates strong endemicity at the species-level. Local endemism is very pronounced, ranging from 25% (e.g. Foxe basin) to 75% (e.g. Michigan basin) in each basin, a pattern that is also reflected in other benthic faunas such as brachiopods. Multivariate (ordination) analyses of the ostracod faunas allow demarcation of a Midcontinent Province and a southern Marginal Province in Laurentia. While these are most clearly differentiated at the stratigraphical level of the Our work establishes a refined methodology for assessing marine benthic arthropod micro-benthos provinciality for the Early Palaeozoic. Ostracods are small bivalved crustaceans with a fossil record extending back to the Cambrian In this paper we evaluate the distributional patterns of the Ordovician ostracods of palaeocontinental Laurentia gracilis and bicornis graptolite biozones Unlike fossil Ordovician plankton, whose distribution patterns can be evaluated from global datasets  Krausella? spinosa  Eurychilina? aff. Chilobolbina hyposulcata sensu Kraft, 1962 A Sandbian dataset  comprising 13 regions with 229 ostracod species from 88 genera was compiled from published literature . TaxonomNemagraptus gracilis. The graptolite Ensigraptus caudatus defines the base of the succeeding clingani Biozone and of the Katian Stage (gracilis Biozone (ca 3 million years duration) and 117 taxa to the bicornis Biozone  conodont biozones are considered equivalent to the gracilis graptolite Biozone, and the upper A. tvaerensis Biozone  as equivalent to the bicornis graptolite Biozone Graptolites are the main biostratigraphic markers used for correlating our chosen rock successions together with the coeval conodont biozones gracilis Biozone time slab) to show the relevant influence of inter-continental versus intra-continental environmental and geographical effects.Laurentia was selected for analysis because it yields one of the most diverse and geographically widespread ostracod faunas from the Late Ordovician (Sandbian) and because it includes a broad latitudinal range , with five localities from Avalonia and six localities from Laurentia. We then analysed the Laurentian dataset for three time intervals, the gracilis Biozone (ca 3 million years), the bicornis Biozone (ca 2 million years), and the entire Sandbian (ca 5 million years). In order to test whether a significant stratigraphical or latitudinal/geographic signal was present in the entire Sandbian dataset, we used the direct equivalent of CA, viz. Canonical Correspondence Analyses (CCA) with stratigraphy (dummy variables for gracilis and bicornis) and palaeolatitude  as the only variables respectively. Significance was tested using Monte Carlo permutation tests .Ordination is a tool that allows the representation of complex multivariate datasets in simple diagrams in which the axes represent the main gradients in species composition in the original dataset. These ordination axes thus represent environmental gradients  which drive the gradient in species composition. In ordination diagrams, samples are ordered with respect to one another on the basis of their species composition (occurrence in the sample set) Eridoconcha during the early Sandbian (gracilis Biozone), and Ceratopsis and Easchmidtella during the late Sandbian  shows Avalonian and Laurentian localities as two discrete clusters of samples (data not shown). Ostracod fauna from the early Katian (clingani Biozone) of Avalonia are sparse, only six species being documented and none of these are common to Laurentia For much of the Ordovician, Laurentia was separated by the Iapetus Ocean from the palaeocontinents of Baltica and Avalonia, though this ocean narrowed by the Late Ordovician gracilis and bicornis biozones) ostracod fauna revealed a clear latitudinal signal, with all southern marginal localities lying on the right side of the first CA axis, and most midcontinent localities on the left  consistently cluster together on the basis of region, not stratigraphy  identified the samples from Kentucky (5), Michigan (7) and Mackenzie (13) as outliers. These three samples are characterized by the highest percentages (>65%) of endemic species in the whole dataset, and were therefore omitted from further analyses. CA analysis of the entire Sandbian . Within this province 33 species have occurrences restricted to a single depositional basin and are thus endemic at a local level. Oklahoma (Bromide Formation) shares ten species with the southern Marginal Province and nine species with the Midcontinent Province.As in the entire Sandbian dataset analysis (see paragraph above), two ostracod provinces can be distinguished for the ime slab . These aime slab . The ostime slab , 3 showsime slab , 3. Oklaime slab , 3 repre and see . The Midgracilis Biozone of Laurentia includes materials from Virginia, New York, Pennsylvania, the Mackenzie District (Canada), and Oklahoma , latitude (climatic), and substrate.The Palaeozoic geography of Laurentia has been reviewed and discussed in detail by piecing together information from palaeomagnetic studies and faunal distribution patterns Seabed substrate is recognised as an important factor in the distribution of Ordovician ostracods at a continental scale Eohollina, Platyrhomboides, Dicranella, Cryptophyllus, Winchellatia, Baltonotella, Tetradella and Euprimitia. The former six of these are found in shallow to deep shelf facies of the Bromide Formation of Oklahoma, whereas species of Euprimitia are found in shallow shelf facies of the Crown Point Formation of New York and species of Tetradella are present in the shallow shelf facies of the Hull Formation of Ontario Baltonotella parsispinosa are also present in the shallow shelf facies of the Crown Point Formation of New York and deep shelf facies of the Edinburg Formation of Virginia Eurybolbina bispinata that occurs only in the deep shelf of the Bromide Formation is also present in the shallow to deep shelf facies of the lower Esbataottine Formation of the Mackenzie District and deep shelf facies of the Lincolnshire and Edinburg formations of Virginia Leperditella rex in peri-tidal and innermost shelf facies of the Bromide Formation is also present only in the peri-tidal facies of the Hatter and Benner formations of Pennsylvania and the inner shelf facies of the Bucke Formation of Ontario In previous studies of Late Ordovician ostracods water depth has been considered to have a strong influence on the distribution of ostracods Platybolbina punctata, \u2018Ctenobolbina\u2019 ventrospinosa, Shenandoia acuminulata and Eurychilina strasburgensis from the Marginal Province. Also, some 28 species  are restricted only to the Midcontinent Province  both the Marginal province faunas and the Midcontinent Province faunas possessed generic links with Baltica Longiscula perfecta, L. tersa, Medianella longa, Steusloffina cuneata and species of Hemiaechminoides and Kinnekullea) that are restricted to the Marginal Province of Laurentia are also present in the early Katian of the Baltic region  to 75% (e.g. Michigan basin), with the exception of Girvan which is an allochthonous fauna;gracilis and bicornis time slabs allows for demarcation of Midcontinent and southern Marginal ostracod provinces;Multivariate analyses of the entire Sandbian, Midcontinent and southern Marginal ostracod provinces appear to persist from the Sandbian into the Katian, and faunal contacts with Baltica and Avalonia are strongest with the Marginal Province, including the first species-level links, possibly reflecting greater geographical proximity and water depth tolerance of these faunas;The Midcontinent and southern Marginal provinces could, in part, reflect the Tropical and Subtropical climate belts that have earlier been identified based on zooplankton distributions;The strong regional endemicity of the Laurentian ostracod fauna at species-level is reflected in other faunas such as brachiopods. The strong endemicity suggests that local environmental parameters operating at the microhabitat scale may have been significant in driving local speciation events from ancestor species in each depositional basin.Table S1Sandbian ostracod localities of North America, Canada and southwest Scotland. Ostracod distribution shown by lithology, depositional setting, palaeolatitude, sampling points, taphonomy, total number of species in each Formation and basin, and the number and percentage of endemic species in each depositional basin.(DOCX)Click here for additional data file.Appendix S1Entire Sandbian time slab ostracod dataset of palaeocontinental Laurentia.(XLSX)Click here for additional data file.Appendix S2Sandbian (bicornis) time slab ostracod dataset of palaeocontinental Laurentia.(XLSX)Click here for additional data file.Appendix S3Sandbian (gracilis) time slab ostracod dataset of palaeocontinental Laurentia.(XLSX)Click here for additional data file."}
+{"text": "In humans, there are large individual differences in the levels of vagal modulation of resting heart rate (HR). High levels are a recognized index of cardiac health, whereas low levels are considered an important risk factor for cardiovascular morbidity and mortality. Several factors are thought to contribute significantly to this inter-individual variability. While regular physical exercise seems to induce an increase in resting vagal tone, chronic life stress, and psychosocial factors such as negative moods and personality traits appear associated with vagal withdrawal. Preclinical research has been attempting to clarify such relationships and to provide insights into the neurobiological mechanisms underlying vagal tone impairment/enhancement. This paper focuses on rat studies that have explored the effects of stress, psychosocial factors and physical exercise on vagal modulation of resting HR. Results are discussed with regard to: (i) individual differences in resting vagal tone, cardiac stress reactivity and arrhythmia vulnerability; (ii) elucidation of the neurobiological determinants of resting vagal tone. The sinoatrial node has an intrinsic rate of spontaneous automaticity that sets the basic rhythm of the heartbeat  how resting vagal tone is regulated and measured, (ii) the relations among individual differences in resting vagal tone, cardiac stress reactivity, and arrhythmia vulnerability, and (iii) the role of stress, psychosocial factors and physical exercise on the neural determination of resting vagal tone.Cardiac vagal activity is generated by cardiac vagal pre-ganglionic neurones mainly located in the nucleus ambiguous (NAmb) of the lower brainstem Figure . Their aCardiac vagal activity is dependent on excitatory and inhibitory synaptic inputs  recorded by telemetry  or low (LAB) anxiety-related behavior  and autonomic neural control of resting HR was the focus of one of our recent investigations . On this regard, an elegant study conducted by Beig et al. (One possible limitation of these studies is that they applied protocols of forced exercise (treadmill or swimming). In doing so, the effects of physical exercise g et al.  investigg et al. . Rats sug et al. . ImportaAergic inhibition of neurons in the NTS involved in HR control  the effects of stress, psychosocial factors, and physical exercise on vagal modulation of resting HR, and (ii) the consequences of such effects on cardiac stress reactivity and arrhythmia vulnerability. Moreover, the results of these studies have provided preliminary insights into the central neural mechanisms underlying vagal tone impairment/enhancement, which may be exploited by future experiments aimed at developing pharmacological approaches for enhancing vagal activity and cardioprotection.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The development of alcohol dependence involves elevated anxiety, low mood, and increased sensitivity to stress, collectively labeled negative affect. Particularly interesting is the recent accumulating evidence that sensitized extrahypothalamic stress systems  are evident in withdrawn dependent rats, supporting the hypothesis that pathological neuroadaptations in the extended amygdala contribute to the negative affective state. Notably, hippocampal neurotoxicity observed as aberrant dentate gyrus (DG) neurogenesis  and DG neurodegeneration are observed in withdrawn dependent rats. These correlations between withdrawal and aberrant neurogenesis in dependent rats suggest that alterations in the DG could be hypothesized to be due to compromised HPA axis activity and associated hyperglutamatergic activity originating from the basolateral amygdala in withdrawn dependent rats. This review discusses a possible link between the neuroadaptations in the extended amygdala stress systems and the resulting pathological plasticity that could facilitate recruitment of new emotional memory circuits in the hippocampus as a function of aberrant DG neurogenesis. Accumulating evidence over the past four decades shows that forebrain neural stem cells populate two main areas, the subventricular zone of the lateral ventricles and subgranular zone (SGZ) of the hippocampal dentate gyrus  that proliferate into preneuronal progenitors (type 2 and type 3), which in turn differentiate into immature neurons and eventually mature into granule cell neurons  receptor activation reduces the proliferation of neural precursors in a normal state, and blockade of NMDA receptors increases the birth and survival of neural precursors in the DG, suggesting that neuronal inputs into the hippocampus regulate DG neurogenesis  model. The incorporation of these models has allowed us to determine the toxic and neuromodulatory effects of ethanol in specific brain regions and reward systems. The in vitro organotypic hippocampal cell culture model is commonly used to study hippocampal excitotoxicity associated with alcoholism. The in vitro model harbors critical hippocampal heterogeneity that is necessary for neuron\u2013neuron and neuron-glia interactions to occur, thus maintaining the structural and functional integrity of hippocampal circuitry and pharmacology  receptor-mediated currents] and decreases hippocampal (CA1 and DG) long-term potentiation  and produces tolerance to acute ethanol-mediated impairment of NMDA activity and hippocampal-dependent behaviors  resulting from termination of ethanol exposure may be regulated by a variety of neuroadaptations in the extended amygdala. These alterations may regulate the plasticity in the hippocampus to produce the withdrawal hyperexcitability associated with dependence  basal stress hormone levels (adrenocorticotropic hormone and corticosterone) compared with non-dependent drinking animals (enhanced stress hormone levels). It has been demonstrated that the blunted stress response is a consequence of chronic ethanol exposure (Zorrilla et al., in vitro organotypic hippocampal cell culture model (Wilkins et al., The aberrant stimulation of cell proliferation in the DG during withdrawal from chronic ethanol exposure has been demonstrated in the 1 receptors. Specific knockdown of CRF1 in BLA glutamatergic neurons produces anxiolytic-like effects (Refojo et al., 1 levels (Sommer et al., Possible mechanisms underlying ethanol withdrawal-induced aberrant DG cell proliferation and neurogenesis can be postulated based on the available literature. For example, the increased synthesis of hippocampal CRF during withdrawal (Criado et al., A related mechanism for ethanol withdrawal-induced increases in cell proliferation and DG neurogenesis could be ethanol withdrawal-induced blunting of corticosterone levels (Richardson et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Evaluation of right ventricular function is still technically challenging because of the complex anatomy of the RV. CMR has been used as the gold standard for quantitative assessment of RV function, but it is not used routinely in clinical settings since it is expensive and sometimes contraindicatedWe sought to evaluate right ventricular (RV) function by Cardiac Magnetic Resonance (CMR) and compare it with Doppler derived strain and strain rate (SR) imaging in patients with repaired tetralogy of fallot( TOF).34 patients  late after total correction of tetralogy of Fallot were evaluated. Absolute values of peak systolic strain and strain rate (SR) in the basal, mid, and apical segments of the RV free wall were measured and each segment and mean of three segments were compared with RV ejection fraction measured by CMR.RV function measured by CMR was negatively correlated with peak systolic strain of mid RV free wall and also negatively correlated to both mean of strain  and SR  of basal , mid and apical segments of RV.Overall, in the assessment of RV function , echocardiographic measurement of strain and SR and peak systolic strain of mid RV free wall have significant correlation with RV function measured by CMR."}
+{"text": "The Dutch Society of Infection Prevention in Healthcare society was founded in 1973 and is since 1987 member of the International Federation of Infection Control (IFIC). VHIG has currently 350 members entitled: Consultant Infection Prevention (CIP).Supporting the members in carrying out their task in all healthcare settings and disseminating information about the prevention and control of infections. The VHIG attempts to achieve its objectives by means of: giving information, instructions, advice, conferences, lectures and publications. VHIG takes care of Accreditation and re-registration every 5 year for all the members if they fulfil the requirements.Since 2006 the Dutch advice is 1 FTE CIP per 5000 admissions, or 1 / 178 hospital beds, which cannot fulfilled for different reasons. Dutch hospitals are committed to pursuing active infection control policies based on the Working group Infection Prevention (WIP). These guidelines are considered as professional standards by the Healthcare Inspectorate. The CIP gives shape to this standard. The professional background of the CIP is Nurse, Lab Technician, and Epidemiologist who graduate with a diploma after an in-service Post-Bachelor training of 18 month.\u2018Kwaliteitsrichtlijn voor Infectiepreventie in Ziekenhuizen\u2019 The document is based the ISO 9001:2000 series and the derived Directive for Healthcare.With the Dutch Society for Microbiology the VHIG drafted in 2008 a guideline for quality assurance to achieve continuous quality improvement File:2009/0003 (CNS. Hand hygiene and Surveillance surgical side infections are continuous on the agenda.NPR-CEN/TS 15224:2005. The VHIG try to implement the Recommendations of the Council of European Union on patient safety, including the prevention and control of healthcare associated infections (None declared."}
+{"text": "An allergist is a physician who has successfully completed both a specialized training period in allergy and immunology and a training period in either internal medicine, or a sub-specialty of internal medicine such as dermatology, pneumology, or otorhinolaryngology, and/or pediatrics. Subject to national training requirements, allergists are also partially or fully trained as clinical immunologists, because of the immune basis of the diseases that they diagnose and treat. In most countries, the approved period of specialty training in allergy and immunology will be two to three years of specific, intense training. Depending on national accreditation systems, completion of this training will be recognized by a Certificate of Specialized Training in Allergy, in Allergy and Immunology, or in Allergy and Clinical Immunology, awarded by a governing board. In some countries this will follow successful completion of a certification test, and in other countries by competencies being signed-off by a training supervisor.Fully trained allergists make an important contribution to designing local care systems and delivering the necessary care for patients with allergic diseases. Allergists act as advocates for patients, and support and argue the case for better education of the primary and secondary care physicians and other health care professionals who also care for allergic patients. Allergists should be available to provide care for the more complicated problems that are beyond the purview of well-trained primary and secondary care physicians and other health care professionals. The main defining characteristics of an allergist are the appreciation of the importance of external triggers in causing disease, and the knowledge of how to identify and manage these diseases, together with ex-pertise in appropriate drug and immunological therapies. This approach to diagnosis and therapy is a core value of the allergy specialist, and contrasts the allergist with many of the organ-based specialists whose patient bases may overlap with the specialty.http://www.worldallergy.org/allergy_certification/index.shtml.The unique training requirements for an allergist are detailed in \"Requirements for Physician Training in Allergy: Key Clinical Competencies Appropriate for the Care of Patients with Allergic or Immunologic Diseases: A Provisional Position Statement of the World Allergy Organization.\" In that The allergist is a physician who has a broad range of highly specialized clinical and diagnostic skills and a strong knowledge base covering:Disease manifestations, including those for every allergic, immunologic and overlapping disease, and the cellular basis of immune and allergic reactions;Rhino-conjunctivitisSinusitisOtitisAsthmaCoughBronchitisHypersensitivity pneumonitisAlveolitisAtopic dermatitis/eczemaContact dermatitisUrticaria and angioedemaDrug allergyFood allergyLatex AllergyInsect Allergy and Stinging-insect hypersensitivityGastrointestinal reactions resulting from allergyAnaphylactic shockImmunodeficienciesOccupational allergic diseasesRisk factors for progression of allergic diseases--the \"allergic march\"Other specific organ reactions resulting from allergyConditions that may mimic or overlap with allergic disease;The epidemiology and genetics of allergic diseases and auto-immune diseases, and a specialist knowledge of regional and local allergens, including aero allergens, drugs, venoms, occupational allergens, and food allergens;The effector cells involved in allergic disease ;The molecules involved in the immunological response (both innate and acquired), including chemical mediators; immunoglobulins; antibodies; complement; cytokines, including interleukins; chemokines and their receptors; and human leukocyte antigen/major histocompatibility complex (HLA/MHC) antigens;The main hypersensitivity reactions;Cell-to-cell interactions;in vitro laboratory diagnostic tests for allergy andtheir selection and interpretation, including radio-allergosorbent tests (CAP-RAST\u00ae); enzyme_linked immunosorbent assays (ELISAs); Western blotting; tests for inflammatory markers (eosinophil cationic protein [ECP] and tryptase); cellular antigen stimulation tests (CAST\u00ae), and histamine release assays.The scientific The allergist is especially competent in performing/interpreting the following:Allergic history and physical examinationSkin testingOrdering and interpreting allergy- and immunology-related laboratory testsEvaluation of total IgE and allergen specific IgE measurementsProvocation testing for allergic and immunologic diseaseAnalysis and advice regarding local environmental/airborne allergens and irritantsAnalysis and advice regarding ingested allergens/irritantsConducting and/or evaluating tests of pulmonary function and tests of inflammatory markersConducting and/or evaluating tests of nasal function; this may include examination of nose and throat via fiberoptic rhinoscopy and nasal endoscopySpecific allergen and venom immunotherapyPharmacotherapy of allergic disorders and related diseasesWhere necessary, investigating alternative diagnosesEnvironmental modification strategies to reduce allergen exposureImmunomodulatory therapyDrug desensitizationEvaluation and treatment of allergic and immunologic competencePrimary, secondary and tertiary prevention of allergic diseaseEducation for patients, caregivers and primary care physiciansAll societies that have commented and approvedAmerican Academy of Allergy, Asthma and ImmunologyAmerican College of Allergy, Asthma and ImmunologyArgentine Association of Allergy and ImmunologyAustralasian Society of Clinical Immunology and AllergyBangladesh Society of Allergy and ImmunologyBrazilian Society of Allergy and ImmunopathologyChilean Society of Allergy and ImmunologyColombian Allergy, Asthma, and Immunology AssociationDanish Society for AllergologyEgyptian Society of Allergy and Clinical ImmunologyFrench Society of Allergology and Clinical ImmunologyGerman Society for Allergology and Clinical ImmunologyHungarian Society of Allergology and Clinical ImmunologyItalian Society for Allergology and Clinical ImmunologyJapanese Society of AllergologyMalaysian Society of Allergy and ImmunologyMexican College of Allergy, Asthma and Clinical ImmunologyMongolian Society of AllergologyNetherlands Society of AllergologyParaguayan Society of Immunology and AllergyRomanian Society of Allergology and Clinical ImmunologyRussian Association of Allergology and Clinical ImmunologyAllergy Society of South AfricaSingapore Society of Immunology, Allergy & RheumatologySwiss Society of Allergology and ImmunologyAllergy and Immunology Society of ThailandTurkish National Society of Allergy and Clinical ImmunologyVenezuelan Society of Allergy and ImmunologyVietnam Association of Allergy, Asthma and Clinical ImmunologyZimbabwe Allergy SocietyThe Asia Pacific Association of Allergology and Clinical ImmunologyCzech Society of Allergology and Clinical Immunology"}
+{"text": "Dendritic cells (DCs) were first described by Steinman and Cohn in 1973 . The worDendritic cells are highly heterogeneous. Two major classes of DCs have been described: classical or conventional and plasmacytoid DCs (pDCs). Classical DCs are cells of myeloid origin capable of efficiently capturing microbial antigens, and, after homing to lymph nodes and antigen processing, present these antigens to prime naive T cells. Diversely, pDCs are poorly phagocytic but recognize viruses very well. Upon encounter of microbial stimuli, they also differentiate into efficient antigen-presenting cells and express high levels of type I interferons (IFNs) . Based oThe DC capacity of inducing both immunity and tolerance may seem a contradictory aspect of DC biology, nevertheless the acquisition of these two different properties may depend on stimuli DC are exposed to or may be a specific feature of different DC subsets.Dendritic cells sense the presence of exogenous microbial signals through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms or endogenous danger signals. The consequences of the activation of these receptors on DCs have been implicated in the acquisition of the immunogenic functions characterized by the increase of antigen presentation and costimulation as well as the release of proinflammatory cytokines. The attainment of the tolerogenic function by DCs seems instead to be more linked to the exposure to endogenous factors sensed in peripheral tissues under steady state conditions.In the present Research topic, contributing articles describe a number of aspects determining the tolerogenic or immunogenic functions of DCs. In particular, the themes that will be discussed concern the role of DCs in controlling the threshold of activation of T cells; the role of the diverse costimulatory molecules, either secreted by DC subsets or expressed on the cell surface, in determining the DC immunogenic or tolerogenic functions; the role of endogenous or exogenous stimuli in influencing the DC functional state; some specific roles of DCs in preventing particular organ autoimmunity and, finally, possible therapeutic potentials of immunogenic or tolerogenic DCs.Understanding the mechanisms that regulate the functional properties of DCs will allow exploiting these cells in new effective therapeutic strategies, including cancer immunotherapy and control of autoimmunity, to improve intervention outcomes. Understanding DC biology and their responses to activating stimuli will also help the identification of novel adjuvants to be used in new vaccine formulations."}
+{"text": "Larus hyperboreus), Ivory gull (Pagophila eburnea), Great skua (Stercorarius skua), Arctic fox (Alopex lagopus) and Polar bear (Ursus maritimus). The POPs include both old  and new contaminants (polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs) and polychlorinated naphthalenes (PCNs). While the contaminants which are subjected to global bans or restrictions are decreasing, new and emerging chemicals are increasing in Arctic birds and mammals. Several species are also exposed to contaminant metabolites  that, at times, are more bioactive than their precursors. Of high concern are the potential effects of the POPs and their metabolites in exposed seabird species. The present presentation summarizes recent studies on biological effects in relation to POP exposure in seabirds.Persistent organic pollutants (POPs) and their degradation and metabolic byproducts have been found in high levels in blood and tissues of several Arctic seabird- and mammal species (Glaucous gull ("}
+{"text": "X-linked hypohidrotic ectodermal dysplasia  has been classically described as affecting hair, sweat glands and dentition. What may be underappreciated is the effect ectodysplasin deficiency has on glands surrounding the airways and eyes and the resulting chronic health issues. In this study, we evaluated respiratory and ocular symptoms in XLHED patients.EDA genotype were included in correlation analyses.12 male children and 14 male adults with XLHED, age range 6 to 58 years, and 12 healthy controls were assessed for signs of asthma by pulmonary function tests and measurement of exhaled nitric oxide (FeNO), and for dry eye disease by investigating ocular surface lubrication. Descriptive statistics were calculated. Standardized sweat duct counts and EDA gene expression, correlated with milder disease in two XLHED subjects with mutations affecting the collagen-like domain of ectodysplasin.Respiratory symptoms and elevated FeNO as a sign of pulmonary inflammation were detected in the majority of XLHED subjects, in similar numbers of children and adults. Increased tear osmolarity, reduced tear film break-up time and other ocular abnormalities were also present at an early age. Approximately half of the patients not reporting a history of asthma or dry eye showed at least two abnormal test results in the respective organ system. The presence of residual sweat ducts, suggestive of partial The high prevalence of asthma-like symptoms and dry eye syndrome in XLHED patients as young as 6 years indicates that screening evaluation, regular monitoring and consideration of therapeutic intervention should begin in early childhood."}
+{"text": "With the advent of multimodality imaging, molecular information by tracer techniques can be combined with high resolution structural and functional imaging by MRI. Specific tracers address biological processes of the oncogenic process, which allow not only early detection of malignant tissue, but may also provide prognostic information of oncological diseases. Most importantly, imaging biomarkers can be used to select patients for a given therapy (companion diagnostics) and to monitor response in order to optimize therapeutic strategies tailored to the needs of the individual patient. Examples of new molecular tracers are Gallium-68 labeled peptides targeting integrins, ligands of the chemokine CXCR4 and somatostatine receptors. These tracers do not only address cell surface proteins (receptors), but also the interaction of cells as well as cell migration, which have been linked to angiogenesis and metastasis. Since FDG is not very useful in patients with prostate cancer, the recent introduction of Gallium-68-PSMA has added excellent diagnostic sensitivity and specificity for PET diagnosis of prostate cancer, especially in patients with recurrent disease. The combination of molecular targeting of prostate cancer with measurements of regional perfusion (DCE) and cellularity (DWI) provided by MRI offers a comprehensive and innovative multimodality diagnostic approach. Regional phenotyping of malignant tissue addresses the spatial as well as dynamic heterogeneity of cancer, which may provide unique insights into mechanisms of therapeutic response and resistance. It can hypothesized, that multimodality molecular imaging and radionuclide therapy will be an important part of the emerging concepts of \u201ctheranostics\u201d and further strengthen the role of Nuclear Medicine in precision medicine evaluating cancer patients."}
+{"text": "Introduction: Anti-inflammatory drugs (NSAIDs) represent one of the classes of drugs commonly recommended for patients with osteoarthritis. These drugs have side effects that sometimes affect the digestive tract.Patients and Methods: 30 patients with either axial or peripheral osteoarthritis, hospitalized between January 2013 and January 2015 in the Rehabilitation Clinic of the Clinical Emergency County Hospital of Craiova, were followed. All the patients included had upper gastrointestinal endoscopy performed, excluding patients who had a history of gastritis, endoscopically demonstrated ulcer or those with a history of gastrointestinal dyspeptic phenomena.Results: The endoscopic examination found acute erosive gastritis in eight cases, gastric ulcer (four cases) and duodenal ulcer (six cases). No serious complications were encountered. Four patients had no clinical manifestations with endoscopic expression. Lesions were mainly mild esophagitis (Grade I) and only in three cases, esophagitis grade II or III was found. Twelve patients (40%) had Helicobacter pylori infection and had endoscopic changes .Conclusions: The adverse effects of NSAIDs in patients with osteoarthritis vary in severity. Patient age significantly influences the severity of injuries. We have not found significant differences in the incidence of COX2 selective and non-selective NSAID-induced lesions. Pathogenic interaction between the NSAID and Helicobacter Pylori infection is most often a synergistic effect in the development of gastritis or gastroduodenal ulcer. In addition to the specific effect of improving the symptoms of painful and inflammatory conditions, these agents sometimes have significant side effects usually related to the dose and duration of administration [2\u20136].Anti-inflammatory drugs (NSAIDs) represent one of the classes of drugs commonly recommended for patients with osteoarthritis [The main adverse effects described in the upper digestive tract after prolonged administration of NSAIDs are:7]- Esophagitis and esophageal strictures - Acute erosive gastritis and/ or bleeding [5]- Gastric or duodenal ulcer, sometimes complicated by perforation [5\u20137]- Upper gastrointestinal bleeding .The pathogenesis of NSAID-induced gastrointestinal lesions requires the intervention of several local and systemic mechanisms .NSAIDs with acid structure cannot biochemically dissociate in the intragastric acid environment and remain in lipophilic form, which facilitates their penetration through the mucus layer on the surface of the gastric epithelium. The interaction with the phospholipid membrane surface of the epithelial cells leads to loss of the hydrophobic capacity and favors retrodiffusion of the H + ions (the main cause of ulcers) .- \u201cIon capturing\u201d and depletion of ATP - within the intracellular environment of the stomach, NSAIDs dissociates in H + and the ionic form that cannot leave the cell and remains sequestered. Both intracellular components have toxic effects either by the absence of the coupling of oxidative phosphorylation, or by inhibiting the respiratory chain [10]. The consequence is the decline in local, intracellular, stocks of ATP, altered intercellular junctions, H + ions retro diffusion fostering and facilitating effect of endogenous aggressive factors  involved in ulcers .- Systemic effects of inhibition of cyclooxygenases 1 and 2 are the main mechanism of action of NSAIDs [12\u201314]. The decrease in prostaglandin synthesis causes an impairment of local defense mechanisms of the gastric mucosa with a decreased local production of mucus and reduced local microcirculation blood flow.- 10,15].Cyclooxygenase 1 is involved in the production of prostaglandins in the gastric protective inhibit gastric acid secretion, stimulates the synthesis of mucous and bicarbonate and the immune cell function in the stomach lining .Cyclooxygenase 2 has local and systemic proinflammatory effects. Therefore, it follows that the use of selective NSAIDs (COX-2 inhibitors) has, at least theoretically, less risk of developing mucosal lesions in the upper digestive tract . Gastroduodenal lesions are the most common side effects of NSAIDs long used by patients with arthritis.Local inflammation caused by acid reflux is followed by healing with excessive synthesis of collagen fibers, which leads to esophageal strictures .Most studies published so far assessed the advanced age of patients as being the main risk factor for NSAID induced gastrointestinal complications [18].There are several hypotheses on the role of comorbidities or other medication associated with specific diseases of this age, but it seems however that the main mechanism is the decreased regeneration ability of mucosal defense in the elderly .There are substantial differences between gastroduodenal tolerability of various classes of NSAIDs used in practice. An inverse correlation between COX2 selective NSAIDs and digestive complications was suggested. In our study, we did not find these differences, endoscopic changes being encountered in the 10 patients who were treated with COX2 selective NSAIDs . In our study, 12 patients (40%) were infected with HP and had endoscopic changes at the gastric or duodenal level Pathogen interactions between HP infection and consumption of NSAIDs in the digestive tract lesions are currently arousing much controversy [7\u20139]. Both factors inhibit the secretion of mucus and bicarbonate . However, the effect on local microvasculature is different. NSAIDs decrease local blood flow by reducing prostaglandin synthesis while HP infection does not affect this mechanism. However, experimental studies have shown that the gastric and duodenal mucosa regeneration is much better after administering therapy for eradicating the HP infection [9].There are a number of common mechanisms by which NSAIDs and HP contribute to digestive tract lesions, even though they have divergent mechanisms [NSAID adverse effects seen in patients with osteoarthritis who use this medication for long periods vary in severity from functional digestive phenomena to gastric and duodenal ulcer.The pathogenic mechanisms are local and systemic but all target local factors aimed at the defense of the digestive tract .Patient age significantly influences the severity of NSAID-induced lesions due to lower defense capability and regeneration of the digestive tract, comorbidities, and other associated treatments.In our study, we found no significant differences in the incidence of NSAID-induced lesions of both COX2 selective and nonselective variants, although references in literature showed a less aggressive potential of selective COX2 inhibitors on the gastrointestinal mucosa.Pathogen interactions between NSAIDs and HP infection are mostly synergistic in the development of gastritis or peptic ulcer, a fact sustained by the faster recovery of the integrity of the digestive mucosa after eradication therapy."}
+{"text": "The data was double entered with adequate checks and validated in EpiData. Final data after correcting the data entry errors has been shared here. In addition, we have shared data entry plan, EpiData triplet files for data entry and program file for data analysis. They may be used by other researchers who intend to replicate this research in their setting.This Data in Brief article contains individual level data of a randomized trial in a primary care setting. This trial offered mobile reminder to follow up for definitive tests during opportunistic screening of diabetes mellitus in Puducherry, India (2014).   Among those who were eligible for definitive tests, the variables collected were group (intervention/control), whether the mobile reminder call was answered (for intervention arm), follow up done (yes/no), fasting and post-prandial blood glucose (for those who followed up). Some variables were derived during data entry: eligibility for definitive tests based on RBG value and diabetes status based on the fasting and post-prandial blood glucose values. Additional variables were derived during data analysis: epidemiologic diagnosis of diabetes and pre-diabetes (if either one of the two definitive tests was within the diabetic or pre-diabetic range).In this dataset, the variables collected for each study participant (QuEStionnaire file defines the structure of the database and layout of data entry. RECord file holds the entered data and into which data is entered. CHecK file holds the data checking rules during data entry. These EpiData triplet files are simple text (ASCII) files [2].We are also sharing the case record form, data entry plan (codebook), empty EpiData files, EpiData files which include the REC file containing data and EpiData program file (computer code) for analysis . EpiData triplet files include questionnaire (QES), record (REC), and check (CHK) files. 2The study was approved by the Institute Ethics Committee, Indira Gandhi Medical College and Research Institute, Puducherry. The study was registered with Clinical Trials Registry \u2013 India (CTRI/2014/10/005138). The data collection was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).This was a randomized trial conducted in a primary health care setting offering routine opportunistic screening for diabetes mellitus A codebook or plan of data entry was prepared using a Microsoft Excel sheet before data entry. With the codebook as the base, EpiData triplet files were created for electronic data entry. A program file was prepared for data analysis and can be run using EpiData analysis software.This was an operational research carried out using available resources and manpower at the Primary Health Centre. The authors declare that there was no source of funding separately for the research.Conflict of interestNone declared."}
+{"text": "Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA) has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction. Gonadotropin-releasing hormone (GnRH) neurons constitute the final output neurons in the neuroendocrine control of reproduction Freeman, . PulsatiA   was more positive than the resting potential in mouse GnRH neurons    determines the polarity of the GABA response , which couples the K+ electrochemical gradient to Cl\u2212 extrusion, is the principal molecule which maintains low [Cl\u2212]i in mature neurons , which mediates inward transport of Cl\u2212, maintains high [Cl\u2212]i  , is an allosteric antagonist. Allopregnanolone increased GABAergic miniature postsynaptic current frequency, amplitude and decay time. DHEAS reduced mPSC frequency and amplitude but did not alter decay time  agonists reduced the frequency of GABA transmission to GnRH neurons  displayed disruption of cyclicity and fertility (Catalano et al., B1KO mice showed increased Gnrh1 and Gad1 expression but decreased Kiss1 expression in the medial basal hypothalamus of neonatal mice (Di Giorgio et al., B receptors is also important for regulating the estrous cycle.GABA plays a critical role in mediating both estradiol negative and positive feedback and appears to control the timing of the switch in estradiol feedback action. The frequency of GABA transmission to GnRH neurons is directly correlated with estradiol negative and positive feedback. Frequency of GABAergic postsynaptic currents was low during negative feedback but frequency and amplitude of GABAergic postsynaptic currents was increased at surge onset (Christian and Moenter, Metabolic signals have influences on fertility. GABA neuron-specific leptin receptor knock-out female and male mice show significantly delayed puberty onset (Zuure et al., in utero, the size and frequency of GABAergic postsynaptic currents were increased (Sullivan and Moenter, In human, GABAergic axons exhibiting VGAT immunoreactivity innervate the soma and dendrites of GnRH neurons (Hrabovszky et al., in vitro studies, further work is needed to determine the precise functional roles of direct GABAergic inputs to GnRH neurons in vivo. Because most GnRH neurons show the unusual characteristic of being excited by GABA, the excitatory action of GABA might make a major contribution to the regulation of GnRH neuron activity and secretion. As aberrant central GABAergic signaling is seen in polycystic ovary syndrome model mice, change in neuronal GABA activity appears to alter reproductive status both physiologically and pathologically. Therefore, determination of the precise role of GABAergic transmission in the regulation of GnRH neurons is important for understanding the regulation of normal reproduction as well as the hypothalamic abnormalities of fertility disorders.Although the importance of GABAergic inputs has been demonstrated in The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Epithelial ovarian cancer is the most lethal and second most common gynecologic cancer in the United States. Previous studies have demonstrated the favorable prognostic value of tumor infiltrating lymphocytes in this disease. The objective of this study was to evaluate the prognostic value and the biological correlates for lymphocyte specific kinase (LCK) expression in high grade serous ovarian cancer.LCK mRNA and protein (included in the reverse Phase protein array (RPPA) data) expression was evaluated using the ovarian cancer TCGA dataset. Gene expression was compared between the LCK high and normal tumors was compared. LCK protein expression was also evaluated using IHC in an independent set of high grade serous ovarian cancers, borderline tumors, benign cystadenomas, and normal fallopian tubes (tissue of origin of serous neoplasms).Using a SD of 1.86 above the mean as a cutoff, LCK mRNA high samples were associated with both an improved progression free and overall survival (pLCK serves as a biomarker of prognostic and biological importance in ovarian cancer. Ongoing investigation is aimed at better understanding the immunological correlates of high LCK expression in ovarian cancer."}
+{"text": "The local circuitry of the tegmental area (VTA) consists primarily of dopamine (DA) and GABA neurons. Interactions between DA and GABA neurons are critical for regulating DA neuron activity, and thus DA efflux throughout the brain. One striking example that demonstrates the significance of local interactions between DA and GABA neurons is related to nicotine reinforcement. Experimentally, it was shown that activation of nicotinic acetylcholine (nAch) receptors on GABA neurons by Ach leads to an increase in both firing and bursting of the DA neuron, while nicotine produces an opposite effect . In orde"}
+{"text": "Yomo and Hayashi reported results of stereotactic radiosurgery alone for brainmetastases from small cell lung cancer. This strategy aims to avoid theneurocognitive effects of whole-brain radiation therapy. However, radiosurgeryalone increases the risk of distant intracranial relapse, which canindependently worsen cognition. This concern is heightened in histologies likesmall cell with high predilection for intracranial spread. The majority of studypatients developed new brain disease, suggesting radiosurgery alone may not bean optimal strategy for preserving neurocognitive function in this population.We suggest whole-brain radiation therapy should remain the standard of care forsmall cell lung cancer. Letter to the Editor:Radiation Oncology their experiencewith upfront stereotactic radiosurgery (SRS) for brain metastases from small celllung cancer (SCLC) [Yomo and Hayashi recently reported in r (SCLC) . The autThe strategy of upfront SRS is gaining increasing prominence , spurredWhich is more important for preserving neurocognition: limiting the volume ofirradiated brain or maximizing intracranial tumor control? The answer is uncertain,and ongoing studies aim to resolve this question . Should these trialsfavor SRS, we anticipate increased enthusiasm for radiosurgery in all tumorhistologies \u2013 including SCLC \u2013 and Yomo and Hayashi\u2019s study willbe an important initial report in this population. In the meantime, however, wesuggest that WBRT remain the standard of care for patients with brain metastasesfrom SCLC.MAB is Chief of the Central Nervous System Service and CBS 2nd is Chief of theThoracic Service in the Department of Radiation Oncology."}
+{"text": "The possibility of pRT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment.Palliative radiotherapy (pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer (CRPC). However, evidence that pRT influences prostate-specific antigen response in patients with CRPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel ( All patients had received at least two previous lines of therapy. Two patients were receiving salvage treatment with palliative chemotherapy using docetaxel and one patient was on abiraterone acetate. All patients were also receiving synchronous prednisolone, bisphosphonate (zoledronic acid), and LHRH analogue therapy. Patient and disease-related characteristics combined with initial management and subsequent lines of therapy are summarized in Patients receiving docetaxel chemotherapy received up to four cycles (three weekly), and the patient on abiraterone acetate received 10 weeks of treatment. All patients showed evidence of symptomatic and rapid biochemical progression with increasing PSA velocity and doubling time of less than 6 weeks, thereby raising a strong argument for the discontinuation of salvage systemic treatment. However, all patients were referred for fractionated pRT (20 Gy in 5 fractions) because of increasing bone pain. Two patients received radiotherapy to the spine, and one patient received radiotherapy to the pelvis. Chemotherapy was interrupted during radiotherapy, and docetaxel was recommenced in patients at least 2 weeks after completion of radiotherapy. However, the patient receiving abiraterone acetate continued with treatment during radiotherapy. The PSA kinetics during systemic treatment and following completion of radiotherapy are displayed in Following completion of radiotherapy, a dramatic biochemical response was observed with a marked reduction in PSA levels in all patients, which was associated with symptomatic response and clinical improvement. The biochemical response after radiotherapy was striking, with PSA reducing to 30%-60% from baseline peak levels within 6 weeks of completion of treatment. All patients recommenced previous systemic therapy, and subsequent treatment cycles were associated with preserved biochemical response and disease stabilization on repeat staging investigations (et al.The possibility of pRT influencing metastatic disease has been reported previously in the context of metastatic melanomaThe aforementioned cases demonstrated remarkable similarity in terms of advanced castrate-resistant disease and signs of rapid disease progression on systemic therapy prior to fractionated pRT for metastatic bone disease. Subsequently, these patients demonstrated an excellent response with marked reduction in PSA levels that matched the rate of progression and PSA velocity prior to radiotherapy. The probability of delayed PSA response to systemic therapies remains a distinct possibility in this situation. However, the paradoxical and extremely rapid levels of PSA reduction are relatively uncommon in the context of systemic treatment of prostate cancer. The timing and unusual nature of the PSA response does raise the provocative probability of likely association with immune stimulatory effects of pRT that may promote a synergistic interaction between radiation and systemic therapy. Indeed, the possible existence of such a phenomenon may enable the exploration of several novel therapeutic strategies in the future management of CRPC."}
+{"text": "Very recently, a limited number of publications on animal-based models of alcoholic fatty liver diseases have reported that Parkin-mediated mitophagy may mitigate hepatocyte apoptosis, improve mitochondrial quality and suppress steatosis (lipid accumulation). From this perspective, the authors focus on the mechanisms of Parkin mitochondrial translocation (a key consideration in mitophagy activation) and therapeutic implications of mitophagy in liver disease. DNA repair and other functions of Parkin beyond mitophagy are also briefly discussed. The paper additionally shows original data from the authors\u2019 current research indicating enhanced hepatic mitophagy in ethanol-treated rats, which is associated with Parkin mitochondrial translocation triggered by oxidative mitochondrial DNA damage. Natural or pharmaceutical products that may trigger Parkin mitochondrial translocation in hepatocytes and/or suppress repressors of such translocation could be a potential therapeutic target in alcoholic and non-alcoholic fatty liver disease.A growing body of evidence based on  Autophagy (macroautophagy) is a prosurvival pathway for lysosomal degradation of most cellular components in response to diverse conditions of stress, such as oxidative stress, DNA damage, and lipid overload. Selective autophagic elimination of proapoptotic mitochondria is called mitophagy . The PINin vitro studies, it is considered that various mechanisms  and mitochondrial DNA (mtDNA) damage may activate mitophagy , a marked increase in the number of mitophagic vacuoles  was observed in the majority of normal hepatocytes in ethanol-treated rats (ETRs) within 6 h of a single intraperitoneal injection of ethanol (5 g/kg). However, the level of apoptotic hepatocytes was very low (data not shown). This enhanced mitophagy of ETRs hepatocytes was associated Parkin mitochondrial translocation as shown by IEM  and immunofluorescence double labeling of Parkin and cytochrome c . Also, Parkin also was detected clearly in mitophagosomes as shown in Supplementary Figure S1. Interestingly in ETRs, and as a novel unreported finding revealed by IEM, Parkin was observed to be selectively translocated to hepatocyte mitochondria and mitophagosomes enriched with 8-OHdG, which is a marker of oxidative mtDNA damage and mutagenicity . We confirmed this colocalization of Parkin and 8-OHdG using immunofluorescence double labeling technique (Immunoelectron microscopy (IEM) techniques play important roles in the exploration of components and trafficking in autophagic machinery, especially in relation to membranous structures that can only be clearly identified and localized using electron microscopes . As mostgenicity   may be a signal for mitophagy induction and formation of mitophagosomes via the triggering of Parkin mitochondrial translocation  with metformin was found to enhance prosurvival mitophagy in hepatocytes by suppressing the inhibitory interaction of cytosolic p53 with Parkin, allowing Parkin mitochondrial translocation and increasing the degradation of mitofusins (A cumulative body of evidence indicates that the mitochondrion is the main target for alcohol toxicity . Accorditofusins . Howevertofusins .The proper understanding of the molecular mechanisms of mitophagy may be essential for the treatment of fatty liver disease induced by or associated with mitochondrial damage. IEM may be a powerful tool for detecting changes in subcellular localization of mitophagy proteins under various conditions, which may have diagnostic and therapeutic implications. Selective stimulation of Parkin-mediated mitophagy via the enhancement of its expression and/or mitochondrial translocation using natural or pharmaceutical products may have therapeutic potential for improving mitochondrial quality and survival, suppressing steatosis and preventing mutagenicity in fatty liver disease.The animals were maintained and treated according to the guidelines set by the Experimental Animal Research Committee of Osaka Medical College.NE performed the experimental work, electron microscopic studies, and wrote the manuscript, YI participated in experimental work and design, YO participated in design of experiment and revised the paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Molecular functional imaging (MFI) has given a newer insight to the medical imaging and has diversified the role of imaging in the field of the translational cancer medicine and has an indispensible role to play in screening, early diagnosis, staging, predicting prognosis, therapy delivery, therapy monitoring and follow-up. Overall there has been a significant development in the field of molecular imaging and its utilisation in the perspective of the biomedical research which has led to better understanding of the signalling pathways in the tumourigenesis and novel drug discoveries.Review and Highlight the complementary role of these techniques in the detection and staging of tumours and which of these techniques is more adequate for clinical scenarios in oncology.\u2022 Cancer And Molecular Functional Imaging (MFI)\u2022 MFI Of Gene Expression, Receptors And Signalling Pathways\u2022 MFI of Multidrug-Resistance In Cancer\u2022 MFI Of Extracellular Matrix And Its Key Components\u2022 MFI Of Neoangiogenesis, Hypoxia And Metabolism\u2022 MFI And Small Animal Imagingst century and beyond.The future of molecular functional imaging in the coming era is its exploitation into understanding the gene expression profiling in-vivo and optimising the patient specific therapies using gene expression profiling. Quantitative molecular functional imaging, in conjunction with quantitative structural imaging, will be the future of 'personalised radiology,' 'personalised oncology,' 'personalised medicine,' and of oncologic research in the 21"}
+{"text": "With increasing emphasis on patient and family-centred care, it follows that patients and their family members should be included when priorities for improving care are established. We therefore used a novel methodology that employs former patients and family members as researchers to describe the experiences of critically ill patients and their families with ICUs and to identify opportunities for improvement.Using the patient engagement framework developed by Marlett and Emes, we engaged four former patients and family members trained in qualitative research methods to conduct and analyse semistructured focus groups and interviews with adult patients who had recovered from critical illness and family members of both surviving and deceased patients. Participants were recruited from 13 ICUs in Alberta, Canada. Focus groups and interviews were recorded, transcribed and analysed using phenomenological reduction. Data collection continued until thematic saturation was reached.n = 11) and family members (n = 21) participated in five focus groups (n = 23 participants) and eight interviews (n = 9 participants). Participants articulated themes reflecting important components of care organised across three phases of the ICU experience; admission to ICU, daily care in ICU and after ICU discharge. Admission to ICU comprised three themes: patient and family transition into ICU, patient and family disorientation upon admission to ICU and preferred staff actions to help patients/ family adapt to the ICU. The daily care phase of ICU consisted of five themes: honouring patient's voices, needing to know, making decisions, culture in ICU and medical care. The experience after ICU discharge comprised two themes: transition from ICU to a hospital ward and long-term effects of critical illness. Participants identified five priorities for improvement: provide families with a guide/navigator; educate providers about the fragility of family trust; improve provider communication skills; inform patients about the long-term effects of critical illness; and develop strategies to facilitate continuity of care between providers.Thirty-two participants including patients (Patients and family members are an untapped resource and engaging them as researchers is a viable strategy to identify opportunities for quality improvement that are patient and family centred."}
+{"text": "The study examined the prevalence of trauma and posttraumatic stress disorder (PTSD) symptoms among community dwelling Chinese adults in Hong Kong. The relationship of traumatic life events (including loss) and mental health has been investigated.The sampling of the collaborative study  adopts a multi-stage stratification approach with the distribution of residential premises in different geographical districts and the relative proportion of private versus public housing units taken into consideration. In Phase I of this study, 4,644 adults were screened for PTSD with the Trauma Screening Questionnaire (TSQ) and Life Event Checklist (LEC), Beck's scales and CIS-R . In Phase II of the study, clinical psychologists conducted the Structured Clinical Interview for DSM Disorders (SCID) for 92 participants (results not reported here).p<0.001. Findings of hierarchical regression showed that type of trauma  contributed significantly to the prediction of all the mental health indices after demographic and social variables were controlled.Among Phase I participants, 65% reported traumatic experience . Age and gender make a difference in traumatic experience. When compared to participants who reported no traumatic experience in the past, participants who reported to have personal experience of sudden death of significant others or other traumatic experiences were found to have higher TSQ scores, higher psychological distress, lower social support , and lower life functioning , Public education on the association of traumatic experience and psychological health, as well as the monitoring of mental health for at-risk individuals are suggested for early identification of people in need of mental health services."}
+{"text": "QST\u2014FST comparisons, (i) no effect of selection (QST \u2248 FST); (ii) diversifying selection (QST > FST); (iii) convergent selection (QST < FST) [51\u201352].There is an error in the third sentence of the sixth paragraph of the Introduction. The correct sentence is: There are three widely accepted scenarios of QST estimates were calculated for each measured trait using the equation QST = VPOP/(VACC+VPOP) where VPOP is the estimated variance component for the population effect and VACC is the estimated variance component for the accession (= genotype) effect.There is an error in the fourth sentence of the second paragraph of the Assessment of quantitative trait variation subsection of the Materials and methods. The correct sentence is: The"}
+{"text": "Preventable infections contribute significantly to disease burden in Nigeria. Improving hand hygiene in healthcare, communities and general population can break the chain in the spread of most germs that threaten health and drag on socioeconomic development. Hand hygiene is fundamental to patient safety and important to occupational health \u2013 both are interconnected. The occupational health benefits of hand hygiene to healthcare workers provide additional incentives / motivation \u2013 acting in their own self-interest as well as duty of care. Implementing hand hygiene improvement at national and facility level involves managing behaviour and expectations and managing change.This presentation seeks to share our experience in implementing hand hygiene partner programme (HHPP) in Nigeria between 2012 and 2013 with the support of a reputable external private sector partner.The HHPP was implemented in partnership with the Federal Ministry of Health in three key components - stakeholders training, mini targeted local seminars and conferences, carefully structured and committed introduction of WHO multimodal hand hygiene improvement strategy focusing on maternal and child units.High level of interest and awareness in hand hygiene in general and the use and role of alcohol based hand rub in infection control were created among key decision makers and opinion leaders, government officials and healthcare workers in Nigeria.As we continue to work hard and drive our hand hygiene programme, we hope that the lessons from our experience would be useful in sustaining hand hygiene improvement and public health in Nigeria as well as prove transferable across the big diverse population of over 170 million people and other developing countries as part of strengthening health systems. The Ebola Virus Disease pandemic provides additional advocacy to strengthen infection prevention and control systems. Improvement in hand hygiene is one of the pillars for success.S. Kama-Kieghe Employee of: SKD Productivity Center, Shareholder of: Managing Partner, B. Okeke Employee of: GOJO industries-Europe Ltd."}
+{"text": "The Remote Associates Test (RAT) is widely used in experimental psychology to assess verbal creative thinking . SubjectIn order to elucidate possible neural mechanisms underlying the RAT, we here propose a neural field model that combines the idea of Hebbian cell assemblies (CAs) with a winner-take-all competitive process for assembly selection (WTA), and inhibition-of-return (IOR)  to allowWe present computer simulations of the search process in a space of associated words under different conditions regarding association strength between close and remote associates, search time limits, and the impact of noise on RAT performance. We also analyse the network dynamics to determine conditions that allow for the existence of remote associates and that support a Markovian search dynamic as described experimentally ."}
+{"text": "In this paper, a fractional complex transform (FCT) is used to convert the given fractional partial differential equations (FPDEs) into corresponding partial differential equations (PDEs) and subsequently Reduced Differential Transform Method (RDTM) is applied on the transformed system of linear and nonlinear time-fractional PDEs. The results so obtained are re-stated by making use of inverse transformation which yields it in terms of original variables. It is observed that the proposed algorithm is highly efficient and appropriate for fractional PDEs and hence can be extended to other complex problems of diversified nonlinear nature. Fractional differential equations arise in almost all areas of physics, applied and engineering sciences In this section, we give some basic formula and results about fractional calculus, and then we discuss the analysis reduced differential transform method (RDTM) to fractional partial differential equations.Some useful results and properties of Jumarie's fractional derivative were summarized p, q, k, and l are unknown constants, The fractional complex transform was first proposed To demonstrate the basic idea of the DTM, differential transform of The differential inverse transform of Eq. (8) is known as the Taylor series expansion of Theorem 1: If the original function is Theorem 2: If Theorem 3: If Theorem 4: If Theorem 5: If Theorem 6: If Theorem 7: If Theorem 8: If Theorem 9: If In this section, we shall apply the reduced differential transform method (RDTM) to construct approximate solutions for some nonlinear fractional PDEs in mathematical physics and then compare approximate solutions to the exact solutions as follows.Applying the differential transform to Eq. (14) and Eq. (13), we obtain the following recursive formula The series solution is given byThe inverse transformation will yieldsThis solution is convergent to the exact solution : Surface plot of approximate and exact solutions of (12) for different values of th order of RDTM solution are:Applying the transformation Applying the differential transform to Eq. (21) and Eq. (20), we obtain the following recursive formula Finally, after applying the inverse transformation the approximate solution isThe exact solution : Surface plot of approximate and exact solutions of (19) for different values of th order of RDTM solution are:Applying the differential transform to Eq. (28) and (27), we obtain the following recursive formula The series solution is given byFinally, the inverse transformation will yields the solutionWhere the exact solution is: Surface plot of approximate and exact solutions of (26) for different values of th order of RDTM solution are:Applying the RDTM to (35) and (34), we obtain the recursive relationThe series solution is given byFinally, the inverse transformation will yields the solutionWhere the exact solution is: Surface plot of approximate and exact solutions of (33) for different values of th order of RDTM solution are:Applying the transformation Applying the RDTM to (42) and (41), we obtain the recursive relationThe series solution is given byFinally, the inverse transformation will yields the solutionThe exact solution : Surface plot of approximate and exact solutions of (32) for different values of th order of RDTM solution are:Applied fractional complex transform (FCT) proved very effective to convert the given fractional partial differential equations (FPDEs) into corresponding partial differential equations (PDEs) and the same is true for its subsequent effect in Reduced Differential Transform Method (RDTM) which was implemented on the transformed system of linear and nonlinear time-fractional PDEs. The solution obtained by Reduced Differential Transform Method (RDTM) is an infinite power series for appropriate initial condition, which can in turn express the exact solutions in a closed form. The results show that the Reduced Differential Transform Method (RDTM) is a powerful mathematical tool for solving partial differential equations with variable coefficients. Computational work fully re-confirms the reliability and efficacy of the proposed algorithm and hence it may be concluded that presented scheme may be applied to a wide range of physical and engineering problems."}
+{"text": "The electronic MEdical Records & GEnomics (eMERGE) network was established in 2007 by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) in part to explore the utility of electronic medical records (EMRs) in genome science. The initial focus was on discovery primarily using the genome-wide association paradigm, but more recently, the network has begun evaluating mechanisms to implement new genomic information coupled to clinical decision support into EMRs. Herein, we describe this evolution including the development of the individual and merged eMERGE genomic datasets, the contribution the network has made toward genomic discovery and human health, and the steps taken toward the next generation genotype-phenotype association studies and clinical implementation. In addition for the potential for large sample sizes of diverse groups, biobanks linked to EMRs make possible the study of many different outcomes and traits, many of which may not be routinely collected by traditional epidemiologic cohorts. And, in this burgeoning era of precision or personalized medicine, biobanks in clinical settings offer unprecedented opportunities to quickly translate research findings to improvements in patient care.In recognition of the potential for EMR-linked biobanks to genomic discovery and personalized medicine, NHGRI established the electronic MEdical Records & GEnomics (eMERGE) network. The eMERGE network began in 2007 with a Coordinating Center (Vanderbilt University) and five study sites: Group Health/University of Washington, Marshfield Clinic, Mayo Clinic, Northwestern University, and Vanderbilt University .The first few years of the eMERGE network required data generation both at the phenotype and genotype levels  or the Illumina 1M (primarily for participants of African ancestry) at either the Broad Institute Center for Genotyping and Analysis or the Center for Inherited Disease Research (CIDR). The eMERGE Coordinating Center established a pipeline to process each study site's data for quality control, data cleaning, and eventual Database of Genotypes and Phenotypes (dbGaP)  and IMPUTE2  samples with GWAS-level genotypes or other large-scale data [such as Metabochip . The eMERGE-PGx project will help establish best practices for implementing personalized medicine including exploring and establishing guidelines for returning results to physicians and patients  using DNA capture and contemporary sequencing technologies (known as PGRN-Seq)  pooled analysis across the network, (2) meta-analysis within and with outside consortia, and (3) generation of new phenotype and genotype data for new studies. In the first strategy, each eMERGE study site deployed not only the phenotype used to select study subjects for the genotype-phenotype association studies of the site's primary phenotype, but also the phenotype algorithms designed by other sites to identify additional cases and controls with existing GWAS-level genotyping for these secondary phenotypes, This strategy was successful and identified >15,000 additional samples with existing GWAS-level data to be repurposed for other phenotypes. This effort to share and deploy phenotype algorithms across sites enabled network-wide genomic discoveries for a variety of quantitative traits  growth charts . The eMERGE network is significantly poised to contribute to GWA studies for populations of non-European ancestry given that several study sites  include participants of African ancestry. eMERGE I has already contributed genome-wide associated variants (at a threshold of p < 10\u22125) in participants of African ancestry to the NHGRI GWAS Catalog for LDL-C  and environmental (G \u00d7 E) modifiers of common, complex phenotypes. In an early example, eMERGE investigators used extrinsic biological knowledge via the Biofilter algorithm (Bush et al., The majority of GWAS described to date for the eMERGE network represent data and efforts from phase I of the network's existence. Phase II analyses of larger, more diverse sample sizes are on-going (Gottesman et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Oregon Health Plan (Medicaid), a national leader in health-care transformation, contracts with 16 regional Coordinated Care Organizations (CCOs) to provide integrated medical, behavioral, and dental care in patient-centered primary care homes. The transformation seeks increased access to primary care, better control of health-care cost increases, and improved health outcomes using global budgets and shared savings to promote quality of care rather than quantity of care.A mixed-methods analysis assesses the implementation of CCOs and the impacts on treatment for alcohol and drug use disorders through qualitative Interviews with stakeholders in each CCO and quantitative analysis of Medicaid encounter data.During the first year of implementation, qualitative interviews with the 16 CCOs and participating addiction treatment programs suggest little systematic attention to addiction treatment issues. Baseline data on screening for alcohol and drug use (less than 3% of adult patients have a CPT code for screening) suggest CCOs have not yet incorporated screening and intervention services into clinical practice. There is little change, moreover, in the use of medications to treat alcohol and drug use disorders and in the number of patients treated for alcohol and drug use disorders. A stakeholder observed in a public meeting, \u201cUsually when a clinic remodels, there is a sign asking patients to \u2018Pardon our dust: Remodeling to serve you better.\u2019 The Oregon Health Plan is undergoing a major transformation without signs alerting patients about the changes.\u201dOregon\u2019s ambitious agreement with the Federal Government seeks to reduce its rate of spending growth by 2 percentage points without diminishing the quality of care. This arrangement represents one of the most significant efforts to slow health spending and transform the delivery system. Many of the highest cost patients have untreated mental health, alcohol, and drug use disorders. The Oregon health-care transformation offers opportunity to facilitate integrated care for mental health and substance use disorders. Slow implementation and organizational reluctance to change appear to inhibit progress."}
+{"text": "Inhibitory transmission through the neurotransmitter \u03b3-aminobutyric acid (GABA) shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons. In vivo studies have shown that dendritic spines, the morphological correlate of glutamatergic synapses in excitatory neurons, are formed and eliminated in response to synaptic activity patterns induced by learning behavior  releasing neurons has proven to be unexpectedly successful and cover many different aspects of the physiological properties of inhibitory cell\u2019s, including glutamatergic inputs, dendritic and axonal structure, passive properties and GABAergic synapses onto target cells , the cytoskeleton and various cell adhesion and signal transduction proteins  by their ultrastructural features Figure  are arras Figure .Inhibitory synapses are non-uniformly distributed along the different subcellular compartments of pyramidal cells. In the hippocampus, the highest density of GABAergic inputs is found in the soma and proximal dendrites compared to intermediate and distal dendrites  driving force , which allows the unequivocal identification of symmetrical GABAergic synapses and the analysis of synaptic ultrastructure at very high resolution. This technique has shown that patterns of activity that produce functional and structural changes in excitatory synapses also induce structural remodeling of inhibitory synapses. Both Chronic sensory deprivation by whisker trimming induces a net decrease in the number of symmetric GABAergic synapses in the dendrites of layer 4 neurons of barrel cortex, the main target neurons for the thalamocortical axons relaying sensory information from the whiskers , a brain-specific basic helix-loop-helix transcription factor, whose expression is tightly regulated by synaptic activity and postsynaptic calcium influx  Collybistin  what are the structural determinants of GABAergic synapse function? (ii) what is the driving force for remodeling of GABA synapses, GABAergic or glutamatergic neurotransmission (or both)? (iii) how is the persistence of GABAergic synapses controled? (iv) how is structural plasticity of GABAergic and Glutamatergic synapses coordinated? (v) why spine inhibitory synapses are more dynamic than shaft inhibitory synapses? Addressing all these questions will surely advance our knowledge of the brain mechanisms of plasticity and define the precise roles of inhibitory synapse remodeling in the neuronal adaptation to experience, and in particular, for learning and memory.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Editorial on the Research TopicSystems Biological Aspects of Pituitary TumorsPituitary adenomas are a category of neoplasms with a high degree of heterogeneity that occur in the central regulatory organ pituitary, which plays important roles in the hypothalamus\u2013pituitary-targeted organ axis systems that impact on important physiological functions of human body \u20133. RapidHalupczok-\u017by\u0142a et al.). Vitamin D deficiency and alteration in calcium\u2013phosphate balance are associated with a wide spectrum of diseases, such as cancer, diabetes, cardiovascular disease, and respiratory disease. Data demonstrate that acromegaly patients are at the higher risk of vitamin D deficiency and have a tendency to a lower level of calcium and higher level of inorganic phosphate. Data suggest the importance of inorganic calcium\u2013phosphate homeostasis in the pathogenesis of acromegaly patients (growth hormone pituitary adenomas) from the systemic view point. (ii) The second topic addressed the alteration in the chemokine network in pituitary adenomas from a systemic view . Chemokines are a category of inflammatory mediators that exert their roles through typical and atypical chemokine receptor signaling pathways. An alteration of chemokines and receptors is associated with cancer and inflammatory diseases. The chemokine network is proposed as the target of biomarker and new therapeutic approach for pituitary adenomas. (iii) The third topic addressed the proteomic variations in pituitary adenomas (Zhan and Wang). Proteomics is the key component of functional genomics and systems biology. Much progress has been achieved in pituitary adenoma proteomics to expand and enrich the systems biology analysis of pituitary adenomas. This topic emphasized the significance of variations in proteome and protein molecular networks for personalized and precise studies of pituitary adenomas. (iv) The fourth topic focused on molecular network variations in different subtypes of non-functional pituitary adenomas (Zhan and Long). That topic emphasized the integrative molecular networks derived from multiple omics data at the genome, transcriptome, proteome, peptidome, and metabolome levels, and on their variations in different subtypes of non-functional pituitary adenomas. These studies will benefit discovery of effective and reliable biomarkers and therapeutic targets for personalized and precise studies of highly heterogeneous non-functional pituitary adenomas.This present issue focuses on systems biological aspects of pituitary adenomas, which contains four topics. (i) The first topic addressed vitamin D status and calcium\u2013phosphate homeostasis in acromegaly patients , and especially for different subtypes of pituitary adenomas , 9. SystFuture issues will collect different levels of omics studies, especially the integrative omics studies together with genetics and clinical information with developed advanced computational biology approaches.All authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "District level healthcare serves as a nexus between community and district level facilities. Inputs at the district level can be broadly divided into governance and accountability mechanisms; leadership and supervision; financial platforms; and information systems. This paper aims to evaluate the effectivness of district level inputs for imporving maternal and newborn health. We considered all available systematic reviews published before May 2013 on the pre-defined district level interventions and included 47 systematic reviews.Evidence suggests that supervision positively influenced provider\u2019s practice, knowledge and client/provider satisfaction. Involving local opinion leaders to promote evidence-based practice improved compliance to the desired practice. Audit and feedback mechanisms and tele-medicine were found to be associated with improved immunization rates and mammogram uptake. User-directed financial schemes including maternal vouchers, user fee exemption and community based health insurance showed significant impact on maternal health service utilization with voucher schemes showing the most significant positive impact across all range of outcomes including antenatal care, skilled birth attendant, institutional delivery, complicated delivery and postnatal care. We found insufficient evidence to support or refute the use of electronic health record systems and telemedicine technology to improve maternal and newborn health specific outcomes.There is dearth of evidence on the effectiveness of district level inputs to improve maternal newborn health outcomes. Future studies should evaluate the impact of supervision and monitoring; electronic health record and tele-communication interventions in low-middle-income countries. District level healthcare is the cornerstone of primary health. An ideal district health system should not only offer primary care services but also provide first level of outpatient care and referrals for more specialized care. They also serve as a nexus between community and facility level care for health information; play a direct role in training health care workers; and provide necessary data to guide national health policy. This role is fundamental to effective health care delivery and failure to recognize the interrelationship between community and district-level facilities might result in inefficiency and fragmented delivery of meaningful public health interventions. Community based intervention impacts discussed in paper 2 of this series  could noDistrict level facilities play a pivotal role for maternal newborn health (MNH) programs. In some countries, programs like Safe Motherhood Initiative and Integrated Management of Childhood Illness (IMCI) are based on district-level health systems. Outpatient clinics at district hospitals provide primary prevention services for MNH including universal maternal and childhood immunizations. However these programs may vary in structure and functioning from country to country depending on the healthcare needs and infrastructure. The core components of district level inputs include training, supervision and monitoring of health workers in the peripheral health centers and managing health information systems for strategic planning and monitoring of the district health system. In this paper, we have reviewed the effectiveness of care delivered through district level inputs for improving MNH outcomes. For this review we have broadly categorized these interventions into four categories: governance and accountability mechanisms; leadership and supervision; financial incentives; and information systems.Governance is achieved through a combination of strategies including clinical competence, patient involvement, risk management, use of information, staff management, maintaining medical registries, and implementation of continuous quality improvement (CQI) tools. Accountability involves audit and feedback mechanisms that entail a systematic approach to ensure that the services are accountable for delivering quality healthcare. Audits involve any summary of clinical performance of healthcare professionals over a period of time which is presented to them in a written, electronic or verbal format for self-accountability. Healthcare professionals are prompted to modify their practice if the feedback is inconsistent with the standards or accepted guidelines. Audit tools for evaluating maternal and perinatal deaths have been an integral part of quality improvement in obstetric care. These are effective in defining the context specific problem and propose solutions. Although these mechanisms have been used widely as a strategy to improve professional practice, they have not shown consistent effectiveness majorly due to the inconsistencies and variations involved in implementation ,3.Supervision plays a key role in primary healthcare (PHC) service delivery and it requires the district level staff to supervise the public health activities and provide appropriate clinical care -6. Good It involves provision of monetary benefits as a source of motivation for performing desired health related actions. Financial interventions are aimed at creating a greater demand for health services and include scale-up of preventive health interventions, as well as provision of free access to basic health care. In recent years there has been an increase in the utilization of financial support platforms to reduce out of pocket client expenditure and strengthen service delivery and utilization at the district level. The targeted health services can include seeking care, behavior modification, immunization, compliance to health professional\u2019s clinical behavior and performance. Incentives directed towards care providers include capitation (payment for each patient enrolled), fee for service and pay for performance. Those directed towards users involve conditional cash transfers (CCT), vouchers, health insurance and fee exemptions. Diverse and innovative financial support platforms are being implemented in some of the fragile states such as Cambodia, Afghanistan, Pakistan and Haiti as well as more established economies of Latin American countries ,12 howevIt is one of the essential building blocks of health system  that capWe aim to systematically review and summarize the available evidence from relevant systematic reviews on the impact of the outlined district level inputs panel  to improWe considered all available systematic reviews on the pre-defined district level interventions published before May 2013 as outlined in our conceptual framework [a priori defined district level interventions for improving quality of care for MNH. We excluded the reviews pertaining to nursing documentation, computerized pharmacy system or those focusing on certain specific chronic illnesses only as these were not included in the scope of our review. Search was conducted in the Cochrane library and PubMed and reviews that met the inclusion criteria were selected and data was abstracted by two authors on a standardized abstraction sheet: Quality assessment of the included reviews was done using Assessment of Multiple Systematic Reviews (AMSTAR) criteria [Our priority was to select existing systematic reviews, which fully or partly address the criteria  as detaicriteria . Any discriteria .Our search identified 326 potentially relevant review titles. Further evaluation of the abstracts and full texts resulted in the inclusion of 47 eligible reviews: 14 on governance and accountability mechanisms, 7 on leadership and supervision, 11 on financial strategies and 15 on information systems , Diphtheria, pertussis and tetanus (DPT) immunization , health service utilization, child nutritional status and health outcomes ,45 with Among provider-directed financial strategies, target payments to primary care physicians (PCP) and pay-for performance showed positive trends for immunization rates  while thWe included fifteen ,51-65 reDistance communication significantly improved immunization rates (Range: 6.4%-27.2%) and number of mammograms (Range: 14%-25%)  with nonThere is very limited evidence on interventions to promote information communication technologies (ICT), improvements in knowledge about the electronic sources of information and use of electronic databases and digital libraries by healthcare professionals ,65. StudAt district level, audit and feedback mechanisms can effectively improve immunization rates; healthcare worker performance and compliance with desired practice; and prescription rates for generic drugs. Generalizability of these findings are however limited to HIC only. Involving local opinion leaders in informal/formal teaching, preceptor-ship and evidence based intervention dissemination can improve compliance with the desired practice. User-directed financial incentives have the potential to improve MNH outcomes, with CCT and maternal voucher schemes having the most significant positive impact across a range of outcomes. These findings are generalizable to both HIC and LMIC. There was limited and inconclusive evidence on the effectiveness of information technology with some positive impacts of distance communication on immunization rates and screening uptake. Evidence for structured interventions requiring electronic technologies are mainly evaluated in HIC settings hence limiting the generalizability of these findings to HIC only. This might be attributable to the gaps in access to and simultaneous underutilization of the existing electronic information resources in LMIC. Likewise, even within HIC, inequity exists in online information access between professionals in rural versus urban health settings.There is a dearth of evidence from MNH perspectives in some domains of the district level inputs. Although financial incentives have been widely evaluated for their effectiveness in improving MNH outcomes; audits, feedbacks and information systems are mostly evaluated for general health outcomes. Furthermore, it is challenging to systematically measure and analyze data for subjective outcomes like patient/provider satisfaction and other process indicators. Reviews focusing on MNH specific interventions like maternal and perinatal mortality audits report lack of data to evaluate their effectiveness. There is also lack of qualitative data describing the individual components of the intervention for reproducibility since most of the interventions are not uniform but rather a range of approaches. For example, studies have not reported on the optimal format and frequency of audit and feedback ; superviMost of the district level interventions require a pre-existing primary health care service infrastructure and measures to ensure sustainability hence the major challenge is to ensure adequate political, financial, human and material commitments; optimal use of available resources; utilization of advanced technologies, changing management techniques including decentralization; measures to ensure accountability and effective community participation and intersectoral collaboration . Hence iFocus on basic primary health care interventions at the district level to improve coverage of effective public health interventions will help direct the attention towards essential preventive and promotive interventions and commodities required to deliver quality care to mothers and newborns . InterveANC: Antenatal care; AMSTAR: Assessment of Multiple Systematic Reviews; CCT: Conditional Cash Transfers; CI: Confidence Interval; CQI: Continuous Quality Improvement; ED: Emergency Department; FFS: Fee for Service; HIC: High Income Countries; ICT: Information Communication Technology; IMCI: Integrated Management of Childhood Illnesses; LMIC: Low Middle Income Countries; MD: Mean Difference; MNH: Maternal Newborn; NHI: National Health Insurance; PCP: Primary Care Physicians; PNC: Postnatal Care; RBF: Result Based Financing; RD: Rate Difference; RR: Relative Risk;We do not have any financial or non-financial competing interests for this review.All authors contributed to the process and writing of the manuscript.Peer review reports are included in Additional file Click here for file"}
+{"text": "A 65-year-old man came to our clinic with progressive disequilibrium and gait problem since 6 years. During this period, he had also urinary incontinency.On neurologic examination, he had scanning speech and bidirectional nystagmus. There was hypokinesia in upper and lower limbs and on cerebellar tests finger to nose and heel to shin were impaired (severe dysmetria); he was unable to walk without bilateral support.The brain magnetic resonance imaging (MRI) of the patient showed severe cerebellar and pontine atrophy and a typical hot cross bun sign in pons, which is typical for MSA .Characteristic features of MSA on brain MRI are hyperintensity and thinning of putamen, narrowing and hyperintensity of posterolateral part of putamen, atrophy of brainstem  and cross hyperintensity of pons (hot cross bun sign). The cause of hot cross bun sign is degeneration of pontine neurons and pontocerebellar fibers."}
+{"text": "Cell adhesion molecules of the immunoglobulin superfamily (IgSF) including the neural cell adhesion molecule (NCAM) and members of the L1 family of neuronal cell adhesion molecules play important functions in the developing nervous system by regulating formation, growth and branching of neurites, and establishment of the synaptic contacts between neurons. In the mature brain, members of IgSF regulate synapse composition, function, and plasticity required for learning and memory. The intracellular domains of IgSF cell adhesion molecules interact with the components of the cytoskeleton including the submembrane actin-spectrin meshwork, actin microfilaments, and microtubules. In this review, we summarize current data indicating that interactions between IgSF cell adhesion molecules and the cytoskeleton are reciprocal, and that while IgSF cell adhesion molecules regulate the assembly of the cytoskeleton, the cytoskeleton plays an important role in regulation of the functions of IgSF cell adhesion molecules. Reciprocal interactions between NCAM and L1 family members and the cytoskeleton and their role in neuronal differentiation and synapse formation are discussed in detail. IgSF CAMs are cell surface glycoproteins highly expressed in the developing and mature nervous system. They are characterized by a large extracellular domain containing one or several immunoglobulin-like (Ig) repeats  cells used as model system, overexpression of NCAM results in an increase in the levels of polymerized \u03b2I spectrin indicating that NCAM not only binds to but also promotes polymerization of the \u03b2I spectrin meshwork beneath the cell surface plasma membrane  , N-methyl-D-aspartate (NMDA) receptors, and intracellular enzymes including protein kinase C (PKC) and CaCurrent data indicates that the cytoskeleton plays a direct role in IgSF CAM-mediated functions. Soluble and substrate-immobilized ligands of IgSF CAMs, including antibodies against the extracellular domains of IgSF CAMs or recombinant fragments of the extracellular domains of IgSF CAMs, trigger changes in the interactions between IgSF CAMs and the cytoskeleton and also function as potent regulators of neuronal differentiation and function. For example, application of recombinant extracellular domains of L1 triggers interactions between the intracellular domain of L1 and ankyrin B and induces neurite initiation in cultured mouse cerebellar granule cells  have been shown to reduce the interaction between L1 and ankyrin indicating that disruptions in the association with the cytoskeleton can directly contribute to the mechanisms of neuronal dysfunction in human X-linked mental retardation (Needham et al., All authors listed, have made substantial, direct, and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) is a cooperative implementation science initiative launched by NIDA in July 2013. The project seeks to reduce unmet substance use disorder needs for delinquent youth under community supervision by assisting juvenile justice (JJ) agencies in their efforts to implement best practices and improve service utilization along a behavioral health services cascade . Although many youth under JJ supervision have substance use and associated mental health disorders, there are numerous gaps in the identification of these problems and referral to appropriate services. Linkages between the JJ and behavioral health systems can be problematic because of the lack of shared mission, limited training of JJ staff on behavioral health issues, and limited sharing of information across service systems. Ideally, JJ staff will screen and assess youth for substance use and related disorders, and refer them to appropriate evidence-based treatment when needed; the youth should initiate treatment and be retained for a clinically effective period. The ultimate goal is to maximize the proportion of substance-involved youth identified and retained in treatment. Based on the HIV services cascade, we developed a conceptual framework, the Behavioral Health Services Cascade. This framework provides a useful heuristic for visualizing and measuring movement through the continuum of services. It illustrates the level of unmet needs at different points and provides a measurement framework for tracking improvements in reducing unmet needs. The model helps agency staff and leadership and policymakers understand the sequential and related stages of the services continuum and identify stages/linkage points that may need improvements. In the main JJ-TRIALS protocol, we are using the cascade framework to: 1) monitor and evaluate the primary outcome of reducing unmet service needs; 2) use local data to populate the cascade and provide feedback to agencies for need assessments and site feedback reports; and 3) help site staff select and monitor strategic goals to reduce gaps in one or more component of the cascade. We will also be developing measures related to the quality of the services delivered at each point in the cascade. Some challenges being addressed include: 1) defining and collecting consistent measures across multiple states and counties; 2) inconsistency in data availability across sites, especially on treatment engagement and continuing care; and 3) accounting for multiple and sometimes nonlinear processes at different points in the cascade."}
+{"text": "Displacement Encoding with Stimulated Echoes (DENSE) directly measures tissue displacements and can be used to quantify cardiac mechanics. Multi-dimensional DENSE results in lengthy scans that require respiratory gating, acquiring data only while the diaphragm is within a pre-specified \"acceptance window.\" Because it is not possible to perform respiratory gating during data acquisition, DENSE can employ the following respiratory gating strategies: 1) acquire data and keep it if the diaphragm is inside the window after acquisition (retrospective) 2) acquire data and keep it only if the diaphragm was inside the window right before data acquisition (prospective) or 3) a combination of retrospective and prospective where the diaphragm must be inside the window both before and after data acquisition (combined)  Director's Early Independence Award (DP5 OD-012132); the University of Kentucky Cardiovascular Research Center, grant UL1RR033173 from the National Center for Research Resources (NCRR), funded by the Office of the Director, National Institutes of Health (NIH) and supported by the NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH."}
+{"text": "Indonesia, Malaysia, and Thailand experienced changes in government expenditure in health. Indonesia and Thailand, move to more public financing. These countries did not have history of universal coverage and the governments have political motive for universal coverage. The case of Malaysia works in opposite direction: some members of communities (the affluent ones) are not satisfied with certain services and demand better health service using private financing. The policy issues is: how does the government policy for achieving universal health care also manage health service as an industry? This analysis of the issue shows: (1) universal coverage will have pressure for government fiscal condition; (2) private medical service will be \u201ca good safety valve\u201d in reducing the burden of public finance for health; (3) medical industry policy should support the development of private medical services but considering equity issues. The impact of universal coverage and medical industry policies are: more segmented hospitals based on technology and economy status; more diverse sources of health financing (public and private); more mechanisms of funding: fee-for-service, indemnity in commercial health insurance, managed care, and others. These impacts need a carefully crafted health policy within the broader social and economic/industrial policy."}
+{"text": "This book is written by multidisciplinary pioneers in early psychosis intervention in South-East Asia and is a product of two decades of development in this rapidly growing region, a cultural mosaic. In the foreword, Professor Patrick McGorry highlights that the essence of such intervention is to bring maximum recovery for young people with psychotic experiences.sijueshitiao, meaning imbalance of thinking and perception. The second part discusses the cultural issues in management of early psychosis. The authors tactfully compare and contrast different Asian beliefs of mental illness including Islam , Hindu (bad karma), Buddhism and Taoism (attacks by ghosts) and Christianity (demonic possession). The local cultural beliefs may increase duration of untreated illness because patients and families often consult their traditional healers instead of medical practitioners.The book is unique and attempts to connect early psychosis with transcultural psychiatry. The first part describes service structures of early psychosis programmes in Hong Kong, Singapore, Japan and Korea. The authors define early psychosis afresh by introducing the culturally adaptive translation in Chinese, The authors present interesting data on public misconceptions about psychosis. They highlight salient points in early psychosis treatment such as recommended dose of each antipsychotic drug, topics to be covered in peer support groups, strategies for family work and medication adherence. I personally found the chapter illustrating the state-of-art information technology and database design very interesting.I highly recommend this book to mental health professionals who are keen to establish early psychosis intervention services in other parts of Asia, Africa and South America. The authors carefully insert clinical vignettes throughout the book and enrich its clinical relevance. Mental health professionals working for well-established early psychosis intervention programmes may find the culturally adaptive strategies helpful in their clinical practice. In the near future, I hope Professor Eric Chen and his colleagues may consider writing a book on the neurobiology of early psychosis."}
+{"text": "Recent genetic discoveries conclusively link the two diseases, and several common molecular players have been identified . The definitive etiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarize the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterizing these two disorders and may represent more effective interventions for disease progression and treatment options in the future.Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and  Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing multisystem neurodegenerative syndrome, characterized by the degeneration of the motor neurons (MNs) in the motor cortex, brainstem and spinal cord  of intronic regions of the C9ORF72 gene were discovered in sporadic and familial forms of ALS and FTD , which respectively encode for the proteins TDP-43 and FUS, are associated with ~9% of familial, 2% of sporadic cases of ALS and rarely in FTD  and mutations have been identified in ~2\u201311% of familial FTD cases , and cytoskeletal, vascular and protein dysfunction .Inflammatory glia have been repeatedly reported in animal models of FTD  and sporadic cases were also neurotoxic to co-cultured MNs  ALS iPSCs were also toxic to co-cultured MNs  of familial  and Single Positron Emission Computed Tomography (SPECT) or Magnetic Resonance Imaging (MRI) in patients targeting activated microglial receptors or astrocytic metabolites have shown gliosis throughout various symptomatic stages of ALS and FTD while absent in non-disease controls  and may confer elevated risk of developing Alzheimer\u2019s disease and ALS  have been identified in familial ALS , cell specific transcriptome analysis of the mouse cortex indicates that all three genes are highly transcribed in microglia  have been found to segregate with both familial and sporadic forms of ALS and Parkinson\u2019s disease , NHMRC Project Grant (APP1034816), The Snow Foundation and BitFury.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "This qualitative study examined the experience of parents of children and adolescents with eating disorders after having participated in a skills-based training intervention.Participants were interviewed and transcripts were analysed using inductive thematic analysis.Parent responses were organised around key themes of (1) effectiveness and acceptability of the intervention; (2) interpersonal experience of the group process; and (3) feedback on intervention content. Overall, the program was seen by parents to be highly relevant with direct application to supporting their child in home and hospital environments.This study reports on preliminary evidence that skills-based training is acceptable to parents and improves parent functioning including parent self-efficacy, and reduces psychological distress, anxiety, and burden. The study also demonstrated that the intervention can be delivered in a tertiary paediatric treatment setting and it may become cost-effective method for supporting parents and other carers. Future research is required on treatment efficacy and patient outcomes.Parental Roles in Prevention and Support stream of the 2014 ANZAED Conference.This abstract was presented in the"}
+{"text": "Juvenile idiopathic arthritis (JIA) may lead to permanent damage of the articular cartilage and bone. Because the prevention of irreversible joint changes is a key objective in the long-term management of chronic arthritis, evaluation of radiographic joint damage represents an important clinical tool for assessing disease severity and progression and for monitoring the effectiveness of therapeutic interventions. Although newer imaging techniques, such as MRI and ultrasound, allow earlier detection of bone and cartilage changes, conventional radiography remains the gold standard for the demonstration of structural joint lesions in patients with JIA. Importantly, mapping the prevalence and location of structural abnormalities in different sites on conventional radiology may provide useful information to guide future investigations with MRI and ultrasound.To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp-van der Heijde (aSH) score, in individual joints in the hand and wrist in patients with JIA, and to compare progression of damage among different JIA categories.A total of 372 radiographs of both wrists and hands obtained at first observation and at last follow-up visit (after 1 to 10 years) in 186 children with polyarticular-course JIA were evaluated. All radiographs were scored using the aSH scoring system by 2 independent readers. Radiographic assessment included evaluation of joint space narrowing (JSN) and erosions on baseline and last follow-up radiographs and of progression of radiographic changes from baseline to last follow-up radiographs.nd and 3rd metacarpal bases. Patients with extended oligoarthritis were distinctly less susceptible to JSN in hand joints, whereas patients with polyarthritis showed a greater tendency to developing erosions in hand joints.Both JSN and erosions occurred in all aSH areas. Overall, radiographic damage and progression were more common in the wrist and less common in metacarpophalangeal joints. The hamate and capitate areas appeared particularly vulnerable to cartilage loss. Erosions were identified most frequently in the hamate and capitate bones as well as in the 2Radiographic joint damage and progression in our patients with JIA were seen most commonly in the wrist and less commonly in MCP joints. The frequency and localization of structural abnormalities differed markedly across disease categories.None declared."}
+{"text": "Literature pertaining to the role of occupational therapy in recovery from eating disorders spans 40 years; however, has not been systematically synthesized.To develop a comprehensive understanding of reported roles of occupational therapy in recovery from eating disorders and inform intervention and research, we conducted an integrative literature review. Searches were conducted in ten online databases and six occupational therapy journals. Theoretical or empirical publications in peer-reviewed journals in English explicitly describing occupational therapy intervention or role of the occupational therapist for eating disorders were included. Thematic analysis was conducted across selected articles and research articles critically reviewed.Thirty-two pieces of evidence published in English from 1974 through 2014 were included in this review; twenty-four were theoretical and eight were qualitative, descriptive or quasi-experimental studies. Analysis revealed the domain and process of occupational therapy with persons with eating disorders. Results are represented as a conceptual model illustrating a variation of the American Occupational Therapy Association Practice Framework. Appraisal of the studies suggests a need and opportunity to document and disseminate the evidence-base for this practice area.Findings of this integrative literature review inform research, practice and clinical training of occupational therapists in the specialty area of eating disorder recovery."}
+{"text": "Trial oversight committees (TOC) including Trial Steering Committees (TSCs) and Trial Management Groups (TMGs) are integral to trial conduct. Patient and public involvement (PPI) in trial design and conduct is frequently stipulated although there is little empirical evidence to optimise roles and inputs. We aimed to use qualitative research to understand the experiences of PPI involvement in TOCs to enhance PPI contributions to trial conduct.1 study. Sixty seven members of these TOCs underwent in-depth interviews, which included looking at the role and inputs of PPI members. PPI members interviewed (n=3) also described their experiences and examples of influence on trial conduct.The TSC and TMG meetings of eight large trials that were undergoing challenges (e.g. recruitment issues) were observed and audio recorded (n=14) in the QuANTOCThe degree to which PPI members were included in TOC influenced their impact on trial conduct. Successful involvement of patients and the public in trial oversight committees can be facilitated through: clarity and transparency of PPI roles; active engagement with the route to and reasons for PPI group membership; and the development and maintenance of support mechanisms during and outside of meetings. Discussions within the trial team are needed to facilitate these components including identifying who is responsible for their completion.Greater inclusion of PPI members in TOC can enhance their contributions to trial conduct. The practical suggestions identified can assist in optimising PPI in trial oversight."}
+{"text": "Regulatory T cells (Treg) are important players in keeping the immune system in balance. In juvenile idiopathic arthritis (JIA), an autoimmune disease characterized by chronic inflammation of the joints, this balance is disturbed. Recently, different functional subsets of regulatory T cells (Treg) have been described in mice and human that mirror the T helper subsets. A lot remains unknown about the function and mechanism of action of Treg (subsets), especially in inflammatory environments.In our study we aim to investigate the adaptability of regulatory T cells based on phenotype and function. In particular, our focus is on Treg derived from different inflammatory environments.Treg will be isolated from peripheral blood and synovial fluid of JIA patients and peripheral blood of healthy controls and analyzed based on the expression of chemokine receptors CXCR3, CCR6 and CCR4. Currently, autologous suppression assays, allogenic T cell suppression assays and monocyte suppression assays are performed with these Treg subsets derived from different environments.Treg subsets that mirror Th subsets can be found and discriminated based on there chemokine receptor profile  in peripheral blood of healthy control and JIA patients, and in the synovial fluid of JIA patients.Different subsets of Treg can be identified in the synovial fluid of JIA patients. This allows us to further look in to Treg subset function.None declared."}
+{"text": "The incidence of MRSA infections at the Neonatal Intensive Care Unit (NICU) of the King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia was highest in February of 2014 when an outbreak occurred. Our department conducted a thorough investigation.The NICU is a 45 bed level 3 unit with an average of 58 per month. Per hospital policy, only neonates delivered at outside facilities are screened nasally for MRSA carriage by the PCR techniqueTo rapidly identify the cause of the outbreak and implement strict measures to contain the further spread of MRSA.Our investigation employed the following modalities over a nine month period: Placing all neonates in contact isolation as a precautionary measure; conducting weekly Point Prevalence Surveillance screening (PPS); strict enforcement of hand hygiene by health care workers (HCWs) and visiting family members; curtailing of nonessential movement of neonates; enhancement of environmental cleaning protocols with flourescent gel and ATP validation and nasal swab screening of HCWs. Speciation of all MRSA identified was performed by Pulse field gel electrophoresis (PFGE).533 and 201 nasal swabs were performed on the neonates and HCWs respectively with a positive MRSA culture in 17 neonates and 5 HCWs. Four different strains of MRSA were identified by PFGE. All 5 MRSA positive HCWs were furloughed and had undergone with MRSA decolonization regimen. Assessment of the environmental cleaning process revealed significant defects.Our investigation revealed that the outbreak was not caused by spread of a single MRSA clone. The causes were likely multifactorial and most likely relate to a breakdown of infection control practices, highlighting the importance of strict adherence to infection control practices, including, but not limited to proper environmental cleaning.None declared."}
+{"text": "Secondly we demonstrate how knowledge about the embryonic development of striatal interneurons is of particular help for the development of differentiation protocols from PSC and by this depict potential ways of deriving in vitro disease models of dystonia. We furthermore address the question as to whether cell replacement therapies might represent a beneficial approach for the treatment of dystonia.Interneurons comprise a minority of the striatal neuronal population of roughly 5%. However, this heterogeneous population is of particular interest as it fulfills an important relay function in modulating the output of the only type of striatal projection neurons, i.e., the medium spiny neuron (MSN).One subtype of this heterogenous group, the cholinergic interneuron, is of particular scientific interest as there is a relevant body of evidence from animal models supporting its special significance in the disease process. The development of protocols for directed differentiation of human pluripotent stem cells (PSC) into striatal interneurons provides a unique opportunity to derive  Dystonias are a heterogeneous group of movement disorders characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation  cytochemical, and electrophysiological properties   develops from the lateral (LGE) and medial ganglionic eminence (MGE) located in the basal part of the telecephalon. While striatal projection neurons (namely MSN) arise from the lateral ganglionic eminence  can be differentiated into cells of the entire body, including neurons. iPS even allow generating patient-specific cells, sharing all possible genetic deviations and variants of the donor patient , bone morphogenetic proteins (BMPs), and agonists of the wingless/Int-1 pathway  cannot be achieved in this way. One more recent protocol reported achievement of 94% forebrain cholinergic interneurons by transient overexpression of GBX1 and LHX7 (L3/LHX8) (Bissonnette et al., Under optimal conditions, over 90% of the cells express NKX 2.1, thereby demonstrates MGE identity. These neurons are 45% cholinergic and 55% GABAergic (Liu et al., Cell replacement strategies as potential treatment for neurodegenerative disorders have been carried out for a couple of decades with promising results in animal models but mixed outcome in clinical trials (Bjorklund and Kordower, The absence of neurodegeneration identifies isolated dystonias as neuronal network diseases. Interneurons representing roughly 5% of the striatal neural population play an important role in modifying the output of the MSN as projection neurons and relaying thalamo-striatal and cortico-striatal inputs, especially cholinergic interneurons play an important role in integrating sensory input and redirecting attention. Using the example of DYT-TOR1A as the best studied form of isolated dystonia, we present the current knowledge as to how striatal cholinergic interneurons may play a central role in the pathophysiology of dystonia through an altered response to dopaminergic input leading to overactivity and dysfunctional gating of thalamostriatal input.We summarized the origins and developmental processes of forebrain interneurons in combination with the molecular mechanisms that switch between GABAergic and cholinergic phenotypes.in vitro. Although to date no published study employed PSC-derived striatal interneurons in order to study dystonia, this technique holds great potential for deciphering the underlying disease mechanisms of dystonia, as the necessary protocols have already been published and just await their application for in vitro modeling of DYT-TOR1A. We finally discuss potential neurorestaurative approaches for different subtypes of dystonias: while isolated dystonias most likely are no suitable candidates for this procedure due to the lack of neurodegeneration and complex dystonias are commonly characterized by too widespread a neural damage, transplantation of MSN precursors could be a potential field of application in XDP or DYT-TAF1 with its relatively confined degeneration of striosomes.We demonstrated on the basis of recent protocols, how knowledge of the developmental mechanisms can be employed for directed neural differentiation of PSC in order to obtain human forebrain interneurons The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Both ACTH and cortisol are secreted in a diurnal rhythm. Underlying this is an ultradian rhythm of discrete pulses  as a resTwenty male patients presenting for elective CABG (on-pump and off-pump) were recruited. Blood samples were taken for 24 hours from placement of the first venous access. Cortisol was sampled every 10 minutes, ACTH was sampled every hour and cortisol binding globulin (CBG) was sampled at baseline, at the end of operation and at the end of the 24-hour period.Cortisol and ACTH were pulsatile throughout the perioperative period and the cortisol-ACTH interaction persists Figure . The senBoth cortisol and ACTH remain pulsatile during and after cardiac surgery and the pituitary-adrenal interaction persists, although the sensitivity of the adrenal glands changes throughout the perioperative period. Our study shows that endogenous glucocorticoid levels reach very high oscillating levels following cardiac surgery, which not only invalidate the interpretation of point measures of adrenal function to diagnose adrenal insufficiency but also demonstrate that constant infusions of hydrocortisone are unphysiological."}
+{"text": "A number of tools have been developed to seek the views of family members of critically ill patients but the most widely validated is the Family Satisfaction in the Intensive Care Unit 24-item questionnaire (FS-ICU-24), which asTo assess family satisfaction with critical care in the United Kingdom using the FS-ICU-24, compare results internationally, and explore the impact of family, patient and other factors on comparisons between ICUs.The Family Reported Experiences Evaluation (FREE) Study recruited family members of patients staying at least 24 hours in 20 participating adult general ICUs between May 2013 and June 2014. Consenting family members were sent a postal questionnaire three weeks after the patient died or was discharged from ICU. Up to four family members were recruited per patient. Multilevel multivariable models were used to identify factors associated with satisfaction.12,346 family members of 6380 patients were recruited to the FREE Study and 7173 (58%) family members of 4615 patients returned a completed questionnaire. Multiple imputation of missing item response enabled inclusion of all responders. Overall, satisfaction scores were high  and were similar to other reports, internationally. Satisfaction was higher for family members of ICU non-survivors. Factors associated with overall satisfaction for family members of ICU survivors were family member age, ethnicity, relationship (to patient), visit frequency and patient acute severity of illness and receipt of invasive mechanical ventilation. Factors associated with overall satisfaction for family members of ICU non-survivors were patient age, acute severity of illness and duration of ICU stay. No other factors (of those explored) were associated. Significant variation existed across ICUs which reduced following adjustment for family and patient factors, resulting in fewer ICUs being identified as potential outliers.The large sample size and robust multilevel multivariable modelling of factors associated with overall satisfaction indicated the need for adjustment for these when comparing ICUs. The FREE Study and the FREE Study database are an important foundation and resource for future studies evaluating family satisfaction with critical care in the United Kingdom.NIHR Health Services and Delivery Research Programme."}
+{"text": "Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: (1) molecular mechanisms shared by various types of environmental stressors, (2) the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and (3) interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders. The development of the cerebral cortex consists of very intricate multifaceted steps including proliferation/differentiation of neural progenitor cells, neuronal migration and maturation .\u201d FASD patients show higher rates of co-morbidity with various types of neuropsychiatric problems, such as attention deficit hyperactivity disorder (ADHD) and epilepsy  to environmental stress can be classified mainly into two groups  and Growth Arrest and DNA Damage 45 (GADD45) signaling pathways , a canonical transcription factor that controls transcription of Hsp genes revealed that activation of this signaling is required to reduce the risk of cortical malformation, such as heterotopias and small size of the cortex, upon prenatal exposure to various types of environmental stress, thereby reducing susceptibility to epilepsy . The transcriptional activity is increased in response to such as alcohol               cells taken from subjects diagnosed with polygenic diseases such as schizophrenia or autism. iPS cells are not only becoming useful tools to obtain functional human cortical neurons  mutant mice combined with MIA, in vivo evidence for the interaction of gene and prenatal environment in the pathogenesis of schizophrenia and depression was also provided. The Disc1 is one of the risk genes for psychiatric disorders such as schizophrenia and mood disorders  that allow observation of the iPS cells during cortical development.As outlined in this review, research on polyepigenetic mechanisms associated with many types of environmental stress that disturb cortical development and on potential prophylactic or preventative interventions of these disturbances are just beginning to emerge. To further facilitate this type of research, patient-derived iPS cells will become one of several powerful tools. Although there are a number of limitations in their use, easy application of environmental stress and the potential for high throughput analysis substantiate their usefulness. Challenges include: (1) limited availability of iPS cell lines that are fully characterized; (2) lack of validated differentiation protocols for specific types of neurons; and (3) lack of validated A type of the environmental stress can lead to various phenotypes in the cerebral cortex, however, this variability cannot be explained exclusively by different regimens of exposure. Recent studies have revealed potential factors that may affect the resultant phenotypes, including gender (Mooney and Varlinskaya, Another recent interesting observation that needs to be addressed at the molecular level is the transgenerational effects of prenatal exposure to environmental stress, as reported in the cases of alcohol (Govorko et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Understanding the mechanisms regulating gene expression in the course of development and adaptation of the organism to the permanently changing environment and in the case of pathology is fundamentally important. Special attention in recent years has been paid to the processes of epigenetic regulation of neuronal genes involving chromatin modifications at the level of DNA methylation and histone acetylation. In these processes an important role belongs to the histone deacetylases (HDAC) which control gene silencing. Recently it was shown that the amyloid precursor protein (APP) and its intracellular domain (AICD) participate in regulation of expression of a number of neuronal genes, including those involved in amyloid metabolism and clearance. The list of APP-regulated genes includes the major amyloid-degrading enzyme neprilysin (NEP), a transport protein transthyretin (TTR), aquaporin and others. Our studies strongly indicate that AICD regulation of NEP and TTR is APP isoform-dependent and cell-type specific. In this process AICD competes for gene regulation with HDACs and treatment of cells or animals with HDAC inhibitors such as valproic acid results in up-regulation of NEP and TTR mRNA and protein levels and increased NEP activity leading to a reduction in total cellular amyloid (A\u03b2) peptide levels. Regulation of other proteins, e.g. acetylcholinesterase, does not involve AICD but requires full length APP molecules. APP overexpression in neuronal cells was also shown to affect the levels of HDAC gene products which might explain its role in gene regulation. Further studies of the APP interactome are important for better understanding of its role in brain development and functioning and for designing the drugs protecting the brain against neurodegeneration, in particular Alzheimer\u2019s disease."}
+{"text": "Large-scale identification of metabolites is key to elucidating and modeling metabolism at the systems level. Advances in metabolomics technologies, particularly ultra-high resolution mass spectrometry enable comprehensive and rapid analysis of metabolites, which is impractical to achieve by conventional methods. However, a significant barrier to meaningful data interpretation is the identification of a wide range of metabolites including unknowns and the determination of their role(s) in various metabolic networks. Our recent development of chemoselective (CS) probes to tag metabolite functional groups provides additional structural constraints for metabolite identification, but remains limited by the lack of functional group-resolved metabolite databases.a priori knowledge.We have developed a novel algorithm to allow for the rapid detection of functional groups within existing metabolite databases such as KEGG Ligand and the Human Metabolome Database in order to create functional group resolved versions of both databases. These databases will allow for combined molecular formula and functional group (from CS tagging) queries to aid in metabolite identification based on accurate mass information without In silico analysis of various CS-tagging strategies under different conditions for adduct formation demonstrate that the combination of FT-MS derived molecular formulas and CS-tagging can significantly increase the unique identification of isotopologues based on the entries in KEGG and HMDB databases.An isomeric analysis of both HMDB and KEGG demonstrates a high percentage of isomeric molecular formulas, indicating the necessity of techniques such as CS-tagging with detection via MS and NMR to help assign specific metabolites and their isotopologue and isotopomer distributions based upon both molecular formula and distinct composition of functional groups. Furthermore, these two databases have only moderate overlap in molecular formulae. Thus, it is prudent to use multiple databases in metabolite assignment, since each of the major metabolite databases represents different portions of metabolism within the biosphere."}
+{"text": "The connection between bacterial pathogens and unfolded protein response (UPR) is poorly explored. In this review we highlight the evidence showing that group A streptococcus (GAS) induces endoplasmic reticulum (ER) stress and UPR through which it captures the amino acid asparagine (ASN) from the host. GAS acts extracellularly and during adherence to host cells it delivers the hemolysin toxins; streptolysin O (SLO) and streptolysin S (SLS). By poorly understood pathways, these toxins trigger UPR leading to the induction of the transcriptional regulator ATF4 and consequently to the upregulation of asparagine synthetase (ASNS) transcription leading to production and release of ASN. GAS senses ASN and alters gene expression profile accordingly, and increases the rate of multiplication. We suggest that induction of UPR by GAS and by other bacterial pathogens represent means through which bacterial pathogens gain nutrients from the host, obviating the need to become internalized or inflict irreversible cell damage. The endoplasmic reticulum (ER) is an essential organelle that controls protein and lipid biosynthesis, protein folding and trafficking and calcium homeostasis , inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) Figure . As mentUnder viral infection these questions seem most relevant as viruses cause both cell stress through their replication and by over-expressing viral proteins  cascades  are genetically and structurally related cytotoxins expressed by the enteric pathogens Caenorhabditis elegans infected with bacteria expressing PFTs, UPR is induced and lose of ATF6 and IRE1 pathways , is unable to induce UPR. Furthermore, induction of UPR by ER-stressors before infection with L. monocytogenes reduces bacterial intracellular loads, suggesting that UPR may represent a defense response of the host against L. monocytogenes infection  that constitute the largest class of bacterial toxins and are produced by the most clinically important bacterial pathogens. In s Figure . Brucellex-vivo and in-vivo studies  of keratinocyte cells due to dysregulation of intracellular calcium , which is widely used as a chemotherapeutic agent  when present extracellularly. This in turn reduces the level of intracellular bacteria, due to the triggering of host defense responses (Pillich et al., L. monocytogenes regulates LLO expression also upon sensing of host metabolites that are released upon UPR induction. Finally, it was reported that Mycobacterium tuberculosis, which induces ER stress in granulomas during infection in humans (Seimon et al., Helicobacter pylori (Shibayama et al., Campylobacter jejuni (Hofreuter et al., It was observed that low levels of SLO inhibit GAS internalization by human keratinocytes (Logsdon et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Aortic Coarctation (AoCo) accounts for 5-8% of the children with CHD. Even after successful early repair, life expectancy is still markedly reduced (80% at 50 years after surgery) compared to normal population due to long term complications (hypertension). Usually, invasive diagnostic catheter investigations are required to evaluate the pressure gradient across the aorta at rest, or unmask such a gradient by use of isoprenaline stress to mimic physical exercise. The application of image-based computational fluid dynamics (CFD) in patients with AoCo appears promising as an alternative non-invasive diagnostic tool, as it may allow the avoidance of cardiac catheterization to determine pressure gradients. The motivation of this research is to know if a MRI based CFD model can accurately predict the pressure gradient in patients with AoCo and therefore be incorporated in the clinical practice.The study included 7 cases with aortic coarctation  Fig.  and cardThe pressure gradients obtained in REST were in good agreement with the ones obtained from catheterization Fig. In conclusion, we can predict the non-invasive pressure gradient with a good agreement using CFD simulation and cardiovascular magnetic resonance imaging, with the purpose that in the future incorporate this process in the clinical practice.European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 307532, the United Kingdom Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. FONDECYT #1141036 and #11121224. JS thanks CONICYT and Ministry of Education of Chile, with his higher education program, for scholarship for doctoral studies."}
+{"text": "The purpose of this exhibit is to describe and compare the high-resolution MRI features of rectal carcinoma after chemoradiation treatment (CRT) and to correlate with the histologic findings after total mesorectal excision (TME).High resolution T2-W MR imaging (HRMRI) was performed in a 1.5 T unit between January 2013 and February 2014 before and immediately after CRT in the care of 25 patients with locally advanced adenocarcinoma of the rectum. After total mesorectal excision (TME) the piece was cut by the pathologist under the supervision of the radiologist, who indicated areas of residual tumour after neoadjuvant therapy or changes such as fibrosis, oedema, cellular and acellular mucin, desmoplastic reaction and pseudotumour appearance. Thus, initially we did a correlation between the macroscopic and MR imaging. Subsequently, we performed the same correlation but in this case between microscopy and MR imaging. Changes in morphologic and signal intensity features were evaluated with respect to primary tumour and nodal downstaging.Emerging evidence has shown the prognostic importance of reassessing rectal cancer using HRMRI after completion of CRT. A systematic cooperation between radiologist and pathologist is essential for optimal treatment planning and patient care."}
+{"text": "Problem-based learning (PBL) is an innovative and contemporary method of learning that has become more prevalent within health professions education, with some medical schools in the United Kingdom (UK) now teaching a fully integrated PBL curriculum . This apIn 2012, we conducted a cross-sectional study of 260 first-year medical students at the University of Birmingham, where both PBL and traditional teaching methods are employed. An anonymous questionnaire was used to explore the students\u2019 preferred teaching methodology, resources utilised, and learning behaviours.Prior to entering medical school, virtually all (99%) students had been taught by traditional methods during UK secondary school education; of these, over half (59%) did not feel prepared for university medical education. Not surprisingly, the vast majority (97%) preferred traditional teaching over PBL\u2014citing more structure and greater clarity. The Internet was the most common resource used in PBL study, whereas textbooks were the most used resource in traditional learning.Despite the growing integration of PBL into medical school curricula, our first-year students strongly preferred the more traditional approach to learning with which they were familiar. While PBL provides a platform for students to develop responsibility for managing their own learning needs, a more holistic approach might be delivered via the phased integration of PBL into medical school curricula\u2014allowing for the gradual acquisition of new learning methods. Preliminary findings suggest that implementing a combination of both PBL and lecture-based teaching can be quite well received by students .Any use of PBL must include a concerted effort to establish a positive ethos with clearly stated objectives from which students can build a foundation for lifelong learning. However, recognising the positive aspects of more traditional approaches, and incorporating these within the modern PBL method, may be the optimal strategy to achieve a harmonious transition from passive to active learning.Faraz Mughal Public Health, Epidemiology and Biostatistics Unit School of Health and Population Sciences University of Birmingham Birmingham, United Kingdom Email: farazm@doctors.org.ukAlice Parsloe School of Health and Population Sciences University of Birmingham Birmingham, United KingdomRachel Stores School of Health and Population Sciences University of Birmingham Birmingham, United KingdomJennifer Clark School of Health and Population Sciences University of Birmingham Birmingham, United KingdomAlexander Ryan School of Health and Population Sciences University of Birmingham Birmingham, United KingdomHelena Lee School of Health and Population Sciences University of Birmingham Birmingham, United KingdomCatherine Barton School of Health and Population Sciences University of Birmingham Birmingham, United Kingdom"}
+{"text": "Recent epidemiologic and experimental data reinforced the concept that diabetes mellitus (DM) is an independent risk factor for osteoarthritis (OA). Besides a systemic inflammatory response that can affect joint tissues and contribute to OA pathogenesis, direct effects of hyperglycaemia have been shown to cause cell damage and induce inflammation by various mechanisms in several tissues associated to diabetic complications. Whether and how glucose directly affects joint tissues and cells is just beginning to be unraveled. Indirect effects of high glucose can result from enhanced formation of advanced glycation end products (AGEs) which accumulate in OA cartilage in an age-dependent manner and play a pro-inflammatory and pro-catabolic role mediated by activation of their specific receptor, RAGE, on chondrocytes and synovial cells. Some direct effects of high glucose have also been demonstrated, namely induction of IGF-1 resistance. Our stuElucidating how high glucose modulates joint tissue homeostasis will identify novel targets for development of innovative strategies both to identify diagnostic and prognostic biomarkers of OA and to effectively modify disease progression."}
+{"text": "Nosocomial infections are among the leading causes of mortality and morbidity especially in neonatal intensive care unit (NICU) . The intStaphylococcus aureus is a multidrug-resistant nosocomial pathogen; a recent review of literature [The mechanisms of action of probiotics are strain specific but can be summarized mainly in three areas: changes of gut ecology, modulation of gut mucosal barrier and regulation of the immune response through interaction with gut-associated immune system . Severalterature  showed tDue to the significant heterogeneity between the studies in literature it is not possible to draw consistent conclusions on extensive use of probiotics in prevention and treatment of nosocomial infections, except for acute gastroenteritis, AAD, CDD and NEC."}
+{"text": "In Rwanda, 30,000 volunteer community health workers (CHWs) treat children under five for pneumonia, diarrhoea and malaria. A 2010 community supply chain (SC) assessment identified a lack of SC skills and poor coordination between CHWs, health centres (HCs) and districts as barriers to CHW product availability. SC4CCM tested standard resupply procedures (RSPs) and multi-level quality improvement teams (QITs) to strengthen coordination and problem-solving between levels to improve supply chain processes and outcomes.In 2013, SC4CCM conducted a mixed-methods midline evaluation and an endline study in 2014 to understand sustainability and scalability of the QIT approach. A quantitative survey measured key supply chain indicators to compare results 12 months after launching the intervention (at midline), and another 12 months later to understand if results were sustained. Qualitative data at endline assessed enabling factors and barriers for scale up after the MOH began implementing RSPs and QITs nationally.Midline results showed that the team-based approach led to improved outcomes. CHWs in QIT districts had 25% greater availability of the five community health products on the day of visit than the comparison group. Qualitative results confirmed the importance of multi-level teams and a structured approach in achieving results. Endline findings confirmed the role of district leadership in maintaining and scaling this intervention. While CHWs in all districts affirmed the value of the approach, establishment of QITs in new districts and continued use of data relied on leadership of HC staff, frequently predicated upon district staff engagement and participation.Product availability and performance of SC tasks among CHWs can be improved by establishing multi-level teams that aid coordination and communication across levels in the health system and use data to prioritize areas for problem solving and develop local solutions. To establish and maintain meetings, leadership and on-going engagement from district staff ensures HC staff call meetings and prioritize the activities among their many other tasks. Meetings should have a known agenda, be short, and have a consistent approach to the use of data for performance monitoring and identification of problems and solutions within the team\u2019s ability to address.CHWs are often isolated from the mainstream health system. Strengthening their connections with HC and district staff through teams improves coordination and sets a culture of continuous improvement. Engagement by district coaches is necessary to establish QITs and ensure HCs provide the necessary leadership to sustain meetings and the approach."}
+{"text": "Investigators from the Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society reported a consensus statement on indications for the use of critical care continuous electroencephalographic monitoring (ccEEG) in adults and children. Investigators from the Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society reported a consensus statement on indications for the use of critical care continuous electroencephalographic monitoring (ccEEG) in adults and children . The conAssessment of the electrographic background with ccEEG may also help predict outcome in a range of acute neurologic conditions, and could allow for early detection and treatment of cerebral ischemia in at-risk patients. ccEEG recording for at least 24 hours is recommended in most cases, although the authors acknowledge that there may be situations where shorter or longer periods of recording are necessary. Review of ccEEG by technologists is suggested as often as feasible, with interpretation by neurophysiologists at least twice daily. COMMENTARY. Observational studies in both pediatric and adult intensive care units have found frequent NCS and NCSE in critically ill patients, with rates of electrographic seizure ranging from 10 to 40% in children , 4. WhilThis consensus statement provides a valuable starting point for development of ccEEG protocols based on the best currently available evidence. The clinical impact of ccEEG on seizure management and patient outcome remains an important area of ongoing research."}
+{"text": "Journal of Drug Assessment, Axthelm et al.2) and diabetic patients as well as individuals with at least one metabolic risk factor  that were inadequately controlled by prior use of SPC olmesartan 40\u2009mg/amlodipine 10\u2009mgIn a recently published paper in the Cardiovascular disease (CVD) represents the main cause of death worldwide and thus research still focuses on potential genetic and physiological biomarkers, imaging techniques, healthcare technologies and indices for both CVD prevention and treatment as well as personalized prediction modelsWith regard to hypertension, the 2009 reappraisal of the European guidelines (European Society of Cardiology/European Society of Hypertension)Perindopril, an angiotensin converting enzyme (ACE) inhibitor, and amlodipine SPC can be also used to adequately treat hypertensivesIt should be noted that the combination of an ACE inhibitor with an ARB is currently not recommended based on the results of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study where more adverse effects were reported in the combination group than monotherapy groupsDual ACE inhibitor (or ARB) and aliskiren treatment is also currently not recommended based on the results of the Aliskiren Trial In Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE)The best combination therapy differs with regard to patient populations; for example, African-American individuals and patients with heart failure will benefit more from a RAAS inhibitor plus a diuretic, whereas a RAAS inhibitor combined with a CCB will produce a greater reduction of CVD riskSPCs of three antihypertensive drugs are also commercially available including ARBs or aliskiren combined with amlodipine and hydrochlorothiazideWith regard to hypolipidemic drugs, the first fixed-dose combination includes simvastatin and ezetimibeOf note, atorvastatin has been also combined with metformin or sitagliptin with similar efficacy and safety as the individual componentsIn the field of hypoglycemic drugs, SPCs of metformin and dipeptidyl peptidase (DPP)-IV inhibitors  are frequently used in daily practice as they achieve sufficient glycemic control with less gastrointestinal adverse eventsThe first available fixed-dose combination of antiplatelet drugs included acetylsalicylic acid (ASA) and extended-release dipyridamole which was both efficient and safe in atherothrombotic events prevention settingsFixed-dose combination of aspirin plus low-dose warfarin was proven insufficient to protect from thrombogenesis in patients with chronic atrial fibrillationIn general, it is more likely to achieve better compliance with the use of SPCsThe use of one polypill that will contain different drugs targeting CVD risk including a beta-blocker, diuretic, ACEi, aspirin and statin has also been suggested although long-term data are missingOverall, the use of SPCs seems both needed and promising in CVD prevention. However, as certain disadvantages may exist, further and larger clinical trials are required to establish their role in daily practice.None to declare.None to declare; this editorial was written independently. The authors did not receive financial or professional help with the preparation of the manuscript.None to declare."}
+{"text": "Measurement of toe and ankle blood pressure is commonly used to evaluate peripheral vascular status, yet the pre-test rest period is inconsistent in published studies and among practitioners, and could affect results. The aim of this systematic review is to evaluate all research that has investigated the effect of different periods of pre-test rest on toe and ankle systolic blood pressure.The following databases were searched up to April 2012: Medline (from 1946), EMBASE (from 1947), CINAHL (from 1937), and Cochrane Central Register of Controlled Trials (CENTRAL) (from 1800). No language or publication restrictions were applied. Eighty-eight content experts and researchers in the field were contacted by email to assist in the identification of published, unpublished, and ongoing studies. Studies evaluating the effect of two or more pre-test rest durations on toe or ankle systolic blood pressure were eligible for inclusion. No restrictions were placed on participant characteristics or the method of blood pressure measurement. Outcomes included toe or ankle systolic blood pressure and adverse effects. Abstracts identified from the search terms were independently assessed by two reviewers for potential inclusion.1658 abstracts were identified by electronic searching. Of the 88 content experts and researchers in the field contacted by email a total of 33 replied and identified five potentially relevant studies. No studies were eligible for inclusion.There is no evidence of the effect of different periods of pre-test rest duration on toe and ankle systolic blood pressure measurements. Rigorous trials evaluating the effect of different durations of pre-test rest are required to direct clinical practice and research. Duration of pre-test rest time for blood pressure measurement varies markedly in the literature, ranging from 5\u2009minutes -3 to 30\u2009The length of pre-test rest time is not only an important factor for stabilisation of blood pressure, reliability of the measurement, and accurate diagnosis of peripheral arterial disease (PAD), but also for clinical efficiency. Mohler III and colleagues  surveyedThis systematic review aims to evaluate all research that has investigated the effect of different periods of pre-test rest time on toe and ankle systolic blood pressure measurements in humans. Determination of the shortest duration of pre-test rest that produces both valid and reliable results may improve clinical efficiency, increase vascular assessment utilisation, and guide future research. This systematic review has been published as conference proceedings .All studies measuring toe or ankle systolic blood pressure in any person after two or more periods of pre-test rest were eligible for inclusion. We planned to include all methods of blood pressure measurement, including automated or manually operated devices, and blood pressures measured from any toe and from either the dorsalis pedis or posterior tibial arteries. We excluded exercise stress tests, post-occlusive hyperaemia tests, and studies of toe or ankle systolic blood pressure measurement that used only one pre-test rest period.The primary outcome was change in toe and ankle systolic blood pressure over time and the secondary outcome was adverse events associated with taking the measurements.The following databases were searched up to April 2012:1) MEDLINE (from 1946)  EMBASE (from 1947)  CINAHL (from 1937)  Cochrane Central Register of Controlled Trials (CENTRAL) (from 1800)  independently assessed titles and abstracts (where available) of all studies identified by the search. No disagreements occurred while screening for inclusion so no arbitration by a third reviewer (VC) was needed. Data extraction was planned to be conducted by one reviewer (SS) using a pilot-tested form and to be cross-checked by a second reviewer (FH).As no gold standard appraisal tool exists for studies investigating measurement agreement, we planned to assess risk of bias of included studies using the QAREL tool  and the Electronic searches retrieved a total of 1658 citations . After screening all identified studies at a title and abstract level, none was eligible for inclusion therefore no full text versions of studies were required. Thirty three content experts and researchers in the field .Click here for fileExperts contacted; the list of content experts and researchers in the field contacted and studies suggested for potential inclusion.Click here for fileEmail sent to experts; the email text sent to content experts and researchers in the field requesting published, unpublished, or ongoing studies.Click here for filePRIMSA flow diagram; PRIMSA flow diagram of retrieved, screened, included, and excluded articles.Click here for file"}
+{"text": "Traumatic brain injury (TBI) is a significant cause of disability in the United States and the mild TBI (mTBI) is the most prevalent. Previous research indicates the positive effect of mindfulness training on symptoms of chronic mTBI such as cognitive functioning and emotion . HoweverFourteen veteran students with mTBI were recruited through campus advertisements. We used 2 weeks of integrative body-mind training as mindfulness intervention, previously reported in our series of randomized studies ,4. All dResting DCM can differentiate the causal brain connections before and after mindfulness training, and provide insight into the brain mechanisms of altered DMN dynamics underlying mTBI recovery, suggesting the changes in information flow in these distributed systems involved in mTBI intervention."}
+{"text": "Myocardial inflammation has been described as a global finding in the acute phase of Kawasaki Disease. Despite normal LV systolic function by routine functional measurements, reduced longitudinal strain (S) and strain rate (SR) have been detected by echocardiography in the acute phase, which may potentially predict late onset heart failure.We aimed to determine whether left ventricular (LV) myocardial deformation indices can detect subclinical myocardial abnormalities in Kawasaki Disease (KD) convalescence. We hypothesized that subclinical myocardial abnormalities due to inflammation represent an early manifestation of the disease that persist in convalescence.Peak systolic LV myocardial longitudinal, radial and circumferential S and SR Figure  were exaComparisons were made between normal controls and (i) the entire KD group, (ii) KD group subdivided by coronary artery involvement. Table  ComparedIn this CMR-FT study in KD convalescent patients with preserved conventional functional indices, we observed a trend for lower circumferential and longitudinal strain in KD patients compared to normal controls, irrespective of their coronary artery status.The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The Division of Imaging Sciences receives also support as the Centre of Excellence in Medical Engineering  as well as the BHF Centre of Excellence (British Heart Foundation award RE/08/03)."}
+{"text": "Endometrial cancer belongs to the most frequently diagnosed malignant neoplasms of female genital organs, and its incidence is steadily growing. For the timebeing, no chromosomal aberrations have been determined unequivocally, which would be specific for the particular stages of endometrial hyperplasia and neoplastic transformation development.The goal of the undertaken studies was an identification of the earliest and specific genetic changes, which could be attributed to an increased risk of neoplastic transformation in a group of patients with endometrial hyperplasia plus the characteristics of genetic changes associated with the mature form of neoplasm.The study involved forty-four (44) patients, including five (5) histopathologically unconfirmed hyperplasia, twenty-six (26) with histopathologically confirmed endometrial hyperplasia and thirteen (13) with diagnosed endometrial cancer.The applied aCGH (array Comparative Genomic Hybridisation) method enabled selection of a few chromosomal regions which indicated a higher incidence of chromosomal rearrangements than in the control group. The study included also an evaluation of the frequency of mutations of the genes specific for neoplastic transformation development, the genes at chromosomal loci, which most frequently presented with genomic imbalance.In cases without hyperplasia, changes were diagnosed, described as CNVs (Copy Number Variations), which occurred with varying prevalence in the genome of the population of healthy subjects. Significant genomic imbalance was identified in 26 (100%) patients with diagnosed hyperplasia and in 11 (84.6%) of the patients with diagnosed endometrial cancer. Also other, till now unreported changes were found, localised at characteristic regions of the genome."}
+{"text": "Revealing novel cancer targeting biomarkers is a great challenge, and especially urging in cancer types with a more pronounced metastatic feature. We focus on potential anti-tumor immune reactions of the host. In order to harness the natural humoral immune response a novel immunological and molecular genetic panel assay has been developed for the investigation of patients with melanomas.Punch biopsies were taken of surgically removed fresh cancerous tissues and peripheral blood was gathered from the patients involved into the study (n= 125). Ethical permission was provided by the Scientific and Research Ethics Committee of the Medical Research Council of the Hungarian Ministry of Health (ETT TUKEB 16462- 02/2010). We established and standardized two experimental strategies (Epstein Barr virus transformation and cloning with limiting dilution assay (LDA) and tumor infiltrating B cell (TIL-B) antibody phage display technology) and started basic processes for a detailed immunglobulin repertoire analysis at DNA level. We set up a novel native tumor cell membrane preparation technique extremely useful for specific detection of tumor reacting antibodies or antibody fragments . Defining essential tumor-associated antigens on the cancerous tissue specimen by immunohistochemistry became the other part of the tumorimmunological panel assay. Results: We claim that this complex quantitative and qualitative analysis of antibodies in sera and in the tumor microenvironment results in revealing tumorspecific antibodies of human origin. Our antibody profile analysis revealed glycoprotein and sialylated glycolipid based tumor-associated antigen-specific antibody-variable regions in various patterns.The present technological developments enable the specific detection of cancer associated sialylated glycolipid and glycoprotein antigens with unique characteristics. The study helps to understand the question of \u201cabnormal glycosilation\u201d and its role in cancer. We conclude that the complex tumorimmunological assay has important potentials in evaluating the host\u2019s anti tumor immune status."}
+{"text": "Cardiac surgery regularly provokes inflammation and oxidative stress which contribute to the development of organ failure and mortality of patients. While the assessment of single markers does not reflect a comprehensive investigation of redox status, the measurement of oxidation-reduction potential (ORP) provides a reliable measure to assess the balance between total prooxidant and antioxidant balance in the blood. The aim of the present study was to investigate the overall redox potential in patients undergoing cardiac surgery.This is a prospective observational study in patients scheduled for elective cardiac surgery. Serum samples were drawn prior to surgery, after connection to cardiopulmonary bypass (ischemia), after opening of cross-clamp (reperfusion) and after termination of surgery.The redox status of patients was measured using the bedside point of care RedoxSYS Diagnostic System\u2122 . Simultaneously the antioxidant capacity in serum samples were calculated in all perioperatively obtained serum samples.n = 17) demonstrated a significant increase of ORP upon start of myocardial ischemia  and compared with reperfusion  corresponding to the increase of oxidative stress (Figure All patients' sera (s Figure .This preliminary study is the first to highlight the time course of overall redox potential and antioxidant capacity in cardiac surgery patients. Further studies are underway to evaluate the clinical significance on outcome in cardiac surgery patients."}
+{"text": "The PPTCT program in India focuses on prong 3 (Provision of Nevirapine to pregnant infected mothers) and reports quote that it reaches only 32% of pregnant mothers who need it. Preventing unintended pregnancies among HIV positive women (Prong 2) could help reduce the burden on Prong 3. To improve use of dual protection and prevent unintended pregnancies among women infected with HIV, an operational research study was implemented in two randomly selected tertiary hospitals in Mumbai (supported by ICMR).The main intervention in this experimental control study was linking ICTC/PPTCT with family planning services by capacity building of providers , provision of IEC material, referral slip, maintaining MIS and testing the acceptability of dual methods among 300 women infected with HIV attending ICTC/PPTCT.Sixty percent of the referred participants reached Family planning centres. Statistically significant improvement in knowledge about contraception and dual protection, three times increased acceptance of dual methods, significant increase in consistent use of condoms and lesser numbers of unwanted pregnancies and births were observed in the experimental than control group. The cumulative failure rate of contraception in the experimental group reduced resulting in preventing 12 women from risk of getting pregnant in first year of use compared to control.The study demonstrated the feasibility to establish this linkage and improved dual method use among participants. The study recommends expanding the current mandate of PPTCT to focus on prong 2 and improve use of dual methods."}
+{"text": "Global awareness of growing demand for oral health care services became prominent over past several decades . Far reaSerbia, as the largest successor state of former Yugoslavia, has its health system legacy in many ways different from Post-Semashko systems of other South East European countries . It is fSince 2004, National Agency for Medicines and Medical Devices of Serbia (ALIMS) issue commercially available periodic reports on precise structure of prescription dispensing and value of sales of all pharmaceuticals within the publicly funded health care facilities, pharmacies, and wholesalers. Recent research of trends over past decade has shown bold growth in local market size  dominateDental medicine is one of the rare examples of flourishing of private-owned clinical facilities rising from historical legacy of state-owned health care in the region. Nevertheless, due to several core weaknesses, pace of contemporary Serbian oral health efforts seems to be insufficient to cover long-term population needs. Surprisingly, strong development of pharmaceutical market in other areas of clinical medicine occasionally reaches several fold annual growth. Due to public funding limitations, such setting creates significant pressures against financing of dental services. Accumulated public debt toward multinational industries of pharmaceuticals and medicinal devices will most likely continue to grow further . Some ofThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques.The plasma-membrane monoamine transporters (MATs), including the serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homolog of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and non-competitive inhibitors have been determined. In addition, several structures of the  The family of sodium coupled plasma membrane monoamine transporters (MATs) include the serotonin (SERT), dopamine (DAT), and norepinephrine (NET) transporters . They arXenopus oocytes established that substrate translocation is electrogenic and involves the movement of sodium and chloride ions (The MATs are members of the neurotransmitter:sodium symporter (NSS) SLC6 family of transporters that also include GABA transporters . Immediaide ions . Some ofide ions . Studieside ions . Though A dramatic change in our structural understanding of the MATs occurred with the elucidation of the 3D structure of LeuT, a bacterial leucine transporter homolog of the MATs. The first structure that was elucidated was of LeuT bound to its substrate leucine occluded from the extracellular and intracellular environment . The strDrosophila DAT was crystalized and a high resolution structure was obtained  and a template identity less than 30%.A few studies have directly targeted the TCA/S2 pocket for screening novel ligands. The study by In addition to the well-known S1 and the allosteric TCA/S2 binding pockets of MATs, we have utilized molecular dynamics simulations and comparative genomics techniques to identify allosteric pockets outside the translocation pathway of MATs that when engaged can specifically modulate the binding of known transporter ligands . The hybMonoamine transporters play an important role in the brain by actively translocating MAs thereby modulating numerous physiological processes that are regulated by MAs. In addition, these plasma membrane transporters bind to a variety of compounds that achieve their effect through the inhibition of the monoamine uptake. These compounds include psychostimulant drugs and antidepressants that are therapeutically relevant and illicit drugs such as cocaine and methamphetamine. Dysfunctions of MATs are implicated in a variety of disorders including depression, mania, addiction and cognition suggesting their key role as therapeutic targets. Despite advances in protein crystallography techniques, 3D structure of only a few members of the NSS family that include MATs are available. Computational techniques including homology modeling, molecular dynamics simulations and virtual screening techniques have resulted in a better understanding of the structure-activity relationships of various inhibitors and substrates with MATs and the design of novel chemotypes to the orthosteric and allosteric pockets. Improvements in screening technologies and the availability of larger chemical libraries have also significantly improved the quality of these ligands resulting in highly efficacious and sub-type selective ligands. Since MATs can be significant targets for both disease modifying and symptomatic treatments of many psychiatric diseases, novel chemotypes that can uniquely target these transporters with improved side effect profiles will be highly desirable.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Lung cancer, the most prevalent and deadly malignancy in the world, poses a particularly critical healthcare challenge to China due to the rapidly increasing new cases and the unique cancer genetics in Chinese patient population. Substantial progress has been made in molecular diagnosis and personalized treatment of the disease. The field is now moving towards multiple new directions to include (1) new generation of targeted agents such as epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors to overcome resistance to their early generation counterparts; and (2) deeper understanding of tumor genetics of each individual patient and consequently the application of biomarkers to guide personalized treatment as well as novel drug development including combination therapy. The increasing capacity in innovative cancer drug research and development is supported by extensive collaboration within China and globally, and across academia and industry, to build up expertise and infrastructure in early-phase clinical testing of novel drugs. With these combined efforts, new and better medicines will be available for lung cancer patients in China in the near future. Chinese Journal of Cancer (CJC), we have organized a series of articles reviewing the global collaborative effort in improving lung cancer treatment in China.Lung cancer, the most prevalent and deadly malignancy, accounts for a staggering 1.6 million new cases diagnosed every year and approximately 21% of cancer deaths to the global cancer burden . In thisEGFR) inhibitor, demonstrated superiority to carboplatin and paclitaxel in treating patients with lung cancer in East Asia [EGFR mutation is the strongest predictive biomarker for progression-free survival and tumor response to first-line gefitinib versus carboplatin and paclitaxel [ALK) inhibitor, has shown superiority compared with chemotherapy in lung cancer patients with ALK translocation [EGFR mutations (32.7%) and ALK rearrangements (6.8%) among lung cancer patients in China has further expanded the use of these targeted agents [Lung cancer treatment in China has shown substantial advancements in recent years exemplified by the integration of targeted therapies in standard of care. In the landmark Iressa Pan-ASia Study (IPASS) study, gefitinib (Iressa), a mutated epidermal growth factor receptor  capacity, the enhanced global collaboration, and the expanding capability in cancer drug clinical development will lead to the next wave of breakthroughs in the treatment of lung cancer in a personalized fashion in China."}
+{"text": "The use of omalizumab in severe persistent allergic asthma may lead to decrease health care utilization through emergency room (ER) visits, hospitalizations, visits to health care providers, as well as, decrease the use of corticosteroids and improve the overall quality of life (QoL).Xolair Data collected from patient enrollment and QoL questionnaires completed at specific intervals during treatment with omalizumab at our large tertiary care clinic from 2004 to 2014 was analyzed.A steady number of patients were enrolled each year since 2004, showing its greatest increase in enrollment numbers since 2012. Our data indicates that the majority of patients improved with significantly less asthma exacerbation, less ER visits and hospitalizations, less use of inhaled and oral corticosteroids and better QoL.Omalizumab is effective in the treatment of moderate and severe allergic asthma. It improves QoL and reduces asthma exacerbations, ER visits and hospitalizations, and use of inhaled and oral corticosteroids."}
+{"text": "Environmental toxicology is one of the most interdisciplinary subjects and it aims to study the effects of toxic chemicals on living organisms using various toxicological methods. The experiments that examine the deleterious effects of environmental pollutants on animals provide scientific basis for developing environmental standards. Results of such experiments and the techniques and practices used to minimize environmental effects of toxic chemicals will help in formulating sound environmental policies and appropriate decision-making.The special issue addresses various topics, such as biomarkers for environmental pollution monitoring; bioaccumulation of chemicals; bioassays and biomarkers in water monitoring and biomonitoring of water bodies; ecotoxicity of emerging chemicals; biological effects of monitoring; laboratory techniques and field quantitative structure-activity relationships (QSAR); ecosystem health and environmental health risk assessment.This special issue is a compilation of selected peer reviewed papers that range from biomarkers, bioconcentration and toxication, oxidative stress defuse pathways to cytotoxic effects of pesticides, phytoremediation of polluted soil, and so forth.The editors believe that the results presented in these papers are valuable and will stimulate discussion on further development of potential techniques and devices for effective assessment of deleterious effects of environmental pollutants on animals and the environment."}
+{"text": "Rare skeletal diseases are a diverse group of diseases that primarily affect development of the skeleton. There are more than 450 unique phenotypes that, although individually rare, have an overall prevalence of at least 1 per 4,000 children. Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal diseases caused by missense mutations/deletions in the genes encoding important cartilage extracellular matrix proteins (ECM), and are characterized by disproportionate short stature, joint pain and early-onset osteoarthritis.In-depth characterization of MED and PSACH mouse models has revealed that endoplasmic reticulum (ER) stress, reduced cell proliferation and abnormal ECM assembly are important pathological consequences of mutant protein expression. Ongoing work aims to consolidate data from other models of skeletal disorders using a systems biology approach as part of the EU FP7 SYBIL  project, in order to gain a mechanistic understanding of disease processes and to deliver new and validated therapeutic targets.Key to delivery of new targets and therapies is the identification of relevant disease biomarkers, which will allow the monitoring of responses to therapeutic interventions. This is particularly critical for skeletal diseases, for which biopsy material is not readily accessible. We have identified differences in the extractability of a number of ECM components from the cartilage of MED and PSACH mouse models, relative to controls. The differences in extractability of these proteins (which include FACIT collagens (types XII and XIV), tenascins (C and X), and fetuin A) may represent differences in the stability of these proteins within the cartilage ECM, which might potentially be exploited for use as biomarkers of disease progression. We are currently using biochemical and mass spectrometry analysis of easily obtained biological samples such as blood, urine and cell culture medium in order to identify and validate novel biomarkers for skeletal diseases."}
+{"text": "The turnover of fat cells and their lipid content is constantly ongoing in adult life. Fat cell turnover has importance for development of adipose tissue consisting of many small fat cells (hyperplasia) or few but large cells (hypertrophy). The latter is linked to metabolic disorders. Variations in lipids turnover in fat cells is also linked to metabolic disease.We are interested in measuring the turnover of human fat cells and their lipid content and study their impact on hyperplasia/hypertrophy and its clinical consequences.Lipid and fat cell turnover is measured by incorporation of atmospheric 14C into triglycerides and DNA of human fat cells. Hyperplasia/hypertrophy is determined by measuring fat mass and fat cell size.Decreased turnover of fat cells and their lipid contents is associated with insulin resistance, dyslipidemia and altered metabolic function of fat cells. Low fat cell turnover leads to adipose hypertrophy which is linked to insulin resistance in subcutaneous fat and to dyslipidemia in visceral fat. A transcription factor (EBF-1) regulates hyperplasia/hypertrophy in human adipose tissue and in animal models. Changes in adipose EBF-1 expression is linked to abnormal metabolic function of fat cells and to in vivo insulin resistance.Altered turnover of fat cells and their lipid content is important for common clinical disorders."}
+{"text": "Plasmodium falciparum malaria, and in combination with other effective interventions will undoubtedly play a vital role in elimination programmes. The gametocytocidal properties of ACTs are a bonus attribute; there is epidemiological evidence of reductions in malaria incidence and transmission in African regions since the introduction of these agents. Many studies and analyses have specifically investigated the effects of artemether-lumefantrine (AL) on gametocyte carriage.Despite significant advances made in the prevention and treatment of malaria in recent years, these successes continue to fall short of the World Health Organization (WHO) goals for malaria control and elimination. For elimination strategies to be effective, limited disease transmission, achieved through rapid reduction in infectious parasite reservoir and decreased gametocyte carriage, will be critical. Artemisinin-based combination therapy (ACT) forms the cornerstone of WHO-recommended treatment for uncomplicated P. falciparum malaria in several African countries and the high number of clinical trials that have evaluated the product. Impact of AL on population gametocyte carriage and potential future role of AL in malaria elimination initiatives are also considered.A systematic review of 62 articles published between 1998 and January 2014 was done which compares effects of AL on gametocyte carriage and malaria transmission with other ACTs and non-ACTs. AL was assessed based on its widespread usage of ACTs recommended by WHO, in the treatment for uncomplicated The gametocytocidal effect of AL was proportionately con-sis tent across the studies reviewed, despite inherent difficulties in comparing data from a range of studies that utilized different diagnostic approaches to assess baseline gametocyte counts and differences in study designs. However, the specific place of AL is the subject of ongoing research and will be dependent on its use in combination with other intervention measures, rational use of the product, interaction with other medicinal agents in situations of malaria co-infections and comorbidities, and demographic differences. Use of ACTs like AL in malaria elimination strategies will therefore require balancing potential increased roll out with rational use and protection against resistance development.AL  will continue to play a vital role in treatment of malaria by rapidly clearing asexual parasite load and reducing gametocyte carriage in both symptomatic patients and asymptomatic carriers. Consequently, AL, an ACT with this significant dual activity on asexual and sexual parasite forms, can help shrink the infectious parasite reservoir that will in turn reduce infection of mosquitoes and ultimately minimize malaria transmission."}
+{"text": "Hypovolaemia is generally believed to induce centrali sation of blood volume. Therefore, we evaluated whether hypovolaemia and hypervolaemia result in a change in central blood volume ) and we explored the effects on the distribution between PBV and circulating blood volume (Vd circ).After local District Governmental Animal Investigation Committee approval, blood volume was altered in both directions randomly in steps of 150 ml (mild) to 450 ml (moderate) either by haemorrhage, retransfusion of blood, or infusion of colloids in six Foxhound dogs. The anaesthetised dogs were allowed to breathe spontaneously. Blood volumes were measured using the dye dilution technique: PBV was measured as the volume of blood between the pulmonary and aortic valve, and Vd circ by two-compartmental curve fitting . The PBVA total of 68 alterations in blood volume resulted in changes in Vd circ ranging from -33 to +31% (Figure Mild to moderate alterations of blood volume result in changes of PBV and Vd circ. However, against the traditional belief of centralisation we could show that the cardiovascular system preserves the distribution of blood between central and circulating blood volume in anaesthetised dogs."}
+{"text": "The \u2018Precision Medicine for Cancer\u2019 was the first meeting of a new series of conferences organised biannually by the European Association for Cancer Research (EACR) and the Organisation for European Cancer Institutes (OECI). The main objective of the meeting was to focus on novel topics in precision medicine by allowing strong interactions between participants and to access the speakers easily. As the first implementations of personalised medicine are appreciated in the clinic, the aim of the meeting was to further educate both researchers and clinicians and learn more from the novel approaches in the field. Similarly, the interaction between two organisations\u2014the research-oriented EACR and the clinic-oriented OECI\u2014was of a great value for the meeting. This OECI-EACR 2015 report will highlight the major findings of this outstanding meeting. Professor Simone Niclou, the local organizer from the Luxembourg Institute of Health, the head of the NorLux Neuro Oncology laboratory; Professor Richard Marais, the head of the Molecular Oncology Lab, the Director of the CRUK Manchester Institute and the EACR President; and Professor Giorgio Stanta from the University of Trieste , representing the OECI. They all stated the aims of the conference: educating people and scientists in the new era of personalized medicine.The conference took place in Luxembourg, a place known more as a financial center rather than a research site. The conference started with the welcoming words from the organisers: Dr Frank Glod, the head of the FNR\u2019s \u2018Strategic Research Programmes\u2019 unit, which include funding national and international research projects, promoting scientific culture and interest in research in the society.During recent years, as part of socio-economic changes in the country the Luxembourgish government established a strategic plan to invest in the fundamental and applied research and to put Luxembourg on the map of European research centers. The National Research Fund  is the key player in establishing a high-quality research environment in Luxembourg. The strategic objectives of the organisation were presented during the conference by The conference was followed by scientific talks from lead experts in the field of personalised medicine.The opening session of the conference focused on novel approaches and main challenges in translating precision medicine protocols in the clinic.Professor Thomas A. Sellers, the director of the Moffitt Cancer Centre and Research Institute in Tampa, Florida (USA), featured the opening keynote lecture. Professor Seller is a worldwide expert in molecular and genetic epidemiology and he aims to use the existing knowledge to predict risk and response to current therapies. In his opinion much can be learned outside of the clinical trials form the existing information, including somatic and germline variants, pathological and surgical parameters and lifestyle of the patients. The precision medicine protocols are designed not only to increase therapeutic outcome but also to decrease cost on health care. During the lecture we have learned about the remarkable effort made by the Moffitt Cancer Center in establishing the outstanding infrastructure for the research protocols. Importantly, as highlighted by the speaker, the platform was created not only for the clinicians and researchers but also is of a great use for the hospital administration and patients themselves. The data includes patient information and consent, health records, tissue collection, and data maintenance. Even more impressive, the Moffitt Cancer Center further expands the collection of patient information with the other cancer centres in USA within the Oncology Research Information Exchange Network (ORIEN) in hope to accelerate the development of targeted therapies and match patients more appropriately to the ongoing clinical trials. The two following talks of the session focused on the importance of the tumour heterogeneity in designing novel therapies and understanding drug resistance mechanisms. Professor Simone Niclou, the head of Norlux Neuro-Oncology laboratory at the Luxembourg Institute of Health (L.I.H), summarized our current understanding on very strong inter- and intra-tumoural heterogeneity in glioblastoma, the most aggressive and incurable type of brain tumours. She presented current attempts to stratify the glioblastoma patients based on genetic profile, transcriptome, epigenome and altered molecular pathways. Within the adult glioblastomas the integrative analysis at different levels revealed so far only one clear subgroup of patients with IDH1 mutation associated with hypermethylated phenotype and better survival prognosis. Unfortunately all recent clinical trials failed and more effort is needed to better understand this very heterogeneous and rare disease. The additional challenge in designing novel treatments lies in the strong intertumoural heterogeneity. Evolution of tumours in time together with regional heterogeneity needs to be evaluated in more detail in the future. Professor Niclou highlighted the novel data from her group showing very strong inter- and intratumoural heterogeneity at the ploidy level [Professor Alberto Bardelli from the Candiolo Cancer Institute at the University of Torino  presented recent data on how his group endeavours to define relationship between genotype and response to drug treatment in colorectal cancer. Importantly colorectal cancers represent molecularly distinct diseases, therefore personalised protocols are needed to improve therapeutic outcomes. The strong genetic heterogeneity is present not only between patients but also between multiple metastatic sites of the same patient and even within the same lesion. Professor Bardelli focused particularly on the primary and secondary resistance to EGFR-targeted therapies that remarkably are driven by the mutations in the same genes and lead to activation of the same key signalling pathways (MEK/ ERK activation) [A gold standard for testing novel therapeutical protocols involves randomised controlled clinical trials, however the precision medicine should also make a use of information from existing treatments and epidemiology. dy level , where ady level  but alsody level . A stronivation) , 26. He ivation) . He intrProfessor Anne-Lise B\u00f8rresen-Dale from the Institute for Cancer Research at the Oslo University Hospital (Norway) presented a remarkable effort of her group in assessing tumour heterogeneity with use of numerous high-throughput techniques [Professor Carlos Caldas from the Cancer Research UK Cambridge Institute (UK) presented novel classification of breast cancers into 10 genomic-driven based subtypes. Breast cancer is mainly driven by the somatic copy number alterations which strongly correlate to gene expression [Dr Jerome Paggetti from the Laboratory of Experimental Hemato-Oncology at the Luxembourg Institute of Health (L.I.H.) focused on the role of exosomes in communication between tumour and stromal cells. Exosomes are small extracellular vesicles originated from tumour endosomes that carry small RNAs , mRNA, DNA and proteins. Circulating miRNAs are sensitive prognostic markers for chronic lymphocytic leukemia (CLL) [The second session of the conference focused mostly on the current challenges and heterogeneity in breast cancer. chniques . The comchniques . We havechniques . Professpression . IntCluspression . IntCluspression . Hopefulpression . This wiia (CLL) , 28 and Professor Manel Esteller from the The Bellvitge Institute for Biomedical Research (IDIBELL) in Barcelona (Spain) showed us that both in health and disease, DNA methylation is a key determinant of the epigenome. Professor Manel Esteller recapitulated the essential contribution of DNA methylation in the evolution of pharmacoepigenetics accross different cancer types. In glioma the promoter methylation of the DNA repair enzyme (O(6)-Methylguanine-DNA methyltransferase (MGMT) is a prognostic marker of patient response to Temozolomide currently used in the clinics. This marker also predicts the clinical response to dacarbazine in metastatic colorectal cancer [Professor Jukka Westermarck from the Institute of Molecular Medicine at University of Helsinki (Finland) presented the second proffered paper. His results showed that PP2A is a major determinant of therapeutic response in cancer cells and its inactivation is linked to a poor prognosis in about 12 cancer types. PP2A is inhibited by the oncoprotein CIP2A, Cancerous Inhibitor of Protein phosphatase 2A [Professor Ultan McDermott from the Sanger Institute in Cambirdge (UK) presented how use of large scale sequencing generated through the International Cancer Genome Consortium and The Cancer Genome Atlas allows the current definition of cancer genome patterns. These impressive resources provide a catalogue of mutational processes and genomic alterations for pancancer and cancer specific analyses [Professor Stefan Pfister from the German Cancer Research Centre (DFKZ) in Heidelberg (Germany). Unlike many others cancers, clinical decisions for patients with brain tumours rely mainly on histopathology which should, in the future be complemented with molecular informations for accurate diagostics [l cancer . In ovarl cancer . Outsidel cancer . Of inteatase 2A . In headatase 2A . Professanalyses . Synthetagostics . We haveagostics . The impProfessor Richard Marais, the director of the CRUK Manchester Institute (UK) and the EACR President. He showed us how the history of melanoma treatment has changed since the discovery of BRAF as an oncogene in cancer [Dr Maria Romina Girotti from the Molecular Oncology Lab at the CRUK Manchester Institute (UK) presented the third proferred paper where she descirbed a new platfrom for personalised medicine in melanoma patients. Dr Girotti showed that BRAF inhibitors such as vemurafenib or dabrafenib, or MEK inhibitors, trametinib and cobimetinib, block the RAS-RAF-MEK-ERK pathway, inhibiting cell growth and increasing progression-free and overall survival in patients whose tumours carry BRAF mutations. However, responses are generally limited and after a relatively short period (6-8 months) of disease control, most patients develop resistance. Selecting second line therapies is challenging and current advice includes an option to continue targeted treatment beyond progression. To develop approaches improving patient outcomes with targeted therapies she described the importance of integrating several methodologies, including whole exome sequencing (WES), patient derived xenografts (PDX), longitudinal analysis of circulating tumour DNA (ctDNA) as a liquid biopsy from melanoma patients on standard chemotherapy and targeted therapies. The session was followed by Professor Daniel Peeper from the Netherlands Cancer Institute (NKI) in Amsterdam. Professor Pepper presented importance of parallel in vivo and in vitro negative-selection short hairpin RNA (shRNA) screens for genes that preferentially contribute to tumour cell proliferation and survival in vivo in melanoma. He found that melanoma cells harboring shRNAs targeting several DNA damage response (DDR) kinases had a greater selective disadvantage in vivo than in vitro, indicating an essential contribution of these factors during tumour expansion. DDR kinases became activated following hypoxia and either the depletion or pharmacologic inhibition of DDR kinases were toxic to melanoma cells. This included resistance to the BRAF inhibitor, and this could be enhanced by angiogenesis blockade. These results reveal that hypoxia sensitizes melanomas to targeted inhibition of the DDR showing the utility of in vivo shRNA dropout screens for the identification of pharmacologically tractable targets [Professor Jeffrey Sosman from the Vanderbilt University Medical Center in Nashville (USA), focused on BRAF wild type melanomas. His approach has centered on finding ways to better target NRAS mutant melanoma and better define subsets in the NRAS, cohort that may be responsive to specific therapies. Preclinical experiments have shown a greatly enhanced anti-tumour response when CDK4/6 inhibitors were added to MEK inhibitors [This session featured leaders in the field of melanoma presenting their advances in precision medicine for this disease. The session started with n cancer . New tarn cancer , 15. Morn cancer  revealinn cancer  and highn cancer . Importan cancer . Then Dr targets . Professhibitors . This fiProfessor Susan Critchlow from AstraZeneca in the UK presented metabolic reprogramming in cancer and novel drugs targeting cancer metabolism. The metabolic phenotype of many tumours switches from oxidative phosphorylation to aerobic (Warburg Effect) or anaerobic glycolysis increasing the rates of glucose consumption and lactate production enabling tumours to meet their energy and biosynthetic demands even under conditions of low nutrients and O2. The final product of glycolysis, lactate, is a metabolic \u2018dead-end\u2019, which if allowed to accumulate in the tumour cell can cause feedback inhibition of glycolysis, intra-cellular acidification and inhibition of cell growth. Therefore pharmacological inhibition of lactate transport represents a promising therapeutic strategy to target a range of human cancers. Monocarboxylate transporters (MCT1-4) catalyse proton-linked transport of monocarboxylates across the plasma membrane with MCT1 and MCT4 being the key tumour-associated lactate transporters. AZ has developed a new drug AZD3965 which targets MCT1, representing the first class small molecule inhibitor targeting glycolytic phenotype of tumours with great antitumour effects in renal cell carcinoma. Professor Eyal Gottlieb from the CRUK Beatson Institute in Glasgow (UK), focused on metabolic adaptation of cancer cells to changing environments and stress. We have learned that fatty acid synthase (FASH) is over-expressed in numerous cancers, presumably because there is a limited source of fatty acids for growth. Cancer cells are sensitive to FASH inhibitors upon stress conditions (low serum). Compared to normoxia, upon hypoxia fatty acids present reduction in polysaturated lipids indicating limited de novo fatty acid synthesis. Interestingly, although 13C carbon incorporation from glucose is reduced in hypoxia the total amount of lipids is higher, suggesting use of another carbon source by hypoxia-stressed cells. Acetyl-coA synthetase 2 (ACSS2) is focally amplified in breast cancer and correlates with poor prognosis. ACSS2, which uses acetate to produce Acetyl-CoA-a key metabolic hub- was found to be essential for survival upon metabolic stress and in vivo. Characterization of acetate metabolism confirmed it was consumed by cancer cells under hypoxia in an ACSS2-dependent manner and was used to synthesize lipids and TCA-cycle intermediates [Dr Bassam Janji from the Laboratory of Experimental Hemato-Oncology at the Luxembourg Institute of Health (L.I.H.) focused on the role of autophagy in regulating anti-tumour immune response in hypoxia. Hypoxia, a feature of most solid tumours, is known to influence different aspects of tumour biology including metabolism and contribute strongly to chemo- and radioresistance. Hypoxia is also involved in immunosuppression, an important drawback for targeted immunotherapies. Dr Janji stressed that even under active immune response, tumour cells escape immunosurveillance under hypoxic stress. Hypoxic tumour cells can escape both the cytotoxic T lymphocyte (CTL)-mediated adaptive response [mediates . Interesresponse  and the response  by activDr Zhi Xiong Chen from the National University of Singapore. Number of neuroblastoma (20\u201330%) carry a deletion of 1p36 on which is located KIF1Bb, a possible tumour suppressor gene. The work of Dr Chen provides some molecular basis of this mechanism. KIF1Bb interacts with DHX9 and is required for KIF1Bb-mediated apoptosis. This complex regulates the level of the apoptotic gene XAF1 [Dr Anna Golebiewska from the Norlux Neuro-Oncology laboratory at the Luxembourg Institute of Health (L.I.H) presented the sixth proffered paper. Her talk touched on the glioblastoma xenograft model based on organotypic spheroids. The xenografts derived in eGFP expressing NOD/Scid mice allow appropriate discrimination between tumour and stromal cells and in detail characterisation of the two compartments without manipulation of the patient-derived material [Professor Sergio Quezada from the UCL cancer Institute at the University College London (UK). The intra-tumour balance of immune cells is dynamic upon tumour growth and evolves towards a low ratio between effective and regulatory T cells. The outcome of this homeostasis is of utmost importance for survival and often results in the immune control escape of tumour cells. Immunomodulatory strategies using antibodies against CTLA-4 modify this balance and increase the proportion of effective T lymphocytes. The work presented by Professor Quezada investigated this therapeutic strategy in a murine model of melanoma. His results showed that the expression of FcgRIV on myeloid cells expressing CD11b is required for intratumoural T reg depletion [This session started with the fifth proferred paper presented by ene XAF1 . As a rematerial , 17. Impepletion . SpecifiProfessor Passi Janne, director of the Lowe Center for Thoracic Oncology and Scientific Director of the Belfer Institute for Applied Cancer Science in Boston (USA) communicated on EGFR and resistance in SCLC. The most common mechanism of resistance involves mutation of the target. This results in pathway reactivation, so new drugs or new drug combinations are needed. Importantly, the therapy should be both effective and tolerable. The most common mutation in lung cancer is T790M in EGFR. Alternative/covalent EGFR inhibitor should overcome increased affinity to ATP in the EGFR T790M. Unfortunately afatinib, a covalent EGFR inhibitor, failed in clinic due to very high effective concentrations which led to too strong toxicity. By using a cell line model with mutation and a screen for novel class of inhibitors Professor Janne found agents that were ~100X more potent. Not only were they more active, they were also mutation selective. There are currently many next generation drugs in the pipeline for single and combinational studies; two have received advanced drug status: AZD9291 and WZ4002. AZD9291 trial resulted in 50% objective responses (tumour responses) and more importantly due to acceptable IC50 for both EGFR wt and T790M it can be used further for combinational studies. WZ4002, another covalent EGFR T790M inhibitor, while combined with trametinib, a MEK inhibitor, prevents emergence of resistance from the onset of the treatment. Professor Caroline Dive from the CRUK Manchester Institute (UK), presented exciting results about the role of Circulating Tumour Cells (CTCs) in small-cell lung cancer (SCLC). This is an aggressive tumour with early dissemination and bad prognosis, and biopsies to investigate SCLC biology are difficult to obtain. Professor Dive focused on the function and potential biomarker role of CTCs, which are prevalent in SCLC, and present another \u2018liquid biopsy\u2019 option. CTCs in SCLC can be used not only as a prognostic marker but also as a potential predictive biomarker. Importantly, CTCs from patients with either chemosensitive or chemorefractory SCLC are tumourigenic in immune-compromised mice, and the resultant CTC-derived xenografts (CDXs) mirror the patient\u2019s response to chemotherapy. The genetic characterization of CTCs and CDX showed considerable similarity [Dr Safia Thaminy presented the seventh proffered paper from the ETH in Zurich (Switzerland) and the Institute for Systems Biology, Seattle (USA). She studied the role of hypoxia in breast cancer and used breast cancer cell lines with distinct aggressiveness properties to develope an innovative strategy based on a system-wide quantitative proteomics in combination with a high-throughput migration screen and protein network analysis. Dr Thaminy found that the less aggressive cell line temporally regulated cell migration under hypoxia and the underlying mechanism involved the PTPRG and TACSTD2 driver genes. In a large-scale migration screen, stathmin (STMN1) remarkably discriminated the poorly invasive from the highly invasive cell line and STMN1 knockdown dramatically enhanced cell migration of poorly invasive cells only under hypoxia. With these results she proposed a model of cancer progression based on the hypoxia-dependent trafficking of vesicles and their release in the extracellular space. Finally Professor Anton Berns from the Netherlands Cancer Institute (NKI) in Amsterdam presented the closing keynote lecture. Professor Berns is a world leader in creating genetically engineered mouse models for analysis of tumour initiation, progression and metastasis. Genetically engineered mouse models (GEMMs) for SCLC and other high-grade lung neuroendocrine (NE) carcinomas are crucial for translational research. He presented five GEMM models representative for the entire spectrum of human high-grade NE carcinomas and also useful for the study of multistage pathogenesis and the metastatic properties of these tumours [milarity . She pro tumours . He partThe conference hosted two independent poster sessions including 63 posters in total. Posters covered different aspects associated with personalised medicine, including analysis of inter- and intratumoural heterogeneity at different molecular levels in multiple tumour types, differential response to treatment and resistance. 31 participants received a travel grant of 1000E each to assist with the cost of the conference. Anne Harttrampf from the Necker Enfants Malades and Saint Anne Hospital in Paris (France) and Stefania Libreros from the Florida Atlantic University (USA) won the 2 poster prizes worth 100 \u20ac each.The conference accommodated two satellite symposia presented by NanoString and Affymetrix. Both companies presented their novel technologies in personalised medicine. NanoString nCounter technology promises a high multiplex amplification-free system for detection of hundreds of targets simultaneously via digital detection. Affymetrix highlighted their new OncoScan FFPE Assay for the high resolution whole-genome copy number analysis of as little as 80ng DNA. Both technologies can be applied to challenging samples (FFPE).Precision Medicine is a novel approach for disease diagnosis and treatment that takes into account individual differences between patients. Significant improvements were made to implement targeted protocols in several cancers, however it is far from being a general clinical practice. Before the precision medicine protocols become standard we need to better comprehend the molecular drivers leading to a very strong inter- and intratumoural heterogeneity and emergence of resistance. In that respect, integrative analysis of a high-throughput techniques combined with use of patient-derived xenografts will be of a great value in the future. In addition improved understanding of tumour microenvironment and interactions with immune system will be crucial for a success of encouraging novel cancer immunotherapies and combinatory treatments. The diagnosis for precision medicine protocols needs to be straightforward and cost-effective, therefore emergence of tailored molecular tests, including analysis of circulating free DNA or circulating tumour cells appear as promising strategies. Novel clinical trials for targeted therapeutics will be essential, nevertheless much can be already learned from the existing treatments and epidemiology."}
+{"text": "Surgery is an example of expanded practice scope that enhances podiatry and incorporates inter-professional collaboration. By 2050 demand for foot and ankle procedures is predicted to rise nationally by 61.9%. Performance management of this increase motivated the development of an online audit tool. Developed in collaboration with the Australasian College of Podiatric Surgeons (ACPS), the ACPS audit tool provides real-time data capture and reporting. It is the first audit tool designed in Australia to support and improve the outcomes of foot and ankle surgery.Audit activity in general, orthopaedic, plastic and podiatric surgery was examined using a case study design. Audit participation enablers and barriers were explored. Case study results guided a Delphi survey of international experts experienced or associated with foot and ankle surgery. Delphi survey-derived consensus informed modification of a generic data set from the Royal Australasian College of Surgeons (RACS). Based on the Delphi survey findings the ACPS online audit tool was developed and piloted. Reliability and validity of data entry and usability of this new tool was then assessed with an online survey.The case study found surgeon attitudes and behaviours positively impacted audit participation, and also indicated that audit data should be (1) available in real time, (2) identify practice change, (3) applicable for safety and quality management, and (4) useful for peer review discussion. The Delphi process established consensus on audit variables to be captured, including the modified RACS generic data set. 382 cases of foot and ankle surgery were captured across 3 months using the new tool. Data entry was found to be valid and reliable. Real-time outcome reporting and practice change identification impacted positively on safety and quality management and assisted peer review discussion. An online survey showed high levels of usability.Surgeon contribution to audit tool development resulted in 100% audit participation. The data from the ACPS audit tool supported the ACPS submission to the Medical Services Advisory Committee to list podiatric surgery under Medicare, an outcome noted by the Federal Minister of Health."}
+{"text": "Post-cold war developments and accelerated pace of globalization among many changes led to the creation of so called emerging markets. These classical national economies represent few among large number of developing world countries, which are distinguished by their exceptionally strong promise of rapid and long-term stable growth of gross domestic product. Either we assess it on nominal or purchase power parity (PPP) terms, four distinct economies obviously lay ahead all other rapidly developing global markets. Acronym BRIC  forged to describe these countries brought glory to its creator Jim O\u2019Neil, Goldman Sachs\u2019 economist of the time . Since hEach one of BRICs countries enjoyed prolonged period of geopolitical stability. Local governments via different mechanisms succeeded to use welfare of the society to improve access and quality of health care . Rising Global health expenditure database (GHED) relying on national health accounts (NHA) system to track financial flows within national health systems of all World Health Organization (WHO) members across the globe was established since 1995 with latest official release of 2012 data (All aforementioned data point out to the several important facts. In the beginning of observation period, Brazil was dominating the BRICs landscape both in terms of nominal and PPP and percentage of gross domestic product health spending . Over thMany forecasts actually point out to the growing competitiveness of BRICs compared to major OECD markets. OECD\u2019s joint share of global health expenditure still far exceeds the one of BRICs although OECD/BRICs ratio of joint THE fell from 22 times in nominal terms in 1995 to 7 times in 2012. This same ratio expressed in PPP terms felt from ninefold larger THE in favor of OECD in 1995 to only fourfold larger THE in 2012. OECD\u2019s proportion of global health spending fell from 91 to 81% in nominal terms and from 82 to 72% in PPP terms. The global trend of gains and losses in health spending clearly went in favor of largest emerging markets at the expense of mature, traditional high-income OECD economies . We shouHealth policy makers are aware they should stay precautious about newly built socioeconomic welfare of many developing countries. Their national capacities to direct investment and growing capacities into the most rewarding, evidence based and cost-effective medical procedures and drugs remain very limited. Knowledge-based resource allocation still has to make roots in health policy traditions of BRICs and other emerging nations . Health The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Tamura et al. explore in more detail the function of novel nucleoskeletal proteins specific to plants and how nuclear morphology effects plant cell function. Zhou et al. review the various functions of Sad1/UNC84 (SUN) domain \u2013 Klarsicht/Anc1/Syne homology (KASH) bridges with particular emphasis on plant-specific KASH proteins and their role in plant development. The impact of the nuclear periphery, and in particular of nucleoporins, on gene regulation is comprehensively examined by Parry. The author also illustrates the role of NPC and NE components in chromatin organisation and RNA export. In addition, MacGregor and Penfield detail the complex functions and pathways that are affected by the nucleoporin HOS1. This protein is a fascinating example of how nuclear periphery components affect signalling pathways during plant growth and development \u2013 in the case of HOS1 during temperature responses and flowering time. Schubert and Weisshart present novel insights into the distribution of active and inactive RNA Polymerase II molecules as revealed by super resolution microscopy techniques Structured Illumination Microscopy (SIM) and Photoactivated Localization Microscopy (PALM). Finally, Petrovska et al. compare various techniques used for identifying nuclear components in plants \u2013 including NE associated proteins. This is particularly exciting as still only a few membrane-intrinsic NE components are known. In addition, most of the identified NE, NPC and nucleoskeletal proteins identified still remain to be functionally characterised, such as many of the nucleoporins. The research presented here is an example of the exciting discoveries that are driving this field forward. The authors are part of the International Plant Nucleus Consortium (IPNC), which is a platform to facilitate networking and sharing of researchers and their expertise of the plant nucleus.Part of this special edition highlights the latest advances made in understanding the structure and functions of nuclear periphery components in plants. The plant nuclear envelope (NE), with its inner and outer nuclear membrane components, the NE\u2013embedded nuclear pore complexes (NPC) and the NE\u2013associated nucleoskeletal plant lamina have been of great interest in recent year. While some of their components and structures are conserved in other eukaryotes, for instance the majority of nucleoporins, many plant-specific NE associated proteins and functions have been discovered. As a result, we have gained fascinating new insights into how plant nuclear periphery components affect various nuclear functions such as gene regulation, chromatin organisation and nuclei positioning. Both Tamura"}
+{"text": "The mechanism of disease causation is usually due to haploinsufficiency of certain critical genes of that region. The genetic changes of these microdeletion syndromes are often not detected by the current band resolution using the routine or high resolution karyotyping (2-5 Mb) but require application of molecular cytogenetic techniques like Fluorescence FISH is now the standard technique for the diagnosis of common microdeletion syndromes like Prader Willi syndrome, Angelman syndrome, Velocardiofacial (DiGeorge) syndrome, William syndrome etc. It is also possible to diagnose rare syndromes like Wolf Hirschhorn syndrome, Smith Magenis syndrome etc by FISH if the degree of clinical suspicion is high. With the advent of chromosomal microarrays, detection of newer microdeletion syndromes and better characterization of existing syndromes has become possible."}
+{"text": "To analyse predictors of early response after two treatment cycles with Onabotulinumtoxin type A (OnabotA) in patients with chronic migraine (CM).Thirty-one patients  with IHS criteria for CM and an inadequate response or intolerance to other oral preventatives were included. Data regarding the frequency and intensity of headache attacks, analgesic use and migraine disability assessment scale (MIDAS) before and after OnabotA treatment was collected; as well as, headache location and the presence of allodynia or bruxism. The current oral preventive therapy was continued in all patients.Good responders were patients who after treatment improved in all of these four categories: headache frequency (CM to low-frequency episodic migraine), headpain intensity (reduction of >75%), analgesic/triptan use (reduction to a use of two days or less per week), and disability . Partial responders were those who only improved in two of the four categories.Patients were classified into 3 categories: good responders (58.1%), partial responders (29%), and non-responders (12.9%). The age (younger subjects) and the presence of a shorter migraine history are the two indicators of a better response to the treatment . Unilateral headache, presence of allodynia and/or bruxism appears not to be predictors of response to OnabotA in our study.Age and the years of migraine history are predictors of early response to OnabotA in our experience. The younger the patient and less years of migraine chronification are good predictors of early response."}
+{"text": "For the follow-up scans, three groups of children  were examined at the term equivalent age and after the first year of life. MRI and histological abnormalities were analyzed in the following compartments: (a) periventricular, with periventricular fiber system; (b) intermediate, with periventricular crossroads, sagittal strata, and centrum semiovale; (c) superficial, composed of gyral white matter, subplate, and cortical plate. Vulnerability of thalamocortical pathways within the crossroads and sagittal strata seems to be characteristic for early preterms, while vulnerability of long association pathways in the centrum semiovale seems to be predominant feature of late preterms. The structural indicator of the lesion of the long association pathways is the loss of delineation between centrum semiovale and subplate remnant, which is possible substrate of the diffuse periventricular leukomalacia. The enhanced difference in MR signal intensity of centrum semiovale and subplate remnant, observed in damaged children after first year, we interpret as structural plasticity of intact short cortico-cortical fibers, which grow postnatally through U-zones and enter the cortex through the subplate remnant. Our findings indicate that radial distribution of MRI signal abnormalities in the cerebral compartments may be related to lesion of different classes of axonal pathways and have prognostic value for predicting the likely outcome of prenatal and perinatal lesions.The developmental vulnerability of different classes of axonal pathways in preterm white matter is not known. We propose that laminar compartments of the developing cerebral wall serve as spatial framework for axonal growth and evaluate potential of anatomical landmarks for understanding reorganization of the cerebral wall after perinatal lesions. The 3-T MRI ( The process of complex growth of white matter tracts  \u20138 occur As demonstrated previously, axons are more vulnerable to hypoxia ischemia and other pathogenetic factors such as periventricular hemorrhages during the period of intensive growth , 30\u201339. The presence of well defined laminar architecture of cerebral wall , 54 as wThe first step in the analysis of vulnerability of transient cerebral compartments and related cell classes is their histological delineation and elucidation of their developmental history. Based on our preview studies on laminar organization and developmental reorganization of fibers, cells, and extra-cellular matrix (ECM) in fetal and infant brain, we can reconstruct location of different classes of afferent axonal pathways within compartments of the cerebral wall , 65\u201367. The objectives of the present study were: (1) to define anatomical and developmental relationships between cerebral compartments and major axonal pathways and (2) to use this data for study of laminar location and extent of structural cerebral lesions in preterm infants at birth and during early postnatal life. We rely on structural criteria and parameters developed during our long-term study of normal and damaged cortex , 66.The specific aims of this study are: (a) to define anatomically periventricular, intermediate, and superficial cerebral compartments, to identify incorporated classes of axonal pathways and to describe laminar landmarks for typical lesions in the preterm brain ; (b) to show the extent and characteristics of MR signal abnormalities in different cortical compartments and white matter segments at birth and in the subsequent longitudinal MR structural follow-up until the third year of life ; (c) to elucidate whether there are differences in structural abnormalities after the lesion in early versus late preterms, with special consideration of the subplate zone (question: when?).The idea behind this approach is to determine whether analysis of structural abnormalities of laminar compartments and white matter segments along radial axis (from ventricle to pia) may reveal selective time-dependent and laminar-dependent radial vulnerability of the different classes of axonal pathways preterm brain (question: which pathways are lesioned in the white matter injury?). We expect that our findings will contribute to better classification and scoring of white matter injuries in preterm infant.In vivo MRI examination was conducted using a set of MRI sequences, as described previously  from our large and versatile Zagreb collection. For the analysis of the specimens with pathological changes, we have used same techniques as applied for normal brains in our previous studies. The details on histological, histochemical, and immunocytochemical techniques as well as selections of antibodies were described in details in our previous papers , 66. In eviously , 66 on teviously .The first group, consisting of 21 patients (age range at birth: 23\u201342 PCW), was selected from a cohort of 152 children included in another longitudinal study. The exclusion criteria were: the presence of developmental anomalies, higher-grade hydrocephalus, and massive infarctions. The inclusion criteria were: the presence of other structural lesion (visible on MRI scans) related to perinatal pathology. The severity of these lesions was graded according to the surveillance of cerebral palsy in Europe (SCPE) classification system , 69 as fin vitro experiments was performed in accordance with the Declaration of Helsinki and also was approved by the Institutional Review Board of the University of Zagreb School of Medicine. All MRI data were evaluated by two independent observers (Milan Rado\u0161 and Ivica Kostovi\u0107), while histological sections were analyzed by the first author. Clinical data and testing were provided by neuropediatrician and psychologist.The third group was composed of four normal children born at term, who were scanned during the neonatal period , and had neither notable brain pathology nor any signs of neurological disorders. This group of newborns was regarded as normal. In each case, the parental consent for MRI scanning was obtained and all examinations were controlled and approved by the Institutional Review Board of the University of Zagreb School of Medicine. Sampling of the tissue for the For delineation of transient cerebral compartments, we use generally accepted classification  while thPreviously described MRI abnormalities at term  , 71\u201373 wDeep (periventricular) compartment includes proliferative fetal zones (ventricular\u2013subventricular zone and ganglionic eminence) and adjacent periventricular fiber systems . This coIntermediate compartment  contains crossroads of projection pathways (segment IIa) , their gSuperficial compartment is composed of three transient zones constituting the neocortical anlage: the subplate, the cortical plate, and the marginal zone Figures D,G. DuriThe analysis of histological sections stained with histochemical (AChE histochemistry) and immunohistochemical methods (fibrillar staining) and structural post-mortem MR images revealed that these compartments are arranged in radial direction from ventricular (deep) to the pial surface  , 54.DeeThe main differences between the cerebral wall of late versus early preterms were described recently . For thein vivo MRI changes after the first year of life in the same group of patients who were scanned at term age.Using the above described spatial  and temporal  criteria, we will describe: (a) typical lesions and their laminar landmarks in preterm infants, (b) morphological types and radial extent of MR abnormalities in preterms at term age, and (c) structural longitudinal Periventricular lesions occupy area medial to the radiation of internal capsule Figure B. The gaLarger cystic lesions Figure E also inWe conclude that these periventricular focal lesions in preterm infant damage segment I of white matter (PVP) and segment IIa (crossroads) and cause MR abnormalities, leaving intact the subplate zone/centrum semiovale and gyral white matter (in later preterms). Lesions of the occipital crossroads are accompanied with lesions of the root of radiation of the posterior limb of the internal capsule (PLIC) and may also affect occipital sagittal strata. The lesions of periventricular and crossroad segments also damage proliferative and migratory zones within the cerebral wall.As stated above, the centrum semiovale is situated between sagittal strata and the subplate, and was developed only in later preterms Figure G. The moWe found that decrease in visibility of anatomical border between sagittal strata and centrum semiovale \u2013 subplate, may be more indicative of the prospective acute lesion of centrum semiovale than the change in MRI signal intensity alone Figure F. The exIn this study, lesions of the subplate and the cortical plate have not been described convincingly at MRI level. However, at the histological level, there is evidence for significant reactivity of astroglia in the deep portion of subplate after hypoxic-ischemic lesions  and wideThe neonatal brain at term age shows well developed deep and intermediate segments of white matter , while distal segment  is still developing. The subplate is reduced in thickness and is described as the subplate remnant . The neoSmall hemorrhagic lesions (five cases) were seen to occupy territory of Muratoff\u2019s subcallosal fascicle in the PVP, lateral to the angle of the ventricle Figure B. PeriveLarger periventricular cysts stretch to the exit of internal capsule/root of corona radiata Figure D and invThe presence of the subplate remnant, defined as narrow ECM rich transitional zone between the gyral white matter and the cortical plate, is marker of normal cortical organization at birth . AccordiThe longitudinal developmental changes of cerebral compartments were analyzed in the same cohort of patients, which was described at term age.As expected, small hemorrhagic lesions in PVP area transformed in focal well delineated \u201cscar-like\u201d formation of increased T2 MRI signal intensity  imaging. The concept of transient cellular compartments as a crucial spatial framework for analysis of neurogenetic events in the developing cerebral cortex has been elaborated for decades since the beginning of modern era of developmental neurobiology , 19, 22.Due to the fact that neurogenetic events take place in specific, developmentally important cerebral compartments, the laminar extent of cerebral lesion may help to understand developmental disturbances after hypoxia ischemia and hemorrhagic lesion in the third trimester of gestation and equivalent preterm period , 53, 62.We found that both focal and diffused lesions, depending on their radial extent, affect well identified and spatially segregated classes of axons: periventricular pathways of mixed modalities within ventricular/subventricular zone , major pThus, loss of \u201cnormal\u201d border between external sagittal stratum and centrum semiovale is indicative of lesion of thalamocortical pathways and may be accompanied with thalamic lesions , 83, 84.One of the most interesting observations in our material is lesioning of centrum semiovale with preservation of the subplate remnant. This developmental lesion results in loss of border at term, but shows \u201cenhanced\u201d delineation of subplate remnant from centrum semiovale (segment III) during the subsequent development. This reorganization of borders between cerebral compartments requires developmental interpretation of subplate zone, centrum semiovale, related thalamocortical and associative pathways.The centrum semiovale develops in the late preterm, between 32 and 36 PCW, when thalamocortical fibers have already relocated from the subplate zone , 10, 19.The lesion of subplate neurons is the most enigmatic. There is no doubt that subplate neurons are vulnerable during preterm period and form a neuronal substrate in Volpe\u2019s \u201ccomplex amalgam of destructive and developmental disturbances.\u201d This prediction was confirmed in neuropathological studies after hypoxic ischemic lesion . ConsideThe mechanisms that contribute to the pathology of axonal pathways in preterm brain are poorly understood. It is also not clear whether, when and how growing axons are primary target for hypoxia ischemia or their lesion occurs secondary to the damage of their cell bodies of origin, other connected neurons, such as subplate neurons or glia cells , 53.Haynes et al.  have shoThis complex axonal guidance system is the main mechanism in the complex process of path-finding and target selection , 5\u20137, 19Although it is not known which cells produce ECM molecules such as chondroitin sulfate, containing glycosaminoglycans, it is very likely that these cells reside along axonal growth trajectories and in the subplate. It is logical to assume that cytotoxic substances produced during hypoxic ischemic events damage not only pre-oligodendrocytes , 91 but The concept of radial vulnerability and data presented in this paper are limited due to the fact that we did not analyze connected subcortical structures . This will be subject of our future studies.In conclusion, developmental vulnerability changes along radial axis in relation to growing axonal strata and deep to superficial differentiation of neurons in the subplate and cortical plate. Deep, periventricular lesions  damage fronto-occipital associative, cortico-striatal, and corticopontine projection pathways and will result in cognitive and motor deficit Figure . Perivenin vivo MR scans. All authors  have participated equally in interpretation of data, article writing, and approval of final version.All authors have participated equally in the work and have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Ivica Kostovi\u0107 has proposed basic concept of cerebral compartments, corridors of axonal growth, and radial vulnerability. Vesna Benjak and Mirna Kostovi\u0107-Srzenti\u0107 have performed clinical testing of preterm children and Nata\u0161a Jovanov-Milo\u0161evi\u0107 has performed histochemical and immunohistochemical staining of post-mortem brain. Milan Rado\u0161 has performed all The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Consolidated Framework for Implementation Research (CFIR) draws together the unique and common elements of 19 different theories and frameworks and offers a common taxonomy for exploring the effectiveness of implementation within a specific context. Using the framework, the researcher or evaluator is able to address not only the question of \"Does the intervention work\" but more importantly for implementation and dissemination \"For Whom?\" and \"Under what conditions?\" Since its publication in 2009, the CFIR has been applied to 51 published syntheses or studies; a greater understanding of its current application will enhance its utility for future implementation research.The panel will present three applications and adaptations of the CFIR: (1) a synthesis of findings from six studies within the VA setting based on CFIR construct ratings from each; (2) the adaptation of CFIR to complex system interventions; and (3) results from a systematic review of quantitative measurement of CFIR constructs. This recent experience in using the CFIR in Implementation research suggests it can be a useful tool for assessing the complexity of healthcare transformation, particularly given the wide array of available quantitative instruments. The CFIR guides the user in considering the complex contexts of implementation in research and quality improvement, producing insights and results that can guide tailored implementation strategies. These strategies can be more systematically synthesized to inform the appropriateness, replicability, and sustainability of system transformation efforts to optimize care for patients. Together, through innovative methodologies , these projects will advance implementation science by identifying key contextual factors central to implementation success, delineating high quality measures for evaluating these factors and gaps in measurement, and highlighting an exemplary practical application of the CFIR to transforming complex systems.Work presented in this panel was supported by the Agency for Health Care Research and Quality (HHSA 290-2007-10056-I), National Institutes of Mental Health  and the Department of Veteran Affairs, Health Services Research & Development Quality Enhancement Research Initiative (QUERI) RRP 12-494)."}
+{"text": "CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01\u201314) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I\u2013IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family.Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of"}
+{"text": "We announce the complete consensus genome sequence of 27 African horse sickness viruses, representing all nine African horse sickness virus (AHSV) serotypes from historical and recent isolates collected over a 76-year period (1933 to 2009). The data set includes the sequence of the virulent Office International des Epizooties AHSV reference strains which are not adapted to cell culture. Culicoides midges  was first identified as a disease in horses in South Africa in 1891 and the viral nature of its etiological agent, African horse sickness virus (AHSV), was established in 1900  used at the ARC-Onderstepoort Veterinary Institute (OVI), South Africa, consist of at least one pathogenic isolate of each serotype from AHS outbreaks between 1955 and 1963 (de novo sequence assembly were done as described previously (The histories of the viruses used in this study  were com6\u2013eviously .Here we announce the first complete consensus genome sequence of each of the nine original pathogenic OIE reference strains of AHSV prior to the adaptation of the viruses to cell culture , some ofThe nucleotide sequences have been deposited in GenBank under the accession numbers listed in"}
+{"text": "Human pluripotent stem cells (hPSCs) possess unlimited proliferative potential while maintaining the ability to differentiate into any cell type including skeletal muscle cells (SMCs). hPSCs are amenable to genetic editing and can be derived from patient somatic cells, and thus represent a promising option for cell therapies for the treatment of degenerative diseases such as muscular dystrophies. There are unresolved challenges however associated with the derivation and scale-up of hPSCs and generation of differentiated cells in large quantity and high purity. Reported myogenic differentiation protocols are long, require cell sorting and/or rely on ectopic expression of myogenic master regulators. More recent advances have been made with the application of small molecules to enhance the myogenic differentiation efficiency and the identification of more selective markers for the enrichment of myogenic progenitors with enhanced regenerative potential. Here we review the field of myogenic differentiation and highlight areas requiring further research. With the added benefits of being amenable to genetic editing  muscles of immunocompromised (SCID/Beige) mice and monitored noninvasively. A substantial fraction of cells did not survive the first week of transplantation due to cell death. However, the transplanted cells stablized and persisted over a period of 6 months forming 7% of the myofibers in the host muscle as determined by human-specific laminin. The long-term engraftment of the hESC-derived SMCs suggests the persistence of myogenic progenitor cells that can contribute to prolonged rounds of regneration. In a different approach, myogenic differentiation of hESCs was induced by formation of floating cell spheres called embryoid bodies (EBs) followed by attachment on gelatin in media containing FBS and epidermal growth factor (EGF)  to induce their differentiation into multipotent mesenchymal precursors  into another   and might have a safer profile due to its tumor suppression activity  using EB based method and serum-rich media, followed by PAX7 (and GFP) induction and cell sorting based on GFP expression. The sorted cells showed progenitor-like characteristics exhibiting high proliferative capacity and minimal signs of terminal differentiation when cultured in the presence of Dox, FGF, and serum. Upon culture in differentiation media (with 2% horse serum) and withdrawal of Dox and FGF, the myogenic progenitors differentiated efficiently into multinucleated myotubes with only rare cells maintaining PAX7 expression. To test their myogenic potential in vivo, the progenitor cells expressing transgenic PAX7 were injected into cardiotoxin-injured TA muscles of immunocompromised DMD mouse model (NSG-mdx4Cv). The hPSC-derived progenitors led to considerable engraftment that was much higher than that observed with control human primary myoblasts. Injection with the hPSC-derived progenitors led to restoration of Dystrophin expression in the dystrophic muscles and significant functional improvement as demonstrated by increased isometric tetanic force, absolute force, and specific force. Interestingly, transplantation of primary myoblasts did not result in improvement of any of these functional parameters. In addition, PAX7+ hPSC-derived progenitor cells were detected within the sarcolemma of myofibers, indicating that hPSC-derived progenitors seeded the SC compartment. This contribution to the stem cell niche was associated with long-term engraftment of hPSC-derived progenitors that was sustained close to a year after transplantation into NSG mice.Using a different approach and learning from their previous studies in mouse -mCherry double transgenic zebrafish line, with myf5 marking early myogenic commitment and mylz2 marking terminal differentiation (Xu et al., Major advances were made toward improving the generation and selection of SMCs and myogenic progenitors from hPSCs Table . It is nin vivo, their contribution remains localized as engrafted cells do not migrate more than few microns from the site of injection (Goudenege et al., While hPSC-derived SMCs showed high engraftment and regenerative potential The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Cow's milk allergy (CMA) is the commonest food allergy in UK children with many misleading presentations. In 2011, the National Institute for Health and Care Excellence (NICE) provided primary care guidelines on food allergy. In Northern Ireland (NI), a regional expert group was convened in 2012 to develop a CMA-focused guidance document, later published as Milk Allergy in Primary care (MAP) guideline, along with other infant feeding issues. MAP was designed for shortcomings of national and international guidelines in the initial clinical recognition and management of mild to moderate non-IgE-mediated disease in primary care.Longitudinal data collected of infant feeding products prescribed by general practitioners (GP's) in NI from June 2012 to November 2013 were analysed to assess variations in prescription patterns. Intervention of the Health and Social Care Board (HSCB) in February 2013 provided regional guidance with subsequent training of practical algorithms.The total number of amino acid-based and extensively hydrolysed formulae significantly increased comparing a 6-month period from June to November in 2012 and 2013 before and after implementation (p<.05). The total quantity and total cost of colic treatments, lactose free formulae and comfort milks significantly decreased (p<.05). Over the study period, the percentage of recommended CMA prescribing increased from 12,9% to 24%, over 15,3% during the implementation period from October 2012 to February 2013 (p<.001 for trend).We present the first study evaluating the impact of CMA guidelines in the UK primary care. HSCB and MAP algorithms significantly increased the prescribed number of more expensive CMA formulae, at the cost of symptomatic colic, comfort and lactose free milks. The total cost of infant feeding products was however not affected. Practical advice and teaching of community-based health professionals allowed for effective implementation of regional guidelines, with appropriate diagnosis and treatment of a range of infant feeding issues and significant impact on GP prescription patterns. This shows promising results for randomised national research."}
+{"text": "Sites in the stable region shared distinct clades that might have led to greater diversity, whereas sites in the unstable region shared close relatives. Taken together, these results indicate that speciation, environmental filtering and limited dispersal are complementary drivers of beta-diversity of amphibian assemblages in the Brazilian Atlantic Forest.Current patterns of biodiversity distribution result from a combination of historical and contemporary processes. Here, we compiled checklists of amphibian species to assess the roles of long-term climate stability (Quaternary oscillations), contemporary environmental gradients and geographical distance as determinants of change in amphibian taxonomic and phylogenetic composition in the Brazilian Atlantic Forest. We calculated beta diversity as both variation in species composition (CBD) and phylogenetic differentiation (PBD) among the assemblages. In both cases, overall beta diversity was partitioned into two basic components: species replacement and difference in species richness. Our results suggest that the CBD and PBD of amphibians are determined by spatial turnover. Geographical distance, current environmental gradients and long-term climatic conditions were complementary predictors of the variation in CBD and PBD of amphibian species. Furthermore, the turnover components between sites from different regions and between sites within the stable region were greater than between sites within the unstable region. On the other hand, the proportion of beta-diversity due to species richness difference for both CBD and PBD was higher between sites in the unstable region than between sites in the stable region. The high turnover components from CBD and PBD between sites in unstable  Studies integrating compositional beta diversity  and phylogenetic beta diversity  have provided different insights into the ecological and evolutionary mechanisms that structure communities The Atlantic Forest is a highly threatened global biodiversity hotspot We compiled data on amphibian species composition to develop a thorough understanding of the processes driving the CBD and PBD patterns of amphibian distribution in the southern range of the Brazilian Atlantic Forest. First, we partitioned CBD and PBD into two distinct components: spatial turnover and nestedness. The partition of total beta diversity allowed us to infer the different processes (replacement or gain/loss of species) that structure communities Leptodactylus sp.) were excluded from the analysis. Although we recognize the difficulties posed by studies considering data from different inventories, we maintain that the above-cited criteria provide a more reliable checklist than geographic range maps We used checklists of local amphibian communities from 44 sites along the southern range of the Brazilian Atlantic Forest  into two additive components. Specifically, Baselga's jtu), which measures the proportion of unique species in two sites pooled together if both sites are equally rich, and ii) the nestedness-resultant component (\u03b2jne), which measures how dissimilar the sites are due to a nested pattern. Carvalho et al.'s -3), which describes a species at one site that is substituted by a species at another site, and ii) richness disparities (\u03b2rich), which reflect the absolute difference between the number of species that each site contains, irrespective of nestedness. In this study, Baselga and Carvalho et al.'s approaches produced qualitatively similar results. Therefore, we will present only the results from Baselga's approach  and phylogenetic diversity gradients (UniFracPD) et al. Turn measures the relative amount of gains and losses of unique lineages between communities that is not attributable to their differences in phylogenetic diversity. In contrast, UniFracPD measures the amount of phylobetadiversity caused by differences in phylogenetic diversity between phylogenetically nested communities. Following Leprieur et al.We quantified phylogenetic dissimilarities using the UniFrac index http://www.worldclim.org/past) and MIROC  at a resolution of 2.5\u2032 The major processes that control the distribution of species diversity may vary depending on the spatial or temporal extent of the study system In order to reduce the data dimensionality and multicollinearity, we performed a principal component analysis (PCA) based on a correlation matrix of the data considering temperature variables , precipitation variables  and elevation-related variables . The first three axes of the principal component explained 85% of the variations in the climatic and topographic data  and phylogenetic diversity (UniFracPD\u20132%)  .jtu and UniFracTurn between sites in different regions or between sites within stable region were on average 0.25 and 0.16 higher, respectively, than between sites within unstable region  were only recorded in sites within the stable region while nine genera  were only recorded in sites within the unstable region , indicating low lineage dispersal across regions Furthermore, the variation in CBD and PBD among the amphibian assemblages indicates that stable and unstable regions have different biogeographic histories. We observed the highest values of CBD and PBD between sites of different regions Click here for additional data file.File S1et al. . Appendix S3, Cladogram of anuran demonstrating the phylogenetic relationships of our data-set based on the phylogenetic hypotheses proposed by Pyron & Wiens (2011). Appendix S4, Taxonomic classification and occurrence of amphibian species in stable and unstable sites from Brazilian Atlantic Forest. Appendix S5, Analysis summary of the principal component analysis (PCA) for 44 sites in the Brazilian Atlantic Forest.Appendix S1, Description of 44 sites of Brazilian Atlantic Forest used in the analysis. Appendix S2, Partition of the variance of Compositional Beta Diversity components based on Carvalho's (DOC)Click here for additional data file."}
+{"text": "In this issue of BMC Medical Genomics Griffin et al. present a user-friendly and freely accessible HIV-associated neurocognitive disorder (HAND) genomic database that compiles viral (HIV-1) genetic sequences and other relevant clinical and treatment data. We discuss the benefits and caveats of public data sharing in NeuroAIDS research, while emphasizing the importance of such novel initiatives for advancing knowledge. And it is expected that as the database evolves new requirements will be developed similarly to already existing HIV database which however do not collect information on HAND [Novel research initiatives are needed to alleviate and hopefully eventually cure complex diseases such as HIV-associated neurocognitive disorder (HAND). The paper by Griffin et al.  in this  on HAND . The aut on HAND .The benefits of such an initiative are immediate: because this is a public data sharing system, of which I along with many other scientists am a strong advocate , almost One important caveat not mentioned in the paper (probably because it was beyond its scope) is the issue of international variability in policies around data sharing . BecauseFinally, the authors might include a more refined phenotyping of HAND and in particular one that matches the current diagnostic criteria in any future development of the database . Other iDr. Cysique is supported by the National Heath and Medical Research Council of Australia Career Development Fellowship APP1045400 (Cysique CIA/PI). Dr. Cysique received honoraria from Abbvie Ltd, CogState Ltd, ViiV healthcare, partial salary support in 2012 from Mercks Sharp Dome and CogState Ltd. Dr. Cysique has research support from Abbvie Ltd, ViiV healthcare and the Australian National Association of People Living with HIV/AIDS (NAPWA) and Gilead Sciences."}
+{"text": "Sharing Individual Participant Data (IPD) from completed clinical trials offers numerous well recognised advantages that can advance clinical research and benefit patients. The clinical trial community, including publicly funded trials, has a duty to facilitate this process.In our recent survey, publicly funded clinical trials units (CTUs) from the UKCRC registered CTUs network were supportive of the principle of sharing IPD. However, concerns were also raised including complex and varied sponsorship arrangements of the trials they coordinate, inappropriate reuse of clinical trial data, additional resource required for CTUs to prepare and share data, potential loss of ability to publish further research, and the potential risk to trial participant privacy. The CTUs preferred the use of a controlled access approach, with systems in place to review data access requests from researchers.We have used the results of this survey, input from an expert committee and an open consultation involving the UKCRC registered CTUs to inform the development of a guidance document summarising good practice principles for sharing IPD and associated documentation from publicly-funded clinical trials. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UK CRC Registered CTUs Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance."}
+{"text": "Conclusion of the abstract has been corrected as: CD patients with CM and BBB or BBB alonehave increased evidence of dispersion of repolarization compared to controls. QTd and (Tp-Te)dwere associated with increased mortality and/or need for transplant."}
+{"text": "The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. The synaptic vesicle (SV) cycle is the most highly regulated membrane traffic event in cells and the proteins involved, as well as the arrays of protein-protein interactions that guarantee the fidelity of the process, are getting increasingly clear.Kinases and phosphatases, as well as small GTPases and their effectors, are emerging as molecular machines acting at the synapse to regulate synaptic function and plasticity by rapidly modulating several synaptic targets and adapting the synapse to the needs of the network.The high tunability of synaptic strength is obtained presynaptically from changes in quantal size, SV availability for release and number of active synapses, and all these parameters are directly or indirectly controlled by the cycling fate of SVs.Here we provide an update on two molecular machines recently reported to act on the fate of recycling SVs in the nerve terminal: the cyclin-dependent kinase 5 (cdk5)/calcineurin (CN) system with its multiple synaptic substrates and the small GTPase Rab and ADP ribosylation factor (Arf) systems with their relative regulators and effectors.Kinases and phosphatases post-translationally regulate the function of a plethora of proteins and play a major role in regulating cellular functions. Phosphoproteins are highly expressed at the synaptic terminal together with dedicated kinases and phosphatases, and their activity regulates many aspects of SV cycling. The role of phosphoproteins in SV cycling has been extensively reviewed elsewhere  are substrates for the two enzymes -bound and inactive guanosine diphosphate (GDP)-bound states. Their cycling is regulated by two families of regulatory proteins, namely guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). GEFs function as activators by facilitating the conversion from a GDP-bound form to a GTP bound form, whereas GAPs function as repressors by enhancing GTP hydrolysis. The vast number of Rab and Arf proteins and the multiple GAPs and GEFs for each isoform make the small GTPase family an ideal spatial and temporal regulator of virtually every aspect of membrane trafficking (Stenmark, More than 30 distinct Rabs were indeed identified by proteomic analysis in highly purified SV fractions (Takamori et al., Drosophila mutants for TBC1D24/Skywalker, Uytterhoeven et al. (A role for Rab35 in SV cycling originated from the identification of TBC1D24, an epilepsy gene involved in neuronal development and protein partner of the small GTPase Arf6 (Corbett et al., n et al.  revealedn et al. . Moreoven et al. . WhetherBy investigating the molecular mechanisms leading to synapse elimination, Binotti et al.  recentlyThe Arf proteins are a family of six small, ubiquitously expressed GTP-binding proteins (Donaldson and Jackson, Although Arf proteins are less abundant in purified SVs or isolated nerve terminals as compared to other small GTPases, the Arf analogs Arl10b and Arl10c and the Arf-interacting protein arfaptin 2 have been identified as components of purified SVs (Takamori et al., Xenopus NMJ (Ashery et al., Drosophila NMJ (Uytterhoeven et al., The class III Arf protein Arf6, involved in constitutive trafficking between the plasma membrane and early endosomes and actin dynamics, has been reported to increase basal synaptic transmission at the C. elegans (Klassen et al., In support for a presynaptic role for Arf proteins, the Arf-like small G protein, Arl-8, has been identified as a critical regulator of presynaptic patterning and axonal transport in Drosophila NMJ by employing SD-dSTORM high-resolution microscopy and revealed that the protein localizes at the periphery of the active zone. Indeed, GIT interacts with the endocytic adaptor stoninB and regulates the localization and function of stoninB at the presynaptic site. A Drosophila GIT mutant showed accumulation of endosomal structures and vacuoles and marked defects in post-stimulus SV endocytosis and/or re-acidification (Podufall et al., Considering the prominent roles of Rab and Arf proteins at the synaptic terminal, it is noteworthy the lack of data on synaptic GAPs and GEFs that dynamically regulate their activity and potentially represent targets to finely modulate neurotransmission in both homeostatic and hebbian plasticity Table . In addiDrosophila (Steinert et al., The ArfGAP1, acting as a GAP for Arf1, has been found to interact and regulate the activity of Leucine-rich repeat kinase 2 (LRRK2, Xiong et al., The cdk5/CN system is a master regulator of synaptic strength and synaptic functional heterogeneity by modulating calcium signaling and SV distribution in the nerve terminal. The system is highly regulated by homeostatic plasticity and represents a target for research on the molecular markers of synaptic dysfunctions and on the design of novel drugs (Shah and Lahiri, For the Rab/Arf system, we expect that additional GAP and GEF functions at the synapse will be clarified in the near future, together with the role of specific GTPase effectors in synaptic function. The synaptic targeting and/or the activity modulation of GAP and GEF will emerge as main factors in synaptic plasticity processes and in the pathogenesis of synaptic dysfunctions. Interestingly, several mutations in genes encoding proteins belonging to the Rab and Arf small GTPases families, or proteins regulating their GTP-binding cycle, have been recently described as causative for inherited neurological diseases (Falace et al., AF drafted the article and prepared the figure. MF assisted in drafting the article. FB drafted and revised the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Endovascular intervention of peripheral chronic total occlusion (CTO) is technically challenging and time consuming. Various techniques and devices are used to facilitate lesion crossing and improve the success rate of the procedure. However, these new devices are quite expensive and not readily available. We report 2 cases of peripheral CTO wherein the occlusions were successfully crossed by using stiff end of Terumo glidewire. This sharp recanalization may be a useful technique for the recanalization of calcified peripheral CTOs when conventional techniques fail and new devices are not readily available, but it is accompanied by the risk of distal atheroembolism. Endovascular intervention (EVI) for the recanalization of peripheral chronic total occlusion (CTO) is technically challenging and time consuming. Patients with peripheral CTOs usually present with critical limb ischemia or disabling claudication . RecanalA 67-year-old woman with a medical history of hypertension, end-stage renal disease, and left femoropopliteal artery bypass that was performed 3 years ago was referred to our institute for EVI because of gangrene of the left second toe and intractable pain. The ankle brachial index (ABI) was low at 0.35. The extremity of angiography revealed occlusion of the left superficial femoral artery (SFA) from its ostium with collaterals supplying the distal portion of the SFA and tibial arteries . EVI wasAn 82-year-old woman visited our hospital with critical left limb ischemia and impending foot cyanosis. The patient had a history of hypertension, diabetes mellitus, and coronary bypass surgery and had undergone SFA stenting and below-the-knee (BTK) angioplasty for the right leg in 2009. The ABI of the left leg was 0.45 at the time of admission, and the diagnostic angiography revealed heavily calcified occlusions in the proximal popliteal artery and very slow blood flow to the BTK area . The antPercutaneous endovascular techniques have revolutionized the management of symptomatic peripheral arterial occlusive disease (PAOD) when conservative medical treatment fails; patients who undergo treatment using these techniques have lower morbidity and recover earlier than patients treated by surgical bypass . Periphe In this report, we describe the use of the stiff end of the glidewire in facilitating intraluminal crossing of highly resistant calcified peripheral CTOs when conventional techniques fail or new devices are not available. We have found that sharp recanalization by cautious use of the stiff end of the glidewire can facilitate lesion crossing and be a useful technique for the management of peripheral CTOs; however, the possibility of distal atheroembolism should be considered."}
+{"text": "CDC continues to work closely with the World Health Organization (WHO) and other partners to better understand the public health risk posed by a novel coronavirus that was first reported to cause human infection in September 2012 . GeneticThree of the confirmed cases of novel coronavirus infection were identified in the United Kingdom (UK) as part of a cluster within one family . The indhttp://www.cdc.gov/coronavirus/ncv). Persons who develop severe acute lower respiratory illness within 10 days after traveling from the Arabian Peninsula or neighboring countriesThis recent cluster provides the first clear evidence of human-to-human transmission of this novel coronavirus, coinfection of this novel coronavirus with another pathogen (influenza A), and a case of mild illness associated with this novel coronavirus infection. In light of these developments, updated guidance has been posted on the CDC coronavirus website , case investigation, and specimen collection and shipment for testing, are available at the CDC coronavirus website. Additional information and potentially frequent updates will be posted on the CDC coronavirus website. State and local health departments with questions should contact the CDC Emergency Operations Center (770-488-7100)."}
+{"text": "The Namibia Ministry of Health and Social Services (MoHSS) approached People that Deliver (PtD) for support in addressing supply chain management (SCM) workforce challenges at its central and regional medical stores (CMS/RMS). PtD leveraged the expertise of member organizations CapacityPlus and SCMS to provide technical assistance in planning, deployment, training and retention of the SCM workforce; document the process and lessons learned; and draft a case study on the process for PtD to share globally.The MoHSS and PtD partners collaborated on four key interventions to address SCM workforce challenges. These included developing a SCM competency framework, identifying the number and types of supply chain personnel required using the Workload Indicators of Staffing Need (WISN) tool, conducting targeted capacity building starting at the central medical store through the Supply Chain Performance Improvement (SCPI) program, and identifying context-specific incentives to encourage staff retention using the Discrete Choice Experiment (DCE) activity.Preliminary results indicate that there are opportunities and political will to reduce role overlap between pharmacists, pharmacist assistants, and clerks at CMS/RMS and to tailor in-service and pre-service training programs based on the newly drafted competency frameworks for these cadres. By the time of the conference additional results from the November 2013-September 2014 collaboration will be presented on the number and types of staff needed to fulfil these three cadres at CMS/RMS, the package of salaries and incentives most likely to attract and retain them in these positions, and progress against a set of key performance indicators.This collaboration focused on three cadres within the CMS/RMS level of the supply chain; however, in the future expanding the application of activities to hospital and clinic levels will produce a more thorough picture of the SC workforce. The tools utilized in the Namibia pilot will be shared in order to apply this unique approach in other countries; currently Mozambique, Burkina Faso, and Liberia have plans to introduce a similar collaboration. The collaboration was possible due to the coordinating power of the PtD Initiative and is suggestive that similar opportunities for future innovative pilots in strengthening the SC workforce exist.This collaboration was successful due to a combination of MoHSS support and leadership, and the leverage of PtD in convening global expertise in HR and SCM. USAID regarded these activities as a \u201csmart investment\u201d given the minimal additional funding required and strategic use of in-country partner presence and tools."}
+{"text": "The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. Chronic heart failure (CHF) is a diverse clinical syndrome in which impairments of ventricular filling or emptying compromise the ability of the heart to match cardiac output to metabolic demand. This activates multiple maladaptive mechanisms such as inflammation, oxidative stress, the renin-angiotensin system (RAS), and the sympathetic nervous system (SNS), which over time contribute to disease progression  compared to healthy rabbits  Grant P01 HL62222. AS was supported by an American Heart Association pre-doctoral fellowship (13PRE14700045); PP was supported by a NIH NHLBI F30 pre-doctoral fellowship (1F30HL118974-01A1).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The heart is a perfect machine whose mass is mainly composed of cardiomyocytes, but also fibroblasts, endothelial, smooth muscle, nervous, and immune cells are represented. One thousand million cardiomyocytes are estimated to be lost after myocardial infarction, their loss being responsible for the impairment in heart contractile function  from bone marrow, adipose tissue or induced pluripotent stem cells (iPSCs). On the other hand, the contribution of cells derived from the heart tissues is here considered of outmost importance since these cells are believed to retain the potential to become highly differentiated cardiomyocytes.Studies on the differentiation of embryonic cells into cardiomyocytes started in 1989  as candidate to produce new cardiomyocytes has been even longer: after a seminal paper published by the group of Keiichi Fukuda in 1999  three-dimensional (3D) scaffolds reproducing myocardial structural properties.The ideal cardiac-specific scaffold would comply with cardiac muscle architecture, be deformable enough to sustain cardiac contraction, while being colonized by host vasculature and resorbed/degraded in due time. The biomaterials and scaffolds so far proposed for cardiac tissue engineering can be grouped into three categories: (1) scaffolds mimicking extracellular matrix (ECM) structure and/or the elasto-mechanical properties of the myocardium, (2) per se  mold was recently used to pattern polyurethane (PU) and poly(lactide-co-glycolide) (PLGA) hydrogels via UV-assisted or solvent-mediated capillary force lithography (CFL)  (PGS) films  into polycaprolactone (PCL) electrospun meshes  and embryonic fibroblasts in skeletal muscle engineering  were then seeded (Pagliari et al., Alternatively, a heterogeneous neonatal cardiac cell preparation was seeded onto fibrin gels until endothelial cells grew and an adequate contractile activity was registered (Tao et al., Scaffolds may represent a very useful device to deliver cardiac stem cells to the ischemic or damaged heart. Besides the dream of generating personalized proto-tissues with finely controlled size and shape to match the particular need of the patient, the formulations proposed are far from reproducing the complexity of the cardiac tissue.The use of medical devices may help researchers to reduce the number of implanted cells and to drive their differentiation through the use of embedded molecules or growth factors. And while the physico-chemical features of the scaffold proved to be important in prompting stem cell alignment and commitment, the role of the immune response in cardiac tissue engineering deserves more attention.Although promising in terms of technology advancement, the extent to which these studies address the hierarchical organization of the myocardium is still far from being relevant. Cardiac tissue engineering holds the promise to revolutionize the future of heart disease treatment and the use of scaffolds may provide valuable 3D cues for stem cells to grow, differentiate, and distribute into an organized tissue.The common limitation of the studies so far proposed in cardiac tissue engineering remains the lack of a credible signature of complete cell maturation toward the cardiomyocyte phenotype. Most of the investigations showcased the expression of proteins typical of the cardiac tissue, and a spatial distribution or alignment of the cells inside the scaffolds. Some research groups were able to show a striation typical of myofibrils (Engelmayr et al., While waiting for bio-instructive scaffolds displaying a modular distribution of differentiative cues, the possibility to combine different cell subsets with distinct potential with 3D scaffolds reproducing the hierarchical structural complexity of the native tissue represents a valuable approach to generate complex cardiac constructs to treat cardiopathic patients.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Calabria Cephalalgic Network represents a novel healthcare delivery context which, according to a patient-centered vision, allows to effectively integrate different care settings (mainly primary and secondary care) by developing and implementing evidence based clinical workflows. On this basis, the Network is able to effectively support continuity of care, outpatient-inpatient integration, efficient use of health care resources and reduction of economic costs.We present the architectural organization of the network, the structure of the clinical workflows and the related technology platform providing a captivating and pro-active informative and decision making dashboard in order to effectively and efficiently support the Headache integrated care processes.The proposed organization of the Cephalalgic Network is based on a new integrated care program characterized by: (i) the set of relevant health care \u201cactors\u201d with roles and responsibilities; (ii) the services for sustaining collaborative and cooperative interactions among the end-users; (iii) the services for supporting the planning and operative management of all involved health care resources; (iv) the decision-making services for supporting integrated clinical workflows among the several healthcare settings.The Calabria Cephalalgic Network is currently under validation by a piloting activity involving a set of healthcare actors  and enrolled patients. Relevant cost-benefit indicators have been defined and collected during the validation activity.The current results confirm the effectiveness of the proposed approach, since it allow more efficient clinical service planning and management by making the best use of available hospital resources.No conflict of interest."}
+{"text": "Drosophila melanogaster and the mollusks Aplysia and Lymnaea, have proven invaluable tools for identification of highly conserved molecular processes in memory. Recent research from invertebrate systems has outlined the influence of sleep and the circadian clock upon synaptic plasticity. In this review, we discuss the effects of the circadian clock and sleep on memory formation in invertebrates drawing attention to the potential of in vivo and in vitro approaches that harness the power of simple invertebrate systems to correlate individual cellular processes with complex behaviors. In conclusion, this review highlights how studies in invertebrates with relatively simple nervous systems can provide mechanistic insights into corresponding behaviors in higher organisms and can be used to outline possible therapeutic options to guide further targeted inquiry.Across phylogeny, the endogenous biological clock has been recognized as providing adaptive advantages to organisms through coordination of physiological and behavioral processes. Recent research has emphasized the role of circadian modulation of memory in generating peaks and troughs in cognitive performance. The circadian clock along with homeostatic processes also regulates sleep, which itself impacts the formation and consolidation of memory. Thus, the circadian clock, sleep and memory form a triad with ongoing dynamic interactions. With technological advances and the development of a global 24/7 society, understanding the mechanisms underlying these connections becomes pivotal for development of therapeutic treatments for memory disorders and to address issues in cognitive performance arising from non-traditional work schedules. Invertebrate models, such as  In the past century, the nature of human society has been dramatically altered by technological innovations, communication advances, transportation improvements and urbanization. Non-traditional work schedules and round-the-clock manufacturing shifts have become increasingly common worldwide with the proportion of individuals working non-traditional work schedules rising. Recent research indicates approximately 3.7% of employed adult workers in the United States work a night shift with an additional 23.5% of individuals working non-traditional shifts including evening, rotating or split shifts  and higher organisms, differences in the levels of behavioral complexity, and the recent technological advances for targeted genetic studies in mammals, the reader may wonder whether research using invertebrate model systems will continue to advance progress in neuroscience research. Although vertebrate and invertebrate lineages diverged more than 900 million years ago , characterized by changes in neuronal activity as measured by electroencephalograms  and rebound following rest deprivation (homeostasis) Tobler, . As the C. elegans in which quiescence is characterized by reduced sensory responsiveness, a characteristic rest body posture, and is timed through the expression of an ortholog of the canonical clock gene period  has the ability to mediate neuronal firing rates in response to light through potassium channel conductance  determine how individual neurons or neuronal circuits involved in memory formation are stabilized through time, reactivated, undergo periods of malleability and degradation/pruning; (2) determine how the effects of sleep as a network property or at the level of individual neurons affects neuronal plasticity; (3) determine how the core circadian clock regulates sleep in individual neurons and circuits; (4) determine how sleep and circadian time modulate neuronal and synaptic activity for specific tasks or memories; (5) determine how effects analogous to modern life such as non-traditional sleep/wake cycles or shifted circadian rhythms affect this interplay transiently and chronically; and ultimately; (6) identify mechanisms through which these interactions can be modified by drugs or optimized behavioral patterns.Drosophila  and bottom-up (in vitro) approaches in the experimental design and the exquisite detail possible with investigations at the level of individual neurons or neuronal circuits. In gastropod mollusks, the precisely wired nervous system is comprised of large neurons with determinate location and in many cases functions of individual neurons identified (see for example Benjamin et al., Lymnaea and Aplysia, the advantages of multilevel approaches combining in vivo behavioral studies with in vitro cellular studies to correlate complex behaviors with individual neuronal behavior have been well-documented.One of the greatest benefits of the molluscan model system is the spectrum of techniques permitting an integration of top-down (Aplysia, long-term facilitation provides a cellular correlate for behavioral sensitization that can be investigated in reduced preparations and cultured neurons (see for example Kandel, Aplysia (Lyons et al., Aplysia that demonstrates changes in sensory arousal accompanying sleep and homeostatic rebound rest following sleep deprivation (in situ techniques as shown in Aplysia (Sweedler et al., in vivo as well as in the reduced preparation can further be co-cultured in a dish (Cai et al., Aplysia neurons and determinate neuronal position also allows for genomic and metabolomic analysis at the scale of the individual neuron (Moroz and Kohn, For example in rivation . IndividLymnaea in which multi-electrode arrays have been used in order to record from up to 60 electrodes simultaneously (Harris et al., Lymnaea demonstrated that learning-induced non-synaptic plasticity contributed to specific, compartmentalized presynaptic changes through calcium signaling (Nikitin et al., Similar anatomical advantages for studies of individual neurons or neuronal circuits exist in Aplysia memory processes to develop a training paradigm predicted to lead to a stronger induction of the molecular cascades necessary for memory. Testing these predictions behaviorally, they found that the modeled training protocols resulted in stronger and longer lasting memory (Zhang et al., Given the availability of abundant data underlying neuronal network function in molluscs, mathematical modeling can be leveraged to drive further experimental inquiry (Vavoulis et al., Aplysia presents the scientific community with a powerful toolset to identify the cellular and molecular pathways from the whole animal to mathematical models, laying the foundation to identify the basic principles and mechanisms of memory modulation. Unraveling the intricate relationships between sleep, the circadian clock and learning and memory is essential to identify key molecules or interacting nodes for the development of future therapies to improve cognitive performance and decrements associated with shift work, sleep disorders, aging or neurological disorders.The multi-level combinatorial approaches outlined above set the stage to yield unprecedented insight into the mechanisms through which sleep or the circadian clock affects neuronal plasticity. The high degree of phylogenetic conservation as previously discussed permits the rapid translation of research in invertebrate systems to mammalian models (see also Abrams, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Functional Magnetic Resonance Imaging (fMRI) records the blood oxygenation level dependent (BOLD) endogenous contrast, a physiological surrogate for brain activity. Experimental and analytic procedures for fMRI remained largely unchanged in the decade following discovery of BOLD contrast, detecting localized magnitude changes in response to external stimuli. Observations of persistent patterns of activation present under a wide variety of cognitive conditions, now known as the default mode network  connected by edges with associated strengths (edge weights) that represent functional proximity, often inter-regional synchronicity measured by Pearson's correlation of BOLD time-series. Other strengths can be estimated; for example, coherence, cross-correlation , the National Institute for Health Research (NIHR) (grant: 06/05/01) and the Behavioural and Clinical Neuroscience Institute (BCNI), University of Cambridge. The BCNI is jointly funded by the Medical Research Council and the Wellcome Trust. Additional support was received from the NIHR Cambridge Biomedical Research Centre.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field. Glaucoma is one of the most common causes of blindness in the world with over 70 million people (79 million by 2020), including 400,000 Canadians, affected by this disease  levels  such as neurotrophin-4 (NT-4), brain-derived neurotrophic factor (BDNF)  that express these enzymes, insert the recognition sequence of these enzymes in to the plasmid DNA vector closely upstream and downstream of the therapeutic transgene expression cassette, and transfer the plasmid into engineered E.coli cell  the miniDNA vector  comprising the therapeutic transgene expression cassette, and (ii) the miniplasmid containing the bacterial backbone elements  of minicircle DNA and parental plasmids were delivered  , Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR).Permanent expression of therapeutic genes is generally carried out by three different approaches: (i) random integration (illegitimate insertion); (ii) homologous recombination (HR); or (iii) site-specific insertion of the transgene into the chromosome of an anticipated cell. Random integration is mostly carried out by viral vectors to achieve insertion of an exogenous transgene into the host human cell's genome. However, lack of control over the site and position of integration would result in undesirable side effects such as unpredictable expression level or silencing of the integrated transgene, potential mutagenesis of neighboring genes, activating oncogenes/deactivating tumor suppressor genes, and eventually cancer. Therefore, random integration by viral vectors is not a safe method for permanent and sustained expression of therapeutic transgene in The interest in precise gene modification is growing dramatically owing to recent advances in targeted genome engineering. Targeted genetic engineering techniques allow very specific modifications such as gene insertion, deletion, and replacement. Permanent modification of cells has been extensively used in regenerative medicine as a new clinical tool.Some examples are engineering glial progenitor cells to permanently express adhesion molecules to increase homing of these cells into the brain \u201d and \u201cpiggyback (PB) transposon system\u201d are the two transposon systems that have been successfully used as non-viral gene delivery carriers for gene modification and generation of clinical grade human cells for gene and cell therapy. These systems have lower cost for design, construction, and production of pharmaceutical grade products on a large scale as well as stimulating low levels of innate immunity and the capacity to co-deliver multiple therapeutic transgenes compared to viral integrating systems.Non-viral transposon systems have been widely used to generate genetically modified and clinically relevant human cells including but not limited to induced pluripotent stem (iPSC), embryonic stem cells (ESC), and mesenchymal and hematopoietic stem cells \u201d is a non-viral plasmid-based integration system that combines the integration benefits of viral vectors and ease of production and manipulation of naked DNA vectors and ease of delivery by nanoparticles. The SBTS consists of (A) a plasmid transposon carrying the therapeutic transgene expression cassette flanked by the terminal Inverted Repeats (IR) that contain binding sites for the transposase enzyme; and (B) a source of transposase enzyme, which is a 360-amino acid DNA-binding protein with a transposon binding domain, a nuclear localization signal (NLS), and a catalytic domain.\u201cThe SBTS systems mostly target the TA rich sites of the hosting genome to insert the intended therapeutic transgene expression cargo. The gene encoding for the transposase enzyme can be assembled either on the same plasmid that express the therapeutic transgene (sis) or can be located at a different plasmid (trans). In case of trans expression, the two DNA vectors (one carries the transposase enzyme encoding gene and the other carries the therapeutic transgene expression cassette) could be packed within the same nanoparticle carrier and co-transferred into the intended host cell. Few hours after delivery, the transposon system would reach the nucleus of the host cell, the transposase enzyme would be expressed in the cytoplasm and the NLS that has been added to its sequence would direct import of the transposase into the nucleus, cut the IR sequences, and facilitate relocation and insertion of the therapeutic transgene expression cargo from DNA vector into the host genome  In a in phase II clinical trial of cancer immunotherapy research, patients-derived T cells were genetically modified by SBTS system to express a chimeric antigen receptor (CAR) and were injected back to patients with B-cell malignancies in order to redirect the specificity of human T cells in these patients  transposon derived originally from Lepidopterans is composed of two identical short inverted terminal repeats (700 bp) and a transposase-encoding sequence (coding a 594 amino-acid transposase). The PB transposase catalyzes the transposition of the therapeutic gene expression cargo that is flanked by the inverted terminal repeats carrying by a plasmid and insertion of therapeutic transgene into TTAA rich sites of the host genome. The short IR are the key elements of the PB transposition system \u201d and \u201cbacterial attachment site (attB)\u201d  as source for several stem-cell like cell types  type 2  from somatic cells  generating new cell lines to study basics of disease progression, cell growth, and differentiation; (B) screening, identification, and developments of novel therapeutics and their targets; (C) generating disease animal models; and (D) developing new candidates for cell replacement or cell rescue therapies (Yin et al., Neurotrophic factor therapeutic genome engineering is a highly coveted clinical aspiration of glaucoma therapy, but only recent technological advances in improved delivery techniques, the new generation of bacterial sequence-depleted DNA vectors carrying only the desired therapeutic transgene expression cargo, and the availability of modern genome editing techniques could provide the necessary tools for the modification of complex genomes and gene therapy in a targeted fashion. We previously highlighted the rationale for NTFs and their transgene delivery into cell candidates and discussed the significant effects of several NTFs on the support and protection of retinal cells and other cell candidates that might be potential therapeutic options for glaucoma neuroprotective gene therapy (Nafissi and Foldvari, In general, compared to cell replacement therapies to replace and integrate functionally active stem/progenitor cells into the retina, it was shown that cell-based neuroprotective therapies by prolonged secretion of NTFs is a more straightforward strategy to nourish and support dying RGCs in progressive glaucoma. In addition to supplying NTFs, cell-based neuroprotective therapies may also be able to promote RGCs survival directly through modifying gene expression in surrounding cells to enhance NTFs expression on-site (Madhavan et al., ex vivo modified cells can achieve therapeutic efficacy for clinical glaucoma treatment in human, many limitations remain to be overcome. A reliable and expandable source of retinal cells must be isolated, expanded, characterized and established. These cells must demonstrate appropriate engraftment within the retina. Even with the aforementioned challenges, the in vitro, ex vivo, and pre-clinical support for genetically modified cell-mediated RGC repair is undeniable, and warrants the kind of robust investigation that is currently under way. These methods, if successful in human trials, could offer several advantages over traditional pharmacological approaches. While much work remains to address the safety issues for all of the above mentioned approaches, evidently, this is a multi-disciplinary field which undeniably needs collaboration from different scientific domains to bring the bench results to the clinic.Thus, genetically modified NTFs secreting cell-based therapies provides new avenues to fight with the irreversible loss of RGCs associated with glaucoma. Currently we have efficient tools for permanent, reversible, or conditional genetic manipulations of almost any type of cells. The success of clinical trials in other disorders gives rise to similar approaches in the context of neurodegenerative diseases including glaucoma. Ultimately, a better understanding of cell development and stem cell biology at the molecular level, along with improvements in the techniques for non-viral gene delivery, advances in nanotechnology and nanomedicine for synthesis of more cell-friendly structures, and in-depth knowledge of gene modification systems at the molecular level would encourage scientists to develop novel treatments for degenerative disorders. Non-viral gene delivery techniques such as electroporation (Helledie et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition\u2014from entire diets to specific nutrients\u2014affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this  As the aged population expands, the economic burden of care and treatment of those with age-related health disorders also increases. Between 2012 and 2050, the United States will experience significant growth in its older population, with the size of the population aged 65 and over almost doubling from an estimated 43.1 million in 2012 to 83.7 million in 2050  methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs) along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI) of brain structure and function. We begin by surveying recent methodological advances in nutritional epidemiology, followed by a review of contemporary methods for the neuroscientific study of brain aging. By integrating methods from nutritional epidemiology and cognitive neuroscience, the burgeoning field of nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.The aim of this KEY CONCEPT 1. Nutritional cognitive neuroscienceNutritional cognitive neuroscience is an interdisciplinary field of research that investigates the impact of nutrition on cognition and brain health across the life span. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, specifically highlighting the utility of nutrient biomarkers in predicting healthy brain aging. Our proposed framework integrates research across nutritional epidemiology and cognitive neuroscience, combining: (i) methods for the precise characterization of nutritional status with (ii) modern measures of brain health.Observational studies indicate that particular nutrients have beneficial effects on brain aging, including antioxidant nutrients, calcium, fiber, folate, zinc, omega-3 polyunsaturated fats, and vitamins A, B12, C, D, and E  diet  diet, which consists of nutrient dense foods and low-sodium intake, is associated with reduced hypertension and improved psychomotor speed . This approach applies Principal Component Analysis to capture the effects of nutrients in combination, enabling discovery of patterns of nutrient biomarkers. This method detects NBPs in plasma and therefore avoids methodological problems in traditional food frequency questionnaires, such as faulty recall of dietary intake and failure to account for variability in nutrient absorption  enables the study of structural and functional brain changes associated with aging and the prediction of neuropathological processes in the aging brain  total and regional brain volume (volumetry), (2) integrity of white matter fiber tracts (diffusion tensor imaging), (3) axonal microstructure of brain tissue (MR-elastography), and (4) altered mineral content (MR-gradient echo imaging) Grady, . Applica total anAs a precise method of measuring age-related changes in the brain, structural neuroimaging is vital to the development of predictive dietary patterns of brain aging. Indeed, several structural aspects of brain health have been shown to be amenable to diet, indicating that neuroimaging can be a useful tool to characterize the relationship between nutrition and brain aging Table . HoweverFunctional neuroimaging methods enable the investigation of functional brain changes that are associated with cognitive aging. Functional magnetic resonance imaging (fMRI) measures the ratio of oxygenated to deoxygenated hemoglobin in the blood as a marker of change in neural activity related to cognitively demanding tasks or rest  that capture the robust effects of nutrient interactions. Furthermore, cognitive neuroscience has shown that brain aging is a heterogeneous process characterized by widespread changes in structure and function. This field has developed neuroimaging methods to measure these changes with high-resolution. Predictive nutrient patterns of healthy brain aging will emerge from the integration of methods that sensitively capture variability in both diet and brain aging Figure .Recent findings from Zamroziewicz et al.  indicatenutritional interventions that takes into account individual variability in nutritional status and brain health. The goal of personalized nutrition is to enhance the precision of nutritional intervention and to enable novel applications to psychological health, aging, and disease. To achieve this goal, considerably more research is needed to elucidate the complex interactions within nutrient patterns, within processes of brain aging, and finally, between nutrient patterns and brain aging. Unanswered questions to guide future research are as follows:Research at the frontiers of nutritional cognitive neuroscience seeks to establish a personalized approach to How do the individual interactions between nutrients within dietary patterns benefit the aging brain?How does age-related structural decline relate to changes in functional activity, and what mechanisms underlie associated declines in cognition?How can variability in both diet and brain aging be captured and linked to build predictive patterns of healthy brain aging in precise and comprehensive ways?How might known moderating variables\u2014including age, genes, environment, and lifestyle\u2014determine nutrition's impact on cognitive function and brain health?KEY CONCEPT 4. Nutritional interventionsBy integrating methods from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience seeks to elucidate nutrition's impact on the aging brain and to drive innovation in the design of nutritional interventions that promote healthy brain aging.Focused Review highlights recent advances in nutritional cognitive neuroscience, with a focus on methods that investigate nutrient biomarkers that predict healthy aging. By applying cutting-edge techniques from nutritional epidemiology (nutrient biomarkers in a priori hypothesized dietary patterns and data-driven methods) and cognitive neuroscience (high resolution MRI measures of brain structure and function), the burgeoning field of nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain. Ultimately, the development of predictive nutrient patterns for healthy brain aging will provide an empirically sound foundation for developing nutritional therapies that support the targeted treatment of cognitive and neurological impairments in the aging brain.Recent innovations in nutritional cognitive neuroscience hold promise for addressing the problems posed by a rapidly changing demographic landscape. This MZ is the primary author of this review. AB is the primary investigator and contributed to drafting and editing of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Slow recruitment and poor retention are common challenges to the successful delivery of clinical trials, particularly surgical trials. Patient and public involvement (PPI) in designing and conducting clinical trials has the potential to enhance recruitment and retention but there have been few attempts at rigorous evaluation. The aim of PIRRIST is to develop a PPI intervention that improves recruitment and/or retention in surgical trials.The study comprises four stages, beginning in July 2015: (1) Mapping current PPI practice in UK surgical trials through a survey and analysis of National Research Ethics Service data; (2) Focus groups with key stakeholders  to explore their needs, the challenges associated with PPI and how PPI might support recruitment and retention; (3) A survey of key stakeholders\u2019 views about the possible components of one or more potential PPI interventions; (4) A consensus workshop with a broad, purposive sample of stakeholders to select the PPI intervention that we put forward for future evaluation.This study will lead to a robust, evidence-based PPI intervention ready for evaluation. Although tailored to surgical trials, the findings will enhance understanding of whether and how PPI might improve recruitment and retention in clinical trials.The study is part of the Trial Forge initiative to improve trial efficiency."}
+{"text": "Saccharomyces boulardii showed the stronger evidences of benefits in different clinical trials and meta-analysis [Probiotics are viable microorganisms that can exert potential benefits to human health. Use of probiotics in different human diseases and clinical conditions has gained much attention in the last decades. Several data exist about the potential benefits of probiotics in pediatric age for the management of some clinical conditions, with different and sometimes contrasting results. Currently, strong evidences support the use of probiotics for treatment of acute infectious diarrhoea and prevention of antibiotic-associated diarrhoea: bacteria belonging to the genus of lactobacilli and analysis ,2. For oanalysis . Discuss"}
+{"text": "Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. Currently, activities in human disease genetics are primarily centered upon large-scale empirical studies and, to a lesser extent, statistical methods, with limited contribution to theory.Broadly speaking, scientific progress is predicated on a robust interplay between three activities: (1) empirical experimentation and observation, (2) the development of theoretical models and extraction of predicted patterns thereof, and (3) the statistical evaluation of the probabilistic correspondence between the predicted patterns and empirical data. Highly impactful discoveries can certainly occur in the absence of formalization of these activities, but these three aspects are nonetheless critical. To exemplify, consider the relatively recent remarkable finding of complex, low-level admixture between modern humans and archaic humans   monogenic and two-locus models with a biallelic markers and typically one of four classical modes of inheritance , and (2) direct derivatives of the IPMAE model. One only has to go as far as to look at commonly-used power calculators for genetic association or linkage studies to observe this rather ubiquitous, long-standing, yet fairly impotent state of affairs. Parametric linkage studies using monogenic models produced spurious results for complex diseases  Is the distribution of chromosomal regions shared by affected individuals indicative of disease loci? (2) Are the observed phenotypic variance within families and familial aggregation patterns consistent with specific disease genetics models? (3) Are the transmission patterns within families consistent with disease genetics models? And (4) Given a specific disease genetics model, what is the optimal size of family structure for finding chromosomal regions linked and associated with complex diseases ? Just as with population-based studies, the development of theoretical models of disease genetics illuminates the path to jointly testing numerous observed genetic patterns within familial structures. Wray and Goddard have started to explore some of these issues and have shown that three disease models are roughly consistent with data on disease risk in relatives   and NIMH RO1MH097464. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The main basis of this thesis is twofold: (a) the molecular similarity of the structures of nNOS \u03b1 and \u03bc, similar mechanisms of localizations to \u201cactive zones\u201d of nitrergic synthesis, and same mechanisms of electron transfers during NO synthesis and (b) pragmatic difficulty to routinely obtain full-thickness biopsies of gastrointestinal tract, even in patients presenting with the most recalcitrant manifestations of stasis and delayed transit of luminal contents. This opinion attempts to provoke dialog whether this approach is feasible as a surrogate to predict catalytic potential of nNOS\u03b1 and defects in nitrergic neurotransmission. This discussion makes an assumption that similar molecular mechanisms of nNOS defects shall be operant in both the enteric nerve terminals and the skeletal muscles. These overlaps of skeletal and gastrointestinal dysfunction are largely unknown, thus meriting that the thesis be validated in future by proof-of-principle experiments.The pathophysiology of gastrointestinal motility disorders is controversial and largely unresolved. This provokes empiric approaches to patient management of these so-called functional gastrointestinal disorders. Preliminary evidence demonstrates that defects in neuronal nitric oxide synthase (nNOS) expression and function, the enzyme that synthesizes nitric oxide (NO), the key inhibitory neurotransmitter mediating mechano-electrical smooth muscle relaxation, is the major pathophysiological basis for sluggishness of oro-aboral transit of luminal contents. This opinion is an ansatz of the potential of skeletal muscle biopsy and examining sarcolemmal nNOS\u03bc to provide complementary insights regarding nNOS\u03b1 expression, localization, and function within enteric nerve terminals, the site of stimulated  The main basis of this argument is twofold: (a) the molecular similarity of the structures of nNOS \u03b1 and \u03bc, similar mechanisms of localizations to \u201cactive zones\u201d of nitrergic synthesis, and same mechanisms of electron transfers during NO synthesis and (b) pragmatic difficulty to routinely obtain full-thickness biopsies of gastrointestinal tract, even in patients presenting with the most recalcitrant manifestations of stasis and delayed transit of luminal contents.Recent evidence of a novel C-terminal tail region mutation involving neuronal nitric oxide synthase (nNOS) as causative for global gastrointestinal achalasia has been reported in two probands of an Arab family . This stNitric oxide synthesis involves oxidoreduction of the nitrogen atom of guanidino group  Figure Ai. The e2O3, the oxidized product of NO] ; DAF detects Nt of NO] . The rat847 and unphosphorylated forms, raising the possibility of a toggle between active and inactive isoforms that may initiate and terminate nitrergic neurotransmission  differential transcriptional and post-transcriptional regulations of myosin Va and nNOS, both in terms of the specific factors involved and the temporal relationships. Given the pragmatic problem of obtaining regional and full-thickness biopsies of the gut, examination of skeletal muscle biopsies might provide extremely useful information relating to pathophysiology of enteric nitrergic neurotransmission. Despite the invasive nature of the proposed biopsies, endeavor may be directed to obtain primary clinical evidence to obtain precision in the management of gastrointestinal motility disorders.Though the stoichiometry of gene expression and protein translation of myenteric nNOS\u03b1 and skeletal muscle nNOS\u03bc may not match, examination of skeletal muscle nNOS\u03bc from biopsy samples has the potential to provide three important information: (a) microscopic visualization shall provide the location site of nNOS, including at the membrane, the active site of nitrergic neurotransmission; (b) nNOS may be extracted and purified for The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Currently, 382 million people, or up to 8.8% of total world population, live with diabetes mellitus  or glycotoxins and action of advanced lipoxidation products (ALEs) either of dietary origin or from intracellular sources  and prescription of drugs with antioxidant properties  heparin or subcutaneous (SC) low-molecular-weight heparin (LMWH) should be individualized. It takes approximately 3 days for the INR to reach 2.0 once oral anticoagulant is restarted postoperatively (Frykberg et al., Frequently, therapy of the related comorbidities including the underlying chronic or acute disseminated intravascular coagulation allows for more significant improvement of microcirculation than poorly justified aggressive invasive vascular interventions (O'Reilly et al., Further assessment and treatment of concomitant acute regional septic arteriitis and phlebitis is paramount, as infection control will help to reverse the microcirculatory impairment (Corathers et al., Severe diabetic neuropathy is the principal contributor to development of neuropathic osteoarthropathy of Charcot\u2014a rare limb-threatening foot deformity, characterized by presence of pulsatile pedal arteries, development of complex and diverse fractures, subluxations, and reactive soft tissue swelling after a minor and usually underestimated trauma. The disease is triggered in susceptible individuals through a process of uncontrolled inflammation leading to osteolysis, progressive fractures and articular malpositioning due to joint subluxations and dislocations (\u0160poner et al., In the acute phase, avoidance of weight bearing is a prerequisite for prevention of mid-foot collapse. Even after consolidation, abnormal bony prominences may cause ulcerations and foot infections. Surgical reconstruction is indicated if the deformity can't be adequately managed by shoe modifications and bracing.per se, however, the risk increases significantly in patients with underlying diabetic polyneuropathy and chronic tissue hypoxia/ischemia (Lipsky et al., Generalized and local infections are risk factors which may prevent recovery, exclude favorable outcome, and increase the rate of limb amputations in diabetic foot patients (Wu et al., Approaches to surgical and pharmacological management of septic wounds are well established. The therapy of infected diabetic foot requires meticulous surgical debridement and decompression of viable tissues, mechanical, and pharmacological destruction of the microbial biofilms in combination with targeted systemic and local antibacterial therapy. In addition to the local therapeutic measures, systemic correction of cardiovascular, respiratory, renal, and blood coagulation functions is mandatory (Frykberg et al., In conclusion, patients undergoing surgery for diabetic foot are characterized with disorders of local and systemic functions. The final surgical outcome will depend on perioperative correction and stabilization of organ-systems, tight control of blood glucose levels and aggressive infection control.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Our understanding of the plasma membrane of eukaryotic cells has profoundly changed over the past 40 years  (Beckmann et al., Milovanovic and Jahn review the roles of microdomains in neurobiology focusing on the molecular mechanisms mediating domain organization at the presynaptic membrane (Milovanovic and Jahn, Navarro and co-workers discuss the therapeutic potential of targeting caveolae (Shvets et al., in cis with other membrane proteins and intracellular proteins forming so-called \u201ctetraspanin microdomains\u201d (Tarrant et al., Tetraspanins belong to the superfamily of four-transmembrane proteins that interact in vitro, antibody treatment of tumor-bearing mice resulted in significantly delayed tumor growth. Binding of the Tspan8 antibody to the tumor cells may modify their response to the tumor microenvironment possibly by disrupting the assembly of tetraspanin microdomains containing integrins, growth factor receptors, and/or signaling molecules.Ailane et al. describe the potency of targeting the tetraspanin Co-029/Tspan8 on colorectal tumor cells (Ailane et al., The effectiveness of tetraspanin targeting in hematological malignancies is concisely reviewed by the group of Muthusamy (Beckwith et al., The use of transmembrane proteins as target for intracellular drug delivery is an exciting possibility discussed by Popov-\u010celeketi\u0107 and Van Bergen en Henegouwen, who elaborate on the role of cancer-specific growth factor receptor domains in receptor-mediated endocytosis (Popov-Celeketic and van Bergen En Henegouwen, Together, we believe our Review Topic provides an exciting overview of the various targeting and effector strategies of drugs that selectively target membrane domains. This synergistic overview brings together previously detached research fields and disciplines. Given the increasing appreciation of the fundamental importance of membrane domains in cellular function, we hope that this overview will foster the development or optimization of new pharmaceutical strategies for a wide range of human diseases and disorders.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "An introduction to the 2015 CCP4 Study Weekend on Advances in Experimental Phasing. Advances in Experimental Phasing, held on 8\u20139 January 2015 at the East Midlands Conference Centre of the University of Nottingham, UK.This issue publishes the proceedings of the 2015 CCP4 Study Weekend on Crystallographic phasing using experimental approaches remains an important, and often the only successful, route for solving crystal structures, especially for structures with novel folds. These are often large and complex assemblies diffracting to limited resolution, but also those likely to provide the most novel biological insights. Our speakers were invited to cover both practical aspects, such as sample preparation and data collection strategies, and computational aspects, relating to the analysis and use of diffraction data from derivatized or anomalously scattering crystals. A session on radiation damage was included to remind experimentalists of the unavoidable side effects of using X-rays for diffraction data collection, while a final session on evolving methods provided a forum for ideas for (perhaps) solving the phase problem employing unconventional approaches.Neil Isaacs (University of Glasgow) sharing his personal view of the history of crystallographic phasing from the structure determination of zincblende, solved with the logic of constructive and destructive interference alone, via the heroic early macromolecular structure determinations by multiple isomorphous replacement, all the way to the routine exploitation of weak anomalous signals for the phasing of macromolecular crystals structures. Janet Smith (University of Michigan) then described the foundations of anomalous phasing demonstrating its current capabilities by way of a tour-de-force of phasing using raw data from many crystals.The meeting began with a lecture by Liz Carpenter (University of Oxford), comprised three recent case studies of challenging structure determinations; cluster-compound based phasing of the multi-subunit membrane protein bestrophin-1 by Veronica Dickson (University of Cambridge); the determination of the COP9 signalosome structure by Richard Bunker (Friedrich Miescher Institute Basel); and the use of artificially introduced anomalous markers for the validation of the structure of the AP2 clathrin adapter by Bernard Kelly (University of Cambridge).To demonstrate the power of experimental phasing methods, the second session, after an introduction to the practicalities of preparing derivatized crystals by TomTerwilliger  introduced a new metric for assessing the potential of SAD data to lead to a successful structure solution. Randy Read (University of Cambridge) then discussed a log-likelihood-gain based framework for an improved accounting of measurement errors and uncertainties by means of a formulation in terms of diffraction intensities instead of the structure-factor amplitudes. Garib Murshudov (MRC Laboratory of Molecular Biology) described how experimental phases can be used as additional observations in structure refinement. Having last been discussed at a CCP4 Study Weekend in 2009 , radiation damage as a major problem in experimental phasing was highlighted in the first session of the second day. Robin Owen (Diamond Light Source) dissected the effect of radiation- and/or derivatization induced structural changes by carefully inspecting the effects on individual reflections. How radiation damage, deliberately induced by UV irradiation, can be harnessed, through optimized data collection schemes was demonstrated by Max Nanao (EMBL Grenoble). The design and the implementation of interleaved data collection protocols for the minimization of systematic errors due to radiation damage effects was described by Gerard Bricogne . The use of data from multiple crystals as a means of dealing with limited life-time of individual crystals was then discussed by Gwyndaf Evans (Diamond Light Source).The scientific program of the first day of the Study Weekend was concluded with a session on the computational side of experimental phasing methodologies. Paula Salgado (Newcastle University) gave an overview of the different ways of exploiting dispersive and/or anomalous differences measured on one or several potentially non-isomorphous crystals. Michele Cianci (EMBL Hamburg) showed how micro-focused low-energy X-ray beams can be used to extract optimum anomalous data from small crystals. The advantages of multi-circle goniometry in terms of increasing multiplicity and correcting for systematic errors was discussed by Andy Thompson (Synchrotron SOLEIL). Daniele de Sanctis (ESRF) described experimental options for achieving optimum data in different scenarios, while Vincent Olieric (Swiss Light Source) described generally applicable strategies for native SAD phasing exploiting anomalous signals from sulfur and or phosphorus. Finally, Armin Wagner (Diamond Light Source) described progress and first results from the new I23 in vacuum beamline at the Diamond synchrotron.The next session featured representatives from several synchrotrons advocating the modern experimental approaches available. Bjorn Panyella Pedersen (Aarhus University). The potential use of introducing differences in dispersive and anomalous signals by X-FEL radiation and the subsequent exploitation of these differences for phase determination was explained by Sang-Kil Son . Finally, two methods of iteratively generating improved phase sets by were presented. Monarin Uervirojnangkoorn (Stanford University) employed genetic algorithms for the production of updated phase sets. Julien Jorda (UCLA) demonstrated the use of human perception for the scoring of updated electron densities with crowdsourcing software, which required audience participation.The final session of the Study Weekend concerned evolving methods. The successful use of molecular replacement for boot-strapping heavy-atom localizations in large macromolecular complexes in a parallelized computer implementation was described by We would like to express our gratitude to the CCP4 staff, in particular Karen McIntyre, for their invaluable help with the practical aspects of the 2015 Study Weekend. We thank all our speakers for their careful preparation and enthusiastic presentation of their talks. We hope that their papers will inspire young and seasoned crystallographers alike."}
+{"text": "Tools that allow for in silico optimization of available malaria control strategies can assist the decision-making process for prioritizing interventions. The OpenMalaria stochastic simulation modeling platform can be applied to simulate the impact of interventions singly and in combination as implemented in Rachuonyo South District, western Kenya, to support this goal.Combinations of malaria interventions were simulated using a previously-published, validated model of malaria epidemiology and control in the study area. An economic model of the costs of case management and malaria control interventions in Kenya was applied to simulation results and cost-effectiveness of each intervention combination compared to the corresponding simulated outputs of a scenario without interventions. Uncertainty was evaluated by varying health system and intervention delivery parameters.The intervention strategy with the greatest simulated health impact employed long lasting insecticide treated net (LLIN) use by 80% of the population, 90% of households covered by indoor residual spraying (IRS) with deployment starting in April, and intermittent screen and treat (IST) of school children using Artemether lumefantrine (AL) with 80% coverage twice per term. However, the current malaria control strategy in the study area including LLIN use of 56% and IRS coverage of 70% was the most cost effective at reducing disability-adjusted life years (DALYs) over a five year period.All the simulated intervention combinations can be considered cost effective in the context of available resources for health in Kenya. Increasing coverage of vector control interventions has a larger simulated impact compared to adding IST to the current implementation strategy, suggesting that transmission in the study area is not at a level to warrant replacing vector control to a school-based screen and treat program. These results have the potential to assist malaria control program managers in the study area in adding new or changing implementation of current interventions. Important progress has been made in the past decade in reducing malaria morbidity and mortality in Kenya, but it is not obvious which additional tools and strategies should be the next priority to include in the package of malaria control interventions in a given area to keep transmission levels low, especially given the threat of resistance of the parasite and vectors to antimalarial drugs and insecticides OpenMalaria, a stochastic simulation modeling platform Plasmodium falciparum is transmitted not only by Anopheles funestus and An. arabiensis, but also by another, as yet unidentified secondary vector with outdoor-active, early-biting behavior, potentially challenging the effectiveness of current vector control interventions targeting indoor-biting mosquitoes Rachuonyo South District in Homa Bay County of Nyanza Province, Kenya is a highland fringe area with altitude between 1,400 and 1,600 meters. Ethnicity is predominantly Luo and homesteads are distributed broadly across a rolling landscape intersected with small streams and rivers. The area is characterized by generally low malaria endemicity with marked seasonal and inter-annual variations in transmission The main malaria control methods are currently mass-distribution of LLINs, annual indoor residual spraying (IRS) with pyrethroids, and prompt and effective treatment Rachuonyo South is one of a number of field sites of the Malaria Transmission Consortium (MTC), a project with the goal of enabling operational program managers to achieve optimal implementation of transmission-reducing malaria control techniques. Active between 2009 and 2012, MTC surveys provided detailed entomological studies of species composition and biting behavior The study proposal received ethics approval from the Ethical Review Committee (ERC) of the Kenya Medical Research Institute (KEMRI) Nairobi under proposal number SSC 2163, the London School of Hygiene & Tropical Medicine ethics committee (#6111), and from Centers for Disease Control and Prevention (with exempt status).A team at the Swiss Tropical and Public Health Institute (Swiss TPH) and Liverpool School of Tropical Medicine (LSTM) developed the OpenMalaria platform comprising stochastic simulation models of transmission of malaria based on the simulation of infection in individuals. These models are able to evaluate the impact  of numerous intervention strategies for malaria control The scenario describing the current intervention mix was parameterized using a previously-published model of malaria epidemiology and control in Rachuonyo South District, validated with observed data from the site-specific MTC studies described above Combinations of interventions for the experiment were chosen in collaboration with malaria control personnel in the study area to correspond to a 2011\u20132012 intervention evaluation trial www.malariacontrol.net).Each intervention strategy was simulated in a population of 100,000 individuals. To simulate the status quo prior to interventions, simulations were run for one human life span to induce an \u201cequilibrium\u201d level of immunity. Forward simulations of each intervention combination were made using an ensemble of 14 model variants for malaria in humans to address model uncertainty Malaria case management costs were based on a societal perspective; direct costs to the health systems are considered, as well as direct expenditures associated with malaria episodes at the household level. Indirect costs, including productivity loss due to illness, were not accounted for. While the latter tend to dominate the economic cost of illness Treatment costs are evaluated following a model of malaria case management developed for endemic settings and is described elsewhere Text S1.On the provider side, cost per episode covers drugs, diagnosis, medical personnel, facility charges, and other consumables. In addition to the first-line antimalarial as per national malaria guidelines, a portion of uncomplicated cases were assigned to treatment with sulfadoxine pyrimethamine (SP) given evidence on moderate uptake of AL, the first line artimisinin combination therapy (ACT) in the study area Direct patient costs associated with a malaria episode include travel expenses to and from healthcare facility and other consumables  and were based on the multi-country literature review. Spending on consumables is generally considered negligible; only a few studies recorded these data with an average of $0.20 per visit Both average and marginal health system costs were calculated for each outcome. The average cost includes all costs involved in delivering a health intervention, including the use of spare capacity or slack in the system, health care resources diverted from other uses, and existing health sector resources shared with other health programs. In the marginal analysis only costs of drugs, diagnosis, and patient spending per visit were considered, as broader savings to the health system including labour and capital costs would not be immediately affected by changes in consumption of medical services due to lower diseases burden achieved by control interventions A sensitivity analysis was conducted for the costs of test and cost per ACT dose by varying costs \u221250%/+100%, and for proportion of fevers that access medical care by varying access \u2212/+50% Table 2.A general approach for costing malaria interventions using secondary data was applied as outlined by Kolaczinski et al The simulated effectiveness of malaria control interventions and intervention combinations was evaluated by calculating the mean and inter-quartile range (IQR) of all model variants and seeds for each intervention combination for the difference in disease burden over a five year period from the start of intervention deployment compared to the mean of the simulations of the base case scenario with no interventions other than the existing case management system. Outcomes evaluated include decrease in parasite prevalence, number of uncomplicated episodes, hospitalizations and deaths averted in the general population. In addition to indicators for severity of illness, the overall population burden averted in terms of disability adjusted life years (DALYs) is calculated by combining mortality and morbidity measures as described by Murray and Lopez Estimates of effectiveness of control interventions and intervention mixes are combined with the added costs of implementing these control measures. Treatment cost savings, or the reduction in cost to the health system due to the reduction in cases seen by the system, achieved by implementing the control strategy, are used to offset implementation costs and thus cost effectiveness ratios are calculated based on net rather than total intervention costs.cmNO\u2212DCcmIC, where DCcmNO are the direct costs (DC) of case management in the scenario without interventions and DCcmIC are the direct costs of case management in the case of each intervention combination. These cost savings are subtracted from the direct cost of implementing each intervention combination (DCint) to give a net intervention combination cost (NC) computed as follows: NC\u200a=\u200aDCint\u2212(DCcmNO\u2212DCcmIC). Cost effectiveness is evaluated in two ways. The first is by calculating the average cost effectiveness ratio (ACER), as the net cost (NC) of the intervention divided by the net effects (NE) of the intervention. The second is by calculating the incremental cost effectiveness ratio (ICER), which follows the same methodology for calculating the ACER, except the net costs and net effects of each intervention combination are calculated against the currently implemented strategy.The cost savings to the case management system and households (CM) associated with implementing each intervention combination (IC) instead of a scenario without interventions (NO) are computed as DCBoth marginal and average cost-effectiveness ratios over a five year reference period are reported to illustrate the likely short-term financial impact of the intervention, as well as the longer-term impact associated with the intervention including structural changes in health care delivery in response to lower disease burden achieved by the program. Cost effectiveness ratios are reported without discounting of future costs and benefits due to the short implementation time frame of the study and the recommendation from the revised GBD study Compared to an intervention scenario with no malaria control outside of routine case management, and after five years of implementation, the intervention combination with LLIN use by 80% of the population, 90% of households covered by IRS with deployment starting in April, and IST of school children using AL with 80% coverage twice per term result in the largest simulated reduction in all-age parasite prevalence , average averted cases of uncomplicated malaria per person , hospitalizations averted (thousands), deaths averted , and DALYs averted (thousands)  Table 4.Simulation results indicate that increased coverage of vector control has a larger impact than adding an IST intervention to the current control strategy. However, adding the highest IST coverage and frequency to the current strategy could reduce parasite prevalence by an additional nine percentage points Figure 1, Despite moderate levels of self-reported LLIN use, simulations indicate LLINs, and not IRS, account for the majority of impact on parasite prevalence. Removing LLINs and continuing only with a higher level of IRS coverage resulted in a similar number of averted uncomplicated cases compared to the IST interventions Table 4.Depending on coverage level and frequency, without vector control interventions, simulations suggest IST could reduce annual average parasite prevalence in the population by 9\u201322% Table 4.Table S1. Program costs always exceeded savings in case management. The top contributor to uncertainty in the highest coverage intervention combination scenario was the cost per LLIN distributed, followed by cost per child screened, ACT cost, cost per person protected by IRS, and access to treatment Click here for additional data file.Text S1Costing the Kenya malaria case management system and interventions. Contains Tables A\u2013C.(DOCX)Click here for additional data file."}
+{"text": "According to some clinical feature of similarities  Familial Mediterranean Fever (FMF) and Henoch-Schonlein Purpura (HSP) we attempt to identify membranes aspects of pathogeneses these diseases.The aim of our study is to identify some changes of individual phospholipids (PL) in erythrocyte membranes and comparative analysis of FMF and HSP patients.The examinations have carried out in 42 non complicated 7-15 ages of FMF patients and 24 healthy volunteers. Clinical studies have carried out in the National FMF Children Center, Center \"Arabkir\". Biochemical changes have studied in Hematological Center. 42 patients in erythrocyte membranes by the separate individual PL are studied: phosphatidylcholines (PCH), phosphatidylethanolamines (PE), phosphatidylinosites (PI), sphingomyelins (SPM), phosphatidic acids (PA), phosphatidylserine (PS) and citotoxic-LysoPCH (LPCH) qualitative and quantitative changes. Previously it has been investigated the changes of indicators during the HSP diseases . The fractions of separate PL in erythrocyte membranes are carried out by thin-layer chromatography methods and decay their enzymes (phospholipase A) activity was determined by the spektrofotometrik method.Comparative studies are identified on the basis of membrane structural metabolism disorders, for the prevention and regulation some changes of FMF and HSP. Based on the results obtained by our research is an attempt to separate the membrane lipids metabolism disorder specific agencies which are responsible for affection of membrane's.According to our investigation we can conclude, that level of phopholipase A and citotoxic-LPCH are increase in mentioned diseases.None declared."}
+{"text": "Elderly surgical patients frequently experience postoperative delirium (POD) and the subsequent development of postoperative cognitive dysfunction (POCD). Clinical features include deterioration in cognition, disturbance in attention and reduced awareness of the environment and result in higher morbidity, mortality and greater utilization of social financial assistance. The aging Western societies can expect an increase in the incidence of POD and POCD. The underlying pathophysiological mechanisms have been studied on the molecular level albeit with unsatisfying small research efforts given their societal burden. Here, we review the known physiological and immunological changes and genetic risk factors, identify candidates for further studies and integrate the information into a draft network for exploration on a systems level. The pathogenesis of these postoperative cognitive impairments is multifactorial; application of integrated systems biology has the potential to reconstruct the underlying network of molecular mechanisms and help in the identification of prognostic and diagnostic biomarkers. Networks built on the list of the seed genes/proteins reviewed in this article may indicate enriched pathways that are related directly or indirectly to POD/POCD. We can proceed with prediction of the upstream regulators, hubs and bottlenecks of the given pathways and sub-networks. Such regulators are potentially interesting as targets since they could modulate the network state and dampen imbalance and deregulation. Network approach enables us to study dynamical changes of the system such as responsiveness, adaptation and stability. For example, network analysis of the metabolic positron emission tomography scans from Parkinson\u2019s disease patients identified two distinct disease-related patterns  using the following query: \u201c(biomarker OR marker) AND [(postoperative delirium) OR delirium OR (postoperative cognitive dysfunction) OR POCD] AND (hasabstract[text] AND Humans[Mesh]) NOT (Alzheimer OR Parkinson)\u201d. The search yielded 254 publications. The ones cited in the review are those that, in the author\u2019s view, make a substantial contribution to the knowledge about existing and potential biomarkers of POD/POCD.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The supporting stroma of breast cancer is believed to support the growth and metastasis of cancer cells and are responsible for suppressing anti-cancer immune responses. In this regard we attempted to isolate and characterise the cancer associated fibroblasts (CAFs) of murine model of spontaneously developed breast cancer.CAFs were isolated by explants culture of tumour tissue. The Fibroblast activated protein-alpha( FAP-\u03b1)-positive fibroblasts were co-cultured with splenocytes where the splenocyte proliferation and production of inflammatory and regulatory cytokines were assessed by ELISA. Also the inflammatory enzymes iNOS and the production of matrix metaloproteinases 2 and 9 by these cells were evaluated using Real-Time PCR.Findings indicated enhanced in vitro immune suppression in co-cultures of CAF and splenocyte. Additionally, increased regulatory cytokine and inflammatory mediators was observed.The secretory profile of these cells, as the supporting matrix, is a massive physical and immune barrier to anti-cancer immune therapy. Therefore it is proposed for enhancing the effect of therapy must take into acount the contribution of cancer associated fibroblasts on the chronic inflammatory microenvironment of breast cancer."}
+{"text": "Manually delineating the left ventricle (LV) is considered the clinical standard for quantification of cardiovascular magnetic resonance (CMR) images, despite being time consuming and observer dependent. Previous automatic methods generally do not account for the long-axis motion, which is a major contributor to the stroke volume. Therefore, the aim of this study was to develop and validate an automatic algorithm for time-resolved segmentation covering the whole LV, including basal slices moving out of the imaging plane during systole.Ninety subjects were imaged using a routinely applied cine balanced steady state free precession (bSSFP) sequence .The automatic algorithm uses deformable model with Expectation-Maximization (EM), followed by automatic removal of papillary muscles and detection of the outflow tract.The reference standard was manual delineation and second observer analysis was performed in a subset of patients (n=25).Typical automatic segmentation and reference manual delineation is shown in three selected slices in Figure The proposed automatic LV segmentation algorithm reached accuracy comparable to that found between observers, taking automatic segmentation one step closer to clinical routine. The algorithm and all images with manual delineations will be made available for benchmarking.This study has been funded by the Swedish Research Council, The Swedish Heart and Lung Foundation, The Medical Faculty of Lund University, Sweden, and Region of Scania, Sweden."}
+{"text": "The research carried out aimed to encourage evidence-based cost-effective pharmaceutical prescribing, reduce medicine related adverse reactions, improve patient quality of life and reduce pharmaceutical wastage. Prescribing data was evaluated and interventions were subsequently developed in an attempt to improve pharmaceutical prescribing by General Practitioners (GPs) across an enrolled population.(1) To evaluate the effectiveness of interventions being developed to optimise prescribing by GPs, (2) To recognise factors affecting prescribing patterns of medicines targeted by the programme, and (3) To identify other medicines information sources which influence GP prescribing.Policy targeted(s): Pharmaceutical prescribing of medicines, in particular medicines available funded through the Pharmaceutical Management Agency (PHARMAC) was evaluated to observe trends in prescribing. These funded medicines are generally generics which are highly accessible to populations in which they are necessary.Stakeholder: ProCare Health NZ is a Primary Health Organisation which was responsible for data collection and recruiting GPs within its District Health Board.Region covered: New Zealand WPRO, Region number 13.Retrospective delay analysis of pharmaceutical data was conducted using Excel to identify potential reductions in expenditure and volume of targeted pharmaceuticals and pharmaceuticals overall. A pilot prospective, cross-sectional study investigating the perceptions held by GPs regarding the influence of Optimising Prescribing interventions on their prescribing practices was also carried out. Research was carried out over a two year period (July 2009 to March 2011). An overview of methodology and interventions used is shown in Figure Some medicines showed changes in prescribing volume and pharmaceutical expenditure in response to the initiation of the interventions. For example, the prescribing volume of calcium carbonate in ProCare Network Manukau and East Health dropped sharply after the initiation of Optimising Prescribing interventions, which consists of medicines information bulletins and cell focus groups. However, the prescribing volume of calcium carbonate in ProCare Network Auckland declined before the intervention was initiated, implying that there are other sources of influence involved. From the pilot survey, Best Practice Advocacy Centre (BPAC) was cited by GPs as the most influential source of medicines information in their prescribing practice.There is evidence, following the changes in pharmaceutical expenditure and prescribing volume in some investigated medicines. These show Optimising Prescribing interventions to be effective in influencing GP prescribing practices."}
+{"text": "Receptor for advanced glycation end products (RAGE) triggers an intracellular signalling pathways of various proinflammatory ligands. Solubile form of RAGE (sRAGE) in human plasma can hinder the function of RAGE and can have the role in the pathogenesis of inflammatory diseases. In patients with multiple sclerosis (MS), altered level of sRAGE in plasma and cerebrospinal fluid has been found. In our study, we tried to identify possible association of sRAGE serum level with MS. Serum levels of sRAGE were detected by ELISA in 44 MS patients (22 patients with rapid progression of MS and 22 patients with slow progression of MS according to the MSSS score) and 32 healthy control subjects. We found significantly increased level of sRAGE in serum of MS patients when compared to controls. No significant differences in serum level of sRAGE where found between rapidly progressing and slow progressing subgroup of MS patients. Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression."}
+{"text": "Morbillivirus genus members causing these mass mortality events, along with the reason(s) behind their \u201csudden\u201d appearance among wild aquatic mammals, are still unknown  of the new Cetacean morbillivirus (CeMV) strains infecting wild cetaceans  in the Southern Hemisphere  as well as to Peste des Petits Ruminants Virus (PPRV) and Rinderpest Virus (RPV), the archetype morbillivirus  found stranded during the first mid of 2013 along the Tyrrhenian coast of Italy, IHC evidence of morbilliviral antigen was obtained from the brain of only one of these animals (Casalone et al., Interestingly enough, two recent papers have reported the existence of Morbillivirus-cetacean interaction dynamics (Di Guardo, In conclusion, while more data are certainly needed on the genetic \u201cmake-up\u201d of the newly discovered CeMV strains infecting cetaceans in the Southern Hemisphere (Groch et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Garin et al. reported that recreational drug use is higher in HIV infected persons than the general population and cannabis is the highly used recreational drug in the Europe followed by cocaine, amphetamines and ecstasy.Drugs of abuse plays a major role in increasing the risk of HIV transmission, disease progression, and less adherence to the antiretroviral therapy, which significantly contribute for morbidity and mortality of the HIV infected patients , naltrexone (opioid-receptor antagonists) reported to recover the expression of these miRNAs . Also, Lan et al. discussed about the association of Apolipoprotein L1 (APOL1) variants  in Heroin-associated Nephropathy (HAN) and Human Immunodeficiency Virus associated Nephropathy (HIVAN) in African Americans which opens an interesting point to explore the onset of focal and segmental glomerulosclerosis (FSGS) in HIV infected heroin abusers in African Americans. In the post-mortem brain tissues of HIV-infected subjects with neurocognitive impairment (NCI) \u00b1 HIV encephalitis (HIVE), Dever et al. reported the dysregulation of autophagy genes and proteins; and in in vitro, supernatant from HIV-1-infected microglia/HIV-1 Tat protein in combination with morphine reported to alter autophagic activity and reduced dendrite length. Morphine in combination with HIV-1 gp120 has been reported to increase oxidative stress, DNA damage, and subsequently affecting cell cycle process .Opioid abuse increases the HIV disease progression by effecting host immune function, promoting the virus entry into the immune cells and replication and it also causes severe neurocognitive disorders by inducing the neuro-inflammation  reduces the neurotoxic effects (reduced dendritic synapses) of cocaine in combination with HIV-1 Tat in an estrogen receptor beta dependent manner. Roy et al. reported the reduced levels of DJ1 protein  and associated increased ROS production in HIV exposed neuronal cells in combination with cocaine. Also two comprehensive review articles focused on the effect of cocaine abuse on HIV pathogenesis  and role in progression to HIV-1 associated neurocognitive disorders .Cocaine is the second most commonly abusing drug in US and cocaine abuse in HIV infected patients reported for rapid progression to AIDS and are prone to develop severe form of neurocognitive disorders  levels compared to the control and SIV alone infected animals which can aggravate the neuroinflammation. Borgmann and Ghorpade have contributed a comprehensive review on alterations in astrocyte intrasignaling pathways, gene expression, and function in the presence of HIV and its proteins in combination with METH that contributes to the neuroinflammation and also focused on the therapeutics for astroglial activation and function. Mediouni et al. discussed about effect of METH and HIV-Tat on the development of HAND.In North America, methamphetamine is the widely used recreational drug especially in men who have sex with men (MSM) infected with HIV  and also observed differentially modulated HIV infection, altered MDDC endocytic function and cytokine production in combination with cannabinoids (THC and JWH-015).Alcohol use disorder is more common in the United States and in persons living with AIDS, rates of heavy drinking are even higher than those in the general population Petry, . Heavy aZhu et al.). Rao and Kumar reviewed the effect of smoking on HIV replication and role of polycyclic aromatic hydrocarbons (PAH-important constituents of cigarette smoking) and CYP1 enzymes (CYP1A1 and CYP1B1- activators of PAH) in HIV pathogenesis. Chinnapaiyan and Unwalla reviewed the mechanisms of mucociliary suppression in people living with HIV who are smokers or illicit drug abusers.In US, the prevalence of cigarette smoking range from 40 to 75% in HIV-infected individuals compared to 20% in general population ; role of miRNs during HIV infection and effect of drugs of abuse on the expression of miRNAs and its effect on HIV associated neurocognitive disorders (Pilakka-Kanthikeel and Nair); effect of HIV-1 Tat and drugs of abuse during HIV infection and their role in the development of NeuroAIDS ; and anti-HIV effects of different natural compounds .Also, this special issue include review articles on epigenetic alterations in drugs of abuse and HIV infection that affects Vitamin D receptors (The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Several studies have shown that detectable levels of HIV are observed in semen in spite of undetectable viral load in blood following antiretroviral therapy (ART). Also, different HIV variants have been detected in blood and semen of the same individual, suggesting that drugs may not be uniformly effective to control the viral load and infectivity in different tissues and secretions, which in turn may affect sexual transmission of HIV. Hence, genotypic characterization of HIV variants in PBMCs and sperm of the same individual may provide information about the association of these variants with sexual transmission of HIV.env of HIV-1 C in PBMCs and Spermatozoa of 14 and 5 individuals, respectively. The sequences were analysed for presence of N linked glycosylation sites using the program N-Glycosite. Also, Co receptor usage predictions were done using an online tool, Geno2pheno [Co receptor] 1.2.Present study describes characterization of translated amino acid sequence of C2 v3 region of Significant differences in the number of N linked glycosylation (NLG) sites were observed in PBMCs and spermatozoa of the same individuals as well as samples collected from different individuals.This study describes presence of compartmentalization between blood and semen which may influence the effect of ART in control of HIV/AIDS and influence sexual transmission of HIV."}
+{"text": "Piccolo and Bassoon are also important for the maintenance of presynaptic structure and function, as well as for the assembly of CAZ specializations such as synaptic ribbons. Recent findings suggest that they are also involved in the regulation activity-dependent communication between presynaptic boutons and the neuronal nucleus. Together these observations suggest that Bassoon and Piccolo use their modular structure to organize super-molecular complexes essential for various aspects of presynaptic function.Bassoon and Piccolo are two very large scaffolding proteins of the cytomatrix assembled at the active zone (CAZ) where neurotransmitter is released. They share regions of high sequence similarity distributed along their entire length and seem to share both overlapping and distinct functions in organizing the CAZ. Here, we survey our present knowledge on protein-protein interactions and recent progress in understanding of molecular functions of these two giant proteins. These include roles in the assembly of active zones (AZ), the localization of voltage-gated Ca Synapses are sophisticated cellular devices designed for the efficient and rapid communication between neurons via the regulated release of neurotransmitter substances from presynaptic boutons and their detection by postsynaptic receptor systems. The release of neurotransmitters is mediated by the recruitment and fusion of synaptic vesicles (SVs) at specialized regions of the presynaptic plasma membrane called active zones (AZ). The molecular and ultra-structural characterization of these release sites revealed that they are composed of a dense cytomatrix assembled at the AZ (CAZ). This matrix is organized by a small number of multi-domain proteins, including Munc13s, Rab3-interacting molecules (RIMs), RIM-binding proteins (RBPs), Liprins-\u03b1, ELKS2/CAST as well as the two large scaffolding proteins Bassoon and Piccolo  or Munc13  to AZs . Ca2+ influx and CaV1.3 density is reduced in Bassoon (Bsn)-mutant mice  gene  and induces a conformational change in this domain . Moreover, Piccolo can interact with the cAMP-sensor Epac2  from large dense-core vesicles comes from the investigation of While Piccolo and Bassoon share a great deal of structural homology, each also contains unique segments, implying divergent functions. Studies of Piccolo have shown that it is selectively required for activity-induced F-actin assembly within presynaptic boutons and efficient synaptic transmission (Waites et al., Intriguingly, two of these Piccolo binding partners, Abp1 and GIT1 are also linked to SV endocytosis (Fenster et al., In addition to their roles in the structural and functional assembly of presynaptic AZs, Piccolo and Bassoon are involved in the maintenance of SV pools (Mukherjee et al., +/NADH and contributes to activity-dependent distribution of CtBP1 between presynapses and the nucleus. High activity shifts the equilibrium between synaptic and nuclear CtBP1 pools to synapses, low activity to the nucleus (Ivanova et al., Communication between synapses and the soma, in particular the nucleus, of a neuron is essential for neuronal survival as well as for processes of homeostatic and associative plasticity. While multiple synapto-nuclear signaling pathways have been reported for the postsynapse (for review, see Jordan and Kreutz, Of note, the interaction of CtBPs with Bassoon and Piccolo has long been known (tom Dieck et al., in silico analysis of their structure (Figure The detailed analysis of protein binding partners for Piccolo and Bassoon support the concept that they are fundamentally involved in scaffolding a large number of proteins involved with various aspect of presynaptic function within AZs. State of the art e Figure  reveals e Figure  has yet e Figure .EDG and CCG have written the article. CR contributed essential discussions and designed Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Cortical/cerebral visual impairment (CVI) is the leading cause of pediatric visual impairment in children in developed countries and has become a significant public health concern  and magnetic resonance imaging (MRI) can help characterize gross changes in cerebral structure. However, the underlying micro-architecture of key white matter pathways (such as the optic radiations) cannot be fully ascertained, nor can the function of visual cortical areas be assessed. Advances in diffusion based imaging  modalities such as high angular resolution diffusion based imaging (HARDI) combined with tractography analysis techniques can be used to reveal the organization of specific white matter projections Jones,  see alsoIn this study, we used a combined structural and functional multi-modal neuroimaging approach to characterize the underlying maldevelopment of the geniculo-striate pathway in an adolescent with CVI. The patient presented here had a documented inferior visual field deficit determined on clinical ophthalmic examination. Despite her diagnosis of CVI and associated visual impairments, she was able to participate in formal testing and provide reliable data (including maintaining fixation during perimetry and retinotopic stimulation) and also remain immobile in the scanner environment without the need of anesthesia. Thus, , we had the opportunity to obtain high quality structural and functional imaging data on the same subject in order to investigate the relationship between the structural integrity of the optic radiations and the functional organization of early visual cortical areas with respect to her clinical visual field impairment. We demonstrate the feasibility of combining this structural and functional imaging approach in a patient with CVI along with an age/gender matched normal developed control for comparison. By combining these imaging modalities, it is possible to provide further insight regarding the functional manifestations of early onset developmental damage to key visual pathways and their relation to specific impairments of visual function.The CVI patient (and age/gender matched control subject) and parents provided written informed consent prior to participating in the study. The protocol was approved by the investigative review board of the Massachusetts Eye and Ear Infirmary  and the study was carried out according to the tenants of the Declaration of Helsinki and conformed to the requirements of the United States Health Insurance Portability and Privacy Act (HIPPA). Ophthalmological examination of the patient was conducted by an experienced pediatric neuro-ophthalmologist. At the time of study, the CVI patient was a 17-year-old girl, born prematurely at 32 weeks gestational age. In the perinatal period, she developed a grade III intra-ventricular hemorrhage with subsequent post-hemorrhagic hydrocephalus, periventricular leukomalacia (PVL), and spastic diplegia. She underwent bilateral strabismus surgery at 11 months to correct an esotropia. Best corrected visual acuity (Snellen) at the time of testing was 20/50 (right eye) and 20/40 (left eye). Her sensorimotor exam was notable for latent nystagmus and a residual microtropia. Funduscopic examination revealed evidence of optic atrophy in each eye, but was otherwise unremarkable. Visual field assessment was performed with automated visual field testing on a Humphrey Field Analyzer using a SITA-Fast 24-2 protocol .As a control, an age and gender matched subject  with normal visual acuities and no history of prematurity or neurological/ophthalmic disorders was also recruited for comparison.Automated perimetry using the Humphrey Field Analyzer revealed a stable, bilateral visual field defect involving the inferior visual fields Figure . Inspecthttp://dsi-studio.labsolver.org/) with diffusion decomposition and sparse solution of the fiber orientation distribution function (ODF). HARDI images were aligned to the anatomical data using boundary based registration . For white matter tract reconstruction, high angular resolution diffusion imaging (HARDI) was chosen given its superior ability in revealing intravoxel white matter fiber heterogeneity and delineation of multiple fiber orientations within an individual voxel . Using standard FreeSurfer methods  were visualized on the inflated and flattened cortical surfaces.All structural and functional data were analyzed with FreeSurfer and FS-FAST packages  and ventral (v) regions of interest (ROI) were identified in each hemisphere and in each participant using block-design retinotopic fMRI analysis  and to the lower visual field wedge, within each ROI for each subject for each run. Since the dorsal parts of V1 and V2 are responsive to lower visual field stimulation and ventral parts are responsive to the upper visual field stimulation, this allowed us to create an in-field vs. out-of-field metric for each ROI and for each subject, normalized by the standard deviations of the blood oxygen level dependent (BOLD) signals. This in vs. out metric was computed as follows:Where \u201cpreferred\u201d is the BOLD percent signal change evoked by the preferred stimulus for each ROI  and \u201cnonpreferred\u201d is the BOLD percent signal change evoked in the ROI by the other, nonpreferred wedge. Standard deviations in BOLD percent signal change were computed within subjects and across runs. The in vs. out metric was contrasted between the CVI and control subject for each visual quadrant ROI as a ratio. A ratio of 100 indicates that the CVI patient and the control demonstrate similar responsivity profiles, while a ratio less than 100 indicates that the representation of the upper/lower visual field is less strongly segregated in the CVI patient than in the control subject.Both the CVI patient and the control subject were able to maintain adequate central fixation during the fMRI scans allowing for the identification of retinotopically specific cortical activation patterns . Functional MRI assessments resulting from the stimulation of horizontal and vertical visual field meridians were used to reveal the boundaries between visual cortical areas and the boundaries of early visual areas  visual field deficit, damage to superior (and greater in the right hemisphere) branches of the optic radiations, and the reduced activation of early visual cortical areas within the inferior visual field (greater in left). This correspondence is in accordance to the known anatomical and functional organization of visual pathways and geniculo-cortical representation of visual field space Wandell, . To our Previous studies have employed various neuroimaging methodologies to investigate the impact of pathology and/or the maldevelopment of the visual system  may also reflect the relative contributions of top-down  to both striate and extra-striate cortices from higher order visual areas. At this juncture, it is reasonable to speculate that the optic radiation damage characterized in this CVI subject is responsible for the focal visual field deficit observed. There is evidence however that children with CVI can successfully undergo intensive rehabilitative training and recover a certain degree of visual function (Farrenkopf et al., Further, research is needed to fully understand how the developing brain reorganizes itself in relation to sensory and functional recovery and provide a neurological rationale for individually tailored rehabilitative strategies for these patients. Thus, fully characterizing the associations between underlying structural and functional changes with clinical assessments of visual dysfunction may ultimately help us understand how individuals develop, and adapt, in response to early damage to the visual system.Designed the study: LM and DS. Collected data: CB and LM. Interpretation and Analysis of data: all authors. Contributed to preparation of the manuscript: all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Oxford classification system was based on actual clinical data, international collaboration, and validation of the reproducibility of defining pathologic lesions. The strongest pathologic predictor of clinical outcome in IgA nephropathy is the extent of tubular atrophy and interstitial fibrosis.et al.\u00a0examined the effect of global glomerular sclerosis on a cohort of 136 IgAN patients from Isfahan, Iran. They showed a significant positive correlation between proportion of globally sclerotic glomeruli and serum creatinine, amount of proteinuria and also quantity of IF/TA  have been completely observed by the author.None."}
+{"text": "In many fields of biological sciences including embryology and cancer research, understanding of 3-dimensional structures is crucial to uncovering normal and pathological phenomena. While the most optimal method would be to directly observe the complete object without any destruction, staining and imaging of thick sections and whole mount samples can be challenging. For decades, researchers have serially sectioned large tissues stained each with chromogen-based immunohistological methods and painstakingly reconstructed the 3-dimensional volume. The limiting factor with immunohistological staining is the difficulty in detecting multiple antigens with different chromogens on the same tissue. At our Molecular Cytology Core Facility at Memorial Sloan-Kettering Cancer Center, we successfully and routinely perform immunofluorescent staining using automated staining machines and have combined IF staining and 3D reconstruction of serial sections. This method allows simultaneous detection of up to four different antigens on the same sections in a highly reproducible and specific manner. The resulting stack can be a stunning visualization of 3D structure and be quantitatively analyzed.Human tumor samples as well as embryonic and adult mouse tissues were embedded in paraffin and sectioned serially. The slides were immunofluorescently stained for multiple antigens in sequential manner using Ventana Discovery XT  autostainers. All slides were digitally scanned using Pannoramic FLASH (3DHistech) and autoaligned using Voloom (MicroDimensions) and/or AutoAligner (Bitplane). 3D visualization and analyses were performed using Imaris (Bitplane).By combining automated immunofluorescent staining and tried-and-true method of reconstructing adjacent sections, we were able to visualize, in detail, not only the geometric structures of the sample but also the presence and interactions of multiple proteins and molecules of interest within their 3-dimensional environment .Advances in technology and software algorithms have significantly sped up the entire process of 3D reconstruction of serial sections. The addition of automated, multiantigen, immunofluorescent staining will significantly broaden the range and complexity of scientific questions that can be answered with this methodology."}
+{"text": "Background: In popular media and on Internet, the neuropeptide oxytocin is often advertised as a miracle drug that cures all types of disorders, reduces stress, saves marriages, all conveniently with a nasal spray. Here we will present the effects of intranasal oxytocin on brain function in recently traumatized individuals and patients with posttraumatic stress disorder (PTSD) and discuss clinical implications and further research. PTSD is characterized by exaggerated fear responses to threat and trauma-related stimuli, reflected in altered neural salience processing and emotion regulation  to perform a series of functional neuroimaging studies on the effects of a single intranasal administration of the neuropeptide oxytocin on neural emotional and reward processing in PTSD patients versus healthy traumatized controls, and in recently traumatized individuals at high risk for PTSD due to high levels of distress acutely after trauma.These studies were based on literature showing that intranasal oxytocin impacted a variety of the behavioral, neural, and neuroendocrine dysregulations observed in PTSD patients and individuals vulnerable for PTSD. Thus, intranasal oxytocin appeared to be a promising candidate for PTSD prevention and augmentation of treatment response Olff, .Objective: We aimed to investigate the neurobiological mechanisms of fear  and reward processing underlying oxytocin's potential therapeutic effect for PTSD prevention and treatment. Regarding neural salience processing and emotion regulation, it had been found that oxytocin administration in healthy individuals dampened amygdala reactivity toward threat-related stimuli  emotional faces in both recently traumatized individuals with high levels of distress as well as highly traumatized individuals without psychopathology. Additionally, we found opposing effects of oxytocin administration on functional connectivity of the amygdala with brain areas involved in emotion regulation and salience processing between our study populations. In rest, male PTSD patients showed increased connectivity within the emotion regulation network after oxytocin, while female PTSD patients showed decreased connectivity within the salience network. In contrast, oxytocin administration resulted in decreased resting state connectivity within the emotion regulation network and increased connectivity within the salience network in recently traumatized individuals after exposure to trauma-related script-driven imagery. Regarding neural effects on reward sensitivity, oxytocin administration increased striatal responses to both reward and loss anticipation in PTSD patients and highly traumatized controls.Conclusions: Combined, our findings on the effects of oxytocin administration on neural salience processing and emotion regulation indicate that a single oxytocin administration has differential effects in (recently) traumatized individuals and PTSD patients. This is in line with more recent literature on differential effects of oxytocin administration depending on interpersonal differences and (the interpretation of) the salience of contextual cues , the Netherlands organization for Health Research and Development (grant no. 40-00812-98-10041) and the Academic Medical Center Research Council (110614).All authors declare that they have no biomedical financial interests and no potential conflicts of interest."}
+{"text": "Traumatic total brachial plexus injury (TTBPI) is a severe and disabling form of injury. Reconstructive modalities are complex and outcomes are variable. This is mainly because of the multitude of functions lost and relative scarcity of donor nerves to reconstruct these functions. As a result, there are several different opinions and ideologies on TTBPI.Several papers report the functional outcomes of nerve transfers and free muscle transfers (FMT). Only few papers report retrospectively on the quality of life recovery. There are no studies which compare pre and postoperative objective and subjective parameters of quality of life.We conducted a prospective comparative study of functional outcome and quality of life (QoL) measures of patients with TTBPI, before and after surgical treatment. The three current representative treatment modalities for elbow with/without finger function used were: double free muscle transfer (DFMT), single muscle transfer (SMT), and intercostal to musculocutaneous nerve transfers (NT).From 2002 to 2011, Eighty-one patients, who underwent reconstructive surgery consisting of double free muscle transfer (DFMT) in 47 patients, single muscle transfer (SMT) in 16 and intercostal to muscultocutaneous nerve transfers (NT) in 17, following nerve transfer for shoulder function, were evaluated for functional outcome and QoL assessment using the Disability of Arm, Shoulder and Hand (DASH) questionnaire, pre and post-operatively for more than 24 months to be compared among three groups.The mean shoulder abduction and flexion was comparable in all three groups, but external rotation was significantly better in the DFMT group. The range and quantitative power strength of elbow flexion were significantly larger in DFMT. Reasonable total active finger motion and power of hook grip was achieved in DFMT patients. DFMT group also showed a significant improvement in the DASH score. Amongst the 30 items of DASH, DFMT achieved superior improvement of the motor function items, but NT provided only improvement of social-mental items.DFMT provided superior functional outcome and QoL recovery as compared to NT and SMT in patients with TTBPI."}
+{"text": "The mature cerebral cortex harbors a heterogeneous population of glutamatergic neurons, organized into a highly intricate histological architecture. Classically, this mixed population of neurons was thought to be generated sequentially from a seemingly homogenous group of progenitors under the influence of external cues. This view, however, has been challenged in the last decade by evidences pointing to the existence of fate-restricted neuronal progenitors in the developing neocortex. Here, we review classical studies using cell transplantation, retroviral labeling and cell culture, as well as new data from genetic fate-mapping analysis, to discuss the lineage relationships between neocortical progenitors and subclasses of excitatory neurons. We also propose a temporal model to conciliate the existence of fate-restricted progenitors alongside multipotent progenitors in the neocortex. Finally, we discuss evidences for a critical period of plasticity among post mitotic excitatory cortical neurons when environmental influences could change neuronal cell fate. The mammalian cerebral cortex harbors a heterogeneous population of neurons, which has been classically divided into two major groups: spiny and smooth neurons  and multi-modal neurons . Physiological classes of cortical neurons can also be distinguished according to their electrical intrinsic properties  or BrdU. Later, the neuronal fate and laminar position of cells labeled with such molecules was determined by auto-radiography (TH3) or immunohistochemistry (BrdU).Cortical neurons in the mammalian cerebral cortex are generated in a limited period of development, varying from days to months depending on the species. In humans, cortical neurogenesis starts at gestational week (GW) 5 and finishes around GW20  ventricular zone (VZ) progenitors or radial glia cells (RGC); and (ii) subventricular zone (SVZ) or intermediate progenitors. VZ progenitors are the first cells in the developing telencephalon and generate SVZ progenitors and neurons  environmental cues are important to determine the laminar fate of glutamatergic neurons; (ii) specification occurs at the level of progenitors; (iii) early progenitors respond to late extrinsic signal, but not the contrary; and (iv) post mitotic neurons are specified according to the environment where they are generated and do not change layer identity when exposed to new extrinsic signals. More generally, these experiments are cited as evidence of restriction in the fate potential of progenitor cells over developmental age. However, the data are also consistent with the existence of multiple progenitors, but where early and late progenitors behave different in different environments such as the late environment is conductive for the survival and differentiation of late-stage progenitors, while only the early environment sustains early progenitors.+ neurons alongside neurons that do not label for other markers used. Since the panel of layer-markers available at the time to label subtypes of neurons was very restricted , data could be interpreted in at least two ways: (1) Progenitors for deep and upper layer neurons comprise two different populations; or (2) Single progenitors can generate deep and upper layer neurons, but the markers used could not reveal this phenomenon.Cell culture systems were also employed to study the potential of cortical progenitors to generate neurons and macroglial cells  to analyze the neuronal output from single RGCs (Gao et al., Collectively, the new findings are consistent with a model where neuronal subtype specification occurs in part already at the level of progenitor cells. Perhaps, the cortical VZ is a mosaic of progenitors with different fate potentials, where a multipotent progenitor gives rise to lineage restricted progenitors Figure . Of cour+ subcerebral projection neurons (D\u00edaz-Alonso et al., Indeed, there are compelling evidences for an additional degree of plasticity at the level of post mitotic neocortical projection neurons. Both connectivity and electrical properties of neocortical neurons are affected by manipulations of sensory inputs after the neocortical neurogenic interval (Van der Loos and Woolsey, According to the notion that post mitotic neocortical projection neurons are plastic, two inspiring studies have shown that forced expression of a single transcription factor can shift fates of early post mitotic neurons (De la Rossa et al., The temporal sequence for generation of neurons towards different cortical layers and/or lineages is also regulated by environmental cues. The neurotrophin Ntf3 acts as a feedback signal from post mitotic neurons to progenitors, promoting the generation of upper layer at the expense of deep layer neurons (Parthasarathy et al., de novo generation of deep layer neurons at the expense of upper layer neurons (Toma et al., Genetic ablation of deep layer neurons also affects the fate of cortical progenitors, inducing Generation of the large variety of neocortical spiny neurons starts at the level of progenitors in the neocortical VZ with the generation of at least two major classes of progenitors identified by expression or absence of Cux2. These progenitors are likely derived from a multipotent progenitor population and environmental cues may contribute for the establishment and balance of these populations.Specification programs are inherited by post mitotic neurons and contribute to the laminar organization of the neocortex. The role of environment in the specification of neocortical spiny neurons at a post mitotic level requires more investigation, but is a potential mechanism to further refine the neocortical cytoarchitecture.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Arthritis Research & Therapy.Rheumatoid arthritis (RA) is a systemic autoimmune disease manifesting in joint destruction. The recognized hallmark of RA pathogenesis is the involvement of immune cells which produce many mediators potentiating an inflammatory environment. RA synovial fibroblasts (RASFs) contribute significantly to disease progression by initiating and regulating many pathways of joint destruction. Detailed molecular insights into RASF biology may lead to identification of important therapeutic targets. The discovery of common molecular targets for joint resident and inflammatory cells may help to develop the most effective therapeutic strategy. One such pathway includes semaphorin 4A as reported in a recent article in  Arthritis Research & Therapy, Wang and colleagues [Rheumatoid arthritis synovial fibroblasts (RASFs) produce a variety of cytokines, chemokines, and matrix metalloproteinases (MMPs) which potentiate the effects of inflammatory and immune cells in rheumatoid arthritis (RA). In a recent article in lleagues  report nSema4A belongs to a family of glycoproteins that were originally found in the nervous system and that function as axon guidance molecules. The pioneering semaphorin immunology research by Kumanogoh and colleagues  identifiWang and colleagues  demonstrTaken together, the data presented by Wang and colleagues  pave the"}
+{"text": "Myriophyllum spicatum) invasions on lakefront property values of single-family homes in an urban-suburban landscape. Milfoil often forms dense canopies at the water surface, diminishing the value of ecosystem services  and necessitating expensive control and management efforts. We compare 1,258 lakeshore property sale transactions (1995\u20132006) in 17 lakes with milfoil and 24 un-invaded lakes in King County, Washington (USA). After accounting for structural , locational , and environmental characteristics  of lakes, we found that milfoil has a significant negative effect on property sales price , corresponding to a 19% decline in mean property values. The aggregate cost of milfoil invading one additional lake in the study area is, on average, $377,542 USD per year. Our study illustrates that invasive aquatic plants can significantly impact property values , justifying the need for management strategies that prevent and control invasions. We recommend coordinated efforts across Lake Management Districts to focus institutional support, funding, and outreach to prevent the introduction and spread of milfoil. This effort will limit opportunities for re-introduction from neighboring lakes and incentivize private landowners and natural resource agencies to commit time and funding to invasive species management.Economic evaluations of invasive species are essential for providing comprehensive assessments of the benefits and costs of publicly-funded management activities, yet many previous investigations have focused narrowly on expenditures to control spread and infestation. We use hedonic modeling to evaluate the economic effects of Eurasian milfoil ( Despite the long history of investigating the ecology of nonindigenous species Orconectes rusticus) into lakes in northern Wisconsin (USA) is estimated to generate damages of about $1.5 million USD annually to the panfish recreational fishery Dreissena polymorpha) cost an estimated $267 million USD in lost power generation and drinking water treatment facilities in Lake St. Clair (USA) during the first 15 years of infestation In freshwater environments, previous studies have largely focused on the economic impacts of invasive species on fisheries, power plants, water treatment facilities, and recreation Myriophyllum spicatum L., herein referred to milfoil) is an ideal study organism to enhance our knowledge regarding the economic effects of aquatic invasive species because extensive information is available on the ecology and management of this invasive plant Eurasian milfoil (Freshwater ecosystems are often severely impacted by milfoil invasion. Milfoil form dense canopies in the water column (extending to the water surface) altering water chemistry, displacing native plants, and creating habitats that are unsuitable for wildlife In this study we evaluate the potential economic impacts of aquatic invasive plants on lakefront properties, using Eurasian milfoil as an illustrative example. Such impacts are largely unexplored but see , yet are2) from 1995 to 2006 . This county has the highest population density in the state  and it is intersected (north-south) by the Interstate-5 highway, which serves as an invasion corridor for non-native plant species both in terms of high human populations (introduction via the aquarium trade) and movement of recreational boaters (introduction via entrainment on trailer boats). Lakes throughout King County are located along a distinct urban-rural land use gradient, and many have primary residences and support public recreation  to 2006 , prior tHP\u200a=\u200af, where HP represents home (property) price, S are structural characteristics , L are locational characteristics , and E are environmental characteristics .We used hedonic modeling to quantify the effect of milfoil invasions on lake property values. This technique has proven useful in estimating the economic value of nonmarket amenities, for example, the effect of water quality on the recreational and aesthetic value of freshwater resources and shoreline properties HP as a function of key property characteristics  to generate the value  consumers give to each characteristic. These estimated values were then used to evaluate the effect of milfoil presence on property value. A suite of independent variables  using the house price index (purchase only) from the US Federal Housing Finance Agency. Independent variables used in the analysis included structural characteristics , locational attributes  and environmental descriptors  .The choice of endogenous and instrumental variables is influenced by geography and the specific characteristics of the focal property market e.g., . Our varMilfoil presence was treated as an endogenous variable; a choice supported by Horsch and Lewis A series of regression models were developed and compared using the modified Akaike\u2019s Information Criterion for small samples (AICc). AICc is a model selection technique based on the trade-off between model accuracy and parsimony We estimated the aggregate cost of milfoil invading one additional small lake in our study area by discounting a homeowner\u2019s willingness to pay for a property on a lake free of milfoil by 5% , will the optimal economical management of invasive species be possible Similar economic damages have been reported in northern Wisconsin, where waterfront property values in a popular recreational and rural area declined by approximately 8% after milfoil invaded a lake The costs of preventing new invasions of aquatic weeds are often thought to be greater than the benefits, thus leading to inaction. Our study, however, indicates there are benefits to preventing the spread of milfoil given that the invasion of one additional study lake leads to a high aggregate cost of over $375 thousand USD annually. This aggregate cost represents a third of the amount spent annually ($1 million USD) on managing milfoil across Washington State Lakefront property owners stand to benefit greatly  from preventing milfoil invading their lake. In addition, it is necessary to engage recreational boaters in prevention efforts as well regardless whether or not they live on a lake, because they are an important dispersal vector of milfoil and other aquatic invasive species Property owners could also benefit from aquatic weed control. Zhang and Boyle A key component for long-term management of invasive species is the participation of multiple groups representing ecological and socio-economic perspectives sensuEconomic research on invasive species is essential for comprehensive assessments of the benefits and costs of management strategies aimed at increasing the effectiveness of publicly funded programs"}
+{"text": "The transition to farming is the process by which human groups switched from hunting and gathering wild resources to food production. Understanding how and to what extent the spreading of farming communities from the Near East had an impact on indigenous foraging populations in Europe has been the subject of lively debates for decades. Ethnographic and archaeological studies have shown that population replacement and admixture, trade, and long distance diffusion of cultural traits lead to detectable changes in symbolic codes expressed by associations of ornaments on the human body. Here we use personal ornaments to document changes in cultural geography during the Mesolithic-Neolithic transition. We submitted a binary matrix of 224 bead-types found at 212 European Mesolithic and 222 Early Neolithic stratigraphic units to a series of spatial and multivariate analyses. Our results reveal consistent diachronic and geographical trends in the use of personal ornaments during the Neolithisation. Adoption of novel bead-types combined with selective appropriation of old attires by incoming farmers is identified in Southern and Central Europe while cultural resistance leading to the nearly exclusive persistence of indigenous personal ornaments characterizes Northern Europe. We argue that this pattern reflects two distinct cultural trajectories with different potential for gene flow. The transition to farming represents a major shift in the history of mankind. It corresponds to the process by which human groups switched from hunting and gathering wild resources to a reliance on a system of food production based on domesticated plants and animals. In the Fertile Crescent, farming, herding and sedentism progressively took place 12,000 years (y) ago, and then spread across Europe from 8,800 until 5,500 y ago . IncreasIn their pioneer study, Newell et al. (1990) examined time and space diversity of personal ornaments produced by the post-glacial hunter-gatherers of Western Europe, and used ethnographic data and explicit sets of statistical analyses to identify the geography of Mesolithic social, ethnic and linguistic groups . VanhaerHere we use, for the first time, personal ornaments to comprehensively investigate cultural and population dynamics at work during transition to farming in Europe. Our analyses are aimed at documenting changes in cultural geography that occurred during the transition and identifying the mechanisms responsible for those changes in various regions of Europe.Such reconstruction is based on the first extensive record of personal ornaments recovered from well preserved stratigraphic units, assigned to distinct archaeological cultures, and spanning over three millennia, from the Early Mesolithic to the Final Early Neolithic . We submEach stratigraphic unit was assigned to one of the 48 European archaeological cultures defined in the literature according to lithic technology and ceramic production  an enduring cultural boundary exists between the North of Europe and the rest of the continent throughout the Mesolithic and the Neolithic, ii) a persistence of forager cultural attributes in Early Neolithic personal ornamentation, reflecting incorporation of Mesolithic cultural traits by emerging farming societies, is observed in the North of Europe, iii) the adoption of a large variety of novel bead types associated with a minor persistence of Mesolithic bead types characterizes Southern and Central Europe, iv) Early Neolithic geographic bead-types configuration is consistent with the two main roads of Neolithic diffusion in Europe proposed in the past on the basis of other cultural elements ,37 and gThe history of personal attires supports the view that the Neolithisation of Central and Southern Europe took place in the context of a profound reconfiguration of symbolic and social codes while that of Northern Europe was characterized by a marked persistence of those codes. Such a persistence is consistent with a scenario of cultural continuity between the last hunters and the first farmers in the North of Europe as evidenced by other categories of the material culture ,41. IdenOur results imply that reconstructions of the processes leading to the spread of production economies must not only consider the diffusion of novel techniques and know-how of food production but also the degree of cultural cohesiveness of local communities, which may have been more or less pervious to newcomers and their symbolic systems.Although bootstrap values are not high for the major clusters, the Neighbor-Joining analysis identifies a geographically and chronologically coherent tree . MesolitDi  and chronologically (DEN vs WEM) distinct archaeological sets. Instead, a lower R value , reflecting low cultural similarity, is observed when comparing MEN vs WEM. The smallest R value is observed between BEN and BM, suggesting strong similarities in the bead-types between the two sets of archaeological cultures.Results show highly significant  and significant  bead-type differentiation between geographically  between geographic and cultural distance between sites indicating that geography explains a small portion of the cultural variance. Pairs of spatially close sites will be more culturally similar than distant sites.The map of interpolated bead-type diversities throughout Europe, based on 48 archaeological cultures, shows a persistent sharp divide between bead-type associations from the Baltic area and those from Southern Europe during the Mesolithic and the beginning of the Neolithic . The higAnalysis of Mesolithic and Neolithic bead-type associations throughout Europe identified diachronic and geographical patterns in the use of personal ornaments. Our main findings can be summarized as follows: (1) bead-type diversity decreases northwards, (2) well-defined long-lasting geographic boundaries persist through time between the South and the North of Europe, (3) bead-type diversity and geographic distances are only slightly correlated; (4) the Mesolithic and Early Neolithic of Northern Europe show a clear continuity in bead-types while (5) a significant discontinuity is observed in Central and Southern Europe, (6) bead-type associations at the longitudinal extremes  are more similar than expected considering their geographic location.Littorina transgression , CLECOM, Check List of European Continental Mollusca  and the Paleobiology database for the fossil species .Taxonomic identifications given in the literature for marine and fresh water shells were updated and standardized using CLEMAM, Check List of European Marine Mollusca Database  and the excavation methods. Systematic sieving of the sediment with small mesh grids can for example significantly increase the number of small beads recovered . Since dPresence or absence of bead-types was coded as \u20181\u2019 or \u20180\u2019 respectively, to produce a matrix of 437 archaeological sites coded across 223 binary traits. Binary variables were rejected if bead-types were present at less than three sites.The presence/absence matrix was converted to a Dice distance matrix reflecting pairwise cultural distances between sites and archaeological cultures. The Dice distance is particularly appropriate for analyzing this cultural dataset because it stresses joint occurrences more than mismatches . The DicNa: Number of bead-types present in site aNb: Number of bead-types present in site bNab: Common bead-types between sites a and bDi is the proportion of total variability owing to differences between sites, and was calculated pairwise as a measure of bead-type divergence between sites.The parameter Geographic coordinates were used to calculate pairwise Euclidian geographical distance between archaeological sites.Di was entered into a Principal Coordinates Analysis (PCoA) performed in PAST software,  based oDi was also used in a \u2018Neighbor-net\u2019 analysis [Pairwise analysis  to deteranalysis .The isolation-by-geographic distance model predicts a positive relationship between increased cultural differentiation and geographic distance. To account for the effect of geographic distance on cultural diversity, correlation between cultural distance and geographic distance matrices was calculated using a Mantel test , performS1 Dataset(XLS)Click here for additional data file.S1 Text(PDF)Click here for additional data file."}
+{"text": "The last decade has seen the advent of a variety of novel biologic agents, which are now used widely across a range of the inflammatory rheumatic diseases. Normally introduced after the trial and failure of conventional disease modifying anti-rheumatic drugs (DMARDs) the biologic class of medicines has been a revolutionary in terms of the scope and depth of response now sought in treating rheumatic diseases. Those best characterized are TNFi, IL-6Ri, rituximab and abatacept, all of which bring about improvement in clinical signs and symptoms, and variously mitigate articular destruction and improve function. Application of drugs developed for other indications but now being tested in rheumatic diseases has raised interest in the possible value of agents such as ustekinumab (inhibiting IL-12/23), and several antibodies that block the biology of IL-17. The latter appear to exhibit especial benefits in the spondylo arthropathies and psoriatic variants of inflammatory arthropathy. Other studies targeting GM-CSF receptor have similarly shown benefit in early studies in rheumatoid arthritis. The long promised possibility that chemokines and their receptors would deliver benefit now has some tentative evidence for benefit. In this presentation I shall describe the successes and failures of recent biologic therapeutic studies in the rheumatic disease, and wider inflammatory arena, and from this draw inferences as to new emerging understanding of the molecular taxonomy of the inflammatory diseases.None declared."}
+{"text": "Mechanical forces are essential contributors to and unavoidable components of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development. The heart is the first functional organ to develop in the embryo, convecting nutrients to surrounding tissues to facilitate growth. As the embryo grows, the heart transforms from a linear valve-less tube to a multi-chambered structure complete with 4 fibrous valves , fuse at the ventral midline, to form the tubular heart   fiber interactions and cell adhesions are important early mechanical stimuli. Through fibronectin and mesodermal cell tracking, Zamir et al. showed that convective tissue motions contribute significantly to total cell displacement  stage 9 before myocyte contraction begins  and blood flow induced shear stress in EC development for zebrafish embryos  Figure  Damon e. Cell prCell morphologies have also been shown to contribute to the ballooning process of heart chambers. Ballooning involves the expansion and bulging of the linear walls of the looped heart tube into bean-shaped chambers, with a convex outer curvature and a concave inner curvature  and left atrial ligation (LAL). In CTB, a knot is tied around the conotruncus region of the OFT at HH18 in order to induce an outflow flow constriction  following LAL  form initially in the AV canal at HH16 (E9.5 in mouse), followed by the appearance of two mural/lateral cushions on the left and right side of the AV canal at HH19  and distal zones (just after a \u201cdogleg\u201d bend in the OFT) become cushions around HH22/E10, while the rest of the cardiac jelly regresses. The proximal/conal cushions are alternatively referred to as the septal/sinistroventral and parietal/dorsodextral ridges  and endothelial nitric oxide synthase (NOS-3) are shear stress responsive genes linked to cardiovascular development by knockout mice that display a wide range of cardiovascular defects (Yanagisawa et al., In vitro analyses suggest that TGF\u03b23 induces cell migration, invasion, and matrix condensation; BMP2 induces invasion; VEGFA inhibits invasion but increases migration (Tan et al., in vitro system, Tan et al. were able to show the flow-regulated development of the fibrous AV valves is dependent on rhoA expression (Tan et al., A number of studies have demonstrated the shear sensitivity of valvular morphogens The great vessels are derived from the pharyngeal arch arteries. A total of six arch pairs sequentially emerge, regress, or remodel throughout OFT development. While arch arteries I and II ultimately regress, the third arch pair forms the mature brachiocephalic arteries. The mature aortic arch is derived from the right fourth arch in chicken and the left fourth arch in mammalian embryos (Wang et al., Hemodynamic forces initiate extensive remodeling of the symmetric aortic arch system in a highly asymmetric fashion (Hu et al., The embryonic heart adapts ventricular geometry and function to optimize mechanical efficiency (Lin and Taber, BAV is the most common congenital anomaly of the heart, marked by two aortic valve leaflets rather than three. This two cusped configuration constrains the patient, as the free edges of the bicuspid valve are more straight than round and offer limited mobility. The leaflets are usually of unequal size with a raphe, or seam-like union, apparent in the larger leaflet (Yener et al., Recent advances in cardiac imaging, have allowed scientists to map these regions and collect 3D spatial visualizations of flow patterns over time (Bissell et al., HLHS is characterized by acute underdevelopment of the left ventricle. No strong genetic correlation exists. In a study of 83 HLHS patients, nine had underlying chromosomal abnormalities, four had single gene defects, 10 had one or more extracardiac anomaly and two were patients of insulin-dependent mothers (Natowicz et al., In vitro 3D culture and bioreactor studies work to further our understanding of how specific mechanical forces influence multi-scale biological responses. As our insight into CHD etiology improves, so will our ability to effectively and targetedly restore proper remodeling of cardiac tissues.Mechanical forces are essential drivers of cardiac morphogenesis, transforming the linear heart tube into a multichambered unidirectional machine capable of adapting to environmental demands. CHDs arise when the heart is prevented from following the normal pathways of development; understanding the intricate mechanisms involved in heart development is necessary for the advancement of clinical solutions. The majority of CHDs result from improper positioning of the cardiac OFT, impaired remodeling of the cushions into valve leaflets, or abnormal remodeling of the arches into great vessels. Quantitative imaging modalities provide a gateway into elucidating CHD formation. Integrating these imaging modalities with CFD and growth modeling will greatly strengthen our inference of causative mechanical forces of CHDs, such as BAV and HLHS. Targeted surgical techniques, including laser ablation, can help scientists distinguish between the effects of flow and tissue deformation alone. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Triatoma infestans. The Guatemalan project revealed close links between house infestation by rodents and Triatoma dimidiata, and vector infection with Trypanosoma cruzi. A novel community-operated rodent control program significantly reduced rodent infestation and bug infection. In Mexico, large-scale implementation of window screens translated into promising reductions in domestic infestation. A multi-pronged approach including community mobilisation and empowerment, intersectoral cooperation and adhesion to integrated vector management principles may be the key to sustainable vector and disease control in the affected regions.This article provides an overview of three research projects which designed and implemented innovative interventions for Chagas disease vector control in Bolivia, Guatemala and Mexico. The research initiative was based on sound principles of community-based ecosystem management , integrated vector management, and interdisciplinary analysis. The initial situational analysis achieved a better understanding of ecological, biological and social determinants of domestic infestation. The key factors identified included: housing quality; type of peridomestic habitats; presence and abundance of domestic dogs, chickens and synanthropic rodents; proximity to public lights; location in the periphery of the village. In Bolivia, plastering of mud walls with appropriate local materials and regular cleaning of beds and of clothes next to the walls, substantially decreased domestic infestation and abundance of the insect vector  However, a much longer list of sylvatic triatomine species may also infest peridomestic structures and eventually establish domestic colonies, contact humans and transmit T. cruzi. These species are hard to control by classical strategies and include Triatoma brasiliensis in northeastern Brazil;4Rhodnius pallescens in Central America;5 and Rhodnius ecuadoriensis in Ecuador and northern Peru,6 among others. Yet another group of triatomine species may be in the process of adapting to domestic habitats, pushed by large-scale changes in land use.Of the approximately 140 species of triatomine bugs identified, only a handful has adapted to live in houses and blood-feed on humans and domestic animals.T. cruzi infection has relied almost exclusively on residual insecticide spraying campaigns conducted by vertically-structured vector control programs starting in the late 1940s. The only two drugs available for treatment since the early 1970s were until recently restricted to the acute or recent stage of infection.7 A series of intergovernmental initiatives created in the 1990s coordinated vector control efforts at regional levels and substantially reduced house infestation indices and disease incidence in several countries of South and Central America.8 Progress was uneven, and what was effective in some areas  had lower impact elsewhere, such as in the case of T. infestans in the Gran Chaco region of Argentina, Bolivia and Paraguay.10 For R. prolixus in South America,12T. dimidiata in Central America and Mexico,8 and T. brasiliensis,4 the goal of vector elimination is not feasible and control programs have to grapple with the recurrent nature of house invasion and recolonisation, vector surveillance and insecticide treatment.In the absence of vaccines, the primary prevention of human 9 in a context of unstable developing economies and sociopolitical situations. This problem was further compounded with the low political priority assigned to Chagas disease by many of the affected countries. In the absence of permanent vector suppression, the question of how to sustain the open-ended vector surveillance phase still is unresolved.Centralized vertical control programs are ill-equipped to deal with these recurrent tasks, especially in resource-constrained rural areas with low-density, dispersed human populations that are difficult to access, resulting in high operating costs. Furthermore, the operational capacity of most Chagas disease vector control programs has been seriously compromised by the health care reforms  started in the early 1980s,13 Rural housing programs and other environmental management measures14 were rarely considered part of an integrated Chagas disease control strategy and reliance on insecticides has stayed approximately the same since they first came into use more than 60 years ago.Failure to achieve the stated program goals of vector elimination led to 1) the search for more sustainable, integrated control strategies that address ecological and social determinants of parasite transmission; 2) more emphasis on participatory frameworks and intersectoral cooperation (to ensure sustainability); 3) the application of integrated vector management (IVM) principles .15 in 2007 the Special Programme for Research and Training in Tropical Diseases (TDR/WHO) and the Ecosystem and Human Health Program of Canada's International Development Research Centre (IDRC) launched a research and capacity building partnership named \u2018Innovative community-based ecosystem management interventions for improved dengue and Chagas disease prevention in Latin America.\u2019 This initiative aimed to improve dengue and Chagas disease vector control through innovative interventions based on sound principles of community-based ecosystem management ,16 IVM13 and interdisciplinary analysis. The initiative's goals were to achieve a better understanding of ecological, biological and social  determinants of vector abundance and parasite transmission,17 and to develop, implement and evaluate intersectoral, community-centred interventions directed at reducing transmission risks.Building upon a multi-country research initiative for targeted dengue vector interventions in Asia,20 We briefly review the characteristics of study sites and methods, describe the main results obtained before implementing carefully designed control interventions and assess the initial impacts of these interventions in search of common patterns. This cross-site comparison is intended to bring together the main outcomes of the three projects and their repercussions for Chagas disease vector control beyond the specificities of each site and vector species implicated.Here we provide an overview of the three research projects on Chagas disease vector control interventions whose results are published in this issue.T. cruzi in domestic and peridomestic habitats  with common objectives: 1) To assess three key ecosystem dimensions affecting the presence and abundance of Chagas disease vectors in human dwellings and their interactions: vector biology/ecology and related environmental factors; the social, cultural, economic and community context; vector control program organisation and functioning; 2) To analyse the relative importance of eco-bio-social factors associated with different levels of vector presence and abundance; 3) Based on the situational analysis, to identify and design specific interventions appropriate to the domestic and peridomestic environments through a community-based, participatory process. Consideration of the specificities of each study site and triatomine species led to a range of interventions and their combinations. Phase II included three objectives: 1) to implement and monitor the designed interventions; 2) to evaluate their effectiveness; 3) to recommend community-centred intersectoral ecosystem intervention approaches.20The research teams used the outcomes of the situational analysis to design specific intervention packages tailored to each system through a participatory process involving multiple stakeholders and the affected communities Table\u00a0. Their c22 The package integrated the following: 1) educational workshops; 2) improved insecticide spraying procedures with full coverage of tiled roofs and walls; 3) participatory training workshops and implementation of rodent control activities; 4) multisectoral training in organic waste management and productive household activities; 5) a participant-based reflective process.19In Guatemala, the intervention package was based on the PRECEDE-PROCEED model for situational analysis, implementation and intervention evaluation.18 The goals were to eliminate refuges for bugs in the walls through plastering the surface with appropriate local materials; to promote house cleaning activities directed at beds and objects next to the walls; to remove chickens and dogs from human sleeping quarters, over a 6-month period.18 To promote community participation the research team used a multi-pronged strategy based on interpersonal communication, community mobilization, lobbying at community and regional levels, and supported advertising.In Bolivia, the intervention package included low-cost housing improvement techniques and community participation in two intervention versus two control villages.21 proposed the installation of window screens as a barrier against triatomine bugs in two intervention communities, and implemented the interventions in more than 800 houses.20 Education workshops addressing management and cleaning of chicken coops were also implemented in one of the villages.In Yucatan (Mexico), the research team conducted a series of meetings with multiple stakeholders to review the main findings of phase I,20 and end-point assessments were planned for late 2014.The main outcomes measured included the degrees of acceptance, support and community participation throughout the intervention process. Control and intervention groups were compared in terms of domestic infestation indices at baseline, in a midterm evaluation and at the end point. Measurement of knowledge, attitudes and practices regarding Chagas disease, risk factors and related issues were conducted at set time points. The impacts of interventions were assessed initially within six months of finishing their implementation,T. cruzi in the three study sites ,22 and one in which house invasion is seasonal and domestic colonization appears to be transient with occasional human-vector contact .21 Baseline domestic infestation levels ranged from 14.9% (46/308) in the Mexican Yucatan region to 95% (76/80) in the Bolivian Chaco region, as determined by different methods, and in most cases are expected to underestimate the actual infestation.23 House infestations in Bolivia and Guatemala  implied that there were established vector colonies in domestic and peridomestic habitats, whereas \u2018domestic infestation\u2019 in Yucatan actually represented transient infestations or house invasions detected by householders and notified to the local health post. Householders' bug collections are appropriate for continued domestic vector surveillance and corroborated that in Yucatan, house invasion was seasonal and stable across years.21The research projects covered two different model systems of house infestation by triatomine bugs: one in which there is stable domestic and peridomestic colonization  residual spraying with insecticides whereas full-coverage of domestic and peridomestic sites is recommended for T. infestans.The three study locations were rural and differed in house density, infrastructure, degree of remoteness, resource constraints and history of insecticide spraying. Housing quality in Yucatan was substantially better (owing to extensive housing development plans during recent decades) than in Bolivia and Guatemala, households were much less isolated and poverty levels were apparently lower. For example, Teya in Yucatan had street signs and public lights. Conversely, rural villages in Bolivia were very poor, especially in the Chaco region. The Bolivian and Guatemalan studies produced strong evidence of vector-borne transmission of 22 These results confirm previous findings that housing design and construction materials combined with their degree of maintenance affect the susceptibility of a house to bug invasion and subsequent development of domestic bug colonies.28 More specifically, the surface structure of indoor walls and the occurrence of thatched roofs were significant predictors of domestic infestation and abundance for the four major domestic vectors of T. cruzi elsewhere.32The initial situational analysis provided a deeper understanding of the study systems, guided the design and successful implementation of control interventions in community-centred efforts and gained support from several stakeholders. The key factors explaining variations in domestic bug infestation across study sites may be grouped according to housing quality, availability of animal hosts and location effects. Housing quality affected the availability of refuges for bugs in human sleeping quarters  and in peridomestic habitats .T. dimidiata which displays singular camouflage behaviour with dirt, unlike other triatomines.33 In the past, however, the predicted effects of earthen floors were not always supported by multivariate analyses of relatively large numbers of houses.34 Using a multi-model inference frame and an extensive database, the Guatemalan study documented that earthen floors and wall plaster condition were of high relative importance for domestic infestation.22 The Bolivian project emphasized the role of bags, objects on the walls and beds as important refuges for T. infestans.18 Beds were also a prime bug habitat in the Argentine Chaco:25 bugs from beds have immediate access to a human blood meal and are frequently infected with T. cruzi. Regular cleaning of beds and removing objects and clothes from the walls were therefore predicted to substantially decrease domestic infestation and bug abundance in the Bolivian study sites. The midterm assessment of intervention effects demonstrated substantial impacts on both outcome measures overall and in the specific bug habitats, especially in the Chaco region of Bolivia.18However, the specificities of how housing quality affects domestic infestation vary between settings and triatomine bug species. Earthen floors are highly important for T. dimidiata in Yucatan,35 the large-scale situational analysis corroborated these results and provided another entry point for intervention.21 The intervention package addressed the concerns of the affected communities and stakeholders and gained their full support. It was successfully implemented at a village-wide scale and showed promising reductions in domestic infestation by T. dimidiata.20 The planned end-point assessment will take into account seasonal effects on house invasion and provide concluding evidence on intervention impacts.Following a pilot trial showing that window screens greatly reduced house invasion by 27 and poorly-built goat or pig corrals36 with many refuges and hosts were productive sources of T. infestans and other triatomines in the Argentine Chaco before and after residual insecticide spraying. These habitats provide better conditions and resources for the triatomine bugs than sylvatic habitats where the local hosts may not be available throughout the year. Improvement of goat corrals37 and other peridomestic structures38 may therefore reduce local infestations and contribute both to integrated vector control and enhanced livestock or poultry production, because high-density triatomine colonies also cause significant blood loss and anaemia. Implementing these environmental management measures indispensably requires the participation of householders and rural development agencies.The three studies highlighted the relevance of peridomestic structures as breeding or resting sites and sources of the triatomines that invade human sleeping quarters despite the fact that the study settings were notably different. Chicken coops or nestsT. dimidiata depending on other unidentified factors.35 Cleaning peridomiciles may both reduce peridomestic bug habitats and (peri)domestic infestation, as observed in Costa Rica,38 but it may also facilitate the invasion of domestic premises by sylvatic triatomines that are no longer deflected by suitable peridomestic sites. In line with these findings, elsewhere in Guatemala the plastering of walls combined with insecticide spraying modified substantially the relative abundance of domestic and peridomestic T. dimidiata compared with insecticide spraying alone: reduction in the abundance of domestic refuges was followed by a decrease in the abundance of domestic bugs and an increase of peridomestic bugs.28 These results highlight the need for integrated environmental management of domestic and peridomestic habitats.The Yucatan project suggests that regular clean-up of peridomestic areas may have mixed effects on domestic infestation by 27 Blood meal identification tests also demonstrated that chickens, dogs and humans are major hosts of domestic and peridomestic T. dimidiata and T. infestans in the study areas and elsewhere.40 The frequent practice of keeping chickens indoors for protection in rural areas with a subsistence economy notoriously resists change,18 and so does the habit of letting domestic dogs wander freely and share domestic premises with house-dwellers in poverty-stricken regions. These challenges still need to be addressed effectively.Host availability includes the presence or abundance of domestic and synanthropic hosts as blood meal sources. The key roles of chickens and dogs in the domestic ecology of Chagas disease vectors have been corroborated across multiple settings and triatomine species.T. cruzi, combined with the strong association between T. dimidiata and rodent infestations, are novel findings with clear implications for the design of innovative, integrated vector control strategies. Although synanthropic rodents were infected by T. cruzi in various settings,42 their role as (peri)domestic reservoir hosts and the effects of rodent control measures on bug infestation and parasite transmission had not been assessed. The Guatemalan project corroborated large house infestation rates with rodents,31 and revealed strong links between rats and mice in walls and tiled roofs, infestation with T. dimidiata and T. cruzi infection.22 These results paved the way for a novel community-based rodent control program that received immediate acceptance and was fully implemented by the affected communities. The endpoint assessment showed significant reductions in rodent infestation or abundance and in the prevalence of T. cruzi infection among early-stage nymphs.19 It remains to be seen whether reducing the abundance of rodents will decrease house infestation with T. dimidiata and bug infection over time, and how this may impact on human-vector contact rates. If rodent numbers have an additive effect on bug population growth and infection, as domestic dogs do in northern Argentina,43 the risk of bug infection is predicted to decline with effective rodent control, as the impact assessment suggests. However, the direct effects of reducing the abundance of rodents on domestic bug infestation may not be obvious in the presence of several other domestic hosts  to which the bugs may shift. Furthermore, sylvatic T. dimidiata may still invade the premises and confound the relationship between domestic bug infestation or infection and rodents.The additional contribution of house mice and rats to domestic bug infection with T. dimidiata were identified in Yucatan, where proximity to the periphery of the village apparently favoured house invasion from the surrounding sylvatic habitats.21 These results are consistent with other risk factor analyses of (peri)domestic infestation by Triatoma pallidipennis and R. prolixus, which showed that the spatial characteristics of residences or their distance to specific vegetation harbouring bug colonies need to be considered more closely.44Spatial risk factors for domestic infestation by 45 and household insecticide use.27 Because of the close links between domestic triatomines and humans as main blood meal sources,46 the absence of statistically significant effects of household size on domestic infestation needs to be interpreted with caution.Other risk factors usually associated with domestic triatomine infestations were found to be relatively not as important as in many other studies, including the number of people resident in the household47 combined measures of bug abundance and infection at well-defined habitats; domestic host infection10) is needed to translate reductions in house infestation into transmission risks and human infection. Improved estimates of local bug abundance (rather than presence/absence estimates) are needed for assessing habitat suitability and transmission risks. Knowledge on the key sources of triatomine bugs in domestic, peridomestic and sylvatic habitats and their relative habitat suitability may be used for targeted vector control and risk stratification,48 as with R. prolixus and Attalea butyracea palm trees in Venezuela.12 The combined use of site-specific timed manual searches and bug sensing devices for continuous monitoring of infestations may give valuable information on the different demographic processes involved in house (re)infestation. The frequent finding of peridomestic colonies of T. dimidiata49 suggests that IVM (including modification of key peridomestic habitats combined with carefully administered peridomestic insecticide sprays) may be justified in areas with recurrent domestic infestation and transmission risks. More investigations including the social determinants of health, house infestation and domestic transmission of T. cruzi are needed.50Future efforts to identify relevant risk factors for house infestation may take advantage of current results and explore further avenues. Measuring the impact of control interventions on additional response variables  and may also help prevent dengue in Yucatan,The three projects identified quasi-stable determinants of domestic infestation that most likely underlie the recurrent nature of house recolonisation by triatomine bugs. Improving the quality of rural housing and living conditions results in healthier homes with direct repercussions on community health beyond Chagas disease. Partnering with stakeholders working on other diseases or disciplines may help address problems that have similar causes. A multi-pronged approach including community mobilisation and empowerment, intersectoral cooperation and adhesion to IVM principles may be the key to sustainable vector and disease control in the affected regions."}
+{"text": "Blood proteins at the neurovascular unit (NVU) are emerging as important molecular determinants of communication between the brain and the immune system. Over the past two decades, roles for the plasminogen activation (PA)/plasmin system in fibrinolysis have been extended from peripheral dissolution of blood clots to the regulation of central nervous system (CNS) functions in physiology and disease. In this review, we discuss how fibrin and its proteolytic degradation affect neuroinflammatory, degenerative and repair processes. In particular, we focus on novel functions of fibrin\u2014the final product of the coagulation cascade and the main substrate of plasmin\u2014in the activation of immune responses and trafficking of immune cells into the brain. We also comment on the suitability of the coagulation and fibrinolytic systems as potential biomarkers and drug targets in diseases, such as multiple sclerosis (MS), Alzheimer\u2019s disease (AD) and stroke. Studying coagulation and fibrinolysis as major molecular pathways that regulate cellular functions at the NVU has the potential to lead to the development of novel strategies for the detection and treatment of neurologic diseases. The plasminogen activation (PA) system is an enzymatic cascade with key regulatory functions in fibrinolysis and degradation of extracellular matrix proteins  in the PA system are highlighted by studies showing that fibrin acts: (1) as a main substrate of plasmin during fibrinolysis; (2) as a feed-back regulator of PA by binding tPA/PAI-1 or Plg directly; and (3) as a signaling molecule for cell activation in the CNS. By highlighting the PA system as a molecular link between coagulation, fibrinolysis and inflammation, this review will focus on cellular mechanisms and molecular signaling pathways driven by fibrin deposition and fibrinolysis in the CNS, specifically at the neurovascular unit (NVU).Under healthy conditions, plasma proteins like fibrinogen and Plg are not found in the brain parenchyma\u2014a relatively immune-priviledged environment sealed by the selectively permeable blood-brain-barrier (BBB). Activation of the Plg system in the CNS parenchyma occurs in response to BBB disruption in which components from the blood enter the brain milieu Figure . The BBBBBB opening can result from tight junction (TJ) complex disassembly or downregulation, increased transcellular transport, or physical damage to the blood vessel  were identified as direct activation pathways of innate immune response  in fibrin-induced macrophage activation  and tPA/plasmin can be potent modulators of neuroinflammation.Emerging evidence suggests a pivotal role of fibrin in the regulation of CNS innate and adaptive immune responses  and neural dysfunction  plaques and intracellular neurofibrillary tangles of tau protein  signaling in astrocytes  are commonly used as biomarkers to assess the severity of trauma after injury, in sepsis, or myocardial infract. Components of the coagulation cascade and FDPs have been detected in MS patients (Aksungar et al., Several FDA-approved drugs target different aspects of the coagulation cascade leading to reduced fibrin formation. Although new generation anticoagulants have reduced hemorrhagic effects, target-based drug design would be preferable to selectively inhibit the pathogenic effects of coagulation in the CNS. Indeed, pharmacologic inhibition of fibrin interactions with CD11b/CD18 using a fibrin peptide suppressed EAE pathology without adverse effects in blood clotting (Adams et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The dorsal raphe nucleus (DRN), representing the main source of brain\u2019s serotonin, is implicated in the pathophysiology and therapeutics of several mental disorders that can be debilitating and life-long including depression, anxiety and autism. The activity of DRN neurons is precisely regulated, both phasically and tonically, by excitatory glutamate and inhibitory GABAergic axons arising from extra-raphe areas as well as from local sources within the nucleus. Changes in serotonin neurotransmission associated with pathophysiology may be encoded by alterations within this network of regulatory afferents. However, the complex organization of the DRN circuitry remains still poorly understood. Using a recently developed high-resolution immunofluorescence technique called array tomography (AT) we quantitatively analyzed the relative contribution of different populations of glutamate axons originating from different brain regions to the excitatory drive of the DRN. Additionally, we examined the presence of GABA axons within the DRN and their possible association with glutamate axons. In this review, we summarize our findings on the architecture of the rodent DRN synaptic neuropil using high-resolution neuroanatomy, and discuss possible functional implications for the nucleus. Understanding of the synaptic architecture of neural circuits at high resolution will pave the way to understand how neural structure and function may be perturbed in pathological states. The dorsal raphe nucleus (DRN) comprises the majority of cells in the brain with the capacity of synthetizing the neurotransmitter serotonin   to explore the organization of the DRN synaptic neuropil  were spatially related to GABA boutons, and among them relationships between GABA and VGLUT2-containing boutons were the most abundant Figures . This inin vitro electrophysiological recordings. Indeed, we found opposite modulation of DRN glutamate synaptic transmission by GABA-A and GABA-B receptors. Specifically, GABA-A receptor activation facilitated glutamate release while GABA-B receptors on the contrary mediated an inhibitory effect (Soiza-Reilly et al., Complementary ultrastructural studies using immuno-electron microscopy for GAD2 in the DRN showed the presence of GABA axon boutons in close apposition to unlabeled axons with the morphology compatible with glutamatergic axon boutons (Soiza-Reilly et al., Synaptic triads involving GABA and glutamate axons could at least partially explain previous pharmacological studies suggesting the interaction of these neurotransmitter systems to modulate 5-HT release (Tao and Auerbach, From a GABA system perspective, only a proportion of GABA axon boutons were implicated in axo-axonic arrangements with glutamate axons. This raises the question of whether these GABA boutons arise from a particular subpopulation of GABAergic neurons located within or outside the DRN. Further studies combining the use of axonal tract-tracing with AT will give further insights into the selective role of GABAergic neurons in the presynaptic modulation of glutamate transmission in the DRN.The complete view of molecular and fine structural features of DRN synaptic circuits represents a stepping stone towards understanding of their role in normal and pathological neurotransmission, as well as if alterations in the structure of circuits could contribute to the pathophysiology of mental diseases. For this purpose, the use of recently developed high-throughput imaging techniques like AT has opened new avenues to characterize and better understand synaptic aspects of human neuropathology (Koffie et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Throughout evolution, plants and pathogenic fungi have been in a constant battle where fungi have developed new mechanisms to infect plants while plants have co-evolved to combat the infection. The early stages of plant-pathogen interactions occur in the intercellular spaces of the plant tissue and thus involve a myriad of secreted factors. Traditionally, all proteins released into the extracellular space were thought to be transported via the ER-Golgi dependent classical secretory pathway. However, non-classical secretion of proteins/RNA through extracellular vesicles (EVs) has recently been reported to contribute to the milieu of extracellular molecules that mediate plant-fungal interactions   proteins, many of which inhibit fungal growth or directly kill fungal cells  leaves. Though the detection of plant MVBs at the site of infection provides indirect evidence of their role in plant defense , paramural space, and extrahaustorial matrix. In addition, vesicle budding and fusion of MVB-like structures with the fungal plasma membrane has been observed in this interaction, although the microscopic evidence did not reveal whether the vesicles were derived from the plant or the fungus  and heat shock proteins (Hsp60 and Hsp70) which may have an essential role in the fungal defense mechanism (Albuquerque et al., Alternaria infectoria. Several species of this genus Alternaria are also considered major plant pathogens (Silva et al., MVBs were first reported in the appressoria and haustoria of the powdery mildew fungus s Hippe, . More reBiochemical analyses of EVs from various human fungal pathogens has revealed the presence of a variety of lipids, proteins and RNA (Peres Da Silva et al., H. capsulatum. Similarly, S. cerevisiae secreted more than 20 proteins implicated in cell wall assembly including glucanases and glucanosyl transferases (Oliveira et al., Neurospora crassa (Riquelme et al., Finally, cell wall remodeling is a key process on both sides of the plant-fungus interaction (Bellincampi et al., Recent findings pertaining to the role of EVs in the interaction between fungal pathogens and humans have led us to ask whether EVs also have a major role in plant pathogen interactions. It is still unknown how effectors and defense molecules are packaged and transported across the plasma membranes and cell walls of the plant and fungal cells. We propose that proteins lacking secretion signals could be packaged into EVs for passage through the plasma membrane and the cell wall Figure . AlternaThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Secondary cell walls (SCWs) comprise the main portion of plant biomass and represent an abundant renewable resource of polysaccharides for conversion into sugars and subsequent fermentation to liquid biofuels. An upswing in lignocellulosic biomass-derived biofuels, including from grass and woody energy crops and agricultural residues, offers significant environmental and socio-economic benefits over the use of dwindling and polluting non-renewable fossil fuels. A key challenge for realizing commercial biofuel production resides in the economically unfeasible sugar yields after enzymatic hydrolysis of lignocellulosic biomass. This low saccharification efficiency is caused by the recalcitrant nature of the cell wall owing to the crystallinity of cellulose and interactions between the polysaccharides and lignin polymers within the cell wall matrix (Himmel et al., Arabidopsis (Handakumbura and Hazen, Arabidopsis. Their innovative strategy to identify transcriptional regulators involved the exploitation of several Arabidopsis SCW-related transcriptome datasets combined with in silico expression and histology-based phenotyping screens. Since lignin is commonly acknowledged to inhibit biomass digestibility, their systematic approach proved useful as six T-DNA lines from candidate TFs revealed altered lignin deposition profiles; including hyper- and hypo-lignification as well as ectopic lignin deposition (Cassan-Wang et al., Research efforts have revealed an extensive, complex and hierarchical regulatory network of SCW-related TFs predominantly comprising NAC and MYB family members in The list of potential SCW-related TFs identified by Cassan-Wang et al.  highlighhb5 line and earlier flowering in the hypolignified blh6 and zinc finger lines. This corroborates previous reports that some TFs of the SCW thickening and xylem formation program are coupled with the flowering induction program (Melzer et al., Although TFs provide attractive targets for altering complex cell wall traits, the intricacy of regulatory networks and their integration with different metabolic and signaling pathways, means that changing the levels of a certain TF can result in pleiotropic effects. In accordance, Cassan-Wang et al.  observedArabidopsis should therefore provide compatible tools for the engineering of woody and grass energy crops alike. Indeed, researchers developing switchgrass as a dedicated bioenergy feedstock have exploited this apparent conservation; over-expression of the MYB TF PvMYB4, an orthologue of Arabidopsis AtMYB4, results in repression of genes involved in lignin biosynthesis, leading to reduced cell wall recalcitrance and a more than doubling of the bioethanol yield (Shen et al., Arabidopsis to tailor the biochemistry of SCWs in lignocellulosic feedstocks for improved performance. An important consideration is the trade-off between reduced cell wall recalcitrance and biomass yield, often encountered in genetic engineering efforts aimed at modifying SCWs. New synthetic biology approaches may alleviate such growth penalties. This is illustrated by a study in which SCW biosynthesis and TF genes were used to re-program the spatial deposition patterns of lignin and polysaccharides in Arabidopsis, doubling the sugar yields after mild pre-treatment and enzymatic hydrolysis without affecting plant growth (Yang et al., As eudicots and monocot grasses exhibit differences in cell wall composition and architecture as well as morphological and anatomical distinctions Vogel, , one couKnowledge of the TFs involved in SCW formation can also be exploited for breeding of cultivars with improved cell wall characteristics. Several QTLs for lignin- and saccharification-related traits in maize and sorghum have been shown to co-localize with TFs that regulate SCW biosynthesis (Barriere et al., Arabidopsis SCW formation, providing a solid platform for more detailed functional analysis. The emerging picture is that of an increasingly complex regulatory network underlying SCW formation. Fitting together the pieces of the transcriptional puzzle will be challenging but the process will provide us with essential knowledge and tools to re-program and improve cell wall related traits.In summary, Cassan-Wang et al.  have higThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Having visited many health care facilities in some countries of sub-Sahara African region, I have come to notice that alongside often insurmountable difficulties by health personnel per se such as water supply or electricity supply lay an important rather more surmountable problem of health care waste (HCW) management. In 2002, WHO assessment in 22 developing countries showed that 18-64% of Health care facilities do not use proper waste disposal methods [I noticed in approximate same conditions that some reference hospitals either in the same country or between countries were performing better than others and I suspected some hypothetical reasons: The overall performance of the managing board; The overall concern of health workers about public health issues; The poor motivation to care about public goods as compare to private ones; The socio-economic standards of the catchment area of the health care facility; The number of Non Governmental Organisations working on health performing in the catchment area of the health care facility.The concern about biomedical waste management was seriously considered by WHO in 2000 and grounds for good management laid down , but ove"}
+{"text": "In the era of rising prevalence of serious infections caused by multidrug-resistant (MDR) organisms and the paucity of in-flow of newer antimicrobial agents, the relatively older antibiotics that had been left out of clinical practice for various reasons are now being increasingly considered as the potential agents to combat such infections. Fosfomycin, known for almost four decades, has a broad spectrum of activity against several Gram-negative and Gram-positive bacteria.in vitro sensitivity of fosfomycin against isolates identified from various clinical specimens from different parts of Kolkata. After confirming the identity and antibiogram by Microscan Autoscan 4, the isolates were tested for fosfomycin sensitivity by the Epsilometer test. MIC values were interpreted in accordance with the currently recommended Clinical and Laboratory Standards Institute (CLSI) criteria for urinary tract isolates of Escherichia coli and Enterococcus faecalis and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria for Enterobacteriaceae and Staphylococcus aureus.This study, conducted in the Microbiology Department of Medica Superspecialty Hospital between July and November 2014, was aimed at testing the in vitro susceptibility against 90%, but only 64% against MDR strains. Among the MDR organisms nearly 78% of E. coli and 70% of Klebsiella spp. and 40% of MRSA isolates showed provisional MICs in the sensitive range while among the sensitive strains fosfomycin showed around 92% susceptibility. Our study results were comparable with the results obtained from an Indian study published from CMC Vellore in 2013 showing a fosfomycin susceptibility of around 75% among MDR uropathogenic E. coli.Out of the 1,895 isolates tested, fosfomycin displayed an overall Being a broad-spectrum bactericidal agent usable both orally and parenterally with low toxicity profiles and lesser prevalence of cross-resistance with other antimicrobials, fosfomycin can be an alternative to other broad-spectrum agents to treat uncomplicated infections as well as in the case of infections with MDR organisms where treatment options are very few. This study possibly reveals a much-needed solution for the rising carbapenem resistance and also for the treatment of infections with such MDR pathogens, thereby bringing down the length of stay in hospital, cost of therapy and suffering on the part of the patients."}
+{"text": "Kisspeptin (KISS) is the most potent stimulator of LH release and it has been recently demonstrated to also stimulate PRL release. There are two KISS neuronal populations in the rodent brain, located in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC). The ARC population coexpress kisspeptin, neurokinin B and dynorphin and are called KNDy neurons.In females, ovulation is coordinated by a complex set of interactions between the hypothalamus, the anterior pituitary and the gonads. Luteinizing hormone (LH) and prolactin (PRL) are pituitary hormones that have complementary roles in reproduction. There is a surge of both hormones prior to ovulation that is essential for adequate reproduction and can be mimicked by estradiol E2) treatment in ovariectomized (OVX) rats , [2]. Bo treatmenWe have developed a reduced model for kisspeptin control of PRL and LH secretion in animals without (OVX) and with E2 treatment (OVXE), based on experimental data and literature describing the roles of the two kisspeptin subpopulations (KNDy and AVPV) in PRL and LH secretion Fig . Without"}
+{"text": "EURORDIS Care Survey program conducted with over 12000 patients in 23 countries (2002-2008) has concluded that \u00absocial security systems are usually designed around common diseases and are not flexible enough to take into consideration unprecedented health needs\u00bb [To compile information on social challenges of RD patients and their families.The identification of challenges is performed based on a literature review of:- Communication from the Commission on Rare Diseases: Europe's Challenges 2008) [008 [2];- Council Recommendation on an Action in the Field of Rare Diseases (2009) ;- Communication from the Commission: European Disability Strategy 2010-2020 (2010) ;- EUROPLAN Report on 15 National Conferences (2010-2011) [- EURORDISCare Survey Programme (2002-2008);- \u2018Rare Diseases: Addressing the Need for Specialised Social Services and Social Policies\u2019 .Main social challenges identified:- Lack of long term, funded and sustainable policies and structures at national level for the integration of patients with RD into social services and policies;- Weak coordination between health and psychosocial complementary care, between central and regional/local infrastructures, leading to a consequent lack of multidisciplinary holistic approach;- Lack of systems to accurately evaluate patients\u2019 disability degree and consequent lack of adequate compensation measures;- Lack of information and understanding of patients\u2019 disabilities and corresponding implications in patients\u2019/families\u2019 daily lives;- Lack of training of social sector professionals to deal with rare, complex cases, resulting in unprepared services/structures and insufficient sharing of best practices;- Scarcity of social services and social policies/benefits. Difficulties in accessing services;- Lack of case managers guiding patients/families to access the different types of care and structures;- Lack of personalised/flexible measures and policies;- Lack of measures to remove burden from family in daily care;- Lack of systems to deal with transition from adulthood to childhood and ageing.To improve the access from RD patients/families to adequate and high quality social policies and services there is a need to address these current social challenges by shaping national policies and implementing solutions at MS level. Guiding principles to address some of these challenges are currently being compiled within the European Committee of Experts on Rare Diseases Join Action Work Package 6."}
+{"text": "Clinical and Translational Medicine [The abstract of the original article in Medicine  containeIncorrect sentence:Application of tumor cell surface adhesion molecule Anti-epithelial cell adhesion molecule (EpCAM)-dependent antibody capture, and intracellular cytokeratins (CKs)-dependent immunostaining strategies to detect disseminated or circulating tumor cells (DTCs or CTCs), is limited by highly heterogeneous and dynamic expression or absence of EpCAM and/or CKs in CTCs and DTCs, particularly in their capturing and identifying CTCs/DTCs shed from diverse types of solid tumor, thus being biased and restricted to the only both EpCAM and CK positive cancer cells.Corrected sentence:Application of tumor cell surface adhesion molecule EpCAM-dependent antibody capture, and intracellular cytokeratins (CKs)-dependent immunostaining strategies to detect disseminated or circulating tumor cells (DTCs or CTCs), is limited by highly heterogeneous and dynamic expression or absence of EpCAM and/or CKs in CTCs and DTCs, particularly in their capturing and identifying CTCs/DTCs shed from diverse types of solid tumor, thus being biased and restricted to the only both EpCAM and CK positive cancer cells.The abstract in the original article has been corrected."}
+{"text": "There is emerging evidence that exocytosis plays an important role in regulating T cell receptor (TCR) signaling. The trafficking molecules involved in lytic granule (LG) secretion in cytotoxic T lymphocytes (CTL) have been well-studied due to the immune disorder known as familial hemophagocytic lymphohistiocytosis (FHLH). However, the knowledge of trafficking machineries regulating the exocytosis of receptors and signaling molecules remains quite limited. In this review, we summarize the reported trafficking molecules involved in the transport of the TCR and downstream signaling molecules to the cell surface. By combining this information with the known knowledge of LG exocytosis and general exocytic trafficking machinery, we attempt to draw a more complete picture of how the TCR signaling network and exocytic trafficking matrix are interconnected to facilitate T cell activation. This also highlights how membrane compartmentalization facilitates the spatiotemporal organization of cellular responses that are essential for immune functions. The key signaling molecules involved in the T Cell Receptor (TCR) signaling network have been well-characterized. T cell signaling is initiated upon TCR engagement by major histocompatibility complex (MHC) molecules bound to peptide antigens (pMHC). Upon TCR engagement, the TCR-associated CD3 dimers are phosphorylated by the kinase Lck on intracellular immunoreceptor tyrosine-based activation motif (ITAM) consensus sites, leading to the recruitment and activation of downstream signaling molecules, such as the adaptor protein Linker for Activated T cells (LAT). Subsequent activation responses including the secretion of lytic granules (LG) target infected or cancer cells for lysis. The formation of a structured interface between a T cell and an antigen-presenting cell (APC), termed the immunological synapse, is critical for the efficient delivery of effector molecules to the APC and intracellular signals in the T cell. The architecture of the immunological synapse was first described in 1998 as a \u201cbull's eye pattern,\u201d consisting of the central supramolecular activation cluster (cSMAC), where signaling molecules such as the TCR accumulated, surrounded by a ring of adhesion molecules known as the peripheral SMAC (pSMAC), with other molecules such as CD45 being excluded and localized in the distal SMAC  and SNX27 are implicated in recycling TCR toward the immunological synapse  and National Health and Medical Research Council of Australia (APP1037320 and APP1059278 to KG and APP1102730 to JR).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "A group of clinical conditions with the spectrum of adult onset Spondyloarthritis (SpA) characterized at presentation by the inflammatory involvement of the lower limb joints and entheses and in some cases, particularly those with HLA-B27, sacroiliac and spinal joint involvement. Enthesitis Related Arthritis (ERA) and Psoriatic Arthritis (PsA), both categories of Juvenile Idiopathic Arthritis correspond to juvenile-onset SpA at some extentWith the advent of new classification criteria for axial SpA (axSpA) and peripheral SpA (pSpA) proposed by the Assessment of SpondyloArthritis internationalSociety (ASAS) to identify patients with ankylosing spondylitis in the earliest pre-radiographic stage of the disease to treat them with Tumor Necrosis Factor (TNF) alpha blockers and halter disease progression, there is a tendency to search for early sacroiliac involvement with Magnetic Resonance Imaging (MRI) and peripheral disease with Ultrasonographic (US) studies in childrenThere is clearly a risk in trying to resemble the objective and procedures developed for the adult patients in the pediatric population. In the first place, the most frequent and often severe inflammatory and structural changes in children and adolescents with SpA occur at peripheral sites five to 10 years before the onset of axial disease. Peripheral involvement might be so severe that TNF blockers may be indicated years before sacroiliitis and spondylitis. It is therefore obvious that searching for axial disease with MRI may be useless.Both anatomy and biomechanics of peripheral sites and axial skeleton change throughout childhood and adolescence. In consequence, it is important to understand basic aspects of the sacroiliac and spinal joints before developing plans to search such sites to detect inflammation and prescribe TNF blockers.None declared."}
+{"text": "To develop and evaluate a fidelity measure of the evidence based collaborative care model for maternal depression care in multidisciplinary primary care sites caring for low income and race/ethnic minority populations.Fourteen federally qualified community health centers (FQHCs) in Seattle and King County, Washington participated (2008-2015) in an effort to implement collaborative care for depression in high risk mothers. An expert panel based framework was used to identify key elements of the collaborative care model. This theory based framework guided operationalization of fidelity measures of this intervention from quantitative metrics from an electronic clinical care management and health record (CMTS) used by all of the sites.1748 of 2500 (70%) unique women who received care for depression symptomatology over the course of the study period were eligible for inclusion in this analysis. Six fidelity measures were created from the CMTS database covering elements such as the use of a patient registry, evidence based measures, and appropriate clinical follow up. A simple dichotomous score for each element was associated with increased clinical improvement in depression for four of five of the measures after adjusting for age, pregnancy status, race/ethnicity, baseline depression and anxiety symptoms, and suicidal ideation . A summary measure of these scores had a higher point estimate of clinical benefit than any individual item  supporting our hypothesis that these reflect distinct components of a summary scale.A fidelity measure based on a theoretical framework and constructed from existing clinical data was predictive of clinical outcomes. Additional work is needed to determine if these measures are useful for monitoring implementation success of the collaborative care model.Public Health Seattle & King County, Eitel Family Foundation (Unutzer), Agency for Healthcare Research and Quality (Bennett), University of Pennsylvania Implementation Science Workgroup (Bennett)."}
+{"text": "Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is defined as a tumor growing in the main duct or branch duct of the pancreas, with differentiated papillary features and production of atypical mucin, as well as segmental or diffuse dilation of the main pancreatic duct (MPD), cystic dilation of the secondary branches, or both. Histologically they exhibit a wide spectrum of dysplastic changes from low and moderate grade dysplasia to high grade dysplasia (in situ carcinoma) to eventually, invasive carcinoma. The international consensus guidelines 2012 for the management of IPMNs and mucinous cystic neoplasms of the pancreas have been issued. The new international consensus guidelines recommend multidetector row CT or MR imaging with MR cholangiopancreatography (CP) in the evaluation of pancreatic cysts larger than 1 cm to check for high-risk stigmata or worrisome features. In cysts that show high-risk stigmata, surgical management is recommended. In this lecture, I would like to discuss the diagnostic performance of magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) and diffusion weighted imaging, and MDCT in determining the malignant potential and surgical resectability of pancreas IPMNs using pathologic and surgical analyses as reference standards. In addition, I would like to discuss interobserver agreement of each diagnostic criterion on CT and MRI for evaluation of the malignant potential of IPMNs."}
+{"text": "Considerable heterogeneity has been observed in the selection and reporting of disease-specific pediatric outcome measures in randomized controlled trials (RCTs) . This maWe searched MEDLINE, EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL from 2001 until December 2012. We also searched websites listing ongoing trials. We included randomized and controlled trials of anaphylaxis treatment in patients 0-18 years of age. Two authors independently assessed articles for inclusion.No published studies fulfilled the inclusion criteria Fig .There is an alarming absence of RCTs evaluating the treatments for anaphylaxis in children. High quality studies are needed and are possible to design, despite the severe and acute nature of this condition. Consensus about the selection and validation of appropriate outcome measures will enhance the quality of research and improve the care of children with anaphylaxis.CRD42012002685"}
+{"text": "Investigators from Children's National Medical Center and George Washington University School of Medicine, Washington, DC, studied the correlation between white matter tract changes and developmental outcomes in a series of infants with hypoxic ischemic encephalopathy (HIE) treated with whole body cooling. Investigators from Children's National Medical Center and George Washington University School of Medicine, Washington, DC, studied the correlation between white matter tract changes and developmental outcomes in a series of infants with hypoxic ischemic encephalopathy (HIE) treated with whole body cooling. Using magnetic resonance imaging (MRI) with quantitative diffusion tensor imaging (DTI), fractional anisotropy, as well as mean, axial and radial diffusivity of the corpus callosum (CC), posterior limbs of the internal capsule (PLIC) and cortical spinal tracts (CST) were calculated in 50 infants at a median age of 8 days of life, and compared with neurodevelopmental outcomes using a Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI) derived from the Bayley Scales of Infant Development at 15 months (42 patients) and 21 months (35 patients) of age.Controlling for gestational age, birth weight, socioeconomic status and gender, there was a statistically significant correlation p<0.001) between decreased fractional anisotropy of the CST and lower PDI scores as well as decreased fractional anisotropy of the CC and lower MDI scores. Increased axial diffusivity of the CC and lower radial diffusivity of the CST also correlated with lower PDI and MDI scores (p=0.018 and p=0.03respectively). [ between COMMENTARY. HIE is a common cause of mortality and long-term morbidity in neonates. Early assessment of the degree of neurologic injury is important for prognosis and rehabilitation planning, but can be challenging by conventional imaging methods. Evaluation by standard MRI is complicated by observer variability as well as significant differences in imaging findings depending on the timing of the exam , 3.Diffusion Tensor Imaging (DTI) is an advanced magnetic resonance imaging technique that uses the restricted movement of water molecules perpendicular to the long axis of white matter tracts as a measure of axonal integrity and a decrease in fractional anisotropy in HIE patients suggests microstructural injury . DTI may"}
+{"text": "Progressing loss of sensory function is a major problem of aging populations. In humans and animals, loss of auditory function becomes evident by increased hearing thresholds, altered sound processing, and abnormal perception of above-threshold sounds or phantom perceptions like hyperacusis and tinnitus ,2. RecenSynaptic structures, afferent synaptic contacts, and auditory fibers were studied in an animal model on young (3-9 month old) and aged (20-24 month old) rats. The hearing sensation was monitored by auditory evoked brainstem responses (ABR) and otoacoustic emissions (DPOAE) giving insight for the central and peripheral (hair cell function) auditory capacity, respectively. Hyperacusis and tinnitus sensation in the rat were tested using a behavioral approach . We pharAuditory thresholds were increased and the auditory response range was reduced over age. The characteristic changes over age were similar to the changes observed after exposure to traumatizing sound. sGC treatment interacts with the loss of age related and auditory trauma induced loss of hair cell synaptic ribbons in a complex way, proposing that a subclass of auditory fibers with a special vulnerability can be rescued by sGC treatment within a defined time window.Age related and noise induced decline of hearing function are correlated with auditory responses and morphological specifications of hair cell molecular phenotype. The data need to be discussed regarding the proposed cGMP generators in the inner ear and their role for an otoprotective molecular cascade after noise induced damage of the ear or progression of presbycusia."}
+{"text": "Current statistical procedures implemented in general software packages for pooling of diagnostic test accuracy data include hSROC (Rutter and Gatsonis 2001) regression and the bivariate normal model (BRMA) , Arends (2006) and Chu and Cole (2006)). However, these models do not report the overall mean. The hSROC model is less intuitive and therefore less popular while the bivariate normal model has difficulties estimating the correlation parameter when the number studies in the meta-analysis are small and/or when the between-study variances are relatively large. As a result, the between study variance estimates from the BRMA are upwardly biased as they are inflated to compensate for the restriction on correlation parameter . We present advanced statistical methods for meta-analysis of diagnostic accuracy studies and demonstrate the use of different software packages in R or with an R interface together with code, to apply different model strategies for obtaining appropriate meta-analytic parameter estimates. The focus is on the joint modelling of sensitivity and specificity using copulas as well as using the concept of sharing random components.The methods are applied to two datasets: the classical example of Glas et al. (2003) on diagnostic accuracy of telomerase as urinary tumour marker for diagnosing primary bladder cancer and a second dataset from a systematic review by Arbyn et al. (2013) that aimed at comparing sensitivity and specificity of human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions."}
+{"text": "Despite advances in prevention science in recent decades, the U.S. continues to struggle with significant alcohol-related risks and consequences among youths, especially among vulnerable rural and American Indian communities. The Prevention Trial in the Cherokee Nation is a partnership between prevention/implementation scientists and Cherokee Nation Behavioral Health to implement and evaluate an integrated multi-level intervention designed to prevent underage drinking and associated negative health outcomes among American Indian and other youths living in rural high-risk underserved communities. The primary partnership is augmented with partnerships with Oklahoma public school districts, the Oklahoma Department of Human Services, and a local nonprofit organization. The intervention builds directly on results of multiple previous RCTs of two conceptually distinct approaches. The first is an updated version of an evidence-based community environmental change intervention, and the second is our newly developed population-wide implementation of screening, brief intervention and referral to treatment delivered within high schools by school service providers hired through the Department of Human Services. Six key research design elements optimize causal inference and experimental evaluation of effects of intervention implementation, including purposive selection of towns, random assignment of towns to study condition, controlled interrupted time-series, nested cohorts as well as repeated cross-sectional observations, a factorial design crossing two conceptually distinct interventions, and multiple comparison groups. Interim results indicate a high uptake of intervention implementation with some variation by community, as well as trends toward decreased alcohol use among youths in the intervention conditions compared to the control condition. The trial demonstrates the effectiveness of scientists building strong partnerships for implementation of evidence-based strategies within underserved communities. Our collaborative partnerships also demonstrate it is feasible to implement a rigorous scientific trial while incorporating community-based participatory research methods.Research was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA020695."}
+{"text": "Evidence linked exposure to internet appearance-related sites to weight dissatisfaction, drive for thinness, increased internalisation of thin ideals, and body surveillance with Facebook users having significantly higher scores on body image concern measures . This study explored the impacts of social media on the body image of young adults aged 18-25 years. A total of 300 students from a Victorian university completed a survey including questions about the use of social media and 2 measures of body image: The Objectified Body Consciousness and both female and male version of the Sociocultural Attitudes towards Appearance Questionnaire 3. Results showed participants mostly used Facebook to keep in touch with friends and family. While using social media, they felt pressure to lose weight, look more attractive or muscular, and to change their appearance. Correlations were found between Instagram and concerns with body image and body surveillance, between Pinterest and body shame and appearance control beliefs and between Facebook and Pinterest and perceived pressure. Findings contribute to the growing body of knowledge about the influence of social media on body image and new information for the development of social media literacy programs addressing negative body image."}
+{"text": "The paper by Thac et al. is an important paper from the point of view of health care providers and policy makers in the context of Integrated Management of Childhood Illnesses (IMCI) in developing countries like India .Improving case management skills of health-care staff.Improving overall health systems.Improving family and community health practices.The paper highlights the importance of the third and valuable component of IMCI, that is, \u201cimproving family and community health practices\u201d by health education of mothers of under-five children. The figures mentioned in the paper clearly show that it is successful in achieving this third component.IMCI is an integrated approach which includes three main components :ImprovinIndia has made notable strides in tackling neonatal and childhood illnesses through a number of initiatives. These are in the form of addition of neonatal component in IMCI (IMNCI), training of community level grass-root workers such as Accredited Social Health Activists (ASHA) and Anganwadi Workers (AWW), Home Based Neonatal Care (HBNC), facility based IMNCI, infant and young child feeding practices (IYCF), and Rashtriya Bal Swasthya Karyakram (RBSK) to name a few .Health education and training of grass-root workers are being done in India, but organized component of health education of mothers needs to be incorporated for improving health practices at family and community level. This can be systematically introduced at national level using the community based platforms of Village Health Sanitation and Nutrition Committees (VHSNC) and Mahila Arogya Samitis (MAS) in India."}
+{"text": "Deep brain stimulation (DBS) of the basal ganglia is a widely used and effective treatment for patients with medication-refractory Parkinson's disease (PD). However, tuning the stimulation parameters to maximize therapy while minimizing side effects is performed mostly through a trial and error approach, consuming time and energy of both clinician and patient . As such"}
+{"text": "Several studies have demonstrated the important role of non-coding RNAs as regulators of posttranscriptional processes, including stem cells self-renewal and neural differentiation. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (ihPSCs) show enormous potential in regenerative medicine due to their capacity to differentiate to virtually any type of cells of human body. Deciphering the role of non-coding RNAs in pluripotency, self-renewal and neural differentiation will reveal new molecular mechanisms involved in induction and maintenances of pluripotent state as well as triggering these cells toward clinically relevant cells for transplantation. In this brief review we will summarize recently published studies which reveal the role of non-coding RNAs in pluripotency and neural differentiation of hESCs and ihPSC. Personalized medicine is expected to benefit from the combination of genomic information with the high throughput studies including transcriptomic, proteomic and metabolomic profiling. Measuring gene expression in individual cells is crucial for understanding the gene regulatory network. In order to decipher the genetic regulatory network in cells significant efforts have been made over the years to develop technology platforms for transcriptome characterization such as DNA microarray hybridization, serial analysis of gene expression SAGE;  or next-The latest techniques which involve bioinformatic expertise made a revolution in transcriptome analysis enabling not only the identification of cDNA and gene isoforms but discovery of long non-coding RNA  and short non-coding RNA . Non-coding RNAs include transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear and small nucleolar RNA, microRNA (miRNA), and small interfering RNA (siRNA), which do not encode any proteins. Several of these non-coding RNA species, like miRNA or SiRNAs, are of particular interest to transcriptomic and particularly in stem cell research due to their role in post-transcriptional regulation of numerous biological processes . During in vitro platforms for studying diseases, basic cell biology and development.Human pluripotent stem cells encompassing hESCs and induced pluripotent stem cells (ihPSCs) show great potential for regenerative biology providing the unique human Human embryonic stem cells can be derived from inner mass from human blastocyst maintaining unique capacity for unlimited self-renewal through long-term maintenance using laboratory culture conditions . Since tBesides the abundance and efficient differentiation without traces of pluripotency, the main requisite for personalized regenerative medicine is to derive disease cells that genetically match the patient. Although the technique of somatic cell nuclear transfer (SCNT) and successive derivation of hESCs  could bein vitro  indispensable for endogenous activation of OCT4, SOX2, and NANOG  called lincRNA-RoR . OverexpThese studies indicate that non-coding RNAs, especially miRNAs have the potential to be used as small-molecule therapeutics to promote more efficient reprogramming or to induce the pluripotent stem cells toward other cell lineages.In the context of regenerative medicine it is crucial to develop protocols for efficient and reproducible differentiation of pluripotent stem cells toward homogeneous population of desired cells without traces of pluripotency. Since the generation of the first hESCs line  and deriTo reveal whether lincRNAs play important role in hESCs and neural differentiation Stanton and colleague , employeHOX gene (HOXA and HOXB), genes involved in early patterning of anterior posterior axis during the neural development. These results coincided with results obtained with neural progenitors derived from hESCs as an additional prove that these two sources of pluripotent stem cells has similar neuronal differentiation potential (POU3F2, MYTIL, RFX4, ZNF804A, SMARCA2, and NPAS3. These changes in the transcriptome profiles and the role of lincRNA during early human neural differentiation using pluripotent stem cells reveals important use of ihPSC technology in studying human disease as a unique human assay of human neurogenesis. Integration the novel transcripts in more global systems of analysis is must in order to elucidate their abnormally regulation in a subgroup of patients.In order to clarify the contribution of lincRNA in developmental and neurological disorders, otential . The autComparing the miRNA profiles of neuroectodermal cells to epidermal cells both derived from hESC, Zhang and colleague  identifiStudying of non-coding RNA in modeling exhaustive networks of gene interactions as an ultimate application of systems biology in systems biomedicine, could substantially contribute to understanding and modulation of developmental and differentiation processes in humans. Although the expression of newly correlated non-coding RNA is strongly associated to pluripotency and neural differentiation their possible role in different neurodegenerative disorders is still to be elucidated. These studies undoubtedly contribute to better understanding of the biological processes during pluripotency and neural differentiation and reveal the important interplay between multiple pluripotency transcription factors and non-coding RNAs especially miRNAs. However, the understanding of the impact of miRNA-based regulation in human neural development is still at its dawn. The future studies will confirm the potential of controlling differentiation and pluripotency of human pluripotent stem cells by modulating the expression of selected non-coding RNAs and integrate them into models that reveal the global behavior of the biological process in biomedicine and neural diseases in order to ultimately improve patients\u2019 quality of life.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Cell competition is identified as a crucial phenomenon for various conditions like cancer, aging and organ development. MicroRNAs (miRNAs) may play an important role in regulation of expression of genes involved in cell competition at the post-transcriptional level. In silico screening of miRNAs involved in a cell competition is an effort to identify potential miRNAs and to reduce, economize and expedite experimental work. In the present study we have identified miRNAs of Drosophila genome involved in a cell competition using in silico screening strategy.We used four steps of in silico (i) Selection of cell competition related genes of Drosophila genome through literature survey; (ii) Identification of miRNAs that target selected cell competition-related genes; (iii) Sequence conservation analysis of identified miRNAs with Human genome; (iv) Identification of genomic location of that Drosophila miRNAs and exploration of their expression profiles in tissues by use of host gene expression profile.In this study we have identified seven potential Drosophila miRNAs that are most probably involved in cell competition. Human homologs of these seven potential miRNAs may be very important in cell competition related diseases like cancer. Proof of this concept will be established with wet lab experimentation to reassert the role of miRNAs in cell competition."}
+{"text": "Clinical phase I/II studies have demonstrated the safety of gene therapy for a variety of central nervous system disorders, including Canavan\u2019s, Parkinson\u2019s (PD) and Alzheimer\u2019s disease (AD), retinal diseases and pain. The majority of gene therapy studies in the CNS have used adeno-associated viral vectors (AAV) and the first AAV-based therapeutic, a vector encoding lipoprotein lipase, is now marketed in Europe under the name Glybera. These remarkable advances may become relevant to translational research on gene therapy to promote peripheral nervous system (PNS) repair. This short review first summarizes the results of gene therapy in animal models for peripheral nerve repair. Secondly, we identify key areas of future research in the domain of PNS-gene therapy. Finally, a perspective is provided on the path to clinical translation of PNS-gene therapy for traumatic nerve injuries. In the latter section we discuss the route and mode of delivery of the vector to human patients, the efficacy and safety of the vector, and the choice of the patient population for a first possible proof-of-concept clinical study. The peripheral nervous system (PNS) consists of primary sensory neurons in the dorsal root ganglia and motor neurons in the ventral horn of the spinal cord Figure . Most peSurgical repair of peripheral nerves has reached its optimal refinement. Recovery of function as a result of surgical repair has significantly improved but remains limited. Novel adjuvant therapeutic strategies to promote axon regeneration in the injured peripheral nerve are needed to further improve recovery of function. One of these strategies is gene therapy. Successful gene delivery to primary sensory and motor neurons and to Schwann cells, the resident glia cells of peripheral nerves, has been reported with various viral vectors . Second, continued growth factor expression may have unacceptable side-effects, e.g., Nerve growth factor (NGF) may induce hypersensitivity  and motor neurons and muscle cells (neuromuscular disorders) are the primary target cells  for clinical trials on pain  delivery. In the rat a single intraganglionic injection of an AAV vector results in efficient transduction of sensory neurons with very little if any spread of the vector to other locations  exist. Previous trials to test experimental treatments to promote nerve regeneration involved patients that sustained very different types of injuries. A recent successful clinical trial on the beneficial effect of electrical stimulation was performed on patients with complete transection injury of the digital nerve (Wong et al., Gene therapy for neurotrophic factors was well-tolerated in Alzheimer\u2019s (NGF; Rafii et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "MR imaging is encountering an expanding application in the assessment of patients with paediatric chronic rheumatic diseases. By providing multiplanar tomographic imaging with unparallel soft tissue contrast, MRI allows the simultaneous evaluation of all joint structures involved in inflammatory arthritis and it is regarded as one of the most attractive imaging modalities for the investigation of juvenile idiopathic arthritis (JIA). MRI provides additional and more sensitive information over clinical examination and other imaging modalities and holds great promise in supporting diagnosis of JIA, assessing its severity and prognosis, monitoring disease course and treatment efficacy.The use of MRI in the assessment of the musculoskeletal system in children has important differences from its adult counterpart. Growing joints change anatomically over time making imaging in JIA a real challenge without the availability of normative data. A sound knowledge of growth-related changes, in fact, is of foremost value to establish whether joint surface changes reflect a real damage or are actually part of normal development.Main indications for musculoskeletal MRI in paediatric rheumatology, technical issues and diagnostic accuracy, pitfalls in image analysis and newer MRI and scanner techniques (i.e whole-body MRI) will be discussed thus providing an overview of the recent advances and challenging in imaging children with rheumatic disorders.None declared."}
+{"text": "To evaluate the effects of health education and self management intervention combined with drug therapy in school-age children with asthma.320 cases of school-age children with asthma were divided into management group and control group, two groups of children were receiving standardized drug inhale treatment, management of children receive regular health education and self management behavior intervention.Times of asthma attacks, emergency and missing school days decreased significantly compared with the control group. Pulmonary function improved.The health education and self management behavior intervention combined with drug therapy can improve the level of understanding of disease in children with asthma, medication compliance, reduce symptoms,improve lung function and improve the quality of life."}
+{"text": "Paw= Rrs\u00d7 V' + VT/Crs+ PEEPtot during inspiration [rs) and elastance (Ers) in presence of inspiratory muscle activity and in absence of an adequate neuromuscular coupling. We reasoned that NAVA  ventilation should assure a better neuromuscular coupling compared to PSV and hence the coefficient of determination (CD) of the above equation should be much higher during NAVA ventilation.The Least Squares Fitting (LSF) is a computerized method of analysis of respiratory system mechanics. It is based on applying a regression analysis for every sample points of the loop of pressure, flow and volume by fitting the equation piration . This tepiration . HoweverThe aim of this study was to prove the efficacy of the LSF method in obtaining reliable respiratory mechanics data in two different ventilatory modes.Twelve patients with acute respiratory failure were enrolled at the admission to the ICU and ventilated using in random order either PSV or NAVA for 3 hours with the same Positive End Expiratory Pressure (PEEPe) and tidal volume (VT) settings. Flow and pressure traces were recorded and subsequently analyzed using the LSF method to obtain data of Rrs, Ers, PEEPtot and coefficient of determination (CD). NAVA and PSV were first compared in terms of CD during the 3 hours of recording. Furthermore, we selected 100 consecutive breaths for each patient in each ventilatory mode to compare the values of elastance (the only non-flow dependent of the equation of motion) obtained either in NAVA or PSV.rs values for PSV and NAVA are presented in Figure The CD during NAVA ventilation was statistically higher than that obtained during PSV Figure  (Chi-squOur results seem to confirm that the neuromuscular coupling is much better preserved during NAVA than during PSV."}
+{"text": "The Kokobera group of flaviviruses circulates in Australia and Papua, New Guinea, and has been associated with occasional human polyarticular disease. To facilitate future studies to identify virulence determinants, the complete coding regions of the Stratford virus, and isolates of the Bainyik virus and Torres virus were obtained. Flaviviridae; genus, Flavivirus) currently includes 5 candidate species: Kokobera (KOKV), Stratford (STRV), Bainyik (previously strain MK7979), Torres (previously strain TS5273), and New Mapoon (NMV) viruses  as a scaffold. Any discrepancies in the sequence were resolved by construction of primer sets which spanned the region in question, followed by amplification and Sanger sequencing.Sequencing was as described in detail previously . BrieflyThe nucleotide sequence length obtained varied  mainly due to inefficiencies in the ability of the method to amplify the RNA genome termini. Nucleotide alignments with the complete 10874\u00a0nt KOKV genome sequence indicated that the Bainyik virus was more closely related to it than STRV or the Torres virus, as expected . This was consistent with previous reports based on analyses of the untranslated regions (UTR) and envelope sequences (KM225263), Bainyik virus (KM225264), and Torres virus (KM225265).The GenBank accession numbers for the virus sequences are STRV ("}
+{"text": "This Research Topic consists of 14 manuscripts discussing the cognitive and neural organization of speech processing. The contributions are grouped around four themes: (1) Spoken language comprehension under difficult listening conditions; (2) Sub-lexical processing; (3) Sensorimotor processing of speech; (4) Speech production.Seven papers addressed speech perception under challenging listening conditions. Van Engen and Peelle  discuss Strau\u00df et al.  examinedThree papers focused on perception of speech at sub-lexical levels. Deschamps and Tremblay  studied Two papers addressed sensorimotor processing of speech. Komeilipoor et al.  report hTwo papers focused on speech production. Etchell et al.  provide This Frontiers Research Topic allows new insights into the neurobiology of speech perception and production, and demonstrates how the field of speech science is now addressing issues at its very core. We believe that the future of the research in the field lies in the effective combination of research methods, e.g., EEG and TMS, or fMRI and EEG, as research will benefit from the strengths of each method. In conclusion, this Research Topic consists of 14 excellent contributions, and we are convinced the Topic will provide readers with novel ideas for future studies that will elucidate the cognitive and neural architecture of speech processing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Anxiety disorders are very common and burdensome mental illnesses worldwide, characterized by exagerated feelings of worry and fear. These disorders are highly comorbid with other conditions.The aim of our study is to explore the physical and psychiatric comorbidities and their clinical correlates. The second objective is to identify the predictors of recurrence of anxiety disorders.Our study concerned 436 outpatients who met DSM-V diagnostic criteria for anxiety disorders and were followed in the Department of Psychiatry of Monastir (Tunisia) between 1998 and 2017. Selective mutism and seperation anxiety were excluded for lack of cases.Our results demonstrated that Generalized Anxiety Disorder (GAD) was significantly associated with cardiovascular comorbidity (OR=3.208). Social Anxiety Disorder (SAD) was significantly correlated to avoidant personality disorder (OR=17). Patients with suicide attempts are more likely to have a comorbid personality disorder (OR=11.606). Being married and having a later age of onset are predictors of having comorbid depressive disorder. Furthermore, being married, having an anxiety-anxiety comorbidity and a longer duration of untreated illness (DUI) are predictors of recurrence.Our study highlights the fact that comorbidities  call for a closer follow up due to the higher risk of recurrence, the higher risk of suicide attempts and the poorer treatment response.No significant relationships."}
+{"text": "Although the advancements in pharmacogenomics (PGx) may bring true advantages of personalized medicine into daily clinical practice, the integration and inclusion of the field in routine clinical decision support systems are still very low . This isAbove mentioned reasons not only reduce the speed of PGx investigations and guideline development but also produce several external barriers to the integration of clinical PGx tests into a routine clinical setting. Factors like lower background and expertise for clinical interpretation of PGx test result in physicians and clinicians, lack of particular cost and time benefit instruments and facilities for test implementation through clinical centers, absence of sufficient guidelines for every genomic variant in drug-related genes, no existence of appropriate variant calling tools for many pharmacogenes, no willing and hesitance of insurance parties to cover the tests in clinics, etc. are seen and introduced as the major issues for prevention of combination of PGx and primary care everywhere .However, recent years were witness huge motivations and efforts on overcoming such challenges. Several research groups explored the possibility of adding PGx tests as part of clinical decision systems in hospitals and/or private clinical centers . CurrentUmetsu et al.). The next article in our special issue investigated the possible effects of CYP2D6 special genotype and Metoprolol tolerance in Chinese elderly with cardiovascular disorders. The study proved the association between intermediate metabolizers showing lower tolerance and may develop higher incidence of Metoprolol adverse reactions in such patients . The third paper, thiopurine therapy via TPMT and NUDT15 testing, confirmed the benefits of the implementation of single gene PGx testing, which can guide the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care . The fourth and fifth articles  explored the prospect of prevention of adverse drug reactions (ADRs) through the utilization of clinical PGx tests and demonstrated the advantages of pre-emptive genotyping on anticipation of ADRs and acceleration of integration of PGx tests into daily primary care .The authors of the Neuropsychiatric and Montelukast article tried to clarify the relation between montelukast and neuropsychiatric in raising adverse events, which resulted in a significant association between neuropsychiatric adverse reactions and montelukast. Such data from real-world samples may add invaluable knowledge to the physicians\u2019 background on PGx and encourage the utilization of results in daily clinical settings (To introduce PGx tests into daily practice, future efforts may focus on offering population-specific pharmacovariant evidence and panel-based sequencing approaches. Widespread access to genomic databases alongside the PGx maps for individuals in a portable format might be also worth consideration."}
+{"text": "The national oesophago-gastric cancer audit evaluates the care given to patients with OG cancer diagnosed in England and Wales, identifying areas for local services to improve and so achieve better patient outcomes. While the audit follows a standard approach by collecting a core dataset, it extends this by linking to other national databases in order to (1) reduce the burden of data collection, (2) add data that could not otherwise be obtained, (3) verify the quality of audit data. This presentation will provide an overview of the modern approach to national clinical audits and introduce anticipated future developments. The data collected by hospitals and submitted to the audit is expanded by linkage to radiotherapy data (RTDS), date of death from the Office for National Statistics and administrative hospital admission data (HES). The linked data enables the Audit to: (1) examine whether radiotherapy regimens used in definitive oncology comply with guideline recommendations, using dosage information drawn from RTDS; (2) publish comparative short-term survival figures for NHS trusts and surgeons using ONS date of death; and (3) assess the quality of data submitted from hospitals by comparing coded procedural information in HES and the audit dataset.The analysis of the linked data has led to several important audit findings, namely: (1) Access to RTDS data confirmed reasonable compliance with official guidelines on recommended radiotherapy dosing schedules. (2) Linked mortality data has provided robust and credible estimates of surgical outcomes and is a critical output to NHS trusts and surgeons, as well as the wider public. Our analysis has highlighted a gradual decline in post-operative mortality. (3) Linkage of audit and HES data identified gaps in the recording of endoscopic stenting, with many procedures not being submitted by participating trusts. These diverse results underline the usefulness of linked data in revealing a more complete picture of the care received by OG cancer patients.Linked data has become integral for the successful implementation of a national clinical audit, supplementing the core dataset with information that would otherwise be unavailable or difficult and costly to collect. Linkage enhances the audit's ability to assess health services' compliance with professional standards and to give service providers the opportunity to benchmark their performance. Future developments are expected to expand on this by including primary care service use before diagnosis."}
+{"text": "Many studies on contextual health effects suffer from compositional bias and selective migration into neighbourhoods. Longitudinal natural experiments have the potential to overcome these limitations, and there are several opportunities for this research design in the migration context. We aimed to synthesize evidence from natural experiments among migrants studying the effect of contextual factors on health and healthcare.Peer-reviewed literature in English or German was systematically searched in four major databases in December 2021. Following systematic abstract- and fulltext-screening, 32 studies were included for analysis. Evidence on contextual impacts on physical and mental health, mortality, and healthcare was narratively synthesized and quality appraisal conducted.We found four types of contextual health effects: factors of the place of residence in receiving countries (n = 6), migration-context interactions (n = 10), policy environments (n = 15) and cultural factors (n = 1). Results show the negative impacts of post-migratory contexts on physical health and mortality and the favourable impacts on child health. Impacts on mental health are mixed. Analyses of policy contexts indicate the negative impacts of restrictive migration and social policies on healthcare utilization, mental health and mortality as well as the positive effects when restrictions are lifted.Natural experiments can serve as powerful tools in disentangling the effect of context on health and reducing bias through self-selection. Results demonstrate the negative impacts for health which lie at the nexus of migration and neighbourhood disadvantage. At the same time, studies uncover the potential of health, welfare and visa programs to counteract such disadvantages and create healthy post-migratory contexts. With careful consideration of causal pathways, results from migration contexts can serve as a magnifying glass for effects of context in other population groups.\u2022\u2002Natural experiments can serve as powerful tools in disentangling the effect of context on health and reduce bias through self-selection.\u2022\u2002Results show the negative impacts for health that lie at the nexus of migration and neighborhood disadvantage, as well as the potential of inclusionary policies to counteract them."}
+{"text": "The AuthorInformation of theCorresponding Author Zhixu Ni in the original manuscript should becorrected to the following:Center of Membrane Biochemistryand Lipid Research, Faculty ofMedicine Carl Gustav Carus of TU Dresden, 01307 Dresden, GermanyThis is corrected in the affiliations of this Correction."}
+{"text": "Mireji et al.), potential genes and neuropeptides for reproductive regulation in Bombyx mori  and Rhipicephalus sanguineus , a meta-analysis method to evaluate insecticide resistance , screening of plant metabolites acting as physiologically active compounds in Rhipicephalus microplus , and a review concerning delivery of dsRNA molecules within the cells of targeted pest control insects . Together, these research papers present recent advances in understanding the manipulation of both invertebrate physiology and ecological elements using refined molecular approaches and represent innovative perspectives in the field of environmentally friendly strategies for the control of important arthropod populations, avoiding the use of insecticides toxic to animals and humans.Enhancing our knowledge concerning the control of invertebrate populations, mainly of agricultural pests and disease vectors, is nowadays one of the World\u2019s greatest scientific challenges. In the context of environmentally friendly interventions to control crop pests and insect vectors, this Research Topic focuses particularly relevant scientific articles on aspects of arthropod physiology. These include insect responses to plant and animal volatiles which enhance attraction and repellence in Tsetse flies ("}
+{"text": "The mild encephalitis (ME) hypothesis of severe mental disorders, ME to be caused by infections, autoimmunity , toxicity and trauma , is now emergingly supported from neuroimaging and CSF and postmorten findings.Review about the present status of ME hypothesis and autoimmune psychosis and remainig challenges to assess and categorize mild neuroinflammation.expert reviewAutoimmune Encephalitis presenting with exclusive psychiatric symptoms and all cases of Autoimmune Psychosis  match the proposed ME criteria ( Bechter 2001 & 2013). Majority of these cases of an autoimmune type of ME are well treatable with immune modulatory treatments. It remained unclear, whether CNS antibodies are causal or contributive by shaping the observed clinical syndrome. The increasing evidence of mild neuroinflammation present in considerable subgroup of schizophrenia or psychosis spectrum cases from ongoing clinical studies, including CSF  and neuroimaging plus the observed clinical improvement with immune modulytory therapies, strongly support ME hypothesis, potentialy even in considerably larger subgroup of SMDs,supported by brain biopsy  and post mortem studies .Beyond ME even more refined categories of mild neuroinflammation, including parainflammation ( proposed by Medzhitov 2008) and neuroprogression  need to be considered in further research on the possible role of mild neuroinflammation in SMDs .No significant relationships."}
+{"text": "Chronic pain leading to a reduced quality of life is one of the most important health problems worldwide. It has been estimated that 10% of adults are diagnosed with chronic pain each year. However, despite the high prevalence of chronic pain, its treatment options are limited, in part, due to the variety of chronic pain conditions with different aetiologies  and because their pathophysiological mechanisms are only partially known and can change with time. Therefore, there is a huge unmet need for new effective therapies for the control and/or prevention of multifarious chronic pain conditions.Chronic pain is associated with neuroinflammation where cellular and molecular immune components such as microglia and astrocytes, cytokines, complement, and pattern-recognition receptors act as key regulators of pain signalling. Emerging evidence indicates long-term effects of COVID-19 infection can exacerbate neuroinflammation conditions underlying chronic pain. The exact mechanisms underlying the link between neuroinflammation, and chronic pain are still not clear and the study of innovative approaches targeting neuroinflammation pathways and their resolution is currently an emerging field of pain research.The goal of this Research Topic is to compile a series of articles focused on identifying, treating, and modulating neuroinflammation-associated chronic pain, aiming to improve our understanding and enhance the development of novel therapeutic strategies.O\u2019Brien and McDougall demonstrated that the role of PAR4 may be engaged early in OA disease progression i.e., during the acute predominantly inflammatory phase, but not late phase. Blockade of PAR4 may therefore be most suitable for early OA pain treatment or during episodic flares. Chronic inflammation and associated pain can also be caused by oxidative stress during ferroptosis, a process of apoptotic lipid peroxidation caused by iron overload. SIRT2 (a NAD + - dependent deacetylase) may regulate oxidative stress  and increasing evidence indicates that SIRT2 is involved in inflammatory processes particularly prominent in e.g. arthritis . In this Research Topic Zhang et al. presented the first data that SIRT2 relieves mechanical allodynia, enhances ferroportin 1, inhibits intracellular iron accumulation and reduces oxidant stress levels in a rat spared nerve injury (SNI)-induced neuropathic pain model. Two other studies support this view  consequently, understanding the physiological mechanism of SIRT2 may help inform clinical treatment of neuropathic pain.The immune system plays a fundamental role in the generation of inflammation which is a protective reaction of the body against injury or infection. Dysregulation of the immune system can lead to conditions such as cytokine storm which can be life threatening. Protease activated receptors (PARs) play an important role in mediating some of the inflammatory and pain responses associated with immune-mediated inflammatory conditions for example Osteoarthritis (OA). Johnston et al. review how the interaction between the immune system and the nervous system contribute to the development and maintenance of chronic pain in production animals  highlighting important gaps in our knowledge of the pathophysiology and measurement of pain states in livestock. Livestock offer promising translational models of naturally occurring painful conditions in humans  due to their larger size , similar anatomy and histomorphology of regions of interest to human neuroimmune and pain processing . The development and application of objective measures of pain per se e.g., biomarker tests in production animals  present exciting opportunities to improve our fundamental understanding of chronic pain and better inform human clinical pain management and animal husbandry practices and pain interventions. Gada et al. review and emphasise the importance of identifying signature miRNA regulatory networks  in neuroinflammation and associated neuropathic pain with a focus on human and rodent microRNAs. This they suggest, will help facilitate the discovery of novel miRNA/target biomarkers for more effective diagnosis, prognosis, and management of neuropathic pain in the future. Li et al. provide a mini review for the theoretical basis (regulation of pro-inflammatory cytokine expression and modulation of estrogen receptors) and clinical treatment of multiple types of chronic pain  using the traditional oriental herbal drug Panax ginseng (ginseng and its active constituents including ginsenosides). Finally, Valentine et al. emphasize an important link between vascular-immune interactions and chemotherapy-induced proinflammatory neuropathic pain. This perspective highlights the fundamental importance of the permeability of the vasculature within the somatosensory nervous system in promoting a pro-inflammatory environment and the development of neuropathic pain.The current Research Topic also includes critical reviews and a perspective paper. Panex Ginseng, PAR4 and SIRT2. However, as reflected by the original research papers and reviews, it is clear that more research is needed to identify central neuroinflammatory mechanisms driving chronic pain as well as the identification of reliable and translational objective biomarkers of pain in both the preclinical and clinical setting.In conclusion, the Research Topic explores an array of neuroinflammatory mechanisms from serine proteases in early OA, ferroptosis in NP, miRNA regulatory networks and vascular-immune interactions linked to chronic pain. Evidence has been presented for innovative therapeutic target approaches for chronic pain, including"}
+{"text": "AJing Xu's name, affiliation and E-mail address were incorrectly reproduced in the published article. The correct versions are shown here.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."}
+{"text": "Personality disorders (PD) in adolescence are widespread. It creates problems of social adaptation of patients and represents significant risk factors for auto-aggressive behavior, including suicidal one. The neurobiological basis and EEG markers of PD in adolescence have not been adequately studied.The aim of the study was to reveal the EEG features and their correlations with clinical parameters in male adolescents with borderline personality disorder (BPD) and narcissistic personality disorder (NPD), possibly mediating some aspects of their clinical traits.28 BPD patients  and 24 NPD patients , as well as 24 healthy controls (HC) aged 16-25 years were enrolled in the study. HDRS-21 and HAM-A scales were used for quantitative assessment of patient\u2019s conditions. Pre-treatment resting EEG was recorded, and EEG spectral analysis was carried out in 8 narrow frequency sub-bands. Descriptive statistics and correlation analysis of EEG and clinical data were performed.EEG spectral parameters in BPD group did not differ significantly from those of HC. NPD group shows the EEG signs of more activated brain cortex than in both BPD and norm groups caused by decreased functional state of the anterior cortical regions. The structure of correlations between EEG parameters and clinical scores also differed between BPD and NPD groups.The data obtained suggests that these features of the brain activity may contribute to the disturbance of emotion regulation and of behavior control in adolescent patients with BPD and NPD, more pronounced in NPD group.No significant relationships."}
+{"text": "What can muscles, gait, and brain activity tell us about cognitive decline? Are there certain markers we can track that are early predictors of cognitive status years later? In the current symposia, our goal is to address these questions with recent pilot, longitudinal and cross-sectional studies that measure potential markers of cognitive decline in different older adult cohorts. The first speaker will present findings on changes in skeletal muscle adiposity and 10-year change in global cognition from the Health Aging and Body Composition  study. The second speaker explores cross-national comparisons of gait speed and its association with cognitive function from the Cohort Studies of Memory in an International Consortium (COSMIC). The third speaker investigates changes in brain activity with functional near infra-red spectroscopy (fNIRS) from single to dual-task walking and its relation to changes in several gait quality parameters. The fourth speaker presents pilot work that examines dual-task gait and tapping with fNIRS and compares the dual-task performance and brain activity of older adults who report experiencing subjective cognitive decline to those that do not. The final speaker presents findings from the Baltimore Longitudinal Study on Aging (BLSA) that demonstrate that early markers of slow gait and metabolic dysfunction could identify those at risk of progression to dementia 7 years prior to onset. Taken together, the findings from this symposium present novel markers of changes in cognitive function in older adults and ultimately targets for prevention or slowing of cognitive declines in older adults at risk for dementia."}
+{"text": "Transgender people represent a broad spectrum of individuals that transiently or persistently identify with a gender different from the one assigned at birth . Transgender healthcare issues have become an increased matter of interest over the last years, as shown by the growth of publications on the subject and by the increase of referrals reported worldwide in all age groups. However, transgender people report encountering numerous obstacles in accessing and receiving appropriate health care with professionals being described as not properly trained on specific gender issues. Considering the diversity and complexity of the gender spectrum in the different age groups and in light of the recent changes in the formal psychiatric classification, mental health providers play a critical role in meeting the needs of gender non-conforming children, adolescents and adults, according to individualized paths. This course has the following aims: (1) learn the principles of assessment of gender incongruence in childhood, adolescence and adulthood; (2) address co-occurring psychopathology (if present); (3) identify different treatment paths according to age and individualized psychological and/or medical needs; (4) work in a multidisciplinary team in line with an integrated model.No significant relationships."}
+{"text": "Deng et al.) and to revise the effect of resistant starch on non-alcoholic fatty liver disease via the gut-liver axis . One brief research report was devoted to analyse the accumulation of flavonoids in Dendrobium moniliforme (L.) Sw.  by the integration of metabolomic and transcriptomic approaches . The other seven papers were published as original research contributions and were focused on (i) the integrated analysis of metabolome and transcriptome data for uncovering flavonoid components of Zanthoxylum bungeanum Maxim leaves under drought stress ; (ii) the integrated metabolomic and transcriptomic analyses to reveal novel insights of anthocyanin biosynthesis on color formation in cassava tuberous roots ; (iii) the identification of iron and zinc responsive genes in pearl millet using genome-wide RNA-sequencing approach ; (iv) the identification and analysis of major flavor compounds in radish taproots by widely targeted metabolomics ; (v) the development of a new indicator of overeating saturated fat based on serum fatty acids and amino acids and its association with incidence of type 2 diabetes using two randomized controlled feeding trials and a prospective study ; (vi) the optimization of the ultrasound-assisted extraction of naturally occurring glucosinolates from by-products of Camelina sativa L. and their effect on human colorectal cancer cells  and (vii) the investigation of the molecular mechanisms of flavonoid accumulation in germinating common bean (Phaseolus vulgaris) under salt stress . We hope this article collection may help, inform and provide direction and guidance to many colleagues working in this hot field of research.Nutrition and Food Science and Technology is facing important challenges nowadays, mainly related to the roadmap toward the achievement of the Sustainable Development Goals (SDGs) such as zero hunger SDG-2), good health and wellbeing (SDG-3), responsible consumption and production SDG-12), climate action (SDG-13), life below water (SDG-14), and life on land (SDG-15), among others. To be able to advance in these goals, sustainable food production systems are needed, while ensuring food safety (2, climat, good heInsights in Nutrition and Food Science Technology. AC supervised and wrote the editorial article. EI reviewed the final version of the editorial article. Both authors approved the final version of the manuscript for publication.EI and AC acted as editors of all the manuscript submitted to the Research Topic"}
+{"text": "For seven years, the University of Rhode Island (URI) Engaging Generations Cyber-Seniors Program has utilized university student mentors through an internship format and integration within service learning courses. In 2019, community interest in the program significantly increased as did student interest in gerontology internships. This led us to develop a robust internship program focused on building age and digital inclusivity across campus and the state of RI. The program integrates a three-pronged approach where students complete field hours within the URI Cyber-Seniors program, focus on enhancing the Career Readiness Competencies employers seek in graduates today as determined by the National Association of Colleges & Employers, and complete the components necessary to earn the Geriatric Education Center Interprofessional Teamwork in Geriatrics and Gerontology Certificate. This process has enabled 350 students from different majors, including Pharmacy and Human Development & Family Science, to complete internship experiences ranging from 30 to 210 hours."}
+{"text": "The term pathological pseudoreligiosity (PPR) has been chosen for description of mental disorders with religious content (MDRC), accompanied with distortion of acceptance and assimilation of religious convictions, and with significant changes in patient\u2019s religious behavior and way of life.To assess the entire spectrum of mental pathology with religious content and relate it to the depth of mental disorder.857 patients , with religious worldview and mental disorders were observed with psychopathological and follow-up methods.The pathological pseudoreligiosity was detected in 326 patients \u2013 38%. Follow-up period estimated mean 9,5 years. Next mental disorders with religious content were identified and described. Specific PPR types were correlated with register of the depth of mental disorder (K. Schneider):Management and treatment of patients suffering from MDRC with pathological pseudoreligiosity requires a particular approach. The consideration must be given to religious content of mental disorders and to clinical specifics of these disorders.No significant relationships."}
+{"text": "Even though cognitive impairment is considered a hallmark of schizophrenia, it has not been included as a criterion into major diagnostic systems.To test whether a set of clinical-defined cognitive impairment criteria can have utility in the assessment of psychosis patients in clinical practice.We assessed 98 patients with a psychotic disorder, diagnosed using DSM 5 criteria. We developed a set of cognitive impairment associated with psychosis (CIAPs) criteria following the format of current DSM criteria and based on previous literature. The CIAPs criteria include: A) criterion for evidence of cognitive impairment after the beginning of illness; B) cognitive impairment clinically evidenced, affecting functioning in everyday activities in at least two out of six cognitive domains; C) and D) exclusion criterion for either delirium or other neurocognitive disorders, respectively, as causal agents of the cognitive impairment. The psychosis patients dichotomized by the CIAPs criteria were tested regarding the neuropsychological performance in attention, speed of processing, verbal memory, visual memory, working memory, executive function and social cognition tasks. Also a Global Cognitive Index was calculated.Forty-three patients with psychosis fulfilled the CIAPs criteria (43.9%). MANOVA profile analyses revealed a pattern of statistically significant deficits in all the cognitive dimensions except for social cognition in CIAPs+ patients regarding CIAPS-, with prominent deficits in processing speed and memory functions.The CIAPs criteria could be an auxiliary method for clinicians to assess cognitive impairment. It may also permit clinical estimation of the influence of cognitive deficits on the ecological functioning of patients.This work was supported by the Government of Navarra  and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148). Both had no further role in the study des"}
+{"text": "Indigenous peoples worldwide face unique challenges growing old. Many of these challenges are remnants of previous colonization practices and current oppressive systems often leading to out-migration from rural to urban environments. Despite Anchorage having the highest population of Alaska Native Elders little is known about the experience of relocation. This study investigated the impact of culture on the experience of successful aging within the Alaska Native context. Twenty-five semi-structured qualitative interviews with rural (N=13) and urban Elders  were conducted. The use of Gee\u2019s discourse analysis tools provided the framework for analyzing the discourse of Elders based on location and traditional or western influences on subjective successful aging. We explored the use of language within two identified discursive patterns: cultural discourse and Elder identity discourse. Social and contextual determinants of successful aging involve aspects of minority and majority culture and self-appraisal of successful aging based on cultural assumptions."}
+{"text": "Older adults with non-traditional family structures (unpartnered and childless) may be at higher risk for loneliness. Yet, experiences of loneliness during COVID-19 can vary depending on a country\u2019s context . We explore associations between older Europeans\u2019 family structure and loneliness to assess risks for those with non-traditional family structures  during the pandemic across a variety of country contexts. We analyze data from the Survey of Health, Ageing and Retirement in Europe (SHARE) collected before (2019/2020) and twice during  the pandemic to examine if unpartnered and childless older adults are at higher risk of loneliness, and compare results by multiple indicators of country context . Results of this study can potentially inform current and future pandemic mitigation strategies."}
+{"text": "This Special Issue focuses on the rapidly evolving field of immune-mediated inflammatory diseases (IMIDs) and the achievements that were made over the last 10 years. With the advent of novel technologies such as single-cell RNA sequencing (scRNAseq) and state-of-the-art imaging techniques, researchers in our field have made tremendous progress in unraveling the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA), vasculitis and systemic lupus erythematosus, as well as \u201cautoinflammatory\u201d diseases such as spondyloarthritis (SpA) and fever syndromes. The novel technologies have also provided insights into the contribution of specific (subsets of) immune cells and stromal cells to the inflammatory response, and into the molecular pathways associated with the pathological processes involved. These advances have led to the identification of promising new therapeutic targets for these diseases and paved the way for novel treatments. However, for rare IMIDs, we are far from fully understanding the mechanisms leading to the development and progression of disease, as well as the response to therapy. A better understanding of the molecular and cellular signatures of these diseases may elucidate potential new treatment options.Several contributions to this issue focus on the role of B lineage cells in systemic autoimmune diseases. Merino Vico et al. review the current literature and highlight the importance of these cells in ANCA-associated vasculitis . In an oThe importance of a tightly regulated innate immune system is underscored by an intriguing report demonstrating that efficient neutrophil activation requires the simultaneous ligation of two different receptors by two independent stimuli . The reqAlthough the involvement of immune cells in the pathogenesis of IMIDs has long been recognized, the crucial role of stromal cells in these diseases has only recently been appreciated. The importance of stromal cells was recently highlighted by an innovative approach in which pathogenic cells were depleted by photodynamic therapy (tPDT) that activated photosensitizer (IRDye700DX)-conjugated antibodies directed against fibroblast activation protein (FAP) on fibroblasts. This novel phototherapy strategy led to the dose-dependent depletion of primary skin fibroblasts revealed in lesional skin biopsies of systemic sclerosis (SSc) patients upon light exposure in a 3D culture system . In anotBesides these more basic and translational studies, the Special Issue includes comprehensive review articles on the pathophysiology and treatment of idiopathic inflammatory myopathies  and the Collectively, the articles in this Special Issue illustrate the breadth of recent advances in IMIDs research and demonstrate the potential of novel technologies such as advanced microscopy methods and (sc)RNAseq to dissect pathological processes and identify novel therapeutic targets to solve unmet clinical needs in these diseases. The future is looking bright!"}
+{"text": "The scarcity of human data, the limitation of time and resources for experimental testing, and societal pressure to develop animal-free testing strategies are driving the field of toxicology toward new methods to generate and interpret data for chemical risk assessment . ComputaThe ability to rapidly screen chemicals for biological activity and reduce the use of animals in toxicity testing has been the goal of regulatory toxicology for several decades. With current technological and scientific advances, scientists seek to apply high throughput screening assays and computational toxicology techniques to evaluate and screen large numbers of chemicals and drug data sets for biological activity .in vitro toxicokinetic data is essential to meet the growing regulatory need to improve chemical safety assessments  and toxicityin vitro to in vivo extrapolation (QIVIVE) in environmental risk assessment\u2022 Development and application of a computational workflow for probabilistic quantitative \u2022 Data harmonization and curation from human studiesThis research topic on applying computational tools to health and environmental sciences brings together exemplars of current modeling efforts that seek to play an important role in next-generation risk assessment, such as:The overall aim is to develop and engage model developers and users to promote and maximize benefits from basic and applied research that is being undertaken to protect public and environmental health.Nicolas et al. presented a case study demonstrating the utility of exploiting existing computational methods  at the pre-assessment phase of a tiered risk-based approach to prioritize thousands of untested chemicals quickly and conservatively for further research.Pierro et al. developed a data-driven model to identify chemicals associated with all-trans retinoic acid (ATRA) pathway bioactivity and prenatal skeletal defects. The model provides potential avenues for new mechanistic discoveries related to ATRA pathway disruption and associated skeletal dysmorphogenesis due to environmental exposures.Khalidi et al. presented an R-based workflow for automated high-throughput PBK simulation with the Simcyp \u00ae simulator called \u201cSimRFlow.\u201d It is a time-efficient tool for simulating the biokinetics of many compounds without the manual curation of physicochemical or experimental data necessary to run Simcyp\u00ae simulations.Mandal et al. performed a correlation analysis of variables from the Atherosclerosis Risk in Communities (ARIC) Study. The developed workflow could be incorporated into data harmonization efforts to reduce the human effort required for initial variable mapping and provide crucial quantitative information to assist with the harmonization.Zhao et al. provided a basis for exploring toxicokinetics, toxicity, and valuable mechanistic insight. Integrating toxicokinetics of arenobufagin (ArBu) with lipidomics and proteomics approaches based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) can accurately identify and quantitatively compare proteins, which is of great significance in the determination of ArBu cardiotoxicity and efficacy mechanisms.Tan et al. developed a physiologically-based pharmacokinetic (PBPK) model capable of simulating cefadroxil concentrations in plasma and tissues in mice, rats, and humans. The model is helpful for dose selection and informative decision-making during clinical trials and dosage form design of cefadroxil and provides a reference for the PBK studies of hPEPT1 substrate.Loizou et al. provided a state-of-the-art computational workflow that integrates PBK modeling, global sensitivity analysis (GSA), approximate Bayesian computation (ABC), Markov Chain Monte Carlo (MCMC) simulation, and the Virtual Cell Based Assay (VCBA) for the estimation of the active, free in vitro concentration of a chemical in the reaction medium were developed to facilitate quantitative in vitro to in vivo extrapolation (QIVIVE).In summary, this research topic presents some recent developments and perspectives on the challenges in computational toxicological modeling, their applications, integration of data and tools, and their potential to meet different case scenarios within environmental and human health risk assessment. The development of computational toxicology tools and approaches should accelerate with the availability of open-source toxicological databases to provide a more quantitative, biologically based assessment of the risk of chemicals in the environment."}
+{"text": "The vast amount of data produced by healthcare systems both structured and unstructured, termed `Big Data' have the potential to improve the quality of healthcare through supporting a wide range of medical and healthcare functions, including clinical decision support, disease surveillance, and population health management. As the field of big data in healthcare is rapidly expanding, methodology to understand and analyze thereby enhancing and optimizing the use of this data is needed. We present priorities determined for future work in this area.An international collaboration of health services researchers who aim to promote the methodological development and use of coded health information to promote quality of care and quality health policy decisions known as IMECCHI -proposes areas of development and future priorities for use of big data in healthcare. Thematic areas were determined through discussion of potential projects related to the use and evaluation of both structured /codeable and unstructured health information, during a recent meeting in October 2015.Several themes were identified. The top priorities included: 1) electronic medical record data exploration and utilization; 2) developing common data models and multimodal /multi-source databases from disparate sources development; 3) data quality assessment including developing indicators, automated logic checks and international comparisons; 4) the translation of ICD-10 to ICD-11 through field-testing 5) Exploration of non-physician produced/coded data; and 6) Patient safety and quality measure development.A list of expert views on critical international priorities for future methodological research relating to big data in healthcare were determined. The consortium's members welcome contacts from investigators involved in research using health data, especially in cross-jurisdictional collaborative studies."}
+{"text": "In Response: I thank the authors for their favorable commentary (Underreporting of chikungunya cases in Jamaica has been acknowledged and has multiple factors (It is possible that many excess deaths in Jamaica during 2014 were the result of chikungunya virus infections escaping surveillance. Chikungunya fatalities may be difficult to capture with limited surveillance capacity. Furthermore, chikungunya virus infections, particularly in the elderly, may exacerbate existing comorbidities and lead to extended hospitalization that could result in nosocomial infections; either event may prove fatal and ultimately be considered the cause of death (During the COVID-19 pandemic in Jamaica, surveillance systems have been bolstered; the Ministry of Health and Wellness introduced broad community-based testing, many diagnostic laboratories have introduced real-time PCR testing, and the University of the West Indies has introduced next-generation techniques sequencing techniques for whole-genome sequencing of viruses. Further enhancing responses to emerging viruses, the University of the West Indies recently became a member of the Abbott Pandemic Defense Coalition that aims to increase virus surveillance and discovery ("}
+{"text": "This study examined the trajectory of family function of Chinese stroke survivors and its impact on cognitive impairment.We conducted a prospective longitudinal study and assessed family function of 170 stroke survivors and their family caregivers by Family Assessment Device(FAD) during acute stage and at 3, 6 months after onset via face-to-face follow-ups interview in Nanjing, China from January to October, 2020.Group-based Trajectory Model was applied to analyze trajectories of family function. Family function deteriorated with time. Four patterns of FAD trajectory  were identified. Healthy and stable family function was associated with better cognition and quality of life . Future studies are needed to further explore the reason why family function deteriorated and the linkage between family function and stroke survivors\u2019 outcomes."}
+{"text": "While public health experts cannot yet say how to prevent Alzheimer\u2019s disease and related dementias (ADRD), emerging science indicates that ADRD may be slowed through the implementation of risk reduction strategies, early diagnosis, and better education and training of front-line health care professionals. The Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer's Act was introduced into the Senate (S. 2076) on November 6, 2017 and signed into law on December 31, 2018 (P.L. 115-406) amending the Public Health Service Act . CDC's Alzheimer's Disease and Healthy Aging Program (AD+HAP) was authorized to implement the activities outlined in BOLD which were designed to create a uniform national public health infrastructure. This presentation will provide an overview of BOLD and the demonstrate how BOLD Program and Public Health Centers of Excellence recipients are working together to build a uniform national public health infrastructure."}
+{"text": "Coverage of essential prevention and control services and adequate monitoring schemes for viral hepatitis are often suboptimal in prison settings. Yet, evidence shows that targeted interventions are feasible and effective in reducing viral hepatitis burden and decreasing virus circulation among people living in prison and the community at large. To promote transferability and improvement of prison health quality in EU/EEA the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) will identify and disseminate models of care for viral hepatitis elimination in prisons.The models of care were gathered using a data collection tool that has been designed for this purpose based on the literature review and agreed with an expert advisory group. Based on the results of the data collection, a survey for healthcare staff working in 5 selected prison institutions in the EU/EEA has been developed.The following models of care were collected: HCV micro-elimination in prison; transitional care for HCV treatment or HBV prevention/treatment; HCV or HBV care services tailored to women living in prison; HBV or HAV/HBV vaccination in prison settings. Harm reduction and drug treatment services in the prison are essential at all steps of the prevention and continuum of care. Among barriers identified were: engagement of people living in prison and prison governance structure, availability of infrastructural and human resources, daily prison organisation, inter-sectorial collaboration within prison and between prison and community services, training for prison staff and lack of systematic monitoring.Evidence of effective and acceptable interventions in prison to prevent and control viral hepatitis is essential to foster inclusion of prison setting within national elimination programmes. Intra-EU benchmarking may help promote awareness, to allocate adequate resources, monitor of impact and ultimately the achievement of the elimination goal."}
+{"text": "The regulation of cerebral blood flow (CBF) is a complex and tightly controlled function ensuring delivery of oxygen and nutrients and removal of metabolic wastes from brain tissue. Cerebral vasoreactivity (CVR) refers to the ability of the nervous system to regulate CBF according to metabolic demands or changes in the microenvironment. This can be assessed through a variety of nuclear medicine and imaging techniques and protocols. Several studies have investigated the association of CVR with physiological and pathological conditions, with particular reference to the relationship with cognitive impairment and cerebrovascular disorders (CVD). A better understanding of the interaction between CVR and cognitive dysfunction in chronic and particularly acute CVD could help improving treatment and rehabilitation strategies in these patients. In this paper, we reviewed current knowledge on CVR alterations in the context of acute and chronic CVD and cognitive dysfunction. Alterations in CVR and hemodynamics have been described in patients with both neurodegenerative and vascular cognitive impairment, and the severity of these alterations seems to correlate with CVR derailment. Furthermore, an increased risk of cognitive impairment progression has been associated with alterations in CVR parameters and hemodynamics. Few studies have investigated these associations in acute cerebrovascular disorders and the results are inconsistent; thus, further research on this topic is encouraged. Cerebral circulation delivers oxygen and nutrients and removes metabolic products from the brain tissue to ensure neuronal health and brain function. The high metabolic needs of the brain require a large volume of blood flow, comprising almost 20% of the total cardiac output. Therefore, the regulation of cerebral blood flow (CBF) is a complex and tightly controlled function Aaslid . The maiCerebral autoregulation refers to the intrinsic ability of blood vessels to maintain CBF relatively constant within a wide range of values of systolic blood pressure (50\u2013150\u00a0mmHg). Beyond these boundaries, CBF depends passively on perfusion pressure, thus entailing potentially harmful hypo- or hyperperfusion of cerebral tissue  refers to the ability of the nervous system to regulate CBF according to the metabolic requirements or chemical variations of the microenvironment Wolf .The evaluation of CVR is of great interest as an index of \"hemodynamic reserve\"(HR) in patients with cerebrovascular disease. The HR consists of potential residual vasodilatory capacity plus the possibility of increasing the rate of oxygen extraction from the blood compartment in critical CBF conditions   compared to basal values , single photon emission computed tomography (SPECT), fMRI, computerized tomography (CT) with xenon-enhancement, and transcranial doppler sonography (TCD) , allowing a simple, non-invasive, reliable and reproducible method  exploits hypercapnia generated by 30-s apnea to calculate a response index defined as breath-holding index (BHI). BHI is a non-invasive, easy to perform, well-tolerated and widely accepted test (Markus and Harrison 2 (approximately 3\u20134\u00a0mmHg), the need for patient collaboration and the reduced reproducibility of this approach.In clinical practice, several tests are available to evaluate CVR. The COAging is physiologically accompanied by changes of cerebral autoregulation mechanisms with the decrease of CBF and blood volume flow and the reduction of elasticity of small intracranial arteries  brain circulation ; (ii) cerebrovascular diseases  (iii) cognitive impairement . Search strategy included a combination of keywords, using the Boolean operators \u201cAND\u201d and \u201cOR\u201d. Search fields were restricted to the abstract, title, and keywords. Included papers were original peer-reviewed scientific journal articles, editorials, case studies, letters or reviews. Studies not examining the correlation between CVR, cognitive functions and CVD were excluded. Two independent reviewers [MS and GS] screened the titles and abstracts of all studies to identify potentially relevant articles. Duplicates were manually removed. Full texts of all included studies were then obtained and reviewed. The following 5 parameters were reviewed from the retrieved articles by two independent reviewers: (1) study characteristics; (2) participant characteristics; (3) tools for measuring CVR; (4) measure of cognitive function; and (5) main findings. Quantitative analysis and assessment of the risk of bias were not performed due to the narrative design of the study. The quality assessment was appraised by two independent reviewers ; disagreements between evaluators were resolved through discussion.Several studies demonstrated the correlation between alteration of brain vessel reactivity and impaired cognitive functions in patients with cognitive derangement. Arteriolosclerosis, amyloid angiopathy, atherosclerosis and lipohyalinosis have been associated with impaired cerebral hemodynamic and cognitive impairment  . Microangiopathy represents a prominent cause of lacunar stroke and vascular dementia (VaD)  is a frequent disease in aging and a well-described condition associated with CVR impairment. OSAS is a disorder characterized by recurring episodes of obstruction and partial or complete collapse of the rhino\u2010oropharynx during sleep. These are caused by anatomical upper airway alteration combined with impaired ventilatory control or alteration of neurofunctional control of rhino- and oropharyngeal muscles. The episodes lead to intermittent oxygen desaturation and are associated with sleep fragmentation, cerebrovascular and cardiovascular disease, excessive daytime sleepiness and cognitive dysfunction. A comprehensive review by Beaudin et al.  addresseIn recent years, evidence has accumulated on the association between impaired cerebral hemodynamics and cognitive functions in patients suffering from neurological disorders, in particular cerebrovascular diseases, as if reduction of cerebral blood flow and brain perfusion may contribute to cognitive derangement (Mori et al. Executive functions are essential for regulating goal-oriented behaviors and responding to new and novel settings, by combining working memory, planning, orientation problem-solving, self-monitoring and error correcting. Recent studies suggest that executive dysfunction in stroke patients produces reduced performances in both basic and complex activities of daily living and compromises rehabilitation outcomes (Zinn et al. Table"}
+{"text": "Increasing educational attainment (EA) could decrease the occurrence of depression. We investigated the relationship between EA and depressive symptoms in older individuals across four European regions.1) examine association between EA and depressive symptoms 2) determine, if there is an upper limit to this association 3) explore regional and demographic differences within this relationship across EuropeWe studied 108 315 Europeans  in Europe assessing EA and depressive symptoms. Logistic regression estimated the association between EA and depressive symptoms, adjusting for sociodemographic and health-related factors; testing for sex/age/region and education interactions.Higher EA was associated with lower odds of depressive symptoms, independent of sociodemographic and health-related factors. A threshold of the lowest odds of depressive symptoms was detected at the first stage of tertiary education . Central and Eastern Europe showed the strongest association  and Scandinavia the weakest . The association was strongest amongst younger individuals. There was a sex and education interaction only within Central and Eastern Europe.Level of EA is reflected in later-life depressive symptoms, suggesting that supporting individuals in achieving EA, and considering those with lower EA at increased risk for depression, could lead to decreased burden of depression across the life-course. Further educational support in Central and Eastern Europe may decrease the higher burden of depressive symptoms in women.No significant relationships."}
+{"text": "The mild encephalitis hypothesis(ME)  proposed that mild neuroinflammation triggered by infections, autoimmunity, trauma or toxicity (including from stress) might causally underly a spectrum of severe mental disorders (SMDs), especially disorders of the schizophrenic and affective spectrum.The development from ME hypothesis to the new diagnoses of Autoimmune Psychosis (AP) and a subgroup of Autoimmune Encephalitis (AE) and beyond into future research is reviewed and discussed.Expert reviewThe subgroup of AE with exclusive or predominant psychiatric symptoms  and all cases of AP  match the previous poposed ME criteria. AE and AP can now successfully be treated in majority of cases by immune modulatory treatments. These new insights challenge both, the implementation of diagnosis and treatment into clinical reality and forthcoming research on the causality underlying severe mental disorders (SMDs). CSF studies showed in 50-70% of therapy resistant cases of affective and schizophrenic spectrum disorders some abnormalities compatible with mild neuroinflammation , recently confirmed in large patient samples from various university hospitals in Germany .Also post mortem findings are compatible with ME hypothesis in a larger subgroup of SMDs. Open questions of new clinical categorization by refined grading of mild neuroinfalmmation by improved diagnostic methods appear increasingly required, which will be discussed ( Bechter Frontiers Psychiatry 2020).Mild neuroinflammation appears causally involved in SMDNo significant relationships."}
+{"text": "Older immigrants in affordable housing have unique sets of challenges during the COVID-19 pandemic posed by limited English proficiency and resources. The aggregated living condition could increase their risk of being exposed to the contagious disease. This symposium reports empirical findings of the social Network of Immigrant Chinese older adults in affordable Housing Environment (NICHE) project, which focused on the influence of COVID-19 on underprivileged Chinese older immigrants. We conducted 27 semi-structured interviews with foreign-born older Chinese immigrants  in an affordable housing in Los Angeles to learn about their lived experiences and coping strategies during the COVID-19 pandemic. The first presentation focused on the changes in older Chinese immigrants\u2019 social life after the onset of the pandemic and aimed to understand the pandemic\u2019s impact on their depressive symptoms and loneliness. The second presentation describes older Chinese immigrants\u2019 perceived pandemic-related stressors and resilience across phases of the pandemic, including at the beginning, after they got vaccinated, and the rising of delta variant. The participants explained what supportive services had been helpful and what support they wished they could have over the past two years in the pandemic. The third presentation reports the experience of being discriminated against during the pandemic, the Chinese older adults\u2019 attitudes towards these discriminatory events, and coping strategies. Together, these three presentations will depict the lived experience of Chinese immigrants over two years during the pandemic and discuss intervention strategies and policy considerations for preparing for future crisis like the COVID-19 pandemic."}
+{"text": "Infante and Etienne-Manneville; Kim et al., in this research topic issue) cell polarisation  epithelial-mesenchymal transitions and inflammatory responses . Their integrative role in mechano-signalling  is well founded and super-resolution microscopy demonstrates that stretching filaments will reveal new, and quite possibly novel, functional nanodomains  study the keratin intermediate filament network in the developing mouse embryo revealing a kaleidoscope of temporally and spatially determined expression profiles in embryonic and extraembryonic tissues which are interpreted as plastic adaptations of cell mechanics to growth and morphological changes. The review by Green and colleagues in this research topic issue focuses on the epidermal desmosome-keratin system as an integrator of mechanically-determined signalling. In concert with other junctions, desmosomes dictate epidermal polarization and differentiation forming a barrier by stratum-specific junctional and cytoskeletal arrangements. The authors suggest that these arrangements counteract inflammation. The paper by Yoon and colleagues in this research topic issue presents technical advancements for multidimensional and multimodal monitoring of keratin filament architecture and function. High resolution microscopy of fluorescent keratins is enabled on defined matrices and combined with traction force microscopy. In this way, the interrelationship between extracellular matrix cues with global 3D cytoskeletal network properties at the keratin filament/keratin bundle level and local forces is quantified by refined image analysis. It is further illustrated that these tools can be used for monitoring the consequences of local keratin network perturbations and ECM composition on cell mechanics in the context of transcellular network arrangement.The Research Topic highlights aspects of epithelial keratin network organization. Using a Krt8:YFP reporter mouse Desprin-Guitard and colleagues (see Infante and Etienne-Manneville in this research topic issue summarize current knowledge about the spatial arrangement and integration of cytoplasmic and nuclear intermediate filaments and their interaction with other cytoplasmic filament systems during cell migration. They emphasize the different properties of the different intermediate filament types as a basis of cell type- and function-related cellular mechanics. They further highlight the cooperativity between intermediate filaments with the other cytoskeletal systems determining motile properties of single cells and cell collectives. Direct experimental assessment of vimentin\u2019s function during metastatic invasion is finally provided by Kim and colleagues in this research topic issue. Using a novel vimentin-stabilizing drug they report on altered vimentin network morphology with consequences on adhesion and contractility resulting in cell shape changes, increased tractions forces and perturbed migration."}
+{"text": "To assess the learning needs of the memory team multidisciplinary (MDT) staff working in South East Wales, in relation to diagnosis of dementia, types of dementia, anti-dementia medications and risk associated with dementia.An online anonymised survey was designed and distributed via email among memory team MDT staff of 3 different health boards of the South East Wales area which included Aneurin Bevan University Health Board, Cwm Taf Morgannwg University Health Board and Cardiff and Vale University Health Board.The survey was designed to gather information about their understanding of the common type of dementia, treatment with medication, indications and cautions related to medications, the potential side effects and risks associated with Dementia. The survey had a mixture of `Likert Scale` format with free text segments where their opinion was sought in their own words.Twenty-one (21) staff members responded to the survey. The majority (16) were psychiatric nurses, rest were psychologists and support workers.Thirteen (13) staff members reported they feel confident in identifying subtypes of dementia whereas the rest reported they can benefit from additional knowledge. Majority of staff felt they understood the indications of anti-dementia medication side effects of medications and risks associated with Dementia but do not fully understand the contra-indications and cautions related to anti-dementia medications.Participants suggested that regular teaching, lectures and updates should be arranged especially targeting the diagnostic criteria, medication and risk assessment. Sessions providing bite-size information on a regular basis to build on their knowledge base were suggested.Participants also suggested shadowing doctors and consultants in memory clinics as a useful tool to improve their knowledge base.MDT staff working with memory teams are at the front line of screening, assessments and providing help and treatment to patients and their families. It is important to make sure our staff are equipped with evidence-based accurate knowledge and training.This survey study indicated that MDT staff working within the memory team appreciate more training and helped identify the specific areas and mode of teaching required.Prescription of medication may be seen as a doctor's responsibility but we need to ensure our MDT staff has up to date knowledge of types of medications used, their indications, contra-indications, monitoring requirements, and side effects.Regular teaching, online modules and experience of shadowing with doctor's clinics should be offered to all the MDT staff."}
+{"text": "To assess the comparative accuracy of risk assessment models (RAMs) to identify women during pregnancy and the early postnatal period who are at increased risk of venous thromboembolism (VTE).Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.MEDLINE, Embase, Cochrane Library and two research registers were searched until February 2021.All validation studies that examined the accuracy of a multivariable RAM (or scoring system) for predicting the risk of developing VTE in women who are pregnant or in the puerperium (within 6\u2009weeks post-delivery).Two authors independently selected and extracted data. Risk of bias was appraised using PROBAST (Prediction model Risk Of Bias ASsessment Tool). Data were synthesised without meta-analysis.Seventeen studies, comprising 19 externally validated RAMs and 1 internally validated model, met the inclusion criteria. The most widely evaluated RAMs were the Royal College of Obstetricians and Gynaecologists guidelines (six studies), American College of Obstetricians and Gynecologists guidelines (two studies), Swedish Society of Obstetrics and Gynecology guidelines (two studies) and the Lyon score (two studies). In general, estimates of sensitivity and specificity were highly variable with sensitivity estimates ranging from 0% to 100% for RAMs that were applied to antepartum women to predict antepartum or postpartum VTE and 0% to 100% for RAMs applied postpartum to predict postpartum VTE. Specificity estimates were similarly diverse ranging from 28% to 98% and 5% to 100%, respectively.Available data suggest that external validation studies have weak designs and limited generalisability, so estimates of prognostic accuracy are very uncertain.CRD42020221094. A number of risk assessment models for venous thromboembolism (VTE) in pregnancy and puerperium have been developed using a variety of methods and based on a variety of predictor variables.This systematic review provides a comprehensive review of risk assessment models for predicting the risk of developing VTE in women who are pregnant or in the puerperium (within 6 weeks post-delivery).The newly developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) was used to evaluate the risk of bias and applicability of the available evidence.Heterogeneity in the included studies  and variable reporting of items precluded meta-analysis.Limitations of the existing evidence and areas of future research are highlighted.Venous thromboembolism (VTE) remains an important cause of maternal morbidity and mortality in the developed world.Risk assessment models (RAMs) have been developed to help stratify the risk of VTE during pregnancy and the early postnatal period. These models use clinical information from the patient\u2019s history and examination to identify those with an increased risk of developing VTE who are most likely to benefit from pharmacological thromboprophylaxis. Inappropriate use of VTE prophylaxis may not reduce VTE rates and may cause unnecessary harm especially through bleeding and bruising.The aim of this systematic review was to identify primary validation studies and determine the accuracy of individual RAMs that identify pregnant and postpartum women at increased risk of developing VTE who could be selected for thromboprophylaxis.A systematic review was undertaken in accordance with the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.All studies evaluating the accuracy  of a multivariable RAM (or scoring system) for predicting the risk of developing VTE were eligible for inclusion. We primarily sought and selected studies that included validation of the model in a group of patients that were not involved in the development of the prediction model. Although the included studies could have reported derivation of the model , we only used the external validation data to estimate accuracy, where appropriate. The study population of interest in our review consisted of pregnant and postpartum (within 6 weeks post-delivery) women who are at increased risk of developing a VTE and receiving care in both hospital, community and primary care settings. Studies that focused on non-pregnant women were excluded as these patient groups have VTE risk profiles that differ markedly from the obstetric population.https://www.cochranelibrary.com from inception), ClinicalTrials.gov  and the International Clinical Trials Registry Platform (WHO from 1990). All searches were conducted from inception to February 2021. The search strategy used free text and thesaurus terms and combined synonyms relating to the condition  with risk prediction modelling terms.Potentially relevant studies were identified through searches of several electronic databases and research registers. This included MEDLINE (OvidSP from 1946), Embase (OvidSP from 1974), the Cochrane Library (10.1136/bmjopen-2022-065892.supp1Supplementary dataAll titles were examined for inclusion by one reviewer (GR) and any citations that clearly did not meet the inclusion criteria  were excluded ). All abstracts and full-text articles were then examined independently by two reviewers (GR and AP). Any disagreements in the selection process were resolved through discussion or if necessary, arbitration by a third reviewer (JD) or the wider group  and included by consensus.For eligible studies, data relating to study design, methodological quality and outcomes were extracted by one reviewer (GR) into a standardised data extraction form and independently checked for accuracy by a second reviewer (AP). Any discrepancies were resolved through discussion, or if this was unsuccessful, a third reviewer\u2019s opinion was sought (JD). Where multiple publications of the same study were identified, data were extracted and reported as a single study.The methodological quality of each included study was assessed using PROBAST (Prediction model Risk Of Bias ASsessment Tool).Due to significant levels of heterogeneity between studies  and variable reporting of items, a meta-analysis was not considered possible. As a result, a prespecified narrative synthesis approachPatients and the public were not involved in the design or conduct of this systematic review.The design and participant characteristics of the 17 included studies are summarised in 24 27 32 34 36\u201338The majority of studies were conducted across antenatal and postnatal periods,Only a few studiesThe studies included in this review evaluated 19 externally validated RAMsThe overall methodological quality of the 17 included studies is summarised in 23\u201334 36\u201338Assessment of applicability to the review question led to the majority of studies being classed either as unclear (n=13)et al,This systematic review identified 19 externally validated RAMs  that aimed to predict the risk of VTE in pregnant and postpartum women and who could be selected for thromboprophylaxis. Although various risk models (based on a variety of predictor variables) are being used, most of these lacked rigorous development and evaluation. The predictive accuracy of the RAMs was highly variable, and the substantial risk of bias concerns and the general lack of methodological clarity and unclear applicability make meaningful comparisons of the evidence difficult.Despite the development and use of various RAMs to predict the risk of developing VTE in women who are pregnant or in the puerperium (within 6 weeks post-delivery), VTE remains the leading cause of direct maternity mortality in the UK (MBRRACE-UK report 2021). Several explanations for this are possible: the risk assessment tools are inadequate; the application of these tools is incomplete or inaccurate; the underlying VTE risks of the pregnant population  are changing from when the RAMS were developed; or all three problems are operating.The use of thromboprophylaxis was reported in nine studieset al,et al,To our knowledge, there are no previous systematic reviews on this topic. However, recently several large registries have been interrogated in an attempt to derive robust prediction rules for this population, although with some methodological concerns. Sultan This systematic review has several strengths. It is the first systematic review to evaluate RAMs for predicting the risk of developing VTE in women during pregnant and the puerperium periods, and was conducted with robust methodology in accordance with the PRISMA statementThe main limitations of this study related to the observational nature of the studies reviewed and their own limitations. Most of the included risk prediction studies were retrospective cohorts. Retrospective cohort studies of large health database registries are limited by poor data quality and failure to accurately ascertain outcomes and case\u2013control designs are prone to bias including uncontrolled confounding, temporal and selection bias.41Due to the high levels of heterogeneity between studies, we were unable to undertake any meta-analysis or statistical examination of the causes of heterogeneity due to the small number of external validation studies per risk model. Potential sources of heterogeneity include variation in study design, the study population, risk model implementation, outcome definition and measurement and the use of thromboprophylaxis. As a result, we reported descriptive statistics to provide a better understanding of the evidence base applicable to the subject matter, and shortcomings regarding reliability and validity of the data. Finally, assessments on study relevance, information gathering and validity of articles were unblinded and could potentially have been influenced by preformed opinions. However, masking is resource intensive with uncertain benefits in protecting against bias decisions.44et alVTE risk assessment is challenging for numerous reasons. Many risk factors for VTE are pre-existing and non-modifiable (such as parity and inherited thrombophilia). These are then often combined with evolving risk factors which can change over the course of a pregnancy or postnatal period. Despite wide scale awareness of VTE being a major contributor to maternal mortality, numerous challenges with VTE risk stratification have been highlighted. In the UK, the MBRRACE-UK report Despite lack of evidence, many guidelines and clinical care bundles include the use of RAMs to guide VTE prophylaxis. Recently published ACOG guidelines state that most RAMs have not been validated prospectively in the obstetrical population and that current usage of such models is based on extrapolations from non-pregnant women, who differ biologically from pregnant women. The practice bulletin emphasises the need for more research to identify optimal models.Currently, there are a number of risk assessment models for assessing risk of VTE in pregnancy and the puerperium. Our review has shown that none of these models has been adequately validated and they have limited abilities to detect those at risk of VTE."}
+{"text": "Cochlear implants (CIs), hearing prostheses that bypass sensory hair cells in the cochlea to directly stimulate the auditory nerve, have been shown to restore hearing for individuals with severe to profound hearing loss. Recent research has demonstrated enormous CI benefits for speech recognition, sound localization, as well as language development in children. The effectiveness of CIs is, however, affected by many factors, including the duration of deafness/hearing loss, implantation age, and duration of CI use. Whereas recent studies have largely focused on the effects of CIs on speech perception and production, further investigation is needed to study the effects of CIs on emotion processing, music perception, prosody perception, etc. The aim of this Research Topic Collection is to bring together studies addressing recent discoveries in the benefits and outcomes of cochlear implantation. A total of 17 papers are included in this Research Topic.Tao et al. investigated the connection between auditory segregation of competing speech in Mandarin-speaking bimodal CI users and the P300 component of event-related potentials elicited by 1 vs. 2 kHz contrast. Their results showed that the P300 amplitude was significantly correlated with the speech reception threshold in the same target-masker voice gender  condition in the CI group, which suggests the potential of P300 amplitude as a clinically useful neural indicator of central auditory processing capabilities that are susceptible to informational masking in bimodal CI users. (2) Xie et al. explored the relationship between the ability to detect frequency changes or temporal gaps and speech perception using psychophysical and neurophysiological methods among post-lingually deafened CI users. Their multiple regression analysis showed the predictive ability of gap detection threshold (GDT) and the amplitude of acoustic change complex (ACC) response on speech perception performance. This indicates that GDT  may work as an easy, quick and non-linguistic tool, and ACC amplitude induced by the temporal gap  may have the potential to predict speech outcomes. (3) Cartocci et al. studied the emotion processing of children with unilateral CI via EEG and behavioral measures. Compared to normal-hearing (NH) children, less accurate vocal emotional state recognition was observed in children with unilateral CI, which was correlated with increased gamma activity lateralization index (relatively higher right-hemisphere activity) in response to emotional speech stimuli. The implantation side for children with unilateral CI did not affect the contralateral gamma activity, but the age at implantation influenced emotion recognition. These indicate that a deficit in engaging the left hemisphere for emotional tasks exists in unilateral CI users and early implantation may be beneficial to children's emotion recognition. (4) Raghavendra et al. investigated the sound quality of speech produced by CI users from the perspective of NH listeners' perception. They decoded and re-constructed the speech envelope from single-trial EEG recorded on the scalp of the NH listeners using a regenerative model and computed the correlation between the actual and reconstructed speech envelope waveforms. They found that the perceived sound quality rating was associated with the cortical tracking of speech envelop, and speech produced by NH speakers was more closely tracked relative to that produced by CI speakers. (5) Lu et al. focused on the cortical coding of prosody measured by fNIRS in pre-lingually deafened children with CIs. They recorded cortical responses to natural sentences with strong or weak prosodic features, and evaluated participants' speech communication ability in three tasks of picture description, video content statement and free conversation. Weaker cortical activation and characteristic deficits in perceiving strong prosodies were observed in children with CIs compared to NH children. Sensitivity to strong prosodic information was significantly correlated with the speech communication ability of all children who participated in this study. This suggests the importance of speech prosody in children's speech development.Five papers utilized neuroimaging techniques, including electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS), to investigate CI users' cortical response characteristics on a range of auditory perception tasks. (1) As P300 is closely related to cognitive processes , Lu et al. retrospectively examined clinical results of children with cochlear nerve deficiency (CND) and CIs in order to identify main predictive factors and develop predictive models using machine learning. A parameter-optimized support vector machine based on the vestibulocochlear nerve (VCN) area and the number of nerve bundles (measured with high-resolution computed tomography) was constructed to predict speech perception performance. These two factors were suggested to have the ability to predict CI outcomes in children with CND , providing guidance on surgical side selection and prognosis. (2) Chao et al. focused on the predictive ability of pre-implantation imaging results for electrically evoked compound action potentials (ECAPs) of auditory nerve fibers in response to electrical stimuli in children with CND. They found that the width of the bony cochlear nerve canal or the VCN diameter did not correlate with ECAP responses, while the ratio of the VCN to facial nerve (FN) diameter was significantly correlated with the slope of the ECAP input/output function and the ECAP maximum amplitude. This suggests that the VCN to FN diameter ratio may be an effective predictor of the cochlear nerve function in children with CND and CIs. (3) Zheng and Liu reviewed CI outcomes in patients with auditory neuropathy caused by Otoferlin (OTOF) gene mutations. They concluded that patients with OTOF mutations had excellent performance in both sound perception and speech recognition, and suggested the importance of genetic analysis in localizing lesions and informing clinical decision-making. Early implantation for patients with biallelic OTOF mutations was encouraged. (4) Zhang et al. investigated the predictive power of imaging results but for the long-term auditory and speech perception development of pediatric CI users with common cavity deformity (CCD). Auditory and speech behaviors  improved over time after implantation in children with CCD, but were poorer than those of CI users with normal inner ear structures. The volume and lumen surface range of CCD reflected inner ear development and influenced CI outcomes.Understanding the predictive factors of CI users' auditory performance is crucial to prognosis and clinical decision-making. Factors that have reached general consensus such as age at implantation and duration of device use cannot explain all the variance in CI performance; exploring new independent factors that have predicative power is thus needed. (1) Mao et al. themed around Mandarin tone production of pre-lingually deafened children with CIs. They recorded monosyllables produced by each participant and calculated the differentiability and hit rate of different tones using acoustic analyses. In general, children with CIs exhibited significantly poorer tone productions in both measures compared with NH children. A weak correlation between age at implantation or duration of CI use and acoustic measures  of tone productions was noted. (2) Balkenhol et al. focused on the benefits of adding a hearing aid (HA) on the contralateral side of a CI for sentence recognition and auditory evoked potential (AEP) responses. Their results suggest that bimodal listeners can take advantage of head shadow and binaural summation effects, but cannot make use of binaural squelch and spatial release from masking at 6 months post-CI. The perceptual benefit of bimodal hearing may be objectively evaluated by the AEP responses, supported by a significant correlation of binaural summation effects with AEP latency differences between the bimodal and CI-only conditions. (3) Matz et al. studied auditory stream segregation in CI users by changing the spectral- and amplitude-modulation rate of narrowband noise (NBN) bursts. Their results showed the deficits of CI users in segregating NBN bursts into different auditory streams when they were moderately separated in the spectral domain compared to NH listeners. Both groups were able to utilize build-up effects to segregate auditory streams when lengthening the duration of stimulus sequences. (4) Liang et al. investigated the effect of implantation side on CI outcomes through behavioral measures and brain activation measured by ACC. Their results indicated that the implantation side may affect neural plasticity patterns in the adult population, demonstrated by a unique correlation between ACC activation patterns and performance in frequency change detection in subjects with a right-ear CI. (5) Yao et al. presented a literature review on the research status and future development of cochlear reimplantation. Although techniques are relatively matured since the 1980s, several issues were identified by the authors. The need for an international consensus statement on cochlear re-implantation in relevant problems  is highlighted. (6) Wang et al. studied changes in vestibular function in patients who received a minimally invasive CI surgery 1 year before the study. The functions of semicircular canals and otolith were assessed by a comprehensive battery of tests. Most of the vestibular functions could be preserved with no damage discrepancy among the otolith and three semicircular canal functions at 12 months post CI. (7) Di Nardo et al. explored the benefits of CI in tinnitus suppression. Single-channel stimulation resulted in a significant reduction of tinnitus loudness. Their results provided insights into the mechanisms of tinnitus and the development of tinnitus therapies. (8) Bissmeyer et al. examined the effect of a computer-based musical training program on musical interval identification of CI users and listeners with no known hearing loss and the correlation between low-level psychophysics and higher-level musical abilities. They observed strong correlations between pitch sensitivity and musical interval identification for the two participant groups. However, the effect of the training program in this study on musical interval identification was small among CI users. The authors discussed directions toward improving pitch access and auditory training of musical interval appreciation for CI users.The remaining eight papers cover a broad range of new topics on the outcomes of cochlear implantation. (1) The papers presented in this Research Topic provide a snapshot of the latest discoveries in the benefits and outcomes of CI. We believe that this Research Topic provides an interdisciplinary forum for researchers working in the fields of speech and hearing science, computational neuroscience, medicine, and biomedical engineering to present the most recent ideas, methodologies, and studies for understanding and improving the benefits and outcomes of CI. Future studies on the benefits and outcomes of CI could continue in several aspects, including establishing neural biomarkers of central auditory processing, discovering new predictive factors of CI outcomes, and exploring CI benefits in speech production, emotion processing and spatial listening. Utilizing multi-disciplinary methods in future CI studies is also recommended, e.g., combining neuroimaging and psychophysical tools to assess CI outcomes and integrating traditional statistical tests and artificial intelligence algorithms to analyze clinical findings.The editors sincerely thank all the authors, reviewers, and Frontiers editors as well as the staff involved in the preparation of this Research Topic.FC, JC, and XL contributed to the drafting and revision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
+{"text": "Most persons with dementia live at home and are cared for by family carers and professional carers. Together, they form care arrangements to address the needs of persons with dementia. The aim of this study is to (1) uncover the underlying structures of home-based care arrangements for persons living with dementia, (2) construct types of these care arrangements, and (3) compare these types with regard to their stability. In this secondary analysis, data from 320 care arrangements for persons with dementia are analysed using multiple correspondence analysis and hierarchical cluster analysis. The multiple correspondence analysis identified 27 axis that explained the entire variance between all care arrangements. The subsequent cluster analysis identified four types of care arrangements. Two types included spouse-centred care arrangements, and two types included child-centred care arrangements at different phases of the dementia and care trajectory. The types differ with regard to their stability."}
+{"text": "To investigate whether the dose intensity of chemotherapy received by Adolescent and Young Adult (AYA) cancer patients impacts on their survival.To assess and compare the utility of existing healthcare data available at a regional, national and international level to answer this question.A regional dataset has been created through linkage of the Yorkshire Specialist Register of Cancer in Children and Young People to electronic chemotherapy prescribing data from Leeds Teaching Hospitals NHS Trust, providing a detailed dataset. The national dataset comprises of data from the National Cancer Registry and Analysis Service (NCRAS) linked to the Systemic Anti-Cancer Therapy (SACT) dataset which collects chemotherapy prescribing data from all hospitals in England. This dataset provides bigger patient numbers but data at a pseudonymised level. The international dataset comprises of anonymised data from clinical trials.The data has being linked, cleaned and validated. Survival analysis is being carried out using a causal inference framework.This study will describe the value of existing healthcare care sets in the AYA cancer population. Identification of areas in which the datasets are lacking will help inform data controllers regarding ways in which data collection can be optimised for this important patient group."}
+{"text": "Genetic factors play a key role in the pathogenesis of several neurodegenerative disorders, both as monogenic causes of inheritable disease forms and as modifiers of susceptibility to sporadic phenotypes.Over the last two decades tremendous advances have been made in identifying the genetic underpinnings of multiple neurodegenerative conditions, and such developments are critically informing both new disease models and more targeted therapeutic strategies.With the growth of gene-focused clinical trials it is imperative to better characterize genotype\u2013phenotype correlations and improve our knowledge of the underlying pathological mechanisms.In this context, neuroimaging provides a particularly promising tool to investigate the neurobiological processes mediating genotype\u2013phenotype associations. Different imaging modalities are providing complementary information on many mechanisms involved in the pathophysiological cascades, including regional vulnerability to atrophy, microstructural damage and alterations in functional activity.Of note, recent studies also suggest that these changes are detectable even in the asymptomatic/presymptomatic disease phases, opening unprecedented possibilities for unraveling compensatory mechanisms and developing preventive therapeutic strategies.The goal of this Research Topic was to give an overview of clinical and neuroimaging studies focusing on the complex interplay between genetic signatures and phenotypic expressions in neurodegenerative diseases.Starting from the description of clinical features characterizing genetic disease forms, the usefulness of different imaging modalities to unravel the underlying pathological mechanisms was further evaluated and commented.The Research Topic included five articles and provided an overview of neuroimaging approaches for investigating genotype-phenotype correlations.Chai et al. applied a combination of consensus weighted gene co-expression network (WGCNA) and single-sample gene set enrichment (ssGSEA) analyses to compare the gene co-expression networks of gray matter (GM) and white matter (WM) lesions in multiple sclerosis (MS), observing both significant similarities and differences.+T-cell, while differentially expressed genes were mainly distributed in the CD56 bright natural killer cell pathway. These findings provided an example of the relevance of transcriptomics approaches for better clarifying the pathological mechanisms sustaining MS onset and progression.In particular, the authors identified common gene expression patterns in signaling pathways related to the immature and activated B-cell and the central memory CD4Wang et al. explored the prevalence and clinical relevance of novel neuroradiological markers in fragile X-associated tremor/ataxia syndrome (FXTAS) premutation carriers using quantitative susceptibility mapping (QSM).In another contribution, The authors evaluated the presence of globus pallidus abnormal T2-signals in addition to the classic middle cerebellar peduncle (MCP) sign, showing that such characteristic features are associated with greater cognitive impairment and faster age-related iron depletion and variability, providing preliminary evidence that the interaction between MCP and pallidal T2-signal changes may underlie the heterogeneous clinical manifestations of FXTAS.Ruiz-Barrio et al. contributed with a review on clinical and neuroimaging features of genetic progressive supranuclear palsy (PSP) syndromes and further proposed a diagnostic algorithm that may help the genetic diagnosis when there is clinical suspicion of a monogenic disease form.The collected data and the suggested diagnostic workflow have the potential for a significant impact both on clinical practice and therapeutics development, since the recognition of larger case series with well-defined mutations, combined with a specific evaluation of their clinical and neuroimaging features may add new insights into the pathophysiological mechanisms leading to neuronal damage in these complex conditions.Spinelli et al. provided an example of such potential in motor neuron diseases (MNDs). By combining voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in a relatively large sample of TARDBP mutation carriers, the authors were able to identify a distinctive parietal pattern of cortical atrophy and greater damage of motor and extra-motor WM tracts, providing preliminary evidence that TDP-43 pathology due to TARDBP mutations may cause deeper GM and WM morphologic alterations in this pathological spectrum.The work by Kong et al. further highlighted the relevance of neuroimaging investigations in genetic neurodevelopmental disorders, particularly in Rett syndrome (RTT) with MECP2 mutation.Finally, the review by Specifically, the authors provided a detailed overview of the diverse pathological signatures of the syndrome as revealed by the application of distinct imaging modalities, and further discussed the associations of different metrics with clinical manifestations, confirming the potential of neuroimaging application for elucidating the complex interplay between genes, abnormalities in neurotransmitter pathways, and clinical symptoms.In summary, over a wide spectrum of diverse neurological conditions, the articles included in this Research Topic have provided converging evidence on the relevance of investigating genetic disease forms to unravel the biological complexity and clinical heterogeneity of neurodegenerative and neurodevelopmental disorders.The common focus on the application of diverse neuroimaging modalities has highlighted the utility of multimodal approaches to gain complementary information on the diverse pathological mechanisms involved in the onset and progression of such complex disorders, opening new possibilities for improved disease modeling strategies.In conclusion, through the collection of original research articles and reviews focused on clinical and neuroimaging signatures of genotype-phenotype correlations, we believe this Research Topic has contributed to advancing our understanding of the complex interaction between genetic underpinnings, phenotypic manifestations and underlying pathological mechanisms across multiple neurological disorders.Future studies will advance this research field, possibly through the evaluation of larger case series and an increasing focus on presymptomatic disease phases, finally enabling the translation of the obtained findings into the development of early personalized therapeutic strategies.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."}
+{"text": "Background and aim: Temperament and personality traits are important factors underlying the vulnerability for both initiation and continuation of addictive behaviors. In SUDs there is a high comorbidity with mood and anxiety disorders and personality disorders. As there is a growing interest in the possible transdiagnostic role of Effortful Control in both SUDs as in their comorbid disorders the current study therefore investigates the influence of reactive  and regulative  temperament and their interaction in relation to clinical symptomatology and PDs in adult inpatients with SUD. Methods: The EC, BIS/BAS, SCL-90-R and ADP-IV questionnaires were administered to 841 patients (age between 17 y and 71 y) with a SUD admitted at the treatment unit for addiction of a psychiatric hospital. Results: Hierarchical regression analyses showed that both, clinical symptomatology and PDs were related to low levels of effortful control (EC). Furthermore, cluster C PDs were related to high levels of BIS and low levels of EC; whereas cluster B PDs were related to low levels of EC and high levels of BAS for the narcissistic and histrionic PD. An interaction effect (BIS*EC) was found for the Schizotypal PD, all other interactions (BIS*EC and BAS*EC) were not significant. Discussion: We found that low EC is involved in all clinical symptomatology and PDs in a sample of inpatients with SUDs. Therapeutic interventions aiming at strengthening effortful control can possibly result in better treatment outcomes for both the addiction as the comorbid psychopathologyNo significant relationships."}
+{"text": "The generalist assistance at the Primary Attention is fundamental to face the increase of type 2 diabetes mellitus cases through the relationship physician-patient. This sets the therapeutic plan and its continuous review. Therapeutic Plan could be affected by the same psychocultural phenomena related to the increasing cases numbers of DM2. Therefore, new trends in Medical Psychology have been promoted during medical undergraduate course. These incorporate methods and concepts of Liberal Arts to develop specific psychosocial management skills to DM2 clinic.AIM: To understand the experience of medical students in the simulated care of DM2 cases in two different moments: 1) to diagnose and start treatment; 2) start insulinization.METHOD: Clinical-Qualitative design; data collected through an semidirected interview of open-end questions in depth; thematic analysis generated categories discussed in light of Medical Psychology of psychodynamic framework.RESULTS: Ten clinical clerkship students attended as clinicians two cases of Standard Patients of DM2. They reported their reflections toward the role they should sustain: being doctor in front of the patient and their colleagues; difficulty to play the leading and show skills and knowledge in a scenario full of surprises and fantasies; an existential and professional gains in simulation activity; and considerations about responsible in conduct so impacting situations to patients.FINAL CONSIDERATONS: The themes translate moments during their simulated attending experience in which they have not sustained their semblance \u2013 the intended rule. These could be enriched though group reflecting, supervisor discussion, and patient dialog in the process of developing Medical Psychology skills.No significant relationships."}
+{"text": "Episodes of lucidity among people with advanced Alzheimer\u2019s disease and Alzheimer\u2019s disease related dementias (AD/ADRD), reportedly evidenced by an unexpected return of meaningful communication or connection, are an area of growing interest. Event transient recovery of abilities in the setting of advanced AD/ADRD are potentially significant for caregivers and the person living with dementia; as well as for shaping our understanding of AD/ADRD more broadly. Despite the potential significance of these events, existing evidence is largely comprised of anecdotal reports and retrospective/case reports. Recently, the National Institute on Aging funded six studies to advance empiric studies on episodes of lucidity in advanced AD/ADRD. This symposium will provide an update on progress and findings across these funded studies. The first presentation focuses on acceptability and feasibility of a prospective observation study focused on characterizing potential observable indicators of episodes of lucidity in individuals with advanced AD/ADRD near end of life encompassing audiovisual observation, informant field interviews and case reviews. The second presentation will provide an overview of a 3-phase mixed methods study focused on development of preliminary types of lucid episodes. Collectively, presentations demonstrate a variety of approaches to investigating episodes of lucidity and shed light on emergent methods for operationalizing these events. Implications of various conceptualizations for EL and conceptual decisions across studies will be reviewed."}
+{"text": "Wienhold et al.).\u2022 The increase of sensitivity of smartphone cameras, for example, is allowing the development of fast biosensing devices for point of care health and environmental applications, as can be seen in the manuscript  and,\u2022 the development of intracellular calcium sensing proteins based on photoproteins with FP-tagged calcium binding domains, which allows the fast and sensitive detection of calcium flows cultured mammalian cells .\u2022 the development of a fusion protein based on a brighter firefly luciferase and ZZ-protein, which is used to detect antibodies and antigens in bioluminescent immunoassays, with sensitivity matching the commercially available chemiluminescent assays  which emits in the NIR, and\u2022 A novel form of infralluciferin , and\u2022 The engineering of the secreted recombinant ostracod luciferase which is allowing to better understand the structure/function relationship and to improve its expression in different heterologous systems .\u2022 The improvement of the thermostability of firefly luciferase which is allowing to develop more robust protein\u2013protein interaction assays \u201cFlimPIA\u201d based on the functional complementation of mutant firefly luciferases (Fluc) .Bioluminescence is also being effectively used in biosensors for safety purposes, to detect dangerous explosives such as the optimized Escherichia coli-based bioreporter for the detection of 2,4,6-trinitrotoluene (TNT) and derivatives (DNT) (E.coli bioreporter based on the randomly mutagenized ribose binding protein (RbsB) associated with the GFP-based screening was constructed to bind and detect the non-natural ligand 1,3-cyclohexanediol (13CHD) (Tavares and van der Meer).Finally, an The above papers reflect some of the continuous advances and prospects of bioengineering of bioluminescent systems and its associated detecting technologies in the fields of biomedical, environmental and safety bioanalysis."}
+{"text": "Flavoured tobacco products increase smoking uptake and create dependence. By June 2020 all cigarettes with a characterising flavour, including menthol were banned across the EU, UK and Moldova but many low and middle income countries (LMIC) are yet to develop and implement bans despite high smoking prevalence. This paper has two objectives: to establish whether (1) flavoured tobacco products are present and marketed in LMIC and (2) the experience of bans in Europe can guide development of legislation elsewhere.Research involved analysis of menthol/flavour market data, review of academic and commercial literature and online media.The median menthol/capsule market share of the cigarette market grew significantly in middle income countries (p < 0.05) between 2005 and 2019, both in lower and upper middle-income countries . No market data were available on low-income countries, but the academic literature suggested high prevalence of menthol use in Zambia. Tobacco industry strategies underpinning growth of menthol/flavoured tobacco use in LMICs included in-store marketing and display, colourful packs and non-conventional flavour names. Tobacco industry attempts to circumvent the EU ban included introducing new flavoured tobacco products and accessories not included in the ban and exploiting the ban on characterising flavour (as opposed to an ingredient ban) by introducing cigarettes with lower levels of menthol.Banning flavoured and menthol cigarettes in LMIC would impact a growing proportion of smokers in these countries. From the European experience, menthol and flavour bans that include all tobacco products and accessories and ban flavour as an ingredient rather than a characterising flavour is recommended. Currently, lack of marketing bans and standardised packaging in LMICs exacerbate the impact of flavours.Flavoured and menthol tobacco products are a growing problem in LMICs.Bans should include all tobacco products and accessories and ban flavour as an ingredient."}
+{"text": "This symposium embraces diversity and discovery to address contextual issues in aging, specifically issues of race and ethnicity in the study of cognitive health and Alzheimer's Disease and Related Dementia (ADRD). Rooks and colleagues compare dementia risk among African American and White men and women in the context of work using the longitudinal Health, Aging, and Body Composition data. They consider the effects of productive activities on dementia risk in gender stratified models, adjusting for socio-demographic and genetic factors. Siddiq and colleagues consider the contexts of migration. Using a multi-method approach, they establish priorities for interventions addressing ADRD risk among older adult immigrants and refugees from Afghanistan and the Middle-East and North Africa (MENA) in California. Sayed also investigates the context of migration, and uses qualitative data (N=31) to identify the psychosocial impact of COVID-19 on cognitive aging in Middle Eastern/Arab Americans immigrants and refugees in Michigan. Finally, Meier and colleagues consider contexts of metal exposure for cognitive decline among Latinos aged 65 and older using the Sacramento Area Latino Study on Aging. In total, this symposium highlights the benefits of reimagining contextual factors that influence ADRD to improve our understanding and the potential to reduce health disparities research in underrepresented racial and ethnic populations."}
+{"text": "Substitutes for meats and sausages are growing both in demand and supply in Germany. Monitoring their nutritional composition helps characterise this novel product group in terms of its dietary contribution.Data on substitutes for meats and sausages were collected in a baseline survey in 2016 and an in-depth follow-up survey in 2021. In both surveys, mandatory nutrition declaration (\u201cBig 7\u201d) and other packaging information were collected via online research and supermarket visits. Products were categorised according to the substituted animal products and their contents of energy, fat, saturated fatty acids, and salt investigated. Changes in energy and nutrient contents between baseline and follow-up survey were assessed statistically using Welch\u2019s t-test.The follow-up survey included 421 meat substitutes and 292 sausage substitutes, split into 27 subgroups. Substitutes for meat products like meat strips and schnitzel show widely varying energy contents. Sausage substitutes show higher medians for fat, saturated fatty acids and salt than meat substitutes; spans of salt content  and saturated fatty acids  are particularly wide. Relative to the baseline survey, which included 69 meat substitutes and 61 sausage substitutes, the follow-up revealed significantly higher contents of energy and saturated fatty acids overall and in some subgroups (e.g. nuggets and burger patties). The sole significant reduction was seen for energy in substitutes of precooked sausages.The observed wide spans of energy and nutrient content imply 1) the potential to reformulate substitutes for meats and sausages at the top end of the spectrum 2) the availability of healthier choices within the various subgroups. The increases shown in energy and saturated fatty acids content warrant further monitoring.\u2022\u2002Wide spans of energy and nutrient contents reveal the potential for the development of more nutritionally favourable substitutes for meats and sausages.\u2022\u2002As substitutes for meats and sausages are perceived to have nutritional advantages the observed increases in energy and saturated fatty acids contents over time should be further monitored."}
+{"text": "General practices are experiencing increasing pressures due to rising demand, declining staff numbers, and knock-on impacts on patient care. The COVID-19 pandemic has added further challenges and reinforced the importance of teamwork and organisational settings. We undertook a mixed-method systematic review to explore which interventions can improve teamwork within primary care and improve inter-sector partnerships with other health and social care services.Five major bibliographic databases were systematically searched for relevant studies from inception to February 2022. We included controlled intervention study designs and linked qualitative studies. For amenable data, meta-analysis is being undertaken using random effects models taking into account the between study heterogeneity (quantified using the I2 statistic) and potential publication bias (funnel plots and Egger's test). The qualitative studies are analysed using thematic analyses.The original search yield of 3012 studies, of which 14 studies with 1,534 participants were include in our analyses. Most of the evaluated interventions focused on improving non-technical skills and provided evidence of improvements in the quality of teamwork in primary care. Meta-analysis and narrative synthesis is undertaken to examine the impact of the teamwork interventions on staff outcomes , and patient outcomes .The findings provide information of immediate importance for the mental health and wellbeing and teamwork support of professionals entering primary care and for the organisation of primary care services."}
+{"text": "Shielding was introduced as part of the UK government\u2019s response to the SARS-CoV-2 pandemic to protect Clinically Extremely Vulnerable (CEV) people from infection and serious illness. Various research questions emerged in relation to non-clinical vulnerabilities of those shielding which could be addressed by utilising available health and administrative data.The Shielded Patient List (SPL) was linked with various datasets on the UK Secure Electronic Research Platform (UKSERP) including the Pupil Level Annual School Census (PLASC), National Survey and Ordnance Survey data for Wales. Some of these were anonymised datasets contained in the Secure Anonymised Information Linkage (SAIL) databank. Algorithms were applied to determine household composition and whether private outdoor space was available for the shielding group. Results were then extracted for Wales broken down by local authority.Results from the various strands of research related to shielding will be presented covering provision of outdoor space, household characteristics and composition.These analyses demonstrate how population-level data resources can be leveraged quickly to answer newly-emerging policy questions as part of the response to the SARS-CoV-2 pandemic."}
+{"text": "Existing evidence regarding the association between hypertensive disorders of pregnancy (HDP) and the risk of maternal mental illness is inconclusive.This study aimed (i) to investigate the relationship between HDP  and the risk of depressive and anxiety symptoms during pregnancy and in the postpartum period and (ii) to test whether parity moderates the association between HDP and antenatal and postnatal anxiety and depressive symptoms.The study cohort consisted of more than 8500 mothers who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC), UK. Maternal antenatal and postnatal depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the Crown-Crisp Experiential Index (CCEI), respectively. Univariable and multivariable logistic and linear regression analyses were used to examine the associations.Mothers with pre-eclampsia had a 53%  increased risk of antenatal depressive symptoms compared with those without pre-eclampsia. Having pre-eclampsia and being a nulliparous woman resulted in a 2.75 fold increased risk of antenatal depressive symptoms . Gestational hypertension was associated with antenatal depressive and anxiety symptoms. We found no associations between pre-eclampsia and/or gestational hypertension and postnatal anxiety and depressive symptoms.Our study showed that mothers with HDP were at higher risk of antenatal depressive and anxiety symptoms. Nulliparous women with pre-eclampsia are a higher risk group for depression during pregnancy.No significant relationships."}
+{"text": "Molecular tests in solid tumours for targeted therapies call for the need to ensure precision testing. To accomplish this participation in the External Quality Assessment Program (EQAS) is required. This evaluates the consistency of diagnostic testing procedures and offers guidance for improving quality. Outbreak of COVID-19 pandemic led to worldwide lockdown and disruption of healthcare services including participation in EQAS.The present study describes the extended scope of EQAS offered byMPQAP , the first proficiency test provider for solid tumor diagnostics in India. The study surveys the preparedness of molecular testing laboratories in routine diagnostics and participation for quality assessment scheme.A documented guideline for measures and precautions to be carried by testing laboratories in performing routine diagnostic tests during the lockdown period were charted and distributed to all MPQAP participant centres. A survey was conducted for MPQAP participants to check whether laboratories were involved in COVID-19 testing and to evaluate the impact of lockdown on the operations of diagnostics procedures. From the acquired response of the survey, 2 cycles out of initially proposed 11 cycles were executed with transformed approach using digital tools and image interpretation modules.Out of 25 solid tumour testing laboratories registered as participants, 15 consented to participate in survey. The summary of survey conveyed the impact of COVID-19onroutine operations of diagnostics tests such as shortcomings in inventory and human resource management. Thirteen participants showed active willingness and consented to participate in EQAS test scheme.The survey findings and assessment of EQAS cycles endorsed the quality testing procedures carried by participating laboratories throughout the lockdown. It highlighted the utility of EQAS participation during pandemic along with emphasis on safety measures for continual improvement in quality of diagnostic services. Molecular diagnostic tests provide the requisite guidance for target-based therapy in solid tumours, which plays an integral part of diagnostic arsenal for improved management of cancer and keeping up with the current standards . The priFluorescent in-situ hybridization), Sanger Sequencing, PCR and Real time PCR (Numerous proficiency testing (PT) providers and EQAS bodies have been set up across the globe for oncology diagnostics, out of which limited organizations probe into solid tumor based testing. EQAS program for oncology in India has been instigated by National Cancer Grid (NCG) in form of \u2018MPQAP\u2019 . MPQAP EQAS is the first initiative in the country providing PT schemes for solid tumor molecular diagnostics. It follows Method based Proficiency testing (MBPT) approach that assess the skills of participant laboratories in various aspects of testing. These include performance in technical skills, diagnosis and interpretative skills with compliance to the standard recommendations. MPQAP has been continuously rendering these services across the country since 2019 for various types of molecular diagnostics tests based on methods namely FISH (time PCR .The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) also known as COVID-19,declared as pandemic by the World Health Organization (WHO)professed an imposing threat to health care providers and patients . With liIn solid tumor molecular diagnostics, the journey of the tissue encompasses three stages of testing-pre-analytical , analytical  and post-analytical . Such schematic plan involves interdisciplinary team of pathologist, laboratory scientists and scientific assistants to provide an integrated diagnosis . This inAdditionally, as per international bodies such as ISO 15189/CLIA , it is an obligate need for oncology diagnostic laboratories to involve in PT schemes in order to ensure that Good Laboratory Practices(GLP) and competency in testing are maintained . AlthougPrior to pandemic, MPQAP had been instrumental in giving suggestions for improvement of participant laboratories\u2019 efficacy in diagnostic testing and reporting of results through confidential assessment reports (CAR). This role was impeded due to ongoing COVID-19 crisis.Recognizing the health emergency, international accreditation bodies and PT providers such as CLIA and College of American Pathologists (CAP)had adopted lenient approaches for PT of participating laboratories with the following points :Exemption from being penalized for delay in submission of results, suspension or cancellation of participationNon-withdrawal from participation, if involved in COVID-19 testing or temporarily suspension of diagnostic tests due to shortage of manpower and reagentsExemption from evaluation in situations of discontinuation of diagnostic testsExtended time scales for delayed receipt of testing itemsExemption from participation, if test material is received in unsuitable conditions or unfit for testingLikewise, guidelines were laid down by WHO and Centre for Disease Control (CDC) for safe operation of laboratories \u201311. AlsoWith reference to such initiatives at international level, it was deemed essential to have documented measures and strategies to be followed in molecular oncology testing compassing brief points to be employed in the country to resume elective procedures , 13.Since molecular diagnostic work in solid tumours mainly constitutes Formalin Fixed Paraffin Embedded (FFPE) blocks and blood samples; it was imperative to introduce proper risk assessment for procedures such as isolation of nucleic acids, PCR, sequencing and staining. Also, molecular pathology work being non-propagative in nature, it entailed the need to carry all procedures in level II Biosafety Cabinet (BSL-2) or facilities equivalent to it .The responsibility of PT providers expands in such situations where it plays a valuable service of monitoring performance and recommending guidelines for quality sustenance . In contThe present study describes the extended role played by the MPQAP as EQAS provider in assessing the preparedness of testing laboratories during the pandemic and fortifying the importance of quality sustenance in testing procedures even amidst the crisis.The MPQAP PT program was approved by the Institutional Ethics committee (IEC) of Tata Memorial Hospital (TMH) and was initiated in the year 2019. This program has been offering EQAS schemes to 25 participant testing laboratories in India registered under MPQAP. The details of the registration procedure are available on the NCG-MPQAP webpage on the TMH website .The testAt the inception of pandemic, a documented guideline including interim actions to be undertaken related to laboratory biosafety in handling and processing clinical samples/infectious agents was outlined by NCG-MPQAP coordinators. This guideline was offered to all participants via email and was also uploaded on NCG-MPQAP website  S1 FileS1 File.The interim guidelines to be followed in molecular diagnostic laboratory for routine procedures concentrated on patient and healthcare worker safety is summarized in Staff SafetyUse of PPECollection & handling of specimensRoutine diagnostic proceduresSpill Clean upWaste ManagementA survey was designed to ascertain the current testing status of participant laboratories associated with MPQAP EQAS. The objective of the survey was to identify which testing laboratories were involved in COVID-19 testing apart from routine molecular diagnostics and whether adequate facilities were available within them to carry all these tests efficiently. The survey was carried out using Google survey forms with 15 questions taking approximately 5 minutes to complete. Participants who consented to take up the survey were given a duration of 30 days to fill the survey form. The survey responses were collected and collated in June 2020.The survey questions addressed the following points:Whether the testing laboratories are involved in COVID-19 testingWhether adequate supply of consumables is availableImpact on diagnostic test requisitionsShortage of reagents, kits and consumablesImpact on manpower, revenue and remunerationImpact on Turnaround time (TAT) for reportingQuality measures employedReady/willingness to participate in EQAS cyclePrior to inception of pandemic, the calendar schedule of EQAS cycles for the year 2020\u20132021 had been prepared and was uploaded on MPQAP website . The schAfter assessing the status quo of testing laboratories from the survey responses and the willingness to participate in EQAS cycle, the release of test cycles was planned. To ensure COVID-19 safety and social distancing norms are followed and workflow of pre to post analytics is not hampered, a hybrid design for EQAS cycles was implemented. As per the proposed calendar schedule of MPQAP EQAS cycles of the annual year, two cycles were executed in sequential manner after obtaining consent from participant laboratories.Her2/neu gene amplification test. The consent and confirmation for participation was taken via email and thirteen participants consented to take part in the EQAS cycle. When the inter-state shipment protocols were eased across the country after four months of total lockdown (i.e. from mid-March 2020 to mid-July 2020), the package of test materials were dispatched to the participant centres.The first EQAS cycle for FISH module was executed for In view of the ongoing pandemic, the design of the test scheme was modified to meet the demands of remote reporting, cloud-based data analysis.Digital software tools and digital slide scanners were used for obtaining Haematoxylin and eosin (H&E) slide images. These were utilized with the purpose of sending scanned H&E images of the tissue samples to consultant pathologists for remote reporting on virtual platforms to assess the representative tumor content and histology.H&E stained slides were scanned using whole slide imaging (WSI)system, VENTANA DP200 whole-slide scanner . Unstained slides for performing FISH test and virtual slide images by WSI of H&E slides of the tumour tissues, were provided as test materials for the cycle. Sending the hard copy of testing results was kept optional and provision was made to submit test results via a dedicated online MPQAP portal system.RAS and BRAF mutation detection. Four participants consented via email to participate in the cycle.With reliability of cloud-based analysis tools ensuring social distancing, the theme of remote reporting was utilised and digital EQAS scheme was further implemented for the next cycle of RAS and BRAF mutation participated in the scheme.To assess the interpretative skills of participant laboratory apart from technical quality assessment, Image Interpretation Skill EQAS scheme was executed where digital images were sent as test materials. Participant centres which employ only sequencing methods for detection of BRAF and RAS samples were sent to participants via Google forms in their registered email ids  for each mail ids .Apart from the digital images, FFPE tissue sections were also provided as test materials for assessing the technical performance of participants.The survey data addressed the status of testing laboratories which were involved in COVID-19 testing apart from routine diagnostics and whether adequate facilities were available with them to carry both kinds of diagnostic testing efficiently. Out of 25 centres,15 centres participated in the survey. Among the participants of the survey, 5 centres were involved in COVID-19 testing as a primary responsibility and 10(66%) were indirectly associated with COVID-19 testing facility in their respective premises by means of sharing infrastructure and man power .Discrete effect of pandemic on diagnostic procedures was noted in the operations of participant centres. Out of 5 centres engaged with COVID-19 testing as primary responsibility, 3(60%) of them faced delays in procuring nucleic acid extraction kits, COVID-19 test reagents and Personal Protective Equipment (PPE) kits .Impact on diagnostic kits shortage and reagents was observed in 6(40%) centres and 9(60%) centres faced issues with supply of consumables such as plastic-wares, gloves, filter tips and surgical masks With respect to impact of COVID-19 on test requisitions, 8(53%) centres had no effect on incoming test requisitions whereas 4(26%) laboratories had increased test numbers and 3(20%) centres had decrease in number of requisitions .In terms of revenue generation of the laboratories from the diagnostic tests only 2 (13%) centres reported about less revenue generation during pandemic whereas 9(60%) centres had moderate effect and 4 (26%) centres had no impact on revenue income . LikewisWith regards to effect of pandemic on TAT for reporting and reasons for test discontinuation, responses from two centres were received. One centre stated about slight delay in diagnostic reporting due to lag in procuring consumables and budget issues whereas the other centre had to discontinue FISH and few immunohistochemistry (IHC) tests citing reasons of extreme shortage of reagents and funds to execute the tests .Use of alternate assessment procedures (AAP) by participants other than involvement in EQAS (impeded by lockdown) was investigated in the survey and it was observed that 7(46.2%) labs performed AAP such as running known positive controls, validation of results on different platforms or by modification of some steps. Split sample testing and ILC (inter laboratory comparisons) were employed by one centre each and 4 centres did not employ any AAP .These findings from the survey suggested that the conventional conditions of testing and continual improvement had marginal impact during this pandemic where demand for COVID-19 testing was surging. However, despite such shortcomings, there was a notable response from 1386%,  centres Her2/neu gene amplification test by FISH was based on molecular interpretation of all the samples along with control sample. The performance was assessed for accuracy of testing and prognosis offered based on the findings. Confidential Assessment Report (CAR) of all the participant centres was communicated via online portal system. The competency evaluation of participants for technical skills and reporting was found to be within acceptable limits affirming the reliability and accuracy of reporting by participating centres  from participants for each round of cycle was significantly affected due to the interstate lockdown protocols . This efThere is limited information about the challenges faced in managing clinical laboratory services outside of COVID-19 specific diagnostics, although reports are beginning to emerge. The ongoing pandemic is an awakening experience to carry out EQAS service where conventional rulebook is replaced by innovative measures and novel approaches in all spheres of life.Imposition of lockdown across the country led to impediment of logistics for sending proficiency test materials, impacting the primary role of quality evaluation of EQAS program. Nonetheless, it provided impetus to make use of the secondary objective of PT provider in inquiring into the shortcomings faced during pandemic and ministering necessary guidance.The survey responses imparted a fair idea on prevailing status of diagnostic procedures carried out in different laboratories for molecular diagnostics Figs  and 2.EmImplementation of rotational shifts or staggered duty hours among the technical personnel to minimize social contact, cross-sectoral skill management, positive attitude and the active preparedness among participants to participate in EQAS schemes proved that quality standards can be sustained despite threats posed by the virus.Routine diagnostic procedures were not affected significantly due to pandemic and the active willingness of participants paved the way to conduct EQAS scheme using reformed approach. In an era of digital pathology and artificial intelligence (AI), remote reporting by pathologists has become a reality with use of high-definition WSI and online cloud based digital software tools for molecular analysis . This coThe need of setting up databases for use of alternate protocols and procedures during crisis can help reduce the lag in processing of the samples due to shortage of reagents especially in the presence of heightened pressure of providing test reports on priority. This can be achieved by willingness to actively participate in EQAS programs by testing laboratories, where PT providers like MPQAP, in an advisory role, can aid in data management and monitor the quality change in solid tumour testing over a period of time .Improved and enhanced quality measures related to solid tumour molecular diagnostic testing should be substantiated by PT programs . ParticiS1 Data(XLSX)Click here for additional data file.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file."}
+{"text": "Although several authors have investigated the relationship between demoralization, insight, and suicide risk, the role of these factors in determining suicide risk in patients with psychiatric disorders is still unclear .The main aim of this study was therefore to determine whether suicide risk was associated with better insight and worse demoralization in a sample of 100 adult psychiatric inpatients.The study was performed on 100 psychiatric hospitalized adult patients consecutively enrolled between January 2019 and April 2020 at psychiatric units of Sant\u2019Andrea Medical Center, Sapienza University of Rome. The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess suicide risk, Demoralization was assessed using the Demoralization Scale (DS)  and for the assessment of insight we used the The Insight Scale (IS).Only age was significantly associated with higher suicide risk . The variable mood disorder was significantly associated with higher suicide risk . Non-suicidal self-harm behaviors in the last 3 months  and lifetime suicide attempts  were significantly associated with higher suicide risk. Only the insight-high dimension  and lifetime suicide attempts  were significantly associated with higher suicide risk.Our results don\u2019t confirm the role of demoralization in suicide risk. In our sample of patients, only high insigth of illness and other psychological variables are involved in suicide risk.No significant relationships."}
+{"text": "An 11-year-old girl reported to the Department of Pediatric and Preventive Dentistry, with a chief complaint of discoloration of teeth and poor esthetics due to irregular teeth in the upper and lower front region of jaw. There was no history of trauma in either the primary or permanent dentition. Family history did not reveal any evidence of hereditary dental anomalies. Clinical examination revealed multiple dental anomalies in both the maxillary and mandibular anterior region. Hypoplastic, irregular globular mass on labial surfaces of maxillary right central, lateral and canine (A). Similar irregular hypoplastic mass was seen on the cervical one-third of mandibular right central and lateral incisors (B). The presence of a talon cusp in the permanent maxillary right central incisor interfered with occlusion in the lower right incisor region (C). Dens invaginatus with maxillary permanent right lateral incisor was seen radiographically (D). Management of hypoplastic, irregular globular masses on labial surfaces of maxillary and mandibular teeth was done initially by grounding the tooth surfaces and reformed by composite build-up."}
+{"text": "Sensors on \u2018\u2018Smart and Future Applications of Internet of Multimedia Things (IoMT) Using Big Data Analytics\u201d solicited high-quality research on recent advances related to the intelligent Internet of Multimedia Things (IoMT) and big data analytics. Contributions tackled open research problems, integrated efficient novel solutions, carried out performance evaluation studies, and compared state-of-the-art solutions. The Special Issue attracted numerous submissions. Following a rigorous review process, three outstanding papers were finally selected for inclusion in the Special Issue. Each paper was reviewed by three independent experts. The accepted papers cover a wide spectrum of research topics in the broader area of the Special Issue.This Special Issue is focused on breakthrough developments in the field of Internet of Multimedia Things (IoMT), particularly on smart and future applications of IoMT using big data analytics. The selected contributions report current scientific progress in a wide range of topics covering security challenges and protection methods in IoMT with an emphasis on healthcare applications; specific topics include user behavior aspects of mobile vs. non-mobile users of Internet video streaming services and IoT-enabled statistical and machine learning techniques to recognize cardiac disease features related to heart failure. This Special Issue of the MDPI journal The first paper , entitleThe second paper , entitleThe third paper , entitle"}
+{"text": "Literature showed that patients suffering from disorders belonging to the schizophrenic (SZ) and bipolar (DB) spectrum have a qualitatively similar but quantitatively different neurocognitive impairment that correlates with the outcomes. However, the majority of former studies are conducted on patients in remission phase.This study aims to compare cognitive functions between SZ and DB in the acute phase and their possible correlations with treatment outcomes.In a prospective longitudinal study conducted at the SPDC Ausl unit of Romagna - Cesena, 57 SZ and 82 DB took part in the study. The diagnosis was based on the SCID5 CV and SCID5 DP. Symptom severity was assessed with BPRS and HONOS both at the beginning and at the end of hospitalization. Executive functions were measured with Tower of London (ToL) and Modified Wisconsin Card Sorting Test (MCST), attention with Attentive Matrices (MA) and Stroop Test (ST), non-verbal logic skills with Colored Matrices by Raven (PM47). The statistical analyzes applied are ANOVA and logistic regression.The cognitive tests did not reveal significant differences between SZ and DB. The logistic regression analysis showed that the scores obtained at the MCST and MA positively correlate with the efficacy of the treatment for both groups.Cognition in DB and SZ patients was similarly impaired, supporting recent theories that placed diagnoses on a continuum of severity. Moreover, the results indicated that also in the acute phase the best predictors of the outcome were flexibility in problem solving strategies and visuospatial attention.No significant relationships."}
+{"text": "Flexible work arrangements promote not only acceptable and convenient work modes; for many professionals flexible work leads to increase in workload and in working time . As the result, lack of recreation time could be named as a direct consequence of high workload . The key problem is the investigation of attitudes towards recreation and recovery: are professionals more reactive or proactive in their recreation planning, and do they recover well?The aim of the research: to reveal (1) typical types of recreation planning for professionals with high level of work flexibility and (2) recovery efficiency level.The research was conducted in representatives of various professions, who work in flexible work arrangements (n=378). The diagnostic set included inventories for assessment of recreation planning type  and recovery efficiency .Two types of recreation planning have been found: proactive (26% of respondents) and reactive (74%). For the reactive approach lack of targeted strategies of recreation planning has been found. Proactive approach is characterized by tracking signs of resources decrease and advance planning of work breaks. There are differences in recovery efficiency  in proactive and reactive professionals: non-efficient recovery is typical for the majority of professionals with the reactive type to recreation planning.The detailed analysis of proactive/reactive approaches manifestations and peculiarities of recreation planning could help to predict not only the recovery level, but the mechanisms of advanced self-regulation, adequate to high work flexibility.No significant relationships."}
+{"text": "Regular physical activity is associated with physiological and mental health benefits for adolescents including improved fitness and cardiometabolic health, increased muscle and bone strength and reduced risk of obesity. Despite this, globally, many adolescents (81%) fail to meet physical activity guidelines. Physical activity levels decline as children move into adolescence and through to adulthood and may affect the likelihood of developing chronic health conditions. It is recognised that parental support and friendship networks play an important role in attenuating declines in physical activity during adolescence and it is vital that we develop effective interventions to help adolescents stay active.This symposium will engage policymakers, professionals, scientists and stakeholders to discuss research projects on Engaging peers, parents and pupils to increase physical activity among adolescents. The goals of this symposium are to highlight the challenges and ongoing work to address sub-optimal levels of physical activity in this population and disseminate the results of novel physical activity interventions to develop knowledge and understanding. This symposium will share experiences, learning and best practice in Patient and Public Involvement (PPI), transitioning from formative research to feasibility testing and upscaling interventions and it will also allow for debate and to identify gaps and priority areas for physical activity among adolescents.1. Putting young people at the heart of physical activity research design: The Walking In ScHools (WISH) Study This presentation will outline the importance of youth PPI and demonstrate how PPI can be embedded within research design using the WISH Study Youth Advisory Group as a case study.2. The Girls Active Project (GAP): Co-design and feasibility of an after school-based physical activity intervention This presentation will discuss the factors influencing physical activity behaviour in adolescents, outline how using public and patient involvement (PPI) and the behaviour change wheel provided a framework for developing the Girls Active Project, and the results from our feasiblity trial.3. Supporting our lifelong engagement: mothers and teens exercising (SOLE MATES); from formative research to feasibility testing .Dr Murtagh will discuss the value of formative research in developing interventions and present findings from a novel mother-daughter multi-component physical activity programme.4. Co-production of the Move Well, Feel Good movement behaviours intervention This presentation will describe phase 1 of the Move Well, Feel Good study, which aimed to co-produce and evaluate the feasibility of a primary school physical activity intervention to improve children\u2019s motor competence and mental health.5. The Walking In ScHools (WISH) Study: Development and evaluation of a peer-led school-based walking intervention in adolescent girls from pilot to fully-powered trial Professor Murphy will describe how the WISH pilot study guided the development of a full trial to evaluate the effects of a peer-led walking intervention at increasing physical activity in adolescent girls."}
+{"text": "Outbreaks are occurring at increasing frequency and they require multisectoral and multi-stakeholder involvement for optimal response. The Global Health Security Agenda is a framework that governments and other stakeholders can use to strengthen countries' capacities to prevent, detect and respond to outbreaks but there are few examples of academic programs using this approach.This is a narrative review of contributions of Makerere University through the Global Health Security Program at the Infectious Diseases Institute (IDI). Information was sourced from peer-reviewed publications and grey literature highlighting work done between 2017 \u2013 2021.Aligned to GHSA, IDI made contributions to strengthen national and subnational capacities for biosafety and biosecurity, sample collection and transportation, electronic disease surveillance, infection prevention and control, case management prior to COVID-19 that were subsequently used to support response efforts for COVID-19 in Uganda.The IDI Global Health Security program provides a model that can be used by institutions to deliberately develop capacities relevant to outbreak preparedness and response. National governments have the responsibility and the mandate to protect the health of their citizens. For infectious disease outbreaks, there is not only risk for spread and illness within countries but a potential for spread to other countries and territories that result in a mutual obligation to act prevent spread domestically and to share information promptly with the international community when there is potential for international spread or when high impact events occur. The World Health Organization (WHO) International Health Regulations 2005 (IHR) provides the international framework that defines capacities that member states require to manage outbreaks and other public health eventsWhile investigations into the origins of the virus and initial steps taken since its discovery continue, the critical question is whether countries are better prepared for the next potential pandemic. Are systems in place to prevent, rapidly detect and effectively respond to the outbreak in a manner that prevents another pandemic? The Global Health Security Preparedness Index, which measures preparedness capacities, found similar scores for many countries in 2019 and 2021, suggesting that advancement in these capacities is not the inevitable consequence of the experience gained while managing a pandemichttps://idi.mak.ac.ug/resources/annual-reports/) highlighting work done by IDI relevant to outbreaks). Manuscript searches were conducted in an online database (https://pubmed.ncbi.nlm.nih.gov) using IDI author names (e.g Lamorde M) for papers published between 01 Jan 2017 and 31 December 2021.In 2018, IDI created a dedicated Global Health Security program to support country capabilities to prevent, detect and respond to infectious disease outbreaks and other biological threats. This is a narrative review summarizing information from peer-reviewed manuscripts and conference abstracts and grey literature (IDI strategic plan (8), and IDI annual reports available at We identified the IDI Strategic Plan and the following annual reports  and reviewed content related to the Global Health Security program at IDI. Additionally, using author searches 5 peer reviewed manuscripts were identified relevant to the work of the GHS program.The IDI GHS program aims to support health systems in Africa to develop capabilities to prevent, detect and respond to infectious disease outbreaks and biological threats. Three core areas were identified for action, first, to strengthen national laboratory systems for detection of pathogens capable of causing outbreaks and to enhance biosafety and biosecurity Second, to enhance data systems for surveillance and reporting of outbreaks and prevention of emergence and spread of antimicrobial resistance using a One Health approach. Third, to enhance infection prevention control, case management and medical countermeasures during outbreaks.IDI uses the Potter and Brough Capacity Pyramid model to assess gaps at five levels including cognizance of local context . Identifying structures and systems (e.g defining roles and responsibilities of stakeholders and relevant organizations), provision of staff and infrastructure; developing skills necessary for executing tasks and provision of tools to enable activities or dutiesAn important feature of IDI programming is personnel integration across technical areas, rather than treating individual technical areas as silos, so the same personnel responsible for biosafety and biosecurity activities would also implement work in national laboratory systems for detecting outbreaks or antimicrobial resistance. In addition, staff in selected technical areas would also engage in outbreak response by embedding within government teams leading the effort and providing complementary support in infection prevention and control, laboratory, surveillance and border health, as required. These core technical areas were underpinned by a policy team working with government to advance and monitor progress during the implementation of the Uganda National Action Plan for Health Security. Initial capacity building activities were focused on viral hemorrhagic fever syndromes since outbreaks of Ebola virus disease (Ebola), Marburg virus disease, rift valley fever and Crimean-Congo hemorrhagic fever have all been reported in Uganda 11The program scaled microbiology capabilities of eight laboratories by providing equipment and supplies and training 35 laboratory staff to detect outbreaks using real-time polymerase chain reaction techniquesThe program conducted a successful pilot of the integration of animal samples into the national sample transport of results return system in human health. This allowed leveraging of investments in human health to allow separately packaged suspected outbreak samples collected from animals to be transported from peripheral health facilities and brought to regional veterinary laboratory laboratories and to the national reference laboratory for animal health (NADDEC). In 2017, systems for surveillance were strengthened by working with partners to support a pilot of trainings and mentorships of the electronic integrated disease surveillance and response (e-IDSR) system in 11 districts in West Nile. The eIDSR system consists three platforms; the cell phone messaging android and web-based that can enables data integration using a One Health approachUganda has experienced several outbreaks caused by Ebola and Marburg viruses. IDI joined the Joint Mobile Emerging Disease Intervention Clinical Capability (JME-DICC) consortium in collaboration with Makerere University Walter Reed Project (MUWRP) and United States Department of Defense partners to improve capacity for clinical research for investigational therapeutics for filoviruses with the aim of generating data leading to product licensure by developing: a) clinical capacity to identify and manage potential research participants through training of clinical staff; b) laboratory capacity through lab renovations, provision of equipment, and training of lab staff; and c) clinical research capability through renovations of an isolation research ward. These capacities were developed at the Fort Portal Regional Referral Hospital where an ongoing sepsis observational study is underwayFollowing an outbreak of Ebola in neighboring Democratic Republic of the Congo in 2018, assessments in Uganda revealed infection prevention and control gaps for key capacities in health facilities including screening, isolation and notification systems and capacity to manage suspected Ebola cases. IDI in collaboration with US CDC and other national partners, supported the development of an Infection Prevention and Control preparedness and response training for frontline health workers working in routine health settings and supported the training of the health workers to acquire competencies for routine screening, isolation and notification for suspect Ebola cases while maintaining high standards of IPC and to improve knowledge, skills in management of a suspect Ebola casesFurthermore, with capacity previously established through JMEDICC, IDI also supported erection of semi-permanent isolation unit in Naguru China Uganda Friendship Hospital and renovation of Oli Health Centre IV isolation in Arua. Following these improvements, training and drills were conducted for 41 frontline staff working at Naguru for EVD suspected cases. In high risk districts, 49 clinicians were trained on case management and 40 laboratory staff were trained on laboratory protocols for Ebola12. Through the CAPA-CT II project, IDI conducted a clinical study on the first drug-drug interaction study between the antiretroviral drug tenofovir disoproxil fumarate and remdesivir (an unsuccessful candidate therapeutic for ebola that was subsequently approved for COVID-19)In February 2020, prior to first case of COVID-19 reported in Uganda, IDI initiated its contribution for COVID-19 preparedness and the subsequent response. Internally, IDI adapted its business continuity plan for pandemic influenza to the COVID-19 pandemic. IDI embedded teams in the Ministry of Health to support coordination and planning in various response pillars and it supported development of legal instruments (rules) linked to the Public Health Act for COVID-19 prevention and control, development of capacity building materials, facilitated training of initial case management teams and supported border assessments and laboratory sampling capacity building targeting designated points of entry. With the detection of the earliest cases in Uganda, IDI supported quarantine, contact tracing and surveillance activities, and capacity building for COVID-19 laboratory sample management and reporting by mentoring 1371 laboratory workers in 500 health facilities and training health workers to activate sample collection in 53 points of entryThe COVID-19 pandemic placed health care workers (HCWs) at greater risk of infection and death. Among HCWs, COVID-19 exposures and infections result in work restriction or staff isolation, respectively, leading to loss of personnel needed to continue the delivery of essential health services. Adapting mentorship previously for Ebola, IDI supported the development of a national IPC mentorship program for COVID-19. IDI supported capacity building activities for IPC at regional level in five regions  and implemented direct IPC mentorship at facility level in 27 districts in West Nile, Bunyoro, greater Buganda regions and Kampala, Wakiso, Mubende, Kabarole and Mbale districts. Within 6 months (March \u2013 September 2020), IDI supported intensive and subsequently, monthly mentorship visits reaching 1615 health facilities and 10,500 HCWThe IDI Global Health Security program provides a model that can be used by institutions to deliberately develop capacities relevant to outbreak preparedness and response. Technical collaborations and partnerships contributed to the success of this program."}
+{"text": "This technique has made countless contributions to anticancer drug development due to the vast number of advantages, such as the preservation of the cell repertoire and immune components, identification of invasive ability of tumors, toxicity determination of compounds, quick assessment of therapeutic efficacy, and high predictive performance of drug responses. Importantly, it serves as a reliable tool to stratify therapeutic responders from nonresponders and select the optimal standard-of-care treatment regimens for personalized medicine, which is expected to become a potent platform and even the gold standard for anticancer drug screening of individualization in the near future.Organotypic tissue slice culture is established from animal or patient tissues and cultivated in an  The development of novel drugs is time-consuming, laborious, and costly. In the United States, it requires ~13 years and between 1.8-2.6 billion US dollars from commencement to regulatory approval by the Food and Drug Administration (FDA) in vitro due to its many inherent drawbacks. First, monolayer cell culture rarely recapitulates tumoral heterogeneity and complexity, not to mention the tumor microenvironment (TME) in vivo phenomenon of gradient-degressive diffusion and perfusion-controlled delivery.The most commonly used tool for identifying new antitumor drugs is the two-dimensional (2D) culture of monolayer cells, wherein a standardized high-throughput system is offered to dissect the characteristics of specific cell types The three-dimentional (3D) organoid technique has been developed rapidly for the identification of anticancer drugs and personalized medicine in the past decade 3) and then mixed with collagen before cultivation at the air-liquid interface. Because of the success in the recapitulation of a Wnt-dependent stem cell niche, differentiation, and ultrastructure of stomach cell lineages in vitro tumor tissue culture and strikingly found that the immune cells, T-cell receptor repertoire, and phenotypic and genotypic profiling were highly preserved In 2009, Ootani et al. in vivo microanatomy and the easy manipulation of in vitro work Table 1). This review attempts to summarize and contextualize the contributions of organotypic tissue slice culture in anticancer drug discovery and emphasizes the likely future development in this field.The organotypic tissue slice culture platform is also pragmatic for anticancer drug discovery owing to the integration of the alike Figure 1). Organotypic tissue slice culture systems represent in vitro cultures of explants of patient- or animal-derived tumoral and normal tissues.The prototype of organotypic tissue slice culture was developed by Dr. Harford and coworkers in the 1950s Figure 2). Briefly, the surgically resected tissues are collected and placed into cold media, which then are meticulously cut into cylindrical or cuboid shapes. These cylindrical or cuboid tissues are sectioned via a slicing method  under sterile conditions within ~6 hours after tumor excision. Only well-shaped slices are selected for cultivation. Slices were incubated in a humidified incubator at 37 \u00b0C and 5% CO2 for several days, and the culture media were changed every 2-4 days.The preparation of tissue slice culture mainly involves the following steps . Second, the key immune cell repertoire and the gene expression level of T lymphocytes and B lymphocytes can be entirely preserved for at least 8 days .The organotypic tissue slice culture platform can be used to validate results obtained from 2D culture and recapitulate The generation procedures and culture conditions affect the viability of organotypic tissue slices. Slicing tools, thickness, postresection culture timeframe, and oxygen levels all determine the quality and live cell quantity of slice from the beginning of cultivation to the endpoint of drug assessment. Carefully optimizing the preparation and culture conditions can minimize the artificially induced variations in cell viability.Most studies generate slices with a thickness of 250-500 \u03bcm Various postresection culture timeframes give rise to slices with diverse persistence to preserve the tissue architecture and viability, ranging from 4 to 16 days 2) elicits rapid and significant changes to many stress pathways and is associated with a negative impact on the morphology of tumor slices 2) do not increase the tissue viability, metabolic activity, and proliferation of slices compared to normoxic conditions (21% O2) Appropriate oxygen levels are necessary for the retention of slice morphology The optimal time window for the assessment of therapeutic efficacy needs to be clarified, which should obviate the slicing-caused activation of stress and inflammatory responses in the beginning and the tissue destruction and devitalization of overlong cultivation. Metabolic activity is continuously elevated within the first 24 hours of cultivation but does not fluctuate at later time points The organotypic tissue slice platform allows the selection of optimal treatment regimens for individualization in the context of precision oncology and has won popularity in the elucidation of tumor invasive ability, the potential toxicity of drugs, and the efficacy assessment of multiple treatment paradigms.The tumor invasive tissue slices visualize the tumor invasiveness in near real-time and offer easy maneuverability for testing the pharmacological efficacy of therapies against tumor migration  Table A profound marker  of the invasive phenotype tumor cells has been found on the tumor invasive normal tissue slice culture system in vitro condition Plus, the tumor invasive tissue slices show a promising outlook in the evaluation of the potential pharmacological toxicity. Brain slices can serve as a tool to reflect the toxicity of various neurotoxic compounds and may provide interventions to mitigate toxicity Table 3 and discussed below.Organotypic tumor slice culture demonstrates the suitability to investigate the antitumor activity of small-molecule drug therapy  https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf). Utilizing breast cancer patient-derived slices to assess the CAF response succeeds in the stratification of CAF responders from nonresponders Organotypic slices treated with small-molecule drugs show concentration-dependent and heterogeneous responses in vitro results of immunotherapeutic efficacy. Indeed, Voabil and colleagues Deciphering immune-oncology on organotypic tissue slice was initially described by Sivakumar et al. The filter-supporting tumor slice culture model with a 0.4 \u03bcm pore size membrane culture insert cannot prevent the horizontal lymphocyte efflux and thus may identify the negative result of pembrolizumab  responses Radiotherapy reduces the risk of tumor relapse, ameliorates survival benefits, and has become an irreplaceable component of systematic treatment for many cancers Adoptive cellular therapy is a new type of therapy that aims to leverage the internal immune system to obviate cancers, wherein immune cells are engineered with the expression of anti-specific T-cell receptors or chimeric antigen receptors (CARs) that can better recognize and kill malignant cells Organotypic tissue slice culture platform has many advantages for anticancer drug discovery, including (1) identification of tumoricidal efficacy of anticancer drugs, specifically the immune checkpoint blockade antibodies; (2) high predictive performance of drug responses; (3) quick stratification of treatment responders and nonresponders; and (4) ascertainment of the cooperativity of different combination therapy strategies. Therefore, this technique may tailor the best clinical guideline-recommended regimens for individualization, providing a decision aid for clinicians. Recapitulation of the complexity and TME of original tumors on the slices is of pivotal importance, particularly the indispensable components for specific anticancer drugs . Thus, it needs to consider all aspects of the generation and cultivation conditions for maximally maintaining the consistency of the slices with the original tissues. Notably, accurately judging therapeutic efficacy requires averaging an adequate number of slice results due to intratumoral heterogeneity. In addition, the system is not a reproducible tool similar to 3D-ALI or patient-derived xenografts and is normally unable to test a plethora of drug responses. It is crucial to enhance the efficiency of clinical translation of preclinical findings on this technique, for which it needs to narrow down the drug candidates by prescreening compounds by the 2D monolayer cell culture or selecting agents according to the NCCN clinical practice guidelines in oncology.Table 4. Each of them has been documented with the potential to assess the oncological efficacy of the antitumor treatment strategy. In addition, tissue slices have implicated the availability of uncovering novel biomaterials within the synthesis of anticancer drugs; for example, graphene quantum dots and nanoparticles both show complete penetration and minimal viability damage on slices Different tissue origins and preparation procedures bestow the platform with the intrinsic advantages and limitations in the field of anticancer drug discovery. We enumerated the overlapping but distinct preparation conditions for different organotypic tumor slice models in"}
+{"text": "The fact that self-rated health (SH) predicts mortality and a variety of other health outcomes independent of objective health measures generates questions about mechanisms and etiologies. SH can be considered an indicator of physical health, per se, resulting from active cognitive processing of explicit information about one\u2019s own health and intuitive knowledge of symptoms and physical sensations. The extent to which SH taps shared cultural ideas about health should be reflected in estimates of the shared environmental component of variance (C). SH has also been associated with emotional health measures, such as neuroticism and depression. Previous analyses have been limited by sex (only women), sample size, age (range = 63-76), and failure to include cognitive function. The current analysis used data from 8291 adults ranging in age from 22 to 102 from the international Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium to investigate the genetic architecture of SH. Genetic influences on self-rated health (SRH) were investigated in the context of CIRS , MMSE , and depression (CES-D or CAMDEX). Independent pathways modeling indicated that all genetic variance for SRH was shared with CIRS, MMSE, and depression. Comparison of groups older and younger than 74 indicated age differences in genetic architecture of SRH. Evidence suggests that the discordance between objective and subjective health increases in late adulthood, possibly as a result of greater emphasis on psychological rather than physical components of subjective health assessments by older adults."}
+{"text": "Colorectal cancer (CRC) is one of the main causes of mortality and morbidity worldwide. To date, the relationship between regional deprivation and CRC incidence or mortality has not been studied in the population of Cyprus. The aim of this study was to analyse the geographical variation of CRC incidence and mortality and its possible association with socio-economic inequalities in Cyprus for the periods between 2000 and 2015.A small area ecological study in Cyprus, with census tracts as units of spatial analysis, for the period between 2000 and 2015. The incidence date, sex, age, post code, primary site, death date in case of death or last contact date in case of alive for all cases of CRC from 2000-2015 were obtained from the Cyprus Ministry of Health. Indirect standardization was used to calculate the sex and age Standardize Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs) of CRC while the smoothed values of SIRs, SMRs and Mortality to Incidence ratio (M/I ratio) were estimated using the univariate Bayesian Poisson log-linear spatial model.There are geographical areas having 15% higher SIR and SMR, with most of those areas located at the east coast of the island. Higher M/I ratio values were found in the rural, remote, and less dense areas of the island while lower rates were observed in the metropolitan areas. An inverted U-shape pattern in CRC incidence and mortality was observed with higher rates in the areas classified in the second quartile of the socio-economic deprivation index and lower rates in rural, remote, and less dense areas. A different pattern emerged in the M/I ratio indicating a stepwise increase across increasing levels of socioeconomic deprivation.These findings can potentially provide useful information at local and national levels and can inform public health authorities to appropriately allocate resources for geographically targeted prevention and control plans to increase CRC screening.\u2022\u2002M/I ratio of CRC was positively associated with regional deprivation since a stepwise increase was found across increasing levels of rural-related socioeconomic deprivation.\u2022\u2002Interventions aimed at reducing the risks of CRC should primarily focus on socially deprived communities in Cyprus."}
+{"text": "Little is known about the epidemiology of HIV infection among HIV positive people who inject drugs (PWID) in India. Injecting drug use has emerged as an important route of HIV transmission in India. The objective of this study was to conduct a systematic review on the risk behaviours associated with HIV infection among HIV positive PWID and assess the data reported.A systematic search of six electronic databases, Scopus, PubMed, PsycINFO, CINAHL, Embase and Ovid Medline was conducted. These databases were searched for published studies on injecting risk behaviours, sexual risk behaviours and socio-demographic factors associated with HIV infection among HIV positive PWID in India.A total of 15 studies were included in the review of which 3 studies evaluated HIV/HCV coinfection among HIV positive PWID. Older age, low educational level and employment status were significantly associated with HIV infection. Sharing of syringe and needle, frequency of injection, early initiation of injecting practice, inconsistent condom use and having multiple sexual partners were all commonly associated with HIV infection among HIV positive PWID.Our study identified significant injecting and sexual risk behaviours among HIV positive PWID in India. There is an increasing HIV transmission among PWID in different states, more so in the northeastern states and in metropolitan cities in India. More studies need to be conducted in other regions of the country to understand the true burden of the disease. The lack of sufficient data among HIV positive female PWID does not preclude the possibility of a hidden epidemic among female PWID. The need of the hour is for the prevention of further transmission by this high-risk group through the provision of comprehensive programs, surveillance and robust continuation of harm reduction services.The online version contains supplementary material available at 10.1186/s12889-022-13922-2. The high prevalence of Human Immuno-deficiency Virus (HIV) among many populations of injecting drug users (IDUs) represents a substantial global health challenge and injecting drug use is an increasingly significant cause of HIV transmission in most countries worldwide . An estiInjecting drug use (IDU) has emerged as an important route in HIV transmission in India. HIV was detected in India in 1986 among female sex workers and since then the prevention and transmission of HIV was focused with the commercial sex industry. Unfortunately, because of this, HIV transmission among people who inject drugs (PWID) and the drug-sex interface received little attention . CurrentInjecting drug use has been the principal driver of the HIV epidemic in northeastern states of India, this could be due to its proximity to the \u2018golden triangle\u2019 of heroin production  which has fueled much higher rates of injecting drug use than in other states of the country . HoweverHarm reduction which includes needle/syringe programs and opioid substitutions is an evidence-based approach to HIV prevention and treatment for PWID and is supported by World Health Organization (WHO) and other UN agencies . In IndiOur aim was to explore factors associated with HIV infection among PWID in India by conducting a systematic review of peer- reviewed literature reporting data on the epidemiology of HIV and the sociodemographic, injecting and sexual behaviours associated with HIV among HIV positive PWID.The review was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines . The revRelevant MesH words and sub-headings were used to generate articles from the six databases. The following MesH terms and keywords were used in the search:ANDAND(India)ANDAll articles identified in the search were exported into Endnote X9, where all duplicates were removed and screening and selection of remaining articles were done. The first author (LNP) screened all the titles of remaining publications. The next phase of screening involved reading the abstracts of studies retained from the first phase and eligible articles were retained for full text reading. In the final phase (LNP) read full text of the remaining articles and were assessed for eligibility. Studies were included in the review if they meet the following criteria: i) focused on HIV among people who inject drugs only ii) recorded coinfections with hepatitis C among HIV positive PWID iii) observational studies  iv) published between the year 2000 and 2021 v) published in a peer-reviewed journal vi) written in English vii) focused on India only.Two authors LNP and MVD independently assessed the quality of the studies and extracted the relevant data. All disagreements between the two reviewers were resolved through discussion and consensus on potential eligibility reached. Third and fourth reviewers KA and CT adjudicated the differences that emerged in the selection of the final studies for inclusion.The assessment tools of the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) for quality assessment of Observational Cohort and Cross-sectional Studies and Controlled Intervention Studies was used for the quality assessment of this review . There aIn this systematic review a total of 728 non-duplicate records from six databases were screened. After review of titles and abstracts 67 articles were retrieved for full text review. A total of 15 articles met the inclusion criteria for this review. The review process is presented graphically in Fig.\u00a0Tables Supplementary table SSociodemographic factors evaluated in this review are summarized in Table This review found that sharing of syringes and needles \u201329, 31 wThe reviewed studies demonstrated that sexual risk behaviour associated with HIV infection among HIV positive PWID included inconsistent condom use , 29, 31,Three studies were found in this review that reported HIV/HCV coinfection among HIV positive PWID . The associations between low educational level, employment status and HIV infection in this review is consistent with studies conducted in Malaysia  and IranOur review showed needle/syringe sharing, frequent injecting, early initiation of injection practice and injecting of heroin and buprenorphine as proximal factors associated with HIV infection. We found sharing of syringes and needles to be the most common injecting risk behaviour among HIV positive PWID. This finding is in line with other studies that have focused on HIV among PWID \u201348. Our Three papers in our review showed HIV/HCV coinfection and risk behaviours among coinfected PWID. Of the three papers, two studies were conducted in the northeastern states of India which highlights the need to further study HIV/HCV coinfection among PWID in this region. Understanding the true burden of disease at a community level as well as prevalent risk behaviours are critical for designing effective prevention interventions to curtail the spread of HIV and other infectious diseases among PWID as well as from their sexual partners and the general population . The injPapers reviewed for this study found that blood-borne infections such as HIV, Hepatitis C and Hepatitis B among PWID is spread primarily through injecting risk behaviour related to sharing of needles and syringes as well as through sexual risk behaviours such as unprotected sex and exchange of sex for drugs and money. India, through its National AIDS Control Program (NACP) adopted a comprehensive package of biomedical behavioural interventions as the optimal HIV prevention strategy. This comprehensive package is recommended by World Health Organization (WHO), United Nations Office on Drugs and Crime (UNODC), the joint United Nations Programme on HIV/AIDS (UNAIDS). The package consists of 9 components which include a needle syringe exchange programme (NSEP), Opioid Substitution Therapy (OST) and Targeted Information, Education and Communication (IEC).The NACP-IV \u2018Targeted Intervention\u2019, a package that caters particularly for high-risk groups including PWID includes the delivery of services comprising of needle syringe exchange program (NSEP), opioid substitution therapy (OST), peer education for adopting safer behaviours, primary medical care, condom distribution and referral for other health-care needs . These sWHO, UNAIDS and UN office on drugs and crime has recommended mobile needle and syringe programmes as an alternative or complimentary delivery method of needle and syringe programs . Mobile However, the prevention of HIV among PWID cannot be achieved through one program or service alone but requires comprehensive package of interventions geared towards specific needs of PWID. The national and local government needs to continue robust engagement and support of PWID and continue working with other community organizations supporting PWID. This will strengthen linkage to services and increase the probability of retention in services .Pre-exposure Prophylaxis (PrEP) has been recommended by WHO to be included in the HIV prevention package for PWID . The BanThe strength of our study lies in the comprehensive and exhaustive search through extensive databases and having two independent reviewers undertake the study selection, examined the studies to be included in the review based on the inclusion and exclusion criteria through discussion and consensus as well as quality assessment. However, there are also limitations to our study. One limitation of our study is that there were virtually no HIV data among HIV positive PWID in the majority of the states in India which limited the assessment of the status of the epidemic. Secondly, data on female HIV positive PWID were limited which may result in gender bias. Thirdly, studies on HIV/HCV coinfection among HIV positive PWID was limited which made it difficult to draw conclusion into the associated factors of coinfection. Fourthly, most of the included studies were cross-sectional which may have resulted in recall bias in the findings due to the nature of data collectionAnother limitation is that there is no quality rating for the choice of behaviours selected for the presentation of the results. Lastly, we acknowledge that there are some studies that are done outside of India, however these studies are beyond our study inclusion criteria.The papers reviewed for this study found significant injecting and sexual risk behaviours among HIV positive PWID in India. There is evidence for HIV epidemic among PWID in different states, more so in the northeastern states and in metropolitan cities in India. More studies need to be conducted in other regions of the country to understand the true burden of the disease. The lack of sufficient data among HIV positive female PWID does not preclude the possibility of a hidden epidemic among female PWID. The need of the hour is for the prevention of further transmission by this high-risk group through the provision of comprehensive programs, surveillance and robust continuation of harm reduction services.Additional file 1.Additional\u00a0file 2."}
+{"text": "The COVID-19 pandemic and related restrictions have had negative impacts on mental health. Sexual minorities  have been shown to exhibit mental health disparities stemming from minority stress experiences. The purpose of this study was to examine the mental health trajectories of older sexual minority Canadians in comparison to heterosexual Canadians before and during the pandemic. We used data from the Canadian Longitudinal Study on Aging (CLSA), where data were collected from participants at baseline (2011\u20132015), first follow-up (2015\u20132018), and two time points during the COVID-19 pandemic (April-December 2020). General Estimating Equations (GEE) were used to model changes in depression symptoms  and loneliness , adjusting for covariates . Results showed that LGB participants reported more symptoms of depression  and loneliness  in comparison to heterosexual participants. Mental health outcomes worsened over time for all participants. These findings highlight the impacts of the pandemic on mental health and the need for tailored interventions for older lesbian, gay, and bisexual individuals."}
+{"text": "This complex intervention includes six components  that can be locally adapted. The cluster-randomized interprof ACT trial evaluates the effects of this intervention on the cumulative incidence of hospital admissions (primary outcome) and secondary outcomes  within 12 months. It also includes a process evaluation which is subject of this protocol. The objectives of this evaluation are to assess the implementation of the interprof ACT intervention package and downstream effects on nurse\u2013physician collaboration as well as preconditions and prospects for successive implementation into routine care.To improve interprofessional collaboration between registered nurses (RNs) and general practitioners (GPs) for nursing home residents (NHRs), the This study uses a mixed methods triangulation design involving all 34 participating nursing homes (clusters). The quantitative part comprises paper-based surveys among RNs, GPs, NHRs, and nursing home directors at baseline and 12 months. In the intervention group (17 clusters), data on the implementation of preplanned implementation strategies  and local implementation activities will be recorded. Major outcome domains are the dose, reach and fidelity of the implementation of the intervention package, changes in interprofessional collaboration, and contextual factors. The qualitative part will be conducted in a subsample of 8 nursing homes (4 per study group) and includes repeated non-participating observations and semistructured interviews on the interaction between involved health professionals and their work processes. Quantitative and qualitative data will be descriptively analyzed and then triangulated by means of joint displays and mixed methods informed regression models.interprof ACT intervention package, the changes induced in interprofessional collaboration, and the influence of contextual factors. These data will reveal expected and unexpected changes in the procedures of interprofessional care delivery and thus facilitate accurate conclusions for the further design of routine care services for NHRs.By integrating a variety of qualitative and quantitative data sources, this process evaluation will allow comprehensive assessment of the implementation of the NCT03426475. Registered on 07/02/2018.ClinicalTrials.gov The online version contains supplementary material available at 10.1186/s13063-022-06476-6. For nursing home residents (NHRs) in developed countries, relatively large rates of emergency and hospital admissions are reported, although the benefits of these admissions for the health and well-being of this population are uncertain . In thesIn Germany, as in other countries , medical care for NHRs is provided by general practitioners (GPs) and other medical specialists who run their own offices or are employed by larger offices or ambulatory medical care centers. Because NHRs are frequently not able to visit a GP\u2019s office, GPs visit nursing homes for regular consultations and are accessible in urgent situations during usual working hours on weekdays. Outside these hours, the NHR and the nursing home staff must draw on out-of-hours GP services and other emergency services when they consider medical support to be necessary. The choice of the GP and other physicians is, by law, at the discretion of the individual NHR. Therefore, nursing homes usually collaborate with a variety of GPs and other medical specialists. Empirical data suggest that on average, ten GPs per nursing home are involved in medical care for NHRs in Germany .interprof ACT intervention package,\u201d was developed and piloted to improve the quality of RN-GP collaboration and thus the quality of medical care for NHRs in Germany ; Characteristics of the interprof ACT intervention package (description based on the TIDieR checklist).Additional file 2.\u00a0Overview of standardized instruments used for the quantitative part of the interprof ACT process evaluation; Instrument names, measured outcome domains and subdomains, and description of item and scaling formats."}
+{"text": "Trauma care verification relies on benchmarking, and it has recently moved towards verification of trauma systems rather than individual centresTraumatic injuries are a leading cause of mortality, and can be challenging to treat, particularly in situations of polytrauma.The TCVP is an important quality improvement initiative led by Royal Australasian College of Surgeons (RACS), with active participation from the Australasian College for Emergency Medicine, the Australian and New Zealand College of Anaesthetists, the College of Intensive Care Medicine of Australia and New Zealand, and the Australasian Trauma Society. It is a peer review\u2010based benchmarking process  and partBox 1Box 2Source: Figure reproduced with permission from the Trauma Care Verification and Quality Improvement Writing Group, Royal Australasian College of Surgeons.Trauma care verification relies on benchmarking, a process designed to improve care via the standardisation of clinical and administrative processes .6 TrauIn an analysis of 109 American hospitals, verified level I trauma centres had lower mortality and complications and shorter intensive care unit and hospital stays compared with unverified centres.The ATR was established in 2011 under the Australian Trauma Quality Improvement Program and currently collects data from 34 sites across Australia and New Zealand.Contributing to national research is an essential criterion in the TCVP for level I trauma centres. However, institutions face many barriers when collecting and recording data; examples include a lack of funding and resources and an inability to capture pre\u2010hospital and post\u2010discharge data.Quality indicators are evidence\u2010based metrics evaluating the quality of health care processes that influence patient outcomes.There have been several attempts to develop standardised trauma care quality indicators internationally. A 2021 systematic review proposed a core set of 82 trauma quality indicators following international expert consensus.Following discussion of the above systematic search of the international literature, a working group of trauma professionals  developed 31 novel indicators for Australia and New Zealand trauma care . These aBox 3A recent survey of trauma professionals in Australia and New Zealand highlighted that trauma registries are underutilised.Participation in quality improvement initiatives such as trauma verification and the ATR should be encouraged through additional government funding and policy support. Further research validating the 31 proposed quality indicators relevant to Australia and New Zealand trauma care is needed to determine their utility in practice.Open access publishing facilitated by The University of Newcastle, as part of the Wiley \u2010 The University of Newcastle agreement via the Council of Australian University Librarians.No relevant disclosures.Not commissioned; externally peer reviewed."}
+{"text": "We are delighted to announce the publication of the special issue with the topic \u201cProgresses in the Drug Treatment of Chronic Cardiopulmonary Diseases\u201d. One hundred and thirty two authors made their contributions to this issue and the editors finally assembled 18 full-length articles. The scale of accepted papers is wide covering from basic research to translational medicine and clinical studies. The content includes molecular mechanisms, meta-analysis, candidate compounds, metabolomics and bioinformatics. In our opinion these studies show advanced and useful information in this field, provide new insights into understanding of pathological mechanisms or identification of new therapeutical targets in Chronic Cardiopulmonary Diseases (CCD).via regulating the drosophila mothers against decapentaplegic2/3 (Smad2/3) pathway . Interferon regulatory factor 9 (IRF9) facilitates pulmonary artery smooth muscle cells proliferation by regulating prohibitin1 (PHB1) expression and protein kinase B (AKT) signaling pathway to affect mitochondrial function during the development of PH . MicroRNAs with pleiotropic effects have great potential as biomarkers and therapeutic targets for CCD .The authors paid attention to the pathophysiological mechanisms and biomarkers in challenging diseases including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH) and pulmonary embolism (PE). For example, it is reported that Sirtuin (Sirt2) may participate in the development of IPF  for CCD .Luo et Tettey et al. suggested that several new substances targeting on NO pathway show a promising potential to represent future alternatives. The current knowledge indicates that COPD and OSAS patients may be at higher risk to develop the cardiovascular diseases. Collection and analysis of clinical data demonstrated that patients with OS possessed deteriorating baseline characteristics and an increased prevalence of cardiovascular diseases, among them the heart failure and PH, compared to the patients with COPD or OSAS alone . This is a clear reminder for clinicians to be alerted that OS patients have elevated risk of cardiovascular diseases and that early detection and adequate treatment are crucial for these individuals. Furthermore, it is known that PTE is an important cause of death in the context of cardiovascular diseases , coining a new concept of pulmonary artery thrombotic disease and facilitating our understanding of pathogenesis, differential diagnosis, and personalised therapeutics of the three pulmonary artery thrombotic diseases .There are three articles summarizing the advances in PH, pulmonary thromboembolism (PTE) and chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSAS) overlap syndrome (OS). The nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PH , Tettey diseases . FollowiHe et al.), which would lead to the better understanding of the profound molecular mechanisms in hypoxic PH and provide valuable clues to researchers who would follow these emerging genes in the future. Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) related gene sets were obtained through text mining by Tan et al. Furthermore, the intersection of gene sets was analyzed for functional enrichment through the DAVID and the STRING was used for the determination of the protein-protein interaction network of the overlapping genes and the significant gene modules. As the outcome, the enriched candidate genes were finally analyzed by Drug Gene Interaction database to find 13 drugs targeting six genes which may potentially result in beneficial therapeutic effects against the severe disease, such as CTD-PAH .Metabolomics and bioinformatics are increasingly used approaches to identify the differential features between the states of health and disease . ScientiChen et al.; Zhang et al.). In addition, clinical practice of sodium-glucose cotransporter 2 inhibitors (SGLT2is) is summarized with regard to the prevention of cardiovascular and respiratory dysfunctions . Results of these studies strongly suggested the promising pharmacological effects and revealed the underlying mechanisms of above mentioned natural compounds. One study also indicated the new clinical application of Xuezhikang, an extract of cholestin, which consists of lovastatin, phytosterols and isoflavones and it was previously used to reduce the serum lipid concentrations. Results showed the potential therapeutic effect of Xuezhikang on PH patients with low serum high-density lipoprotein cholesterol (HDL-C) levels . In the past, we became aware of the existence of significant limitations with regard to the monotherapy, and subsequently the clinical drug combinations were continuously investigated  and pyrimidine ring (stimulating soluble guanylate cyclase (sGC) functional group)  . BifunctIn conclusion, it is clear that despite intensive research efforts to identify and develop new therapies over the past two decades, CCD remain a group of diseases characterized with high morbidity and mortality. The urgent clinical needs are still not properly addressed. Research in this field has become a hot and key venue, waiting for exciting new findings emerging from basic and clinical investigations into the pathophysiology and precise molecular pathobiology of CCD. We strongly call for more attention to CCD and the use of more cutting-edge technology to develop better treatment options."}
+{"text": "The successful promotion of health-enhancing physical activity (HEPA) requires authoritative information to enable the design, implementation and evaluation of effective and cost-effective policies. This includes reliable and valid prevalence data of physical activity (PA) that can be compared across European Union Member States populations regardless of the type of measurement instrument used. In order to enable comparison of PA prevalence data between different measurement instruments, an attempt was made to develop a conversion factor between commonly used questionnaires in Europe and accelerometry in the ongoing European Union Physical Activity and Sport Monitoring System project (EUPASMOS) among 18 member states.Data of physical activity (PA) and sedentary behavior (SB) were collected in 18 member states using four questionnaires  and the UKK RM42 accelerometer. The number of measured participants varied between 100 and 1000 among the 18 member states. Participants completed the questionnaires in random order and wore the accelerometer seven consecutive days on their right hip (during the day) and on their non-dominant wrist (overnight). Time spent in moderate-to-vigorous intensity physical activity and sedentary behavior were calculated based on these 5 measurement instruments. The comparison between methods will be examined by using sophisticated regression analyses.The EUPASMOS project is in progress and the final data is collected in the last two member states. In the meantime, a model is being developed to examine whether a conversion factor can be calculated to compare prevalence data based on questionnaires and accelerometry. By developing a conversion factor, prevalence data can be compared between member states although the measurement instruments used differ between member states. In June 2020 the results from these analyses are expected.These results will provide insight into the possibility to compare prevalence data of physical activity among member states, when using different measurement instruments within their monitoring systems."}
+{"text": "We performed this systemic review to investigate the therapeutic potential and safety of adjunctive accelerated repetitive transcranial magnetic stimulation (aTMS) for older patients with depression.We included published randomized clinical trials (RCTs) and observational studies targeting adjunctive aTMS for older patients with depression.n = 29) fulfilled the criteria for inclusion. The included studies reported significant improvements in depressive symptoms from baseline to post-aTMS . One study reported a dropout rate of 10.5% (2/19). Mild headache was the most common adverse reaction.Two open-label self-controlled studies (The currently available evidence from two open-label self-controlled studies indicates that adjunctive aTMS is a safe and effective therapy for older patients with depression. Depression is a leading cause of disability , was approved by the FDA as a treatment for MDD in 2008  protocols have been studied as a potential solution for this problem  independently searched electronic databases  and manually checked reference lists of the included studies  suffering from uni- or bi-polar depression, as defined by the respective studies. Intervention vs. Comparison: real aTMS with antidepressants vs. antidepressant monotherapy or sham aTMS wiht antidepressants; aTMS added to antidepressants . Outcomes: the primary outcome was changed in depressive symptoms as measured by depression scales [i.e., the Montgomery-Asberg Depression Rating Scale (MADRS)  investigating the efficacy and safety of aTMS in combination with antidepressants for older patients with uni- and bi-polar depression were eligible for inclusion. As reported previously  extracted relevant data from each included study. Any disagreements were resolved through consensus or, if needed, through discussion with the senior author (WZ). Missing data were requested by contacting first and/or corresponding authors and/or searching for the data from other reviews  using the Cochrane risk of bias  or bipolar depression (n = 2), are summarized in n = 10)  . In Dardenne et al.'s  suffering from depression. Only two observational studies  examining the efficacy and safety of adjunctive aTMS for older patients with depression were included , National Natural Science Foundation of China (82101609), Scientific Research Project of Guangzhou Bureau of Education (202032762), Science and Technology Program Project of Guangzhou (202102020658), Guangzhou Health Science and Technology Project (20211A011045), Guangzhou science and Technology Project of traditional Chinese Medicine and integrated traditional Chinese and Western medicine (20212A011018), China International Medical Exchange Foundation (Z-2018-35-2002), Guangzhou Clinical Characteristic Technology Project (2019TS67), science and Technology Program Project of Guangzhou (202102020658), and Guangdong Hospital Association (2019ZD06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
+{"text": "This case study is based on an outbreak investigation conducted by multisectoral team from animal and public health offices in Kaktong (a remote village in Zhemgang District Bhutan) during July-September 2010. This outbreak caused by ingestion of infected cow meat which had died after a brief illness (bleeding of unclotted blood from nostrils). The owner of the affected cow had opened the carcass and dressed the meat, which he shared or sold within the village for human consumption. It simulates an epidemiological investigation including active and passive case finding, descriptive and analytical epidemiology, laboratory confirmation, risk communication with implementation of control measures. This case study is designed for the training of front-line public health professional, basic, intermediate and advanced level field epidemiology trainees. The case study will build the capacity of the trainees regarding investigating illnesses caused by animal-human interface. This case study is an added resource for students of epidemiology and public health with specialised knowledge who need further information on the outbreak investigation with management and risk communication. The case study is ideally conducted in groups of about 10-20 participants under supervision of facilitator. Each student will participate in the case study by reading the paragraph on his/her turns. The facilitator will be responsible for engaging students in discussion, clarifying any confusing concepts or data analysis, and encouraging participants to think about the answers of the given questions. Notes for facilitator are coupled with each question in the facilitator version of case study with objective to aid facilitation.This case study was designed for public health professional  and trainees of field epidemiology Before using this case study, participants should have background knowledge on Anthrax , public health surveillance and outbreak investigation.Approximately 3.5 hoursEnglishDownload the case study student guide (PDF - 550 KB)Request the case study facilitator guide: contact info@gibacht.org"}
+{"text": "Concerns have surfaced regarding the quality of assisted living (AL) with calls for quality metrics reporting as essential for consumer choice and organizational accountability. This study presents a framework for quality metrics in ALs using a) results from literature review and environmental scan of existing domains and indicators used to assess quality in AL and 2) a survey of results from MN stakeholders (n=822) on their priorities regarding these quality measures. Our findings showed that consumer-reported measures  were rated as top priority, followed by staff-based measures . Other domains included residents\u2019 safety, resident health outcomes, care services and integration, and the environment of the ALs. These results have implications for states looking to develop and implement quality measures in ALs, especially in the context of rising AL resident acuity and the continued trend away from institutional models of long-term care."}
+{"text": "Timothy McMahon)\u2022Kentucky State Police Forensic Science Laboratory (Laura Sudkamp)\u2022Miami-Dade Police Department, Forensic Services Division (Stephanie Stoiloff)\u2022Minnesota Bureau of Criminal Apprehension Forensic Science Services (Catherine Knutson)\u2022Missouri Highway Patrol Crime Laboratory Division (Brian Hoey)\u2022New York City Office of Chief Medical Examiner's Office (Timothy Kupferschmid)\u2022New York State Police Crime Laboratory System (Dr. Ray Wickenheiser)\u2022Ohio Bureau of Criminal Investigation (Roger Davis)\u2022Texas Department of Public Safety (Brady Mills)\u2022Wisconsin Department of Justice Division of Forensic Sciences (Jennifer Naugle)The National Technology Validation and Implementation Collaborative (NTVIC) was established in 2022 with a vision to collaborate nationally on validation, method development, and implementation. The group is not associated with any organization, corporation, or non-profit. However, the group has connections with prominent forensic science membership organizations, universities, and private technology and research companies. The top leaders of the NTVIC Steering Group are federal, state and large local laboratory directors. The founding group of state and large local laboratory directors share a common vision to share existing resources to work together on these validation and implementation projects to lessen the burden on individual forensic science and forensic medicine providers to perform the work. Currently, forensic providers often duplicate validation studies, method development, or performance verification out of necessity. Forensic science service providers have learned that conducting these studies collaboratively has several benefits: 1) The most informed and brightest minds in the country can be used to generate plans, procedures and troubleshoot issues. 2) The existing resources at laboratories can be pooled to implement the solution more quickly and provide more robust data sets. 3) The validation work can be published as a collaborative effort for purposes of public scrutiny. 4) The developmental validation work product can culminate in a technology transfer and implementation plan for instrument purchase, performance verification, and quick implementation in other laboratories interested in the technology. Founding members of the NTVIC are:2The mission of the National Technology Validation and Implementation Collaborative (NTVIC) is to share resources and strategies to rapidly implement technology and new methods into publicly funded forensic science service provider (FSSP) and forensic science medical provider (FSMP) facilities in a scientifically sound and defensible manner.3The National Technology Validation and Implementation Collaborative is a group of visionary publicly funded FSSPs and FSMPs with a shared desire to perform developmental or other validation of new instruments or methods and facilitate their implementation. The NTVIC invites participation from publicly funded FSSPs and FSMPs, federal government agencies and laboratories, vendors, researchers and technology experts, and others interested in validation and implementation of technology or new methods in publicly funded forensic science laboratories. A NTVIC steering group of forensic science laboratory directors, leaders, researchers, and educators determines projects that the collective team will collaborate on to developmentally or otherwise validate with a focus on sharing the responsibility and workload for validation planning, analytical work, documentation, and peer reviewed publication of findings.Committees will be established for each specific project with interested member participants and contributors. Members will select committees and subcommittees to lead and participate in based on interest, need, resources, and other considerations. Each project committee will address elements of training for forensic science providers, policy development, and technical considerations such as appropriate instrumentation, procedures, and validation required. Each committee formed will solicit appropriate collaborators and partners, determine the contributions needed from each participant, secure funding necessary to accomplish validation, oversee the technical aspects of robust validation and implementation, and ensure that an implementation plan is published for other forensic science providers to implement. The focus of each subcommittee will be validation for participants, creation of an implementation plan for other interested laboratories, and publication of work in peer-reviewed journals. All publications will emphasize best laboratory and quality management processes.4\u2022To increase the speed of technology and method validation and implementation into publicly funded FSSPs and FSMPs\u2022To share available validation resources at publicly funded forensic science facilities for faster implementation\u2022To plan, accomplish, and publish scientifically sound and defensible validation studies in peer reviewed publications\u2022To contribute to standardization of technology implementation in public forensic science entities, utilizing the latest standards\u2022To facilitate the establishment of technology specific working groups to support continuous improvement of validated and implemented technology\u2022To publish, after validation, a performance verification implementation plan for other laboratories, complete with purchasing information, appropriate methods, and performance verification plan\u2022To provide a not-for-profit home for federal funding that supports technology and method implementation\u2022To provide a venue for early adopter forensic science providers to interact and collaborate\u2022To ensure each technology, instrument, or method is implemented with appropriate policy, procedure, and quality managementThe National Technology Validation and Implementation Collaborative members sign a Memorandum of Agreement to participate in good faith and contribute resources to the collaborative. While this group functions independently of any forensic science organization, private company, or government entity, this group has integrated with these organizations to share information and ensure project goals are achieved.51)Train public forensic science practitioners and law enforcement investigators to perform genealogical searching;2)Develop a national network of trained public forensic practitioners that can work as a team to solve difficult cases and teach other public forensic science professionals to use the technology;3)Develop robust policy and procedures for states to immediately implement the responsible use of this technique and technology;4)Determine and standardize terminology that will be used in this forensic science discipline;5)Evaluate the appropriate instrumentation and methods that will be fit for purpose, affordable, and possible for public laboratories to implement in-house for WGS, SNP array testing, or other NGS SNP panels;The first Technology Validation Working Group of the NTVIC is focused on the implementation of Forensic Investigative Genetic Genealogy (FIGG), Forensic Genetic Genealogy (FGG), and Investigative Genetic Genealogy (IGG) in public law enforcement agencies and forensic science laboratories. Over twelve Forensic Laboratory Directors from state or major regional laboratories convened this working group of the NTVIC to investigate transitioning the lab work and also genealogical searching from strictly the private laboratory space into the public forensic science laboratory space. While this group will help establish validation standards in support of the public laboratories that have purchased instrumentation and are navigating implementation of single nucleotide polymorphism (SNP) based technology, the focus of this group will be robust SNP array or sequencing based approaches, with a focus on WGS combined with genealogical searching and building of family trees to develop investigative leads. The working group has engaged with several major research institutions, private companies currently working in the space, federal agencies and laboratories, and top-tier researchers. The short-term goals of the committee are to:1)Purchase and validate the instrumentation and methods and implement WGS and robust SNP array analysis in public forensic science laboratories for investigative purposes;2)Develop a package of resources such as procurement documentation, analytical methods, performance verification plans, publication templates to implement this technology in other public forensic science laboratories for investigative purposes;3)Secure funding for this technology to be implemented in public forensic science laboratories;4)Evaluate the potential viability for SNPs for identity confirmation as an alternative to STR testing for those samples that cannot produce an STR due to degradation, amount of DNA, and other factors.The longer-term goals of the committee are to:The FIGG Technology Validation Working Group (TVWG) includes scientists from government and public laboratories, private DNA laboratories, research universities, and technology and instrumentation companies. While this group is overseen by the National Technology Validation and Implementation Collaborative Steering Group, a variety of experts are invited to participate based on expertise and experience with the technology. Four FIGG TVWG subcommittees have been formed to address the training, policy, terminology and technical issues of FIGG. The work of this group, and updates of the progress, will be presented at forensic science and other scientific meetings. The group will focus on peer reviewed publications in scientific journals as the official work products.6\u2022The focus of the FIGG TVWG is for investigative purposes. The FIGG TVWG will consider following SWGDAM validation criteria as appropriate in developmental validation and performance verification recommendations of SNP based analysis for FIGG and DNA based identification.\u2022The FIGG TVWG has legal advisors from various state agencies and state attorney general offices to guide policy and procedure development, but does not provide legal advice to consumers of Group work products.\u2022Current participants are volunteers on the FIGG TVWG. While their salaries and travel may be paid by public or private employers, their contributions to the Group are not reimbursed. If any federal government or private funding is used for this work, it will be made publicly transparent to avoid conflict of interest concerns.\u2022Idaho State Police Forensic Services (Matthew Gamette\u2014FIGG TVWG Chair)\u2022New York State Police Crime Laboratory System (Dr. Ray Wickenheiser\u2014Subcommittee Chair FIGG Policy/Procedure)\u2022Center for Human Identification, University of North Texas Health Science Center at Fort Worth \u2022University of New Haven and Henry C. Lee Institute of Forensic Science (Dr. Claire L. Glynn\u2014Subcommittee Co-Chair FIGG Training)\u2022Idaho State Police Forensic Services (Rylene Nowlin\u2014Subcommittee Co-Chair FIGG Training)\u2022Colorado Bureau of Investigation Forensic Services (Lance Allen\u2014Subcommittee Chair FIGG Terminology)\u2022BODE Technology (Michael Cariola)\u2022BODE Technology (Sarah Cavanaugh)\u2022California Department of Justice Bureau of Forensic Services (Barry Miller)\u2022California Department of Justice Bureau of Forensic Services (Nicola Marie Duda)\u2022California Department of Justice Bureau of Forensic Services (Daniela Cuenca)\u2022Center for Human Identification, University of North Texas Health Science Center at Fort Worth (Jonathan King)\u2022Colorado Bureau of Investigation Forensic Services \u2022Department of Defense DNA Operations for the Armed Force Medical Examiner Service (Dr. Timothy McMahon)\u2022Armed Forces Medical Examiner System's Armed Forces DNA Identification Laboratory (AFMES-AFDIL) \u2022Idaho State Police Forensic Services (Rylene Nowlin)\u2022Idaho State Police Forensic Services (Taylor Maichak)\u2022Kentucky State Police Forensic Science Laboratory (Laura Sudkamp)\u2022Miami-Dade Police Department, Forensic Services Division (Stephanie Stoiloff)\u2022Miami-Dade Police Department, Forensic Services Division \u2022Minnesota Bureau of Criminal Apprehension Forensic Science Services (Catherine Knutson)\u2022Minnesota Bureau of Criminal Apprehension Forensic Science Services (Ann Marie Gross)\u2022Missouri Highway Patrol Crime Laboratory Division (Brian Hoey)\u2022New York City Office of Chief Medical Examiner (Timothy Kupferschmid)\u2022New York City Office of Chief Medical Examiner (Meredith Rosenberg)\u2022New York State Police Crime Laboratory System (Julie Pizziketti)\u2022New York State Police Crime Laboratory System (Urfan Mukhtar)\u2022Ohio Bureau of Criminal Investigation (Roger Davis)\u2022Ohio Bureau of Criminal Investigation Laboratory Services Division (Kristen Slaper)\u2022Othram Inc (Andrew Singer)\u2022Othram Inc (David Mittelman)\u2022Signature Science, LLC (Erin Gorden)\u2022Texas Department of Public Safety (Brady Mills)\u2022Verogen Corporation (Dr. Swathi A. Kumar)\u2022Verogen Corporation (Dr. Meredith Turnbough)\u2022Wisconsin Department of Justice Division of Forensic Sciences (Jennifer Naugle)\u2022Wisconsin Department of Justice Division of Forensic Sciences (Melisa Wittkowske)Participating members of the FIGG NTVIC are:The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."}
+{"text": "The COVID-19 pandemic and the current war in Ukraine have presented opportunities to increase national leadership on mental health, including support health and care workers. Member States across the region have worked closely with the WHO to strengthen their policy levers to support the mental health and occupational safety policies for the workforce at various levels including government, organization and local service levels. To complement these policies, the WHO will launch the WHO Global Health and Care Compact at the Seventy-fifth World Health Assembly in May 2022.The WHO has convened Member States to discuss the policy levers that can support the mental health of health and care workers. These include online multistakeholder webinar series, national policy dialogs, ministerial discussions during the Regional Committee, preparatory consultations for the World Health Assembly to discuss priority areas and policy. More recently with the crisis in Ukraine, the WHO has been working closely with the UN Interagency Steering Committee (IASC) Reference Group on Mental Health and Psychosocial Support in Emergency Settings rolling out services for refugees, including health workers in these settings.A number of important policy recommendations are emerging from this work: (1) strengthening national and political leadership; (2) adopting stepped approaches; (3) facilitating collaboration across professions, sectors and levels of syste for more effective responses; (4) strengthening capacity and expertise; (5) monitoring effectiveness for continuous improvement; (6) ensuring acceptability and accessibility.Promoting health and well-being and mental health support to the health and care workforce has become a key priority for health systems to enable sustainable national health workforces. WHO will prioritize country support on this area and the development of regional guidance."}
+{"text": "Little is known about the experiences of individuals presenting with complex mental health needs and the provision of care they receive for suicide and self-harm behaviours. There are limited data describing the support individuals receive from services and, where they do, how this support is provided. Research suggests that those presenting with a more complex clinical presentation may have a history of both suicide attempts and self-harm. The aim of the study is to explore the experiences of individuals with complex mental health needs in respect of their self-harm and suicidal behaviours, and experiences of support received from mental health care services.A semi-structured interview methodology was used to generate qualitative data. Representative participants with complex mental health needs were recruited from across Cheshire and Wirral Partnership NHS Foundation Trust, UK. Ten participants were interviewed for the study. Interviews were audio-recorded and transcribed verbatim. A transcript-based conceptual analysis was conducted to identify and explore emerging themes.The following three themes emerged from the service user interviews: (i) Service users discussed suicide attempts following inappropriate discharge; Service users spoke about feeling unsupported and not listened to by care staff, particularly as inpatients; and (ii) Service users expressed a necessity for staff training to improve understanding of self-harm and suicide attempts, having experienced negative consequences of staff handling when they may have self-harmed.This study highlighted the following recommendations for future suicide prevention for mental health services treating service users with complex mental health needs: increasing staff awareness of suicide or self-harm related issues; improving training and risk assessment skills; providing appropriate support for service users following discharge from inpatient settings; improving liaison and collaboration between services to provide better service user outcomes; and increasing awareness in listening to service users\u2019 distress about suicidal or self-harm thoughts for each individual's situational context."}
+{"text": "Results showed CT had the highest rates of glaucoma (28.3%), RI had the highest rates of cataract (67.5%), and NH had the lowest rates of glaucoma and cataract . After adjusting for age, gender, race, marital status, education, income, chronic diseases, communities with higher rates of glaucoma or cataract were significantly associated with higher rates of emotional distress compared to those with lower prevalence . Findings help practitioners and policymakers to allocate emotional support services to areas of high need due to eye diseases.Glaucoma and Cataract are two common leading causes of vision loss and major sources of disability and mental issues for older adults, but few studies investigated glaucoma and cataract among older adults from a community-level perspective. This study describes the rates of glaucoma and cataract among older adults 65+ in New England and examined the association of glaucoma and cataract and emotional distress (depression and anxiety) of older adults at the community level across 794 towns/cities (MA (351), NH (235), RI (39), and CT (169)) in New England. Data sources used to calculate rates of communities were: the American Community Survey  and the Medicare Current Beneficiary Summary File . Small area estimation techniques were used to calculate age-sex adjusted community rates for more than 150 health indicators ("}
+{"text": "Development of an acute cerebral dysfunction in a form of delirium after cardiac surgeries is common general medical problem that associated with prolonged hospital stay after the surgery, risk of development of infection, risk of subsequent neurocognitive changes, and postoperative morbidityTo compare risk of development of postoperative delirium in elderly patients with and without hippocampal dysfunctionSelective observational longitudinal study of the same group of objects in pre and postoperative periodFor the diagnosis of degenerative process in CNS on early stages Free and cued selective reminding test immediate recall (FCSRT-IT) was shown to be the most sensitive. Based on learning of verbal material and semantic cues with recalling, FCSRT-IT allows differentiating amnestic disturbances hippocampal type from secondary disturbances of memory due to neurodynamic changesHippocampal dysfunction is a factor of developing of postoperative delirium in elderly patients that requires using additional measures in patients with mild cognitive disturbance to prevent developing of postoperative deliriumNo significant relationships."}
+{"text": "With the aging of the U.S. population, caregiving has become an emerging public health issue that affects the health and quality of life for millions of care recipients and their caregivers. An increasing number of older adults rely on their family caregiver networks and home-based clinical services for physical, social and emotional support. Caregiving plays an important role in health and wellbeing of older adults both in daily life and in the context of health care, e.g., in post-acute caregiving after hospital discharge. There is a growing interest in identifying caregivers in greatest need of support and developing programs and interventions to help these caregivers. This symposium describes caregiver network and examines the roles of the caregiver network and family caregiving support on care recipients\u2019 and caregivers\u2019 quality-of-life outcomes using the National Health and Aging Trends Study (NHATS) and linked National Study on Caregiving (NSOC). This symposium will 1) evaluate typologies of the structures and compositions of caregiver network and examine their effects on care recipients\u2019 well-being; 2) describe findings on associations between caregiving network and caregiver supports with unmet needs among older adults; 3) describe the role of unpaid caregivers after hospital discharge; 4) evaluate effects of family caregiving support in facilitating the use of home-based clinical services by older adults; 5) examine the effects of family disagreement on caregivers\u2019 emotional difficulty and overload in dementia caregiving. Together, these presentations suggest important public health implications for research, policy and practice for improving late-life caregiving."}
+{"text": "Shielding was introduced as part of the UK government\u2019s response to the SARS-CoV-2 pandemic to protect Clinically Extremely Vulnerable (CEV) people from infection and serious illness. Various research questions emerged in relation to non-clinical vulnerabilities of those shielding which could be addressed by utilising available health and administrative data.The Shielded Patient List (SPL) was linked with various datasets on the UK Secure Electronic Research Platform (UKSERP) including the Pupil Level Annual School Census (PLASC), National Survey and Ordnance Survey data for Wales. Some of these were anonymised datasets contained in the Secure Anonymised Information Linkage (SAIL) databank. Algorithms were applied to determine household composition and whether private outdoor space was available for the shielding group. Results were then extracted for Wales broken down by local authority.Results from the various strands of research related to shielding will be presented covering provision of outdoor space, household characteristics and composition.These analyses demonstrate how population-level data resources can be leveraged quickly to answer newly-emerging policy questions as part of the response to the SARS-CoV-2 pandemic."}
+{"text": "World Health Organization recommends guideline for integrated management of childhood illnesses (IMCI) where Amoxicillin Dispersible Tablet (DT) appears as the first drug of choice for treating childhood pneumonia. The Government of Bangladesh adopted the IMCI strategy in 1998, and scaled it up nationwide by 2014. But, even today, the use of Amoxicillin DT, either in public or private sector, for managing childhood pneumonia is a rare event in Bangladesh. We conducted this exploratory study to understand the existing barriers, both in public and private sector, those have influences on reduced availability of Amoxicillin DT and non-compliance of health service providers to follow IMCI guideline by using Amoxicillin DT for treating a child with pneumonia, in Bangladesh. We conducted desk review of relevant strategy and policy documents, key informant interviews with 19 key individuals from Ministry of Health and national / international NGOs. Collected information were analyzed and interpreted using thematic analysis method. Identified barriers through this study pointed to inadequate policy level focus on IMCI implementation, non-inclusion of Amoxicillin DT in the national essential drug list, single source of Amoxicillin DT producing pharmaceutical in the country coupled with bureaucracy and procurement procedural complexity, lack of training of health service providers and abundant availability of antibiotic over the counter. Study respondents recommended for policy level strengthening of IMCI program, increasing coverage of training for health care provider, including practicing pediatricians both at public and private sectors, facilitating production and procurement procedures and prohibiting antibiotic sell over the counter.\u2022\u2002Facilitation of production and procurement procedure coupled with enforcement of law prohibiting antibiotics availability over the counter are urgent needs.\u2022\u2002Policy level support emphasizing full compliance of service providers for quality of implementation of IMCI program in Bangladesh (and similar other settings) is also important."}
+{"text": "Glycine max (L.) Merr.] is an excellent source of protein. Understanding the genetic basis of protein content (PC) will accelerate breeding efforts to increase soybean quality. In the present study, a genome-wide association study (GWAS) was applied to detect quantitative trait loci (QTL) for PC in soybean using 264 re-sequenced soybean accessions and a high-quality single nucleotide polymorphism (SNP) map. Eleven QTL were identified as associated with PC. The QTL qPC-14 was detected by GWAS in both environments and was shown to have undergone strong selection during soybean improvement. Fifteen candidate genes were identified in qPC-14, and three candidate genes showed differential expression between a high-PC and a low-PC variety during the seed development stage. The QTL identified here will be of significant use in molecular breeding efforts, and the candidate genes will play essential roles in exploring the mechanisms of protein biosynthesis.Soybean [ Glycine max (L.) Merr.]. Furthermore, meat producers have found soybean meal to be the preferred protein source for poultry and livestock. The demand for higher protein content (PC) over recent years has pushed breeders to develop soybean seeds with higher levels of protein (Approximately 68% of the protein powder produced worldwide is derived from soybean 060), Jiangsu Agricultural Science and Technology Innovation Fund (CX(22)5002), the Natural Science Foundation of China (32001455), and the Natural Science Foundation of Jiangsu Province (BK20210154).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
+{"text": "To: (1) outline the research produced using linked data from the Registry of Senior Australians (ROSA) which informed the recommendations from Australia\u2019s Royal Commission into Aged Care Quality and Safety (delivered February 2021); (2) describe the Australian Government Aged Care Roadmap Reforms (announced May 2021) resulting from the recommendations.ROSA was established in 2017 and is led by a partnership of scientists, clinicians, aged care providers and consumer advocates from nine organisations seeking to improve the lives of Australians in aged care. ROSA is a Clinical Quality Registry comprised of linked national and cross-jurisdictional aged and health care data and includes a national historical de-identified cohort  and a prospectively enrolled cohort in the state of South Australia . This is a summary of ROSA\u2019s high-quality evidence used by the Royal Commission and translation of this evidence into policy by leveraging existing data infrastructure.Between 2019-2020 the ROSA team led the delivery of four in-depth reports for the Royal Commission, contributed data and expertise to an additional four published Commission reports. Examples of ROSA outputs informing the Commissions\u2019 recommendations included: evidence of national increased psychotropic medication use following entry to residential aged care, evidence of higher risk of mortality and entry to permanent care while waiting for home care packages, development of quality indicators to monitor quality and safety of care nationally, and to facilitate international comparisons and benchmarking. Examples of recommendations included in the Australian Government Aged Care Roadmap: release of substantial funding to increase the availability of home care packages, public reporting system for quality and safety monitoring and several changes to medication management.Registries are key resources for high quality real-world evidence generation needed to inform national investigations, ultimately leading to significant sector reform. The ROSA experience highlights that cross-sectoral data linkages, together with technical expertise, informed by clinicians and consumers, are invaluable resources for system reform and policy generation."}
+{"text": "Globally, all articles involved 59 authors and 16 reviewers between researchers and clinicians actively engaged in the field of Autism Spectrum Disorder (ASD) and Neurodevelopmental Disorders.Devescovi and colleagues  at the IMarino and his team  at the NThe Abou-Abbas study  at McGilCai and his colleagues  at YangzThe research conducted by Rahman and colleagues , locatedThe review by Podg\u00f3rska-Bednarz and Perenc , conductThe aim of the investigation conducted by Carmona-Serrano and colleagues  at the UIn the study by Narzisi and Muccio  at the S"}
+{"text": "Caregivers face challenges communicating and coordinating health-related needs on behalf of persons living with dementia (PLWD). This presentation will highlight capacity building activities at UCHealth, a large academic health system in Colorado and Wyoming, to prepare for pragmatic clinical trials to test integrated health informatics tools to improve the care of PLWD and their family caregivers. We will describe foundational activities of: 1) convening diverse patient and family caregivers to identify communication priorities and refine health informatics tools, 2) engaging health system leaders to develop a system-based value proposition, and 3) partnering with health informatics teams to adapt tools  and implement reports of pragmatic outcomes. Through support as an NIA IMPACT Health Care System Scholar, we will discuss lessons learned related to highlighting the preferences of diverse caregivers, especially related to use of health informatics tools in the context of dementia care."}
+{"text": "The use of nanomaterials has become more prevalent in modern day society since that fateful day at the California Institute of Technology in 1959 when American physicist and Nobel laureate Richard Feynman envisioned the ability to construct machines down to the molecular level during his lecture \u201cThere\u2019s Plenty of Room at the Bottom\u201d . Fast foFrontiers in Bioengineering and Biotechnology: Nano-Imaging in Translational Cancer Medicine, we present five articles that discuss a wide breadth of emerging uses of nanoparticles (NPs) for the detection and treatment of cancer. A common theme linking several manuscripts is the use of NPs as a theranostic for the detection and delivery of therapies to melanomas  and pancreatic cancer . Taking this one step further into the surgical oncology arena, multidisciplinary clinical perspectives on augmenting the surgical resection of melanoma  and brain tumors Lam et al. using fluorescence-conjugated tumor-detecting NPs, provide a framework of how nanotechnology is being used to improve surgical outcomes and survival for cancer patients (\u00ae) in 1995 , commonly used to encapsulate (PEGylate) different types of NPs, thereby shielding them from clearance by the reticuloendothelial system and increasing systemic circulation time, addresses why rigorous safety and quality controls are required before we will see more widespread translation of NPs for in-human use (Kong and Dreaden). The worldwide efforts to control the spread of SARS-CoV-2 (COVID-19) through global administration of a PEGylated liposomal mRNA-based vaccine uncovered a potential underlying hypersensitivity to the PEG component of the vaccine that may hinder its use in future NP formulations across different biomedical applications  window in pancreatic cancer cells. Their results clearly demonstrated a wide range of in vitro toxicities and in vivo accumulation of these differentially PEGylated NPs in subcutaneous flank pancreatic tumors in nude mice . However, given the recently reported immunogenicity of PEG in humans, one should use an abundance of caution in evaluating the translatability of safety data gathered using immunocompromised animal model systems and addresses the need to design NPs that minimize these adverse events.A recent quantitative bibliometric analysis of cancer nanotechnology research published between the years of 2000\u20132021 mined over 50,000 papers, showing an exponential increase in numbers of papers on nanoparticles published since 2010. Most of these publications originated from institutions located in the United States, China, the United Kingdom, India, and Iran, with an increased ramp up between 2017 and 2021 . Topics ications . This adFrontiers is the use of NPs for the imaging and detection of tumors using NIR fluorescence imaging. These articles are timely as NIR fluorescence-guided surgery (FGS) using the NIR dye indocyanine green (ICG) is increasingly being used for aiding surgical oncologists across multiple specialties in the operating room for visualization of tumor cells that are difficult to discern using conventional white light operating microscopes . However, FGS still remains in its infancy and will require rigorous validation before it can be adopted as standard of care practice (Another recurring theme in this issue of roscopes . The revroscopes , which cpractice .Frontiers showcases emerging and approved nanotechnologies that are poised to help clinical and surgical oncologists offer patients better detection of their tumor burden and delivery of precision cancer therapies. Careful characterization of the toxicity profiles of NPs and adherence to good lab and manufacturing practices for upscale manufacturing will improve the translational value of preclinical phase nanomedicines.In closing, this focus issue of"}
+{"text": "Whole-body magnetic resonance imaging (MRI) permits non-invasive, non-ionizing phenotyping of the human body and ideally complements the epidemiological assessment of the NAKO participants. As such, it allows for the detection of morphologic or functional predisposition, early disease stages prior to overt clinical events as well as evident pathological changes. The assessment of progression and regression of imaging phenotypes over time will provide the basis to identify and understand the relevance of imaging-based risk factor profiles for disease development.Integrated in the general NAKO study program and managed by a central Imaging Core, study participants underwent whole-body imaging at five dedicated MR imaging sites. Imaging was performed on five identical 3 Tesla scanners  applying a one hour protocol, including sequences for the brain, the cardiovascular and musculoskeletal system as well as for the thorax and abdomen. Comprehensive measures to assure high image quality and management of incidental findings were established.As part of the baseline examination program, a total of 30,861 participants successfully underwent the MR imaging program. All measures of quality assurance and incidental findings management were successfully employed throughout the study period and obtained image quality and completeness of all MR sequences was excellent (>94.2% completeness). While MR imaging as part of the first re-examination is ongoing, baseline MRI data is currently accessible for scientific analyses.The MRI-Study of the NAKO will provide a comprehensive imaging phenotypic biobank covering different organ systems with highest morphological and functional detail. MRI data analysis will gain novel insights into the natural history of disease development, the role of subclinical disease burden, and revolutionize our understanding of imaging biomarkers of risk."}
+{"text": "Chinese chestnut is an economically important tree species whose yield and quality are seriously affected by red spider attack. Tannins is one of the most important class secondary metabolites in plants, and is closely associated with plant defense mechanisms against insect and herbivory. In our previous studies, it was revealed that several low-tannin foxtail millet varieties growing under the Chinese chestnut trees could attract red spiders to feed on their leaves and protect the chestnut trees from the infestation of red spiders, meanwhile, the growth and yield of foxtail millet plants themselves were not greatly affected.To identify genes related to leaf tannin content and selection of foxtail millet germplasm resources with low tannin content for interplanting with Chinese chestnut and preventing the red spider attack, the leaves of 4 varieties with different levels of tannin content were harvested for comparative transcriptome analysis. In total, 335 differentially expressed genes (DEGs) were identified. For acquisition of gene functions and biological pathways they involved in, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed, and several DEGs were found to possibly participate in the tannins biosynthesis pathway and transport processes of precursors. In addition, according to the PlantTFDB database, some transcription factors were predicted among the DEGs, suggesting their role in regulation of tannins biosynthesis pathway.Our results provide valuable gene resources for understanding the biosynthesis and regulation mechanisms of tannins in foxtail millet, and pave the way for speeding up the breeding of low-tannin varieties through marker-assisted selection, which could be utilized for interplanting with Chinese chestnut trees to confer protection against red spider attack.The online version contains supplementary material available at 10.1186/s12864-022-08746-8. Castanea mollssina Blume) is an economically important tree species which originated from China. In Yanshan Mountain and Taihang Mountain area of Beijing\u2013Tianjin\u2013Hebei region, the major producing areas of Chinese chestnut in China, the planting area covered by Chinese chestnut has reached about 313.33 thousand hm2, and Chinese chestnut plays an irreplaceable role in economic development of this area. However, it was found that the yield and the quality of Chinese chestnut kernel decrease with the incidence of red spider (Tetranychus cinnbarinus), an agricultural insect pest which can damage more than 110 kinds of plants  is one of the most important commercial crops in Beijing\u2013Tianjin\u2013Hebei region of China, and has a strong resistance to drought and barren soil ."}
+{"text": "African American /Black caregivers make up 13% of the total number of adult caregivers in the United States and 41% more likely to provide help greater than three activities of daily living than other ethnicities. How they perceive socio-cultural factors to influence their care giver roles is less documented. This study aims to synthesize the evidence on the role of culture and social factors in African American caregiver perceptions delivering care to older adults with dementia and COVID-19. Searches of the Ageline, Medline, PsycInfo, Academic search complete Psychology and Behavioral science collection and Google scholar for empirical study publications on socio-cultural factors for dementia care and COVID-19 among African American caregivers yielded six studies. To be included, studies met the following criteria (a) focus on African American caregivers of older adults with dementia and focus on Covid-19 (b) socio-cultural factors (c) perceptions and practices. (d)published between 2019\u20132022. Studies indicate compassionate care practices by African American caregivers of persons with dementia and Covid-19. African American care givers of persons with dementia and COVID19 perceive caregiving as a responsibility they owe and not a job. They also perceived to be guided by their racial identity and faith beliefs, integrating family values and culture into caregiving. African American carers of persons living with dementia and COVID-19 have compassion and resilient care self-perceptions in caregiving to people with Dementia and COVID-19. Supporting compassionate care delivery by African American carers requires understanding social and cultural factors driving their commitment to quality care."}
+{"text": "Scientific Reports 10.1038/s41598-022-18240-6, published online 10 September 2022Correction to: The original version of this Article contained an error in the Acknowledgements section, where\u201cWe are very grateful to the Directorate of the Rusenski Lom Nature Park (Director Tsonka Hristova) for cooperation and support. We thank the responsible Bulgarian authorities (MOEW-Sofia and RIOSV-Ruse) for granting us permission to conduct this research. We would like to thank Stefan Greif for his support in capturing bats in Bulgaria and Katja Pohle for her help in the laboratory analyses. This work was supported by institutional funds of the Leibniz Institute for Zoo and Wildlife Research and the German Research Foundation (DFG Priority Programme 1596). Funding for the research station in Tabachka was provided by the DFG to Holger R. Goerlitz (Emmy Noether Program GO2091/2-1). Open Access funding enabled and organized by Projekt DEAL and was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation\u2013Projektnummer 491292795).\u201dnow reads:\u201cWe are very grateful to the Directorate of the Rusenski Lom Nature Park (Director Tsonka Hristova) for cooperation and support. We thank the responsible Bulgarian authorities (MOEW-Sofia and RIOSV-Ruse) for granting us permission to conduct this research. We would like to thank Stefan Greif for his support in capturing bats in Bulgaria and Katja Pohle for her help in the laboratory analyses. This work was supported by institutional funds of the Leibniz Institute for Zoo and Wildlife Research and the German Research Foundation (DFG Priority Programme 1596). Funding for the research station in Tabachka was provided by the DFG to Holger R. Goerlitz (Emmy Noether Program GO2091/2-1).\u201dAdditionally, the Funding section in the original version of this Article was incomplete.\u201cOpen Access funding enabled and organized by Projekt DEAL.\u201dnow reads:\u201cOpen Access funding enabled and organized by Projekt DEAL. The publication of this article was funded by the Deutsche Forschungsgemeinschaft  - project number 491292795.\u201dThe original Article has been corrected."}
+{"text": "Despite evidence that early detection of mild cognitive impairment and dementia leads to improved patient care, these conditions remain under-diagnosed in primary care. To address this gap at University of Washington Medicine, we have developed and pilot-tested a program to increase cognitive evaluations and improve dementia care by primary care providers (PCPs). The Cognition in Primary Care (CPC) program was designed utilizing stakeholder-selected components of the GSA KAER  Model and Toolkit (2020 Edition), developed by the Gerontological Society of America (GSA). In this presentation we will describe evaluation of the CPC Program including (a) education training; (b) use of assessment tools integrated within the electronic health record ; (c) practice recommendations such as dedicated evaluation appointments, diagnoses and referrals, and (d) PCP use of community resources for post-diagnosis support. A total of 66 PCPs participated in the series of 3 CME educational seminars. Over 93% of participants reported the content to be highly relevant and expected to incorporate it into their practice; commitments to use specific tools were made. Analysis is underway to determine impact of the program by comparing the above metrics before and after the training as well as between trained and untrained PCPs. Results from this evaluation will inform modifications to increase utilization of the CPC Model within UW Medicine, will be used to package the program to share with other primary care systems, and will guide future enhancements to the GSA KAER Toolkit."}
+{"text": "The increasing provision of informal caregiving and the extension of working lives will result in many older workers combining paid work and informal caregiving responsibilities. Specific flexible work arrangement policies have been enacted in many countries to support working caregivers. Flexibility in the workplace has been suggested to promote prolonged employment among older workers. This study primarily focuses on the question of whether use of flexible work arrangements differs between caregivers and non-caregivers and how potential differences can be explained. Participants were 296 carers and 1611 non-carers (aged 55\u201370 years) who completed wave 8 of the New Zealand Health, Work and Retirement survey. The use of flexible work arrangements was analyzed based on five categories; Flexibility in number of work hours, flexible schedule, flexible place, options for time off, and other options. Hierarchical regressions were used to investigate caregiving as an independent predictor of use of flexible work arrangements after controlling for demographic and work characteristics. Results indicate that the studied informal caregivers on average used more workplace flexible arrangements than non-caregivers, both in flexible work hours, flexible schedules, and time off. The caregiver status difference in use of the three significant categories of flexible work arrangements can be explained by differences in socio-demographic and work characteristics. This difference in use of FWAs among older caregivers and non-caregivers warrants attention in discussions about prolonged employment and reconciliation of care and paid work."}
+{"text": "Trust for America\u2019s Health (TFAH) leads the national Age-Friendly Public Health Systems initiative which focuses on expanding the public health role in healthy aging. The roles of public health include creating and leading policy, systems, and environmental changes; connecting and convening multi-sector stakeholders to improve older adult health and well-being; and collecting and translating data on older adult health to inform interventions in communities and states. TFAH will share examples of how public health departments are elevating healthy aging as a core function."}
+{"text": "Compared to Whites, Black and Latinx cancer survivors and their families experience disproportionate adverse effects of cancer and cancer therapy. This is due to extreme psychosocial, physical, emotional, and financial challenges they experience, thus, highlighting racial/ethnic disparity in cancer survivorship. A cancer survivorship care plan (SCP) is important for improving cancer health and quality of life, but the effectiveness of SCP as a tool to address the disproportionately persistent poor health and quality of life of Blacks/Latinx compared to Whites deserve critical attention. This study is part of a larger study on evaluating cancer survivorship in Rhode Island. We explored knowledge and use of SCP among Blacks and Latinx cancer survivors in Rhode Island. The study employed a qualitative descriptive method. Semi-structured interviews in English and Spanish were conducted with a purposive sample of 12 cancer survivors, 8 Latinx and 3 Blacks (Mage = 62 years). Their responses were transcribed and analyzed for themes. The 3 major themes identified were: 1) invisibility of survivors; 2) understanding the needs of cancer survivors; and 3) issues of empowerment. Our findings draw attention to the need for tailored interventions targeting Black/Latinx cancer survivors. One of such interventions include designing programs to increase the accessibility of SCP to help improve quality of life of cancer survivors from disadvantaged population groups."}
+{"text": "Studies on mental health inequalities are usually based on limited sets of mental health indicators.Using a large number of mental health indicators, we explored whether it is possible to identify similar hierarchical rankings regardless of mental health indicators (incl. psychotherapy) among employees representing different socio-demographic statuses, and which groups of employees have the highest mismatch between mental health symptom and treatment.Employees representing different occupational classes and employees from four different areas of Finland were studied and compared. We used national register data to define psychotropic medication (purchases), sickness absence for mood disorders, and the use of psychotherapy between 2017 and 2019 and national survey data from the FinHealth 2017 Study to define the level of psychological symptoms . We assessed the risk of each outcome by population group separately for men and women, and estimated the mismatch between symptoms (BDI/GHQ caseness) and treatment (psychotropic drugs/therapy).In all the studied groups, the prevalence of mental health indicators was mostly considerably higher among women than men. The risk of register-based mental health indicators was typically higher among lower non-manual employees. In the case of some mental health indicators, we observed significant interactions between occupation class and region. Some stark mismatches were detected between symptoms and treatment in some populations, whereas at the other end of the spectrum, the correspondence between symptoms and the mobilization of care was rather high.Although gender is strongly linked to mental health indicators, occupational class and region influence mental health profiles in the population. There are considerable inequalities between populations in the level of professional care associated with mental health problems."}
+{"text": "This Research Topic aims to provide a platform for scholars to report their research progress on studying multimedia environmental pollutions and food safety around the world. Multidisciplinary research is urgently needed to explore a range of health and nutrition inquiries, from issues of the food supply chain to cooking practices and dietary safety management, not only in normal times but also as a function of the COVID-19 pandemic. The Research Topic has attracted wide attention and generated six multi-disciplinary articles in total.Environmental pollution and food safety are closely related critical issues faced by all populations over the world. Safe foods provide the necessary nutrients for human survival and health. Unfortunately, anthropogenic source-driven contaminants could be transported to foods . Another team from University of Veterinary Medicine and Pharmacy (Slovakia) and Menoufifia University (Egypt) performed a health risk evaluation of organochlorine pesticide residues in edible tissue of seafood based on 120 random samples from local markets in Mansoura city, Egypt . Furthermore, the study by Chen et al. proposed a novel theoretical framework for food safety management problem using a case study of China's waste cooking oil (WCO). This paper bridged the research gap by systematically applying grounded theory to real criminal cases to explore the main potential influencing factors of WCO crime comprehensively. Zhang G. et al. from the Affiliated Zhongda Hospital of Southeast University (China) used data from the 2013\u20132014 National Health and Nutrition Examination Survey (NHANES) database to initially explore the relationship between urinary concentrations of Heterocyclic aromatic amines (HAAs) and the risk of kidney stones, which was validated by propensity score matching (PSM) analysis. For detecting botulinum toxin type A, which can cause serious food poisoning, in complex sample matrices. Zhang L. et al. from Anhui Medical University (China) introduced a rapid and sensitive detection tool using AlphaLISA, which was proved to a potentially rapid toxin detection method for foods. Finally, Guanqi et al. evaluated the role of organic food supply chain traceability in food safety and consumer wellbeing using a mediated-moderation investigation.In this Research Topic, a team from Cukurova University (Turkey) and North Carolina A & T State University (United States) conducted a literature review about the impact of COVID-19 pandemic on seafood safety and human health (This Research Topic provides not only a timely reference source for academics, but also has practical implications for decision-makers concerned with environmental pollution and food safety. We thank the members of the Editorial Board and all authors and referees for their valuable contributions to this Research Topic. Of course, these publications would not be possible without the support from the Journal Office.FL wrote the draft of this manuscript. CZ, ZX, and HH reviewed and approved the final version. All authors contributed to the article and approved the submitted version."}
+{"text": "The Coronavirus disease (COVID-19) health emergency has led national states to adopt severe actions forcing many people to cope with new and unexpected challenges. Those constraints risked to jeopardized the mental health and subjective wellbeing (SWB) of individuals.The present cross-sectional quantitative study explored whether and to what extent psychological and social aspects were determinants of parental SWB as outcome variable during the COVID-19 lockdown.The sample was composed of 304 Italian parents . Data were gathered through Computer Assisted Web Interview (CAWI) four weeks after the beginning of the national lockdown. World Health Organization (WHO) wellbeing scale along with other self-reported measures of social support, feelings of abandonment, feeling of being equipped and adequacy of living spaces were administered. Data were analyzed by hierarchical regression models According to the WHO cutoff score, 37.7% of parents reported low well-being levels. The regression model  suggested that the feeling of abandonment and the feeling of being equipped were the most important contributors to SWB. Other statistically significant (but with lower effect sizes) variables were the support received by the partner and the adequacy of living spaces.The findings bear out the pivotal importance of subjective states (such as feelings of abandonment or perceptions of being poorly equipped) in relation to the levels of parental SWB during the COVID-19 lockdown. Implications for planning psychological interventions aimed at strengthening personal resources to face the emergency are discussed.No significant relationships."}
+{"text": "ML and Entropy ML with foam surface condition and both ankle and back vibration on, were able to completely differentiate the non-specific low back pain groups. The proposed methodology can help clinicians quantitatively assess the sensory status of non-specific low back pain patients at the initial phase of diagnosis and throughout treatment. Although the results demonstrated the potential effectiveness of our approach in Low back pain patient distinction, a larger and more diverse population is required for comprehensive validation.The central nervous system (CNS) dynamically employs a sophisticated weighting strategy of sensory input, including vision, vestibular and proprioception signals, towards attaining optimal postural control during different conditions. Non-specific low back pain (NSLBP) patients frequently demonstrate postural control deficiencies which are generally attributed to challenges in proprioceptive reweighting, where they often rely on an ankle strategy regardless of postural conditions. Such impairment could lead to potential loss of balance, increased risk of falling, and Low back pain recurrence. In this study, linear and non-linear indicators were extracted from center-of-pressure (COP) and trunk sagittal angle data based on 4 conditions of vibration positioning , 2 surface conditions (foam or rigid), and 2 different groups . Linear discriminant analysis (LDA) was performed on linear and non-linear indicators to identify the best sensory condition towards accurate distinction of non-specific low back pain patients from healthy controls. Two indicators: Phase Plane Portrait  Likely driven by ageing and population increase, the Global Burden of disease Report reveals a significant increase in both the number of Low back pain (LBP) patients and the prevalence of LBP in all age groups worldwide in the last 2 decades (1990\u20132019). The same report also points out that although the prevalence of LBP increases with increasing age, currently, the 50\u201354\u00a0years age group has the highest LBP prevalence . ExpecteOptimal postural control is task-dependent and dynamically variable during the performance of different daily activities. The human brain performs diverse targeted control adjustments on the ankle, knee, hip and spine in order to maintain postural stability . The cenThe literature demonstrates controversy regarding the causal association between postural control and LBP. Several studies concluded that postural control Impairment can be considered as one of the causal factors associated with non-specific low back pain (NSLBP) , while oMany previous studies focused on the motor output of postural control in NSLBP patients . Others In the past several decades, many relevant studies investigated the biomechanics of the low back by using various approaches, tools and technologies to distinguish NSLBP patients from healthy individuals. Although the literature, including the above-mentioned studies, is rich with quantitative investigations exploring the various dimensions of NSLBP, the multifactorial etiology of the disease and its negative impact on today\u2019s world remain unresolved challenges. Elusive issues include understanding the role of motor control in NSLBP patients and the distinctive motor control strategies adopted by these patients for preserving postural stability. To augment the findings in literature, this investigation was designed to scrutinize the best sensory condition to distinguish NSLBP patients from healthy controls leveraging different surface, and vibration conditions, as well as, linear and non-linear mathematical tools. We hypothesize that the sensory condition of standing on a foam surface with induced vibration, in conjunction with non-linear mathematical tools, can provide a suitable framework to differentiate LBP patients from healthy individuals.The University Internal Ethics Board evaluated and authorized the study involving human subjects . Prior to beginning the trial, participants were fully informed and given their consent.The experimental set up in this study is similar to our prior investigation on chronic low back pain patients  includinAccording to prior investigations, muscle vibration is the most common method for altering proprioception inputs . In ordeA force plate was used for collecting the center-of-pressure (COP) body fluctuation data for each subject . The kinematic data was captured using a Vicon optical motion capture system with reflective markers synced to the force plate. According to the literature, the markers were attached to the C7, T12, lower sternum (xiphoid process), clavicle (Incisura jugularis), right scapula, right and left sides of the PSIS (posterior superior iliac spine), and ASIS (anterior superior iliac spine). On both devices, the sampling frequency was set to 100 Hz. The motor straps were fastened to the bilateral multifidus muscles and the muscular spindle of the triceps surae on each leg. Each subject completed 8 randomized different trials while having their eyesight obscured (by wearing an eye mask) as follows: 1) standing on a motionless rigid surface (without any vibrator-induced movement); 2) standing on a rigid surface with the activation of the triceps vibrators; 3) standing on a rigid surface with the activation of the multifidus vibrators; 4) standing on a rigid surface with the activation of both the triceps and multifidus vibrators; 5) standing on a motionless foam surface; 6) standing on a foam surface with the activation of the triceps vibrators; 7) standing on a foam surface with the activation of the multifidus vibrators; and 8) standing on a foam surface with the activation of both the triceps and multifidus vibrators. The trunk angles were recorded in the three anatomical planes for each trial, and the COP data was obtained in the anterior posterior (AP) and medial lateral (ML) directions. Each trial lasted 30\u00a0s: for the first 10\u00a0s of each trial, the subject stood on the force platform without experiencing any vibration ; for the next 20\u00a0s, the motors were turned on at a frequency of 70\u00a0Hz (the vibration phase).According to the literature, a second-order Butterworth non-linear filter was used to filter the data  using a The phase space of the COP and trunk sagittal angle data was reconstructed in MATLAB  using average Mutual Information (AMI) and False Nearest Neighbors (FNN) methods, which are the conventional techniques for finding the time-delay parameter and the embedding dimension parameter, respectively . The AP By using Recurrence Quantification Analysis (RQA) approach, the features of complexity and amount of recurrence can be calculated as dynamic properties of an observed time series. Upon phase space reconstruction for the COP and trunk angle time series, short and long terms Lyapunov were calculated as stability indicators (more negative indicates more stable) of the dynamic path in reconstructed phase domain according to Normal distribution was verified using a MATLAB Lillie test  for all the calculated parameters . All the parameters were normally distributed, and hence, analysis of variance (ANOVA) and multiple analysis of variance (MANOVA) tests were used to compare linear and non-linear indicators of the COP and trunk data in order to investigate statistically significant differences. The group , vibration location , and foot positioning condition were taken into consideration as the independent variables in this study (rigid or foam) resulting in a nificant . A schemnificant  to identThe results of the ODI and NPRS questionnaires demonstrate significant differences between the healthy participants and the NSLBP group, as shown in ondition . As showThe correlation Matrix of the significant relationship amongst the eight chosen performance parameters and selected primary condition are indicated in This study aimed to identify the best performance indicators and sensory conditions to differentiate NSLBP patients from healthy controls, incorporating various surface conditions (rigid or foam), muscle vibration conditions , and leveraging multiple linear (LDA) and non-linear (Lyapunov and RQA)) mathematical tools. The findings indicated that there were significant differences in the majority of the parameters used in this experiment  between the NSLBP and healthy cohorts. The identification of the best indicators and sensory conditions could enable clinicians to distinguish individuals with proprioception impairment. Our results show that using linear discriminant analysis, only two parameters  on a foam surface, with both ankle and back vibration, that could discriminate the two groups successfully. The current study sheds light on the need to provide a standardized quantitative platform to distinguish NSLBP populations from healthy groups and offers a starting point for future studies to help clinicians assess the sensory status of patients towards preventive medicine and precise patient-centric rehabilitation. Further work is needed to increase the size and diversity of the population studied in order to validate the present results while cautiously recommending it for clinical applications.The main contribution in this study is the development of a relatively simple methodology leveraging linear and non-linear mathematical tools to investigate the main factors (surface and muscle vibration) impacting motor control strategy towards the quantitative discrimination between NSLBP patients with proprioceptive disorders from healthy individuals. LDA analysis identified two indicators (PPP"}
+{"text": "The COVID-19 pandemic added new challenges to health workforce resilience. High workload, increased risk of COVID infection and continuing stress threaten the health and wellbeing of healthcare workers (HCWs) and increase existing (gendered) inequalities, thus reinforcing health labour market problems. Investment in the health workforce and prioritisation of the health and wellbeing needs of healthcare workers in health policy and pandemic recovery plans is therefore called for by the WHO, the European Union and others. However, health systems and policymakers across countries have not sufficiently understood the importance of HCWs.This workshop brings health workforce needs onto the health policy agenda. It seeks to build capacity for a resilient and healthy health workforce, setting the focus on protection and preparedness of HCWs and their individual wellbeing, and reduction of gendered inequalities. The following major questions will be addressed: What do we know about COVID-19 and the health and wellbeing of HCWs? What skills are needed to respond to new demands? What policy approaches are available to improve protection, preparedness and mental health support of HCWs? How to integrate gender equality and the situation of migrant/refugee HCWs in these approaches, and finally build capacity for effective health workforce governance and its implementation.The workshop introduces novel results drawn from European comparative research and country case studies. It connects policy and practice, as well as health system and individual HCW needs. A number of important policy recommendations are emerging from the research. (1) The health and wellbeing of the health workforce must be addressed systematically across all levels of health policy and governance, including the organisation settings. (2) Health systems must take responsibility and leadership in responding to health workforce needs. (3) Important lessons to be learned from HCWs\u2019 experiences should guide future health workforce policy and pandemic recovery plans. (4) Participatory governance and inclusion of HCWs must be strengthened, including gender equality and diversity.The workshop will stimulate critical debate and improve knowledge exchange across countries and between researchers. It will contribute to strengthen resilience of the health workforce and health systems, and to build back better after COVID-19 in a fair and equitable manner.\u2022\u2002Health workforce needs and mental health support must become policy priorities and addressed as part of health system resilience.\u2022\u2002Action has to be taken to strengthen participatory health workforce governance sensitive to new needs."}
+{"text": "The American Rescue Plan Act (ARPA) includes a one year 10 percentage point increase in the Federal Medical Assistance Percentage for Medicaid-funded home and community-based services (HCBS). The goal is to strengthen state efforts to help older adults and people with disabilities live safely in their homes and communities rather than in institutional settings during the COVID-19 pandemic. This presentation provides a detailed description and analysis of this provision, including issues state governments need to consider when expending the additional federal revenue provided. It also draws lessons from the Affordable Care Act\u2019s Balancing Incentive Program to suggest insights for the potential of ARPA to promote further growth in Medicaid HCBS programs. The presentation concludes by highlighting the importance of instituting strategies and processes for maximizing enhanced federal matching funds under ARPA in preparation for subsequent availability of substantial additional federal resources targeting Medicaid HCBS under other proposed initiatives."}
+{"text": "There is no satisfactory definition of orphan disease among the numerous scientific entities in the world. The scientific community has referred to orphan diseases using two separate but related concepts. The first describes diseases neglected by doctors and the second designates diseases of low incidence and prevalence in the population. On average, patients with rare orphan diseases take more than four years before receiving a correct diagnosis. Before that, they usually receive three or more misdiagnoses and consult with at least five different doctors.Orphan diseases have drawn increasing attention and there is a need for multi and interdisciplinary care, with the inclusion of the otorhinolaryngologist. Among these rare orphan diseases of genetic origin, Primary Ciliary Dyskinesia (PCD) and Cystic Fibrosis (CF) stand out and are considered of significant importance for the otorhinolaryngologist, due to the high prevalence of upper airway involvement. While CF has been extensively studied, DCP has not.The concept of United or Unified Airway (UAW) stems from the fact that the upper airways and lower airways, which are anatomically and immunologically related, form a single organ. Both are often comorbid because they reflect manifestations of a single disease related to different parts of the respiratory tract. Thus, as allergic rhinitis is to asthma, which constituted the initial concept of United Airways, chronic rhinosinusitis (CRS) is to CF and PCD. The importance of paranasal sinuses in the contamination of lower airways and the success of the eradication of infections of the two airways, have been recognized in the last two decades.Cystic Fibrosis Transmembrane Regulator) protein modulators and (vi) nasosinusal surgery. Although there is a lack of significant evidence for most of these procedures, most of them have been approved for use in united airways management based on the following facts:For the understanding and management of upper airways, the following interventions have been proposed: (i) Nasal irrigation with saline solutions in different concentrations; (ii) topical or oral corticosteroids, (iii) antibiotics ; (iv) dornase alfa, (v) CFTR (\u2022The unified/united airways (UAW) pathway theory believes that the sinuses are a focus of initial bacterial colonization which reaches lower airways in CF and PCD. Lung disease and quality of life in patients with CF and PCD are improved with a more aggressive treatment of the upper airways.\u2022Almost all patients with CF and PCD have CRS and commitment of the LAW.\u2022Although chronic rhinosinusitis (CRS) can make the bronchopulmonary manifestations of these diseases worse, the reverse is also true, an interrelation explained by the concept of a unified airway.\u2022Additionally, nasal polyps have an estimated incidence of 0.1% in children, and their presence may raise suspicion of underlying systemic disease such as cystic fibrosis, primary ciliary dyskinesia.\u2022The effects of intravenous (IV) antibiotics are substantially smaller on biomarkers of sinonasal disease than on lung inflammatory markers, demonstrating that there are limitations regarding the use of IV antibiotics for CRS in CF and PCD.\u2022Patients with CF and PCD undergoing surgery for CRS exhibit a substantial decrease in the bacterial community in the paranasal sinuses preventing or delaying aspiration into the lower airways.\u2022Pseudomonas aeruginosa in CF and PCD, constituting a stimulus for early detection and eradication of microorganisms in united/unified airways.The upper airways are the site of the first colonization and persistence of infection by \u2022Pseudomonas aeruginosa strains detected in the upper airways and lower airways are genetically identical, both pre and post lung transplantation in patients with CF and PCD, which reinforces the concept of \u201cunited airways\u201d.About 96% of \u2022Pseudomonas aeruginosa from the sinuses occurs before it changes to a mucoid phenotype and forms biofilms, making eradication nearly impossible.Increased chance of eradication of \u2022Pseudomonas aeruginosa.Periodic and rigorous monitoring of lower airways and upper airways colonization and an aggressive treatment results in successful and lasting eradication of \u2022Pre-lung transplantation sinus surgery may decrease the rate of lower airways infection in patients with CF and PCD.Among the rare diseases that can cause commitment of the airways, PCD is one of the most significant and its diagnosis is a great challenge for otorhinolaryngologist.While the diagnosis of CF is broadly defined, the diagnosis of PCD is a problem for all health specialties.5In recent decades, the investigation of clinical signs and symptoms suggestive of PCD can be performed by: (i) Screening: PICADAR Score and nasal Nitric Oxide (nNO); (ii) Structure: Transmission Electron Microscopy (TEM), Immunofluorescence; (iii) Function: High-Speed \u200b\u200bVideo Microscopy Analysis (HSVMA) with assessment of ciliary beating pattern and frequency and (iv) Genetics: Genome/Exome Sequencing, either whole or a group of genes.However, all these methods can give false negative results, and the disagreements between the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines regarding the diagnosis of PCD have resulted in confusion for physicians, making confirmation difficult diagnosis. ATS guideline is based on genetic evaluation, nNO and MET, while the ERS guideline focuses on high-speed videomicroscopy analysis (HSVMA), MET, nNO and Immunofluorescence.Therefore, when considering patients with recurrent or chronic upper and lower airway diseases, the otorhinolaryngologist must establish a differential diagnostic between CF and PCD. The main differences and similarities between these two diseases can be seen in Rare and orphan diseases pose a challenge to all physicians who treat respiratory diseases. The dissemination of knowledge regarding the diagnosis and management of these diseases, among related specialties, can maximize the quality of life of patients.The authors declare no conflicts of interest."}
+{"text": "A stratified random sample of participants was interviewed in each region of Pennsylvania during each phase of the implementation using the Consumer Assessment of Health Providers Survey \u2013 Home and Community Based Services (CAHPS-HCBS) version. In addition, comparison groups were interviewed from the third implementation region. These data were combined with surveys conducted by the three Community HealthChoices managed care organizations (MCOs). Data were weighted to create geographically representative estimates of participant experience across a range of composite measures. We found that participant ratings of their personal care attendants declined on three out of four measures, however measures of medical and non-medical transportation improved as a result of the implementation of Community HealthChoices. There were notable differences between people of different racial and ethnic groups, with non-Hispanic whites consistently reporting lower levels of satisfaction with person care."}
+{"text": "Administrative databases (AD) are repositories of administrative and clinical data related to patient contact episodes with all sorts of health facilities .The large number of patients/contact episodes with pharmaceutical facilities available, the systematic and broad register and the fact that AD provides Real-world data are some of the pros in using AD data.To perform a narrative review on the role of Big Data pharmaceutical registries in Mental Health research.We conducted a narrative review using MEDLINE and Google Scholar databases in order to analyse current literature regarding the role of BigData pharmaceutical registries in Mental Health Research.Administrative variables like drug names and prices may be used and linked to other clinical variables such as patients disease, in-hospital mortality, length of stay,(\u2026). The use of electronic medical records may also contribute to systematic surveillance approaches like local or national pharmacovigilance strategies, identification of patients at risk of developing complications and software pop-up warnings related to medication dosage, duplication and lateral effects. The use of Big Data pharmaceutical registries allows to create predictive epidemiological models regarding drugs lateral effects or interactions and may help to perform pharmacovigilance phase 4 clinical trials. Its use may be applied to the optimization of clinical decision, monitoring of drug adverse events, drug cost and administrative monitoring and as surrogate measures of quality care indicators.Big Data use in pharmaceutical registries allows to collect large and important clinical and administrative data that may be later used in Mental Health care and research.No significant relationships."}
+{"text": "Access to and the quality of long-term supports and services (LTSS) are not equitable for all older Americans. Disparities have been documented qualitatively and quantitatively for marginalized racial and ethnic communities and LGBTQI+ communities but the specific causes of gaps in equity differ by community, locality, and state. To be effective, policy solutions must be grounded in the lived experiences of Black, Latino, Asian American and Pacific Islander, and LGBTQI+ older adults in those communities. This symposium showcases how community-based research can be employed to understand the root causes of inequities in LTSS access and care affecting older adults of color and LTGBTQI+-identifying older adults and presents community-grounded policy solutions to remedy those inequities. Papers 1 and 2 use participatory research methods to understand barriers to equitable LTSS care access and quality and develop locally grounded solutions to those barriers. Caldera (Paper 1) shares results from a study of Cook County, IL nursing home residents and their caregivers focused on racial and ethnic disparities in access to and experiences with nursing home care. Hado (Paper 2) presents findings from research in Georgia and New York examining disparities in access to and experiences with HCBS for older racial and ethnic and LGBTQI+ communities. Fashaw-Walters (Paper 3) discusses the how systemic racism is at the root of inequities in LTSS access for communities of color and shares actionable recommendations aimed at ending racial and ethnic inequities in LTSS policies."}
+{"text": "Despite the limited evidence about the efficacy and safety of dietary supplement use for mental health, people tend to use them quite often. Generally the use of supplements among Saudi population shown to be prevalent, although limited studies that assessed their use for the improvement of mental health.Identify the prevalence of dietary supplements use for mental health among the population in Saudi Arabia and also determine the factors that affect the use of dietary health supplements for mental health.A cross-sectional study of a convenience sample of 443 participants from various regions in Saudi Arabia. Questionnaire includes demographics, dietary use supplement assessment, and mental health assessment via the patient health questionnaire (PHQ-9), generalized anxiety disorder questionnaire (GAD-7), and insomnia severity index (ISI).The prevalence of DS among the Saudi population reached 44%. Vitamin D and Melatonin were the most commonly reported DS used for mental health among the study population. The use of DS was associated with three times higher odds in patients who had previous mental health disorder diagnoses . The chance of using DS almost doubled in patients with subthreshold and moderate-severe insomnia  and  respectively.Despite the limited evidence about the efficacy and safety of dietary supplement use for mental health, people tend to use them quite often. Although the use of supplements among Saudi population shown to be prevalent, limited studies assessed their use for the improvement of mental health.No significant relationships."}
+{"text": "The Michigan Stroke Transitions Trial (MISTT) tested whether in-home social work case management (SWCM) or SWCM combined with access to a website providing stoke-related information improved outcomes relative to usual care for patients discharged home post-stroke and their caregivers. The aims of this secondary analysis are 1) to describe the actual support social work case managers (SWCM) provided to MISTT participants and 2) use select case studies to illustrate the relationship between SWCM and quantitative patient and caregiver outcomes. Data for the study were derived from SWCM case notes on 157 patients and their caregivers who received the MISTT intervention. Case notes were coded in two steps with a subset of cases coded by two researchers and reviewed for interrater reliability in each step. The first round of coding was guided by primary SWCM intervention goals. The second round of coding identified SWCM sub-themes within each primary goal. Key themes indicate SWCMs aided with understanding the post-hospitalization period, helped patients navigate a range of systems and services, identified needs and supported patient goals, provided psychosocial support, and centered support on stroke recovery and prevention. Case studies illustrate ways in which SWCM were key supports during the transition period, but that support does not cleanly align with quantitative findings from patient-reported outcomes. This study aligns with a growing body of work documenting the complexity of transitions of care and has implications for how we support patients and caregivers as they move from inpatient to outpatient care and measure outcomes."}
+{"text": "Pain treatment services and clinical indicators of pain chronicity focus on afferent nociceptive projections and psychological markers of pain perception with little focus on motor processes. Research supports a strong role for the motor system both in terms of pain related disability and in descending pain modulation. However, there is little understanding of the neurological regions implicated in pain-motor interactions and how the motor and sensory systems interact under conditions of pain. We performed an ALE meta-analysis on two clinical cohorts with atypical sensory and motor processes under conditions of pain and no pain. Persons with sensory altered processing (SAP) and no pain presented with greater activity in the precentral and supplementary motor area relative to persons with self-reported pain. In persons with motor altered processing (MAP), there appeared to be a suppression of activity in key pain regions such as the insula, thalamus, and postcentral gyrus. As such, activation within the motor system may play a critical role in dampening pain symptoms in persons with SAP, and in suppressing activity in key pain regions of the brain in persons with MAP. Future research endeavors should focus on understanding how sensory and motor processes interact both to understand disability and discover new treatment avenues. The motor system has a poorly understoodd role in nociceptive processing and pain perception. The relationship between nociception and pain is largely understood as sensory in origin; however, acute and chronic pain is associated with significant physical disability  the relatively lower prevalence of pain in persons with motor altered processing (MAP) than sensory altered processing (SAP), (2) the connection between motor and descending pain modulation areas of the brain, and (3) sensorimotor incongruence subserving learning and long-term potentiation. We predicted that altered afferent feedback, seen in persons with SAP, would be associated with aberrant processing in motor planning areas of the brain and that atypical efferent activity, seen in persons with MAP, would be associated with activation in pain-related regions of the brain.Short and long-range connections between sensory and motor regions of the brain may be implicated in the processing of nociceptive stimuli and pain perception. Incongruence between Populations, Neuroimaging Methods, and Task Specification. These search terms were combined using the operator \u201cAND\u201d reflecting between parameter combinations and \u201cOR\u201d reflecting within parameter searches. If the Pubmed database was being used, key words were first searched through the Pubmed MeSH database to include additional subheadings or quantifiers within the same context of the key word. See Figure 2 for an example of the search methodology. Population key terms  2020 guidelines  and (2) Parkinson's disease: defined as a progressive disease of the nervous system characterized by muscular rigidity and tremor . Participants with Parkinson's disease were all studied during the \u201cOFF\u201d period which was defined as withdrawal of antiparkinsonian medication for 12+ h. The criteria for chronic pain in SAP was defined as the self-reported perception of a localized or generalized unpleasant bodily sensation that caused prolonged physical discomfort or mental distress. Phantom limb pain was defined as pain that is perceived as originating from an amputated limb. Movement imagery was defined as a mental execution of a movement without any muscle activation of the limb imagined to be moved that may, or may not, involve a visual cue. Movement execution task was defined as muscle activation of a limb while performing a task. Studies were excluded from analysis if: (1) stereotaxic coordinates were only reported as between-group comparisons; (2) stereotaxic coordinates included subjects with incomplete spinal cord injuries; (3) stereotaxic coordinates included Parkinson's disease subjects actively taking antiparkinsonian medications; (4) stereotaxic coordinates reported did not differentiate between the two groups of subjects with pain and subjects without pain. One reviewer used the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies  Altered afferent feedback during movement imagery: SAP cohort relative to healthy controls, and (4) Altered efferent motor commands during movement execution: MAP cohort relative to healthy controls. The single dataset analysis had a cluster forming threshold of p=0.005. The contrast threshold was set to p = 0.05 with a minimum cluster volume of 200 mm3. Brain regions reported in Tables 5\u20137 used the Harvard-Oxford Cortical Structural Atlas and the Cerebellar Atlas in MNI152 space after normalization with FMRIB's  Non-linear Image Registration Tool (FNIRT) from the FSL (FMRIB Software Library) program  to moderate (hand movement tasks) difficulty. Imaging modalities used were either PET or fMRI. All included studies were a level II cohort study using levels of evidence pyramid by Forrest and Miller  to complex (writing). Imaging modalities used were either PET or fMRI. All included studies were a level II cohort study using levels of evidence pyramid by Forrest and Miller  that above-normal efferent motor activity is associated with decreased activity in brain regions involved in affective processing. Findings are outlined in the context of sensorimotor integration.Brain activity in persons with atypical afferent input from peripheral nerve or spinal cord injury is modulated based on the presence of pain. Sensorimotor integration is tightly coupled in the central nervous system and depends on feedback from the peripheral nervous system for proprioceptive input. The primary motor cortex is extensively interconnected with descending pain modulatory regions and sensory processing areas of the brain  as opposed to the long-lasting nature of chronic pain (>3 months), has been shown to have an inhibitory effect on the motor cortex  included cohorts: atypical afferent and efferent processing represents the basis for a large myriad of neurological conditions. Including other conditions such as multiple sclerosis or amyotrophic lateral sclerosis may impact the specificity of current findings; (2) hemispheric laterality: based on the limited sample of articles and bilateral projections of sensory and motor circuits, we elected not to split our data based on affected limb; (3) reporting bias: based on the secondary data analysis approach we are limited to the reported data of each study. However, these may be limited to within-group, rather than between-group, stereotaxic coordinates, no reporting of pain, differential reporting basis of pain symptoms, and different clinical standards for neurological disorders.Central nervous system processing of nociceptive input is the basis for understanding acute and chronic pain. To date, research and clinical interests has focused on the primary reception and distributed nature of nociception on the brain; however, there is growing interest on the impact of efferent motor processes on sensory processing. Looking on the other side of sensory processing offers a non-pharmacological source of analgesia that has transcending impacts on physical and mental health. Findings from this investigation point toward an important role of efferent motor processes on dampening central processing of nociception and motor learning in the context of pain.The original contributions presented in the study are included in the article/Study conception and design, analysis and interpretation of results, and draft manuscript preparation: CG and SH. Data collection: CG. Both authors reviewed the results and approved the final version of the manuscript.This work was supported by the Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, Boston MA (Awarded to SH).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
+{"text": "Access to safe drinking water in schools is essential for a good health, wellbeing, learning and dignity of pupils. The rural schools are most frequently connected to the rural water supply system or own water supply source, where the monitoring of drinking water quality is scarced. The study was conducted in the rural regions in Serbia in 2016, aiming at assessing drinking water quality and sanitary conditions of school water supply facilities.In total 238 school facilities, including 108 in \u0160umadija and 130 in Pomoravlje District were investigated using laboratory testing of drinking water and sanitary inspection.Study revealed that 32% of analysed samples showed microbiological faecal contamination with bacteria E. coli, while 52% of samples showed physico-chemical non-compliance with the national standards, where higher nitrates were the most common cause. Overall non-compliance of drinking water from school rural water supply systems amounted to 66% of tested water samples. This study also showed the main technical shortcomings of school water supply facilities and distribution networks such as the lack of fencing of the water source, damaged or absence of drainage channels from the well concrete floor and poor construction characteristics of wells.The results of this study, particularly presence of E. coli in drinking water may affect pupils\u2019 health and is a consequence of poor sanitary conditions and maintenance of small rural drinking water supply systems and individual wells. It is necessary to provide continuous disinfection of water available in schools and to undertake measures for technical improvements in order to provide better sanitary protection of water sources and other water supply facilities in rural schools.\u2022\u2002Drinking water quality in schools is vital for children public health.\u2022\u2002Raise awareness of local community on drinking water safety and enforce continuous monitoring of drinking water quality in small rural water supply systems in schools."}
+{"text": "The number of individuals living in incarcerated settings with dementia will double by 2030 and triple by 2050. Older adults are the fastest growing demographic in incarcerated settings and age is the number one risk factor for dementia. The HRSA-sponsored Geriatric Workforce Enhancement Program, Ohio Council for Cognitive Health, Benjamin Rose Institute on Aging and the Ohio Department of Rehabilitation and Correction (ODRC) worked together to develop Dementia Friends for Incarcerated Settings to impact the lives of those living with dementia within the correctional setting. This pilot furthered the development of this Dementia Friends programming and measured ODRC staff knowledge/attitudes about dementia, as well as uncovered the experiences and needs of staff within the ODRC. Online Dementia Friends sessions were conducted in all 27 Ohio prisons with voluntary, anonymous pre- and post-session surveys based on the Brief Tool for Dementia-Friendly Education and Training Sessions developed to measure the impact of dementia-friendly education efforts on knowledge, attitudes/perceptions, and interacting with people living with dementia and their caregivers. The results of this pilot underscored the need, usefulness and applicability of dementia education throughout the ODRC system, indicating teaching effective communication techniques within a correctional facility are helpful for those working within such settings. The results indicate benefits on both a personal and professional level. These sessions provide a starting point for potential future educational sessions to serve all members of the correctional sector. Future proposed projects will focus on people living in incarcerated settings and those transitioning back into the community."}
+{"text": "Rapid advances, increasing availability, decreasing costs of sequencing technologies, computational pipelines for variant interpretation, and training of clinical personnel, are accelerating the integration of genomic sequencing into routine health care.Although genomic sequencing has demonstrated utility as an indication-based diagnostic tool for certain diseases, the full potential of DNA sequencing as a non-diagnostic tool for population-level screening is not yet realized. DNA-based population screening has enormous potential to identify people with underlying genetic predisposition to serious diseases such as cancer and heart disease, who represent 1\u20132% of the population . Early dNevertheless, the ascertainment of otherwise apparently healthy individuals with underlying genetic risk will necessitate a departure from the traditional model of familial or personal risk-based genetic testing in specialty settings to a population-based model of screening in primary care or community settings . AdditioGiven the low frequency of individuals with a heritable genetic risk, sharing of study methods and data from evidence-gathering pilot studies are needed to foster collaborative linkage of observations and outcomes to address these gaps . With thDNA-based population screening is increasingly viewed through the lens of implementation science methods and frameworks . Use of Wildin et al.) describes feasibility testing of the Genomic Population Health Pilot Program within the University of Vermont Health Network using the well-known Consolidated Framework for Implementation Research (CFIR). The article details the barriers to and facilitators of this unique program that was among the first non-research DNA-based screening pilots.  detail the use of the RE-AIM implementation science framework  to conduct separate pragmatic program evaluations of two different Geisinger DNA screening pilots, the MyCode community health research program and a primary care clinical DNA screening pilot, based on their most relevant and informative domains.In this Research Topic of the journal,  of multi-level barriers, facilitators, stakeholder perceptions, and outcomes of implementing DNA-based population screening supports the need for more research to address significant barriers to health equity, ethical, legal, and social implications (ELSI), readiness for implementation in primary care, and evidence gaps regarding clinical utility and long-term outcomes. Emphasis on the development of metrics for the collection and sharing of aggregated patient, health service, and intervention outcomes is critically important for evaluating the public health impact and cost-effectiveness of DNA-based population screening.The systematic review by (Kingdom and Wright) address this urgent need for a broader genotype-based understanding of risk identification with a comprehensive review of emerging clinical studies of common and rare genetic variation and its effect on human diseases.Currently available evidence does not provide support for the widespread use of predictive genomic screening in healthy populations. Thus, an inherent challenge for DNA-based population screening programs is determining which disease-causing genes and genomic variants to screen for to maximize clinical utility and minimize undue harms to healthy individuals. Incomplete penetrance and variable expressivity of genetic variants can result in a broad spectrum of phenotypes, from subclinical manifestations to severe disease, even among relatives harboring the same disease-causing genotypes. Our current understanding of the natural history of many genetic diseases is based on small cohorts of clinically diagnosed individuals, which raises valid concerns about overdiagnosis and overtreatment in unselected populations.  illustrates the value of combining longitudinal health information from follow-up genetic testing of screen-positive newborns with accompanying clinical information to inform genotype-phenotype correlations and reevaluate the clinical relevance of genetic variant data.  highlight the predictive utility and complementarity of polygenic scores combined with other types of screening data such as family health histories, for providing an earlier and more precise diagnosis in high-risk individuals.Longitudinal data from clinical cases with positive results are also needed to reclassify potential pathogenic variants and link successful standards of clinical care to ascertainment by population-scale implementation of DNA-based screening. The work of  describe the impact of a proband indication on the uptake of cascade testing by family members based on two settings, one in which the proband has a clinical condition and presents for testing in a diagnostic setting as well as a non-diagnostic scenario where the proband was detected via proactive screening.  evaluate whether an alternative approach to population genomic screening\u2014automated sharing of family health history via the electronic health record (EHR)\u2014offers an efficient and cost-saving method to facilitate cascade testing.Cascade screening in blood relatives for a variant that confers an inherited disease predisposition is an important and cost-effective strategy for identifying and improving health outcomes of other at-risk individuals; however, there are substantial barriers to widespread acceptance of this beneficial process. In their manuscript  observe an association between awareness of genetic testing and educational attainment level and public interest in participating in genomic screening to learn about inherited predisposition to cancer.  investigate about whether offering genomic screening as part of routine health visits would stimulate interest and participation by ethnically diverse young women.  explore the perceptions of parents who belong to underrepresented groups in genomic research in making an urgent and difficult choice about whether to enroll in the prenatal arm of the California-based Program in Prenatal and Pediatric Genome Sequencing (P3EGS), part of the Clinical Sequencing Evidence-Generating Research (CSER) consortium. Building on this work,  reports on the expectations of the parents who ultimately did decide to enroll in the P3EGS study and the subsequent value to them of the prenatal genomic sequencing results they received.Understanding the factors that affect public interest in participating in genomic research will ultimately support informed decision-making and minimize enrollment barriers in clinical offerings.  note in their article, the implementation of any health care innovation is generally accompanied by concerns about adequate reach and representation of medically underserved individuals. DNA-based population screening is subject to these concerns due to stark inequities posed by numerous barriers at the patient, provider, and policy levels. However, if the implementation of DNA-based population screening can be effectively moored to public health screening frameworks and community partnerships that center equity and justice as Azriel et al. describe, there is tremendous potential to improve outcomes for all individuals with inherited predispositions to certain actionable medical conditions, add to our knowledge base about the natural history and spectrum of disease in underrepresented populations, and potentially reduce the access gap to clinical and genetic services. In the article by , a collaborative team of parents and researchers illustrate the development of a bidirectional partnership in which community stakeholders are integrated in the design, implementation, and dissemination of knowledge throughout the lifespan of the Age-Based Genomic Screening (ABGS) project. Engagement marketing concepts can foster these types of trust-based relationships with communities that have been historically marginalized in biomedical research to ensure that health disparities are not perpetuated in DNA-based population screening programs, as  describe from their engagement experiences with the All of Us program.  share a protocol for understanding public beliefs and values about stewardship of cloud-based human genomic data that can help to assuage concerns about data access and privacy.As  examines the perspectives of parents of healthy newborns in the BabySeq Project who were surveyed about various aspects of newborn genome sequencing, including whether it should be state-mandated and accompanied by informed consent, and the return of different types of genetic information.  highlights opportunities for modeling to address the challenges of accelerating the process of adjudicating candidate conditions.  describe the development of an ethics- and engagement-informed Genomics England-sponsored Newborn Genomes Program to explore the utility of offering whole genome sequencing (WGS) in the newborn period.Newborn screening (NBS) is a highly successful public health screening program for which early detection and effective interventions have resulted in established health benefits over many decades. Implementing DNA-based screening could significantly expand the number of conditions that NBS could screen for, and the gap between enhanced diagnostic capability and available, effective treatments is rapidly closing. However, effective and equitable implementation of expanded NBS incurs an even higher burden of evidence than screening healthy adults.  describe the development and evaluation of an electronic and patient-centered education and informed consent approach for the large-scale expanded NBS Early Check study.  balance the potential benefits against the possible harms in their assessment of unresolved challenges associated with using universal sequencing as a methodology for population screening of newborns. (Spencer and Fullerton) explore the ethical rationale for coinciding age of screening implementation for highly actionable genetic conditions with the age of maximum clinical utility in the general population.Despite the expected benefit of rapidly emerging new therapies and the critical importance of early initiation of treatment for maximizing health benefits, widespread clinical integration of expanded genomic NBS has been effectively stalled due to substantial ethical, social, and practical challenges inherent in sequencing newborns. Historically, NBS has employed an \u201copt-out\u201d model of consent due to its vast public health importance; however, expanding NBS by hundreds of conditions will concomitantly expand the range, relevance, and recommendations for the results parents might receive and will likely require parents to \u201copt-in\u201d to expanded genomic NBS. This paradigm shift will entail educating parents on a broad array of relatively complex topics in preparation for informed decision-making and consent. Health care practitioners will require education and innovative resources for facilitating informed decision-making, parental consent and return of results.  describe barriers to relevant clinical action following the delivery by the Healthy Nevada Program of important genetic findings directly into participants\u2019 EHR and proposes potential solutions centered on providing additional education and support for healthcare providers.DNA-based population screening has the potential to transform the practice of health care from reactively treating disease symptoms to proactively identifying at-risk individuals in the population and delivering precision care to prevent the onset of disease. Encapsulated in this Research Topic are articles describing broad advancement in research and clinical integration of DNA-based population screening. Creating and utilizing effective infrastructure to translate research to clinical practice remains crucial to realizing actual improvements in public health. The EHR features prominently in patient-centered healthcare as an important data tool for sharing results between providers and patients, monitoring clinical follow up, and, more recently, providing passive and active clinical decision support.  highlight outcomes from The Transdisciplinary Conference for Future Leaders in Precision Public Health, a participatory forum to accelerate solutions for precision public health challenges. Finally,  summarize necessary translational improvements required in practice and policymaking to operationalize the promise for DNA-based population screening for precision public health.Advances in EHR functionality notwithstanding, the necessary infrastructure to enable learning healthcare systems remains elusive. Fertile settings for discussion and problem solving are needed to harmonize collection, analysis, and reporting of data and outcomes. The National Human Genome Research Institute\u2019s Genomic Medicine XIV virtual meeting entitled; \u201cGenomic Learning Healthcare Systems\u201d provides promising support for priority research areas. , readiness for implementation in primary care, and evidence gaps regarding clinical utility and long-term outcomes. This research should use an implementation science framework and build effective governance and infrastructure. We hope our readers find the collection of papers herein useful in advancing the dialogue on DNA-based population screening towards a new era of precision public health."}
+{"text": "In addition to improved AS, the oral route provides advantages to patients, staff and the environment including reduced patient risk of line infections/complications; reduced staff workload and healthcare costs; improved patient comfort/mobility; earlier discharge; and improved sustainability.Antimicrobial stewardship (AS) is essential to minimize the emergence and spread of antimicrobial resistance.To measure baseline proportion of surgical patients meeting the criteria for oral receiving oral metronidazole; introduce tests of change to promote use of oral metronidazole where appropriate; and measure changes in prescribing behaviour to determine if improvement has been achieved, with the aim of increasing the proportion of oral metronidazole prescribed to eligible Royal Alexandra Hospital (RAH) surgical patients to 50% by February 2022.\u00a9 group messages; and West of Scotland Surgical Association presentation. To measure improvement the proportion of oral and IV metronidazole prescribed was measured weekly and oral and IV metronidazole usage data in RAH surgical wards was measured monthly. A questionnaire was used to assess the impact of the project on nursing staff.Baseline metronidazole prescribing data were collected over 6 weeks in surgical wards at the RAH. Exclusions for oral metronidazole included compromised gut absorption, oral route unreliable or worsening clinical condition/sepsis. A quality improvement approach was used to engage and raise awareness of the multidisciplinary surgical team to the benefits of prescribing oral metronidazole where appropriate. A range of methods were used including prospective audit and feedback; departmental presentations to surgical and pharmacy teams; eye-catching posters in key areas; staff champions; staff recognition awards; WhatsAppn = 90) highlighted that only 13.5% of patients meeting the criteria for oral metronidazole were prescribed oral in RAH surgical wards. Post-change: oral metronidazole prescribing increased from a baseline median of 7% to 51%; IV metronidazole usage data decreased by 45%; there were 320 fewer IV metronidazole administrations per month; and nursing staff reported benefits including reduced workload, improved patient comfort and reduced plastic waste.Baseline data (A quality improvement approach to engage and raise staff awareness of the benefits of oral metronidazole resulted in a change in prescribing behaviour and increased the proportion of oral metronidazole prescribed to eligible surgical patients to 50% by February 2022."}
+{"text": "The prevalence of age-related cognitive disorders is increasing. Effective prevention and treatment interventions are unavailable due to a poor understanding of aging biology. Multiple emerging evidence indicates that the gut microbiome is linked with age-related disorders; however, their clinical importance in differentiating and predicting the risk of cognitive decline or dementia is largely elusive. Utilizing samples and data of a large, multi-site clinical study across the state of Florida called Microbiome in aging Gut and Brain (MiaGB) Consortium, our whole genome microbiome sequencing revealed that the viral and archaeal population was significantly reduced in the gut of older adults with dementia (n=8) compared to those with mild cognitive impairment (MCI) (n=25) and normal cognition (n=59). Whereas the fungi were exclusively detected in the controls only. Alpha diversity of the participants with MCI and dementia was lower than the cognitively healthy controls. The abundance of Actinobacteria and Verrucomicrobia phyla was higher, and Firmicutes phylum was lower in the participants with dementia. Bacteriophages Lactobacillus prophage Lj771 and Microbacterium phage Min1 were exclusively detected in the gut of the participants with dementia. The study also identifies key metabolic pathways altered in the controls versus the cognitive impairment state. Our biomarker discovery analyses also revealed that these unique microbiome signatures and pathways might have predictive power for cognitive decline and dementia risk and offer new targets for future therapeutic interventions."}
+{"text": "We assessed associations between social vulnerability  and the provision of evidence-based diabetes prevention and management activities  in South Carolina counties with high burdens of diabetes and heart disease. These associations were examined by using relative risk estimation by Poisson regression with robust error variance. Results suggest that social vulnerability may have differential effects on the provision of evidence-based diabetes prevention and management activities in South Carolina. Findings support calls to identify upstream social factors contributing to adverse health outcomes and provide several potential points for intervention. Evidence-based strategies to improve diabetes outcomes exist , yet little is known about how providing these chronic disease prevention and management activities may differ by social vulnerability .We assessed associations between social vulnerability and providing evidence-based diabetes prevention and management activities in South Carolina counties with high burdens of diabetes and heart disease. Results suggest that social vulnerability may affect the provision of evidence-based diabetes prevention and management activities at Rural Health Clinics and Federally Qualified Health Centers.Findings support calls to identify upstream social factors contributing to adverse health outcomes and provide several potential points for intervention .In South Carolina, 13.0% of adults have diabetes and 34.9% of adults have prediabetes . Severalz scores of diabetes and heart disease burden, weighted as mortality (50%), hospitalizations (30%), and prevalence (20%) for both conditions. RHCs and FQHCs providing only pediatric, behavioral health, gynecologic/obstetric, dental, or pharmacy services were excluded. Health care practices completed the online survey during February through August 2019. FQHCs include several individual health care practices; representatives from 7 FQHCs answered survey questions on behalf of 50 total practices. The decision to have these representatives respond for the individual practices was made in consultation with local partners and 2 statewide associations, the South Carolina Office of Rural Health (SCORH) and the South Carolina Primary Health Care Association (SCPHCA) to reduce the administrative burden on FQHCs. SCORH and SCPHCA assisted with survey distribution and data validation.Data on diabetes prevention and management activities came from a cross-sectional survey of RHCs and FQHCs (N = 71) in the top 50% of South Carolina counties with the highest burden of diabetes and heart disease. The sample was determined by county-level standardized The survey response rate was 78%. Data represented 21 RHCs and 50 FQHCs and included 22 of 46 counties in the state . These cCounty-level social vulnerability measures were extracted from the Centers for Disease Control and Prevention\u2019s 2018 Minority Health Social Vulnerability Index (SVI) ,12. SpecData were analyzed by using Stata version 15 (StataCorp LLC). To reduce confounding and the potential for reverse causality, the analysis did not include social vulnerability related to medical vulnerability (because the sample of counties was chosen on the basis of diabetes and heart disease burden). Descriptive statistics  were calculated for 7 evidence-based diabetes prevention and management activities  and SVI measures and their indicators. Associations between each SVI measure and each of 7 evidence-based activities were examined by using relative risk estimation by Poisson regression with robust error variance. The multilevel analysis accounted for clustering at the county and center levels.About half of health care practices reported implementing the NDPP (51%), and about one-third of practices reported implementing DSMES 34%; . Nearly No significant associations were found between social vulnerability related to housing type and transportation and providing evidence-based diabetes prevention and management activities . PracticResults suggest that social vulnerability measures may have differential effects on the provision of evidence-based diabetes prevention and management activities at RHCs and FQHCs in South Carolina. Across themes, higher social vulnerability tended to be related to providing fewer diabetes activities, with one exception: higher social vulnerability related to health care infrastructure was associated with providing more medication therapy management. These findings may reflect, in part, the demographics and health care\u2013associated vulnerabilities of the Interstate 95 corridor , where mOne limitation of this study is RHC staff answered questions on behalf of their individual practice, whereas FQHC representatives completed the survey for all practices affiliated with their center. However, the multilevel analysis did account for clustering at the center level. Another limitation is that analyses grouped RHCs and FQHCs together. FQHCs may be more likely to have a pharmacist available and, therefore, have greater capacity to implement programs like NDPP and medication therapy management. Lastly, this study only included RHCs and FQHCs, while other medical facilities, county agencies, and community organizations may also offer evidence-based diabetes prevention and management activities.Findings support calls to identify upstream social factors contributing to adverse health outcomes and provide several potential points for intervention . For exa"}
+{"text": "Using large cohort surveys, this symposium includes five studies examining the linkages between oral health and systemic conditions, and social and behaviors factors affecting oral health and dental care utilization in older adults. The first study used the English Longitudinal Study of Ageing (ELSA) and analyzed the effect of changes in self-rated dental conditions on memory among adults age 51+. This study also examined the mediation effect of stroke on this relationship. Using the same data (ELSA), the second study examined the longitudinal relationships between cognitive function and changes in diabetes and oral health status. Results showed that participants with co-occurrence of diabetes and poor oral health had an accelerated decline in cognitive function over the study period. The third study was conducted among 8,744 adults age 51+ using data from the Health and Retirement Study over a 10-year period. The authors found that social isolation had a significant effect on dementia onset and that both dental visits and tooth status had a mediating effect on the association. The fourth study analyzed the Medical Expenditure Panel Survey from 2009-2016 and found that individuals with cognitive impairment had a significantly lower probability of annual dental visits. Using data from the Population Study of Chinese Elderly in Chicago collected between 2017-2019, the fifth study found that spousal support was significantly associated with a lower likelihood of having any dental visit. Findings illustrate the importance of understanding how different aspects of social relationships might play a role in dental care use."}
+{"text": "Cohort studies of aging recruit participants at an age before most of the population experiences the study outcome, to document its natural history. The age of study commencement is usually based on \u201cnormative\u201d aging among Whites. However, \u201cweathering\u201d can cause accelerated health declines in minoritized populations compared to Whites due to cumulative experience of multiple forms of marginalization. Thus, considering if weathering among minoritized individuals could affect selection into cohort studies is necessary to effectively estimate and understand racial/ethnic disparities in aging and disease. Using the Study of Women\u2019s Health Across the Nation (SWAN), a multi-ethnic longitudinal cohort, and its cross-sectional screening survey, we examine the effects of selection on the racial/ethnic differences in the age of onset of 4 cardio-metabolic outcomes . Selection at study commencement (left truncation and left censoring) had greater effects on outcomes with earlier age at onset (hypertension) and right censoring had greater effects on outcomes with later onsets (metabolic). Full adjustment led to an average 20-year decrease in predicted median age of onset for all groups across the 4 outcomes and tended to decrease the predicted disparity in age at onset. However, significantly earlier onset of each outcome for Black and Hispanic women compared to Whites remained. Not considering the full extent of selection bias in cohort studies can misinform our understanding of aging and disease, especially for minoritized populations who have higher prevalence of these leading causes of morbidity and mortality earlier in life."}
+{"text": "The Africa Cancer Research and Control ECHO is a virtual community of practice and knowledge dissemination platform for cancer professionals. Each year, the steering committee completes an evaluation to elicit feedback and inform continuous program improvement. The 2020-2021 evaluation included for the first time a qualitative component, allowing documentation of concrete utilization of knowledge gained from the Africa Cancer ECHO to advance cancer control efforts.Participants were invited to complete a survey about satisfaction, knowledge acquisition, knowledge application, and outcomes of the Africa Cancer ECHO. In addition, six steering committee members completed semi-structured interviews with a focus on program outcomes.A total of 226 unique people from over 40 organizations participated in the Africa Cancer ECHO during 2020-2021, with 19 sessions hosted on topics across the cancer control continuum. Twenty-two participants representing nine countries and multiple sectors of cancer research and control responded to the survey. They reported participating to gain knowledge (57%), network (21%) and strongly agreed that sessions were relevant and engaging (100%). Reported limitations included obstacles of time (74%), technology (13%) and limited opportunities to engage with partners and participants (50%). Participants applied the knowledge gained in various ways including: adding survivorship to their National Cancer Control Plans (for the first time); adapting training materials to initiate a patient navigation program, partnering to strengthen brachytherapy capacity at the national level and collaboratively conducting a situational analysis of cancer survivorship in the Africa region.The Africa Cancer ECHO provides a relevant and engaging platform which encourages community and the exchange of socio-culturally adapted best practices in cancer research and control in the African region. The mixed methods evaluation approach has deepened understanding of how knowledge exchanged in the ECHO sessions is utilized and applied. More targeted recruitment and retention, as well as facilitation of collaborations beyond the sessions will further strengthen this community."}
+{"text": "While women victims of intimate partner violence (IPV) suffer the burden of mental health issues (MHI), they face many challenges accessing mental health services (MHS).We draw on the socioecological model and explore different level barriers for accessing MHS among women experiencing IPV.We conducted a qualitative study in 2020-2021 at three levels: policy, practice and women\u2019s experience. This included in-depth interviews with 19 policymakers from the Ministry of Health (MoH) and the Ministry of Social Welfare (MSW); four directors of shelters for women victims of IPV; 35 women  attending shelters for women victims of IPV (age 22-50), and six focus groups with 26 social workers. Participants were asked about the barriers for utilizing MHS.We identified complex multifaced barriers regarding the accessibility and quality of MHS among women victims of IPV. At the policy level, we identified structural organizational barriers related to the division of responsibilities between the two offices (MoH and MSW). These included lack of collaboration, funding and information transmission and insufficient communication mechanisms. At the practice level, shelters\u2019 directors and social workers raised barriers, most of which were related to divisions in knowledge, terminology, and treatment approaches among mental healthcare providers and social welfare therapists. The women themselves raised issues related to stigma, lack of family support and continuity of MHS.To improve MHS access, it is crucial to overcome the multiple barriers  that are faced by women who are experiencing IPV.No significant relationships."}
+{"text": "Our study has immunohistochemically examined T cells localization and number as well as proliferative activity level for the bulbourethral gland epithelium in men of different ages, using monoclonal antibodies against CD45RO and proliferating cell nuclear antigen (PCNA).We have found that the T cells have been localized mainly in excretory ducts epithelium of the glands in any age group, meanwhile their relative number varies with age. The excretory ducts epithelium has shown a high proliferative activity when in acini the PCNA index has been low. Postnatal dynamics of the epithelium proliferative activity positively correlates with age-related density fluctuations in lymphocytic infiltration of the glands.We consider that intraepithelial T cells may contribute to the regulation of epithelial cells proliferation in the bulbourethral glands. Epithelial proliferation; Human bulbourethral glands; Lymphocytic infiltration; Proliferating cell nuclear antigen; T cells. An informed consent was obtained for all the cases that were analyzed in the current research from the close relatives of the deceased person. The study has been approved by the Local Ethical Committee of Sechenov University on March 2019 (protocol #03\u201319). The cause of death was determined by forensic medical examination. The material has been classified in accordance with the following age periodization: infancy , toddlers and early childhood , late childhood , early adolescence , late adolescence , early adulthood , middle adulthood , late adulthood/young old age , and middle & oldest-old age . Considering that a decrease in the level of testosterone and reproductive function changes are more prominent in men of middle adulthood, namely after 45 years . Prof. Igor Meglinski acknowledges the partial support of innovative programme [101004462] and the Leverhulme Trust and The Royal Society [APX111232 APEX Awards 2021] and the Academy of Finland [325097]. Dr. Gennadii Piavchenko and Prof. Igor Meglinski also acknowledge the support from the Academy of Finland [351068].Dr. Gennadii Piavchenko acknowledges the support of Data will be made available on request.The authors declare no conflict of interest.No additional information is available for this paper."}
+{"text": "Data sharing and administrative data access for multi-jurisdictional research must accommodate all local requirements for the protection of personal information and personal health data. Navigating the different safeguards for data sharing found in all relevant Canadian provincial and territorial legislation requires exploring innovative, privacy compliant solutions.Health Data Research Network Canada (HDRN Canada) and one of its provincial data centre partners, New Brunswick Institute for Research, Data and Training (NB-IRDT), are undertaking unconventional approaches to data sharing that balance legislative compliance and data access needs. Three approaches are being pursued: harmonizing data sharing agreements between a national longitudinal study and 10 provincial data centres; facilitating 4 individual data sharing agreements with one regional cohort of a nationwide study; and coordinating data sharing between 4 provincial government departments and one national data centre. Each approach has unique features that presented problems needing innovative resolutions.The experiences and challenges of these three approaches to data sharing for multi-regional research have been perplexing but ultimately are leading to productive outcomes. Learnings acquired enable partners to move beyond anecdotal perceptions of data sharing limitations to practical solutions that can be applied in future data sharing partnerships.The ongoing project management approach of these initiatives identified a core set of somewhat predictable devices to ensure the advancement of simultaneous multiple regional data sharing agreements. These include the assignment of a project coordinator role, clear and ongoing communication, and the ability to negotiate and manage expectations. More innovative, however, is the roadmap that evolved, laying out the necessary (previously unanticipated) measures and sequence in which they should occur for the most expedient outcome.To harness the potential of multi-regional research in Canada, provinces and territories must identify feasible and efficient data sharing solutions. The identification of adoptable and replicable legislatively compliant data sharing practices will increase potential data accessibility. This will increase available data and data platforms for research informed policy decisions."}
+{"text": "For years, nanomedical research has represented a challenge and an opportunity in terms of imaging techniques. In fact, the development of safe and effective nanoconstructs designed for diagnostic or therapeutic purposes implies the knowledge of their fine structure and their interactions with the biological environment. The need to characterise morphologically newly synthesised nanoconstructs and localise them in living systems (from single cells to the whole organism) resulted in the application of the most varied imaging approaches. The biodistribution, targeting and clearance of nanomedical tools in the whole organism have been investigated using in vivo imaging techniques such as magnetic resonance imaging (MRI), optical imaging and positron emission tomography (PET), while the evaluation of the impact and dynamics of nanoparticulates in cells and tissues required the application of light and electron microscopy techniques ,2,3,4. IThis Special Issue contains various examples of original applications of multimodal imaging to diverse nanomedical topics.In an in vitro study, engineered polarity-sensitive fluorescent fatty acids derivatives were monitored for their distribution in cultured cells by fluorescence lifetime imaging, which provided a dynamic view of the fluidity and microviscosity of different cell membrane compartments . MoreoveIn another in vitro study, various imaging techniques were applied to assess the suitability of ethosomes and transethosomes as potential delivery systems for vitamin D3 to different cell types . Cryo-trAs for in vivo studies, PET was used to map traumatic brain injury in rats by using two radioligands\u201411C]peripheral benzodiazepine receptor (PBR) 28 and [18F]flumazenil\u2014as indicators of neuroinflammation and neuronal activity and death [CperipherIn vivo multimodal imaging and ex vivo investigations were performed to follow labelled lymphoma cells in mice : 2-deoxyExosomes from cultured murine breast cancer cells were simultaneously radiolabelled, fluorescently labelled, and morphologically characterised using TEM to then be monitored with PET. Optical imaging both in living mice and in single explanted organs was carried out ex vivo . The exoIn addition to original experimental reports, this Special Issue provides two review articles that deal with advanced applications of molecular imaging techniques to nanomedicine.Sier et al.  providedTaken together, the articles collected in this Special Issue affirm the vitality of the scientific research in the field of nanomedicine and the great contribution given by the original application of molecular imaging techniques to the development of innovative diagnostic and therapeutic strategies based on nanoconstructs."}
+{"text": "Food quality and safety analysis are of paramount importance to ensure public health. Recent changes in eating habits and the modernization of food value chains have demanded the authentication of food ingredients and products. Adulteration in foods and microbiological contamination are two of the main issues affecting public health. The demand for high quality food increases the standards for quality control, which in turns requires high standard analytical tools to ensure the integrity of food products. The conventional analytical techniques are labor intensive, time consuming, and require often toxic chemicals. Food processing industries are looking for a potential tool for rapid, non-destructive, and online testing of quality of foods during the supply chain. Numerous food researchers are exploring the application of spectroscopic techniques for food quality testing and food authentication. Current research and applications of spectroscopic techniques have been reported for quality evaluation of different forms of the foods such as fresh produce (fruits & vegetables), minimally processed foods and/or cut fruits, food treated by non-thermal technologies, modified atmospheric/controlled atmospheric packed food, freeze dried foods, and microwave applied food have recently gained more attention. The food industry, food quality testing laboratories, and food standard organizations are interested in understanding the practical utilizations of spectroscopy techniques for quality evaluation.This Research Topic provides with recent trend and current information on different spectroscopy methods used for measurement of food quality and safety in the two of the most adulterated food categories: horticulture based fresh and processed food products and animal origin foods including dairy products.Han et al. evaluated the potential application of Fourier transform near-infrared (FT-NIR) coupled with chemometrics to authenticate animal based blood gels. The samples taken under this study were pig blood-based gel, cow blood-based gel, raw duck blood tofu and its binary and ternary adulterated with cow blood-based gel and pig blood-based gel. Amino acid profile and other biochemical nutrients were determined using FT-NIR. These authors have applied four extreme learning machine regression (ELMR) to predict adulteration levels. Overall, it was found that FT-NIR paired with ELM could able to authenticate the animal blood food with an accuracy of 93.89%.Pandiselvam et al.) reviewed the recent applications of NIR spectroscopy techniques to assess safety and quality of horticulture products in terms of biochemical quality evaluation, maturity and variety identification, estimation of textural properties and detection of damage and microbial/fungus contamination. These authors highlighted the importance of computational techniques to improve the prediction ability of NIR spectroscopy. Understanding the pre-processing techniques to analyze the spectral data and proper selection of wavelength would help for rapid and non-destructive checking of food quality using NIR spectroscopy.Authors from India, Romania, Germany and Poland . The authors have prepared silver nanoparticles as enhancer substrates for the detection of glutathione in dairy products. The collected spectral signatures were analyzed by SEIRA method in transmission mode using a cell of calcium fluoride window sheet immobilization solution. They further analyzed the infrared spectrum peak and the bond interaction for the quantitative analysis of glutathione. Further, they obtained good linearity and correlation coefficients with minimum error value. It confirms that spectroscopy could be used for accurate determination of glutathione content in common dairy products.We thank the specialty Chief Editor (Food Chemistry) Dr. Michael Rychlik and his team for their support and guidance. We appreciate the authors and reviewers from different countries for their valuable contributions. Our thanks to Frontiers for publishing this Research Topic.RP wrote the introduction and the conclusion. RP, DC, and AK wrote the central part with comments to the cited papers. All authors contributed to the article and approved the submitted version."}
+{"text": "As individuals are living longer, the prevalence of older adults living with dementia and other complex health and social care needs is on the rise . Correspondingly, efforts to develop supportive programming and policies for persons living with dementia (PLWDs) are of paramount importance . The challenges faced by PLWDs and other complex health and social needs are widely known , however, a systematic understanding of how and if current and long-standing efforts are adequately meeting the needs of these individuals remains elusive. This research sought to understand how program administrators, decision makers, PLWD, and caregivers across five North American jurisdictions  perceived specific dementia care programs and support services within their respective jurisdictions. We performed an inductive analysis of semi-structured interviews (N=37) and identified on-going care gaps experienced by participants. We present three main gaps: 1) disconnected and uncoordinated system infrastructure, 2) lack of comprehensive services to meet the diverse needs of PLWD and their caregivers, and 3) inconsistency in how dementia is understood; with associated perceived remedies. The results suggest that even when attempts to address the needs of PLWD and their caregivers are put in place there remains significant limitations of systems. The perspectives of decision makers, program administrators and individuals with lived experience offer unique insight into how these experiences may be improved to better support the complex needs of PLWD and their caregivers."}
+{"text": "There are well established associations between sensory loss and physical and cognitive deficits with aging, but gaps remain in our understanding of the associations between sensory function and early preclinical indicators of physical and cognitive decline. This symposium will present data from the Baltimore Longitudinal Study of Aging (BLSA) on a series of studies investigating the links among sensory function, motor function, and physical and cognitive outcomes in older adults. In the first study, Dr. Gross will present an operational definition of early cognitive impairment (ECI) based on a combination of two cognitive measures \u2013 the Card Rotations test and the California Verbal Learning Test Immediate Recall \u2013 to predict progression to MCI/AD. In the second study, Dr. Cai will evaluate the relationship between multisensory impairment  and the algorithmic definition of ECI. In the third study, Dr. Armstrong will evaluate the association between multisensory impairment and another biomarker of ECI or preclinical AD, specifically PET-PiB deposition. In the fourth study, Dr. Schrack, will present the joint contribution of multisensory (hearing and vision) impairment and motor function (gait speed) on risk of incident MCI/AD in longitudinal analyses. Finally, Dr. Martinez Amezcua will present the longitudinal association between hearing and vestibular function and decline in higher level physical function and endurance performance. Taken together, these studies present compelling data about the contribution of sensory function to preclinical indicators of physical and cognitive functioning with aging."}
+{"text": "The COVID-19 pandemic has highlighted the importance of providing person-centered care for our vulnerable populations across the globe. This symposium focuses on improving care for persons with cognitive impairment and dementia in various care settings. The first study explored dyadic experiences of living with early-onset dementia pre and during COVID-19 in China through a person-centered care lens. The second concept analysis presented four interrelated dimensions of Asian American caregiver support, including individual, family, community, and professional health system. The third study investigated undergraduate nursing students\u2019 attitudes toward pursuing jobs of providing care for older adults with dementia in rapidly-aging urban areas in China and its associated factors. The fourth study examined the impact of social isolation on cognitive function and Quality of Life among acute ischemic stroke (AIS) patients in China. The last study explored an association between perceived control and cognitive function among acute ischemic stroke (AIS) patients in China. The last two studies suggested that perceived control and social isolation may be potential targets in cognitive interventions for AIS patients. This symposium presents the understanding of dementia caregiver support, the empirical evidence of living with dementia, the attitudes towards dementia care among the next generation of nursing workforce, and the impact of social factors on cognitive functions longitudinally. The presenters emphasize the importance of improving care in long-term care and acute care settings. There is a need to design person and family-centered care to improve health and wellbeing of persons with cognitive impairment."}
+{"text": "The film was not dedicatedly prepared for its opto-acousto-optic evaluation by PLU, exhibiting significant lateral variations in thickness and surface roughness. Therefore, the achieved measurements of the sound velocity and of the optical refractive index, and characterization of the surface roughness confirm the robustness of the PLU technique for thin film evaluation. We hope that the first measurements of the acoustical and optical properties of epitaxial grown Ba1\u2212xSrxTiO3 (0 \u2264 x \u2264 1) by PLU technique accomplished here provide the parameters required for more extended predictive design of the phononic, photonic and phoxonic mirrors and cavities with superior properties/functionalities for novel multifunctional nanodevices.Wide-range continuous spatial variation of the film composition in lateral compositionally graded epitaxial films requires the development of high throughput measurement techniques for their local and non-destructive characterization with the highest possible spatial resolution. Here we report on the first application of the picosecond laser ultrasonics (PLU) technique for the evaluation of acoustical and optical parameters of lateral compositionally graded film, the Ba"}
+{"text": "This paper examines job satisfaction and psychosocial and physical job quality over the late career in three contrasting national settings: Sweden, Japan and the United States. The data come from an ex-post harmonized dataset of individuals aged 50 to 75 years constructed from the biennial Swedish Longitudinal Occupational Survey of Health , Japanese Study of Ageing and Retirement  and the United States Health and Retirement Study . The job quality outcomes were physical labour, psychosocial working conditions  and job satisfaction. Random effects modelling was performed with age modelled with spline functions in which two knots were placed at ages indicating eligibility for pensions claiming or mandatory retirement. Interestingly, in each country, post-pensionable-age jobs were generally less stressful, freer, and more satisfying than jobs held by younger workers."}
+{"text": "The WHO has replaced its active ageing policy framework developed in 2002 with the new Healthy Ageing framework developed in 2015 and declared the decade between 2020 and 2030 as the Decade of Healthy Ageing. Healthy Ageing framework emphasizes the pivotal role of functional ability (FA) among older adults and conceptualizes that FA can be determined by intrinsic capacity (IC), environments (EN), and their interaction. WHO calls for global research to advance theoretical understanding of Healthy Ageing framework and translate the evidence into policy actions. This symposium provides the latest findings on Healthy Ageing from multi-country studies using real-time data and longitudinal study design. Dr. R\u00f6cke explored daily time-out-of-home and place visit diversity with daily emotional and stress processes in Zurich, using sensor-based and self-reported mobility and activity indicators to capture FA. Dr. Lu investigated the EN and 4-year trajectories of IC and their impact on FA trajectories among older adults in Hong Kong. Dr. Liu explored the longitudinal associations between neighborhood physical EN and depressive symptoms of older adults in Hong Kong and the moderating effects of terrain slope and declining daily activity of living. Dr. Guo investigated the relationship between perceived EN  and mental health and the mediating roles of physical activity and place attachment. Dr. Chan explored neighborhood physical EN and cognition among older people and identified whether this association varies among different older age groups. Based on these findings, this symposium will discuss the future research direction on Healthy Ageing and its policy implication."}
+{"text": "Pre-service health training institutions have a key role in training qualified medical and nursing staff deployable in immunisation programmes, making them capable of addressing complex situations, sustaining routine immunisation and introducing new vaccines and technologies. The incorporation of immunisation-related content into nursing and midwifery education is essential to improve and strengthen immunisation service delivery, disease surveillance, logistics, communication and management practices. Clinical and public health training incorporating learning objectives on immunisation that are specific to the Expanded Programme on Immunisation (EPI), will enable students to develop a firm basis of core knowledge and skills in immunisation. To assist health training institutions in the African Region and to facilitate the systematic revision of EPI curricula, two prototype curricula, one for medical and one for nursing/midwifery schools, were developed by WHO/AFRO, NESI/University of Antwerp and other partners in 2006 and revised in 2015. Kenya Medical Training College (KMTC) has been at the forefront in revising and updating their institutional EPI curriculum for the pre-service Kenyan Registered Community Health Nursing programme based on the EPI prototype curriculum. Building on the successful strengthening of the EPI curriculum, KMTC will now embark on improving education and training for effective vaccine and cold chain management for selected training programmes. The different steps taken by KMTC to strengthen EPI teaching and learning can support other health training institutions who are willing to integrate the content of the EPI prototype curriculum in their own institutional curricula by adapting them to the local context. Pre-service health training institutions are key in training competent medical and nursing staff deployable in immunisation programmes capable of addressing complex situations, sustaining routine immunisation and introducing new vaccines and technologies. Nurse lecturers are tasked to educate and train students on relevant knowledge on the Expanded Programme on Immunisation (EPI), skills and attitudes towards immunisation. Such training should be competency based and integrated throughout the curriculum . StudentTraining needs assessments conducted at health training institutions in 12 target countries in the African Region between 2002-2004, identified gaps in pre-service training, including: incomplete or outdated EPI content in the pre-service curricula; lack of demonstration equipment and up-to-date EPI reference material; insufficient time allocation for EPI theory; as well as insufficient knowledge on current EPI theory and practice of lecturers . SimilarThe incorporation of EPI content into undergraduate training programmes is important for strengthening immunisation service delivery, logistics, surveillance, communication and management practices. Healthcare workers have a central role in maintaining public trust in vaccination through direct communication with the vaccinated person or the caregiver of the child. Therefore, healthcare workers need to be knowledgeable about vaccines and immunisation programmes and have good communication skills. In this way, healthcare workers can contribute to improve public confidence in the immunisation services provided, creating sustained demand leading to high immunisation rates.The knowledge and skills of the healthcare worker can be reinforced through refresher training. Evidence exists that in-service interactive workshops and courses improve the performance of healthcare workers -7, whileTo assist health training institutions in the African Region with the systematic revision of EPI curricula, two prototype curricula, one for medical and one for nursing/midwifery schools, were developed by WHO/AFRO, NESI/University of Antwerp and other partners in 2006 and revised in 2015, and are available in English and French , 9. The The first part of the prototype curriculum describes the exit profile and core competencies required for immunisation service providers, including the EPI manager, disease surveillance officer/epidemiologist, cold chain officer, logistics officer, communication/social mobilization/health promotion officer and data manager/statistician. The expected competencies and skills in immunisation for a newly qualified nurse/midwife and a district EPI nurse are outlined in detail. The second part of the curriculum describes the proposed content topics of the EPI curriculum . Each toThe EPI prototype curricula have been widely distributed to health training institutions within countries of the African Region. In 2011, WHO/AFRO and NESI/University of Antwerp carried out an evaluation in nine African countries to assess the status of introduction of the EPI prototype curricula in health training institutions. A total of 61 health training institutions were visited, including 16 medical schools and 45 nursing/midwifery schools . Kenya Medical Training College (KMTC) was one of the six health training institutions in Kenya that participated in the evaluation. With its network of 71 campuses, strategically located across the country in 45 out of 47 counties, KMTC is one of the leading health training institutions in Kenya, and the driving force advocating for updating EPI curricula at all pre-service nursing/midwifery training institutions in the country. All private and public nurse training institutions in Kenya follow a standard EPI syllabus which has been updated and approved by the Nursing Council of Kenya (NCK) in 2011, incorporating EPI priority areas.Since 2013, the KMTC EPI focal person has been part of the WHO/AFRO working group to revise the EPI prototype curriculum for nursing/midwifery schools, which was finalised in 2015. KMTC was committed to immediately implement the revised curriculum with the support from NESI/University of Antwerp. KMTC management together with the College Curriculum Review Committee supported the EPI focal person to review the institutional pre-service curriculum to incorporate the new content of the EPI prototype curriculum .Following a survey to determine the technical competences  of nurse lecturers in EPI at the different KMTC colleges, a workshop was organised to strengthen the teaching and learning of immunisation within the existing curriculum for the pre-service Kenyan Registered Community Health Nursing (KRCHN) programme. Consensus was obtained on the EPI content to be incorporated in the KRCHN curriculum as guided by NCK and in line with the EPI prototype curriculum. Following consensus on the EPI content, an EPI learning guide to be used by students during the skills laboratory sessions has been developed. In the revised curriculum, the time allocation has been increased from 12 hours to 24 hours EPI theory. Practical training includes 6 hours of demonstrations in a skills laboratory, and an integrated clinical placement of 28 weeks in a Maternal, Child Health and Family Planning Clinic.During the final step, refresher training is organised for all KMTC nurse lecturers, using the recently revised Mid-Level Management (MLM) modules as the standard training materials , in ordeA summary of the different key steps taken for strengthening EPI pre-service training at KMTC is listed here: KMTC participation in the WHO/AFRO and NESI pre-service training evaluation; receipt of evaluation report by WHO/AFRO and NESI; receipt of WHO EPI prototype curriculum; sensitization of KMTC managers on EPI prototype curriculum; sensitization of KMTC curriculum review committee on EPI prototype curriculum; sensitization of NCK on EPI prototype curriculum; adoption of the EPI prototype curriculum content in the Syllabus of the NCK Kenya Registered Community Health Nursing; adoption of the EPI prototype curriculum by the Department of Nursing to be used for teaching content while awaiting due curriculum review process; refresher training organised for pre-service nurse lecturers at KMTC and private institutions, including induction on the EPI prototype curriculum, using MLM training modules; review of KMTC Pre-service Nursing Curriculum. Currently pre-service Immunisation Module includes 24 hours theory, 6 hours Skills Laboratory practical demonstrations and 28 weeks of Integrated Clinical PlacementThe introduction of the revised EPI curriculum presents a good opportunity to strengthen capacity for Effective Vaccine Management (EVM) which is required for routine immunisation and deployment of new vaccines, including COVID-19 vaccine. This will ultimately contribute to maintaining adequate vaccine stock levels, reducing wastage, preventing cold chain breakdown and forecasting for immunisation supplies across Kenyan counties.Building on the experience and successful revision of the EPI curriculum, KMTC in collaboration with partners has initiated action to strengthen pre-service education in effective vaccine management by incorporating EVM, cold chain and immunisation supply content within its curricula for specific health cadres .The benefits of incorporation of EVM content in pre-service education are multiple: (1) Sustainability of capacity building initiatives through local institutions; (2) Increase in the pool of healthcare professionals across cadres with better understanding of EVM to support improvement actions within EPI; (3) Enhanced country ownership for immunisation supply chain; and (4) Improved practices in vaccine management.Increasing efforts have been made in the African Region during the past decade to strengthen the capacity of healthcare personnel responsible for delivering quality immunisation services to the public, by addressing both the pre-service and in-service training needs. While in-service training will remain necessary as new technologies and vaccines are being developed and guidelines formulated, pre-service health training institutions are crucial to deliver high quality training and education to future healthcare staff, as well as to support the in-service training in the country. The importance of health training institutions supporting the national immunisation programme has especially been proven important during the COVID-19 pandemic, when in-service training could be delivered by in-country staff only. With the introduction of new vaccines and technologies, increased complexity of immunisation programmes and current challenges with the COVID-19 pandemic, as well as the ambitious goals set by the Immunization Agenda 2030 , capacitTraining needs assessment in some health training institutions in African countries have indicated gaps in EPI theory and practice;The EPI prototype curriculum can assist health training institutions with revising their institutional EPI curriculum;Few health training institutions have adapted their EPI curriculum.KMTC used the EPI prototype curriculum to strengthen their institutional curriculum;The experience of KMTC outlines the different steps required to strengthen EPI pre-service training;Other health training institutions can learn from the experience of KMTC to strengthen EPI pre-service training."}
+{"text": "Though episodes of lucidity (EL) in Alzheimer\u2019s disease and related dementia (ADRD), reportedly more common near end of life, have significant implications for care, they are poorly understood due to underdeveloped methodological approaches for capturing and measuring these events. This prospective observational study addresses these gaps through audiovisual observation among persons with ADRD surrounding end of life to inform data-driven definitions for EL and distinguish EL from routine fluctuations in ADRD. Audiovisual observation is well-suited to addressing gaps in operationalization of EL, providing an objective data source to assess verbal and nonverbal communication, the primary means through which EL are evidenced. Our study is designed to establish optimal procedures for capturing audiovisual data of targeted populations and timeframes to maximize opportunities for detecting EL. Operationalization of EL will be informed by computational linguistic and behavioral-event coding of linguistic and non-linguistic communication features of EL and associated temporal qualities."}
+{"text": "Cerebral arteries play a crucial role in the regulation of blood flow to the brain to satisfy the demand of oxygen and glucose for proper function of the organ. Physiological cerebral blood flow (CBF) is maintained within a normal range in response to changes in blood pressure a mechanism named Cerebral Blood Flow Auto Regulation (CBFAR). Structure and function of cerebral arteries have an important impact on CBFAR. Several studies in human and animals have showed significant morphological and functional changes in cerebral vessels of aged brain associated with a reduced CBF which is also impaired in cerebrovascular pathology linked to brain diseases. Interestingly, one new emergent aspect is the lifelong Calorie Restriction (CR) as a potential intervention to prevent age-related cerebral artery changes and preserve the health of aging brain. This review summarizes the recent literature on the effects of aging on cerebral artery structure and function and the potential of CR as opportunities for prevention and treatment. Significant structural and functional changes occur in the cerebrovascular system with advancing age, even in apparently healthy individuals. Morphological analysis of cerebral arteries from aging human brain have shown abnormalities in both large  and small  arteries and arterioles \u20133. ArterDepletion of vascular myocytes from the tunica media ,9,10,A switch of myocyte phenotype from the contractile to the synthetic phenotype with loss of contractile properties due to alterations of the vascular wall extracellular matrix Endothelial dysfunction including thinning and reduction of endothelial derived relaxation factors ,13.Small cerebral arteries contribute to CBFAR and age-related impairment, including Cerebral Small Vessel Disease (CSVD) that is strongly associated with stroke, hemorrhage and cognitive decline , 14. In In human and animals, changes of cerebral artery biomechanical properties are associated with aging. Aging induces changes in the structure of mouse Posterior Cerebral Arteries (PCA) and in Parenchymal Arterioles (PAs), demonstrating changes in large arteries and the microcirculation . In partIn PAs of mice, wall thickness and cross-sectional area were larger in old (22\u201324 months) vs. young animals (3\u20135 months)  with an Stable CBF in healthy brain is accomplished by the normal function of the cerebral arteries that dilate or constrict in response to physiological chemical messengers and changes in cerebral perfusion pressure. Aging promotes functional alterations in the cerebral vasculature  with higAlthough limited in number, some studies have investigated the molecular mechanisms underlying aging-impaired cerebral vascular reactivity and suggest age-related changes occurred in both vascular Smooth Muscle Cells (SMCs) and Endothelial Cells (ECs). In SMCs, aging disrupted calcium (Ca2+) signaling by modification of gene expression of ion channels and pumps involved in Ca2+ signaling implicated in the regulation of vascular reactivity . In addiAging also affects the function of ECs, the inner cellular layer of cerebral blood vessels that balances coordination of vasodilation and vasoconstriction for optimal blood flow distribution in the brain. Aging reduces endothelial nitric oxide synthase (eNOS) signaling by potential mediators of vascular dysfunction such as Reactive Oxygen Species (ROS), Poly(ADP-ribose) Polymerase (PARP)  and Rho In summary, aging may impair local vasoregulatory mechanisms intrinsic to the vascular wall of cerebral arteries,  leading Altered endothelium-dependent mediators largely attributed to nitric oxide (NO) and endothelin one-1 (ET1) 2)Changes in ion channels expressedion and activity in both endothelial and vascular smooth muscle cells and 3)Activation of Matrix Metalloproteinase (MMPs) critical for the maintenance of the extracellular matrix organization that impacts vessel stiffness. Together, this Aging-related impairments compromise the regulation of cerebral artery diameter with consequent decrease of CBF blood flow to brain.Several lines of evidence suggest that overeating is a challenge in public health. Therefore, considerable effort has been devoted to determine if Caloric Restriction (CR)-a chronic and coordinated reduction in food intake without causing malnutrition-could prevent the pathophysiological consequences of overeating. Numerous studies mainly in rat and mouse showed that animals with food intake restriction by 30\u201360% live longer and have fewer age-associated diseases compared to animals fed ad libitum . The heaThis brief review underlying the importance of the cerebral vessel integrity as a major determinant of a healthy functional brain. Age-induced vascular dysfunction compromises CBFAR and increases the risk of cerebrovascular disease such as stroke and dementia which are major causes of mortality and morbidity in the elderly. Evidence points to the vascular system as a potential therapeutic target for cerebral vascular diseases in aging. Therefore, it is important to identify interventions that could prevent vascular impairments that occur with advancing age. Lifelong CR reduces the onset of age-related cerebral vascular changes to sustain cerebral vascular integrity critical to preserving brain function in aging and reducing the risk of age- related cerebrovascular disorders.The majority of studies on CR in the literature were carried out on rats or mice, with few studies in human. In addition, most of the studies were conducted in male animals and therefore sex differences are not known. Therefore, future studies are needed to investigate the interactions of age and sex on cerebral vasculature properties in aging and CR. In addition, when age- related cerebrovascular dysfunction starts across the lifespan is also an important area of investigation that may allow early intervention to prevent or postpone the onset of cerebrovascular disease especially with CR. Furthermore, the underlying mechanisms by which CR prevents aging-related cerebral vasculature changes are important to understand. Lastly, future studies should take into account genetic background to identify if personalized caloric restriction would be useful to slow brain aging and to prevent cerebrovascular disease."}
+{"text": "One-third of older adults have a discrepancy between perceived and physiological fall risks or maladaptive fall risk appraisal (FRA). Older adults who report high fear of falling and overestimate their physiological fall risk are less likely to participate in physical activity (PA). Limited data suggest the interrelation between fall risk appraisal, body composition, and objective measured PA. This cross-sectional study examines the feasibility of recruitment and acceptability of Assistive Health Technology (AHT), including the BTrackS Balance System (BBS), Bioelectrical Impedance Analysis (InBody s10), and ActiGraph GT9X Link wireless activity monitor. This study demonstrates the benefits of using AHT to study the associations among FRA, body composition, and PA in older adults. We hypothesize that rational FRA is associated with higher levels of PA and skeletal muscle mass and lower levels of percent of body fat and body mass index. Topics presentation included research protocol and preliminary results."}
+{"text": "Hospital antibiotic stewardship programs (ASP) aim to promote the appropriate use of antimicrobials (including antibiotics) and play a critical role in controlling antibiotic costs and antibiotic-resistant bacterial infection risk, and improving patient outcomes. However, unlike other health care quality improvement intervention programs, the ASP implementation strategies vary among healthcare facilities, and little is known about whether different types of ASP implementation will lead to the shifting of antibiotic drug use from one class to another. We proposed an analytical framework using unsupervised machine learning and joint model approach to 1) develop a typology of ASP strategies in facilities from the Veterans Health Administration, America\u2019s largest integrated health care system; and 2) simultaneously evaluate the impacts of different ASP types on the annual antibiotic use rates across multiple drug classes. The unsupervised machine learning method was used to leverage the structural components in the surveys conducted by the Veteran Affair (VA) Healthcare Analysis and Information group and the Consolidated Framework for Implementation Research experts from Boston University, and reveal the underlying ASP patterns in the VA facilities in 2016. We identified 4 groups in the VA facilities in terms of enthusiasm and implementation level of antibiotic control in our ASP typology. We found the facilities with high implementation level and high enthusiasm in ASP and those with high implementation level but low enthusiasm had statistically significant 30%  and 22%  lower antibiotic use rates in broad-spectrum agents used for community infections, respectively than those with low implementation level and low enthusiasm. However, the facilities with high implementation and high enthusiasm also marginally increased antibiotic use rates in beta-lactam antibiotics . The developed analytical framework in the study provided an approach to the granular assessment of the impact of the healthcare intervention programs and might be informative for future health service policy development.Matthew B. Goetz, MD, Nothing to disclose"}
+{"text": "The historical concept of glia just as the glue of brain tissue has been challenged by the accumulation of concrete evidence showing the multifunctional role of these cells during development and in the adult brain . The braIn addition to the major glial cell types, including astrocytes, microglia, and oligodendrocytes, many region-specific glial cells populate the brain tissue. Bergmann glia (BG) are the principal glia in the cerebellum, outnumbering neurons . These cRetinal M\u00fcller glial (RMG) cells are the principal glial cells of the retina and actively participate in maintaining water and ion homeostasis in the retina. Additionally, RMG cells are very responsive to pathogenic stimuli and undergo extensive morphological and biochemical changes. These reactive RMG cells have been identified in the neuroinflammatory environment of different retinal diseases. The study by Lorenz et al. showed the potential immune-related responses of RMG cells after lipopolysaccharide (LPS) stimulation . Mass spNeuroinflammation is a shared feature of different CNS pathologies, which is regulated mainly by specialized brain immune and inflammatory cells, including astrocytes and microglia. The molecular mechanisms and signaling pathways involved in inflammatory activation and diverse neuroimmune responses of microglia and astrocytes are thought to be context-dependent and are yet to be fully disentangled. Using genetic interaction screening in a yeast model expressing a mutant form of human transactive response DNA-binding protein 43 (TDP-43), Kim et al. identified crucial interacting partners of TDP-43 that play an essential role in the inflammatory activation of astrocytes . IntranuTherapeutic modulation of glial inflammatory activation has exhibited promising effects in numerous neuroinflammatory conditions. In their study, Yamashita et al. exploited the same concept\u2014\u2018inhibition of inflammatory activation of microglia\u2019\u2014in the neuropathic pain model . The autThis SI also includes a series of review articles highlighting the roles of various types of glia in regulating CNS homeostasis and their potential contribution to disease conditions. The existence of structural and functional diversity within the glial population explains the diverse roles played by these cells in a region-specific manner. In their review, Buzoianu-Anguiano et al. shed light on molecular and functional aspects of a group of glial cells, collectively named aldynoglia . They fuC9orf72) mutation-induced pathological mechanisms in ALS and FTD [C9orf72 mutation-induced glial neurotoxicity in ALS and FTD pathology. Glial cell activation is positively correlated with neurodegeneration in C9orf72-related ALS and FTD and thus appears to be a fascinating avenue for further investigation for clinical translation. The last review of this Special Issue by Hwang et al. comprehensively discussed astrocytes\u2019 roles in regulating diverse behaviors through neuronal modulation [The review by Ghasemi et al. covers the chromosome 9 open reading frame 72 (dulation . The regThe articles included in the current SI add much to our comprehension of the involvement of glia in the pathophysiological mechanisms of different CNS diseases. The research articles in this SI have employed a range of in vitro- and in vivo-based experiments that hold the potential for clinical implications. The breadth of the work presented here will enhance our understanding of the neuroimmunological roles of glia in diverse neuropathology, with the hope that these findings may pave the way for the discovery and development of therapeutic strategies for treating these devastating disorders."}
+{"text": "Operating room productivity has always been an area of focus to enhance access for patients and the financial solvency. Usually it takes minimum of 30 minutes between each case when patients are extubated in theater and cleaning process before the next patient. There are several studies published regarding the role, efficacy and complications of nurse led extubation in intensive care and in post-operating care unit (PACU). These studies revealed several factors responsible for the potential airway complications associated with Nurse Led Extubation but the overall incidence of complications was similar to the Anaesthetist Led Extubation.Lean is a set of tools used with principles of six sigma to improve the operating theater efficacy.The training leadership included consultant anaesthetists, nursing chief of operating rooms and chief of nursing staff. Initial extubations were supervised by consultant anaesthetists. Further extubations were supervised by chief recovery nurse of the day, trained and experienced at extubations. At all times anaesthesia consultants and senior anaesthesia NCHDs remained immediately available for any help.To the best of our knowledge our hospital is the pioneer in introducing the policy and guidelines on Nurse Led Extubation in adult PACU.ZM and JT: Drafted policy on Nurse LED Extubation, Nurse Training, and Final Write-up.AG: Co-Author for Policy making, Data collection and Nurse Training.SL: Data Collection, Initial write-up."}
+{"text": "The evolution of pluripotent stem cell-derived retinal organoids (ROs) has brought remarkable opportunities for developmental studies while also presenting new therapeutic avenues for retinal diseases. With a clear understanding of how well these models mimic native retinas, such preclinical models may be crucial tools that are widely used for the more efficient translation of studies into novel treatment strategies for retinal diseases. Genetic modifications or patient-derived ROs can allow these models to simulate the physical microenvironments of the actual disease process. However, we are currently at the beginning of the three-dimensional (3D) RO era, and a general quantitative technology for analyzing ROs derived from numerous differentiation protocols is still missing. Continued efforts to improve the efficiency and stability of differentiation, as well as understanding the disparity between the artificial retina and the native retina and advancing the current treatment strategies, will be essential in ensuring that these scientific advances can benefit patients with retinal disease. Herein, we briefly discuss RO differentiation protocols, the current applications of RO as a disease model and the treatments for retinal diseases by using RO modeling, to have a clear view of the role of current ROs in retinal development and diseases. Over the past several decades, our knowledge of retinal diseases has significantly increased  The chemical modification protocol involves docosahexaenoic acid and fibroblast growth factor 1, which can specifically promote the maturation of photoreceptors in ROs  are the retinal cells in ROs that possess the most details. The outer segments connected cilia and inner segments are all well displayed via transmission electron microscopy , AIPL1  demonstrated that SARS-CoV-2 can infect the retinal cells , photoreceptors and retinal progenitor cells has been used for preclinical cell transplantation (Singh et al. CRX promoter, a AAV2-CRX vector can precisely target a distinct apical lamina of the photoreceptor layer in the RO and function properly after infection (Kruczek et al. The success of AAV-mediated RPE65 gene augmentation therapy encourages the application and research on retinal diseases. The prerequisite for AAV-mediated gene therapy involves the efficient infections of specific target cells (Juttner et al. The other gene therapy strategy involves gene editing of the PSC and subsequent differentiation into the RO. There have been four studies using this approach on patient-derived iPSCs (Buskin et al. Retinal organoids provide optimal platforms for modeling retinal diseases and development. More importantly, via large-scale transcriptome analyses, we are able to address the similarities and differences between the human RO and the human retina to determine how well the present RO models are recapitulating the human retina (Collin et al. The progression from the initial 3D retinal organoid generation and characterization of retinal cells to their development into precise disease model agents has occurred at an accelerated pace. Before the development of ROs, transgenic mice were the main models for studies on retinal development and retinal diseases. In less than 10\u2009years, numerous RO differentiation protocols, bioreactors, retina-on-chip and coculture systems have been developed to improve the efficiency and reality of ROs, which brings us closer to the efficient production of desired retinal organoids that are equipped with vascular systems and immune systems. With the rapid development of the RO system that can mimic the native retina, a promising and well-characterized model for retinal development and retinal disease will be established, which can significantly replace mouse models."}
+{"text": "Objectives: Paid care provided in the home or through community organizations includes important support services for older adults with dementia such as cleaning and personal care assistance. These services could delay the transition to long-term care, but access may differ across sociodemographic groups. This study examined the relationship between paid care and transitioning out of the community among diverse older adults with dementia. Methods: Using data from 303 participants (29.4% Black) with probable dementia in the National Health and Aging Trends Study (2011-2019), subdistribution hazard models estimated the association between receiving paid care at baseline and the probability of transitioning out of the community over the next eight years. Covariate selection was guided by the Andersen model of healthcare utilization. Results: Paid care was associated with lower risk of transitioning out of the community . This effect was similar after controlling for predisposing factors and most prominent after controlling for enabling and need for services factors  and was only evident among Whites. There were no racial differences in the use of paid care, but Black participants were less likely to transition out of the community than Whites despite evidencing greater care needs. Discussion: Paid care services may help delay transitions out of the community. Future research should seek to explain racial differences in access to and/or preferences for home-based, community-based, and residential care."}
+{"text": "Fissurina sp.). The dominants, subdominants and species list of benthic foraminifera changed within the core depth. This image dataset helps to fill the gaps in the practical micropaleontological analysis of benthic foraminifera giving better information for the species identification from the modern and Pleistocene sediments.The article presents an image dataset of benthic foraminifera assemblage in long sediment core AMK-5890 obtained during the 71st cruise of the research vessel Akademic Mstislav Keldysh in summer 2018 from the northwestern Iceland slope in Denmark Strait (North Atlantic Ocean). In the area of study, dense cold water masses of the East Greenland Current from the Nordic Seas contact and mix with warm salty water of the Irminger Current from the North Atlantic Ocean creating specific conditions for the benthic microfauna habitat which reflect forming the lower link of the global thermohaline circulation. The benthic foraminifera assemblages are a reliable indicator for paleooceanographic and ecological reconstructions describing the environments on the bottom in present and past. In the core AMK-5890, the benthic foraminifera assemblage consists of 63 species some of which were combined into one genus (for example,  Value of the Data\u2022This dataset presents high-quality images of benthic foraminifera species in core from Denmark Strait, climatically sensitive area of North Atlantic Ocean located at the junction of the boreal and Arctic regions.\u2022It can be useful in palaeoceanographic and paleoenvironmental studies of Denmark Strait and Iceland shelf.\u2022The data are reused for further studies of recoveries palaeoceanographic conditions of past and Quaternary stratigraphy.\u2022It can help fill in the gaps in images of benthic foraminifera species in the high northern latitudes of the Atlantic Ocean and it is of great methodological importance for micropaleontological studies of Meso-Cenozoic associations of foraminifera.\u2022Image dataset are valuable for micropaleontologists and biologists in better routine species identification of benthic foraminifera in North Atlantic sediments.1- map of the northwestern North Atlantic Ocean showing location of studied sediment core AMK-5890, and modern surface and deep currents in Denmark Strait ;- list of all benthic foraminifera taxa revealed in sediment samples of the core AMK-5890 ;- 6 tables with microphotographs of benthic foraminifera taxa and taxonomic descriptions to them (Phototables 1 to 6).We present:2Akademic Mstislav Keldysh in the summer 2018, the gravity core at the station AMK-5890 retrieved 4.24\u00a0m long sediment sequence on the northwestern slope of Iceland in Denmark Strait. Sediments are presented by alternation of light-brown sandy clay with the predominance of carbonate biogenic material, grey sandy-silty-clay, and brown silty-clay, sometimes with gravel inclusions During the 71st cruise of the R/V Liubov Kireenko: Conceptualization, Investigation, Methodology, Formal analysis, Resources, Writing \u2013 original draft, Visualization, Funding acquisition. Anna Tikhonova: Investigation, Writing \u2013 review & editing, Resources. Nina Kozina: Writing \u2013 review & editing, Resources. Alexander Matul: Funding acquisition, Writing \u2013 review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."}
+{"text": "Oxidative stress, though not really on the driver's seat, continues to play key roles within the pathogenic spectrum of many diseases especially cancer, inflammatory, and degenerative diseases. Thus, reactive oxygen species- (ROS-) mediated tissue injury and redox signaling are intensely investigated in disease conditions and model systems for a better understanding of the pathogenesis and identification of new drug targets.The special issue contains 29 articles which describe the involvement of oxidative stress in various clinical conditions and experimental models of diseases, drug actions, and environmental injuries. We can summarize some of the important concepts and results that have emerged from these studies. In the pathogenesis of AD, a body of evidence links the process of neuroinflammation with the increased production of ROS by microglial NADPH oxidase, and this suggests a potential role of NADPH oxidase inhibitors as disease-modifying agents for Alzheimer's disease. U. Ganguly et al., in their review succinctly evaluated the current state of research on NADPH oxidase inhibitors [1]. The important role of oxidative stress and mitochondrial dysfunction in ALS and positive effects of antioxidants in preclinical trials of this disease have been reviewed by T. Cunha-Oliveira et al.; the authors suggested that oxidative stress-related damage mechanisms could be different in different subtypes of ALS having defined mutations, and thus, specific and targeted antioxidant therapy would be needed for different subtypes of ALS for novel and effective therapeutic interventions [2]. In an exhaustive review on the complex mechanisms of atherogenesis, C. Khatana and coauthors highlighted the special role of oxidized-LDL and the crucial involvement of antioxidant enzymes in this process [3]. The authors also discussed the various therapeutic options including the use of antioxidants and life-style management to combat the problem of atherosclerosis and its complications. A rather unusual but elaborate review on the molecular hydrogen as a multipotential therapeutic agent for a variety of diseases including COVID-19 has been presented by M. Yang et al., with a load of direct and indirect experimental evidence of hydrogen acting as an antioxidative or anti-inflammatory agent or a modulator of mitochondrial functions, cell death pathways, and many other biological processes [4].The research articles contained in this special issue examined a wide range of interesting questions related to redox pathophysiology, and we may mention a few of them here just to indicate the diverse nature of these studies. A. Abbasi and others showed how oxidative stress could be detrimental to cancer cells by causing a loss of ionic homeostasis through alterations in the activities of pumps and channels; hyaluronic acid apparently can be used to optimize and target the cytotoxic effects of oxidative stress on cancer cells [5]. The poor prognosis of acute myeloid leukemia (AML) has been attributed to enhanced ROS production; D. Zhang et al., showed using cell-based and animal studies that azelaic acid could impact against AML by upregulating the peroxiredoxins (Prdxs2/Prdx3) with consequent scavenging of ROS [6]. Likewise, the protection of LPS-induced acute kidney injury and ischemia/reperfusion mediated cardiac damage by dexmedetomidine and Klotho protein, respectively, indicated the therapeutic potentials of these molecules which were partly attributable to their antioxidative functions . An interesting clinical study by S. Ahmed et al. indicated the potentiation of antiviral therapy in patients of hepatitis C by cotreatment with black cumin and ascorbate which decreased the oxidative stress and viral load and improved several clinical parameters [9]. Nrf-2 activators have been under scanner for quite some time as potential drugs for a variety of disease conditions where oxidative stress and inflammation are involved. A significant research paper in this issue attempted to explore the reasons for unexpected toxic side effects of a potent Nrf-2 activator called bardoxolone methyl, and the authors showed that the drug caused severe mitochondrial bioenergetic impairment along with apoptosis and necrosis of endothelial cells in a dose-dependent manner which could be related to its toxicity [10]. There are many other interesting articles in this issue which we would not discuss individually, but together, they send out two important messages. Firstly, oxidative stress affects specific aspects of different diseases or environmental toxicities which could be identified by studies in different experimental models. Secondly, attempts should be continued to develop new drugs targeting oxidative stress which should be safe and of higher efficacy or bioavailability, but in most cases, such drugs, though clinically relevant, would be a part of an add-on or adjunct therapy for a disease condition.Luciano SasoSasanka ChakrabartiElzbieta Miller"}
+{"text": "African Americans are dying from COVID-19 at younger ages than Whites. Social distancing (SD) prevents the spread of the virus, but because of work demands, transportation needs, and living arrangements SD may be difficult for many African Americans, many of whom are experiencing higher unemployment, poverty, food insufficiency, and social isolation. This study will determine if the health of African Americans and Whites are differentially impacted by SD measures. SD rules can increase or decrease health disparities by: (a) directly impacting the symptoms and progression of chronic health conditions; (b) influencing availability of protective factors and exposure to risk factors; and (c) mitigating or exacerbating the effects of sources of disparities. These hypotheses will be tested using data from the Understanding America\u2019s COVID Study. Findings can advance understanding of how public health requirements can reduce or increase health disparities and identify protective factors to facilitate adherence to public health guidelines."}
+{"text": "Begin with managing short-term climate risks to control and elimination activitiesIncorporate climate into monitoring and evaluation of malaria control effortsInvest in monitoring and surveillance systems for climate and malariaIteratively review and update malaria eradication strategiesLong-term investmentsBuild capacity and partnershipsFollowing publication of the original article , it was Furthermore, the Box had been incorrectly formatted in the PDF version, with the last sentence placed outside the box.The original article has since been corrected.The publisher apologizes for any inconvenience caused."}
+{"text": "The section on supportive care for renal impairment in the supplementary materials suggests the preferred drugs or the change in their doses according to renal function.The recent guidelines by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO)MM can affect the kidney function in several ways, either as monoclonal gammopathy of renal significance (MGRS) or as acute kidney injury (AKI) as in light chain cast nephropathy (LCCN). Surprisingly, renal complications in MM are not mentioned throughout the paper.2 was focused on treatment of AKI in symptomatic MM and suggested some therapeutic strategies to improve AKI-associated outcomes. In patients with very low glomerular filtration rate (GFR), besides chemotherapy and use of high-permeability dialysis filters (HCO), the abovementioned guidelines suggest hydration and urine alkalinization with the aim to increase both tubular flow and urine pH to reduce intraluminal precipitation of light chains (LCs). Since loop diuretics increase sodium concentration in urine so favoring the precipitation of LCs, the authors suggest that their use should be limited to cases of severe fluid overload only. Another way to increase tubular flow with low effect on intratubular sodium concentration could be intravenously mannitol, which causes an osmotic diuresis thus reducing the risk of cast formation; the use of mannitol in LCCN has recently been supported by a pilot study.3 Moreover, it may be the only possibility to remove LCs in countries where HCO dialysis filters are not available due to their high costA recent work by the International Kidney and Monoclonal Gammopathy Research GroupAdditionally, if prevention of cast nephropathy is widely considered crucial in the management of MM, the guidelines should emphasize the need of accurate information for all patients with MM on the importance of maintaining high-urine output with neutral pH, avoiding nephrotoxic drugs , and having prompt referral to physicians when possible causes of dehydration (vomiting or diarrhea) occur.The authors have no conflicts of interest to disclose."}
+{"text": "Co-sponsored by the Disasters and Older Adults, Loneliness and Social Isolation, and Rural Aging Interest Groups, five presenters will highlight multiple circumstances regarding the intersection of social isolation or loneliness and the impact of COVID-19. Haverhals and colleagues interviewed veterans and their caregivers to identify the impact of changes in care delivery and social isolation as a result of the pandemic. Findings indicated differences in feelings of isolation among individuals living in their own home or assisted living facilities. Hua et al. examined whether individuals in long-term care communities were lonelier than individuals in the community during the pandemic using data from the NHATS COVID-19 module with higher levels of loneliness reported from individuals living in more restricted communities. Henning-Smith and colleagues explored differences in social activities among rural and urban participants in the COVID-19 Coping Study. Their study provides awareness into the ways rural and urban older adults stayed connected during the pandemic. Peterson et al. examined the effect of COVID-19 on care in Florida nursing homes and assisted living communities and on residents\u2019 anxiety with higher levels of anxiety reported by residents in nursing homes. Using the Coping with Loneliness, Isolation and COVID19 Global Survey, O\u2019Sullivan and colleagues utilized the lens of \u2018place\u2019 to examine factors associated with those experiencing loneliness and/or social isolation during the pandemic with insights from a public health perspective. Collectively, these presenters will provide evidence of the challenges associated with older adults\u2019 social isolation and loneliness throughout the COVID-19 pandemic."}
+{"text": "Growth mixture modeling was used to classify multimorbidity (\u22652 chronic conditions) trajectories over a 10-year period (2006-2016) in the Health and Retirement Study . Race/ethnicity  and social relationship quality  were then used to predict trajectory class membership, controlling for age, sex, education, and wealth. We identified three trajectory classes: initial low levels and rapid accumulation of multimorbidity (increasing: 12.6%), initial high levels and gradual accumulation of multimorbidity (high: 19.5%), and initial low levels and gradual accumulation of multimorbidity (low: 67.9%). Blacks were more than twice as likely to be in the increasing  and high  multimorbidity groups compared with Whites, but there were no significant differences between Hispanics and Whites for either trajectory class . Increments in perceived support were associated with significantly lower risk of membership in the increasing  and high classes , and increments in negative exchanges were associated with significantly higher risk of membership in the increasing  and high classes . These results provide important new information for understanding health disparities and the role of social relationships associated with multimorbidity in middle and later life that may aid in identifying those most at risk and suggesting possible interventions for mitigating that risk."}
+{"text": "Advances in next generation sequencing technologies provide wealth of data on genome variations. Understanding missense mutations is crucial to tackling global health problems related to inherited diseases and the emergence of drug resistance in cancers and infectious diseases. Advancement in research at systems and molecular level, is required to study the impact of mutations that affect both the regulation of gene expression and protein function through changes in protein stability and affinity towards other proteins, nucleic acids, biomolecules and small molecule ligands. High-quality experimental data on protein structure, mutant stability, functional annotations and phenotype-genotype associations in combination with the state of art techniques in artificial intelligence and machine will revolutionise development of highly accurate predictive computational models to study the impact of genetic mutations on human health and disease.Predictive computational models offer an effective alternative to expensive experimental studies of genetic variations. These models can identify potential mutations linked to disease conditions and the emergence of antimicrobial drug resistance. At the molecular level proteins, via their interactions with other proteins and biomolecules, play an important role in many biological processes. The growing data on protein three-dimensional structure, along with variations observed in sequence data, will enable the development of new computational methods and tools to predict the impact of mutations on protein function, stability and interaction thereby aiding in the understanding of the basic mechanisms that govern disease conditions.Turina et al. developed a semi-automatic text-mining tool to extract protein mutant thermostability data from the scientific literature. Feng et al. studied the role of phosphatase and tensin (PTEN) homolog gene mutation in low grade gliomas progression and prognosis. Using patient\u2019s RNA sequencing data, differential gene expression and gene ontology analysis they showed that PTEN mutation promote tumorigenesis and immune cell infiltration. Tan et al. trained a predictor using saturation mutagenesis data to access the impact of point mutations on protein stability and function. Mutants are scored using a statistical potential energy function derived from protein structural data in combination with evolutionary sequence conservation and substitution scores. Using the physicochemical properties of amino acids Savojardo et al. grouped variants linked to human genetic diseases into four types and established mapping between mutations, diseases, and phenotypes through the protein family domains. Tunstall et al. designed an in silico framework to understand pyrazinamide resistance mutation in the clinical isolates of four main M. tuberculosis lineages. Using a combination of genomic features and computational mutant stability and drug affinity predictors to explain differences in modern and ancient lineages within the context of drug resistance. Using molecular dynamic simulations, Nangraj et al. investigated the mutation in pncA gene of Mycobacterium tuberculosis that confer resistance to the first line drug pyrazinamide and explained resistance in term of the changes in protein stability and drug binding site. Prabantu et al. modelled protein structures as network where nodes and the edges correspond to residues and interaction between residues respectively. They showed that the differences between wildtype and disease mutants can be explained by their respective changes in the network both locally at the site of mutation and globally that relate to protein allosteric effects. Birolo et al. analysed both pathogenic and benign variants in haploinsufficient genes and reported that variants significantly perturbing stability (both the stabilising and destabilising) correlate with pathogenicity. Mahlich et al. performed mutational analysis using variant effect predictor on human proteins and its orthologous from 20 species. They analysed the impact of common and rare variants in terms of conservation and also suggested that cross-species variants (CSVs) might be more often neutral than non-CSVs. Bhasin and Varadarajan used large scale mutational scanning dataset to study the mutational sensitivity and substitution preferences at buried and exposed positions. They used mutational sensitivity data and predicted sequence-based accessibility values to identify buried, active-site and exposed non active-site residues. Soto-Ospina et al. aimed to understand the impact of pathogenic mutations in amyloid precursor protein Presenilin 1 that are known to cause Alzheimer\u2019s disease. They used molecular modelling and dynamic simulations to explain the impact of mutations in terms of structural modifications of active site mutant residues found at the catalytic pore. In a focused review, Grace et al. explored the use of molecular docking and dynamics to study resistance mutation in Mycobacterium tuberculosis within the context of anti-tuberculosis drugs.This research topic highlights the recent developments in computational approaches to analysis and predict the impact of mutation on protein stability, function and interaction. Development of accurate protein mutant stability requires the availability of properly curated high quality experimental thermodynamic dataset. To facilitate this, Understanding the impact of genetic mutation is critical to tackle disease and drug resistance. Experimental structures of biomolecules are becoming available at a rapid pace due to the recent developments in the field of cryo electron microscopy. In parallel, the technology development in computing hardware and software has enabled development of robust machine learning models to predict the structure of proteins and its interactions. Both these recent developments complement each other to provide high quality structural data of biological macromolecules and small molecules including drugs. The timing of these recent developments will enable decoding the complex mutational landscape and enable our understanding of the genotype to phenotype relationship, paving way to the achievement of precision medicine."}
+{"text": "Over the past several decades, evidence for cumulative dis/advantage as a regular feature of cohort aging has continued to cumulate, while new questions concerning the underlying dynamics continue to emerge. This paper reviews the accumulated knowledge base, and focused on three recently emerging lines of inquiry that hold great promise for expanding more fully our understanding of CDA processes: 1) the intersection of class stratification and race in the operation of CDA processes, 2) factors accounting for cross-national variations, and 3) the intersection of robust intracohort processed that generate cda with intercohort processes and the impact of historical and social change. These three new directions are briefly discussed."}
+{"text": "While death and dying often occur within or adjacent to the healthcare setting, grief & support of patients at end-of-life (EOL) remain largely within the realm of the family. Given this division of roles, healthcare workers intentionally set professional boundaries that balance their need to be empathetic and compassionate for patient and their families during EOL, while also maintaining a sense of objectivity and detachment which allows them to cope with patient loss and manage the competing demands of their workday. Tensions occur when healthcare workers are required to cross boundaries at EOL, either voluntarily or involuntarily. Using unobtrusive digital ethnography of a publicly accessible online forum for healthcare providers, this research investigates the boundaries set by families and healthcare workers at EOL, and how EOL circumstances sometimes require healthcare workers to cross or violate these professional boundaries. We suggest that the needs of the family at EOL (not necessarily the patient) serve as the catalyst for both boundary crossing & boundary violations for healthcare workers. Our data reveal that (1) boundary setting and training ought to address the patient-physician-family relationship (not just patient-physician), since the family members are such an integral part of EOL; (2) these EOL dynamics apply beyond the physician and should include all healthcare workers . As a result, patient & family centered care may not be fully achieved at EOL due to the ambiguity in the expected roles played by both families and healthcare workers during patient death and dying."}
+{"text": "Life course research emphasizes the importance of considering how early life experiences set individuals on specific trajectories over time with implications across multiple health domains. Life experiences of older Latinos are shaped by where they were born and, for the foreign-born, when they immigrated to the United States. Prior research examining the extent to which age of migration is associated with health has largely been limited to regional studies. To address this gap in knowledge, we use nationally representative data from the Health and Retirement Study to examine associations between age of migration and multiple physical health outcomes among older Latinos residing in the United States. We examine 2010 prevalence and follow-up incidence to 2016 of cardiovascular issues, diabetes, one or more activities of daily living (ADLs), one or more instrumental activities of daily living (IADLs), cognitive issues, and mortality incidence. Preliminary results indicate similar health profiles across Latinos who migrated in early life (<18), during adulthood (18-34), and during later adulthood (35+). Most health profiles were similar among Latino men and women except for prevalence and incidence of experiencing difficulties with at least one ADL. Latino women who migrated in later-adulthood have higher prevalence of ADLs and women who migrated early in life (>18) have higher ADL incidence than Latino men who migrated during the same life course periods. A greater understanding of the how immigrant experiences influence physical health outcomes offers important insights into the development of actionable and culturally appropriate social and health policies."}
+{"text": "Early-life adverse events or childhood adversities (CAs) are stressors and harmful experiences severely impacting on a child's wellbeing and development. Examples of CAs include parental neglect, emotional and physical abuse and bullying. Even though the prevalence of CAs and their psychological effects in both healthy and psychiatric populations is established, only a paucity of studies have investigated the neurobiological firms associated with CAs in bipolar disorder (BD). In particular, the exact neural mechanisms and trajectories of biopsychosocial models integrating both environmental and genetic effects are still debated. Considering the potential impact of CAs on BD, including its clinical manifestations, we reviewed existing literature discussing the association between CAs and brain alterations in BD patients. Results showed that CAs are associated with volume alterations of several grey matter regions including the hippocampus, thalamus, amygdala and frontal cortex. A handful of studies suggest the presence of alterations in the corpus callosum and the pre-fronto-limbic connectivity at rest. Alterations in these regions of the brain of patients with BD are possibly due to the effect of stress produced by CAs, being hippocampus part of the hypothalamus\u2013pituitary\u2013adrenal axis and thalamus together with amygdala filtering sensory information and regulating emotional responses. However, results are mixed possibly due to the heterogeneity of methods and study design. Future neuroimaging studies disentangling between different types of CAs or differentiating between BD sub-types are needed in order to understand the link between CAs and BD. Early life adverse events or childhood adversities (CAs) refer to a wide spectrum of stressors and detrimental experiences including physical, sexual and psychological abuses and parental neglect deeply impacting on a child's wellbeing with potential unfavourable effects on development  for all types of CAs except for parental loss ; recent studies suggested that CAs are significantly associated with the onset of more than 40% of all childhood psychiatric disorders and with more than 25% of adult psychiatric disorders  and other white matter (WM) structures  AND  AND . Preclinical studies and case-report were excluded. A flow diagram illustrating the studies selection process is presented in et al., et al., Of all the included studies, 85% (12 out of 14) explored the neuro-structural correlates of CAs in BD  through magnetic resonance imaging and diffusion tensor imaging. Only a handful of studies (two out 14) explored the functional correlates of CAs in BD. Finally, two studies explored the association between brain-derived neurotrophic factor levels and CAs in BD patients showing that patients with a history of CA are marked by lower levels . These alterations are expressed as volume reductions with only a paucity of studies showing opposite trends (Janiri Several limitations should be considered when interpreting the results of our review. First, studies investigating the association between CAs and neurobiological variations from the norm are cross-sectional and retrospective. Moreover, the magnitude of the observed effects is unclear as none of the studies reported the effect size or the confidence intervals of the results. Lastly, only a handful of studies differentiated between different types of CAs or compared patients' group with and without a history of CAs. Therefore, future studies are warranted taking into account these limitations informing future diagnostic systems and interventions about the exact neurobiological firms of CAs in the BD brain."}
+{"text": "Building human organs in a dish has been a long term goal of researchers in pursue of physiologically relevant models of human disease and for replacement of worn out and diseased organs. The liver has been an organ of interest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replica should contain the multiple cell types found in the organ and these cells should be spatially organized to resemble tissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions. Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development of advance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models described range from single to multiple cell type containing cultures with diverse applications from establishing patient-specific liver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform is advantageous for specific applications and presents its own limitations. This review aims to provide a comprehensive summary of major liver organoid platforms and technologies developed for diverse applications. The liver is one of the largest organs in the human body and is responsible for a number of functions  reconstruction of liver tissue structures in vitro  Stem cell and progenitor organoids which consist of proliferative cells that can be expanded in scale and differentiated to liver cell types; 2) Pluripotent stem cell (PSC) derived liver organoids that include hepatocyte or cholangiocyte organoids, hepatobiliary organoids composed of both parenchymal cell types, and multi-cellular liver organoid that consists of the parenchymal cells and the non-parenchymal mesenchymal, endothelial or immune cells; 3) Bio-engineered liver organoids that engaged the use of cell layering and patterning techniques, together with bio-fabrication and bio-printing technologies to create 3D cultures of single or multiple liver cell types. Each liver organoid system presents its unique advantage such as the ease of adoption , scalability and animal-free components for therapeutics application, and cellular and structural maturity for modeling different aspects of liver disease and injury. In the following sections, we will review major studies in each category of liver organoids.+ adult stem cells from small intestine tissues, which expand as spherical cystic structures embedded in a matrix. This study demonstrates the feasibility of establishing adult stem cells (ASCs) from progenitors in human organs and expanding these patient-derived tissues as mini-organ like structures in culture. Using a similar approach, Clever\u2019s group reported the first liver organoid derived from mouse and human adult liver tissue  generated from fibroblast immortalized with SV40 large T antigen, which inactivates p53 and Rb proteins  which are important for organ homeostasis and tissue response during disease and injury. Ouchi et al. described one of the first protocol to create a PSC-derived liver organoid that consist of both parenchymal and non-parenchymal cell types to model steatohepatitis  organoid  Micro-manipulation of cell culture vessels and matrices, 2) microfluidics culture system for fluid exchange and 3) three dimensional scaffolds and bio-printing of matrices and cells. Bio-engineers employ one or more of these strategies as well as different sources of liver cell types  to create different bioengineered 3D liver culture system  that directs cellular adhesion   is the most widely adopted and ideal therapeutic solution for end-stage liver failure and is projected to continue as the gold standard  The absence of functional vascular system to deliver nutrients and air, and facilitate metabolite and waste exchange for centimeter size organoids, 2) various cell types lacks spatial organization and poorly resemble the liver tissue architecture, 3) immature cell types with poor liver functions and 4) dependence on matrices with animal components such as Matrigel for 3D culture. Importantly, any approach to reconstruct the organ likely need to tackle multiple of these challenges at the same time. For instance, in constructing a functional vascular system, the required spatial organization of LSEC in the sinusoid, as well as mature functional LSC features such as membrane fenestration need to be achieved in parallel. Similarly, hepatocytes need to be spatially aligned, exhibit polarity to form functional transport networks, and perform various metabolic and detoxification functions. Overcoming these challenges likely require combinations of approaches such as the use of engineering platforms to introduce media flow and achieve precision placement of cells, and stem cell-based differentiation approach to generate sufficient quantities of various liver cell types from a single donor. The potential of such combinatorial approach was evident in the study by Yanagi et al. where the group employed 3D bio-printing technology to create liver bud culture  with retinal pigment epithelial (RPE) cells. Employing a combination of hydrogels, microfluidics compartments, flow system and PSC-derived RPE and RO, the team generated a polarized layer of RPE that recapitulated its function as a blood-retinal barrier between the retinal organoids and circulation system. The group demonstrated that this setup significantly improved the inner and outer retinal segment formation and integrity, while enabling a direct interplay between the RPE and photoreceptors to recapitulate events such as the phagocytosis of the photoreceptor outer segment by the RPE. Overall, these two studies highlighted the advantages of organoid cultures on microfluidic system which includes the introduction of a functional vascular structure, greater control of organoid size and growth, and precision placements of cells and organoids to recapitulate physiological structures. In the near future, we would likely witness the development of similar liver organoids-on-a-chip which will provide solutions to the highlighted challenges for applications in liver disease modelling and regenerative medicine.We are witnessing an increasing trend in the integration of bio-engineering approaches and organoid culture techniques to create more physiological in vitro organ models  organoids was recently established by the HPB Organoid Consortium (formed by over 60 experts from 16 countries) (Marsee et al."}
+{"text": "Despite the rising prevalence of dementia and the high cost and complexity of care for people with dementia, most dementia care is provided at home by informal caregivers who are not clinically trained. Building caregiver readiness and knowledge of dementia is key to supporting quality care and desirable health outcomes, such as preventing falls and reducing nursing home admissions. We sought to determine and compare the impact of two interventions\u2014Resilient Living with Dementia (RLWD) and Care of Persons with Dementia in their Environments (COPE)\u2014and of their combined delivery (both RLWD and COPE) on increasing caregiver readiness and knowledge of dementia. Between January 2019 and March 2021, 77 caregivers of people with dementia in Connecticut participated in RLWD and/or COPE and completed the Alzheimer\u2019s Disease Knowledge Scale (ADKS) and the Preparedness for Caregiving Scale (PCGS) at baseline and at four-month and ten-month follow-ups. Analyses were conducted to compare outcomes by intervention(s). From baseline to four months and to ten months, we observed statistically significant (p < .05) improvement on the ADKS among participants in RLWD, and on the PCGS among participants in COPE and among participants in RLWD. The most substantial impact on PCGS was observed among participants in both COPE and RLWD. No improvement in the ADKS was observed among participants in only COPE, but ADKS improvement was observed at four months among participants in COPE and RLWD. Findings suggest that the benefits of COPE and RLWD for building dementia caregiver readiness are complementary and mutually reinforcing."}
+{"text": "Peer support is rapidly being introduced into mental health services internationally, yet peer support interventions are often poorly described, limiting the usefulness of research in informing policy and practice. This paper reports the development of a peer support intervention that aims to improve outcomes of discharge from inpatient to community mental health care. People with experiential knowledge of using mental health services\u2014peer workers and service user researchers\u2014were involved in all stages of developing the intervention: generating intervention components; producing the intervention handbook; piloting the intervention.Systematic review and expert panels, including our Lived Experience Advisory Panel, identified 66 candidate intervention components in five domains: Recruitment and Role Description of Peer Workers; Training for Peer Workers; Delivery of Peer Support; Supervision and Support for Peer Workers; Organisation and Team. A series of Local Advisory Groups were used to prioritise components and explore implementation issues using consensus methods, refining an intervention blueprint. A peer support handbook and peer worker training programme were produced by the study team and piloted in two study sites. Feedback workshops were held with peer workers and their supervisors to produce a final handbook and training programme.The ENRICH trial is registered with the ISRCTN clinical trial register, number ISRCTN 10043328, and was overseen by an independent steering committee and a data monitoring committee.The online version contains supplementary material available at 10.1186/s13104-021-05735-0. An increasing number of randomised controlled trials of one-to-one peer support in mental health services have taken place recently, with growing evidence of the effectiveness of peer support in improving self-reported recovery and empowerment outcomes . Peer suThe importance of experiential knowledge of mental distress and of using mental health services in informing the development of peer support initiatives has been indicated . ExperieWe conducted a randomised controlled trial of peer support for discharge from inpatient mental health care (ENRICH), to test the effectiveness of a peer worker intervention in reducing readmission post-discharge . This paThe intervention was developed in three sequential stages, illustrated in Fig.\u00a0Several members of the research team identified as service user or survivor researchers, making explicit use of experiential knowledge in their work, or worked as peer workers. A Lived Experience Advisory Panel (LEAP) and Local Advisory Groups (LAG) at each study site also included people with experiences of using mental health services and peer support. The composition and role of these groups in the intervention development process is indicated in Table An intervention mapping approach was used to generate a list of components that might comprise the intervention . We emplSystematic review A systematic review of one-to-one peer support in mental health services was undertaken . The full method for the search is described in a systematic review and meta-analysis of randomised controlled trials of peer support [Expert workshops Workshops were held with the LEAP and the research team to suggest potential components for the intervention. A third workshop was held with five members of the research team  to consider how a taxonomy of Behaviour Change Techniques (BCT) [es (BCT)  might bePrioritising components LAGs were convened in each of six study sites . Names and descriptors of components identified in Stage 1 were printed on cards and prioritised using a closed card-sorting approach to consensus building [building . In thisProducing and refining the intervention \u2018blueprint\u2019 Using output from the LAGs we produced a blueprint of the intervention in the form of a flow diagram, specifying the processes of recruiting peer workers, training, delivering the intervention, and support received by peer workers. The blueprint included all components retained for discussion so that local implementation issues could be considered.In a second round of meetings LAGs were presented with the flow diagram and invited, using well-established talk-aloud approaches , to \u2018walDrafting the intervention handbook The output of LAG meetings was used to draft the ENRICH intervention handbook and peer worker training programme. Development of the intervention was also informed by our \u2018peer support principles\u2019 [nciples\u2019 . FurtherA pilot randomised controlled trial of the intervention was conducted in two study sites to test feasibility of delivering trial procedures and implementation of the intervention . FollowiA total of 3800 studies were identified in the literature search, of which 97 were included in the review, 85 peer-reviewed and 12 from grey literature (see Additional file Prioritising components Following the first round of LAGs, six components were discounted, 19 added as core components (see Table Producing and refining the intervention blueprint The flow diagram used in the walkthrough exercises in the second round of LAGs is shown in Additional file Drafting the intervention handbook A detailed handbook was produced specifying a full set of procedures defining peer worker and the peer worker coordinator roles, recruitment process, training, support and supervision for peer workers, and how the peer support is delivered in hospital and in the community (see Table An eight-day, manualised training programme was developed, underpinned by ten knowledge and skills sets derived from components prioritised to the training domain in Stage 2, and the peer support principles . The resFive peer worker coordinators involved in delivering training at both pilot sites attended a feedback workshop, with one peer worker coordinator providing individual feedback. Four of five peer workers at one site attended a workshop. Feedback was used to make amendments to the training and aspects of the handbook on recruitment of peer workers and post-training support (see Additional file This paper reports a rigorous process of intervention development, resulting in production of a detailed handbook and manualised training programme for peer support for discharge from inpatient mental health care. We used an intervention mapping approach  that incDevelopment closely followed the Medical Research Council complex interventions guidance , includiAdditional file 1. Flow diagram of inclusion of studies in the systematic review.Additional file 2. Candidate components for the peer support intervention.Additional file 3. Flow diagram used for walkthrough exercise in second round of Local Advisory Groups.Additional file 4. The ENRICH training matrix.Additional file 5. Feedback from intervention pilot workshops."}
+{"text": "Activity engagement is a major component of well-being in later life. However, very few studies have focused on older immigrants who are often at risk for social isolation and psychological distress. We aim to map the pattern of activity engagement and examine its variations in relation to immigration-related factors and social aspects of neighborhoods in a representative sample of older Chinese immigrants. We used data from the Population Study of Chinese Elderly in Chicago (PINE), a population-based epidemiological study of US Chinese older adults that were conducted between 2011 and 2013 . Latent class analysis and multinominal regression analysis were conducted to identify activity engagement patterns and examine the associated factors. Four patterns of activity engagement were identified: restricted (15%), diverse (31%), informal social (32%), and community-based social (21%). Acculturation and family-oriented immigration differentiated the restricted from the diverse class membership. Positive attributes of social environment measured by social network size, positive social support, neighborhood cohesion, and sense of community were associated with the probabilities of class membership relative to the restricted class. Findings point to the importance of positive attributes of social environment in enhancing engagement with life among older Chinese immigrants. Efforts are needed to assist the vulnerable restricted group and recent older immigrants while meeting the demands of older immigrants who are less educated and less acculturated. Creating a supportive environment is important to provide information, access, and resources needed for activity engagement in the marginalized minority aging populations"}
+{"text": "The authors regret that the funding information was incorrectly shown in the acknowledgements section of the original manuscript. The corrected funding acknowledgement is as shown below.This work was supported by Swedish research counsel VR (grant 2016-05904), Swedish research counsel FORMAS (grant 2016-00908), the Estonian Research Council grant PRG627, and the Estonian Centre of Excellence project TK141.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."}
+{"text": "In contrast, the primary degradation products of highly branched isoprenoid alkenes possessing more than one trisubstituted double bond, alkenones, carotenoids and polyunsaturated fatty acids, appear to be too unstable with respect to secondary oxidation or other reactions to serve for quantification in environmental samples.This paper reviews applications of gas chromatography-mass spectrometry techniques for the characterization of photooxidation and autoxidation products of lipids of senescent phototrophic organisms. Particular attention is given to: (i) the selection of oxidation products that are sufficiently stable under environmental conditions and specific to each lipid class and degradation route; (ii) the description of electron ionization mass fragmentation of trimethylsilyl derivatives of these compounds; and (iii) the use of specific fragment ions for monitoring the oxidation of the main unsaturated lipid components of phototrophs. The techniques best geared for this task were gas chromatography-quadrupole-time of flight to monitor fragment ions with very high resolution and accuracy, and gas chromatography-tandem mass spectrometry to monitor very selective transitions in multiple reaction monitoring mode. The extent of the degradation processes can only be estimated if the oxidation products are unaffected by fast secondary oxidation reactions, as it is notably the case of \u2206 Botryococcus Braunii . In. InBerkeh oxygen . Consequ HBI III . Howeverm/z 213.1670 corresponding to \u03b1-cleavage relative to the TMS ether group . If. If1O2 bt leaves , it may t leaves  and is cocesses)  to be us5-sterols, MUFAs, pentacyclic triterpenes and dehydroabietic acid) of phototrophs. The author hope that it will contribute to a better consideration of photooxidative and autoxidative processes almost ignored so far in the literature when studying the degradation of autotrophic organisms in marine and terrestrial environments.In this review, a focus was given to the selection and characterization of stable and specific tracers of photooxidation and autoxidation of lipid components  oxidative stress of specific phototrophic organisms; (ii) paleoenvironmental changes of the conditions of sedimentation (oxic or anoxic); (iii) abiotic alteration of paleoproxies in oxic environments; (iv) environmental problems related to ozone depletion, and (v) abiotic degradation of permafrost released under the effect of global warming .In the future, a special attention should be given to the detection of oxidation products of alkenones and HBI alkenes  sufficiently stable and specific to act as tracers of oxidative alteration of these proxies in oxic environments (water column of oceans and oxic layer of sediments). MALDI-MS and IM-MS techniques, which allow simultaneous characterization of all molecular species in biological tissues and reduce sample preparation artifacts arising from extensive purification procedures , seem toNICI GC-MS, HPLC-MS and IM-MS techniques should be also used to give evidence of the presence of isoprostanoids resulting from PUFA oxidation in environmental samples. Due to the very high reactivity of PUFA towards photooxidation and autoxidation processes, such compounds could be very sensitive tracers of the early stages of oxidative damages."}
+{"text": "At study start-up, the sIRB PM can handle complicated communications among sites and the IRB at the same time the lead site is responsible for many other administrative tasks related to start-up. By absorbing the workload of IRB approval for multiple sites, the sIRB PM provides the lead site more capacity to handle other essential tasks.translates new terminology and facilitates processes that are new for sites.The sIRB PM OBJECTIVES/GOALS: Navigating the NIH Single IRB Policy has been challenging for investigators, study teams, and Human Research Protection Programs (HRPP). In response, the Indiana Clinical and Translational Sciences Institute (CTSI) created an innovative Single IRB Project Manager role (sIRB PM), uniquely placed within the Indiana CTSI. METHODS/STUDY POPULATION: The Single IRB Project Manager role was created in 2018 by the Indiana CTSI in response to the NIH Single IRB Policy for Multi-Site Research. The role of the sIRB PM is to serve as a liaison between the Indiana University HRPP, lead site, coordinating center, and participating sites when Indiana University serves as the Single IRB. This model has proven useful to both the IRB and lead site, notably in the following ways:IRB staff by allowing them to fulfill their duties of screening and review while leaving some of the reliance organization to the sIRBPM.Lead PI by allowing them to focus on conducting the research instead of the many administrative tasks required for single IRB review.Participating sites by having a liaison to enter their amendments and reportable events into an otherwise closed IRB software system.All parties by having the sIRB PM manage document organization, storage, and distribution study-wide.RESULTS/ANTICIPATED RESULTS: Early assessment of this program is predominantly positive. The sIRB PM currently supports 24 external sites. In an NIA-funded 13 site study, all sites were added within 9 months of initial IRB approval of the protocol. This role fills a gap that benefits:DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI sIRB PM role effectively shifts administrative work caused by the sIRB mandate by merging research coordinator experience with regulatory experience while building upon an existing strong relationship with the HRPP. Future focus is on process education, standardizing pricing structure, and ensuring sufficient budget support in grants."}
+{"text": "Women with premenopausal bilateral oophorectomy (PBO) are at increased risk for physical function (PF) declines. This study investigated the relationships of field-based physical activity measures with clinical PF and strength parameters in post-menopausal women with and without PBO. Women with  and without  PBO performed PF and strength tests , leg and chest strength), and wore ankle accelerometers for 7 days . Age, BMI, step count and loading index were entered into stepwise multiple regression to identify significant predictors of PF and strength parameters. Step count was a predictor of SPBB score in both groups. In women without PBO, step count was a predictor of walking speed; loading index was a predictor of leg strength; step count and loading index were predictors of distance; and step count and age were predictors of chest strength. For PBO women, loading index and BMI were predictors of walking speed and distance; BMI was a predictor of leg strength; and there were no predictors of chest strength. These data suggest while field-based physical activity was strongly and positively associated with clinical PF and strength measures for women without PBO, BMI was a dominant negative factor for PF in women with PBO. Future work will include a larger sample size and additional confounders to further elucidate underlying factors of reduced PF and mobility after PBO."}
+{"text": "The negative impacts of stress on older adults\u2019 well-being are well documented, and social integration is posited as protective against such detrimental effects. Previous research illustrates the stress-buffering effect of social relationships on both physical and mental health, such as depressive symptoms, in older adults. The purpose of this study was to expand on prior findings by investigating the longitudinal stress-buffering effect of various dimensions of social integration on depressive symptoms among an older sample. Four waves of data were drawn from the Social Integration and Aging Study, including 416 older adults (ages 60-100). Subscales of the Social Integration in Later Life Scale measuring frequency and satisfaction with social ties and community interaction were used to assess distinct dimensions of social integration. Multilevel modeling demonstrated that two facets of social integration\u2014satisfaction with social ties and frequency of community interaction\u2014moderated the relationship between perceived stress and trajectories of depressive symptoms over time. Participants who reported high levels of stress reported fewer depressive symptoms if they had high satisfaction with social ties and high frequency of community involvement. Interestingly, frequency of contact with social ties and satisfaction with community interaction did not similarly buffer negative effects for depressive symptoms. These findings indicate the value of remaining actively engaged in the community and maintaining meaningful relationships as older adults age. Future research should investigate programs to foster relationships and engagement between older adults and their communities, with particular consideration of populations at a greater risk for isolation."}
+{"text": "The research was conducted between January 22 and February 25, 2021. The data was collected by self-administered questionnaires mailed to the participants at 800 care management centers and comprehensive community support centers in Osaka City. The centers were randomly selected. The response rate was 19.1%. The independent variables were: obtaining the qualification of a Senior Care Manager (SCM), who was a qualified person that acquired advanced knowledge and skills in care management by advanced training; experience years in Social Work (SW); experience years in care management; experiences in training programs for team approach; and experiences in training programs for supporting Old Public Assistance Recipients (OPAR). The dependent variables were the categorized contents in the Care Management Practice for old public assistance recipients. They were: Care planning and Implementation (CI); Assessment; Financial Support and Evaluation (FSE); Contract and Explanations in care management; Coordinating Informal support and Formal services in Care planning; and Arrangements in Financial supports for Formal service costs. The Structural Equation Modeling was performed for the examinations of the relationships. As a result, the goodness of the fit indices was acceptable, and we retained the models. In correlational analyses, CI and Assessment were significantly correlated with SCM (p<.05). FSE was significantly correlated with SW (p<.001) and OPAR (p<.05). In conclusion, the results implied that advanced qualification of a Senior Care Manager and a specified training program for supporting old public assistance recipients were effective in providing appropriate care management services."}
+{"text": "Preparedness for possible nuclear terrorism is important and possible, multiple parts for preparedness are in place.The current state of acute radiation syndrome (ARS) does not substantially differ from the management of pancytopenia in other settings, such as after treatment with myelosuppressive chemotherapy.HSCT patients have a high likelihood of severe dysbiosis early after transplantation which is mediated by broad spectrum antibiotics and GvHD itself while real decontamination is rarely achieved.Microbiota modulation offers a new option for treatment or even prophylaxis of GvHD.The number of patients transplanted using Haplo-HSCT is increasing consistently in Europe and United States.Haplo-HSCT with the use of PTCy for GVHD prophylaxis, allows low incidence of grade III to IV acute GVHD, chronic GVHD, and comparable survival with HLA-matched unrelated and cord blood transplantation.Worldwide radiation accidents are rare, however we learned from the past that these events ask for serious planning in the health care system.. Nuclear accidents in the Chernobyl (1986) and Fukushima (2011) power plants demonstrated that we should draw the attention of the real risk of radiation accidents to the health care. In his presentation Dr Chao will elaborate on the acute radiation syndrome (ARS) in humans. Efficient triage to identify victims without a lethal dose of irradiation who can be rescued is obligatory. On the other hand, the current management of ARS does not differ a lot from the management of pancytopenia in other settings. Extensive triage algorithms and appropriate standardized operation procedures are currently available to improve survival in these victims.Prof E Holler will focus in his lecture on new insights concerning the changes in the microbiome by using antibiotic prophylaxis that are regularly applied in SCT to prevent infectious complications and GVHD. In contrast, using these antibiotics we induce a massive loss of diversity (dysbiosis) which was associated with an increased risk of GVHD and late transplant related mortality. New molecular sequencing techniques demonstrate not only the loss but also the skewing of the microbiome towards an abundance of single pathogenic bacteria, especially anaerobic species. Fecal microbiota transfer (FMT) may play an important role to restore the diversity of the microbiome.The recent introduction of new conditioning regimens and graft manipulation techniques have boosted the implementation of haplo-identical stem cell transplantation and offers better chances of survival in this patient category. Dr Ruggeri will talk in her presentation about the two most frequent used conditioning regimens that changed the world of haplo-identical stem cell transplantation, based either on the use of post-transplant cyclophosphamide (PTCy) or on anti-thymocyte globulin (ATG). She will also discuss different stem cell sources (bone marrow vs PBSC), the intensity of the conditioning regimens (RIC vs MAC), new complications and challenges we have to deal with."}
+{"text": "The GWEP at the University of Rochester (New York) has an established network of nursing homes participating in Project ECHO. This ECHO hub includes geriatric medicine, psychiatry, pharmacy, aging services network and the Alzheimer\u2019s Association focusing on best practices in geriatric mental health and dementia care. With the COVID-19 pandemic, this infrastructure quickly pivoted to expansion of 80 facilities and the addition of expertise in medical direction, trauma informed care, and infectious disease. A stress first aid training module was developed in partnership with Ithaca College and the National Center for PTSD to support front line nursing home workers. Dementia care experts contributed to practical problem-solving in addressing social isolation and mental health. Work now is focusing on vaccination and how to best support trauma-informed needs of residents with dementia."}
+{"text": "Primary care practices have a robust capacity to screen older adults for falls risk and refer them to evidence-based falls prevention programs delivered by Community Based Organizations (CBOs). However, due to a difference in the culture and nature of the work done in these two systems of care, there is often a lack of coordination and communication. Dartmouth has worked to bridge this gap for the past five years through our Health Resources and Services Administration (HRSA)-funded Geriatric Workforce Enhancement Program (GWEP). GWEP goals include the promotion of Age-Friendly Health Systems by focusing on the 4 Ms: What Matters Most, Medication, Mentation and Mobility. GWEPs commonly operationalize the Mobility component via falls risk screening and prevention programs. Though CBOs are well suited to deliver falls prevention programs, implementing, disseminating and sustaining community-based falls prevention programs in an environment of cost containment, limited funds for community-based services and workforce issues is challenging. Previous Administration for Community Living (ACL) grant funding enabled us to develop the Dartmouth Falls Prevention Training Center (D-TC) using our expertise in training and community-based implementation of evidence-based interventions. The D-TC offers training and implementation support to primary care and CBOs on screening, referring and capacity-building for falls prevention programs. We will discuss challenges and successes implementing the Dartmouth falls prevention model with two additional GWEP grantees, Baystate and the University of Rhode Island. Benefits of leveraging ACL and HRSA funding to achieve synergistic goals to reduce falls in older adults will be explored."}
+{"text": "Commun., 2018, 54, 12234\u201312237.Correction for 'CuAAC click chemistry for the enhanced detection of novel alkyne-based natural product toxins' by Edward S. Hems  The authors regret that The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."}
+{"text": "Background: Nursing in the United States of America is an aging workforce. This study sought to better understand the lived experience of aging nurses. Because nurses work in systems where other forms of interpersonal power dynamics may influence internalized and external stereotype an approach based on intersectional theory was applied. Methods: A qualitative thematic narrative analysis of an existing data set of first-person digital stories in the Nurstory project, authored by a group of nurses, was the data source. An emergent coding method was applied. The collection of five digital stories were analyzed. Results: All stories were first person accounts of experiences that represented their internalized reflections and elements of ageism in how their age interacted with their work environment. Dominant themes included: 1) Role constriction 2) Strength 3) Tired and (re)Tired 4) Age perceived and 5)Loneliness. Conclusions: These aging nursing stories add to the contextual layers of the aging healthcare workplace and aging nursing workforce. These individual experiences offer a nuanced understanding of the internalized responses to aging and ageism. These stories highlight socially constructed and socially reinforced attitudes that are complicated by the personal and occupational expectations of nurse\u2019s work, their role and embedded hierarchies in healthcare. Stories such as these are important individual and collective indicators of lived experiences that offer a deeper understanding into the intersections of social identity and aging, that when listened to, can offer insight and a way forward in addressing the stereotype, discrimination and social inequities of ageism."}
+{"text": "Dear Editor,It has been over a decade since the initial US Food and Drug Administration (FDA) approval of Transcranial Magnetic Stimulation (TMS). The technology was first approved for treating Major Depressive Disorder (MDD) in adults who have not responded satisfactorily to prior antidepressant medications in 2008 using the Neuronetics Neurostar System (DEN070003). Since then, refinement and optimization of TMS has paved the way to new and emerging technology that improves and broadens the clinical utility of TMS \u2013 such as pulse train protocols , neuronavigational systems, and electromagnetic coil technology. Alongside ongoing clinical trials, the approval of TMS therapies by the FDA has underpinned clinical adoption in the US. Here we summarize FDA regulatory milestones for TMS and provide a visual timeline of these approvals in Following the 2008 FDA approval of TMS for depression, the Nexstim eXimia NBS System was the first device FDA-cleared for cortical mapping (K091457) under the 510(k) pathway in 2009. Following this clearance, the Nexstim NBS System 4 was subsequently FDA-cleared for cortical mapping in 2012 with the addition of NEXSPEECH for localization and assessment of cortical areas of speech for pre-procedural planning (K112881).The BrainsWay Deep TMS was cleared in 2013 for the treatment of depressive episodes in patients suffering from MDD who have failed to achieve sufficient improvement from prior antidepressant medication (K122288). This same year the eNeura Cerena System become the first cleared for acute treatment of pain associated with migraine with aura (K130556), using a handheld and delivered with minimal training. The following year, in 2014, eNeura was cleared for a portable device for treatment of migraine headache with aura with Spring TMS (K140094).2 System (K143531). Tele-EMG\u2019s Neurosoft TMS (K160309) received clearance for the same indication a year later.Moving into 2015, the field saw an expansion of two additional TMS devices which received clearance for the treatment of MDD in patients who have failed to receive improvements from prior antidepressant medication: Tonica Elektronik (Magventure)\u2019s MagVita TMS (K150641) and Magstim\u2019s RapidAside from MDD, the next psychiatric condition that was FDA-approved was obsessive compulsive disorder (OCD). With the de novo pathway, BrainsWay\u2019s Deep TMS System became the first to receive FDA approval as an adjunct for the treatment of OCD in adults in 2017 (DEN170078). The Nexstim Navigated Brain Therapy System 2 (K171902) was cleared in the same year for treatment of MDD in those who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode. Also cleared in 2017 by FDA regulation was the eNeura Spring TMS (K162797) for both acute and prophylactic treatment of migraine headache.New pulse parameters, such as theta burst stimulation have also demonstrated utility in improving TMS therapeutic effects. The first device receiving clearance for the intermittent Theta Burst Stimulation (iTBS) protocol was the Tonika Elektronik (Magventure) Mag Vita TMS Therapy System with Theta Burst Stimulation (K173620) in 2018 for the treatment of MDD in adults previously failing to improve symptoms with antidepressant medication. Mag & More also received clearance for the Apollo TMS System (K180313) for the same indication that year.The following year, two more devices received clearance for the iTBS protocol. Magstim\u2019s Horizon TMS Therapy System with Navigation (K183376) for MDD added StimGuide for coil positioning using scalp landmarks, in addition to the iTBS protocol. Nexstim\u2019s NBT System 2 (K182700) for MDD also added iTBS treatment capabilities. Also in 2019, the eNeura Spring TMS (K182976) expanded its indications for acute and prophylactic treatment of migraine headaches in adolescents and adults. The same year, Axilum Robotics\u2019 TMS-Cobot TS MV (K182768) indicated for spatial positioning and orientation of the treatment coil of the MagVita TMS System received clearance. The de novo request by Neuronix for the neuroAD Therapy System (DEN160053) for the treatment of Alzheimer\u2019s Disease was denied in 2019.Neuronetics added the iTBS protocol with Neurostar Advanced Therapy with NeuroBurst (K201158) for the treatment of MDD in 2020. Tonica Elektronik also received clearance for the MagVenture TMS Therapy (K193006) for adjunctive treatment of OCD the same year. The Soterix Medical Neural Navigator (K191422) received clearance in 2020 as a neuronavigation system guided by MRI-based measurements for accurate positioning of the treatment coils. BrainsWay\u2019s Deep TMS System (K200957) became the first to be cleared as an aid in short-term smoking cessation for adults in 2020. Finally, the clearance of BrainsWay\u2019s Deep TMS System expanded the technology\u2019s indications to include the treatment of depressive episodes and decreasing anxiety symptoms for those who may exhibit comorbid anxiety, previously failing to achieve satisfactory improvements with antidepressant medication for MDD (K210201).The TMS field has grown substantially over the past two decades, moving from promising research findings to numerous FDA-approved medical devices with broad ranging treatment utility in neurological and psychiatric disorders. Several new indications such as OCD, anxiety comorbid with MDD, and smoking have emerged. Based on this record and ongoing efforts to enhance TMS technology and explore new treatment indications, further meaningful advances are expected."}
+{"text": "We thank Prof. Aksu for this valuable and well-balanced discussion on the possible effect of ablation of atrial ganglionated plexuses (GPs) on the QT interval.Conflict of interest: none declared."}
+{"text": "This review compares the molecular mechanisms of stem cell control in the shoot apical meristems of mosses and angiosperms and reveals the conserved features and evolution of plant stem cells.Physcomitrium (Physcomitrella) patens and Marchantia polymorpha, are emerging as attractive model species to study the conserved features and evolutionary processes in the mechanisms controlling stem cells. Recent studies using these model bryophyte species have started to uncover the similarities and differences in stem cell regulation between bryophytes and angiosperms. In this review, we summarize findings on stem cell function and its regulation focusing on different aspects including hormonal, genetic, and epigenetic control. Stem cell regulation through auxin, cytokinin, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) signaling and chromatin modification by Polycomb Repressive Complex 2 (PRC2) and PRC1 is well conserved. Several transcription factors crucial for SAM regulation in angiosperms are not involved in the regulation of the SAM in mosses, but similarities also exist. These findings provide insights into the evolutionary trajectory of the SAM and the fundamental mechanisms involved in stem cell regulation that are conserved across land plants.The establishment and maintenance of pluripotent stem cells in the shoot apical meristem (SAM) are key developmental processes in land plants including the most basal, bryophytes. Bryophytes, such as  Physcomitrium (Physcomitrella) patens (P. patens) and Marchantia polymorpha (M. polymorpha) have greatly helped our understanding of the evolution of plant stem cells.The establishment of the basic architecture in the shoot system depends on the activity of the shoot apical meristem (SAM)  growth (protonemata) to the three-dimensional (3D) growth of the gametophore Moody . Mosses The existence of both the sporophytic apical cell and the gametophytic shoot apical cell is attractive in the study of the evolution of the sporophytic SAM. Traditionally, there are two paleobotanical hypotheses to explain the evolution of the sporophytic SAM Haig . One hypP. patens and M. polymorpha   treated with auxin and the defects were further strengthened by application of exogeneous auxin , an auxin efflux carrier, is critical for the regulation of auxin distribution in angiosperms , are insensitive to exogenously applied cytokinin, suggesting that the signal transduction pathway of cytokinin is basically conserved in P. patens , an enzyme that catabolizes cytokinin, weakly suppressed gametophore growth, probably due to the decreased level of cytokinin  transcription factor MONOPTEROS (MP) is activated by auxin and enhances cytokinin signaling through direct repression of type-A ARABIDOPSIS RESPONSE REGULATORS (ARRs), a negative regulator of cytokinin signaling. This crosstalk is important for balancing organ formation and stem cell activity in Arabidopsis  family is one of the largest gene families encoding polypeptides in land plants (Fletcher TDIF RECEPTOR/PHLOEM INTERCALATED WITH XYLEM (TDR/PXY) and CLAVATA1 (CLV1), are conserved in the genome of M. polymorpha , and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), but no H-type peptide genes  and MpCLE2 (R-type), and their receptor genes  are preferentially expressed in the SAM. Overexpression of MpCLE1 caused reduced thallus growth, while the reduction was suppressed by introducing the loss-of-function mutation of MpTDR  phenotype  in the P. patens genome   superfamily proteins play crucial roles in establishing pluripotent stem cells in angiosperms , a causal gene of the mutants, was shown to be a member of the ALOG (Arabidopsis LSH1 and Oryza G1) family of transcription factors. The ALOG family were identified as regulators of indeterminate growth of the inflorescence meristem and growth of lateral organs in angiosperms , is expressed in the protonemal tip, gametophore shoot apical cell and cells surrounding the shoot apical cell , an Arabidopsis PRC2 component  in Arabidopsis and a component of the PRC1 complex, phase transition from protonema to gametophore was accelerated and gametophore branching was increased. These defects further support involvement of PRCs in regulation of stem cell identity through repression of genes related to stem cell activity of shoot apical cell.The function of the PRC1 complex is also conserved in P. patens. Macrodomain superfamily proteins bind or cleave ADP-ribose from cellular molecules  encoding a membrane-targeted calpain is indispensable for determination of the cell division plane orientation during gametophore development  gene that encodes an ubiquitin-associated protein  ortholog, PpCESA5, can form relatively normal protonemal tissue and bud initials, however, bud initials fail to develop leafy shoots and form irregular cell clumps  is a master regulator for promotion of stem cell identity in the SAM in angiosperms  orthologs in P. patens (PpWOX13Ls) are preferentially expressed in protonemata during the regeneration process (Sakakibara et al. PpWOX13Ls. STEMIN, an AP2/ERF transcription factor, is sufficient for conversion from gametophore leaf cells to protonemal stem cells (Ishikawa et al. STEMIN genes caused a reduction in the regeneration rate and in side branch formation in P. patens. Regeneration of protonemal stem cells from differentiated tissue was also induced by DNA damage, and STEMIN genes are indispensable for this process (Gu et al. \u03b2-EXPANSIN, were identified as common downstream genes of PpWOX13Ls and STEMIN, suggesting that cell wall control is important for formation of protonemal stem cells (Sakakibara et al. Although the mechanisms for the establishment and maintenance of the protonemal apical cell identity remain unclear, several transcription factors are known to be involved in side branch formation and protonema regeneration from the gametophore tissue. AIL genes, are conserved, whereas the WUS function for stem cell maintenance is not fully evolved in ferns, as in bryophytes (Hirakawa and Bowman The primary pathways involved in the establishment and maintenance of stem cell pluripotency in the angiosperm and moss SAM are summarized in Fig.\u00a0WUS acts as a master regulator promoting stem cell identity under the control of cytokinin and CLV. However, despite cytokinin and CLV conferring conserved functions in the moss SAM, the WUS pathway is absent in bryophytes. This implies the existence of alternative unknown mechanisms promoting stem cell identity downstream of cytokinin and CLV signaling. In fact, recent studies suggested the existence of WUS-independent pathways promoting stem cell identity in angiosperms (Huang et al. KNOXI genes, key players for promotion of the stem cell activity (Schubert et al. KNOXI genes are not crucial at least for stem cell activity of the gametophore shoot apical cell in mosses (Sakakibara et al. A question emerging from the above discussion relates to the common downstream mechanisms to be activated or repressed by phytohormones and their epigenetic regulation. In angiosperms, The morphologically and functionally recognizable single pluripotent stem cell and the highly regular developmental pattern of the moss SAM confer a huge advantage in the study of the molecular and genetic basis of stem cell maintenance and differentiation. We anticipate that further comparative analysis of key factors in moss SAM regulation will provide important insights into the fundamental nature of plant stem cells."}
+{"text": "Understanding communication behaviors between persons living with dementia and family caregivers is essential for meaningful social interaction and decrease problematic behaviors and caregiving burden. The purpose of this study was to develop and test the psychometric properties of a coding scheme for dementia care interactions. The coding scheme items were developed from literature and expert review, and the pilot testing on 16 video-recorded interactions. A secondary analysis was conducted using 77 videos from 21 dyads of dementia family interactions naturally occurred in the participant\u2019s home. The final coding scheme consists of 11 codes for persons living with dementia  and 12 codes for family caregivers . Content validity was excellent . Inter-item correlation was acceptable for both caregiver codes , and patient codes . Intra-rater reliability  and inter-rater reliability  were excellent. Findings suggest the preliminary psychometric properties of the newly developed coding scheme to assess dyadic interactions of persons living with dementia and their informal caregiver in-home care situations. Future testing of the coding scheme for application in communication interventions to improve quality social interaction in dementia care is discussed."}
+{"text": "Following publication of the original article , the autPlease find the corrected second paragraph  below:2864 times higher than the mean excess lifetime risk of our patients. Compared to the female population, the mean excess lifetime risk of our patients is approximately 1817 times lower for all cancer types [3440 times higher than the mean excess risk for our male patients. The female population has a lifetime overall risk of 43% for developing cancer, which is approximately 2084 times higher than the excess risk for our female patients [\u201cBased on information from the US National Cancer Institute\u2019s Surveillance Epidemiology and End Results (SEER) of the American Cancer Society (database: 2010 to 2012), the risk for developing cancer is 42% in the males and 38% in females [And please find here the corrected seventh paragraph :329 (SEER) and 214 (RKI) times higher for males and 73 (SEER) and 51 (RKI) times higher for females [\u201cCompared to our patient risk data, the lifetime overall risk for both genders of the general population for developing bladder cancer is above the mean excess lifetime risk, with values of approximately The authors apologize for any inconvenience caused."}
+{"text": "With an increasingly multicultural and diverse older adult population, health care professionals must be prepared to serve older adults from varied backgrounds and marginalized communities; address health determinants and disparities; and promote diversity, equity, inclusion, and empathy within systems of care. The National Association for Geriatrics Education (NAGE) is a non-profit organization representing geriatric and gerontology education and training programs, including Health Services and Resource Administration (HRSA) funded Geriatric Workforce Enhancement Programs (GWEPs), and Geriatric Academic Career Awardees (GACAs). The 44 GWEPs focus on improving health outcomes for older adults by enhancing geriatrics and primary care training of the healthcare workforce. The 26 GACA awards support leaders in Age-Friendly health care transformation and interprofessional clinical geriatrics training. This symposium examines the role both programs have in reducing racial health disparities in older adults by promoting increased diversity of the geriatrics/gerontology workforce and advancing public policies for racial equity and inclusion. First, presenters will introduce the NAGE Diversity and Racial Equity Workgroup that supports a broader and unified effort across GWEPs and GACAs for equity and inclusion in geriatrics and gerontology education. Presenters will then share strategies to mobilize system-level changes within their institutions. Finally, examples of progress showcase individual GWEP and GACA projects and partnerships aimed at reducing racial health disparities within a multidimensional and local context. Presenters discuss strategies and opportunities to disrupt and transform health professions education at multiple levels and implications for policies supporting optimal aging for all older adults."}
+{"text": "Artificial intelligence (AI) technology has been increasingly developed and studied in cardiac imaging. This systematic review summarizes the latest progress of image segmentation, quantification, and the clinical application of AI in evaluating cardiac adipose tissue.We exhaustively searched PubMed and the Web of Science for publications prior to 30 April 2021. The search included eligible studies that used AI for image analysis of epicardial adipose tissue (EAT) or pericoronary adipose tissue (PCAT). The risk of bias and concerns regarding applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.Of the 140 initially identified citation records, 19 high-quality studies were eligible for this systematic review, including 15 (79%) on the image segmentation and quantification of EAT or PCAT and 4 (21%) on the clinical application of EAT or PCAT in cardiovascular diseases. All 19 included studies were rated as low risk of bias in terms of flow and timing, reference standards, and the index test and as having low concern of applicability in terms of reference standards and patient selection, but 16 (84%) studies did not conduct external validation.AI technology can provide accurate and quicker methods to segment and quantify EAT and PCAT images and shows potential value in the diagnosis and risk prediction of cardiovascular diseases. AI is expected to expand the value of cardiac adipose tissue imaging.The online version contains supplementary material available at 10.1186/s41824-021-00107-0. Artificial intelligence (AI) refers to technology in which computers or other machines simulate human intelligence to enable problem solving  in single-photon emission computed tomography (SPECT), and the approach achieved an area under the curve (AUC) that was higher than that of MPI alone   are one of the most popular deep learning architectures, which utilize convolution operations that effectively decrease the number of parameters, thus requiring less training data  2020 statement  independently reviewed the titles, abstracts, and full texts to select eligible articles. Articles that did not use AI or that did not involve EAT or PCAT were excluded. The same two reviewers independently extracted the data from the included articles, including the article characteristics , sample sizes, imaging equipment, AI methods, and main results. In the process, the two reviewers resolved their disagreement via consensus with the third senior reviewer (XQ.X.).Two reviewers (L.Z. and BB.J.) independently assessed the risk of bias and concerns regarding applicability of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool  automatically segments PCAT radially outwards from the outer wall of coronary vessels in 3D space  and found that the epicardial fat volume was an independent predictor of impaired myocardial flow reserve  in predicting the outcome of MACEs. Lin et al. explored the ability of the radiomics signature of the PCAT in CCTA images to discriminate patients with MI from those with stable or no coronary artery disease  tool."}
+{"text": "ABSTRACT IMPACT: This work will discuss informatics methods enabling the use of exposure health data in translational research. OBJECTIVES/GOALS: 1. Characterize gaps and formal informatics methods and approaches for enabling use of exposure health in translational research. 2. Education of informatics methods enabling use of exposure health data in translational research. METHODS/STUDY POPULATION: We performed a scoping review of selected literature from PubMed and Scopus. In addition we reviewed literature and documentation of projects using exposure health data in translation research. RESULTS/ANTICIPATED RESULTS: Primary challenges to use of exposure health data in translational research include: (1) Generation of comprehensive spatio-temporal records of exposures, (2) Integration of exposure data with other types of biomedical data, and (3) Uncertainties associated with using data as exact quantifications of exposure which are dependent on both - the proximity of measurement to subject under consideration and the capabilities of measuring devices. We identified 9 major informatics methods that enable incorporation and use of exposure health data in translational research. While there are existing and ongoing efforts in developing informatics methods for ease of incorporating exposure health in translational research, there is a need to further develop formal informatics methods and approaches. DISCUSSION/SIGNIFICANCE OF FINDINGS: Depending on the source about 50 - 75% of our health can be quantified to be a contribution of our environment and lifestyles. In this presentation, we summarize the studies and literature we identified and discuss our key findings and gaps in informatics methods and conclude by discussing how we are covering these topics in an informatics courses."}
+{"text": "Nurses and social workers in acute care settings have unique perspectives about providing care to persons living with dementia (PLwD) who experience behavioral and psychological symptoms of dementia (BPSD). Their distinctive roles and training have important implications for the recovery and well-being of PLwDs during hospital stays. This study utilized the \"rigorous and accelerated data reduction\" (RADaR) technique to compare perspectives of social workers (n=12) and nurses (n=5) in a Midwestern tertiary care facility about their caring for PLwds with BPSD. Three major themes were identified: 1) patient engagement and coordination with family and professionals, 2) treatment and medical management, and 3) barriers to care. Similarities between social workers and nurses emerged within the themes, including the importance of family involvement and providing person centered care. Differences emerged particularly within the treatment and medical management theme, as nurses utilize medications to treat BPSD and social workers were more likely to use redirection. While there is distinctive training for nurses and social workers, both identified similar barriers to providing care to PLwDs with BPSD, including time constraints, competing demands, and lack of training on BPSD management. Results demonstrate how an understanding of the critical and complementary roles that nurses and social workers play in dementia care and work together to build a care team can inform best practices to support symptom management and quality of life in PLwDs. Continuing education and training could be beneficial for both professionals to improve the quality of care for PlwDs."}
+{"text": "Postoperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients undergoing knee and hip arthroplasty and hip fracture surgery, while VTE is considered potentially preventable with several modalities of prophylactic management .The VTE prevention guidelines by the American Academy of Orthopedic Surgeons (AAOS) or the American College of Chest Physicians (AACP) have been implemented in most countries in Asia , 3. HoweAmong orthopedic surgeons who practice in the Asia-Pacific (AP) region, some alternative options for VTE prevention in hip and knee arthroplasty and hip fracture surgery are believed to be necessary \u201310. ThesWe hope that this AP VTE consensus will provide orthopedic surgeons who practice in the AP region appropriate options for VTE diagnosis and prevention methods that benefit their patients, with fewer complications."}
+{"text": "GENETICS and G3: Genes|Genomes|Genetics have launched an ongoing series of publications on Fungal Genetics & Genomics.The Genetics Society of America (GSA) journals GENETICS has a long and rich history of publishing landmark fungal genetics papers. Examples include: (1) landmark work done with Neurospora crassa as the model system by George Beadle and Art Tatum, whose studies were recognized via the Nobel Prize for their one gene\u2013one enzyme hypothesis and discovery; (2) a series of publications by Jim Hicks, Jeff Strathern, and Ira Herskowitz and the independent pioneering contributions of Yasuji Oshima that provided robust genetic support for the cassette model of mating-type switching in Saccharomyces cerevisiae; and (3) additional landmark contributions highlighted below.The GSA and the fungal genetics community have a long relationship given their joint sponsorship of the Asilomar Fungal Genetics meeting, and GENETICS and G3.The Fungal Genetics & Genomics Series was launched across both GSA journals in February 2021 with an editorial and a block of research publications. It is overseen by Series Editors Leah Cowen (University of Toronto) and Joseph Heitman (Duke University). These exciting new resources aim to report and thereby further stimulate advances in genetics and genomics across a diversity of fungal species, and authors are invited to submit manuscripts to the series on an ongoing basis. Papers published in the series will continue to be highlighted across both GENETICS may be offered a transfer to G3 as an option. To ensure proper routing of your submission, please choose the \u201cFungal Genetics & Genomics\u201d article type in the submission systems and mention the series in your cover letter.Manuscripts will be reviewed and edited through the standard peer-review process and according to the usual high standards of the journals. Authors should submit to their journal of choice; some manuscripts submitted to Conflicts of interest: None declared."}
+{"text": "It is of interest to document data on oral health care services for adults with cognitive and intellectual disabilities. Hence, a study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with registration number:CRD42020150759. We used PubMed, Science Direct, LILACS and SCIELO to collect data from known literature using keywords containing MESH  terms. The risk of bias rating for the collected data was calculated using the Newcastle-Ottawa assessmentScale. The AHRQ  was used for classifying the level of evidence in the collected data. Analysis of available data shows that there is a lack of dentists with adequate skills to treat people with disabilities resultingin high cost for dental treatment. Thus, we conclude that inconvenient location of dental clinic, lack of dentists willing to treat people with disabilities and attitude of dental staff towards people with learning disabilities were considered as barriers and challengesfaced for dental health service utilization in this context. Oral health has an important influence on the psychological and social health of individuals [1]. The consequences of poor oral health are toothache, difficulty in eating, decreased self-esteem, impaired social interactions. This affects the quality of lifeand general health in aged people -8. DisabSystematic review of population-based survey data was used in this study.The study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with Registration number:CRD42020150759. This study includes five stages: (1) Identifying the research question; (2) Literature search; (3) Study selection;(4) Data extraction; and (5) Summarizing and reporting the results.Population: AdultsProblem: Cognitive disabilitiesOutcome: Barriers to Oral health care services with utilizationsThe factors associated with utilization and barriers to oral health care services by adult participants were considered. Data on study participants with cognitive impairment and learning disabilities from known literature were used.We used PubMed, Science Direct, LILACS and SCIELO to collect data in this regard for keywords containing MESH  terms (Table 1 see PDF).Difference of opinion was resolved by discussing with the third reviewer (ARV). Quality Assessment criteria to evaluate data were carried out using Newcastle-Ottawa Scale guidelines . The NewData were extracted independently as shown in Table 2 (see PDF).Pooling of data was not possible due to hetero-genous nature of the selected information.We used PubMed, Science Direct, LILACS and SCIELO to collect data in this regard for keywords containing MESH (Table 1 - see PDF). Thus,259 articles were selected from databases after removing redundant data. Data was further gleaned using criteria as shown in Figure 1(see PDF).Description of literature data and levels of evidence according to AHRQ is given in Table 2(see PDF). Data on the risk of bias  is given in Table 3(see PDF) and Figure 2(see PDF). Data shows that underthe domain selection, one study  receivedThe importance of barriers to oral health care services varies exponentially with respect to various population segments. Barrier to dental care occurs for functionally dependent individual and the functionally independent person and people with disabilitiesresiding at home or institutions. According to Penchansky and Thomas  the concDental cost, location of dental clinic, lack of dentists prepared to treat people with disabilities, transportation problems and lack of comprehensive oral health care were reported as a barrier in accessing dental care ,36. InfAvailable data shows that there is a lack of dentists with adequate skills to treat people with disabilities leading to high cost of dental treatment. Thus, we conclude that inconvenient location of dental clinic; lack of dentists willing to treat people withdisabilities, attitude of dental staff towards people with learning disabilities were considered to be the barriers and challenges faced for dental health service utilization."}
+{"text": "Introduction: The need for caregiver respite is well-documented for the care of persons with IDD. Social Assistive Robotics (SAR) offer promise in addressing the need for caregiver respite through \u2018complementary caregiving\u2019 activities that promote engagement and learning opportunities for a care recipient (CR) with IDD. This study explored the acceptability and usefulness of a SAR caregiver respite program responsive to feedback from both the CRs and their older family caregivers (age 55+). Methods: Caregiver-CR dyads (N =11) were recruited. A mixed methods research design was deployed in three phases: Phase I with four focus groups to inform the program design; Phase II for program demonstration and evaluation with pre- and post-surveys; and Phase III with post-program interviews for feedback and suggestions. Results: Quantitative data analysis in Phase II showed both caregivers and their CRs scored favorably the social presence of the robot (Pepper) and social engagement with Pepper. Caregivers also reported positive perceptions of Pepper in terms of anthropomorphism, animation, likeability, intelligence, and safety. Content analysis from Phase III interviews suggested that the SAR may offer physical/emotional respite to caregivers by providing companionship/friendship as well as promoting independence, safety/monitoring, and interactive engagement with children. Discussion: SAR has potential in providing respite for older family caregiver demonstrated by the levels of CR engagement and learning with Pepper. Future studies need a longer program design and larger sample size to test the feasibility and efficacy of the intervention."}
+{"text": "A young patient of age 34 years complains of poor aesthetic because of maxillary defect. The patient complains of difficulty in speech, swallowing, mastication and cosmetic disfigurement which was the main concern for which patient reported to the outpatient department (OPD) where examination was done. This revealed absence of incisors and anterior mandibular and anterior maxillary defect and as mentioned by patient poor cosmetics was the main concern, pre-examination was done and surgery was conducted. Consent was taken and case history was recorded. An implant supported Prosthesis was planned for maxilla and mandible in anterior region. Aesthetic rehabilitation was satisfactorily achieved. The (A) depicting pre-operative image of the patient with missing incisors and (B) shows the defect was corrected by prosthesis."}
+{"text": "This symposium presents a collection of papers that examine the concept of social support and its effect on custodial grandparents\u2019 (CG) mental health state. Each paper explores a different perspective about grandparents\u2019 access to and/or use of social support networks and mental health outcomes; several papers view social support within the context of the COVID-19 pandemic. Nadorff and colleagues explore social support by middle-generation family members and its effects on grandparents\u2019 stress and depressive symptoms. Musil and colleagues report on psychosocial and social support predictors of self-appraised healthcare and financial security by CG during the Covid-19 pandemic. Whitley and Kelley describe current social networks relied upon by a preliminary sample of CG while managing the daily stresses and strains associated with COVID-19 and its restrictive mandates. The final two papers report the use of specialized technology and support services delivered to homebound CG during the COVID-19 pandemic. Lee and colleagues describe a telemental health model using Solution-Focused Brief Therapy to serve socially isolated grandparents experiencing mental health distress as during the pandemic. Mendoza and Park report on program challenges and outcomes of implementing a support service for grandparents living under COVID-19 restrictions. The highlights of the papers will be discussed by Yanfeng Xu and give attention to the ways scholars and practitioners can build upon these works to maximize the mental health outcomes of CG, while managing to live in socially restrictive and challenging environments."}
+{"text": "ABSTRACT IMPACT: Quantifying the types of dental procedures patients with healthcare needs receive can help understand and improve modalities of dental care to improve healthcare outcomes. OBJECTIVES/GOALS: 1. Quantify how medical complexity based on special needs diagnosis impacts dental treatment rendered2. Comprehend how medical diagnosis of a special need can affect rate of treatment and type of treatment METHODS/STUDY POPULATION: This study consists of a chart review of all active patients in a dental school setting who have one of the following diagnoses of a special need: autism, developmental disorder, epilepsy, cerebral palsy, neuromuscular disorder, and hydrocephaly. Medical diagnoses were used to extract records and quantify the types of dental treatment rendered for these patients , as well as the rates of appointments for this patient population. RESULTS/ANTICIPATED RESULTS: The medical complexity of patients of this population, as defined by the number medical diagnoses, impacts the type of treatment rendered as well as how frequently these patients are seen for dental care (rate of appointments). DISCUSSION/SIGNIFICANCE OF FINDINGS: Over- or under-utilization of dental treatment modalities can impact the oral health status and outcomes for patients with special needs. The differences in types and frequency/ rate of dental treatment rendered for patients of different medical complexity can further impede their oral health and systemic health status and health outcomes."}
+{"text": "Since the beginning of the COVID-19 pandemic in West Africa, the region has faced a coexistence of epidemics raising questions about the management of the coexistence between COVID-19 and other epidemic prone diseases. We undertook a cross-sectional study covering the period from February to August 2020 in which an extensive desk review was completed and questionnaire was submitted to National Public Health Institutes. In addition, we conducted online interviews with 10 West African countries to discuss in-depth the strategies and challenges in managing the coexistence of epidemics. Eight epidemics coexisted with COVID-19 in West Africa. These epidemics were yellow fever and measles in five countries; meningitis in 4 countries; vaccine derived poliomyelitis and dengue fever in two countries; Lassa fever, Crimean Congo Hemorrhagic fever and hepatitis E virus in one country. COVID-19 pandemic has brought both positive and negative effects to the management of other epidemics. The management of coexistence was similar in most ECOWAS countries with different incident management systems set up to manage separate outbreaks. The experience in managing the coexistence of epidemics led ECOWAS Regional Center for Surveillance and Disease Control to recommend to member states that they should reinforce regular disease surveillance for seasonal outbreaks and country specific epidemiological diseases profile while not forgetting other emerging and remerging infectious diseases. The West African region is recognized as a zone with the recurrence of infectious diseases outbreaks such as meningitis, Lassa fever, cholera, yellow fever, Ebola etc. -7. COVIDOur responses have been elaborated on the basis of a cross sectional study in which questionnaires were answered and online meetings held with National Public Health Institutes of 10 ECOWAS countries namely: Burkina Faso, Cabo Verde, The Gambia, Ghana, C\u00f4te d'Ivoire, Niger, Nigeria, Senegal, Sierra Leone and Togo. These meetings, jointly organized by the ECOWAS Regional Center for Surveillance and Disease Control (RCSDC), West African Health Organization (WAHO) and Africa Center for Disease Control and Prevention (Africa CDC), aimed at promoting experience sharing, good practices and lessons learnt in managing the coexistence of COVID-19 pandemic and other epidemic prone diseases. They were attended by national public health institutes leaders, international health regulations national focal points, laboratory officers, public health experts, non-governmental organizations and other epidemics first line responders in West Africa. Prior to the data collection, an extensive desk review including epidemiological bulletins, events and indicator based surveillance reports from ECOWAS countries and regional organizations such as the Regional Center For Surveillance And Disease Control (RCSDC), West African Health Organization (WAHO), Africa CDC, the World Health Organization - Regional Office for Africa and other regional bodies was done.Coexistence of COVID-19 with other epidemics: between February and August 2020, 8 epidemics coexisted with COVID-19 in ten ECOWAS countries. These epidemics were yellow fever and measles in five countries; meningitis in 4 countries; vaccine derived poliomyelitis and dengue fever in two countries; Lassa fever, Crimean Congo Hemorrhagic fever and hepatitis E virus in one country. Some countries experienced more than one disease epidemics with five in Burkina, Nigeria and Niger, four in Ghana and Senegal and two in Sierra Leone. We also found that the number of epidemic disease cases reported by the countries, were fewer in 2020 compared to previous years during the same period. The decreasing number of confirmed cases of other epidemics reported during the COVID-19 pandemic might be due to overwhelmed surveillance system and the limited capacity for detection in West Africa. This observation was confirmed by the laboratory network records reporting the decrease of number of samples collected.Management of COVID-19 pandemic and other epidemics: the management of coexistence was similar in most ECOWAS countries with different incident management systems set up to manage separate outbreaks. Ivory Coast was the unique country reporting one incident management system managing all ongoing epidemics. Having one Incident Management and Systems was really helpful to implement synergistic public health interventions during the epidemics responses and to make efficient use of available resources during the response. COVID-19 tools for surveillance, laboratory and risk communication leveraged on the pre-existing tools mostly derived from influenza preparedness infrastructure with minor adaptations depending on the conditions of public health response operations and international recommendations. For case management and infection prevention control pillars, COVID-19 guidelines, standard operations procedures and monitoring tools were developed separately from other epidemic prone diseases in order to meet countries requirements. Regarding logistics, guidelines for emergency procurement system to fast track procurement process without circumventing existing laws and regulations were implemented in all member states. This also facilitated the procurement of goods for the management of other outbreaks.Influence of the COVID-19 pandemic management on other epidemics management: COVID-19 pandemic in West Africa has brought both positive and negative effects to the management of other epidemic prone diseases as reported by countries representatives. Positive effects included activation of crisis management committees with involvement at the highest political level, inter-ministerial and inter-agency collaborations including army health services, improved pooling of resources from various sectors, strengthening the skills of health workers at all levels in the health systems, improvement of existing monitoring system including events based surveillance/indicators based surveillance, scaling up of Surveillance Outbreak Response Management and Analysis System (SORMAS) nationwide and linking with DHIS-2 to laboratory data for easing real time reporting in Ghana and Nigeria, scaling up of molecular diagnostics among ECOWAS member states, improving equipments of health structures including laboratory systems, improving infection prevention and control systems in hospitals and communities, active Information sharing and cross border surveillance among ECOWAS member states, better awareness of non-pharmaceutical measures on management of diseases, expanded stakeholders and media network and strengthened relationship, virtual mentorships of responders in several member states and internal manufacture of consumables and goods.The negative effects of COVID-19 pandemic to other epidemics management included overall insufficiency of personal protective equipment , essential drugs, laboratory supplies and reagents, vaccines and other hospital and equipment due to closure of international borders, lack of sufficient human resources, high numbers of health worker infections which added to the lack of adequate workforce and work overload among healthcare workers, lack of community trust to government during the outbreaks response, challenges with governance and power dynamics in some countries, reduced attendance to health facilities and finally disruption of major program activities in and out of the health sector.Conclusion: the COVID-19 pandemic has been a challenging experience in West Africa and has brought major changes in the public health response of infectious diseases outbreaks both in ECOWAS member states and at regional level. The experience in managing the coexistence of other epidemics with COVID-19 pandemic led the RCSDC to recommend to member states that they should reinforce regular disease surveillance for seasonal outbreaks and country specific epidemiological diseases profile while not forgetting the emerging and remerging diseases. Countries should also adapt to their local context and foster the implementation of the third generation of integrated disease surveillance and response guidelines. Countries with the support of RCSDC and other regional and international organizations should develop guidance documents on critical response pillars for improving the management the coexistence of several epidemics in one country and at the same time. In addition, health system strengthening efforts should be maintained and promoted. Finally, partners and funders should give a particular interest on supporting and funding activities intended to see these recommendations implemented."}
+{"text": "Hepatocellular carcinoma (HCC) is considered the second most deadly cancer worldwide. Due to the absence of early diagnostic markers and effective therapeutic approaches, distant metastasis and increasing recurrence rates are major difficulties in the clinical treatment of HCC. Further understanding of its pathogenesis has become an urgent goal in HCC research. Recently, abnormal expression of long noncoding RNAs (lncRNAs) was identified as a vital regulator involved in the initiation and development of HCC. Activation of the Wnt/\u03b2-catenin pathway has been reported to obviously impact cell proliferation, invasion, and migration of HCC. This article reviews specific interactions, significant mechanisms and molecules related to HCC initiation and progression to provide promising strategies for treatment. Liver cancer has become one of most prevalent malignant diseases worldwide, and hepatocellular carcinoma (HCC) accounts for most liver cancer cases \u20133. Owingvia sponging in cervical cancer  accumulates in the cytoplasm and accesses the nucleus, interacting with T cell-specific factor (TCF)/lymphoid enhancer-binding factor (LEF) and activating a wide range of signaling cascades  family have been verified  has a tendency to be abnormally expressed in colorectal neoplasia samples , 116. SuIn HCC, lncRNA ASB16 antisense RNA1 (ASB16-AS1) was found to aberrantly express in high level and have positively association with unsatisfied outcome . On the in vitro and in vivo  protein and the activation of the Wnt pathway  cells into SCID mice, and their biological features resemble those of normal stem cells with self-renewal and differentiation abilities , the Youth Talent Lifting Project of Henan Province (2021HYTP059), and Key Scientific Research Project of Henan Higher Education Institutions ofChina (21A320026). This work was also supported by Leading Talents of Zhongyuan Science and Technology Innovation (214200510027), Henan Provincial Medical Science and Technology Research Plan (SBGJ202102117 and SBGJ2018002), Henan Medical Science and Technology Joint Building Program (LHGJ20210324), Science and Technology Innovation Talents in Henan Universities (19HASTIT003), Outstanding Foreign Scientist Studio in Henan Province (GZS2020004), and the Gandan Xiangzhao Research Fund (GDXZ2022002).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
+{"text": "Our study addresses symptoms and functional management early in acute myeloid leukemia treatment using a PAlliative and Collaborative Care inTervention (PACT) delivered by clinical staff. PACT is an interdisciplinary nurse-led intervention of nursing [RN], occupational therapy [OT], physical therapy [PT] for adults \u2265 60 years of age at time of initial treatment. Finding from our preliminary qualitative work led to use of the Adaptive Leadership Framework for Chronic Illness to guide optimal engagement of the patient in self-management of symptoms and functional activities to address QOL outcomes. We share lessons learned of how the ALFCI was applied to the PACT intervention to empower patients with self-management skills to reduce symptoms and optimize function. In summary, the team and patient identify and address emotional, motivational, attitudinal barriers so that the patient can do the work required for self- management to reduce symptoms and avoid functional decline."}
+{"text": "Access to greenspace has been positively associated with cognition among older adults, however prior research has been limited in temporal and geographic scope. We evaluated associations between neighborhood greenspace and incidence of dementia and change in cognitive functioning using a longitudinal sample of non-demented adults  from the Cardiovascular Health and Cognition Study. Percent greenness  was derived from the National Land Cover Dataset. Cognitive function was measured using the Mini-Mental State Examination (3MSE) and dementia status was clinically adjudicated. Cox proportional hazard and logistics regression analyses were used to examine associations of baseline greenness with risk of incident dementia and risk of mild cognitive impairment, respectively. Generalized linear mixed models accounting for within-subject correlations were used to examine the association between greenspace in the neighborhood at baseline and 3MSE score (1991-1999). Ongoing results will be presented, along with modifiers and mediators of associations."}
+{"text": "Background and Objectives: Though many studies have examined the service utilization of dementia caregivers, there is limited empirical evidence from Asian Americans and the lack of incorporating community resources and sociocultural factors in this field. Guided by the Andersen's Behavioral Model of Health Services Use (ABM), we aimed to understand whether and how predisposing, enabling and need factors were associated with utilizing multiple types of services among Chinese Americans dementia caregivers. Research Design and Methods: We collected survey data from 134 Chinese dementia caregivers in New York City. Logistic regression models were conducted to test the associations between predisposing, enabling and need factors and the likelihoods of using tangible , educational (lectures and workshops), and psychological  services. Results: Consistent with prior literature, caregiver\u2019s knowledge about services, caring tasks, length of care and burden and care recipient\u2019s physical and cognitive deteriorations, were significantly associated with higher possibilities of using multiple types of services among these Chinese American dementia caregivers. Three sociocultural factors, including residing in Chinatowns, availability of alternative family caregivers and diagnosis of cognitive deterioration, were also associated with higher likelihoods of using educational or psychological services. Discussion and Implications: The findings extended the existing literature on service utilization of caregivers by highlighting the importance of distinguishing types of services and the necessity of considering sociocultural factors in future research and practice."}
+{"text": "ABSTRACT IMPACT: This work seeks to improve the diagnostic accuracy of urinary tract infection among hospitalized older adults and mitigate antibiotic overuse in this population. OBJECTIVES/GOALS: Primary objective: To determine the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of symptomatic urinary tract infection (UTI) in hospitalized older adults. Secondary objectives: (1) To develop a predictive model for the diagnosis of UTI; (2) To determine the ability of PCT in discriminating between lower and upper UTI. METHODS/STUDY POPULATION: We performed a prospective observational cohort study of 228 participants from a single institution. The study population included older adults (age 65 or older) who were hospitalized on the general medicine wards with a possible or suspected urinary tract infection (UTI). Upon obtaining informed consent, serum procalcitonin (PCT) was processed on remnant blood samples collected from the emergency department. We performed additional data collection through the electronic health record to obtain demographic information, clinical characteristics, and other laboratory and imaging results. Clinicians were surveyed for the diagnosis of UTI and charts were adjudicated by independent reviews of the medical record by infectious diseases experts to determine the primary endpoint of symptomatic UTI. RESULTS/ANTICIPATED RESULTS: We anticipate that serum procalcitonin predicts the presence of symptomatic urinary tract infection (UTI) by demonstrating an area under the receiver operating characteristic curve of at least 0.85. A predictive model developed in our cohort for the diagnosis of symptomatic UTI will be improved by the addition of serum PCT to the prediction model. Finally, we anticipate the serum PCT will accurately discriminate between upper and lower UTI. DISCUSSION/SIGNIFICANCE OF FINDINGS: Diagnosis of symptomatic UTI in hospitalized older adults is challenging and may lead to overuse of antibiotics and the development of antibiotic resistance in this vulnerable patient population. Serum procalcitonin offers a novel diagnostic strategy in the diagnosis of symptomatic UTI to enable more appropriate antibiotic therapy."}
+{"text": "Pregnant women continue to be excluded from most clinical trials of COVID-19 vaccines and medication, despite very clear pre-pandemic guidance.Vaccine hesitancy in pregnancy is not a new phenomenon. Salmon and colleaguesData suggest that vaccines are a highly effective protection against severe COVID-19 in the non-pregnant populations in which they were initially tested.,,Simultaneously, it has become clear that pregnant and postpartum women are at higher risk of serious illness compared to their non-pregnant contemporaries. This seems especially true for the Delta variant, which increased the risk of intensive care unit admission among pregnant women 2-3 times, with a 50% increase in iatrogenic preterm births.Multiple initiatives to promote uptake of COVID-vaccination in pregnancy have been undertaken, with widely differing uptake rates and uptake estimates varying between 22% in England and 80% in Norway. Surprisingly, data are not available on Covid-19 vaccination rates amongst pregnant women in all European countries. Within the International Network of Obstetric Survey Systems (INOSS)Our findings emphasize the message to unvaccinated pregnant women, their partners, health professionals caring for pregnant women, decision makers and politicians that vaccination protects against severe disease. As the world is entering a new phase of the COVID-pandemic, with the Delta-variant rapidly being overtaken by the Omicron-variant, booster vaccinations are increasingly important to provide protection against severe COVID-19, especially in vulnerable groups such as pregnant and postpartum women or women who want to become pregnant. However, large numbers of pregnant and postpartum women in low, middle and high-income settings have yet to receive even a single vaccination dose. Health system as well as individual actions are now clearly needed. The World Health Organisation recommends COVID-19 vaccination in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. These multi-country data clearly show those benefits in terms of prevention of severe disease. We believe that all governments should now prioritise pregnant and postpartum women as an at-risk group and encourage their vaccination.Hilde Engjom reports funding from the Nordic federation of Societies of Obstetrics and Gynecology (NFOG) research fund and cost refund for travel costs as invited key note speaker at the Norwegian Perinatal Society annual meeting Nov 2021; Marian Knight reports funding from the National Institute or Health Research, the Medical Research Council and Wellbeing of Women; Thomas van den Akker reports funding from the Medical Research Council and the Laerdal Foundation; Anna Aabakke reports funding from The Region of Southern Denmark and Region Zealand's shared fund for joint health research projects and is head of the educational committee of the Danish Society of Obstetrics and Gynaecology (DSOG); Outi Ayras reports funding from the Finnish Medical Foundation and the Nordic Federation of Obstetrics and Gynaecology; Kitty Bloemenkamp reports frunding from the European Medicines Agency (EMA) \u2018COVID-19 infectiOn aNd medicineS In pregnancy\u2019 for the INOSS network; Serena Donati reports funding from the Istituto Superiore di Sanit\u00e0 . Danilo Cereda and Evelien Overtoom have no interests to declare."}
+{"text": "There is little research into evidence-based preconception interventions for women with serious mental illness (SMI). Women with SMI will have specific needs around preconception due to the complexities of the teratogenicity of medications, risk of mental illness relapse and higher levels of stigma around motherhood. If effectively delivered preconception care could mitigate these difficulties and improve outcomes for mother and baby. The aim of this research was therefore to determine to identify and describe studies evaluating preconception interventions for women of child-bearing age who have an existing SMI through searches of the peer-reviewed literature.A rapid review was conducted to search MEDLINE and PsychINFO databases from the year 2000 onwards for peer-reviewed articles describing preconception interventions/resources delivered prior to a pregnancy to women of child-bearing age with a pre-existing existing serious mental illness .A total of 592 results were returned from the searches and 576 of these remained after the removal of duplicates. 11 studies were included in the final narrative synthesis describing the following intervention types: Health warning (1), Health screening (1), Teratogen phone service (2), Psychiatric consultation (5), Family planning information (1) and Peripartum management plan (1). Interventions were delivered in Australia, UK, Italy, Germany, Netherlands, USA and Nigeria.Though the included studies indicated that some efforts have been made globally to meet the preconception needs of women with SMI the numbers included in the studies tended to be low and reflective of small-scale service provision. Future studies utilising a randomised controlled trial design would lower the risk of bias and provide more generalisable evidence of effectiveness for these interventions. The results of this review were used to inform the development of a number of resources to aid the planning of healthy pregnancies in both women with SMI and the health professionals working with them."}
+{"text": "Co-sponsored by the Disasters and Older Adults, Loneliness and Social Isolation, and Rural Aging Interest Groups, five presenters will highlight multiple circumstances regarding the intersection of social isolation or loneliness and the impact of COVID-19. Haverhals and colleagues interviewed veterans and their caregivers to identify the impact of changes in care delivery and social isolation as a result of the pandemic. Findings indicated differences in feelings of isolation among individuals living in their own home or assisted living facilities. Hua et al. examined whether individuals in long-term care communities were lonelier than individuals in the community during the pandemic using data from the NHATS COVID-19 module with higher levels of loneliness reported from individuals living in more restricted communities. Henning-Smith and colleagues explored differences in social activities among rural and urban participants in the COVID-19 Coping Study. Their study provides awareness into the ways rural and urban older adults stayed connected during the pandemic. Peterson et al. examined the effect of COVID-19 on care in Florida nursing homes and assisted living communities and on residents\u2019 anxiety with higher levels of anxiety reported by residents in nursing homes. Using the Coping with Loneliness, Isolation and COVID19 Global Survey, O\u2019Sullivan and colleagues utilized the lens of \u2018place\u2019 to examine factors associated with those experiencing loneliness and/or social isolation during the pandemic with insights from a public health perspective. Collectively, these presenters will provide evidence of the challenges associated with older adults\u2019 social isolation and loneliness throughout the COVID-19 pandemic."}
+{"text": "Based on a large body of evidence documenting activation of host kinases by neurotropic viruses, and on recent work revealing regulation of FAT through phosphorylation-based mechanisms, we posit a potential role of host kinases on the engagement of viruses in retrograde FAT. Finally, we briefly describe recent evidence linking aberrant activation of kinase pathways to deficits in FAT and neuronal degeneration in the context of human neurodegenerative diseases. Based on these findings, we speculate that neurotoxicity elicited by viral infection may involve deregulation of host kinases involved in the regulation of FAT and other cellular processes sustaining neuronal function and survival.Much remains unknown about mechanisms sustaining the various stages in the life cycle of neurotropic viruses. An understanding of those mechanisms operating before their replication and propagation could advance the development of effective anti-viral strategies. Here, we review our current knowledge of strategies used by neurotropic viruses to undergo bidirectional movement along axons. We discuss how the invasion strategies used by specific viruses might influence their mode of interaction with selected components of the host\u2019s fast axonal transport (FAT) machinery, including specialized membrane-bounded organelles and microtubule-based motor proteins. As part of this discussion, we provide a critical evaluation of various reported interactions among viral and motor proteins and highlight limitations of some  The large size and highly polarized cellular architecture of neurons present a major challenge for the replication and propagation of neurotropic viruses. This is because the cellular machinery typically needed for their replication is located in the neuronal soma, far away from axonal terminals where neurotropic viruses typically invade neurons , a cellular process involving the intracellular trafficking of membrane-bounded cellular organelles (MBOs) by microtubule-based motor proteins , is powered by motor proteins that convert energy derived from ATP hydrolysis into mechanical forces [reviewed in  are the major microtubule-based motor proteins powering anterograde and retrograde FAT, respectively  to their site of replication in the nucleus or perinuclear cytoplasm. Following replication, nascent virions can either engage in anterograde axonal transport and move towards the periphery or undergo sorting to dendrites and spread to post-synaptic neurons  is by far the most abundant  and two light chain (KLCs) subunit dimers  and two genes encoding KLC subunits  are expressed in mammalian nerve tissues  and Japanese encephalitis virus (JEV) are unique in that they enter cells through clathrin-independent endocytosis  and a lipid envelope studded with viral glycoproteins , the tegument protein pUL46 (VP11/12), and the DLC subunits RP3 and Tctex1  in pull-down assays  co-precipitated with endogenous KIF5B in pull-down assays , leading to the claim that APP might act as an adaptor protein linking conventional kinesin to MBO cargoes  critically depends on the regulated trafficking, delivery, and recycling of MBOs  has been shown to disrupt synaptic function through a mechanism involving PKC inhibition and reduced phosphorylation of synaptic protein substrates (i.e., MARCKS and SNAP25; Volmer et al., The ability of viral components to affect cellular signaling pathways may also relate to other aspects of viral pathogenesis. For example, viral proteins shed from infected cells may also promote aberrant activation of kinases that in turn impact FAT. The HIV protein gp120 is shed from infected macrophages and undergoes internalization in neurons (Mocchetti et al., Both the symptoms and pathology associated with neuronal infection have been extensively described (Berth et al., Given the number of kinases activated at different stages of the viral cycle and the complexity and crosstalk among kinase pathways, the identification of pathologically relevant ones may represent a major challenge for investigators (Besson et al., GM, AR, and SHB conceived the manuscript and generated the first drafts. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Medication errors represent an avoidable threat to patient safety  and inclSince Hannover Medical School is obliged to a policy of transparent error management, the published cases  have beeIn the aftermath of the disturbing cases of LASA medication errors that occurred at our institution , an inteThe final list which features TML notations in German for 44 LASA drug pairs/groups, comprising a total of 101 individual agents, was presented to, and approved by the Drug Commission of Hannover Medical School (Table The presented TML list Table  may be uESM 1(PDF 63 kb)"}
+{"text": "This work is an updated and extended version of the early local presentation made at KOREA INFORMATION SCIENCE SOCIETY conference by the same authors: \"Bike Sharing Demands Prediction based on GCN\", Proceedings of the KISS Conference p832-834, 2018."}
+{"text": "In 2015, the AGHE Program of Merit was expanded to implement a voluntary evaluation process for health professions programs that integrate gerontology/geriatrics competencies within their curriculum. These competencies augment students\u2019 competence and confidence in the field of aging, preparing them to work with older adults and their care partners. All health professions and medical education programs are eligible to apply for the Program of Merit designation. This international process of evaluation: (1) Verifies program credibility and quality; (2) Informs campus administrators of global guidelines, expectations, and practice in aging for their health professions programs; (3) Assures quality graduates from POM designated programs; and (4) Clarifies for employers the knowledge and skills imparted to student graduates of POM designated health professions programs. Additionally, graduates from POM programs receive a certificate from AGHE stating the health profession program is a designated AGHE Program of Merit."}
+{"text": "One of the first studies on workplace violence in nursing homes was published in 1985. Forty-five (45) years later, resident violence against staff continues to increase in incidence and severity. At the request of a state senator, a New Hampshire psychiatrist formed a research group to conduct the first New Hampshire survey on staff experience of workplace violence. Study questions focused on experiences of workplace violence and incident reporting, and the availability and benefit of workplace violence training programs. Results were consistent with recently published literature: violence is an expected, normalized element when providing care; potential repercussions and perceived resident lack of intent were major reasons for incident non-reporting. Analysis of study results and review of the literature led to the question: Are older residents\u2019 violent behaviors towards staff an act of self-protection?"}
+{"text": "Dear Editor,The nationwide response to curb the spread of the COVID-19 infection in India included a strict lockdown from 25 March 2020 until the end of May, with several restrictions remaining in place for 2 further months. Studies have reported severe economic crisis and serious health service disruptions during this lockdown.As part of an ongoing study, we collect primary data on patient and household costs from four states to estimate TB-related out-of-pocket expenses and catastrophic expenditure in India. Here, we report on the financial impact of COVID-19 as income loss for the families of TB patients during lockdown based on follow-up interviews in two states. We examined monthly household income of the sampled TB patients just before lockdown (February 2020) and during lockdown (April and May 2020) to understand the impact on household income. Monthly household income during lockdown and during the interview period (July and August 2020) were subtracted from monthly household income in February 2020 to estimate any income loss. To ascertain whether the pattern of TB drug collection had changed as a result of the lockdown, patients were asked about the frequency of visits to get drugs, amount of time spent travelling and collecting drugs, and travel and other expenses related to drug collection for two time periods \u2013 before lockdown and during lockdown. The time costs for the patient, household member and accompanying person were calculated by multiplying the total number of hours spent on the activity by the hourly wage. To determine if any TB medication was discontinued during lockdown, patients were asked whether they missed their medicine because of the lockdown. Household income loss was presented in 2020 US dollars (US$) (1 US$ = Indian rupee 74.132). The study covered 202 TB patients from the general population, 379 patients from tea garden areas and 69 patients from urban slum dwellers in the two states.The impact of COVID-19 on household incomes of the sampled patients are shown in the accompanying The COVID-19 pandemic hit India at a time when India\u2019s gross domestic product was slowing down, and unemployment was rising because of poor economic performance in recent years.Studies have reported reduced food consumption during the pandemic.The Government of India provided some relief measures with additional rations (grains and pulses) and additional cash transfers during the lockdown period; however, these were modest and there were disparities in distribution across states and between rural and urban areas."}
+{"text": "ABSTRACT IMPACT: Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery OBJECTIVES/GOALS: The WFUHS CTSA developed an innovative TL1 in Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery METHODS/STUDY POPULATION: Training is centered around formal LHS science coursework and mentored research projects that address a pressing health system issue. Projects are closely guided by a primary mentor and a multidisciplinary mentoring team. Program mission and competencies were carefully evaluated in a competency-course matrix to design new courses for the LHS Certificate and MS program in Translational and Health System Science (THSS). Course domains include biomedical informatics; improvement and implementation science; system science and organizational change management; stakeholder engagement, leadership, and research management; ethics of health systems research; and health systems research methods. Scholars set up Individual Development Plans (IDP) and self-assess 7 domains of LHS core competencies. RESULTS/ANTICIPATED RESULTS: The first professionally diverse group of scholars  began the program in Summer 2020; onboarding was conducted virtually. Scholars currently conduct most of their research and training in a virtual, synchronous format. Each developed a detailed IDP and LHS research project, which was reviewed by their LHS mentoring teams . Coursework, leading to a 1-year certificate or 2-year MS degree, was selected based on individual background and career goals and was begun in August 2020. In addition to the courses noted above, Scholars are embedded in a healthcare improvement team. We use the process of a LHS and hold weekly TL1 leadership meetings to swiftly address challenges and implement improvements DISCUSSION/SIGNIFICANCE OF FINDINGS: We envision that TL1 Scholars will build independent LHS research programs or lead health system innovation. Program evaluation includes assessments of Scholar fluency in LHS competencies and attainment of key milestones during and after training. Annual TL1 faculty retreats will address program fidelity and implementation of program refinements"}
+{"text": "We aimed to identify specific patterns of physical multimorbidity, defined as the presence of two or more physical long-term conditions, and to examine the extent to which these specific patterns could predict future incident and persistent common mental health disorders (CMDs) in middle-aged adults enrolled in the UK Biobank.= 50\u201362 years, 56.5% female, mean duration of follow-up: 7.6 years, standard deviation\u00a0=\u00a00.87). Patterns of physical multimorbidity were identified using exploratory factor analysis. Logistic regression was used to assess prospective associations between physical multimorbidity patterns at baseline and both incident and persistent depression and anxiety at follow-up.We assessed prospective associations between physical multimorbidity status at the baseline assessment (2006\u20132010) and depression and anxiety \u2018caseness\u2019 according to the Patient Health Questionnaire (PHQ)-9 and the Generalised Anxiety Disorder Assessment (GAD)-7 at the follow-up assessment (2016) in 154,367 middle-aged adults enrolled in the UK Biobank  =1.41, 95%CI 1.32 to 1.53), three , four , and five or more  physical conditions was prospectively associated with incident depression at follow-up in a dose response manner. Similar trends emerged for incident anxiety, persistent depression, and persistent anxiety, but associations were strongest for incident CMDs. Regarding specific patterns of physical MM, the respiratory pattern  and the pain/gastrointestinal pattern  emerged as the strongest predictors of incident depression. Similar results emerged for incident anxiety.These findings highlight patterns of physical multimorbidity with the poorest prognosis for both emerging and persisting depression and anxiety. These findings might have significant implications for the implementation of integrated mental and physical healthcare and facilitate the development of targeted preventative interventions and treatment for those with physical multimorbidity.AR is supported by Guy's Charity grant number EIC180702; JAT is funded by Medical Research Council (MRC) number MR/SO28188/1; AD is funded by Guy's Charity grant number EIC180702 and MRC grant number MR/SO28188/1. JD is part supported by the ESRC Centre for Society and Mental Health at King's College London (ES/S012567/1), grants from the ESRC (ES/S002715/1), by the Health Foundation working together with the Academy of Medical Sciences, for a Clinician Scientist Fellowship, and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. The views expressed are those of the author[s] and not necessarily those of the ESRC, NIHR, the Department of Health and Social Care or King's College London. Only one study to date has used exploratory methods to determine specific physical multimorbidity patterns in order to examine their impact on future depression in older adults in China. Moreover, no one has yet assessed the effects of physical multimorbidity patterns on anxiety specifically. In the current study, we used large-scale data from the UK Biobank to identify specific patterns of physical multimorbidity and to examine the extent to which these patterns prospectively associated with depression and anxiety in middle-aged adults in the United Kingdom.There is a significant body of evidence to suggest that physical multimorbidity can lead to the development, or the persistence, of depression. However, less is known about how specific patterns of physical multimorbidity might impact future mental health, particularly in middle-aged adults. Previous studies that have investigated the impact of specific disease clusters on depression have clustered physical conditions To our knowledge, this large-scale study was the first to identify patterns of physical multimorbidity and examine the extent to which these patterns predicted both new onset and persistent common mental health disorders in middle-aged UK adults. We reported a dose-response relationship between baseline physical multimorbidity status and incident depression and anxiety at follow-up. Similar results were found for persisting symptoms of common mental health disorders. We found that the respiratory and the pain/gastrointestinal patterns of physical multimorbidity were most strongly associated with incident depression and anxiety at follow-up.The evidence taken together suggests that physical multimorbidity increases the risk of both new onset and persisting common mental health disorders. Moreover, there is increasing evidence that respiratory multimorbidity and multimorbidity where painful and gastrointestinal conditions cluster together might increase risk of future depression and anxiety considerably more than other physical multimorbidity disease clusters. These findings have implications for the implementation of integrated physical and mental healthcare services and highlight patient groups that might require targeted interventions.Alt-text: Unlabelled box1In the United Kingdom approximately 27% of adults in primary care have multimorbid conditions The relationship between physical multimorbidity and depression is generally thought to be bidirectional a priori based on broad disease categories  Steering Group NHS England and NHS Improvement - Advancing Mental Health Equalities Taskforce Health Education England - Mental Health Workforce Equalities Subgroup Maudsley Learning - Maudsley Learning Advisory Board South London and Maudsley NHS Foundation Trust (SLaM) - Independent Advisory Groups, the SLaM Partnership Group Lambeth Public Health - Serious Youth Violence Public Health Task and Finish Group Thrive London - Thrive London Advisory Board Black Thrive - Black Thrive Advisory Board NHS England and NHS Improvement - The Mental Health Workforce Equalities Subgroup Commissions: Welsh Government's Race Equality Plan; contribution to the evidence review for Health and Social Care and Employment and Income policy areas."}
+{"text": "The Global Network of Age-friendly Cities and Communities has grown steadily over the past decade across the United States, however surprisingly little is known regarding their accomplishments to date. We utilized content analysis to assess the progress reported by American age-friendly communities (n = 30) that joined by end of year 2015 using the Age-Friendly Community Evidence-based Tool with expanded program evaluation measures including health equity as defined by the World Health Organization. We employed deductive analytic techniques to assess reported community performance in eleven thematic areas across the range of structures and processes that characterize age-friendly efforts. We found strong evidence in the areas of leadership and governance, harnessed resources, application of age-friendly framework, and in multisector collaboration as well as reported provisions. All of the communities reported health equity aims, particularly in promoting accessible physical environments and social inclusion efforts. Our analysis further revealed areas for continued improvement."}
+{"text": "Identifying the early origins of adult health has underscored how experiences in the earliest stages of life can have lasting consequences. Whereas most research on the early origins of adult health has linked childhood conditions to worse health in adulthood, this study considered whether childhood conditions are associated with healthy aging. Guided by the World Health Organization\u2019s emphasis on functional ability as a core component of healthy aging, the present study investigated the association between childhood social conditions and avoiding later-life limitations in basic and instrumental activities of daily living, referred to as disability-free status. This study also tested potential health-related and socioeconomic mediators and examined whether these life course antecedents of healthy aging vary by gender. Analyzing a sample of 9,376 adults over age 50 from the Health and Retirement Study over 10 years (2006-2016) revealed that childhood socioeconomic disadvantage reduced the odds of avoiding disability over time. For women, adult health lifestyles mediated this relationship whereas adult socioeconomic status (SES) mediated this relationship for men. Conditional indirect effects indicated that the mediational effects of body mass and education differed between men and women . The direct effects of childhood and adult SES also varied by gender. These results demonstrate that the life course antecedents, especially SES, of healthy aging are distinct for men and women. Interventions should prioritize reducing early-life exposure to socioeconomic disadvantage, especially for women. Given the gendered differences in the mediating effects, midlife interventions can be tailored for men and women."}
+{"text": "This symposium included 4 studies that use national and regional data to examine older adults\u2019 disaster preparedness and coping. The first study examined age differences in preparedness for the continuation of COVID-19 with a sample of 443 residents in Dallas, TX. The findings highlight older adults\u2019 resilience and special needs for different types of support during the pandemic. The second study examined the association of having COVID-19 and intergenerational relationships using the COVID-19 module of the Health and Retirement Study with a sample of 3266 respondents. Using a national sample of 1,467 respondents from the 2017 U.S. National Household Survey, the third study examined age differences relationships among the type of disasters , response efficacy, and disaster preparedness. The findings highlighted older adults\u2019 unique vulnerability and resilience in different types of disasters. The fourth study discussed a pilot virtual reality platform under development to assist older adults to develop tailored household emergency preparedness plans and practice those plans with simulated extreme weather conditions and warnings for older adults to practice disaster response and develop relevant knowledge and skills as well as test and revise their emergency preparedness plans. Overall, this symposium emphasizes the uniqueness of older adults\u2019 needs, vulnerability, and resilience to disasters."}
+{"text": "Evidence indicates an association between emotional well-being (EWB) and underlying brain processes, and that those processes change with both normal and pathological brain aging. However, the nature of these associations, the mechanisms by which EWB and its component domains change with brain aging, and how those changes may be associated with common neuropathologies like Alzheimer\u2019s disease and related dementias (ADRD), are largely unexplored. The NIA-funded Network for Emotional Well-being and Brain Aging (NEW Brain Aging) has the goal of developing a nationwide community of investigators dedicated to research that identifies and tests mechanisms by which brain aging influences EWB and how EWB may impact risk for and progression of ADRD. Synthesizing human and animal literature, our premise is that relationships between EWB and ADRD are bidirectional \u2013 normal and pathological changes in aging brain influence EWB and EWB contributes to brain health and illness, such as ADRD. NEW Brain Aging will identify and coalesce resources for interested investigators and provide pilot funding opportunities to stimulate research and development of the field. Component presentations of this symposium will include (1) an overview by Dr. Robert Kaplan of the current state of research on EWB; (2) the role of animal studies (Kuan Hong Wang) and (3) human subjects research (Feng Vankee Lin) in EWB and aging; and (4) design of NEW Brain Aging and resources it will provide (Yeates Conwell). Janine Simmons will explain NIA\u2019s vision for EWB research and lead open discussion."}
+{"text": "Melanoma brain metastases (MBM) and leptomeningeal metastases (LMM) are two manifestations of melanoma dissemination to the CNS with vastly different survival outcomes. Analysis of single cell RNA-Seq data from 43 clinical specimens has uncovered a distinct, immune-suppressed T cell landscape in the LMM microenvironment that is distinct to those of the brain and skin metastases. An LMM patient with an extraordinarily long survival and documented response to therapy demonstrated an immune repertoire that was distinct from those of typical poor survivors and more similar to CSF from non-LMM donors. Analysis of serial specimens over the course of therapy demonstrated reductions in melanoma cells and macrophages, coupled with increased levels of T cells and dendritic cells in the CSF of the extraordinary responder, whereas poor survivors showed no improvement in T cell responses. In MBM patients, targeted therapy and immunotherapy was associated with increased immune infiltrate, with similar T cell transcriptional diversity noted between skin metastases and MBM - suggestive of immune cell trafficking into the brain. Treatment with targeted therapy was associated with an enrichment of CD8 T cells. Immunotherapy was associated with a more diverse lymphocyte landscape and higher numbers of antibody-producing cells. These findings were confirmed by multiplexed staining of patient specimens and using an immune-competent mouse model of MBM. Correlation analysis across the entire immune landscape identified the presence of a rare, novel population of dendritic cells (DC3s) to be correlated with increased overall survival, regardless of disease site/treatment. The presence of DC3s positively regulated the immune environment of both patient samples and preclinical melanoma models through modulation of activated T cells and MHC expression in the tumor. Our study provides the first comprehensive atlas of two distinct sites of melanoma CNS metastases and identifies rare populations of cells that underlie the biology of this devastating disease."}
+{"text": "The Division of Geriatrics and Clinical Gerontology (DGCG) supports clinical and translational research on health and disease in the aged, and research on aging over the human lifespan, including its relationships to health outcomes. Key areas include development of new interventions for age-related conditions and pathologies, prevention and treatment of multiple chronic conditions, geriatric palliative care, factors influencing the progression of chronic diseases over the life span, and predictive markers of aging that may inform potential interventions for extension of health span. Population diversity and health disparities are critical aspects of science that cut across DGCG research areas. This presentation will highlight several examples of DGCG-supported studies related to health disparities and discuss potential future research directions. One potential upcoming research area of interest involves leveraging large data sets to examine disparities in risks and benefits of long-term osteoporosis drug therapy and drug holidays according to racial and ethnic groupings"}
+{"text": "This report examines the heat and mass transfer in three-dimensional second grade non-Newtonian fluid in the presence of a variable magnetic field. Heat transfer is presented with the involvement of thermal relaxation time and variable thermal conductivity. The generalized theory for mass flux with variable mass diffusion coefficient is considered in the transport of species. The conservation laws are modeled in simplified form via boundary layer theory which results as a system of coupled non-linear partial differential equations. Group similarity analysis is engaged for the conversion of derived conservation laws in the form of highly non-linear ordinary differential equations. The solution is obtained vial optimal homotopy procedure (OHP). The convergence of the scheme is shown through error analysis. The obtained solution is displayed through graphs and tables for different influential parameters. Fluid flows over stretched surfaces have applications in several fields and has significant involvement in the practical usage of several items. Scientists and engineers have made efforts to explore their features and usage in different processes. The mathematical relations of non-Newtonian materials are different as compared with Newtonian material. These materials are divided into different categories according to their properties. An important non-Newtonian fluid is a second grade fluid ,4,5,6,7.Hayat et al.  studied Transportation of heat has applications in different engineering aspects and it is now a hot topic for researchers working in the field of engineering and applied mathematics. Several researchers are working on transport phenomena actively. For instance, Naseem et al.  worked oThe objective of current inspection is to analyze the comportment of variable properties in heat and mass transportation in a second grade steady incompressible model past over a bi-directional elongating surface. This article is organized as follows: x- and y-axis. The sheet is kept at temperature \u201cx-axis, the velocity is An analysis of the transport phenomenon on a second grade fluid ,14 over \u2756Three-dimensional flow;\u2756Bi-directional elastic surface;\u2756Incompressible fluid;\u2756Steady flow;\u2756Viscoelastic second grade fluid;\u2756Heat flux via generalized theory of Cattaneo\u2013Christov;\u2756Temperature-dependent thermal conductivity model;\u2756Space-dependent magnetic field;\u2756Updated mass flux model with temperature dependent diffusion coefficient;The flowing resulting equations  appears Boundary conditions for the dimensional problem areWith the use of the following similarity variables, the governing law reduce toThe study of heat, mass transfer rates and dimensionless stress at the boundary has significant applications and usage in industry. Therefore, scientists and engineers are keenly observing their features against different physical parameters which influence them directly. These quantities are defined as:After boundary layer theory, the dimensionless form is:Modelling of the fluid flow problems results in the form of a set of coupled non-linear differential equations. The derived problem is highly non-linear and coupled. Due to high non-linearity, an exact solution is not possible. Researchers proposed several schemes to handle the non-linear complex differential equations. Here, optimal homotopy analysis procedure (OHAP) ,21,22,23\u2756Linear operator selection;\u2756Using the boundary data;\u2756Determination of unknown constants;\u2756Adopting of initial guesses;This section covers the necessary steps for the adopted procedure. It has the following steps:The linear operators with initial guesses are:The operators in Equation (21) obeys:Using the concepts of minimization of average squared residual error ,21,22,23The minimum error at second order is The assessments of vital applications of thermal energy and mass transport (using second grade liquid) in industrial and engineering areas are addressed, including various features. In this current problem, non-Fourier\u2019s theory is investigated in energy and mass transport equations along with the concept of variable properties . The motion in nanoparticles is induced because of movement of a melting 3D-surface. The simulations of temperature, diffusion of mass and flow behavior are captured in the form of graphs and tables via an analytical approach. The error analysis is presented with the help of Assessments of flow phenomena via physical parameters: the distribution of flow phenomena is analyzed with respect to magnetic number (Assessments of heat energy via physical parameters: the characterization of the thermal energy mechanism against the variation in Assessments of mass diffusion via physical parameters: the distribution in transport of mass diffusion is measured against the variation in Assessments of Nusselt number, divergent velocity and Sherwood number via physical parameters: the characterization of surface force, temperature gradient and rate of solute is analyzed considering large values of second grade fluid, stretching ration and time relaxation numbers. These simulations are captured by The improvement in motion of fluid particles was captured via large values of second grade fluid and stretching ratio numbers while a decrement in flow behavior was conducted via enlargement in magnetic number;The mechanism of heat energy became maximum using higher values of second grade fluid number but an opposite trend was captured via large values of time relaxation, Prandtl and very small numbers;The solute became fast considering large values of second grade fluid, time relaxation and very small numbers. The reduction in solute became slow against variation in Schmidt number;An incline in rate of solute and gradient temperature was addressed against higher values of time relaxation numbers;The surface force was enhanced near the wall of the hot surface via large values of second grade liquid and flow stretching parameters.The physical occurrence of solute, heat energy and flow phenomena in a second grade liquid were visualized passing a 3D melting moving surface. The theory of non-Fourier\u2019s law was imposed in the current flow model inserting variable properties. The current complex model was simulated with the help of an analytical scheme. The main consequences of the current problem are addressed below:"}
+{"text": "The quest for high-performance of heat transfer components on the basis of accommodating shapes, smaller weights, lower costs and little volume has significantly diverted the industries for the enhancement of heat dissipation with variable thermal properties of fins. This manuscript proposes the fractional modeling of Fourier and non-Fourier heat transfer of longitudinal fin via non-singular fractional approach. The configuration of longitudinal fin in terms of one dimension is developed for the mathematical model of parabolic and hyperbolic heat transfer equations. By considering the Fourier and non-Fourier heat transfer from longitudinal fin, the mathematical techniques of Fourier sine and Laplace transforms have been invoked. An analytic approach is tackled for handling the governing equation through special functions for the fractionalized parabolic and hyperbolic heat transfer equations in longitudinal fin. For the sake of comparative analysis of parabolic verses hyperbolic heat conduction of fin temperature, we depicted the distinct graphical illustrations; for instance, 2-dimensional graph, bar chart, contour graphs, heat graph, 3-dimensional graphs and column graphs on for the variants of different rheological impacts of longitudinal fin. In view of preeminent studies investigating the fin problem on Fourier and non-Fourier domain subject to the periodic boundary conditions, a sequential approach has been suggested by Yang in9 with direct and inverse analysis based on the Finite difference and modified Newton Raphson methods respectively. Here, a great conformity has been established in results on the basis of accuracy between exact and non-exact techniques. In context with fin problem of non-Fourier thermal conditions, an analytical study has been carried out by Ahmadikia and Rismanian in4. They invoked the second law of thermodynamic for hyperbolic model to find temperature field. Moreover, they emphasized the impacts of time relaxation for hyperbolic model only. From mathematical point of view, Aziz et al.10 introduced the adjoint conjugate gradient method to evaluate the base temperature in non-Fourier inverse fin problem. The varying thermal conductivity subject to the wavelet collocation method for the nonlinear boundary has been investigated by Singh et al.11. Their main objective was to analyze the linear, constant and exponential temperature. Nagarani et al.12 observed the temperature distribution from the elliptical and circular annular fin through the empirical structure of computational fluid dynamics and optimizing genetic algorithm. Additionally, they validated the elliptical annular fin through both techniques. The porous fin has been quantified subject to predict the impacts of thermal diffusion and porosity through temperature profile on the fin by Das and Prasad13. They invoked differential evolution method to confess the performance with optimized algorithms. For the sake of fin geometry with optimized heat transfer via triangular, convex and concave conditions, analyticity of temperature has been carried out through least square method by Mosayebidorcheh et al.7. Recently Jing et al.14 invoked spectral element method to determine the non-uniform heat generation with variable temperature for irregular fins in porous structure. For the first time in recent literature, none of fractional model via Atangana-Baleanu differential operator is studied. The authors of this manuscript presented fractional modeling of fin on non-Fourier heat conduction in recent literature. They focused the non-singular time derivative on the mathematical model of fin with non-Fourier heat conduction15. In this context, fractional models based on non-singular kernels can have ability to disclose the hidden phenomenon through the memory effects. The distinct studies on fractional models are adhered in this regard as; fractional models based on singular kernel can be viewed in26, fractional models based on non-singular kernel can be viewed in35 and fractal-fractional differential and integral models based on singular and local as well as non-singular and non-local kernel can be viewed in46. Motivating by above discussion, we propose the fractional modeling of Fourier and non-Fourier heat transfer of longitudinal fin via non-singular fractional approach. The configuration of longitudinal fin in terms of one dimension is developed for the mathematical model of parabolic and hyperbolic heat transfer equations. By considering the Fourier and non-Fourier heat transfer from longitudinal fin, the mathematical techniques of Fourier sine and Laplace transforms have been invoked. An analytic approach is tackled for handling the governing equation through special functions for the fractionalized parabolic and hyperbolic heat transfer equations in longitudinal fin. For the sake of comparative analysis of parabolic verses hyperbolic heat conduction of fin temperature, we depicted the distinct graphical illustrations; for instance, 2-dimensional graph, bar chart graph, contour graphs, heat graph, 3-dimensional graphs and column graphs on for the variants of different rheological impacts of longitudinal fin.The parabolic and hyperbolic heat transfer from longitudinal fin has diverse industrial applications especially in air conditioning, refrigeration and few others. The Mathematical modeling of parabolic and hyperbolic heat transfer equations is not an easy task for investigating fractionalized analytical solution as well as fractionalized numerical solution. This is because temperature distribution of parabolic and hyperbolic heat transfer equations involves temperature-dependent properties2 proposed the suitable mathematical models of heat conduction for describing the conductive heat transfer in many engineering problems in 1958. Such mathematical models of heat conduction are based on an independently hyperbolic heat conduction model with a finite propagation speed so called non-Fourier model of heat conduction described as:It is well established fact in literature that Cattaneo and VernotteIn this context, a tip of the longitudinal fin is considered adiabatic subject to ratio of the thickness to the length is mentclass2pt{minimFor the sake of heat dissipation in the environment through convection, we treated convective heat transfer coefficient Equation\u00a0 classical temperature of parabolic heat transfer, (ii) classical temperature of hyperbolic heat transfer, (iii) fractional temperature of parabolic heat transfer. On the contrary, for larger time t\u2009=\u20095\u00a0s, fractionalzed temperature of hyperbolic heat transfer moves faster than (i) classical temperature of parabolic heat transfer, (ii) classical temperature of hyperbolic heat transfer, (iii) fractional temperature of parabolic heat transfer. For the sake of phyical sigficance, all the models have coincidence temperature at unit time t\u2009=\u20091\u00a0s.The comparison of classical and fractional methods measures the closeness of agreement for integer and non-integer differentiations. Such comparison leads to estimate inaccuracy and accuracy of investigated solutions among imposed classical and fractional methods. Figure\u00a0(i)The temperature distribution of parabolic heat conduction of fin has controversial trend in comparison with temperature distribution of hyperbolic heat conduction of fin.(ii)Increasing values of frequency have generated peak oscillations in hyperbolic heat conduction in comparison with parabolic heat conduction.(iii)Either parabolic or hyperbolic heat conduction is subjected for incremental amplitude then amplitude response becomes aperiodic.(iv)The comparison of classical and fractional methods measures the closeness to estimate inaccuracy and accuracy of investigated solutions.In this study, the fractionalized analytical solutions of parabolic and hyperbolic heat transfer based on temperature distribution have been obtained by employing integral transforms as shown in Fig."}
+{"text": "Over one century has passed since William Twort first discovered phages in 1915 and Felix d'Herelle recognized their potential as antibacterial agents in 1917  systems, CRISPR-Cas, abortive infection systems (Abi), adsorption inhibition (A-I), and neutralizing bacteriophage exclusion (BREX), prokaryotic Argonautes (pAgos), and DISARM  determines the enzymatic cleavage of peptidoglycan and the cell wall-binding domain (CBD) is responsible for recognition of the cell surface ligands and for attraction toward its substrate. Narrow host specificity of endolysin facilitates elimination of specific target bacteria without considerable harm to the surrounding microbiome. Moreover, endolysin does not induce bacterial resistance, possibly because endolysin targets highly conserved components of peptidoglycans that are essential for bacterial viability (Fischetti, Rapid detection of pathogenic bacteria is crucial in minimizing the risk of bacterial diseases and food poisoning. Many of the conventional microbiological and biochemical detection methods are laborious, require skilled individuals, relatively slow, and are not always accurate. The specificity of host by phages', dependence of phage replication on bacterial metabolism, and high burst size make phages an ideal platform to develop rapid detection systems with high sensitivity, stability, versatility, selectivity, and long shelf-life (Hussain et al., The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Black/African American participation in non-pharmacological randomized trials and community-based research on Alzheimer\u2019s Disease and related dementias (ADRD) remains low. This presentation introduces Critical Race Theory (CRT), its tenets and how it can be used in tandem with national strategies to encourage participation of Black/African Americans in ADRD research. CRT is a transdisciplinary methodology that draws on anti-racist tenets to study and transform the relationships among race, racism, and power. We describe how CRT constructs  can be used to inform recruitment strategies to enroll Black/African American ADRD caregivers into community-based research by drawing upon two ongoing studies: a randomized trial providing caregiver support through Adult Day Services (ADS) and the evaluation of impact of ADS on stress levels of Black/African American using biomarker measures. In the spirit of CRT this presentation is a call for action and transformation of dementia care research to actively include Black/African Americans."}
+{"text": "We implemented the KAER toolkit in the University of Washington primary care clinics. In this session we share the workflows implemented to promote the KAER model and share the tools we developed within EPIC, the system's electronic medical record (EMR). We collaborated with clinic staff to develop interdisciplinary workflows including: training patient service representatives, social workers, nurses, and medical assistants (MAs) about 'red flags;' training medical assistants to complete the Patient Health Questionnaire (PHQ-9) and Montreal Cognitive Assessment (MoCA); and assuring they are appropriately entered into flowsheets in EPIC. We created a checklist (EPIC 'SmartPhrase') and educated the clinics' interdisciplinary teams to utilize it within their scope of practice. Additionally, we created an order set (EPIC 'SmartSet') of commonly ordered tests and referrals to expedite evaluation of patients with suspected cognitive impairment. Lastly, we created a direct link from our EMR to our website containing community resources."}
+{"text": "Advance care planning (ACP) and hospice services are underutilized by patients living with HIV (PWH). Little is known about how older PWH approach ACP; the purpose of this qualitative study was to understand barriers and facilitators to ACP within the context of the patient-clinician relationship. Data are from a larger multimethod study designed to understand social determinants of health (SDH) that shape the lives and healthcare experiences of veterans aging with HIV. The sample includes 25 veterans from the Veterans Aging Cohort Study (VACS) recruited from an urban VA medical center. Semi-structured interviews were performed and analyzed using thematic analysis. Less than half of participants reported engaging in ACP. Key barriers to ACP include: fragile social ties, distrust of the healthcare system, and fear of disclosure and discrimination. We offer several recommendations for clinicians to engage in these conversations successfully and highlight the importance of considering SDH when designing interventions."}
+{"text": "Chronic viral hepatitis is a key risk factor for liver fibrosis and hepatocellular carcinoma (HCC) . AlthougThe present Special Issue provides an interdisciplinary view on the current challenges in the post-HCV cure era. It outlines the urgently required next steps to tackle the aftermath of the HCV epidemic to improve the care of HCV-cured patients at risk of developing HCC. Furthermore, this Special Issue reviews the risk of HCC in the treatment of patients with chronic hepatitis B.+ T-cell responses by Maike Hofmann [First, the HCC risk needs to become measurable in patients using recent advances in omics studies and biomarker development. Naoto Kubota reviews the clinical and molecular determinants available to predict HCC risk including large transcriptional signatures and artificial intelligence . Identif Hofmann . What ar Hofmann . Finally Hofmann .In summary, the articles published within this research topic not only give a highly comprehensive overview of the recent developments and challenges of virus-induced liver cancer risk but also highlight perspectives and opportunities for the discovery and development of biomarkers and chemo-preventive approaches for patients at HCC risk."}
+{"text": "Racial/ethnic disparities in health among older adults are well-documented. More research is needed to clarify the complex and multifactorial mechanisms underlying these associations. This symposium will feature research that employs innovative theoretical and methodological approaches to understand the biopsychosocial mechanisms that underlie racial/ethnic disparities in older adults\u2019 health and determine sources of within-group heterogeneity in minority aging. Dr. Forrester will integrate stress biology and intersectionality to demonstrate the importance of stress and resilience  with biological aging within Black adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Dr. Brown Hughes will present innovative research using data from the African American United Memory and Aging Project (AA-UMAP) on the importance of Alzheimer\u2019s disease-specific knowledge and perceptions among Black older adults. Dr. Gamaldo will employ a within-race approach to understand how knowledge and perceptions of Alzheimer\u2019s disease and related dementias (ADRD) shape cognitive performance among Black older adults in the AA-UMAP study. Dr. Mitchell will use Health and Retirement Study data to explore the role of midlife stress exposure in accounting for racial disparities in trajectories of cognitive functioning. Drs. Thierry and Farmer will use HRS data to examine how psychosocial resilience  affects the relationship between perceived neighborhood conditions  and cognition among Black older adults. This work highlights the importance of applying an interdisciplinary lens to move the study of minority aging forward and ultimately, to reduce the unnecessary burden of morbidity and mortality among minoritized groups."}
+{"text": "Distress behaviors in dementia (DBD) are common in nursing home settings, are distressing, and result in poorer outcomes for residents and staff. We present on the implementation of STAR-VA, an interdisciplinary intervention for effective management of DBD in Veterans Health Administration (VA) nursing home settings, called Community Living Centers (CLCs). A primary focus of this symposium is the use of implementation science concepts to improve and sustain evidence-based programs through tailored implementation strategies and key partnerships. Key implementation science concepts from conceptual frameworks, including the Consolidated Framework for Implementation Research (CFIR) and the use of organizational Knowledge Reservoirs (KR) for sustaining new clinical practices, formed the basis of this work. Their application in health care practice will be discussed using STAR-VA as an exemplar. Interdisciplinary CLC staff feedback during STAR-VA implementation and sustainment is presented, including feedback regarding barriers to integrating new program interventions into usual care processes. Mapping key implementation strategies onto reported barriers informed development of implementation tools and strategies designed to guide adaptions tailored to the needs of the residents and frontline staff, increasing the chances of successful sustainment. Finally, we highlight the importance of key leadership partnerships in implementation of evidence-based programs to improve care of residents with DBD and present strategies for developing these partnerships. Discussion will include the importance of using implementation science to implement evidence-based interventions for effective management of DBD and strategies for sustainment of these effective practices into usual care."}
+{"text": "The Age-Friendly University (AFU) designation in higher education recognizes the institution\u2019s commitment to a culture of age-inclusivity across programs and policies. While AFU institutions are embracing the demographic shifts in higher education and society at-large, effectively responding to the needs and desires of an increasingly older population requires ongoing acceptance and support from campus leaders to maintain momentum and stay relevant within a dynamic field. This session will describe the intentional and systematic approach utilized by an AFU steering committee to build interest in and develop meaningful collaborations in multiple domains across campus, including at the level of the president. Our initiatives focus on five themes that align with the 10 age-friendly university principles: support for workforce development, broadening community engagement, expanding engagement in aging research and dissemination, addressing barriers related to aging and our physical environment, and facilitating age-friendly efforts across our state. We will present our experiences in expanding awareness of and support for the AFU movement on our campus and share a model for institutions seeking ideas for sustainability of their own initiatives."}
+{"text": "Social isolation and loneliness in older adults are major global public health concerns. Tooth loss is also a common problem in this population. This study examined the effects of social isolation and loneliness on the number of remaining teeth and the rate of tooth loss among Chinese older adults. We included 4,268 older adults age 65+ from three waves of the Chinese Longitudinal Healthy Longevity Survey . Linear mixed-effect models showed higher levels of social isolation were associated with fewer remaining teeth  and accelerated tooth loss  controlled for socio-demographic, lifestyle, oral hygiene behavior, and health status. Loneliness was neither associated with the number of remaining teeth  nor with the rate of tooth loss  before and after controlling for covariates. These findings expand our knowledge regarding the correlation between social connection and tooth loss in non-Western populations."}
+{"text": "ABSTRACT IMPACT: This project successfully implemented a promising team science model by introducing and facilitating best practices to develop high functioning teams working to accelerate health innovations from bench to bedside. OBJECTIVES/GOALS: The goal of this project was to improve the team science knowledge, skills, and attitudes of interdisciplinary engineering students (undergraduate and graduate) who were partnered with health professionals to develop technical solutions to translational health challenges during a year-long Engineering Innovation in Health (EIH) program. METHODS/STUDY POPULATION: We adapted, implemented, and evaluated team science training content and approaches in the EIH program at the University of Washington (UW). EIH faculty and the UW Institute of Translational Health Sciences\u2019 (ITHS) Team Science Core co-developed and delivered highly interactive team science training modules and evaluated their impact with biannual surveys. A student cohort was surveyed prior to the implementation of the team science trainings, which served as a baseline. Descriptive statistics were used to summarize student demographics and survey responses within and between years. Median and interquartile range of responses to Likert-type questions were calculated, and Mann-Whitney U Tests (independent samples Wilcoxin Rank Sum Tests) were used to test for differences within and between years. RESULTS/ANTICIPATED RESULTS: During both the baseline and the team training year, student demographics were similar in terms of gender and past experience working in teams. Team training during the first year of implementation was well-received. Post-implementation surveys of students demonstrated measurable improvement in team dynamics, communication, and effectiveness; including, students reporting higher levels of psychological safety and self-efficacy within their teams. Comparisons within the team training year and between the baseline and team training years identified numerous instances in which differences were statistically significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: Tailored team science training in an interdisciplinary EIH program was successful at improving psychological safety and self-efficacy among undergraduate and graduate students and offers a promising model for similar settings and audiences."}
+{"text": "Across studies on social stress exposure on the mental health of older African Americans, most investigate singular stress exposures (discrimination). Furthermore, this research rarely assesses gender differences in the psychological effects of specific stress exposures. I use the National Survey of American of Life to assess: (1) gendered patterns of stress exposure among older African Americans; (2) gendered nuances in the individual, collective, and cumulative effects of stress exposure on mental health. I find gender patterns of stress exposure differed by type of stressor. Women and men shared some stress predictors of mental health (everyday discrimination). Other stress predictors were specific to women  or to men (perceived neighborhood crime). Study findings challenge gerontologists to consider how race-gender groups are at distinct risks for stressors that elicit poor mental health and provide a call for tailored strategies for improving the psychological health of African American women and men."}
+{"text": "Biological invasions, the establishment and spread of non\u2010native species in new regions, can have extensive economic and environmental consequences. Increased global connectivity accelerates introduction rates, while climate and land\u2010cover changes may decrease the barriers to invasive populations spread. A detailed knowledge of the invasion history, including assessing source populations, routes of spread, number of independent introductions, and the effects of genetic bottlenecks and admixture on the establishment success, adaptive potential, and further spread, is crucial from an applied perspective to mitigate socioeconomic impacts of invasive species, as well as for addressing fundamental questions on the evolutionary dynamics of the invasion process. Recent advances in genomics together with the development of geographic information systems provide unprecedented large genetic and environmental datasets at global and local scales to link population genomics, landscape ecology, and species distribution modeling into a common framework to study the invasion process. Although the factors underlying population invasiveness have been extensively reviewed, analytical methods currently available to optimally combine molecular and environmental data for inferring invasive population demographic parameters and predicting further spreading are still under development. In this review, we focus on the few recent insect invasion studies that combine different datasets and approaches to show how integrating genetic, observational, ecological, and environmental data pave the way to a more integrative biological invasion science. We provide guidelines to study the evolutionary dynamics of invasions at each step of the invasion process, and conclude on the benefits of including all types of information and up\u2010to\u2010date analytical tools from different research areas into a single framework. BecauseGenome\u2010scale datasets have triggered the development of new analytical methods able to deal with large amount of information. Here, we provide an overview of these methods for addressing (i) population structure and colonization routes, (ii) demographic inferences, (iii) local adaptation, and (iv) landscape genetics, the type of data used and the software names, and their utility and their limits Table . These mWhile HTS was revolutionizing population genomics, geographic information systems were revolutionizing ecology. Species distribution models . We discuss the limits and advantages of each of these approaches, from data collection to analytical methods, highlight their complementarity, and identify gaps in our knowledge that need to be filled in order to reach a fully integrative understanding of biological invasion. We structured our review according to the chronological steps of the invasion process although we are aware that assigning the invasive steps can be challenging or may vary in space for a given species.Here, we provide an overview of the demo\u2010genetic and adaptive processes involved at each step of biological invasions, highlighting the approaches and type of information that are needed to fully describe the invasion process, including historical records (detection time series), demographic inferences , phenotypic measures , environmental characterization of source versus invaded areas (niche comparisons), identification of traits and genes involved in adaptation to the novel environment, and their evolutionary history  and then to Europe  identify the most likely source population(s) (colonization routes), (ii) describe the introduction dynamics: levels of genetic diversity in introduced populations and their source(s) or bottleneck intensity (demographic inferences), and (iii) examine the relationship between introduction modalities, the changes in demographic features, and the successful establishment (phenotypic experiments) Box .BOX 2H.\u00a0axyridis has been intentionally introduced for biological control establishing wild populations in America, Europe, and Africa. Historical data on biocontrol practices and the reconstruction of colonization routes from genetic data demonstrated a bridgehead scenario, involving the colonization of NAM from both Eastern and Western Asia (admixture event 1) that served as the source for the South American (SAM), South African (SAF), and European (EU) invasions  reveals a reduced number of haplotypes among invasive populations as compared to the native ones  the introduction history and better understand the role of admixture (heterosis) and inbreeding (purge of genetic load). F1 hybrids display higher  and/or spread farther or faster (geographic distance or occupied area) than low\u2010diversity ones? Concerning the evolution of fitness in introduced populations, the genetic load can be estimated from genomic data  only successfully established populations are observed, and (ii) demographic parameters such as population growth or bottleneck intensity are hardly measurable in the field. For example, quantifying population growth in natural populations would require tedious MRR experiments as soon as new arrivals have been detected and over several generations and then compare the outcome of each detection with the reconstructed invasion history (number of sources and founding diversity). Experimental introductions manipulating the genetics and demography simultaneously have shown that establishment success  increases with the density and/or diversity of founders but depends on the species  and Japan (JAP) (admixture event 1) that served as the source for the initial colonization of North Italy (NIT), and independent introductions from CHI in Albania  and Central Italy (CIT) (admixture event 2)  to human\u2010modified  environments within its native range, and artificial containers are the mode of its introduction worldwide. Because the realized niche also includes biotic interactions, the absence of parallels between climatic distribution in invaded and source ranges may reflect competitive interactions setting each range limits  before introduction by studying adaptive variation within the source range  and insecticide resistance alleles being preferentially transferred from a species to another  or using estimation of genomic admixture rates as a component of demographic history (colonization routes). However, a large number of tools, based on genetic differentiation, local ancestry inference, or phylogenetic relationships, have been specifically developed to detect recent introgression and to determine the population of origin of introgressed fragments Table . Introgr4.3The functional relevance of genes identified using landscape genomics remains unknown until the observed genetic changes have been linked to phenotypic changes of the selected trait. Establishing this causative link represents one of the greatest challenges in invasion genetics. First, it requires experimental settings in order to disentangle phenotypic plasticity from adaptive evolution in natural populations. The role of phenotypic plasticity in biological invasions has been reviewed elsewhere  as compared to neutral genetic differentiation (FST) and phenotypic differentiation (QST) has been largely used to detect the loci targeted by selection . This approach requires identifying the core and edge populations, which is difficult in the absence of dated introductions but genetic diversity gradient along the expansion axis can inform about the location of ESI  and regional  models and multiple environmental predictors (climate and land use) can significantly improve invasive range predictions especially for ongoing expansion violating the equilibrium assumption of SDM  , as demonstrated by landscape genetics surveys in At the local scale, the genetic structure of populations can partly reflect natural dispersal, which can be influenced by geographic distance, by environmental barriers, or by resistance of land\u2010cover features. For example, testing land\u2010cover features as a barrier or corridor for gene flow between populations, Sherpa et al.  demonstr5.4Callosobruchus maculatus and Tribolium castaneum . Historical data are still under\u2010represented in invasion studies because early detection of introductions and careful monitoring of further expansion are challenging and costly. However, SDM might not be conclusive if based on a limited number of occurrences. Participative citizen science projects represent an interesting alternative to monitoring structures, and will potentially provide huge occurrence datasets, providing the invasive species is easily identified, fueling distribution and evolutionary models  and of changes overtime in human activities in ecological studies would allow to go a step further in our capacity to predict future invasive range expansions. Developing new methods explicitly incorporating different types of data rather than performing separately different types of analyses represents the future challenge in invasion science.We thank Nicolas Bierne and three anonymous reviewers for helpful comments on a previous version of the manuscript.The authors declare that they have no conflict of interest.Appendix S1Click here for additional data file.Table S1Click here for additional data file."}
+{"text": "Measure compliance with National Institute for Health and Care Excellence (NICE) recommendations in four Adult CMHT'sGuide further service development.We audited the case notes of 20 patients each currently under care of 9 General Adult Consultants across 6 CMHT's in East side of North Wales against NICE standards using an adapted version of the ADHD audit support tool.My role in the Project & How does this represent my practice?I was the audit and overall lead for this projectI formulated the audit tool and registered my project with Audit Registration Team.I lead data collection and compilation of results.Overall, this is the first audit of Adult ADHD Services in East side of North Wales.It established good compliance with NICE guidance for assessment and treatment.NICE has expressed the need for full mental health and social assessment including full history and physical examination prior to the drug treatment.Good compliance was observed in using & documenting Diagnostic Criteria (DSM-IV and/or ICD-10).There were deficiencies in conducting or arranging recommended physical examination & side effect monitoring.Drug treatment was the first line of treatment in the majority of cases.Antipsychotics were used in some patients referred for ADHD assessment, despite the fact that NICE has ruled out the use of antipsychotic drugs in treatment of core symptoms of ADHD.Prevalence of Adult ADHD clinician case load in Wrexham and Fintshire Counties.Diagnosis of Adult ADHD according to ICD 10 & DSM IV Guidelines.Pre treatment screening of physical health for ADHD patients.Side effects monitoring of patients on stimulant medications.The finding highlights the need for more effort in educating clinicians about safety and effectiveness of antipsychotics in ADHD.Comprehensive treatment programmes that address psychological, behavioural, educational and occupational needs should be established.Development of local ADHD Clinics, support groups and in partnership with the voluntary sector should be encouraged.It is important that mental health professionals receive appropriate training in assessment, management & monitoring of ADHD patients with co morbid substance use disorder and other mental illnesses.BETSI Health Board to participate in national Prescribing Observatory for Mental Health (POMH-UK) Quality Improvement Programme (QIP) focusing on prescribing for ADHD in children, adolescents & adults."}
+{"text": "The COVID-19 pandemic has disproportionately impacted older adults, and the educational service-learning opportunities available to gerontology students. As an applied major, Sacramento State University\u2019s Gerontology Department heavily depends on service-learning. The pandemic affected existing gerontology placements and their ability to host student learning. In addition, at the outset of the pandemic, Sacramento State University immediately terminated in-person service learning. The Gerontology Department prioritized student and community safety while still valuing the need for students to have meaningful and relevant community-based learning experiences. Gerontology faculty worked with community partners to shift these vital learning experiences. This poster presentation focuses on the creative ways the department engaged community partners to continue quality learning opportunities for students while assisting community partners with the unrelenting shifts in operations. Three innovative service-learning and community engagement practices will be addressed, including a) Partnering with the California Office of Emergency Services  to create and provide the statewide Social Bridging Project for older adults throughout California; b) Expanding the relationship with Sacramento State\u2019s Renaissance Society, a lifelong learning and community engagement program for older adults; and c) Partnering with a community-based Cardio-vascular Wellness Program to keep older adults active and engaged while remaining at home. The poster will review the pivot to virtual service learning and share how this shift enhanced student learning and community service. This will include expanding the use of technology and capitalizing on innovative methods to reach out and provide service to older adults, the local community, and the state of California."}
+{"text": "The COVID-19 pandemic presented extraordinary challenges for professionals in the aging field across campuses and communities, calling for rethinking and redesigning how their work was structured, their programs were delivered, and their connections were sustained. The pandemic also made clear the value of being an age-friendly institution of higher education, especially as we experience historic changes in age demographics. This symposium features campus leaders representing institutional partners of the Age-Friendly University (AFU) global initiative (endorsed by GSA\u2019s Academy for Gerontology in Higher Education) who will discuss how their age-friendly programs were adapted during the pandemic to continue to advance age inclusivity. These diverse responses exemplify the vast potential of age-friendly opportunities. June and Andreoletti  will discuss how the Scholars for Life! program supported the engagement of older learners in the neighboring community through the engagement of faculty. Elfenbein (University of North Georgia) will describe how learning experiences for older learners and intergenerational exchange were created beyond the classroom through the Personal Enrichment, Action and Knowledge (PEAK) program. Terhune (Northern Kentucky University) will describe how student support practices and services were adapted to provide working adult students with guidance for navigating their educational needs during the pandemic. Kheirbek  will describe how age-friendly collaborations with the institution\u2019s medical school leveraged intergenerational connections and technology to foster social connection for hospitalized older adults. Gautam and Melillo (UMass Lowell) discuss how a campus partnership with the Learning in Retirement Association (LIRA) adapted efforts around healthy aging."}
+{"text": "Humanities and Social Sciences Communications 10.1057/s41599-021-00906-7, published online 7 October 2021.Correction to: The original paper lacked a clear statement on ethical approval and informed consent. The following statements have now been added to the paper to provide additional clarity for the reader:Ethical approvalThe research is part of an East Tennessee State University Institutional Review Board PCORI approved protocol that embodies the protection of human subjects.Informed consentThe research is part of an East Tennessee State University Institutional Review Board PCORI approved protocol that embodies informed consent."}
+{"text": "The world today is very different from how it was. The consumption rate of fossil fuels compared with the available resources and the calamity of global warming frighten people. The entire planet is at risk, but these are our crises. Mankind is the cause and so mankind should find sustainable and green energy solutions to satisfy the needs of society.Chemical reactions driven by solar energy can not only diminish consumption of fossil fuels and pollution from such consumption, but also achieve high selectivity through exact energy exchange between photons and electrons. Since the pioneering work on electrochemical photolysis of water in 1972, semiconductors and other light-absorbing materials such as plasmonic metals have been widely explored . For a l2 to hollow mesoporous zinc silica composites (HMZS) under mild hydrothermal conditions. The research traces the transformation process under different conditions via semi-in situ technique, and an \u2018adhesive-contraction\u2019 mechanism of hollow structure formation is proposed. Meanwhile, the synthesis strategy ensures controllability of the spatial location of active metals. The situation of AuPt bimetallic nanoparticles inside/on the surface (AuPt@HMZS and AuPt/HMZS) of the hollow structures depends on the order of metal loading and shell coating.To demonstrate the vital role of confined nanospace, a recent cooperative research group led by Prof. Jian Liu from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences and Prof. Jun Huang from the University of Sydney investigated the effect of hierarchically hollow-structured nano-photoreactors loaded with bimetallic catalysts at different positions for photocatalytic oxidation of cinnamyl alcohol . HierarcAuPt bimetallic nanoparticles inside/on the surface of the hollow structures exhibited a broader absorbance region under visible light than monometallic, through the influence of strong metal\u2013metal interactions, as shown in Fig.\u00a02 molecules adsorbed on the Pt surface could receive a hot electron to produce freestanding superoxide radicals (O2\u2022\u2212), which are responsible for the catalytic oxidation of the reactant. For AuPt@HMZS catalysts, there is no doubt that O2 molecules need to diffuse into the confined space through channels in the shell. Therefore, accumulation and collision of reactants in the confined space also accelerate the reaction , may provide more opportunities for rational design of efficient catalysts. The development of new technology to monitor the confined space parameters of nanoreactors renders visible the \u2018black boxes\u2019 of reactions occurring in confined space.This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University (IRT 15R52) of the Chinese Ministry of Education, the National Natural Science Foundation of China (NSFC-U1663225), the Major Programs of Technical Innovation and the Overseas Expertise Introduction Project for Discipline Innovation (111 Project) (B20002).Conflict of interest statement. None declared."}
+{"text": "The APPT project supports the early detection and treatment of age-related cognitive decline and dementia by 1) enhancing adherence to cognitive intervention and assessment protocols, 2) improving understanding of barriers to long-term adherence, and 3) developing algorithms for predicting and preventing adherence failures. Two randomized controlled trials will test an adaptive technology support system predicted to boost adherence to cognitive protocols over a period of six months within samples of older adults with and without cognitive impairment. These studies will provide insight into the benefits of adherence support, and individual difference factors that should shape the adherence protocol, informing the process of identifying individuals who would benefit from additional support and predicting and preventing extended adherence failures before they happen. These studies should improve early detection and treatment of cognitive decline, extend functional independence, and improve lives of those with cognitive impairment as well as the lives of their families."}
+{"text": "Hack and Helmy's method for the histochemical identification of NAD(P)H nitroblue tetrazolium reductase activity was employed to pinpoint reductase activity in certain cells in the mouse. High activity was observed in the following: lower airway epithelium, liver (centrilobular zone), eyelid (meibomian and sebaceous glands), vulval gland and parotid gland . All of these cells had previously been identified as sites of binding of the reactive metabolites formed from the enzymic reduction of misonidazole (MISO) . It had previously been thought that MISO binding would only take place in significant amounts in hypoxic tissues (tumour and possibly liver) since in normoxic tissues oxygen should reverse the initial one electron enzymic reduction, thus preventing progressive reduction to reactive species. We suggest that the very high levels of reductase in the above listed, probably normoxic, tissues contribute significantly to the accumulation of bound reactive MISO metabolite(s)."}
+{"text": "The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed."}
+{"text": "Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to prevent morbidity and mortality by appropriate screening. In medical research recent advances in molecular genetics offer the prospect of isolating the genes involved in the pathogenesis of familial RCC and of the more common sporadic cases. In this article we review the clinical and molecular genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma).Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin"}
+{"text": "Following chemotherapy for metastatic nonseminomatous testicular cancer, 86 patients with normal serum markers AFP and HCG underwent resection of residual tumour masses . Prognostic factors for relapse and survival were analysed with Kaplan-Meier curves and Cox regression analysis. Putative prognostic factors included age, the primary histology, prechemotherapy level of the tumour markers AFP and HCG, the extent of disease  before and after chemotherapy, the histology of the resected material and the completeness of the surgical procedure. Eleven patients relapsed during follow-up (median 47 months), accounting for a 5 year relapse free percentage of 87.4%. Adverse prognostic factors were (1) prechemotherapy level of HCG  incomplete resection; and (3) the extent of disease, especially of lung metastases . The histology found at resection was not associated with the risk of relapse, which might be explained by the effectiveness of postresection chemotherapy, which in the majority of these patients was a salvage regimen rather than two further cycles of the initial cytostatics. A good and a poor risk group were formed, based on HCG level and completeness of resection. The effect of salvage chemotherapy after resection of viable cancer cells needs further investigation."}
+{"text": "An autosampler/injector commutator for flow injection analysis (FIA) was constructed with electronic components of used equipments. The apparatus is controlled by commercially available multifunctional interface (PCL711B) connected to a personal computer, and the software was written in Visual Basic language. The system was applied to water analysis and it presented satisfactory results. The low cost and simplicity are the principal characteristics of the autosampler/injector commutator."}
+{"text": "The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist.Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included.ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial,  It has been revealed by many epidemiological studies including the Framingham study that diabetes mellitus (DM) and hypertension (HT) are respectively risk factors of cardiovascular diseases and that the coexistence of DM with HT considerably increases the risk of cardiovascular diseases -4. The rOn the basis of these knowledge, observations, and findings, optimum target blood pressure levels for HT patients with DM (DM+HT patients) are set at 130/80 mm Hg lower than those for general HT patients in various guidelines -10. WhilThe types of antihypertensive drugs that are recommended to the treatment of DM+HT patients vary with guidelines, but in many cases renin-angiotensin (RA) system depressants and calcium channel blockers (Ca blockers) are recommended, taking into consideration the influence on glucose metabolism.Angiotensin II (A II) is a peptide hormone closely involved with the Na excretion control via the RA system. A II is widely recognized from the action mechanism to influence the onset and exacerbation of HT. ACE inhibitors suppressing A II production and A II receptor antagonists (A II antagonists) have been developed as antihypertensive drugs suppressing the RA system, and used all over the world ,11,12. IOn the other hand, Ca antagonists exert the antihypertensive action to wide-ranging patients, and are commonly used as antihypertensive drugs through the mechanism of inhibiting calcium entry, which triggers constriction in vascular smooth muscle cells. Ca antagonists are recommended as a therapeutic medicine for DM+HT patients, because they have no adverse influence on lipid metabolism or glucose metabolism -28.In recent years, the use of A II antagonists as antihypertensive drugs for DM+HT patients is being increased in Japan. The increase in dose of antihypertensive drug, the combined use of antihypertensive drugs with different mechanisms, and so on, are considered as methods to respond to the inadequate control of blood pressure in HT patients. However, there is no distinct evidence of the measure that will make better control of blood pressure to become a reality in DM+HT patients, whose blood pressure is inadequately controlled with A II antagonist.In hypertensive patients whose blood pressure levels were inadequately controlled by single therapy with an A II antagonist, we designed the ADVANCED-J study to compare different methods for antihypertensive therapy, i.e., the increase in dose of A II antagonist and the combined use of a Ca blocker amlodipine, which is most frequently used in Japan, in terms of the usefulness.Subjects are recruited in outpatient offices of university hospitals or general hospitals from the entire apectrum of patients with coexistent hypertension and type 2 diabetes mellitus.all of the following conditions by investigators, are included in the study.The patients, who are judged as meeting 1) Patients with type 2 diabetes mellitus2) Patients who have been treated by the single use of AII antagonist  at usual doses for at least 8 weeks (including the observation period of 2 weeks or more for the study) or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks (including the observation period of 2 weeks or more for the study).3) Patients who show > 135 mm Hg systolic or > 85 mm Hg diastolic of the ambulatory blood pressure levels measured (in the sitting position) at the time of start of the observation period, and show > 130 mm Hg systolic or > 80 mm Hg diastolic of the mean (home blood pressure level measured after getting up before the start of study) of the home blood pressure levels after getting up for the last 5 days during the last 2-week observation period.4) Patients whose consent is obtained at age 20 years or over.5) Patients whose consent is obtained from themselves in written form.With regard to 2) and 3), however, the case, which shows > 180 mm Hg systolic or > 110 mm Hg diastolic of the mean of the home blood pressure levels measured after getting up for the last 5 days during the first 1-week observation period, is included in the study.one of the following conditions by investigators.This study excludes the patients who are judged as being conformed to 1) Patients with secondary hypertension.2) Patients who show > 180 mm Hg systolic or > 110 mm Hg diastolic of the ambulatory blood pressure levels measured (in the sitting position) at the time of start of the observation period.3) Patients with severe hepatic dysfunction.4) Patients with severe renal dysfunction.5) Patients with a past history of hypersensitiveness to study drugs.6) Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant during the study period.7) Patients who have attended other trials within 3 months before the start of the observation period or who attend other trials simultaneously with the present study.8) Other patients judged as being inappropriate for the subjects of the study by investigators.Investigators confirm that the subjects are consistent with the inclusion criteria and are not contrary to the exclusion criteria and input necessary matters on the Web before the start of the study (before the start of the period when the dose is increased or other concomitant drug is used). The results of the dynamic allocation to two groups according to the eligibility of the relevant patient to the study and background factors (Increased AII antagonist dose group and combined amlodipine group) are indicated on the Web by E-mail.The urinary albumin levels during the observation period  and systolic blood pressure levels  of the home blood pressure levels after getting up before the start of the study are taken into consideration on allocation of the patients (into the increased AII antagonist dose group and the combined amlodipine group).The following commercially-available drugs are used as study drugs in the study , the study drug is taken after breakfast or after getting up once a day.The dose of AII antagonist in the increased AII antagonist dose group is the maximum dose approved. However, in the cases in which the antihypertensive effect is excessive (< 110 mm Hg systolic or < 65 mm Hg diastolic of the home blood pressure after getting up), and in which the dose is required to be reduced, the dose of AII antagonist may be reduced.The dose of AII antagonist in the combined amlodipine group is the same as that  during the observation period, and the dose of amlodipine is 5 mg/day. However, in the cases in which the antihypertensive effect is excessive (< 110 mm Hg systolic or < 65 mm Hg diastolic of the home blood pressure* after getting up) and in which the dose is required to be reduced, the dose of amlodipine may be reduced (See Table * Note: The mean of the blood pressure levels measured for the last 5 days during the 2-week period throughout the study period.Three years after the start of study.The home blood pressure levels after getting up are < 125 mm Hg systolic and < 80 mm Hg diastolic.Note: The mean of the levels measured for the last 5 days during the 2-week period (during the 14-day period between 14 days before the day of ambulatory examination and the previous day of the ambulatory examination day) before the ambulatory examination day (the reference day of the months without ambulatory examination).* (1) The following drugs may be concomitantly used with AII antagonist under individual conditions1) Antihypertensive drugs used concomitantly with AII antagonist before the start of the observation period 2) Antihypertensive drugs other than the study drug from 8 weeks onward after the start of the study.3) Drugs used for the treatment of complications(2) The drugs prohibited to be concomitantly usedAntihypertensive drugs other than the study drug for 8 weeks after the start of the study.(3) Combined therapyCombined therapy including standard diet therapy, therapeutic exercise, prohibition of smoking, etc. is not restricted.A chart of steps to increase doses of the study drug and antihypertensive drugs other than the study drug and to use concomitantly an antihypertensive drug other than the study drug is shown below  period of the increase in dose or the concomitant use .\u2022 Changes in the home blood pressures after getting up (home blood pressure levels)\u2022 The rate of home blood pressure levels accomplishing the target levels (< 125 mm Hg systolic and < 80 mm Hg diastolic)\u2022 Changes in the blood pressure levels measured on an outpatient basis (ambulatory blood pressure level)\u2022 The rate of the ambulatory blood pressure levels accomplishing the reference levels (< 130 mm Hg systolic and < 80 mm Hg diastolic)\u2022 Changes in the home blood pressures before going to bed\u2022 Changes in IMT of the cervical artery\u2022 Changes in PWV\u2022 Changes in echocardiographic findings\u2022 Changes in urinary albumin level\u2022 Changes in BNP\u2022 Changes in hs-CRP\u2022 Medical cost-effectiveness\u2022 Adverse events, adverse drug reactions\u2022 Clinical laboratory dataThe Clinical Protocols Committee and members of the Clinical Protocols Preparation Subcommittee decide the transaction of the cases and to fix the data collected for 12 months and 36 months after the start of the study.1) Population to be analyzed for efficacy\u2022 The major population to be analyzed for efficacy includes those defined according to the principle of intention-to-treat principle.2) Population to be analyzed for safety\u2022 The population to be analyzed for safety include the population in which the dose of the AII antagonist is increased or the additional concomitant use of amlodipine is conducted after the start of the study.Main outcome measures and analytical methods:1) Main outcome measures(a) Changes in the home blood pressures after getting up (home blood pressure level)(b) The rate of home blood pressure levels accomplishing the target levels2) Analytical methods2 test.With regard to (a), the subjects include \"the population to be analyzed for efficacy\", and summarized statistics about difference in blood pressure (the extent of antihypertensive effect) at each instant of survey are calculated from blood pressure at each instant of survey and from blood pressure levels during the observation period. Analysis of variance is applied for the inter-group comparison. In each group the blood pressure levels during the observation period are compared with the blood pressure levels at the instant of survey for reference. The extent of antihypertensive effect is also compared between the groups at each instant of survey. With regard to (b), the subjects include \"the population to be analyzed for efficacy\", and the rates of the blood pressure levels measured 8 and 12 months after the start of the study, which accomplish the target blood pressure levels, are calculated and the frequencies with which the rates are obtained are compared by \u03c7Secondary outcome measures and analytical methods:1) Secondary outcome measures(a) Changes in ambulatory blood pressure levels(b) The rate of ambulatory blood pressure levels accomplishing the reference levels(c) Changes in home blood pressure levels measured before going to bed(d) Changes in carotid IMT(e) Changes in PWV(f) Changes in echocardiographic findings(g) Changes in urinary albumin level(h) Changes in BNP(i) Changes in hs-CRP(j) Medical cost-effectiveness2) Analytical methodsWith regard to items (a) and (c), the analysis includes \"the population to be analyzedfor efficacy\", and conforms to \" (3) 1) (a) Changes in blood pressure levels measuredat home after getting up\". With regard to item (b), the analysis includes \"thepopulation to be analyzed for efficacy\", and conforms to \"(3) 1) (b) The rate of homeblood pressure levels accomplishing the target levels\". With regard to items (d)through (i), the analysis includes \"the population to be analyzed for efficacy\", and theblood pressure levels during the observation period are compared with those at eachtime point of survey in each group. The difference between the blood pressure levelduring the observation period and that at each instant of survey is comparedbetween the groups. With regard to item (j), the analysis includes \"the population tobe analyzed for efficacy\", and the drugs used, the contents of events, and medicalfees required are compiled according to groups for comparison.The statistical analysis follows the fixation of the data collected for 12 months after the start of the study and of the data collected (for 36 months after the start of the study) during the follow-up period.The target number of the patients is 300 patients consisting of 150 in the increased AII antagonist dose group and 150 in the combined amlodipine group.Selection of methods for antihypertensive therapy has been a matter of controversy, but the results of meta-analysis of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which the results of large-scale clinical studies in recent years were comprehensively interpreted, have suggested that the way to decrease the blood pressure, rather than the types of antihypertensive drugs, is important for prevention not only of stroke but of coronary arterial diseases such as myocardial infarction. When the efficacy of the initiated antihypertensive drug is inadequate, physicians adopt either the increase in dose of the antihypertensive drug or the combined use of another antihypertensive drug with the initiated drug as alternative choices. However, there are hardly any studies on comparison of these alternatives in terms of the antihypertensive effect or the influence on cardiovascular events.Some reports have shown that the combined use of antihypertensive drugs is needed to particularly HT patients with DM or nephropathy. Of these drugs, A II antagonists have been reported to have favorable influence on the renal function. In recent years the use of A II antagonists is increasingly used as the first-line medicine for HT patients with DM or nephropathy. On the other hand, it is also true that there are many patients who receive treatment by the combined use of a Ca blocker with the antagonist in many studies of evaluation of the efficacy of these drugs. The results of the meta-analysis in recent years have suggested that adequate control of blood pressure levels is also necessary for adequate exertion of the usefulness of RA system depressants in hypertensive patients.While it has been reported that there is correlation between the antihypertensive action and the dose of A II antagonists, some reports have shown that the increase in the antihypertensive effect is limited even by the increase in dose to more than the usual dose. Since an adverse effect of ACE inhibitors, a dry cough, is frequently observed in Japanese people, the shift to A.R.B. rapidly proceeded. However, NHI drug price of A.R.B. is high. With regard to the use at dose more than the usual dose, its efficacy needs to be reviewed from a viewpoint of medical cost-effectiveness. Based on the background, the ADVANCED-J study was designed to compare the increase in dose of A II antagonists and the combined use of amlodipine with an antagonist in terms of the antihypertensive effect in hypertensive patients whose blood pressure levels were inadequately controlled by single therapy with an A II antagonist.The primary outcome measure of the ADVANCED-J study included the home blood pressure measured in the early morning. The prevalence of home blood pressure monitor in recent years has allowed comprehension of details of the blood pressure condition. As a result, the presence of so-called masked hypertension, which shows the inadequately controlled home blood pressure in spite of the controlled ambulatory blood pressure, has increasingly been revealed.It has been reported that the risk of cardiovascular events in masked hypertension patients is as high as that in persistent hypertension patients. The importance of 24-hour blood pressure control involving home blood pressure is increasingly recognized. In fact, it is not realistic on a point of principle or from the aspect of medical cost-effectiveness to conduct the ambulatory blood pressure monitoring (ABPM) in all hypertensive patients. On the other hand, at least 30,000,000 home blood pressure monitors have been put on the market up to date in Japan, and it can be said from the global aspect that they have become more widespread in Japan. The blood pressure levels measured with home blood pressure monitors, particularly those measured at the time of rising in the morning, have been reported to reflect changes in blood pressure during the course from the night to the early morning. The correlation between blood pressure levels at home in the morning and the onset of cardiovascular events has also been reported. It is considered important for suppression of cardiovascular events in HT patients with DM to control the home blood pressures measured in the morning.There are many DM patients who show the non-dipper type of changes in blood pressure, i.e., the type which shows an only slight spontaneous decrease in blood pressure during the night , and the home blood pressures measured in the morning are predicted to be high in them. It is therefore considered important for prevention of the onset of cardiovascular events to control the home blood pressure measured in the morning even in HT patients with DM.However, there have been only few or no comparative studies on drugs, which have focused on home blood pressures measured in the morning in HT patients with DM. There have been no studies on the point of which is more efficient for controlling of home blood pressures measured in the early morning, the increase in dose of A II antagonists or the additional combined use of a Ca blocker. Based on these circumstances, the home blood pressures in the morning were adopted to evaluation of blood pressure control in this study.The compliance of recording by patients and bias due to selection of levels at the time of data recording have influence on reliability of the measurement of blood pressure levels at home. For this reason, the i-monitoring system was adopted to the ADVANCED-J study, and all the blood pressure levels measured were semiautomatically accumulated in the Data Center. All the data from the measurements and the summary data were supplied to physicians via web when necessary.It has been believed that arteriosclerosis is more likely to progress in DM patients. According to Kawamori et al., it is clear that intimal-medial thickening (IMT), i.e., an indicator of systemic arteriosclerosis, has been increased even in the pre-stage of DM . As methods of assessing arteriosclerosis in the coronary artery, various techniques, such as quantitative coronary arteriography, intravascular ultrasonography, multi-slice CT, MRI, etc., have been developed. It is impossible to widely use these techniques because of some problems with invasion to patients, exposure to radiation and magnetism, etc. and of procedural complexity of measurement. The assessment of IMT by cervical arterial echography or the evaluation of baPWV by measurements of pulse waves at the wrist and ankle yields no invasion to patients. These techniques are methods of assessing arteriosclerosis, which rarely allow physical load to patients. Even for general clinics, these techniques are the less invasive methods for assessment, which are simple to maneuver. IMT and baPWV were applied as indicators in this study, and the influence of antihypertensive therapy on progression of arteriosclerosis was also evaluated.The ADVANCED-J study is a prospective clinical study that is designed to compare the increase in dose of A II antagonist and the combined use of a Ca blocker, amlodipine, in terms of the efficacy for blood pressure control in DM+HT patients whose blood pressure levels are inadequately controlled by the single treatment with an A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure.The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in HT patients with DM. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.The author(s) declare that they have no competing interests.RK and HD functioned as the general control physicians. JK drafted the statistical analysis plan. YI contributed to set out standard blood pressure levels. TY took the initiative in designing study protocol. YT, KM, AK, DH and SI also participated cooperatively to design study protocol. All authors read and approved the final manuscript.Ryuzo Kawamori; Hiroyuki Daida; Yasushi Tanaka; Katsumi Miyauchi; Akira Kitagawa; Dobun Hayashi; Junji Kishimoto; Shunya Ikeda; Yutaka Imai; Tsutomu Yamazaki for ADVANCED-J Study GroupControl physician: Ryuzo Kawamori; Hiroyuki Daida(Department of Cardiovascular Medicine); Responsible physician: Hirotaka Watada; Katsumi Miyauchi(Department of Cardiovascular Medicine); Participating physician: Takahisa Hirose; Hiromasa Suzuki(Department of Cardiovascular Medicine); Takeshi Kurata(Department of Cardiovascular Medicine); Tetsuro Miyazaki(Department of Cardiovascular Medicine); IMT in charge: Emi Miyazawa; Noriko Iijima; CRC: Atsuko Shiratori; Takagi Hospital: Responsible physician: Yasukazu Sato; Participating physician: Chiyoko Endo; Kaoru Tanaka; Keiki Yoshida; Kimihiro Nakahara; Kyosuke Yamamoto; Masahito Sakai; Masao Ohashi; Noriaki Matsumoto; Noriko Fukushima; Rieko Sakamoto; Satomi Fujimatsu; Yasuhiro Ono; CRC: Junko Matsuda; Kumiko Sasaoka; Noriko Takemata; Clerical work: Eisuke Mizokami; Hidenori Seki; International Hospital of Health and Welfare: Responsible physician: Fumio Murayama; Participating physician: Kenichi Oya ; Masao Hiwatari; CRC: Yasuko Otsuki; Clerical work: Kazuya Murakami; Kanazawa Medical Clinic: Participating physician: Shunichi Tanaka; CRC: Keiko Kikuchi; IUHW Atami Hospital: Responsible physician: Motoo Tsushima; Participating physician: Eiko Ikoma; Hisaichiro Tsukiyama; Izumi Kobayashi; Jin Oshikawa; Keiichi Shimoda; Kozo Okada; Ryu Sasaki; Takashi Orii; Tetsuya Fujikawa; Tomohiko Shigemasa; Yoshihiko Yamada; CRC: Asei Kaji; Junko Yamanaka; Takahiro Suzuki; Yoshiko Harakawa; Clerical work: Yoshiyuki Sato; Juntendo University Shizuoka Hospital: Responsible physician: Masahiko Kawasumi; Satoshi Kojima; Participating physician: Akihisa Nishino; Fuki Ikeda; Hidenori Yoshii; Masataka Niwa; Satoru Suwa; CRC: Atsushi Kobayashi; Takuya Uematsu; Yoshiaki Matsui; Juntendo University Urayasu Hospital: Responsible physician: Tatsuji Kanoh; Participating physician: Jong Bock Choi; Kenji Watanabe; Shigeru Matsuda; Takayuki Yokoyama; CRC: Miki Kubota; Shigeko Oyanagi; Sanno Hospital: Responsible physician: Kazuhide Yamaoki; Ikuo Yokoyama; Noriko Tajima; Wataru Hayashida; CRC: Chiyako Minamikawa; Sanno Medical Plaza: Participating physician: Atsurou Kishimoto; Tetsu Matsubara; Tomoko Yamazaki; Clerical work: Koichi Maeda; Kurata Clinic: Responsible physician: Takeshi Kurata; Nakakinen Clinic: Responsible physician: Takeshi Osonoi; Participating physician: Miyoko Saitou; Naoki Owada; Naoko Takayanagi; Shimada General Hospital: Responsible physician: Issei Shimada; Clerical work: Mika Wakaumi; Chiba Tokusyukai Hospital: Responsible physician: Michiko Abe; Participating physician: Miki Takagi; Takahisa Hirose; Koto Hospital: Responsible physician: Eiji Tamiya; IUHW Mita Hospital: Responsible physician: Kunio Ohyama; Participating physician: Atsuhisa Sato; Hideki Koh; Katsumasa Yui; Kunio Nakano; Yoshitaka Akiyama; CRC: Tomoko Shigeoka; National Hospital Organization Ureshino Medical Center: Responsible physician: Shiro Hata; Fukuoka Chuo Hospital: Responsible physician: Masao Ohashi; International Goodwill Hospital: Responsible physician : Akio Kanazawa; Participating physician: Yasuhiro Amagasaki; Ochanomizuhijiribashi Clinic: Responsible physician: Koshiro Monzen; The University of Tokyo Hospital: Responsible physician: Tsutomu Yamazaki; Participating physician: Dobun Hayashi; Koshiro Monzen; Ryozo Nagai; Takahide Kohro; Yasushi Imai; Arisaka Clinic: Responsible physician: Tomoyuki Arisaka; Hatori Medical Clinic: Responsible physician: Hiroshi Hatori; Hattori Clinic: Responsible physician: Akira Hattori; Hayashi Medical Clinic: Responsible physician: Yoshitaka Hayashi; Iwase Clinic of Cardiology and internal medicine:Responsible physician: Takashi Iwase; Junseikai Hospital: Participating physician: Kohji Komiya; Tomoaki Yoshihara; Yoshifumi Tamura; Kitanarashino Hanawa Hospital: Responsible physician: Mikio Tanaka; Matsumoto Clinic: Responsible physician: Yoshihisa Matsumoto; Mizuma Kouhoukai Hospital: Responsible physician: Masayasu Higashijima; CRC: Noriko Takemata; Clerical work: Hideki Nogami; Masayuki Matsufuji; Clinical Trial Management, Graduate School, International University of Health and Welfare: CRC: Ayako Nakahara; Kaoru Hatanaka; Mika Nozawa; Taka Ikarashi; Clerical work: Hideka Ishii; Kazuo Takeshita; Mari Kanno; Masami YoshidaJuntendo University School of Medicine: Metabolism and Endocrinology, Department of Medicine, Juntendo University School of Medicine; Department of Cardiovascular Medicine Juntendo University School of Medicine; Juntendo University Urayasu Hospital; Juntendo University Shizuoka Hospital; Chiba Tokusyukai Hospital; Junseikai Hospital; Sanno Hospital; Sanno Medical Plaza; Takagi Hospital; Mizuma Kouhoukai Hospital; IUHW Atami Hospital; International Hospital of Health and Welfare; Iwase Clinic of Cardiology and Internal Medicine; Ochanomizu Hijiribashi Clinic; The University of Tokyo Hospital; Nakakinen Clinic; Shimada General Hospital; Koto Hospital; Hatori Medical Clinic; Kurata Clinic; Matsumoto Clinic; Kitanarashino Hanawa Hospital; Hayashi Medical Clinic; Arisaka Clinic; International Goodwill Hospital; IUHW Mita Hospital; Kanazawa Medical Clinic; Hattori Clinic; Fukuoka Chuo Hospital; National Hospital Organization Ureshino Medical CenterThe pre-publication history for this paper can be accessed here:"}
+{"text": "Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens."}
+{"text": "The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co-inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co-inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin-positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors."}
+{"text": "A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain."}
+{"text": "Seventy-two consecutive patients were eligible for a study of clinical determinants of response and response duration in small cell lung cancer (SCLC). Pretreatment values of routine laboratory parameters, and three tumour markers: neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and acidic glycoprotein (AGP) were measured. Descriptive clinical variables as performance status (PS), extent of disease, age and sex were also included in the study. All variables were analysed for influence on the type and duration of response. The complete remission probability was only related to pretreatment extent of disease. In a multivariate analysis (Cox) of response duration, only NSE and type of response had significant influence. Consequently, measurements of NSE before therapy will be useful in future clinical trials on SCLC especially in situations, where responding patients are submitted to specific treatment strategies."}
+{"text": "A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique. We found 13 tumours presenting total HLA-ABC loss, five with selective loss of HLA-A antigens and one with absence of HLA-B antigens. These losses were statistically associated with clinical and pathological parameters, such as T stage, degree of differentiation, scores according to the Jakobsson and Glanz grading systems and degree of leukocytic infiltration. Our results lead us to the following conclusions: (a) HLA class I losses were found in a group of tumours showing greater aggressiveness and worse prognosis; (b) these alterations in expression were not associated with an increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to greater local aggressiveness, and the loss of class I antigens seems to constitute an adaptive tumour mechanism to avoid the different anatomical and immunological barriers within the larynx."}
+{"text": "We have carried out a comparison of two different methods for cloning human lung cancer cells. The method of Courtenay & Mills (1978) generally gave higher plating efficiencies (PE) than the method of Carney et al. (1980). The number of colonies increased with incubation time in both methods and the weekly medium replenishment in the Courtenay method was advantageous for longer incubation times of several weeks. In the Courtenay method, the use of August rat red blood cells (RBC) and low oxygen tension were both found to be necessary factors for maximum plating efficiency. The usefulness of heavily irradiated feeder cells in improving PE is less certain; each cell type may have its own requirement."}
+{"text": "Cancer mortality trends were examined for the small areas around fourteen nuclear and five non-nuclear facilities in England and Wales. Using routine OPCS mortality data, standardized mortality ratios (SMRs) for these areas were computed for selected causes of death. Changes in the SMRs were then sought by comparing the SMRs for the five years before the facility opened with the period 10 (in some cases 15) years after start-up, and by computing the weighted regression of the SMRs on calendar year. These analyses indicate no overall pattern of increasing cancer SMRs around nuclear facilities."}
+{"text": "Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence."}
+{"text": "To the Editor:The authors of the abstract \"Reducing Dental Sealant Disparities in School-aged Children Through Better Targeting of Informational Campaigns\"  state:The lack of an association between sealant prevalence and knowledge among low-income families may reflect higher levels of public provision of sealants to this group. This suggests that informational campaigns could increase demand for sealants in both income groups.However, I fail to see how targeted informational campaigns about sealants, regardless of the efficiency or the impact, could increase demand for a service in groups that cannot afford that service."}
+{"text": "The radiosensitivity of human tumour cell lines and cells cultured from xenografts or biopsy specimens was measured using the adhesive tumour cell culture system (ATCCS). For cell lines the derived surviving fractions at 2 Gy were in good agreement with values obtained by clonogenic assay. However, the assay tended to overestimate survival at higher radiation doses, and thus to give a false impression of radioresistance. When cells taken from xenografts or tumour biopsies were cultured there was no evidence for selective growth of tumour cells: fibroblast-like cells commonly grew. Immunohistochemical staining against the intermediate filament, vimentin, supported the mesenchymal origin of the fibroblast-like cells. In cultures of artificial mixtures of tumour cells and fibroblasts, low proportions of fibroblasts were not excluded by the assay and consequently modified the radiation response. The majority of cultures grown from bladder carcinoma biopsy specimens appeared fibroblast-like, although in some cases clearly distinguishable colonies of tumour cells were also grown. In such tumour types the reliable measurement of radiosensitivity in cells taken from biopsies will require further development of techniques that allow the selective growth of tumour cells."}
+{"text": "The 2004 NIEHS Division of Extramural Research and Training\u2019s annual scientific retreat was titled \u201cPredisposing Factors in the Development of Complex Diseases.\u201d The retreat focused on factors related to aging, immunology, infection, and genetics in the context of understanding risk modulators of environmentally induced diseases.In the first session, participants discussed environmental influences on aging, including the contributions of environmental exposures to the development of chronic diseases, as well as new mouse models for aging and the validity of some of the more popular theories of aging in light of recent study results. The role of oxidative stress and accumulated oxidative damage as a factor in the development of chronic diseases was a common thread throughout these presentations.The second session focused on innate immunity, inflammation, and the role of infection as predisposing factors in chronic disease. One presentation examined the role of bacterial load, asthma, and a hypothesized endotoxin switch that results in diametrically different effects in response to an antigen, depending on the dose and timing of exposure. Given that endotoxin potentiated the toxicity of several chemicals noted for their idiosyncratic reactions, these responses may have resulted from low-level, episodic, inflammatory events. Finally, data presented in the final talk of the session suggest that undernutrition in a host organism plays an important role in the rapid evolution of infectious agents including influenza viruses.The final session focused on opportunities and challenges in using population-based studies to investigate gene\u2013environment interactions leading to human disease, including the lack of repeatability of candidate gene association studies. A \u201cunified\u201d approach that assembles overlapping and synergistic networks of pathways for analyses was recommended in place of single candidate gene studies. This unified approach relies on data from expression microarrays, proteomics, and siRNA studies to identify genes that may not be part of recognized pathways. All relevant information can be analyzed using a hierarchical modeling approach.One example given demonstrated some of the challenges of using animal models to study human diseases. Data from mouse models used to study atherogenesis displayed a paradox when considering genotype and phenotype. Contrary to the accepted hypothesis positing downregulation of low-density lipoprotein receptor (LDLR) in humans, expression of the human APOE4 isoform combined with increased LDLR was harmful in genetically modified mice when fed a high-fat Western diet, predicting important interactions between genotype/phenotype and exposure.The topics of this year\u2019s retreat offered potential new research directions by demonstrating some of the challenges in identifying predisposing factors in complex diseases. The Division of Extramural Research and Training will consider these issues as it develops strategic plans for enhancing research programs at the NIEHS.Melinda BeckUniversity of North Carolina\u2013Chapel HillRobert FloydOklahoma Medical Research FoundationJohn GroopmanThe Johns Hopkins UniversityHoward HuHarvard School of Public HealthNobuyo MaedaUniversity of North Carolina\u2013Chapel HillRichard MillerUniversity of Michigan School of MedicineRobert RothMichigan State UniversitySilke SchmidtDuke University Medical CenterDuncan ThomasUniversity of Southern CaliforniaHolly Van RemmenThe University of Texas Health Science Center at San AntonioDonata VercelliThe University of Arizona"}
+{"text": "Objective: To address the putative association of antibiotic use and subsequent yeast vaginitis in a population ofnon-pregnant women.Methods: Three hundred and sixteen women who received medical care in rural family medicine clinics enrolledin this study. Participants were pre-menopausal and non-pregnant and were followed until they used a course ofantifungal therapy for vaginitis, became pregnant or moved from the catchment area. At entry subjects were freeof vaginitis symptoms and had taken no antibiotics for 30 days.Patients were followed by repeated review of clinic records, hospital records and telephone or personal interviews.Data collection included documentation of episodes of antifungal treatment for vulvovaginal candidiasis andconfirmed antibiotic treatment or credible history of antibiotic use prior to the use of antifungal therapy.Physician-reported uses of antibiotic and antifungal as well as patient-reported uses of these were recorded.Results: There were four reported cases of antifungal therapy following within a month of antibiotic use, incontrast to 484 antibiotic uses not followed by antifungal use. If time of observation was extended to 6 monthsfrom antibiotic use, there were 13 uses of antifungal therapy after antibiotics and 475 uses of antibiotics notfollowed by antifungal therapy.Conclusion: Our results cast doubt on the association of antibiotics as a putative cause of yeast vulvovaginitis."}
+{"text": "The three major mechanisms that regulate transcript formation involve the selection of alternative sites for transcription start (TS), splicing, and polyadenylation. Currently there are efforts that collect data & annotation individually for each of these variants. It is important to take an integrated view of these data sets and to derive a data set of alternate transcripts along with consolidated annotation. We have been developing in the past computational pipelines that generate value-added data at genome-scale on individual variant types; these include AltSplice on splicing and AltPAS on polyadenylation. We now extend these pipelines and integrate the resultant data sets to facilitate an integrated view of the contributions from splicing and polyadenylation in the formation of transcript variants..The AltSplice pipeline examines gene-transcript alignments and delineates alternative splice events and splice patterns; this pipeline is extended as AltTrans to delineate isoform transcript patterns for each of which both introns/exons and 'terminating' polyA site are delineated; EST/mRNA sequences that qualify the transcript pattern confirm both the underlying splicing and polyadenylation. The AltPAS pipeline examines gene-transcript alignments and delineates all potential polyA sites irrespective of underlying splicing patterns. Resultant polyA sites from both AltTrans and AltPAS are merged. The generated database reports data on alternative splicing, alternative polyadenylation and the resultant alternate transcript patterns; the basal data is annotated for various biological features. The data (named as integrated AltTrans data) generated for both the organisms of human and mouse is made available through the Alternate Transcript Diversity web site at The reported data set presents alternate transcript patterns that are annotated for both alternative splicing and alternative polyadenylation. Results based on current transcriptome data indicate that the contribution of alternative splicing is larger than that of alternative polyadenylation. The three major regulatory mechanisms that bring about formation of alternative transcript patterns from an expressed gene act at the choice of alternative sites for transcription start (TS), splicing, and polyadenylation -4. Use oWe have been generating data sets on individual variant types; such data sets include AltSplice  and AltPThe transcript patterns as derived by the AltTrans pipeline and the combined list of polyA sites as generated by AltTrans and AltPAS pipelines form the core of the data presented in this work; these basal data are annotated for various biological features. The resulting data for human and mouse is presented to the community in two forms: (i) through an FTP server as flat file distributions; and (ii) through user-friendly web query interfaces. Included in the database are those genes for which at least one transcript pattern (annotated both for splicing and terminating polyA site) was determined.The different pipelines discussed below are (i) AltSplice , (ii) AltTrans  AltPAS . Also discussed are the approaches to integrate the resulting data.flanking side is extracted as AltSplice gene. Transcript (EST and mRNA) sequences as extracted from EMBL database )Data sets of transcript patterns were derived for both human and mouse. Statistics on the generated data is presented in Table The data set of human transcript patterns contains 7669 gene entries for each of which is derived at least one pattern that is fully annotated for both splicing and terminating polyA site. The total number of transcript patterns is 12559 (at an average of 1.6 per gene) encoded by 10221 terminating polyA sites. In 3179 of the 7669 AltTrans genes, two or more alternate transcript patterns could be observed. Inclusion of AltPAS polyA sites annotated an additional 6883 polyA sites raising the number of polyA sites mapped to 17104.The data set of mouse transcript patterns contains 5862 gene entries. The total number of transcript patterns is 7755 (at an average of 1.3 per gene) encoded by 6976 terminating polyA sites. In 1548 of the 5862 AltTrans genes, two or more alternate transcript patterns could be observed. Inclusion of AltPAS polyA sites annotated an additional 2475 polyA sites raising the number of polyA sites mapped to 9451.Examination of data presented in Table There is a large discrepancy in the numbers for observed splice patterns and observed transcript patterns. While the average number of observed splice patterns per human gene is 5.4, the average number of observed transcript patterns is a mere 1.6 (the corresponding numbers in the case of mouse data are 4.6 and 1.3). This discrepancy is due to the fact that for an EST/mRNA sequence to confirm a transcript pattern, it is required that the sequence confirms both the splicing and terminating polyA site. EST sequences do not often cover simultaneously both the internal and 3' regions of the gene \u2013 this is reflected in the observed numbers  Genes and transcript data; (ii) introns/exons, polyA sites; (iii) isoform splice patterns, isoform transcript patterns, isoform peptide sequences; and (iii) alternative splice events, alternative polyadenylation events. Various value-added annotations are also generated, some of which are as described below.An important part of our pipeline is to generate evolutionary profiles of gene expression patterns. Methods based on the identification of conserved introns/exons and of conserved splice events  have beeWe have developed methods (as documented in the ATD web pages) to delineate the allele specificity of observed alternative splice patterns.We have developed methods to delineate the amino acid sequence of the protein sequences encoded by the isoform splice patterns.The data was generated as part of the European Project on Alternate Transcript Diversity (ATD). The data can be downloaded as flat files or queried through web interfaces. The web interface provides single-box query (where a user can search the database against a keyword or gene symbol or database cross-references) or a detailed query page that searches simultaneously both the human and mouse data or a query page that provides advanced searches to either human or mouse data.Genes can be queried by chromosomal location, gene names and synonyms, protein keywords, and database cross-references [such as EMBL and UniProt accession numbers ,45, HUGOAn output page resulting from a query to the database lists for every gene entry all the available database cross-references; an important aspect being hyperlinks to orthologous genes from other organisms (currently implemented for human and mouse).Observed PolyA sites and transcript patterns are presented in tabular forms Fig. . TypicalObserved introns & exons are listed, and are hyperlinked to a page presenting data on EST/mRNA sequences that confirm these features. Observed splice patterns and events are listed Fig.  and are Pattern viewers that give visual presentation of the observed isoform splice pattern structures and of the observed transcript pattern structures are provided. An example of transcript pattern view is presented in Fig. The AltTrans data has been integrated with the Ensembl genome annotation project and is visible as DAS (Distributed Annotation System) tracks from the gene view and contigview pages in Ensembl genome browser Fig. .We present here an integrated data set of transcript-confirmed introns/exons, polyA sites, isoform splice patterns, isoform transcript sequences, isoform peptide sequences, alternative splice events, and alternative polyadenylation events. The data is presented for both mouse and human. Future work will aim to annotate the alternate transcripts for transcription start sites and their variants. In its future extension, this work should ultimately present high quality data on full-length transcript patterns annotated for transcription start site, splice sites, and polyadenylation sites; with each of these individual signals annotated for variations and for biological characteristics such as regulatory motifs and evolutionary profile.. Enquiries on accessing the data can be mailed to asd-ebi@ebi.ac.uk.Release 1 of the integrated AltTrans data, presented in this manuscript, is available from TS: transcription start; FTP: file transfer protocol; EST: expressed sequence tag; mRNA: messenger RNA; cDNA \u2013 copy DNA; polyA: polyadenylation; PAC: polyadenylation cleavage; PAS: polyadenylation signal; dbEST: database of Expressed Sequence Tags; H-Inv: Human-Invitational Database; FANTOM: Functional Annotation of the mouse; BLAST: Basic Local Alignment Search Tool; ASD: Alternative Splicing Database; AEdb Alternative Exon Database; ATD: Alternate Transcript Diversity Database; SAGE: Serial Analysis of Gene Expression; RT-PCR: reverse transcription-polymerase chain reaction; UniProt: Universal Protein Resource.DG is responsible for formulating the AltPAS pipeline. TAT is responsible for formulating and developing the methods for the   AltTrans, AltSplice, the data integration pipelines, the annotation   modules, and the database & query interfaces. TAT has written the manuscript and DG has contributed to the drafting process. TAT headed the team at EBI. VLT has developed the software code for the database & interfaces and   for the annotation module of SNP-mediated splicing. JR has developed the software code for the AltTrans, AltSplice and the data integration pipelines. VK has developed the software code for the module of human-mouse conservation. CG has developed the software code for the module of deriving data on protein isoforms. FL has developed the software code for the AltPAS pipeline."}
+{"text": "Vigna unguiculata (L.) Walp.] is one of the most important food and forage legumes in the semi-arid tropics because of its ability to tolerate drought and grow on poor soils. It is cultivated mostly by poor farmers in developing countries, with 80% of production taking place in the dry savannah of tropical West and Central Africa. Cowpea is largely an underexploited crop with relatively little genomic information available for use in applied plant breeding. The goal of the Cowpea Genomics Initiative (CGI), funded by the Kirkhouse Trust, a UK-based charitable organization, is to leverage modern molecular genetic tools for gene discovery and cowpea improvement. One aspect of the initiative is the sequencing of the gene-rich region of the cowpea genome (termed the genespace) recovered using methylation filtration technology and providing annotation and analysis of the sequence data.Cowpea [Arabidopsis thaliana, Oryza sativa, Medicago truncatula, and Populus trichocarpa. The possible exons and introns on each cowpea GSS were predicted using the HMM-based Genscan gene predication program and the potential domains on annotated GSS were analyzed using the HMMER package against the Pfam database. The annotated GSS were also assigned with Gene Ontology annotation terms and integrated with 228 curated plant metabolic pathways from the Arabidopsis Information Resource (TAIR) knowledge base. The UniProtKB-Swiss-Prot ENZYME database was used to assign putative enzymatic function to each GSS. Each GSS was also analyzed with the Tandem Repeat Finder (TRF) program in order to identify potential SSRs for molecular marker discovery. The raw sequence data, processed annotation, and SSR results were stored in relational tables designed in key-value pair fashion using a PostgreSQL relational database management system. The biological knowledge derived from the sequence data and processed results are represented as views or materialized views in the relational database management system. All materialized views are indexed for quick data access and retrieval. Data processing and analysis pipelines were implemented using the Perl programming language. The web interface was implemented in JavaScript and Perl CGI running on an Apache web server. The CPU intensive data processing and analysis pipelines were run on a computer cluster of more than 30 dual-processor Apple XServes. A job management system called Vela was created as a robust way to submit large numbers of jobs to the Portable Batch System (PBS).CGKB, Cowpea Genespace/Genomics Knowledge Base, is an annotation knowledge base developed under the CGI. The database is based on information derived from 298,848 cowpea genespace sequences (GSS) isolated by methylation filtering of genomic DNA. The CGKB consists of three knowledge bases: GSS annotation and comparative genomics knowledge base, GSS enzyme and metabolic pathway knowledge base, and GSS simple sequence repeats (SSRs) knowledge base for molecular marker discovery. A homology-based approach was applied for annotations of the GSS, mainly using BLASTX against four public FASTA formatted protein databases , and UniProtKB-TrEMBL). Comparative genome analysis was done by BLASTX searches of the cowpea GSS against four plant proteomes from .CGKB is an integrated and annotated resource for cowpea GSS with features of homology-based and HMM-based annotations, enzyme and pathway annotations, GO term annotation, toolkits, and a large number of other facilities to perform complex queries. The cowpea GSS, chloroplast sequences, mitochondrial sequences, retroelements, and SSR sequences are available as FASTA formatted files and downloadable at CGKB. This database and web interface are publicly accessible at  Vigna unguiculata (L.) Walp.] is one of the most important food and forage legumes in the semi-arid tropics and a valuable and dependable commodity for farmers and grain traders with ~21 million acres grown worldwide and an annual production of over 3 million tons [Cowpea [Cowpea growth and yield are constrained by a variety of biotic and abiotic factors. Insects, fungi, bacteria, parasitic plants and nematodes are the major biotic stresses, and drought, salinity and heat are among the major environmental limitations to cowpea productivity ,2. One oThe size of the cowpea nuclear genome has been estimated at 620 megabases (Mb), making it one of the smaller genomes present in leguminous plants as well as among vascular plants . It is w\u00ae methylation filtering technology [\u00ae technology) and unfiltered (UF) libraries were constructed, clones were picked at random from both libraries and the insert sequences determined and analyzed to estimate filtering power. The gene enrichment achieved by GeneThresher was determined by comparing the rate of gene discovery between MF and UF sequences. Detection of genes was accomplished by an NCBI-BLASTX search  of the curated Arabidopsis protein database [\u00ae technology produced a 4.1-fold enrichment of gene-rich clones from cowpea genomic DNA libraries and estimated the size of the hypomethylated, gene-rich space of cowpea to be approximately 151 Mb. Using empirically derived results from the Orion Sorghum GeneThresher project and a simulation conducted on finished Arabidopsis sequence [Methylation filtering (MF) allows for the selective cloning of hypomethylated regions of the plant nuclear genome . MF has chnology  could bedatabase ,17. The sequence , we esti (see figure The Cowpea Genomics Initiative (CGI) funded by the Kirkhouse Trust, a UK-based charity , underto-10 when compared to relevant public databases. A total of 9985 chloroplast sequences, 856 mitochondrial sequences and 2608 transponson/retrotransposon-like sequences were identified in the dataset and these sequences are downloadable from the CGKB website. The remaining 263,425 MF nuclear sequences with average length of 610 bp were subjected to the annotation and data analysis processing pipeline. We used the Perl programming language [The primary sequence dataset for the CGKB consists of a total of 298,848 GSS isolated by methylation filtering of the cowpea genomic DNA. The FASTA formatted cowpea sequence files generated using Phred basecalling were vector trimmed. Contaminant sequences, defined as sequences that at the time of initial annotation are believed to be derived from vector, microbial, fungal (yeast), viral or animal genomes, were removed. Chloroplast, mitochondrial and transposon/retrotransposon DNA sequences were also removed. Choloroplast, mitochondrial and transponson/retrotransposon sequences were determined by BLAST significant similarity scores equal to or less than 1 \u00d7 10language  to implelanguage  in our dArabidopsis thaliana [Oryza sativa [Medicago truncatula [Populus trichocarpa (Torr. & Gray) (black cottonwood) has been completed and is available for comparison [Medicago truncatula, Arabidopsis thaliana, Oryza sativa and Populus trichocarpa for comparative analysis and knowledge integration. BLASTX results with the Arabidopsis proteome were used for the assignments of curated Gene Ontology terms and pathways from TAIR [The complete sequence is currently available for two vascular plant genomes, thaliana  and Oryza sativa . An inteuncatula  as the nmparison . We perfrom TAIR  for eachrom TAIR .Searches were performed with each cowpea GSS using BLASTX with cutoff expectation (e) value of 1e-8, against UniProtKB-TrEMBL , UniprotThe potential domains on annotated GSS were analyzed using the HMMER package  against in-silico methods have been developed that allow rapid discovery of potential SSR markers from plant DNA sequence  datasets. Each GSS was analyzed using the Tandem Repeats Finder program [GGS data from cowpea should be an invaluable resource for the development of molecular markers and genetic maps for comparing syntenic relationships among legume and non-legume species. Simple sequence repeat (SSR) markers are one of the popular DNA markers for plant genome analysis and marker-assisted selection in crop breeding programs. Traditionally, SSR markers were generated through screening of SSR-enriched genomic libraries, a process that was very time-consuming and expensive. Recently,  program  develope program . The ide and the production instance is located on . Both instances are synchronized with the additions of newly processed results, such as contig building, contig annotation and comparative analysis with legume unigenes.We used the PostgreSQL  relationWe have also created an easy-to-use interface for the knowledge bases, mostly based on CGI written in Perl running on an Apache web server . Our useMedicago truncatula, Arabidopsis thaliana, Oryza sativa and Populus trichocarpa. The interface was designed for queries via UniProtKB accession number, GenBank GI number, GSS sequence identification number, sequence feature on annotation, and ortholog/homolog identified via blast homology-based sequence alignments against the above four public protein sequence databases  BlastAll is a local installation of NCBI BLAST program with the cowpea GSS FASTA formatted sequence database. This tool can be used to retrieve homologous overlapping cowpea sequences for sequence extension and contig building.(2) RetrieveAll is a program for quick cowpea GSS sequence retrieval via sequence ID or trace name.(3) Contig Builder is a local web based implementation of the Phrap program for contig building. Overlapping or homologous cowpea GSS can be uploaded into this tool to extend the sequence length or make contigs based on sequence overlaps.(4) Multiple Sequence alignment is a local web based implementation of the CLUSTALW multiple sequence alignment program to check the quality of the overlapping GSS region for forming contigs or extending the length of GSS sequences.Arabidopsis thaliana proteome provides for comparative genome analysis and integration with plant related GO terms and metabolic pathways from TAIR.Genome-related public databases are an invaluable part of the scientific community. There are two major users of these resources. The first is the scientific focus group actively studying the target system or organism. Among this target audience are breeders who can use this resource for the design of molecular markers for use in marker-assisted breeding and introgression programs in cowpea and other legumes. The second group is the broader scientific community interested in relating this specialized information to other systems/organisms. The aim of the CGKB is to provide an annotated, well-organized, and rigorously analyzed dataset of MF clone sequences as a resource for cowpea researchers and pan-legume crop specialists. We have found that comparisons to the NCBI GenBank Protein and UniProtKB-TrEMBL allow for the best coding potential detection of the cowpea GSS since these protein knowledgebases represent global collection of proteins. The UniProtKB-Swiss-Prot is mainly useful for data integration of known domains and enzyme databases. Comparison of the cowpea GSS to the Medicago proteome will be used to anchor cowpea GSS to the physical contig and genetic map of Medicago truncatula and inclusion of additional comparative genomic analysis and syntenic relationships to other legume and non-legume species; and (v) full data integration at database physical level with Arabidopsis and rice knowledge bases.The structure and organization of the CGKB allows for rapid modification of data storage and retrieval and addition/removal of functionalities. Among the future plans for the database are (i) contig building and singlet estimation on the cowpea genomic genespace sequences; (ii) incorporation of PCR primer sequence information for SSR amplification into the SSR database and other data analysis tools associated with marker development for cowpea; (iii) integration with cowpea genetic mapping activities for identification of potential trait-linked markers; (iv) BLASTX analysis with the  The CGKB is published under the GNU General Public License (GPL) which implements the understandings of the Kirkhouse Trust Intellectual Property Statement.The CGKB is publicly available at the URL We have chosen the GPL as the best way to ensure free and unrestricted access to the cowpea genomic data, and to subsequent discoveries resulting from use of this data. This free exchange of knowledge benefits the poor farmers of the world and promotes rapid scientific progress. Users are asked to register at the CGKB site: TWL participated in the design of the CGKB database and database system administration. XC performed the bioinformatics data analysis and web implementation. PJR contributed the web tool design, validation, and data analysis. TAS contributed project coordination, computer cluster setting up and administration. MPT performed data and web interface validation and served as the principal investigator of the project. All authors have assisted in the writing and have read and approved the final manuscript."}
+{"text": "The infiltrated tissues from seven West Indian patients with HTLV-1 positive adult T cell lymphoma/leukaemia (ATLL) have been analysed by immunocytochemical techniques for the presence of immunoreactive parathyroid hormone-related protein (PTHrP), a hormonal mediator of humoral hypercalcaemia of malignancy. Six of the seven were hypercalcaemic at some stage of the course of their disease. Four of the six evaluable patients showed evidence of specific cellular and extracellular expression of PTHrP protein in neoplastic tissues. This finding suggests that PTHrP may be involved in the production of hypercalcaemia in at least some cases of T cell lymphoma - proof of a causal relationship however must await the demonstration of tissue release of PTHrP resulting in raised circulating hormone levels."}
+{"text": "Recent immunocytochemical and biochemical studies have shown the intracellular uptake of alpha-foetoprotein (AFP) by most neural crest and neural tube derivatives of developing mammals and birds. The neural crest origin of neuroblastomas has been known for a long time. While many mouse neuroblastoma cell lines can express several neuronal properties, other lines lack specialized neural functions and may re-express embryonal or foetal antigens, suggesting some reversion towards an earlier stage of differentiation. We have therefore tested the C-1300 Jackson mouse neuroblastoma cell line for its ability to incorporate AFP. The results obtained confirm the significant internalization of protein by these cells, both in vitro and in vivo. External photoscans of mice bearing tumours after injection with [131I]-AFP have proven the usefulness of the protein as a radiotracer for neuroblastoma localization."}
+{"text": "The preparation of primary cultures of control and DHBV-infected duck hepatocytes from embryos and young ducklings is described. Cultures of both embryo and duckling hepatocytes secreted duck serum proteins. Cultures of hepatocytes established from ducklings maintained initial morphology for up to 3 weeks in culture and also exhibited high levels of metabolism of aflatoxin B1. Embryonic cell cultures rapidly lost ability to metabolise AFB1 and became overgrown by spindle-shaped cells. Both embryo and duckling cell cultures secreted infective DHBV, and had intracellular replicative forms of the virus. No integration of the virus into the duck genome was observed, and attempts to induce viral integration in the duckling hepatocytes using irradiation and aflatoxin B1 toxicity were unsuccessful. The results of the study lend further support to the suggestion that the rarity of liver cancer in DHBV-infected experimental ducks is related to an innate resistance of the hepatocytes to develop DHBV-DNA integration. Another possibility may be related to the lower oncogenic potential of the DHBV strain used for the study. However DHBV infected duckling hepatocytes would appear to offer a suitable material for studying viral replication and mechanisms of aflatoxin B1 toxicity during prolonged cell culture."}
+{"text": "In a group of seventy patients with small cell lung cancer the prognostic value of serum tumour markers was determined. Thymidine kinase (TK), tissue polypeptide antigen (TPA) and lactate dehydrogenase (LDH) but not neuron specific enolase (NSE) correlated significantly with survival. Since all markers were strongly interrelated with each other and with the extent of disease, the combined determination of TK, TPA and LDH or the combination of disease extent and a marker yielded no more prognostic information than a single measurement of one of these variables."}
+{"text": "A study of 361 female melanoma patients and age matched controls was conducted in the four western provinces of Canada. Analysis of reproductive factors showed a significant negative association between number of livebirths and risk of melanoma. The relationship persisted for superficial spreading melanomas after adjustment for host pigmentation factors, freckling, and educational status. An inverse association between bilateral oophorectomy and risk of superficial spreading melanoma was also seen. No association was found between risk of melanoma and age at first birth, age at menarche and age at natural menopause. No association was found between risk of superficial spreading or nodular melanoma and use of either oral contraceptives or menopausal oestrogens."}
+{"text": "Current and historical environmental conditions are known to determine jointly contemporary species distributions and richness patterns. However, whether historical dynamics in species distributions and richness translate to functional diversity patterns remains, for the most part, unknown. The geographic patterns of plant functional space size (richness) and packing (dispersion) for six widely distributed orders of European angiosperms were estimated using atlas distribution data and trait information. Then the relative importance of late-Quaternary glacial-interglacial climate change and contemporary environmental factors  as determinants of functional diversity of evaluated orders was assesed. Functional diversity patterns of all evaluated orders exhibited prominent glacial-interglacial climate change imprints, complementing the influence of contemporary environmental conditions. The importance of Quaternary glacial-interglacial climate change factors was comparable to that of contemporary environmental factors across evaluated orders. Therefore, high long-term paleoclimate variability has imposed consistent  Species diversity displays distinct large-scale geographic patterns, which in turn are controlled by both historical and contemporary environmental conditions. The European flora provides one of the best-known examples of how current species distributions and richness patterns are strongly affected by not only contemporary climatic conditions134691213182021There are several ways through which FD patterns may be affected by historical climatic conditions such as the late-Quaternary glacial-interglacial climatic oscillations. First, historical climatic conditions might filter out physiologically or ecologically unsuitable species from either the local assemblage or the metacommunity species pool based on their functional attributes1023813101Rich \u2013 size or range of the trait space28Disp \u2013 packing of the trait space24The underlying idea of this study is that long-term climate dynamics may have affected in a similar way the functional diversity of multiple phylogenetically independent components of the European flora. The working hypotheses of this study are: (1) Geographical patterns in functional diversity will be consistent across phylogenetically independent functional groups; (2) the effects of historical climate change over the last 21,000 years as an important co-determinant of functional richness (FDo plant FD geographic patterns of multiple evolutionary independent European plant groups (orders) exhibit prominent late-Quaternary glacial-interglacial climate change imprints? (2) How does the importance of historical environmental conditions compare to that of contemporary factors across multiple evolutionary independent European plant groups (orders)? To answer these questions, the geographic patterns in FRich and FDisp for six widely distributed and species rich orders of European angiosperms were estimated, by combining data on species distributions from the Atlas Florae EuropaeaeMethods), we evaluated the link between contemporary FD patterns and both late-Quaternary glacial-interglacial climate change  and proximity to glacial refugia , while accounting for contemporary environmental effects.Evidence for associations between historical environmental conditions and FD is, for the most part, indirect and restricted to a handful of studies of the European59133259526The results presented here show that macro-scale, functional diversity geographic patterns for multiple European plant groups were indeed associated with late-Quaternary glacial-interglacial climate change even though the end of the last glaciation occurred ~11,500 years ago. These results indicate that future climate change trends may elicit not only short-term shifts in ecosystem functioning, and potentially long-term functional disequilibria. Consequently, understanding the impact and generality of these historically determined patterns acting in conjunction with contemporary environmental conditions is paramount to developing, particularly for the development of accurate predictive methods for ecosystem function and service responses to future climatic changes.Rich and FDisp for species assemblages from six orders of European angiosperms . Regardless of the differences in FRich and FDisp per-grid values across the evaluated orders, and in agreement with our hypotheses, spatial patterns, and latitudinal gradients were consistent across orders . Association with species richness was significant for FRich , and non-significant for FDisp . Although there is a strong relationship between FRich and local species richness, observed values consistently differ from those expected solely on species richness, and these relationships quickly saturate as the number of species increases , and increased with proximity to refugia .The explained variance  top and e, FRich  and FDisch (Disp  increasech (Disp  top showiversity  and 5. SAIC) were used to determine which predictors had the highest support as explanatory factors of FRich and FDisp. For this purpose, starting with a pool of 576 possible SAR models for each one of the evaluated orders, the WAIC values for all the models including the predictor of interest were added (see Methods for details). The evaluated models described all non-interacting linear and unimodal (linear\u2009+\u2009quadratic responses) combinations of historical and contemporary predictors. Across evaluated orders, contemporary predictors had higher relative importance (highest WAIC) when compared to historical predictors  that provide a buffer against climatic variations, and in regions that are highly accessible to postglacial colonization2Rich and FDisp in areas know to be glacial refugia and have a wide elevation heterogeneity was generalized across evaluated orders.Both FRich and FDisp presented here showed the generality of the strong complementary effects of historical and contemporary drivers. The fact that such effects were consistent across all six evaluated orders highlights their joint importance in determining regional FRich and FDisp patterns, even across evolutionally independent lineages. Support for the importance of historical factors as determinants of contemporary FD comes from the fit of regression models (pseudo\u2013R2), the comparable support of contemporary and historical predictors (WAIC), and the size of SAR model averaged regression coefficients across evaluated orders.The continental-level assessment of historical climatic effects on European FRich and FDisp and historical climatic conditions show that the constraints imposed by late-Quaternary glacial-interglacial climate change on species current ranges also influence the FD geographic patterns observable today. Moreover, these historical effects constitute a general trend across multiple evolutionary independent groups of European plants. Nonetheless, the subtle differences in the geographic patterns observed across the evaluated orders may be attributable to the spatial variability in historical species sorting by glacial-interglacial climate changes. Other possible factors driving the observed differences between groups are differences in dispersal capacity across groups of organisms452632The reported relationships between geographic patterns of European plant FRich and FDisp and historical conditions were consistent with the predictions of a higher FRich and a lower FDisp in areas with stable climatic conditions and proximity to glacial refugia. The consistency in the reported associations and the current knowledge of the vegetation history of this region provide some indications of how the observed influence of historical factors might be the result of multiple interacting mechanisms. Such mechanisms include dispersal-limited recolonization dynamics in climatically suitable areas34238The directions of the association between FRich are consistent with the tendency for past climatic conditions to prune trait spaces via mechanisms altering the number and types of organisms within a location  the significant association between historical predictors with FRich and FDisp, (3) the comparable importance of contemporary and historical predictors, and (4) the generality of these patterns across multiple evolutionarily independent groups.The results presented here provide four strong arguments supporting the relevance of historical climatic legacies as determinants of FD patterns across multiple evolutionary independent groups of European angiosperms: (1) The inability of both multiple and individual trait models solely based on contemporary climates to account for most of the variation in FRich and FDisp levels are not necessarily optimized to the contemporary environment, but may instead be in disequilibrium due to the occurrence of non-random extinctionsRich and FDisp losses due to future climate change trends or other anthropogenic pressures may have long recovery times. Moreover, the results of this study suggest that future climate change will not only elicit short-term shifts in ecosystem functioning but likely will also induce long-lasting ecosystem level effects, strengthened by long-term functional disequilibria. The underlying mechanisms behind such historical effects need to be evaluated in more detail, notably to facilitate incorporating them into predictive models of future dynamics of vegetation and related ecosystem functioning to enhance the accuracy of climate-change impact and dynamics estimations.In summary, this study shows that historical climate stability and distance to refuge locations influence the geographic distribution of FD in multiple evolutionary independent European plant groups. The results thereby also indicate that local FPlant species distribution data for this study comes from the Atlas Florae Europaeae (AFE), which maps the distribution of European flora on an equal-area mapping unit of ~50\u2009\u00d7\u200950\u2009km AFE cells based onAnalyses in this study focus on the distributions of six of the most species-rich, widely distributed, and functionally distinct Angiosperm orders contained in the AFE: Caryophyllales (1384spp), Brassicales (973spp), Ranunculales (654spp), Saxifragales (352spp), Rosales (334spp) and Malpighiales (73spp). The use of orders as independent units of analysis provides the benefit of replicability among groups with an independent evolutionary history, which would translate to their trait values and composition. As a result, any similarity in the observed geographic trends and the effects of contemporary and historical environmental conditions on the regional functional diversity (FD) patterns can be attributed to the similarity in the mechanisms generating the observed pattern across multiple groups, and not to the taxonomic composition of the evaluated species pool. The regional coverage and species richness for each order are presented as 2*g\u22121), maximum stem height , seed mass , stem specific density , and growth form . These traits were selected due to their usefulness for distinguishing functional strategies among concurring plants4344Five ecomorphological traits were used to describe the functional space defined by coexisting species of the same order. Used traits are specific leaf area  and functional dispersion (FDisp). The selected metrics describe two aspects of a species assemblage multivariate trait composition. FRich measures the size of the functional space circumscribed by the species in an assemblage based on the volume of a multivariate convex hullDisp measures the packing of the functional space described by the species in an assemblage based on the distance to the mean trait composition of the communitymax, SWT, and WD). Before the analyses, traits were log10 transformed as they were log-normally distributed and standardized (mean\u2009=\u20090 and SD\u2009=\u20091) to ensure that all traits contribute equally and that the units used to measure traits have no influence on the FD estimationFor each order and imputed dataset, two complementary FD metrics were estimated: functional richness  from the LGM. As in ref. \u22121) was estimated as the sum of inverse distances between an AFE grid cell and regions considered to be suitable for cool-temperate trees during the LGM according to ref. Used variables were divided into historical and contemporary predictors. Historical predictors include climatic stability5\u22121). Normalized Difference Vegetation Index  was obtained from ref. 10-transformed before the statistical analyses. Like historical variables, each of the contemporary factors was summarized as the mean within each AFE cell.Contemporary predictors describe water\u2013energy dynamics49A spatial simultaneous autoregressive error modelling approach (SAR) was used to account for spatial autocorrelation in the data. In all cases, FD was the response variable, and environmental predictors  were used as explanatory variables. The spatial weights matrices in the SAR models were determined as the first neighbour of each site.2 valuesWAIC; calculated following ref. AIC were determined based on all 576 possible SAR models based on the combination of historical and contemporary predictors either as linear or unimodal responses. Last, the relative effect of historical and contemporary predictors was determined using the model averaged regression coefficientsWAIC for the model that contained it. All statistical analyses were conducted using RFor each order, the relative support of each predictor in isolation was determined based on model fits of single-predictor models, and information theoretical approaches based on multiple- predictor models. The variance explained by each historical and contemporary predictor in isolation was assessed based on the model fit of single-predictor SAR models, determined using Nagelkerke pseudo-RHow to cite this article: Ordonez, A. and Svenning, J.-C. Consistent role of Quaternary climate change in shaping current plant functional diversity patterns across European plant orders. Sci. Rep.7, 42988; doi: 10.1038/srep42988 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations."}
+{"text": "Previous studies have examined the neural correlates of emotion regulation and the neural changes that are evoked by music exposure. However, the link between music and emotion regulation is poorly understood. The objectives of this review are to (1) synthesize what is known about the neural correlates of emotion regulation and music-evoked emotions, and (2) consider the possibility of therapeutic effects of music on emotion dysregulation. Music-evoked emotions can modulate activities in both cortical and subcortical systems, and across cortical-subcortical networks. Functions within these networks are integral to generation and regulation of emotions. Since dysfunction in these networks are observed in numerous psychiatric disorders, a better understanding of neural correlates of music exposure may lead to more systematic and effective use of music therapy in emotion dysregulation. In the past two decades, considerable interest has emerged toward identifying neural substrates of emotion regulation (ER)  includes the abilities to monitor, evaluate, and modify one's internal and external emotional reactions, and suppress aversive behavior toward others, in the service of adaptive functioning  of hippocampal neural reactivity to unpleasant sounds  more detailed investigations into the neural correlates of therapeutic effects of music, and (2) possible use of music in treatment of emotion dysregulation. At present, music has demonstrated the effects on depression through behavioral treatment, and is associated with reduced emotional reactivity in sadness-inducing contexts. For example, compared to depressed individuals who just receive standard care only, those who receive Active Music Therapy ; CS: revise manuscript based on his research experience (emotion and brain function); JZ: revise manuscript based on her research experience ; HZ: provide the reference to article structure, help revise on music and emotion section; TB: help revise the manuscript on article structure, logical organization and language .This research is sponsored by: (1) Peak Discipline Construction Project of Education and Large Instruments Open Foundation at East China Normal University; (2) The 58th China Postdoctoral Science Foundation Funded Project (No. 2015M580303); Beijing Institute for Brain Disorders (BIBD-PXM2013_014226_07_000084).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Chasmanthera dependens (Menispermaceae) by amplified fragment length polymorphism (AFLP), a chloroplast DNA sequence marker, and modelled the distribution based on current as well as paleoclimatic data . Current population genetic structure and geographical pattern of cpDNA was related to present as well as historical modelled distributions. Results from this study show that past historical factors played an important role in shaping the distribution of C. dependens across West Africa. The Cameroon Volcanic Line seems to represent a barrier for gene flow in the present as well as in the past. Distribution modelling proposed refugia in the Dahomey Gap, supported also by higher genetic diversity. This is in contrast with the phylogeographic patterns observed in several rainforest tree species and could be explained by either diverging or more relaxed ecological requirements of this liana species.Processes shaping the African Guineo-Congolian rain forest, especially in the West African part, are not well understood. Recent molecular studies, based mainly on forest tree species, confirmed the previously proposed division of the western African Guineo-Congolian rain forest into Upper Guinea (UG) and Lower Guinea (LG) separated by the Dahomey Gap (DG). Here we studied nine populations in the area of the DG and the borders of LG and UG of the widespread liana species,  The African Guineo-Congolian rain forest is the second largest block of rain forest on Earth with about 6400 endemic plant species , and conPhylogenetic and population genetic studies provide valuable data to test the forest refuge theory as well as infer the location of refugia in Africa . These sDistemonanthus benthamianus (Fabaceae) .(XLSX)Click here for additional data file."}
+{"text": "Oral cavity and pharyngeal cancers (OCPc) encompass malignancies arising in variety of anatomical subsites and are homogeneous regarding epidemiology, clinical presentation, associated risk factors and treatment modalities  types 16 and 18, as an important causation factor  (Santric-Milicevic et al., Cancer reporting is obligatory by law in Serbia since 1986 (Milju\u0161 et al., In the US the 2008 health expenditures in treatment of malignancies reached 77,4 billion dollars (American Cancer Society, In Serbia the diagnosis and treatment costs of cancer are dominated by radiotherapy related direct medical costs (Jakovljevic et al., Early diagnosis of OCPc is vital to patient survival (Shield et al., The full societal burden of cancer treatment consists of associated direct medical expenditures and indirect costs including reduced work force participation, loss of productivity and premature mortality (Wissinger et al., Although Serbian public health care expenditure is limited due to the recession, slow market recovery since 2013 has resulted with the substantial increase in oncology related public expenditure (Dagovic et al., All six authors designed the research questions and concept of this opinion article. TK and DB acquired selected published data from the public registry European Health for All Data base issued by WHO. All six authors jointly interpreted the findings stated in the article and contributed important intellectual content to the final manuscript. All six authors checked English spelling and grammar.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer OZ declared a shared affiliation, though no other collaboration, with one of the authors VR to the handling Editor, who ensured that the process nevertheless met the standards of a fair and objective review."}
+{"text": "Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown  brain abnormalities or microcephaly  (The three birth defects surveillance programs identified 747 infants and fetuses during 2013 (North Carolina and Massachusetts) and 2013\u20132014 (Atlanta) with one or more defects that met the 2016 CDC Zika surveillance case definition  . Brain aIn general, the distribution by maternal age was similar across birth defect categories. Among 410 (55%) infants or fetuses with information on the earliest age a birth defect was recorded, 371 (90%) had evidence of a birth defect meeting the Zika definition before age 3 months. More than half of those with brain abnormalities or microcephaly or with neural tube defects and other early brain malformations had evidence of these defects noted prenatally .A congenital Zika syndrome phenotype has been described , and the prevalence of severe congenital microcephaly  was 4.2 per 10,000  (The findings in this report are subject to at least six limitations. First, population-based surveillance programs strive to ascertain the prevalence of birth defects among all members of a specified population. In contrast, the aim of USZPR is to estimate the proportion of birth defects among pregnancies with laboratory evidence of possible Zika virus infection, a specific subgroup of the general population (The birth defects surveillance data in this report were compiled from a period before introduction of Zika virus in the Americas, using the CDC surveillance case definition of birth defects potentially related to Zika virus infection; this is the same case definition adopted by USZPR. The higher proportion of these defects among pregnancies with laboratory evidence of Zika infection in USZPR supports the relationship between congenital Zika virus infection and these birth defects (Zika virus infection causes serious brain abnormalities; however, the birth defects observed are not unique to congenital Zika virus infection, and the full range of effects of congenital Zika infection is not known.CDC used data from population-based birth defects surveillance programs in Massachusetts, North Carolina, and Atlanta, Georgia, to retrospectively assess the prevalence of birth defects during 2013\u20132014 that met the surveillance case definition for birth defects potentially related to Zika virus infection, before introduction of Zika virus into the United States. After introduction of Zika virus, the proportion of infants and fetuses with birth defects born to mothers with laboratory evidence of possible Zika infection reported by the US Zika Pregnancy Registry during January 15\u2013September 22, 2016, was approximately 20 times higher than the prevalence of potentially Zika-related birth defects among pregnancies during the pre-Zika years.Data on birth defects in the pre-Zika years serve as benchmarks to direct rapid ascertainment and reporting of birth defects potentially related to Zika virus infection. The higher proportion of these defects among pregnancies with laboratory evidence of possible Zika virus infection supports the relationship between congenital Zika virus infection and birth defects."}
+{"text": "Latest analyses of defoliation data confirm previous results, indicating a high correlation with weather extremes.Forest health status in Europe is assessed by the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). Established by the Convention on Long-Range Transboundary Air Pollution (CLRTAP) under the United Nations Economic Commission for Europe (UNECE), the ICP Forests has been monitoring forest condition in close cooperation with the European Commission (EC) for 20 years. The present paper describes the latest results of the deposition measurements on permanent monitoring plots and of the extensive defoliation sample survey. The findings reveal marked spatial patterns in bulk and throughfall depositions of nitrate (N-NO"}
+{"text": "Sorption of Cd was more pronounced at pH levels greater than PZSE for all experimental soils. The CEC, OM content, clay mineralogy, and specific surface area (SSA) also had a great influence on the sorption of Cd from soil solution to soils. The relationships of Cd with those parameters were found to be consistent and the results concluded that Cd sorption in soils is strongly affected by the soil characteristics.Concentrations of total dissolved cadmium (Cd) and activity of its free ions in soil solution are suggested to be influenced by soil pH, organic matter (OM) content, cation exchange capacity (CEC), and clay mineralogy. We investigated the sorption of Cd by taking 25-, 50-, and 100-\u00b5M Cd solutions in five noncontaminated soils of West Bengal, India, having differing chemical properties with batch sorption experiments. The charge characteristics and point of zero salt effect (PZSE) of all experimental soils were calculated by the potentiometric titration method measuring the adsorption of H"}
+{"text": "We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer\u2019s Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD."}
+{"text": "Myocardial inflammation may have multiple etiologies; infectious, toxic, and autoimmune. Acute cases are mostly due to myocardial involucre of a systemic viral infection. Although infectious myocarditis is routine in clinical practice for cardiologists, myocarditis presented by autoimmune diseases such as systemic lupus erythematosus also should be considered.RMC was performed in 59 patients with suspected myocarditis: 30 patients with diagnosis of SLE based on the criteria of the American College of Rheumatology and symptoms and signs of lupus activity evidenced by ECLAM (European Consensus Lupus Activity Measurement) scale with or without cardiovascular symptoms, we excluded patients with SLE and recent intake of drugs or other substances associated with myocarditis,renal function failed and history of ischemic heart disease; And 29 patients that were assessed by certified cardiologists who suspected viral myocarditis due to the combination of the following factors: symptoms , previously healthy and with no history of cardiovascular disease, with or without history of infection (upper respiratory tract infection and / or gastroenteritis) in the last 4 weeks. patients with coronary angiotomography and / or angiography for positive for atherosclerotic significant disease and patients with positive myocardial ischemia test.The most common clinical presentation in patients with lupus was dyspnea (83%), in patients with viral myocarditis the symptom was chest pain (72%) of them 62% had a history of a recent viral illness. In lupus myocarditis there was greater involvement of the ejection fraction of the left ventricle, pericardial  and valvulitis (86%) involvement, characteristics that were not identified in viral myocarditis. Lake Louis criteria; in both groups relative and global enhancement were most often negative,relative enhancement positivity percentage was 44 and 33 respectively for viral myocarditis and lupus. The global enhancement was positive in only 31% of lupus cases and 44% of viral. The gadolinium contrast enhancement was positive in the majority of lupus patients and 63% and in less than half of patients with viral myocarditis (41%). The location of these lesions had a similar behavior in both etiologies, anterior and inferoseptal being the most affected segments.Lupus myocarditis unlike viral myocarditis, characteristically presents pancarditis with pericardial and valvular involvement, and most often affected the ventricular function. The late enhancement was the criteria that prevailed in lupus myocarditis. There were no differences in the location of delayed enhancement lesions between the two etiologies."}
+{"text": "Vitis vinifera) have relatively small genomes of about 500 Mb , the short fragment size did not permit resolution of repetitive regions, resulting in an extremely fragmented assembly  DNA sequencing (Pacific Biosciences) has emerged as a leading technology for characterizing complex structural variations, supporting and refining the assembly of complex genomes in hybrid fashion or alone for reconstructing highly continuous assemblies of both small and highly repetitive genomes . The assembled sequences exceed PN40024 contigs and Thompson Seedless scaffolds by nearly two orders of magnitude in size (Figure V. vinifera genome assembly but also among the highest quality plant genomes published to date, including other genomes sequenced with SMRT technology (Sakai et al., Vitis, the length of the primary assembly was inflated with respect to the expected genome size, illustrating one of the challenges of sequencing highly heterozygous genomes (Chin et al., We have recently reported the assembly using SMRT technology and FALCON-unzip of the highly heterozygous diploid genome of Cabernet Sauvignon (Chin et al., e Figure , rankingPreliminary gene model prediction identified over 34,000 protein coding sequences on the primary assembly of the Cabernet Sauvignon genome and nearly 24,000 on the haplotigs (Chin et al., Genome resequencing projects of both prokaryotic and eukaryotic organisms have clearly shown that one genome sequence is insufficient to properly describe the genetic characteristics of a species (Tettelin et al., DC and AM conceived the article. Figure was prepared by AM and DC. AM, JL, BG, and DC wrote the first draft of the manuscript. DC revised and finalized.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The unique biology of RNA binding proteins is altering our view of the genesis of protein misfolding diseases. These proteins use aggregation of low complexity domains (LCDs) as a means to regulate the localization and utilization of RNA by forming RNA granules, such as stress granules, transport granules and P-bodies. The reliance on reversible aggregation as a mechanism for biological regulation renders this family of proteins highly vulnerable to promoting diseases of protein misfolding. Mutations in RNA binding proteins are associated with many neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). The biology of RNA binding proteins also extends to microtubule associated protein tau. Tau is normally an axonal protein, but in stress it translocates to the somatodendritic arbor where it takes on a new function promoting formation of stress granules. The interaction of tau with stress granules also promotes tau aggregation, accelerating formation of the tau pathology that we associate with diseases such as Alzheimer's disease (AD). Pathological protein aggregation is a hallmark of neurodegenerative disorders such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Frontotemporal lobar dementia (FTLD), and Amyotrophic Lateral Sclerosis (ALS). Classically, this aggregation has been viewed as the byproduct of protein misfolding and/or impairment of protein catabolism. In this model, misfolded proteins and protein oligomers accumulate because of increased production or reduced removal. The amount of misfolded protein and oligomer is thought to depend primarily on the initial amount of starting protein and its natural propensity to aggregate. The accumulating misfolded proteins and oligomers lead to the uncoordinated assembly of higher order oligomers, amyloids and eventually large fibrils, which harm the cell and precipitate neurodegeneration.Over the past decade an increasing body of work investigating the unusual biology of RNA binding proteins (RBPs) has shed new insight into mechanisms of protein aggregation in disease , but how nuclear RNP granule deficiency contributes to neurodegenerative disorders is poorly understood. Disease linked RBPs including FUS, EWS and TAF15 mediate a DNA damage response through the formation of an RNP granule around DNA breaks  produce pleotropic pathology that are a major cause of familial ALS, and also contribute to other neurological diseases. This mutant expansion was initially identified and found to induce the formation of RNA foci from the sense strand of the C9 mRNA  mediated by their LCDss  play a key role in responding to many of the same cell stressors that induce stress granules. While stress granules sequester non-essential mRNAs in the cytoplasm, heat shock transcripts are still translated. HSPs reduce protein misfolding and target existing misfolded/aggregated proteins for degradation, protecting neurons from injury caused by the accumulation of misfolded/aggregated proteins. Binding of HSPs to the LCDs of RBPs reduces their aggregation propensity; binding to the disordered domains of proteins such as tau or \u03b1-synuclein reduces the assembly of these aggregation prone regions as well. Hsp27 interacts directly with tau, specifically hyper-phosphorylated tau and PHFs  , PKR-like/Pancreatic Endoplasmic Reticulum kinase (PERK), Heme-Regulated Inhibitor (HRI), or General Control Non-derepressible 2 (GCN) (Taniuchi et al., 7G mRNA cap (Ivanov et al., Translation can also be stalled through eIF2\u03b1 independent mechanisms acting directly on components of the ribosome, particularly the small subunit involved in preinitation complexes (Kedersha and Anderson, Stalling of translation through eIF2\u03b1 dependent or independent pathways allows for disassembly of polyribosomes. The determinant of SG formation lies in whether the ribosomes remain associated with the transcripts. Stalling caused by the protein synthesis inhibitor puromycin disassociates the ribosome, producing naked transcript and initiating SG assembly (Kedersha et al., RNA binding proteins have a rich biology that integrates well with our knowledge of the pathophysiology of neurodegenerative diseases. The core biology derives from the presence of LC domains that undergo LLPS, allowing for reversible aggregation and sequestration of transcripts and other binding proteins. This normally transient biological phenomenon appears to become persistent and pathological in disease, resulting in the interference the normal functions of RBPs and transcripts through excessive segregation. Emerging evidence from several laboratories demonstrate that tau protein contributes to SG biology by promoting SG aggregation in a process that leads to tau concomitant aggregation. In chronic disease, these aggregated proteins become persistent and pathological, which ultimately leads to the accumulation of aggregated protein, disease pathology and neurodegeneration. Fortunately, SG biology is regulated at multiple levels by a variety of pathways, which provides entirely new targets of pharmacotherapy for many neurodegenerative diseases, including ALS and AD.BM, HB, and BW all contributed to writing and editing the manuscript.BW is co-founder and Chief Scientific Officer of the biotechnology company Aquinnah Pharmaceuticals Inc. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "This study compared the executive functions, organization in time and perceived quality of life (QoL) of 55 adults with learning disabilities (LD) with those of 55 matched controls (mean age 30 years). Furthermore, relationships and predictive relationships between these variables among the group with LD were examined.Behavioral Rating Inventory of Executive Functions (BRIEF-A), the Time Organization and Participation  and the World Health Organization Quality of Life (WHOQOL) questionnaires. Chi-square tests, independent t-tests and MANOVA were used to examine group differences in each of the subscales scores and ratings of each instrument. Pearson correlations and regression predictive models were used to examine the relationships between the variables in the group with LD.All participants completed the Adults with LD had significantly poorer executive functions (BRIEF-A), deficient organization in time abilities (TOPS A-B), accompanied with negative emotional response (TOPS- C), and lower perceived QoL  in comparison to adults without LD. Regression analysis revealed that Initiation (BRIEF-A) significantly predicted approximately 15% of the participants' organization in time abilities  beyond group membership. Furthermore, initiation, emotional control  and emotional responses following unsuccessful organization of time (TOPS-C) together accounted for 39% of the variance of psychological QoL beyond the contribution of group membership.Deficits in initiation and emotional executive functions as well as organization in time abilities and emotional responses to impairments in organizing time affect the QoL of adults with LD and thus should be considered in further research as well as in clinical applications. DSM (5th Ed.) )organizational abilities significantly discriminated between children with and without dysgraphia )In accordance with the ICF model concepts, the results of this study demonstrate that adults with LD confront deficiencies in body functions and that these deficiencies are expressed as limitations in their activity and participation in a variety of life domains and not only in their academic performance. These findings strengthen the need to consider this population within a wide health perspective and not only in terms of their academic deficiencies for which they are usually diagnosed and treated ,4. In ad"}
+{"text": "Lung cancer is one of leading causes of cancer-related deaths worldwide. Recent genetic study has identified several driver gene mutations, which leads to the development of targeted therapies and improvement of our knowledge in lung cancer. In 2015, the WHO classification of lung cancer and the IASLC  have updated their criteria and recommendation in lung cancer [Recent systematic reviews and meta-analyses have shown that interobserver disagreement rates on the subclassification of non\u2013small cell lung cancer (NSCLC) are approximately 10-20% in resected specimens and 20-30% in small biopsy specimen without IHC stains [The 2015 updated WHO classification of lung cancer and IASLC emphasizes the critical role of pathologists and IHC markers in the accurate subclassification of NSCLC, and also recommend to preserve tumor tissue for molecular characterization of NSCLC . In smalBased upon the WHO and IASLC guideline and clinical demand, we recently have combined commonly used individual markers TTF-1, P40, and Napsin A into a novel triple marker, and use it in the subclassification of NSCLC ,6. In caTaken together, the current WHO and IASLC criteria as well as our practical approach demonstrate that pathologists play a critical role in the accurate subclassification of NSCLC for targeted therapies and in the era of personalized medicine."}
+{"text": "On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. Increased surveillance of the virus, including the requirement for laboratory confirmation of infection, was recommended. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. The survey indicated that 16/19 (84%) countries had capacity for molecular detection of ZIKV while others facilitated testing through referral. These results suggest that robust laboratory capacity is in place to support ZIKV surveillance in the Western Pacific Region. Aedes mosquitoes, the same vector transmitting other arboviruses of public health impact such as yellow fever virus, dengue virus (DENV) and chikungunya virus (CHIKV). . The survey was completed by 23 laboratories in 18 countries. For the country not responding, information from other sources such as recent peer-reviewed publications was used where possible to augment the data set and cover all 19 countries.AMRO, World Health Organization Regional Office for the Americas; CHIKV, chikungunya virus; DENV, dengue virus; PCR, polymerase chain reaction; US CDC, United States Centers for Disease Control and Prevention; ZIKV, Zika virus.Given the similarity of disease presentation, . (As in our previous survey of regional PCR testing capacity for Middle East respiratory syndrome coronavirus, (While the Region seems prepared overall for testing of ZIKV, it is important to continue strengthening the apparatus for detection particularly through ensuring testing proficiency by EQA participation and enhancing referral mechanisms and International Air Transport Association certification where needed. It should be noted that while the EQA for DENV and CHIKV diagnostics gives confidence about regional testing proficiency for those arboviruses, (The laboratory plays an important role in improving our understanding of ZIKV epidemiology. While this survey reveals a broad availability of molecular diagnostics to support surveillance of ZIKV in the Western Pacific Region, further key roles remain for laboratories in helping to unravel the pathogenicity of the virus and its potential causal role in the observed cases of microcephaly and other neurological disorders."}
+{"text": "Changes of cognitive function in PD have been extensively documented and defined as a \u2018frontal\u2019 type executive dysfunction. One of the main components of this executive dysfunction is the impairment of verbal fluency. The aim of the present study was to assess semantic and phonemic fluency in a large sample of PD patients and to investigate the effect of clinical and sociodemographic variables on verbal fluency in this patient group.Three hundred patients with idiopathic Parkinson's disease who were consecutive referrals to our clinic and 50 age and education matched healthy controls completed the phonemic and semantic verbal fluency tasks. Both phonemic and semantic verbal fluency were significantly impaired in PD patients relative to matched controls. Stage of illness, presence of depression, education and age influenced verbal fluency measures. Regression analyses established that global measures of cognitive ability (MMSE) and executive function (FAB) and side of onset of motor symptoms predicted 36\u201337% of variance of phonemic or semantic verbal fluency measures. Thus, future studies aimed at assessing cognitive functioning in PD patients treated by deep brain stimulation (DBS) should adequately take into account several factors  which may potentially influence performance on verbal fluency tasks."}
+{"text": "The role of CNS neuromodulators in cognitive neurorehabilitation can be related to two main issues: (1) the negative impact on cognition of drug categories prescribed for different neurologic symptoms, such as spasticity, extrapyramidal symptoms, or epileptic seizures; (2) their possible role in neuroprotection and amelioration of the cognitive status of the patient, especially attention and memory. This paper reviews different pharmacological aspects of cognitive neurorehabilitation in epilepsy."}
+{"text": "Accumulated evidence from non-human animal studies suggests that the prominent deficits in memory and executive function that characterise individuals with psychosis may, at least in part, be due to the effects of stress on the brain regions that support these functions. However, studies of patients with established psychosis have yielded inconsistent findings with regards to the relationship between stress and cognition, and research in high-risk populations is notably lacking. Utilising data from the North American Prodrome Longitudinal Study 2 (NAPLS 2), we aimed to further elucidate the relationship between stress  and cognitive function in clinical high-risk (CHR) individuals and healthy controls (HC). We additionally explored the role of potential mediators [hypothalamic-pituitary-adrenal (HPA) axis function] and moderators .The sample comprised 885 participants  who completed measures of stress and cognitive function at the NAPLS 2 baseline assessment. Stress measures included the Daily Stress Inventory and a modified version of the Psychiatric Epidemiology Research Interview Life Events Scale, both of which provided continuous measures of stress exposure (number of events) and distress (subjective feelings of distress). Participants were also interviewed using the Childhood Trauma and Abuse Scale to determine any exposure to childhood trauma . Basal HPA axis activity was determined via salivary cortisol samples obtained at the baseline assessment and standardised scores from selected subtests from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) were used to derive two cognitive domain scores (memory and executive function). To examine relationships between stress and cognitive domain scores, linear regression analyses were performed on standardised variables.Daily stressor exposure, daily stressor distress, and life event exposure exhibited negative quadratic  associations with both memory and executive function . In contrast, the reverse pattern  was shown in the model for life event distress and memory domain scores (P < 0.01) whilst trauma history showed only a trend-level association with poorer memory performance (P = 0.084). These relationships, which did not differ across CHR and healthy control groups, were largely unchanged after adjusting for demographic factors and salivary cortisol. Exploratory analyses suggested that trauma exposure and a family history of psychosis may moderate the relationship between daily stressors/life events and cognitive function.In this large sample of predominately CHR individuals, we observed that the association between stress and cognition is complex and differs across stressor types. The negative quadratic associations that we observed for daily stressor exposure, daily stressor distress, and life event exposure imply that whist lower levels of stress may facilitate memory and executive function, there may be a negative impact on cognition when these stressors become more frequent and distressing. Interventions aiming to minimise stress exposure and promote effective coping strategies might feasibly improve cognition in CHR individuals."}
+{"text": "The Japanese language is represented by two different codes: syllabic and logographic while Portuguese employs an alphabetic writing system. Studies on bilingual Portuguese-Japanese individuals with acquired dyslexia therefore allow an investigation of the interaction between reading strategies and characteristics of three different writing codes. The aim of this study was to examine the differential impact of an acquired brain lesion on the reading of the logographic, syllabic and alphabetic writing systems of a bilingual Portuguese-Japanese aphasic patient (PF). Results showed impaired reading in the logographic system and when reading irregularly spelled Portuguese words but no effects on reading regular words and nonwords in syllabic and alphabetic writing systems. These dissociations are interpreted according to a multi-route cognitive model of reading assuming selective damage in the lexical route can result in acquired dyslexia across at least three different writing codes."}
+{"text": "The purpose of this project was to determine the feasibility of integrating medication therapy management (MTM) services provided by community pharmacists into the clinical care teams and the health information technology (HIT) infrastructure for Minnesota Medicaid recipients of a 12-county community-based accountable care organization (ACO). (2) Methods: The continuous quality improvement evaluation methodology employed in this project was the context + mechanism = outcome (CMO) model to account for the fact that programs only work insofar as they introduce promising ideas, solutions and opportunities in the appropriate social and cultural contexts. Collaborations between a 12-county ACO and 15 community pharmacies in Southwest Minnesota served as the social context for this feasibility study of MTM referrals to community pharmacists. (3) Results: All 15 community pharmacy sites were integrated into the HIT infrastructure through Direct Secure Messaging, and there were 32 recipients who received MTM services subsequent to referrals from the ACO at 5 of the 15 community pharmacies over a 1-year implementation phase. (4) Conclusion: At the conclusion of this project, an effective electronic communication and MTM referral system was activated, and consideration was given to community pharmacists providing MTM in future ACO shared savings agreements. The aim of this project was to integrate medication therapy management (MTM) services provided by community pharmacists into the clinical care teams and the health information technology (HIT) infrastructure for Medicaid recipients of a 12-county community-based accountable care organization (ACO). Southern Prairie Community Care (SPCC) of Southwest Minnesota invited colleagues from the University of Minnesota College of Pharmacy to collaborate on integrating medication management services into the redesigned care delivery and financing system of the 12-county SPCC Accountable Care Organization. This was a novel opportunity to engage community pharmacists in a feasibility test of change related to value-based care model integration and financing. Funding for this feasibility study was obtained from the Community Pharmacy Foundation.The U.S. healthcare system is evolving from fee-for-service reimbursement to an outcomes-based payment system based on reductions in total cost of care and improvements in quality of care performance measures of the Centers for Medicare & Medicaid Services (CMS) Quality Payment Program (QPP) .In this feasibility study, there was an existing reimbursement system in place for the provision of MTM services by pharmacists through the Minnesota Medicaid Program. This existing reimbursement mechanism helped to address a common challenge of providing MTM services. Other common challenges to the provision of MTM services include collaborative relationships with prescribers, billing difficulties, inadequate management support for MTM, and technology barriers such as access to patients\u2019 medical records and bi-directional exchange of health information .The SPCC community-based care system has engaged multiple providers, payers and stakeholders since 2006 in building capacity to increase local control around service decisions made for vulnerable people living in the 12-county region. Local pharmacists contributing to SPCC work groups and planning committees during the stakeholder engagement process provided outcomes research data on the impact of MTMS provided by pharmacists, convincing SPCC decision-makers of the need to help patients confidently manage their medications. Pharmacist engagement in the SPCC stakeholder planning process focused attention on the need for building systems to improve the effective and safe use of medications and to reduce drug-related morbidity and mortality.SPCC is accountable for the medical, facilities, and pharmacy costs of over 20,000 attributable Minnesota Medicaid recipients living in the 12-county region, and there are approximately 36,000 Medicaid recipients in the 12-county SPCC area. Attribution is a method for assigning patients to an ACO based on the utilization history of a patient. Medicaid recipients who are not attributable to the SPCC network typically receive care outside the 12-county area or outside of the SPCC network. It is noted that pharmacy costs constituted nearly one-fourth of total expenditures for SPCC Medicaid recipients, which is well above national averages for pharmaceutical expenditures reported by the Commonwealth Fund based on Organization for Economic Cooperation and Development (OECD) Health Data [The objectives of this project were to: (1) ensure service level expectations of MTM services provided by community pharmacists; (2) equip pharmacists to function effectively in the SPCC healthcare teams; and (3) integrate the electronic documentation of community pharmacists providing MTMS into the SPCC HIT infrastructure. The significance of this initiative relates to community pharmacist integration in new care delivery models supporting the Medicare Access and Chip  Reauthorization Act (MACRA) reimbursement programs.The methodological approach used in this project combined evidence-based medicine with the science of continuous quality improvement. The relationship of evidence-based medicine to the science of quality improvement can be described as consistently doing the right thing right. Pawson and Tilley pointeyearbookd out that evidence-based medicine is deeply vested in experimental design using an OXO evaluation approach of: observe a system (O), introduce a perturbation/intervention (X) to some participants but not others, and then observe again (O) . Dr. Donif pharmacist integration in care model innovation works, but how do we make it work more effectively and efficiently? The introduction of interprofessional and interdisciplinary systems for establishing a rational medication use system in which patients routinely achieve their goals of therapy with zero tolerance for preventable medication harms is a complex, multicomponent intervention\u2014essentially a process of social change.Previous research projects have replicated favorable clinical and economic outcomes of pharmacist integration in comprehensive, team-based medication management ,9,10,11.An alternative evaluation approach applied in this project was the context + mechanism = outcome (CMO) model. This evaluation approach accounts for the fact that programs only work insofar as they introduce promising ideas, solutions and opportunities in the appropriate social and cultural contexts ,5. One eThis was a 24-month feasibility study that included an 8-month community outreach phase, a 12-month implementation phase and a 4-month evaluation phase, spanning from October 2014\u2013September 2016. The study design focused on three major objectives. The first objective relates to understanding the care capacity of pharmacists working in the 12-county region, and coordinating service level expectations of MTMS provided by pharmacists. The second objective was preparing pharmacists to function effectively in high performing teams. The third objective was integrating the electronic documentation of community pharmacists providing MTMS into the SPCC HIT infrastructure.Ensuring service level expectations of pharmacists providing MTMS was the responsibility of the Principal Investigator working in collaboration with colleagues from the MedEdge Rx (formerly UPlan) MTM Network. The MedEdge Rx Network coordinated communications among credentialed providers. Prior to project inception, it is noted that pharmacists throughout the 12-county region were formally introduced to the SPCC Accountable Care Organization initiative in December 2013 at a local Minnesota Pharmacists Association Pharmacy Night in which the SPCC CEO served as the keynote presenter.This project represented an opportunity to build a rational medication use system within redesigned care delivery intended to integrate the resources of pharmacists living and working in the SPCC communities. The pharmacy workforce profile of the 12-county SPCC area includes approximately 80 pharmacists working in 34 community pharmacies, 15 critical access hospitals, three regional hospitals, and 25 area clinics. The 12 Minnesota counties in the SPCC area include (from North to South), Swift, Kandiyohi, Chippewa, Yellow Medicine, Lincoln, Lyon, Redwood Falls, Murray, Cottonwood, Rock, Nobles, and Jackson County. Pharmacists working in 15 community pharmacies and in 2 clinic pharmacies were credentialed providers of the MedEdge Rx MTM Network providing MTMS consistent with State of Minnesota MTM requirements at project inception . All othPharmacists in the 12-county region were provided with the opportunity to take Minnesota DHS-approved MTM training programs, if they had not already completed training. The MedEdge Rx MTM Network coordinated oversight for credentialing pharmacists in the SPCC region, providing access to peer mentors, and assessing and monitoring quality of care delivered by pharmacists. An Exempt Category 4 Institutional Review Board (IRB) application was reviewed by the University of Minnesota Human Research Protection Program .This project was designed to equip MTM pharmacists to function effectively in high performing teams for making valuable contributions toward helping patients achieve their drug therapy treatment goals and resolve drug therapy problems. Pharmacists, healthcare teams, and patient advisors across the SPCC area were brought together to build relationships and capacity utilizing portions of the primary care version of Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) . ModifieIn addition, a series of periodic half-day workshops were produced to bring community care team members together for the purpose of accelerating progress toward community-based medication management collaborations. Each workshop program included an overview of comprehensive medication management generally and the SPCC MTM Network specifically, as well as small workgroup sessions focusing on areas of care coordination. Topics of focus throughout the SPCC MTM Workshop series included, conducting co-visits, promoting the MTM service to SPCC recipients, and clinical topics such as building community-based systems to assist patients with cardiovascular and mental health needs.Creating the legal and regulatory scaffolding supporting community pharmacist integration in the SPCC HIT system,Providing community pharmacists with access to the recently-released national encryption standard for securely exchanging clinical healthcare data and Protected Health Information (PHI) known as Direct Secure Messaging, and,Developing processes to help pharmacists more effectively identify SPCC attributable Medicaid recipients for MTM services.Pharmacist integration into health information technology (HIT) systems and infrastructure is vitally important to effective and efficient team-based care, although access to critical medical information has been historically challenging to obtain for community pharmacists. The third objective of this project was integrating the electronic documentation of community pharmacists providing MTMS into the SPCC HIT infrastructure. Important steps in addressing this objective included:The legal and regulatory infrastructure for pharmacist participation in the SPCC HIT system relates to meeting standard health provider conditions of participation including HIPAA-compliant Provider Participation and Business Associate Agreements. Access to Direct Secure Messaging ensures community pharmacist compliance with the electronic health record technical specifications of the Medicare Access and CHIP Reauthorization Act (MACRA). In addition, pharmacist access to accurate lists of recipients that are both eligible for reimbursement through the Minnesota Medicaid MTM Program, and attributable to the SPCC network would be beneficial in prioritizing SPCC recipients for MTM services. Southern Prairie Community Care is officially recognized by the State of Minnesota as a Health Information Organization (HIO) under Minnesota Statutes \u00a7 2015 62J.4981 . At the Integrating pharmacists into the SPCC HIT infrastructure began with a technology survey to assess interoperability and compliance with meaningful use standards. Results of the technology survey were then used to structure technology site visits to each of the SPCC MTM network pharmacies. Once interoperability capabilities were established, original project plans called for the health integration vendor to assist in delivering a Webex training session on procedures and protocols for exchanging electronic health information. The intent of this project was to provide pharmacies with read-only access to medical records of SPCC attributable Medicaid recipients, and if feasible, select one pharmacy to test the bi-direction transfer of medical records and MTM documentation.Final project results were significantly influenced by major SPCC events and challenges. These challenges were related to the SPCC HIT master integration plan and recurring key personnel transitions. These challenges are briefly discussed below as a pretext to presenting project results.The most significant challenge occurred within the SPCC HIT integration process. As SPCC embarked upon an ambitious goal of creating a common medical records platform across providers, health systems and electronic medical record systems, a number of technical problems were encountered. The goal of creating a common medical record platform for physicians, clinics and MTM pharmacies remained elusive. Early during this project, it became evident that the SPCC timeline for HIT integration was fraught with challenges. The original plan called for HIT integration of physician practices and clinics, followed by SPCC MTM pharmacists and pharmacies. Then, early in 2016, the SPCC HIT Integration Vendor, Sandlot Solutions, abruptly announced it was going out of business . The othif pharmacist integration in care model innovation works, but how it works more effectively and efficiently. Pharmacist integration in health system settings of hospitals, clinics, and nursing homes has been in progress for many years. However, community pharmacist integration in emerging community-based care delivery systems is a relatively recent innovation. Therefore, this program evaluation assessed feasibility from both a near-term and a long-term perspective.As described in the Methods section, the program evaluation question applied to this feasibility study is not The near-term feasibility evaluation utilized the three study objectives of; ensuring service level expectations for MTMS, pharmacist engagement in community-based healthcare teams, and integration into the SPCC Health Information Exchange (HIE). Peer review of MTMS documentation for the 32 SPCC recipient referrals revealed that Minnesota Department of Human Services documentation standards were met for these recipients . InterviLong-term feasibility was made possible by determining the number of SPCC MTM pharmacists continuing to care for SPCC recipients one year after study conclusion. This study was conducted from October 2014\u2013September 2016. Post-study interviews were conducted with MTM pharmacists and SPCC personnel in September 2017 indicating that five of the 15 SPCC community pharmacy MTM sites, and both of the clinic-based MTM sites, were continuing to collaborate with health team members in their communities to provide MTM services. Additional results are presented below within each of the three study objectives.Objective 1: Ensuring Service Level Expectations of Pharmacists Providing MTMSThe University of Minnesota Human Research Protection Program served as the Institutional Review Board (IRB) for this project, and an Exempt Category 4 IRB application was submitted and reviewed in September of 2014. The goal for this project at inception was to have pharmacists at 12 sites approved by MN DHS as MTM providers. There were 24 pharmacists at 17 sites recognized by the Minnesota Department of Human Services and credentialed by the MedEdge Rx Network as MTM providers. The distribution of 17 sites includes 15 community pharmacies, one clinic pharmacy owned by a community pharmacy, and one pharmacy in a family practice clinic. And the distribution of community pharmacies includes 12 sites owned by regional chain pharmacies, and 4 independent pharmacy sites.The Minnesota Medicaid\u2014Resource-based Relative Value Scale reimbursement system was applied to the care delivered by pharmacists in this project. Of the 20,000 attributable SPCC recipients, the approximate distribution of recipients across health plans included, Blue Cross/Blue Shield (BCBS) managed care Medicaid (~50%), other managed care Medicaid plans (~30%), and MN Department of Human Services (DHS) fee-for-service Medicaid (~20%). MTM claims were submitted as a medical care benefit on an electronic CMS Form 1500 platform, which is the same claims format used for all other health care services. Procedures for submitting MTM claims for MN DHS fee-for-service recipients through the MN-eCONNECT system have been used for the past 10 years. It is noted that SPCC, Blue Cross/Blue Shield and University of Minnesota researchers collaborated to facilitate MTM contracting, and to provide three WebEx training programs for BCBS on-line MTM billing. Reimbursement levels and other economic and clinical data for the 32 SPCC referred recipients receiving MTM services was not an objective of this feasibility project.Objective 2: Equipping Pharmacists to Function Effectively in SPCC Healthcare TeamsThe effective delivery of MTM provided by pharmacists is dependent on collaborations with a patient\u2019s health care team. Interprofessional collaboration represents the \u201chigh-touch\u201d element of high-touch/high-tech integration. A series of interprofessional training programs were conducted throughout the course of this project. As part of the community outreach phase, a general MTM Informational Webinar was provided to SPCC community care teams. Then, an interprofessional training program was held that brought pharmacists and SPCC healthcare providers together to start the process of MTM collaboration. During the implementation phase, an SPCC Care Coordinator/MTM Pharmacist workgroup meeting was held to plan the MTM referral process for SPCC recipients, followed by a Care Coordinator workshop and then an SPCC Behavioral Health MTM workgroup meeting.The SPCC ACO presented their proposed Access Design Requirements to the Minnesota Department of Human Services (MN DHS) in February 2016. Pursuant to this formal review and approval, SPCC began preparing the attribution file, or list of eligible recipients, for all healthcare providers across the SPCC network. SPCC ACO leaders then developed a Data Driven Intervention Strategy (DDIS) using recipient\u2019s prior medical, hospital and pharmacy claims in the previous year to help them prioritize recipients for MTM referrals. The claims-based data elements for DDIS referrals included recipients in the top 20% of total cost of care or total pharmacy expenditures, or recipients with three or more hospital or emergency department visits over a six-month period. The original plan to distribute each pharmacy\u2019s list of attributable MTM recipients was delayed on several occasions pending DDIS access design reviews by MN DHS. SPCC prioritized MTM recipient referrals based on total health expenditures, medication expenditures and previous hospitalization and emergency room visits. A total of 32 SPCC recipients received MTM services pursuant to referrals at five community pharmacy sites.Objective 3: Integrating Electronic Documentation in the SPCC HIT InfrastructureIntegrating community pharmacists into the HIT infrastructure of the 12-county Southern Prairie Community Care (SPCC) Accountable Care Organization was a key objective of this project. One of the first HIT integration tasks completed early in the project was to have each MTM pharmacy execute HIPAA-compliant Business Associate Agreements and Health Information Exchange Agreements with SPCC. The University of Minnesota then contracted with Santa Rosa Consulting (the parent company of Sandlot Solutions) to assist in the HIT integration process. Santa Rosa Consulting was the same HIT consulting firm hired by SPCC to facilitate exchange of HIT in clinics and health systems across the 12-county ACO.1Design of a technology survey for SPCC pharmacies providing MTM services,2Technology site visits to SPCC pharmacies with the Health Information Exchange (HIE) Integration Vendor,3WebEx training to prepare pharmacies for receiving read-only access to the SPCC HIE infrastructure via a web based portal,4Development of technical design specifications for bi-directional data interchange between a pilot MTM pharmacy site and a central SPCC medical exchange platform.At the outset of the project there was an ambitious HIE integration plan for community pharmacists that included the following steps:Santa Rosa Consulting met their Step 1 and 2 statements of work. Results of the technology survey revealed that there would need to be a substantial investment to integrate the patient care documentation systems of SPCC MTM pharmacies to facilitate bi-directional data exchange. The primary challenge to bi-directional data exchange of SPCC MTM documentation was because pharmacist care plan HIE standards were not yet established at the time of this study. It is noted that the Pharmacist eCare Plan public/private initiative was recently launched to develop a standardized, interoperable document for exchange of medication management care plans and goals of therapy for pharmacists working in multiple environments .However, the Step 3 and 4 objectives were not met due to insolvency of the HIE Vendor, and funds were reallocated for two alternative HIE integration approaches. A new health care communications portal advocated by the U.S. Department of Health & Human Services, Office of the National Coordinator for Health Information Technology (ONC), known as Direct Secure Messaging, was deployed throughout the SPCC region . Direct Pharmacist/Integration Coordinator MTM co-visits including one with a recipient utilizing 44 Emergency Department (E.D.) visits over a 6-month period. The result was that this recipient had no further E.D. visits over the implementation and evaluation phases of this project. There were two direct quotations from SPCC stakeholders related to the care of this recipient that are noteworthy. The Integration Coordinator performing the MTM co-visit noted that, \u2018I didn\u2019t know that pharmacists had this type of training to help patients with their medication problems.\u201d The other quote came from the Emergency Department Coordinator at a meeting six months after the MTM co-visit lamenting, \u2018We haven\u2019t seen (this recipient) in six months and we thought that (this person) had passed away.\u2019MTM pharmacists at a community pharmacy site located inside a medical clinic were invited to join the clinic\u2019s Primary Care Provider Department with dedicated office space to provide MTM services. In addition, this invitation created the opportunity to create a post-graduate pharmacy residency experience at this site. During a Principal Investigator site visit shortly after the MTM pharmacist joined this practice, a primary care provider described elation in this newfound collaboration noting that, \u2018We always had pharmacists on our teams during my residency training in large health systems, and I never thought this was possible in a small rural setting.\u2019Collaborations with the local Health Department to execute a Centers for Disease Control and Prevention (CDC) cardiovascular health outreach grant in which the Community Health Worker was co-located at the MTM Community Pharmacy.Placement of an SPCC Integration Coordinator inside one of the community pharmacy MTM sites.Placement of an SPCC Somali Cultural Liaison at one of the MTM community pharmacy sites located in a grocery store.The appointment of an SPCC MTM Pharmacist to serve on the Southern Prairie Center for Community Health Improvement Board of Directors.There were a number of new collaborations and serendipitous events that occurred during this project serving as qualitative indicators of care model integration. As community pharmacists, social service providers, mental health professionals, and community health workers began collaborating around a new community-based model of care; there was evidence of team-based medication management similar to characteristics of integrated health systems employing pharmacists on health teams. Some of these indicators included:Although extenuating circumstances that occurred when the SPCC HIT Integration Vendor went out of business coupled with turnover of key SPCC personnel were disappointing, there are a number of highlights and lessons learned that are expected to be helpful in the future. Qualitative indicators and anecdotal reports from the SPCC MTM referrals were encouraging. As community pharmacists in the 12-county SPCC region strive to provide MTM services, discussions have progressed on including SPCC MTM pharmacies in shared savings agreements in the future. Minnesota was one of the first six CMS State Innovation Model (SIM) sites selected to accelerate progress towards value-based reimbursements. And shared savings agreements represent a bridge to global payment systems for achieving better care and better health at lower cost.This feasibility study was designed to address multiple barriers to pharmacist integration in community-based care teams. As noted previously, common challenges to the provision of MTM services include reimbursement, collaborative relationships with prescribers, billing difficulties, inadequate management support for MTM, and technology barriers such as access to patients\u2019 medical records and bi-directional exchange of health information . This stIt became apparent that inadequate management support was the common factor among the 10 community pharmacies that were unsuccessful in this project. The context + mechanism = outcome (CMO) model applied in this study suggests that programs only work insofar as they introduce promising ideas, solutions and opportunities in the appropriate social and cultural contexts ,5. The fIt is important to highlight the relationship of this project to the new physician-focused reimbursement system of the Medicare Access and CHIP Reauthorization Act (MACRA). The two MACRA reimbursement tracks of the Merit-based Incentive Payment System (MIPS) and the Advanced Alternative Payment Models (APM) are founded on achieving Quality Payment Program benchmark measures in the four broad categories of Quality, Improvement Activities, Advancing Care Information, and Cost. The Physician Quality Reporting System served as a backbone of MACRA, and over one-half of the nearly 300 MIPs and APM Program measures are dependent on the effective or safe use of appropriately indicated medications. The profession of Pharmacy has established an extensive research portfolio demonstrating the impact of medication therapy management services on economic, clinical, and humanistic outcomes. And steps taken in this project to integrate community pharmacists in a community-based ACO are expected to help accelerate collaborations with physicians to achieve MACRA benchmarks.The elusive goal of Health Information Integration (HIE) was prominent in this feasibility study. Although the ambitious objective of bi-directional HIE was not achieved, the integration of MTM pharmacists into the SPCC Direct Secure Messaging infrastructure has the potential to accelerate use of the Pharmacist eCare Plan standards, when fully developed . The PhaApplying Value-based Incentive Models within Community Pharmacy Practice presents the landscape for engaging community pharmacists in improving health care quality through innovative care delivery and payment models. Key concepts applied in this PQA White Paper included arrangements for pharmacists/pharmacies to share savings with ACO providers, and implementing value-based insurance programs in community pharmacies [Assessing the need for community pharmacist engagement in value-based healthcare delivery and financing is summarized in a White Paper produced under contract from the Pharmacy Quality Alliance. armacies .how we can make this integration more effective and efficient. The fact that an existing reimbursement system was in place for the provision of MTM services by pharmacists through the Minnesota Medicaid Program facilitated the design of this feasibility study.One potential limitation of this feasibility study is that it was not designed to evaluate clinical or economic outcomes of MTM services. As noted in the Methods section, previous results of research projects demonstrating favorable clinical and economic outcomes of pharmacist integration in comprehensive, team-based medication management has shifted the evaluation question to It is noted that the provision of MTMS for children was not a component of this feasibility study. Although pharmacists may provide MTMS for Minnesota Medicaid recipients under the age of 18, this patient population was not a focus of the SPCC attributable ACO population. Future feasibility studies related to the provision of MTMS for children in evolving MACRA care delivery and financing systems is warranted.Although reducing the burden of ineffective medication use and drug-related morbidity and mortality may seem like a daunting task, there is a solution. Outcomes studies of MTMS provided by pharmacists working in interprofessional care teams have consistently demonstrated improved clinical outcomes, reduced healthcare expenditures, and favorable return on investment ,9,10,11.Future research and pharmacy/pharmacist opportunities will be created by understanding the MTMS service level expectations of community-based care teams, establishing tools and resources for community pharmacists to function effectively in high-performing health teams, and by integrating the electronic documentation of community pharmacists providing MTMS into HIT infrastructure. The health care industry is implementing a range of approaches for succeeding in risk-bearing and outcomes-based financing to shift payments from volume to value . CompetePharmacist integration in healthcare teams in hospitals, skilled nursing facilities, and clinics has grown steadily over the past 30 years. Community pharmacist integration in healthcare teams has unique challenges owing largely to distance, information access, and reimbursement. As healthcare delivery and financing transitions from expensive volume-based services and procedures in hospitals, emergency departments and large facilities, to community-based care delivery and value-based financing, there is a new opportunity for community pharmacists to develop patient care practices. This feasibility study of community pharmacist integration was enabled by a community-based ACO with strong support for community pharmacist integration in new care delivery and information exchange models, as well as the presence of a pharmacist reimbursement system for MTM services.Although the daunting task of bi-directional exchange of health information between health systems and community pharmacists persist, there were small steps forward in terms of using Direct Secure Messaging to communicate with other community health team members, as well as the emergence of new Pharmacy eCare Plan standards for integrating pharmacists\u2019 MTM documentation into electronic health records. A significant lesson learned in this feasibility study is the importance of understanding the skills and abilities of all other care providers in a community and then working together in coordinated action similar to high performing health teams in large medical centers. Equally important are lessons learned from unsuccessful sites in that removing barriers of reimbursement, billing, collaborative prescriber relationships, and technology access are insufficient to advance community pharmacy practice without also guiding management support for social and cultural transformation so that the business of patient care can coexist and complement the prescription dispensing business."}
+{"text": "The authors regret that an incorrect grant number appeared in the Acknowledgements. The correct funding statement should read as follows:National Science Foundation grants DMR-1307138 and DMR-1507830, and through the John and Claire Bertucci Foundation.We gratefully acknowledge funding for this work through The authors would like to apologise for any inconvenience caused."}
+{"text": "Much anti-stigma work suggests that reducing stigma and improving mental health literacy could also improve access to care and support for people with psychotic disorders. This is important given that increasing help-seeking, especially during the early stages of psychosis could reduce the substantial delays to care experienced by people with psychotic disorders. Little is known about levels of personal stigma and mental health literacy among young people at-risk of psychotic disorders, whether there are differences between young people with and without elevated risk for psychosis and how this is associated with actual help-seeking for individuals at-risk of developing psychotic disorders.We interviewed participants from two existing, ongoing prospective cohorts in the UK and in Brazil. Participants were initially recruited from primary schools. Both samples represent enriched community cohorts (including a greater than average proportion of young people at risk of developing psychotic disorders) in Greater London (n=407) and a similar cohort of young people in Brazil . Participants were presented a vignette depicting a young person with early psychosis symptoms and asked about: recognition of the disorder; intended help-seeking; beliefs about interventions and prevention, stigmatising attitudes and whether they knew someone with a similar problem. We also collected detailed clinical data on psychiatric symptoms (via SDQ [Strengths and Difficulties Questionnaire] in the UK and DAWBA [Development and Well-Being Assessment] in Brazil), presence of psychotic-like experiences, and use of mental health services and personal experiences of seeking support for a mental disorder.Findings on the relationship between personal stigma and mental health literacy in relation to psychotic disorders, intended help-seeking and actual mental health service use, will be presented among young people with and without risk of developing psychotic disorders in the UK and Brazil.Reducing personal stigma and improving mental health literacy among young people at risk of psychosis who do not yet use clinical services could be important for future help-seeking. Future research should investigate the impact of anti-stigma interventions among young people with and without risk of developing psychotic disorders and how this facilitates help-seeking and support for this vulnerable group."}
+{"text": "A withstanding question in neuroscience is how neural circuits encode representations and perceptions of the external world. A particularly well-defined visual computation is the representation of global object motion by pattern direction-selective (PDS) cells from convergence of motion of local components represented by component direction-selective (CDS) cells. However, how PDS and CDS cells develop their distinct response properties is still unresolved. The visual cortex of the mouse is an attractive model for experimentally solving this issue due to the large molecular and genetic toolbox available. Although mouse visual cortex lacks the highly ordered orientation columns of primates, it is organized in functional sub-networks and contains striate- and extrastriate areas like its primate counterparts. In this Perspective article, we provide an overview of the experimental and theoretical literature on global motion processing based on works in primates and mice. Lastly, we propose what types of experiments could illuminate what circuit mechanisms are governing cortical global visual motion processing. We propose that PDS cells in mouse visual cortex appear as the perfect arena for delineating and solving how individual sensory features extracted by neural circuits in peripheral brain areas are integrated to build our rich cohesive sensory experiences. To solve this challenging computational problem, it is generally assumed that visual circuits from retina to V1 first dissects direction of motion for components of the object, such as oriented contours  cells (Movshon et al., Based on electrophysiology experiments and computational approaches, the current theory in primates for object motion representation is described with a two-stage model (Simoncelli and Heeger, At this time, three groups have probed the existence of CDS and PDS cells in mouse visual cortex (Juavinett and Callaway, Overall, evidence exist that mouse visual cortex represents and computes local and global motion, and therefore, is a valid model system for studying biophysical and circuit mechanisms of global motion computations in great detail. However, it may be plausible, and not all that surprising, if details in the strategy employed by mouse visual cortex for computing global motion deviates from that employed by humans and non-human primates. We speculate that primates and mice may have fundamental differences in the computational strategy and behavioral requirements of pattern motion computations. First of all, mice lack fovea in their retina unlike primates. Primate MT has a marked emphasis on the fovea; the central 15\u00b0 of the visual field occupies over half of MT\u2019s surface area (Van Essen et al., salt-and-pepper\u201d manner (Ohki et al., The functional organization of mouse and primate visual cortex differs on several levels (Huberman and Niell, We propose five key questions to be addressed where mouse visual cortex would serve as an excellent model. Note however, recent advances have introduced the marmoset monkey as an attractive primate model due to its rapidly evolving molecular and genetic toolbox available (Sadakane et al., First question is: what is the tuning of individual excitatory synaptic inputs onto PDS cells when single gratings or plaids are shown? Models derived from non-human primate research (Simoncelli and Heeger, Second question is: at which synaptic stages does normalization operate? Normalization is a fundamental neuronal computation that operates throughout the visual system and in many other sensory modalities (Carandini and Heeger, in vivo whole-cell patch-clamp recordings (Haider et al., Third question is: what kind of dendritic mechanisms in PDS cells are involved in the integration of synaptic inputs? The response properties of PDS cells seem to be predicted from supra-linear summation of excitatory inputs (Muir et al., Fourth question is: what is the role of brain state on PDS cell tuning? Recordings from CDS and PDS cells are often performed in anesthetized animals (Movshon et al., Last question is: what is the role of PDS cells in perception and behavior? Previous work has implicated MT in psychophysical performance on object motion discrimination tasks (Newsome et al., Chemical lesion of MT caused deficits in smooth pursuit eye movements, important for following moving objects (Newsome et al., How PDS cells develop their distinct response properties to single gratings and patterned plaids is still an open question. Due to the rapidly evolving ability to interrogate neural circuits and single neuron computations using genetic and molecular techniques, PDS cells in mouse visual cortex are the perfect arena for delineating and solving how individual sensory features extracted by neuronal circuits in earlier brain regions are integrated to build our rich cohesive sensory experiences.RR and KY drafted the manuscript, edited and revised the manuscript, and approved final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "More than 100 lipid researchers from across Australia participated in the 3rd Australian Lipid Meeting (ALM3), held on the 21st and 22nd of November 2016 in Melbourne, Australia. The conference was organized by Associate Professor Peter Meikle, a senior research fellow at the Baker Heart and Diabetes Institute, and supported by expertise in lipid research from Professor Ute Roessner, Professor Gavin Reid, Associate Professor Clinton Bruce, Dr. Thusitha Rupasinghe, Dr. Anthony Don, Dr. Andrew Hoy, and Dr. Simon Brown.The 1st Australian Lipid Meeting was held in 2013, and since then the Australian lipid research community has proven to be well connected despite the geographical separation between major cities. Interest in lipid research is expanding in Australia with a substantial increase in participation observed at ALM3. The meeting was highlighted with much discussion about new technologies, realizations of common ground and commiserations of common difficulties in lipid research. The meeting created new opportunities for young scientists to expand their knowledge through expert advice as well as learning big picture concepts for future research. ALM3 was specifically designed to give extensive opportunities for students and early career researchers. Two sessions were focused towards younger researchers, including one session of six lightning talks and one session of student presentations selected from the abstracts.The meeting was coordinated to cover seven topics including integrative lipidomics; metabolic diseases; local developments; neurodegeneration; plant and microbial lipidomics; fluxomics; and lipid signaling. The meeting was highlighted by keynote presentations from three leading international lipid experts. The meeting opened with an integrative lipidomics and data analysis session on Monday 21st November 2016, commenced by a presentation from Associate Professor Daniel K Nomura from the University of California, Berkeley. Professor Nomura discussed the use of chemoproteomic and metabolomics platforms to map drivers of human disease. This was followed by Dr. Brian Drew, discussing the analysis of the genetic regulation of the lipidome and proteome in murine liver, by quantification of more than 5000 proteins with excellent reproducibility within strains and significant variance of more than 2500 proteins between the 107 strains. In addition, quantitative lipidomics analysis of 311 lipid species across 23 lipid classes in which significant variation was shown in more than 100 lipid species and presented identification of numerous novel proteins that associate with an accumulation of pathological lipids in the liver, together with many genetic and protein signatures that define hepatic lipid metabolism. Dr. Magdalene Montgomery presented the identification of the medium chain fatty acid receptor GPR84 as a new player in glucose tolerance and mitochondrial function, concluding that the MCFA receptor GPR84 plays an important role in glucose tolerance, potentially via the regulation of mitochondrial function in skeletal muscle. Dr. Timothy Couttas introduced the bio-mechanism of glucose tolerance and the process of myelin biosynthesis related to Alzheimer\u2019s Disease.The second session in ALM3 was focused on metabolic diseases and how lipid analysis can be used to investigate relevant mechanisms and identify biomarkers. Professor Lisa Horvath from Chris O\u2019Brien Lifehouse presented an identified and validated novel plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer. Professor Matthew Watt from Monash University presented how the protein perilipin 5 (PLIN5) regulates lipid metabolism and insulin action using cultured cells and mice with whole-body and tissue-specific ablation of PLIN5. His study revealed that unique PLIN5 mediated remodelling of lipid metabolism in skeletal muscle and altered cellular stress signalling that impacts on systemic glucose metabolism through metabolic cross-talk. Yow-Keat Tham from Baker IDI institute, Melbourne presented a characterization of lipid modification in the heart of a transgenic mouse model with differential PI3K activity, while Aikaternini Emmanoulid from Curtin University discussed how lysophosphatidylinositol (LPI) triggers signaling in cell proliferation, migration, and survival in pancreatic cancer and the importance of the release of LPI by pancreatic cancer ductal adenocarcinoma (PDAC) cells as this molecule could be used in the future as a bio-marker to allow an early diagnosis.A highlight of the student presentation session was Matthew Summers\u2019 presentation, who won the best student presentation for his research work on a lipidomic approach to investigate the possibility of rescuing neurofibromatosis Type 1 (NF1) genetic disorder by dietary intervention. His findings show strong evidence that lipid storage myopathy underlies muscle weakness in NF1, and that simple dietary modification may be sufficient to dramatically improve muscle function and patient quality of life.The Lightning talks gave an opportunity for six talented early-career researchers to present their findings in lipidomic research in five-minute long talks. Dr. Sarah Abbott presented phospholipid diversity in human red blood cells (RBC), followed by an analytical development with ozonolysis for phosphatidylcholine species in RBC by Dr. Amani Batarseh. Dr. Zhiqian Liu presented how heat stress in dairy cattle could impact on the lipid composition of cow milk; then, Dr. Husna Begum showed the application of plasma lipid profile in a population of healthy Singaporeans, leading to the identification of ethnic differences in lipid levels and association with health risk factors. Dr. Sarah Hancock showed a structural elucidation of hydroxyl fatty acid and Dr. Jeniffer Saville presented an interrogation of brain gangliosides in a neurodegenerative mouse model.The last session of the first day was focused on local developments in lipidomics. Presentations were given on untargeted lipidomics analysis using LC-MS/MS within a mass spectrometry facility by Dr. Russell Pickford; comprehensive targeted plasma lipidomics by Kevin Huynh; bovine milk lipidomics by Dr. Zhiqing Liu; shotgun lipidomics analysis using ultra-high resolution mass spectrometry by Dr. Eileen Ryan; tools and techniques for structural characterization to investigate lipid\u2013protein interactions by Dr. Simon Brown; and analysis of cellular lipids using deuterated water and GC-MS by Dr. Greg Kowalski.The second day of the ALM3 meeting featured two international speakers from the USA: Professor Michelle Mielke from the Mayo Clinic and Dr. Stephen Previs from Merck. The first session of the second day focused on neurodegeneration and Professor Mielke presented her thought-provoking research findings on how sphingolipids play critical roles in pathways for multiple neurodegenerative diseases. Professor Mielke discussed the translation of the work from basic science to clinical and epidemiological studies, with a focus on the relationship between sphingolipids and Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Lewy Body Dementia (LBD), and Multiple Sclerosis (MS), and PD pathology and clinical phenotypes, then explored how plasma and sphingolipids may be best utilized as biomarkers for the development and progression of these neurodegenerative diseases. Presentations were continued by Professor Brett Garner, discussing ATP-binding cassette transporter roles in Alzheimer's disease; Professor Frederic Meunier, discussing the relationship of free fatty acids and lysophospholipids in brain and neuronal communication and memory. The neurodegeneration session was concluded by Professor John Mamo, discussing the effect of long-chain saturated fatty acid enriched diet on the brain lipid status. His findings demonstrated that cerebral abundance of some specific lipid species is strongly associated with plasma lipid homeostasis.The combined plant and microbial lipidomics session was opened by Dr. Surinder Singh from CSIRO, presenting the development of metabolically engineered plants that produce long-chain polyunsaturated fatty acids in plant seeds. Dr. Thusitha Rupasinghe presented an omics approach to identify salinity tolerance mechanisms in barley roots by measurement of changes in the spatial distribution of lipids due to salinity and showed insight into novel mechanisms responsible for salt tolerance of barley. Stephen Klatt discussed microbial lipidomics and the development of a comprehensive lipidomics pipeline for analyzing corynebacterium glutamicum inner and outer membrane lipids and cell wall synthesis.International speaker, Dr. Stephen Previs, opened up a very interesting session on fluxomics, presenting an application of fluxomics in drug discovery. Dr. Andrew Jenner discussed how sterol distribution in human lens changes with aging and Dr. Ahrathy Selathurai showed the role of mitochondrial phosphatidylethanolamine synthesis in the regulation of muscle and mitochondrial structure. The final session of the meeting was focused on lipid signaling. Professor Stuart Pitson opened the session, presenting an approach to target myeloma by a synergetic combination of sphingosine kinase 2 inhibition and bortezomib. Dr. Kieran Scott discussed the relationship of novel secreted phospholipase A2 inhibitors and prostate tumor and Associate Professor Anthony Don presented how selective inhibition of ceramide synthase 1 promotes fat metabolism.During the breaks between sessions, there was ample opportunity for networking across the small yet diverse Australian lipid research community. Attendees had the chance to get information and interact with commercial companies and suppliers for chemicals and instruments. A welcome reception and poster walk were held on the first day, followed by the conference dinner held at Albert Park in Melbourne. The lipid meeting was supported by generous sponsorships, especially from Waters, Shimadzu and Thermo-Fisher as gold sponsors, Sapphire Bioscience, Sciex and Agilent as silver sponsors. Avanti polar lipids sponsored the welcome reception while the poster prize was sponsored by Metabolomics Australia. The Australian Lipid Meeting 3 would not have been successful without the delegates of those who attended, presented and participated in valuable discussions. Our sincere thanks to all sponsors and delegates as well as invited speakers who made this event memorable. We look forward to meeting with you all at the next lipid meeting which will be held in the year 2018."}
+{"text": "Theories of behavior change are essential in the design of effective behaviour change strategies. No studies have assessed the effectiveness of interventions based on psychological theories to reduce sugar intake related to dental caries. The study assessed the effect of interventions based on Social Congition Models (SCMs) on sugar intake in adults, when compared with educational interventions or no intervention.A range of papers were considered: Systematic review Systematic Reviews with or without Meta Analyses; Randomised Controlled Trials; Controlled Clinical Trials and Before and after studies, of interventions based on Social Cognition Models aimed at dietary intake of sugar in adults. The Cochrane database including: Oral Health Group\u2019s Trials Register (2015), MEDLINE (from 1966 to September 2015), EMBASE (from 1980 to September 2015), PsycINFO (from 1966 to September 2015) were searched.No article met the full eligibility criteria for the current systematic review so no articles were included.There is a need for more clinical trials to assess the effectiveness of interventions based on psychological theory in reducing dietary sugar intake among adults.CRD42015026357.PROSPERO: The online version of this article (doi:10.1186/s40359-017-0194-z) contains supplementary material, which is available to authorized users. Theories of behavior change \u20134 are esSocial Cognition Models (SCMs) are a subgroup of psychological theories, which are based on the assumption that the individuals\u2019 attitudes and beliefs towards a behaviour are strongly predictive of the likelihood of them engaging in that behaviour . InterveIn oral health, two comprehensive systematic reviews have been conducted to assess the effectiveness of interventions based on SCMs, which aimed to improve adherence to oral hygiene related behaviours in adults with periodontal diseases. In the first systematic review, Renz and colleagues  reportedHowever, upto date there is no published systematic review of the effectiveness of interventions based on psychological models of health related behaviour to reduce sugar intake related to dental caries in adults. Dental caries is a prevalent issue that affects the majority of the adult population around the world \u201315; for Achieving the target consumption of free sugars is likely to require behaviour change by individuals, and the dental team can play an important part in assisting people to achieve this. The aim of the current systematic review is to examine the effectiveness of interventions based on Social Congitive Models (SCMs), aimed at reducing sugar intake related to dental caries among adults. The review aims to rectify this by addressing the following question: What is the effect of interventions based on Social Congitive Models (SCMs) on sugar intake in adults, when compared with educational interventions or no intervention?The current systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), 2015 database (CRD42015026357). The reporting of the review is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Comparison: oral health educational  interventions, or no intervention controls.\u2022 Types of participantsAdults aged 18 or over.Patients with or without dental caries. For the aim of this review, dental caries is defined on the basis of diagnosis from a dental clinician. This includes diagnoses of any caries lesion active, progressive or arrested, which includes root caries.\u2022 Outcome measures:Three outcome measures were considered to determine adults oral health related behaviours for this review .Behavioural outcomes: reduction of sugar intake, assessed by any method, including self-report, food diary, observation etc.Attitude and belief outcomes:Primary outcomes: Patients\u2019 attitudes, beliefs and their intentions towards sugar intake related to dental caries.Clinical status outcomes: Progression of dental caries in the permanent dentition, assessed via tooth decay increment: DMFS  and/or DMFT scores; filled teeth including replaced restorations; early carious lesions which are arrested or reversed; root caries.This review included interventions based on the following psychological theories and models of health related behaviour:The Cochrane database including: Oral Health Group\u2019s Trials Register (2015),MEDLINE (from 1966 to September 2015),EMBASE (from 1980 to September 2015),PsycINFO (from 1966 to September 2015).Information sourcesThe search included reference lists from relevant articles and the eligible authors of trials were contacted for additional information if necessary. The search was not restricted to a particular language.A detailed search strategy was developed from Medline. An information specialist was consulted to assist with the development of the search strategy, as previous research suggests this improves the quality of the search . This seTwo authors (S Al and JTN) conducted the search and assessed the studies, initially through evaluating titles, keywords, and abstracts. Any articles, which were not considered to be suitable, were rejected at this stage. Full reports of studies were retrieved for all studies if they met the inclusion criteria. Further full review was conducted if the studies met the inclusion criteria for full assessment.Study DesignSample sizePsychological constructs assessed and theoretical framework adoptedMeasures of primary and secondary outcomesEffect of intervention on outcomesData were collected for each study on a data sheet, which includes the following data points:Two authors  to reduce sugar consumption among adults. The review focused on an often neglected area of health psychology that of oral health. No studies were found that matched the inclusion criteria of the review.There is a dearth of intervention studies designed to explore the effectiveness of psychologically based interventions on oral health including oral hygiene as well as diet related behaviour. Harris and his colleagues  examinedWhilst it is disappointing that no intervention studies based on psychological theoretical models were identified from our systematic search, the current review has confirmed the need for high quality, theory-driven interventions to support clinical practice and has highlighted potential opportunities for researchers and intervention designers to explore and examine such approaches.To date there has been no published study of the effectiveness of interventions based on Social Cognition Models (SCMs) aimed at reducing sugar intake related to dental caries among adults. Given the contribution of dietary sugars to caries development and the role of lifestyle change to combat dietary sugar intake, there is a need for trials of theory-based interventions aimed at reducing individuals\u2019 consumption of dietary sugars."}
+{"text": "All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January\u2013February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance  circulating in American Samoa, and the possible long duration of anti-Zika immunoglobulin M (IgM) antibody positivity, serology was considered a less specific method for detection of Zika virus and therefore a less reliable indicator of ongoing Zika virus transmission.During August 31, 2016\u2013October 15, 2016 , routine testing of asymptomatic pregnant women who conceived within 8 weeks after the calculated transmission end date  was recommended  all persons with signs and symptoms consistent with Zika virus disease; 2) asymptomatic pregnant women with an estimated date of conception  on or before December 10, 2016; 3) pregnant women with prenatal findings suggesting congenital Zika virus syndrome (Because many Zika virus infections are asymptomatic (8) can have negative psychosocial repercussions on pregnant women and significantly burden the health care system with only limited benefit. Establishing a timeline for discontinuing screening of asymptomatic pregnant women allows ASDoH to allocate resources appropriately toward early interventions for children and families affected by Zika virus. The surveillance processes outlined and the timeline established for American Samoa might have implications for jurisdictions where small populations and similar population immunity following widespread Zika virus exposure can facilitate interruption of transmission.The increased likelihood of false positive test results that occurs as disease prevalence declines  for active mosquito-borne transmission of Zika virus and to propose a timeline for discontinuation of routine screening of asymptomatic pregnant women in American Samoa .The rationale described in this report might be adapted by similar jurisdictions with small populations and a potential for interruption of Zika virus transmission to help guide decisions about when to discontinue routine screening of asymptomatic pregnant women for Zika virus infection following the end of active mosquito-borne transmission."}
+{"text": "Human skin exposed to solar ultraviolet radiation (UVR) results in a dramatic increase in the production of reactive oxygen species (ROS). The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs). Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application. The skin represents the ultimate protection against multiple environmental insults and functions to maintain systemic homeostasis through multiple mechanisms , UVB (280\u2013315 nm), and UVC (190-280 nm). UVA and UVB are the biologically relevant components of solar UVR; the extremely harmful UVC rays are blocked by the stratospheric ozone layer and therefore do not reach the Earth's surface. UVB stimulates the production of superoxide anion radicals through the activation of NADPH oxidase and respiratory chain reactions  and 6-4 pyrimidine pyrimidone dimers (6-4PP) , a highly mutagenic lesion , activator protein 1 (AP-1) , an essential player in the inflammatory response  and double mutations (CCTT) at adjacent pyrimidine sites  and zinc oxide (ZnO), minerals that reflect and scatter UVA and UVB rays. However, these inert particles are often visible as an undesirable opaque layer on the skin. In addition, increased concern has been raised about the safety of these metal-based particles and their potential toxicity , blueberries  expression , reduction of hydrogen peroxide and decreased lipid peroxidation  has been the most extensively studied polyphenol. Its beneficial properties were first described in 1997  are strong UV absorbing compounds that are abundantly produced by many species of algae and have been incorporated into commercial sunscreens for many years (Hartmann et al., in vivo using both mouse and rat models (Bolfa et al., Propolis is a plant resin collected by honeybees. Its chemical composition and biological activity is very complex and depends on the sources of plants visited by the honeybees (Greenaway et al., Solar ultraviolet radiation in the form of UVA and UVB induce tissue damage in part via the production of ROS. The increase in ROS results in skin inflammation, characterized by vasodilatation that leads to formation of edema and erythema. This process leads to local accumulation of inflammatory T cells and neutrophils. During this process epidermal cells release several cytokines that contribute to the amplification of the immune and inflammatory responses. Anti-inflammatory agents like glucocorticoids, non-steroidal anti-inflammatory drugs can be used with great effectiveness. However, they usually cause adverse effects that limit the possibility of their prolonged use. Growing body of research has been revealing a number of natural products with the ability to reduce most of the damaging effects of solar UVR exposure without causing significant cytotoxicity.The sunscreens currently available offer some ROS protection mainly through the scattering properties of the sunscreen rather than antioxidant effects (Wang et al., SD: Performed literature review and wrote manuscript; LZ: Performed literature review, created figures, assisted in writing manuscript; RO: Assisted in assembling sources, creating bibliography and editing manuscript; LJ: Assisted in assembling sources, creating bibliography and editing manuscript; YZ: Manuscript review; AK: Manuscript review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The sense of taste is a key component of the sensory machinery, enabling the evaluation of both the safety as well as forming associations regarding the nutritional value of ingestible substances. Indicative of the salience of the modality, taste conditioning can be achieved in rodents upon a single pairing of a tastant with a chemical stimulus inducing malaise. This robust associative learning paradigm has been heavily linked with activity within the insular cortex (IC), among other regions, such as the amygdala and medial prefrontal cortex. A number of studies have demonstrated taste memory formation to be dependent on protein synthesis at the IC and to correlate with the induction of signaling cascades involved in synaptic plasticity. Taste learning has been shown to require the differential involvement of dopaminergic GABAergic, glutamatergic, muscarinic neurotransmission across an extended taste learning circuit. The subsequent activation of downstream protein kinases , transcription factors  and immediate early genes , has been implicated in the regulation of the different phases of taste learning. This review discusses the relevant neurotransmission, molecular signaling pathways and genetic markers involved in novel and aversive taste learning, with a particular focus on the IC. Imaging and other studies in humans have implicated the IC in the pathophysiology of a number of cognitive disorders. We conclude that the IC participates in circuit-wide computations that modulate the interception and encoding of sensory information, as well as the formation of subjective internal representations that control the expression of motivated behaviors. Traditionally, sensory cortices have been broadly defined and studied in relation to the encoding of stimuli arising from a single sensory modality. The insular cortex (IC) and the orbitofrontal cortex comprise the primary and secondary taste cortices, respectively, being particularly tuned to receive and integrate inputs relating to the modality , integral to the representation of tastes, oral texture, and temperature . Distinct subclasses of taste receptor cells are known to regulate the perception of salty, sweet, sour, bitter and umami taste in rodents , in contrast to CTA to familiar tastants  over time following repeated unreinforced CS exposures  and its reciprocal long-term depression (LTD) represent the most common cellular model for learning and memory   in rats, indicated that at the IC and BLA, CS- and US-information encoding is associated with increases in cytoplasmic and nuclear Arc mRNA respectively  Arc mRNA at the dysgranular IC, independent of conditioning  in rats, demonstrating that ACh release in the IC increases in response to novel taste presentation and decreases with each subsequent encounter, finally reaching levels observed during water presentation  , and glutamate in the IC, as administration of the muscarinic agonist carbachol into the IC increases the amplitude of unitary inhibitory post-synaptic currents (uIPSCs) within local interneuron networks, but suppresses uIPSCs in local pyramidal cells  downstream of MAPK/ERK kinase (MEK) is known to alter the translation of mRNA to protein through phosphorylation of the 40S ribosomal protein S6 kinase (RSK) and subsequent activation of ribosomal protein S6 -independent  propyl-1 phosphoric acid (CPP) and dizocilpine maleate (MK-801)  IC infusion prior to training  multimers (Brakeman et al., 2+-dependent intracellular activity (Tu et al., Homer1a complexes with PSD-95 and Shank, to physically link mGluR5 and NMDAR-signaling, an important event during late phase LTP (Naisbitt et al., Arc and Homer1a are NMDAR-dependent plasticity markers that exhibit differential temporal expression patterns in activated neurons (Guzowski and Worley, Arc mRNA have been demonstrated minutes following CTA training (Barot et al., Arc as well as Homer1a mRNA expression is differentially up-regulated within minutes of incidental novel but not familiar sucrose tasting (Saddoris et al., Arc and Homer1a to the CS itself (Saddoris et al., Arc mRNA expression at the IC, it is likely that occur at different times points at the BLA and the IC toward the maintenance of homeostatic scaling (Turrigiano, Arc transcription, translation and sub-cellular localization (Bluthgen et al., Okuno et al. have demonstrated Arc to be captured at less active synapses, a phenomenon known as inverse synaptic tagging (Okuno et al., Arc mRNA at the IC following CS administration (Barot et al., Conversely, studies have argued for CREB-independent gene transcription in the IC during novel taste learning Swank, . DespiteArc mRNA in the IC, demonstrated novel taste learning to promote prolonged suppression of Arc transcription (Inberg et al., Arc mRNA in response to hydration alone might suggest ERK activation to underlie drinking-induced increases in Arc mRNA independently of taste learning-induced suppression (Inberg et al., Arc mRNA extends up to 6 h following consumption, despite increases in the number of differentially modulated genes compared to water consumption (Inberg et al., Complementary studies accounting for hydration-induced rapid increases in Arc transcription in the IC might be specific to computations regarding the expectation of negative experiences (Jones et al., Arc expression in specific neurons of the IC and BLA (Barot et al., Novel taste-induced decreases in mRNA expression could relate to necessary adjustments toward levels that are required for optimal synaptic plasticity, achieved upon acquisition of familiarity (Inberg et al., Indicative of a requirement for lateralization of IC Arc expression during incidental taste learning in rats, the effect subsides upon repeated exposures to the same tastant (Inberg et al., The specific evolutionary benefit in such lateralized computations is still a matter of debate (Halpern et al., Other studies have reported increases in Arc protein expression in dendrites of the GC when comparing familiar and novel saccharin (Morin et al., Studies examining transcription and relevant protein expression during extinction and reinstatement of CTA might be more revealing of circuit-wide adaptations that underlie subjective interpretation of sensory experiences and more closely model natural settings. Extinction and reinstatement of conditioned responses is a dynamic process in which the activity of particular brain regions changes, depending on the extent to which the conditioned response has been extinguished Bouton, . ExtinctCTAE represents an inhibitory form of learning modulated by GABAergic signaling at the IC (Akirav et al., Understanding the role of plasticity synaptic within distinct regions and the extended taste circuit during aversive taste CTAE, hold particular potential in explaining how associations regarding the salience and hedonic value of stimuli are modified in relation to experience. Data accumulated thus far is largely correlative, but encouragingly studies are increasingly able to address causality at the circuit level (Kim et al., All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "It is also resulting in land use land cover (LULC) changes affecting the livelihoods of the people and the ecosystems  Specifications TableValue of the data\u2022The data is helpful to Addis Ababa City administrators to speculate the extent of the spatiotemporal expansion of Addis Ababa and its potential impacts on the surrounding areas.\u2022The data provides information on the status of urban expansion towards rural peri-urban areas around Addis Ababa.\u2022The data is vital to model urban expansion towards rural peri-urban areas surrounding Addis Ababa to mitigate its adverse impacts on the livelihoods of the people inhabiting the area and the ecosystem.\u2022The data is useful to researchers, urban planners and experts working in the field.1The data in this article provides information on the spatiotemporal LULC changes in Koye-Feche and Qilinto urban expansion areas around Addis Ababa City between 1986 and 2016. 2x and y coordinates of the sample spatial features using GPS. Depending on the scope of the study and visual interpretation of the satellite imageries, five classes were identified in Koye-Feche and Qilinto peri-urban areas. These are forestland (including riverine bushes and shrubs), plantation , grassland, cropland and built-up area  in the locality.Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper Plus (ETM+) images (with path/row numbers 168/054) as well as GPS-based ground survey records were vital data sources for this data article. The analyses, such as data extraction and LULC classification, were done by using ERDAS IMAGINE Version 2014 software. The images were geo-referenced with World Geodetic System (WGS) 1984 datum and Universal Transverse Mercator (UTM) projection system zone 37 North. Supervised and unsupervised image classifications techniques were employed to extract the data"}
+{"text": "Survey data and wet lab reports presented in this paper were collected from Western coastlines of India from Goan beaches. Oil polluted areas were captured on camera as evidence for oil and tar pollution. Several microorganisms showing diverse characteristics such as pigment producers, salt tolerant and hydrocarbon resistance were isolated and cultured in the laboratory. The dataset presented in this paper supports \u201cA case study on effects of oil spills and tar-ball pollution on beaches of Goa (India)\u201d   Specifications TableArambol beach oil pollution: offshore oil spill impact.Arambol beach oil pollution: shoreline oil spill impact..The following is Supplementary material related to this article Value of the data\u2022This data could be used to identify and study the extent of the impact of oil pollution.\u2022Data presented in this article could be used to study effects of oil pollution on foreshore and backshore of the polluted coastal regions.\u2022Microorganisms isolated in this study would have potential in bioremediation of tar-ball deposition on the seashore, Goan beaches, and other oil-polluted sites.1Data include evidence of oil spills and tar-ball pollution on the coastal ecosystem of Goa. Data of diverse microorganisms isolated from the oil contaminated samples tabulated and figured in the understandable form 2Extensive study and field work were performed for collection of data on oil spills and tar pollution on Goan beaches from Margao (Colva beach) to Arambol (near Maharashtra border). The flight distance between above two places is approximately 52\u00a0km. Questionnaire and oral interviews were the important tools used for gathering information on oil spills and tar-ball pollution prevalent areas. Composite sampling, stratified sampling, grab sampling and accident sampling methods"}
+{"text": "Impaired cellular innate immune defense accounts for susceptibility to sepsis and its high morbidity and mortality in preterm infants. Leukocyte recruitment is an integral part of the cellular immune response and follows a well-defined cascade of events from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration which is concerted by a variety of adhesion molecules. Recent analytical advances such as fetal intravital microscopy have granted new insights into ontogenetic regulation and maturation of fetal immune cell recruitment. Understanding the fetal innate immune system is essential for targeted prevention and therapy of premature infants with severe infections or disorders of the immune system. This review gives an overview of the basic principles of leukocyte recruitment, particularly neutrophil trafficking, and its development during early life and highlights technical limitations to our current knowledge. Prematurity is the most prominent risk factor for neonatal diseases and death . DespiteThe impaired function of the premature immune system has multiple causes: lack of immunoglobulins  and antiLeukocyte recruitment is an integral part of the cellular immune response and follows a defined cascade of events . After rThe initial step of leukocyte rolling is mediated by selectins, which bind to their respective ligands such as P-selectin glycoprotein ligand 1 (PSGL-1), CD44, or E-selectin ligand 1 (ESL-1) , 14. TheUnderstanding the fetal innate immune system is essential for targeted prevention and therapy of premature infants with severe infections or disorders of the immune system. The high vulnerability of preterm neonates to suffer from severe infections and sepsis can partially be attributed to impaired leukocyte recruitment early during fetal life . The obsSperandio et al. showed in vivo that neutrophil rolling and adhesion in murine yolk sac vessels is strongly reduced at early gestational ages and increases throughout gestation . These oPostnatal maturation of immune response and leukocyte recruitment is driven by multiple new environmental factors . SeveralTaken together, the gestational age-dependent upregulation of adhesion molecules leads to functional maturation of leukocyte rolling, adhesion, transmigration, and chemotaxis, which in turn strengthens the innate immune response.Despite technical progress, human neonatal in vivo imaging of immune cell trafficking is not yet available. Thus, fetal leukocyte recruitment has mainly been studied in vitro using leukocytes and endothelial cells in dynamic flow chambers or transmigration assays , 40, 41.While our understanding of the fetal and early neonatal immune system is ever growing, treatment options are still limited and the vast majority of pharmaceutical trials are run in adults with fully developed immunity. Novel analytical tools and models to study innate immunity may facilitate the development of new gestational age- and sepsis stage-specific therapeutic approaches to fine-tune the premature immune system and thereby optimize the treatment of neonatal infections and sepsis ."}
+{"text": "Tropospheric or ground-level ozone (O3) is still the phytotoxic air pollutant of major interest. Challenging issues are how to make O3 standards or critical levels more biologically based and at the same time practical for wide use; quantification of plant detoxification processes in flux modeling; inclusion of multiple environmental stresses in critical load determinations; new concept development for nitrogen saturation; interactions between air pollution, climate, and forest pests; effects of forest fire on air quality; the capacity of forests to sequester carbon under changing climatic conditions and coexposure to elevated levels of air pollutants; enhanced linkage between molecular biology, biochemistry, physiology, and morphological traits.Outcomes from the 22"}
+{"text": "Scientific Reports 10.1038/s41598-018-22883-9, published online 15 March 2018Correction to: The Acknowledgements section in this Article is incomplete.\u201cWe thank Dr. Astrid Lewin for her helpful discussion concerning the mechanism of PZA action. This publication presents independent research supported by the Health Innovation Challenge Fund , a parallel funding partnership between the Department of Health and Wellcome Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health or Wellcome Trust.\u201dshould read:\u201cWe thank Dr. Astrid Lewin for her helpful discussion concerning the mechanism of PZA action. This publication presents independent research supported by the MRC-DBT funded partnership between National Institute for Research in Tuberculosis, Chennai and University of Cambridge . The views expressed in this publication are those of the author(s) and not necessarily those of the MRC or DBT.\u201d"}
+{"text": "Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery. Synthetic biology builds on the transformative assertion that engineering approaches could be used to elucidate design principles of cellular systems and to implement synthetic digital and analog subsystems for a variety of end settings including health applications  that, through conformational changes induced by the binding of small molecules or proteins, regulate the activity of RNA actuators that can operate Actuation can occur through diverse mechanisms including splicing, stability, translation, and mRNA localization. Owing to the known impact of ribonucleases (RNases) on RNA maturation and stability, aptamers have often been combined with RNA substrates for RNase activities  and chimeric antigen receptors (Wilkie et al., One of the most important challenges is represented by cell specificity. A powerful way to enhance on-target activity of therapeutic T cells is to engineer combinatorial receptor systems such as dual receptor AND-gate T cells (Roybal et al., in vivo its potential to remove CAR-bearing T cells (Budde et al., T cell therapies could meet safety concerns if it were possible to eliminate quickly the engineered cells upon adverse side effects. Drug-inducible kill switches are an interesting development to achieve this goal. A recent example employs an inducible caspase 9 in conjunction with a CD20-specific CAR to test The design of negative feedback loops and inducible pause switches is proving a useful alternative to T cell elimination by modulating the immune response amplitude and timing. These circuits exploit the ability of bacterial virulence effector proteins to evade the immune response. The former type creates a negative feedback loop by expressing these proteins under the control of a T cell activation responsive promoter (Wei et al., Finally, a potent tool to regulate the therapy safety and efficacy is provided by growth switches (Chen et al., Gene circuit engineering has greatly improved our ability to programme genes involved in tumor origin and progress. For instance, some high-affinity RNA aptamers against PPAR-\u03b4, a lipid-sensing nuclear receptor involved in cancer (Kwak et al., in vivo delivery (Yoo et al., Today nanobiotechnology provides extremely versatile options to address the localized delivery of genetically encoded tools such as virus-based vectors modified to carry engineered payloads (Ryan et al., Synthetic biology is helping to address previously unfeasible challenges the field of drug discovery. Progress on design of synthetic genetic circuits (Carbonell et al., In this review, we focus on advances in biological engineering which stimulated the development of innovative approaches for precision intervention in oncology. The growing contribution of synthetic biology to drug discovery as well as the widening availability of synthetic circuits, which are already being used in different human compatible cell types and animal models for safe operation of gene- and cell-based therapies, demonstrate the potential of future approaches integrating systems and synthetic biology tools to precisely match therapies to individual cancer patients.The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Syphilis in pregnancy is an under-recognized public health problem, especially in sub-Saharan Africa which accounts for over 60% of the global burden of syphilis. If left untreated, more than half of maternal syphilis cases will result in adverse pregnancy outcomes including stillbirth and fetal loss, neonatal death, prematurity or low birth weight, and neonatal infections. Achieving universal coverage of antenatal syphilis screening and treatment has been the focus of the global campaign for the elimination of mother-to-child transmission of syphilis. However, little is known about the availability of antenatal syphilis screening and treatment across sub-Saharan Africa. The objective of this study was to estimate the \u2018likelihood of appropriate care\u2019 for antenatal syphilis screening and treatment by analyzing health facility surveys and household surveys conducted from 2010 to 2015 in 12 sub-Saharan African countries.In this secondary data analysis, we linked indicators of health facility readiness to provide antenatal syphilis detection and treatment from Service Provision Assessments (SPAs) and Service Availability and Readiness Assessments (SARAs) to indicators of ANC use from the Demographic and Health Surveys (DHS) to compute estimates of the \u2018likelihood of appropriate care\u2019.Based on data from 5,593 health facilities that reported offering antenatal care (ANC) services, the availability of syphilis detection and treatment in ANC facilities ranged from 2% to 83%. The availability of syphilis detection and treatment was substantially lower in ANC facilities in West Africa compared to the other sub-regions. Levels of ANC attendance were high (median 94.9%), but only 27% of ANC attendees initiated care at less than 4 months gestation. We estimated that about one in twelve pregnant women received ANC early (<4 months) at a facility ready to provide syphilis detection and treatment . The largest implementation bottleneck identified was low health facility readiness, followed by timeliness of the first ANC visit.While access was fairly high, the low levels of likelihood of antenatal syphilis detection and treatment identified reinforce the need to improve the availability of syphilis rapid diagnostic tests and treatment and the timeliness of antenatal care-seeking across sub-Saharan Africa. Globally, an estimated 5.6 million new syphilis cases occur every year, including one million cases among pregnant women ,2. Sub-SThe World Health Organization (WHO) recommends syphilis screening at the first antenatal care (ANC) visit, ideally in the first trimester . AntenatTo address this problem, the WHO has called for the dual elimination of MTCT of syphilis and HIV \u201314. StraHealth facility surveys, complemented by household surveys offer an alternative approach to gain valuable insight on the availability, quality and uptake of reproductive, maternal, newborn and child health (RMNCH) interventions including antenatal syphilis detection and treatment \u201322. HealWe conducted a secondary analysis of supply-side data obtained from two types of nationally representative cross-sectional health facility surveys, the Service Provision Assessment (SPA) and the Service Availability and Readiness Assessment (SARA). Both surveys use standardized data collection instruments to provide measures of availability and readiness of health facilities in a given country to provide essential services across several program areas including ANC. The availability of staff, guidelines, equipment, diagnostics, medicines and commodities is based on self-report and direct observation and verification. Further details on the sampling methods and survey procedures are available from final country survey reports ,26. ThisTo track progress in the implementation of antenatal syphilis detection and treatment we used a 3-step process. First, based on data from the health facility surveys, availability of syphilis detection for a given country was calculated as the percentage of health facilities providing ANC with observed availability of a rapid diagnostic test (RDT) on the day of assessment. Given WHO\u2019s push for point of care diagnostics, in this study, facilities referring ANC clients or send blood samples elsewhere for screening were considered as not having syphilis screening available. The availability of syphilis detection and treatment was calculated as the percentage of health facilities providing ANC services with both a screening test for syphilis and treatment .Second, we analyzed demand-side data from publicly available nationally representative household surveys conducted as part of the Demographic and Health Surveys (DHS) program . InformaThird, estimates of the likelihood of appropriate care were calculated by multiplying indicators of service utilization (ANC1+ and timing of first ANC visit) by indicators of health facility readiness at the stratum level. As service utilization and health facility readiness vary within countries, linking was conducted at the stratum level which was defined by health facility type  and managing authority (public/non-public). As women who attended multiple ANC visits can report multiple sources of ANC in the DHS, we made the simplifying assumption that these women sought care at the highest level of facility type reported. The estimates of likelihood of appropriate care for each country were disaggregated by timing of the first ANC visit . Women who attended at least one ANC visit at a health facility with syphilis detection and treatment available were classified as having a high likelihood of appropriate care, while those who sought ANC at a health facility with only syphilis detection available were classified as having a moderate likelihood of appropriate care. Women who sought ANC at a health facility that did not have the necessary diagnostics in stock were classified as having a low likelihood of appropriate care due to low health facility readiness. All other women did not seek any ANC and were considered classified as having no likelihood of appropriate care. This classification formed the basis for our identification of three bottlenecks in the implementation pathway of antenatal syphilis detection and treatment: access, timeliness, and health facility readiness.All analyses were conducted at the country level and took into account the sampling design . Because of important differences in epidemiological and programmatic context, we grouped country-specific results by sub-region. All analyses were conducted in STATA 14.2 .A total of 6,991 health facilities were sampled in the 12 sub-Saharan African countries during 2010 to 2015; health facility survey sample sizes ranged from 95 (Uganda) to 1,555  . If onlyDespite the widespread adoption of antenatal screening and treatment of syphilis as the main strategy for the prevention of MTCT of syphilis, we found suboptimal implementation strength across 12 sub-Saharan African countries. The global campaign to eliminate MTCT of syphilis has targeted achievement of at least 95% on three process indicators: coverage of ANC1+, coverage of syphilis testing of pregnant women and treatment of syphilis-seropositive pregnant women . Using oANC is a key platform for the delivery of evidence-based RMNCH interventions. Access to ANC has improved in recent years . NotablyHealth facility readiness was another major bottleneck. Across countries, a median of 54% of pregnant women who sought ANC in the first six months could not access syphilis detection and treatment due to inadequate supply of syphilis tests and treatment in ANC facilities, representing substantial missed opportunities for the delivery of high impact interventions to pregnant women seeking ANC early. The low availability of syphilis detection and treatment to ANC attendees identified in this study supports the findings that improving access to ANC does not guarantee the delivery of quality RMNCH services ,31,32. TGreater efforts are needed to strengthen implementation, improve the quality of RMNCH services and accelerate progress towards elimination of MTCT of syphilis. Continued efforts to routinely measure and track progress in universal screening and treatment of syphilis during pregnancy and more broadly, key RMNCH interventions are needed ,24. The There are several limitations to this analysis. First, the definition of high likelihood of appropriate care used was the percentage of women who attended ANC in the first three months at a facility with syphilis detection and treatment available. While the availability of basic amenities, equipment, diagnostics, medicines and commodities is a prerequisite for the delivery of antenatal syphilis screening and treatment, it does not guarantee receipt of care. Information on the receipt of syphilis screening and treatment is not typically available, therefore our estimates may overestimate \u2018true coverage\u2019. We did not account for factors such as provider knowledge or other health system factors that may hinder the actual receipt of interventions. Estimates of the likelihood of appropriate care are likely biased upwards. Second, the present analysis linked nationally representative household surveys and health facility surveys covering different survey reference periods. The availability of medicines and diagnostics can vary dramatically over a short time period due to the complexity of logistics, availability of penicillin, and seasonality. While the present study did not assess drug stock-outs, several countries in sub-Saharan Africa have experienced stock-outs of benzathine penicillin . TherefoThis study suggests low levels of availability of antenatal syphilis screening and treatment across 12 sub-Saharan African countries, albeit with wide variability in progress towards the elimination of MTCT of syphilis. Deficiencies in access, health facility readiness and timeliness of ANC identified represent opportunities to improve the coverage and quality of syphilis detection and treatment to pregnant women. Progress towards the elimination of MTCT of syphilis depends on sustained high levels of ANC uptake, improved timeliness of care-seeking, and increased availability of syphilis detection and treatment at health facilities across sub-Saharan Africa."}
+{"text": "The development of the clinical high-risk (CHR) prodromal criteria has facilitated advancement in understanding conversion to psychosis and has provided opportunities for early intervention and treatment for these individuals. However, the majority of CHR cases do not meet full criteria for conversion, yet continue to experience clinically significant symptoms and impairment in daily functioning. It is likely that many of these individuals would also benefit from additional intervention and treatment, but the outcomes and needs of these \u201cnon-converters\u201d are not well characterized. Identifying common longitudinal patterns of symptoms and functioning of non-converters would support the identification of individuals who continue to require treatment and tailoring of services to their specific needs.We used group-based trajectory modeling to identify common longitudinal symptom and functioning trajectories among CHR cases (N=561) in the second phase of the North American Prodrome Longitudinal Study (NAPLS2). Covariant trajectories of symptoms  and functioning  were examined. Models were tested for replicability in an independent sample of CHR cases (N=291) from the first phase of NAPLS (NAPLS1).We identified a subgroup of individuals who exhibited symptom remission and functioning within the normal range, as well as at least two additional subgroups that exhibited different patterns of ongoing, clinically significant symptoms and functional deficits.We are currently investigating the validity of these subgroups by assessing their association with a variety of risk factors and biomarkers."}
+{"text": "This article presents long-term analyzed rainfall and temperature data obtained from the National Metrological Agency (NMA) of Ethiopia. Using tables and graphic trends of analysis, the article shows the low and declining level of average annual rainfall as well as the high inter-annual fluctuations for 18 weather stations located in different agro-climatic zones of the country. The high variation of annual maximum and minimum temperature has been similarly observed for decades in the stations. Ethiopia's average annual temperature has risen between 1955 and 2015 by 1.65\u00a0\u00b0C. The country's agricultural production depends heavily on local temperature and rainfall. The evidence is clear that a slight change in such climatic elements negatively affects the food security condition of both producers and consumers. Although data from the Central Statistical Agency (CSA) show that major cereal crop production has increased at the national level, partly due to the increasing application of fertilizers and modern seeds, Ethiopia's food security condition is deteriorating due to global climatic events caused droughts and rain failure. The rate of food price inflation is thus often higher than the general consumer price inflation rate. Specification TableValue of the data\u2022Gives information on the changing condition of climatic elements' impact on production and food prices.\u2022Can be reproduced by researchers and experts working in the field.\u2022Useful to identify vulnerable communities and social groups to the effects of climate change risk for interventions.1The figures and tables of rainfall and temperature were analyzed based on the data obtained from 18 weather stations located in different agro-climatic zones of Ethiopia. 2The unprocessed long-term elements of climate such as rainfall and temperature data obtain from the National Metrological Agency (NMA) of Ethiopia were analyzed using tables and graphic trends of analysis. Annual rainfall and mean annual temperature of 18 representative weather stations were computed in order to calculate the country's mean annual rainfall and the inter-annual fluctuations and average annual temperature. The article used different year agricultural sample survey reports of Central Statistical Agency (CSA) of Ethiopia. Based on the data, the trends of major cereals crop production, area cultivated under improved seeds, local seeds, types of fertilizer and applied areas and the consumer price index in Ethiopia were calculated and presented. The author used Microsoft EXCEL software to analyze the data and present the result in graphs and tables."}
+{"text": "Cetyltrimethyl ammonium bromide cationic (CTAB) surfactant was used as template for the synthesis of nanoclusters of ZnS composed of nanowires, by hydrothermal method. The structural and morphological studies were performed by using X-ray diffraction (XRD), scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM) techniques. The synthesized ZnS nanoclusters are composed of nanowires and high yield on the substrate was observed. The ZnS nanocrystalline consists of hexagonal phase and polycrystalline in nature. The chemical composition of ZnS nanoclusters composed of nanowires was studied by X-ray photo electron microscopy (XPS). This investigation has shown that the ZnS nanoclusters are composed of Zn and S atoms. Among II-VI compound semiconductors, zinc sulphide (ZnS) is well known due to its wide band gap of 3.7 eV at room temperature and high exciton binding energy of 40 meV. ZnS is used widely in various applications such as ultraviolet light emitting diodes , electroIn this study, ZnS nanowires were synthesized by using cetyltrimethyl ammonium bromide cationic (CTAB) surfactant as a template for the growth. The effect of CTAB on the formation of nanowires was also investigated. Zinc acetate dihydrate was used as zinc source and thio urea as sulpher source, and CTAB as template for the growth. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used for the structural characterization of prepared sample of ZnS nanowires. X-ray photoelectron spectroscopy (XPS) was used for the study of chemical composition.Typical SEM images of ZnS are shown in Distinctive TEM, high resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) images are shown in 2+ ions and result in the ZnS nanomaterial. The possible reaction involved in the formation of nanoclusters of ZnS includes:The growth mechanism of ZnS nanoclusters composed of nanowires by hydrothermal growth method could be explained in terms of liquid-solid mechanism. By using CTAB as a growth template, it increases the concentration of sulpher free radicals in the growth solution during the heating of precursors in the Teflon vessel. The released free S radicals then might combine with the ZnXPS analysis was carried out for the study of chemical composition and purity of prepared sample of ZnS nanoclusters.The XPS spectra of ZnS nanoclusters are shown in The commercially available fluorine doped tin oxide (FTO) glass substrate was purchased from Sigma Aldrich Sweden and was used for the growth of ZnS nanostructures. The growth methodology was based on the following steps. Firstly, FTO glass substrate was washed with isopropanol in ultrasonic bath for 5 to 10 min and dried at room temperature. The growth solution of 0.5 M zinc acetate dihydrate and 0.75 M thio urea was prepared in 50 mL deionized water using 0.5 g and 1 g of CTAB respectively as a template for the growth of ZnS. The cleaned FTO glass substrate was affixed in the Teflon sample holder and growth solution was poured into Teflon vessel of 125 mL capacity and the Teflon vessel containing FTO substrate was sealed in the stainless steel autoclave and kept at 200 \u00b0C in the preheated electric oven for 12 h.The characterization of ZnS nanostructures was performed by using SEM, XRD and HRTEM techniques. XPS technique was used to study the chemical composition of the prepared sample of ZnS.In this study, the hydrothermal method was used for the synthesis of ZnS nanoclusters and the investigation of morphology further showed that the nanoclusters are composed of nanowires using CTAB as the template for growth. Structural, morphological and chemical composition studies were conducted. The nanoclusters of ZnS composed of nanowires are reported for the first time by hydrothermal method in this study. The effect of the CTAB concentration on the morphology of ZnS nanostructures was also investigated."}
+{"text": "Immunoglobulin free light chain (FLC) kappa (\u03ba) and lambda (\u03bb) isotypes exist mainly in monomeric and dimeric forms. Under pathological conditions, the level of FLCs as well as the structure of monomeric and dimeric FLCs and their dimerization properties might be significantly altered. The abnormally high fractions of dimeric FLCs were demonstrated in the serum of patients with multiple myeloma (MM) and primary systemic amyloidosis (AL), as well as in the serum of anephric patients. The presence of tetra- and trimolecular complexes formed due to dimer-dimer and dimer-monomer interactions was detected in the myeloma serum. Analysis of the amyloidogenic light chains demonstrated mutations within the dimer interface, thus raising the possibility that these mutations are responsible for amyloidogenicity. Increased \u03ba monomer and dimer levels, as well as a high \u03ba/\u03bb monomer ratio, were typically found in the cerebrospinal fluid from patients with multiple sclerosis (MS). In many MS cases, the elevation of \u03ba FLCs was accompanied by an abnormally high proportion of \u03bb dimers. This review focuses on the disease-related changes of the structure and level of dimeric FLCs, and raises the questions regarding their formation, function, and role in the pathogenesis and diagnosis of human diseases."}
+{"text": "Ultrasound guidance for central venous catheter (CVC) placement reduces complications, increases safety and enhances the quality of the procedure . ExistinSmaller studies have shown that patient positioning during cannulation of the subclavian vein  can alter the relationship between the subclavian vein and the internal jugular vein and can also alter the cross-sectional area of the vein, thus potentially affecting the safety and success of cannulation , 5. Furt"}
+{"text": "The articular puncture brought back a sterile inflammatory fluid. The radiographs of the frontal knee (A) and profile knee (B) and CT of the knee  showed destruction of the internal femoral condyle with osteolysis of the medial border of the internal tibial plateau associated with multiple bone constructions with the presence of intra-articular fragments, intra-articular effusion and thickening of the synovium. The diagnosis of tabetic arthropathy in its hypertrophic form was retained following a 20-year history of syphilitic inoculation chancre, posterior radiculocordonal syndrome, imaging data and positive syphilitic serology (TPHA-VDRL) in the blood and cerebrospinal fluid. The patient was treated with penicillin G (24 million/day) for 15 days. Tabetic arthropathy is a type of neuropathic arthropathy that has become rare and unfamiliarity with the clinical presentation of this disease may lead to considerable delay in diagnosis. This disease means progressive painless joint destruction that is related to neurosensory deficits caused by syphilis. His diagnosis is difficult as its clinical presentation is not specific and differential diagnosis is wide ranging. Hence, his diagnosis requires clinical suspicion and an appropriate serological test."}
+{"text": "Trend analyses of non-polio AFP and stool adequacy rates in Amhara Region showed optimal performance over the years. However, sub regional gaps continue to persist in certain zones where the reasons for low performance were not well documented. The objective of this study was to assess the performance of the disease surveillance and immunization system in Amhara Region, Ethiopia with emphasis on low performing woredas and zones.A descriptive cross-sectional study was conducted from July 2-10, 2015 to assess the structure, core and support surveillance functions in five zones and two town administrations that were purposively sampled based on differing performances, geographic location, and history of vaccine preventable disease outbreaks among others.Of the 82 sites reviewed, 71 (87%) have a designated surveillance focal person. Less than half 36(44%) of these focal persons have written terms of reference. Twenty-six (93%) of the health offices had a written surveillance work plan for the fiscal year. Only 17 (81%) of woreda health offices and town administrations had prioritized active surveillance sites into high, medium and low during the last 12 months. Only 4(17%) had independent active case search visits to these sites as per the priority. Seventy-eight (95%) and seventy-seven (94%) sites have a designated immunization focal person and updated EPI performance monitoring charts, respectively. There had been vaccine stock out in the 3 months before assessment in 28 (34%) of the sites.Though there is an existence of well-organized surveillance network with adoption of the integrated disease surveillance and response, gaps exist in following the standard guidelines and operation procedures. Improvements needed in reporting site priority setting and regular visiting for active case search, outbreak investigation and management, vaccine supply and overall documentations. Effective communicable diseases control relies on effective surveillance and response systems that promote coordination and integration of surveillance functions. Recognizing this, an initiative to strengthen the disease surveillance system by promoting integration of surveillance activities was started in 1996 in Ethiopia. Later in 1998 the World Health Organization Regional office for Africa (WHO-AFRO), following the resolution of the 48th assembly, started promoting Integrated Disease Surveillance and Response (IDSR) for all Members States to adopt as the main strategy to strengthen national disease surveillance systems . VaccineStudy area: Amhara Region is one of the nine administrative regions in the country. It is the second most populated region in Ethiopia with a projected total population of 20,398,999 (from 2007 Census) as per the national Central Statics Authority (CSA) with a mean annual growth rate of 1.8% [Study design: we conducted a cross-sectional study between 2-10 July 2015 in South Gondar, North Gondar, West Gojjam, South Wollo zones and two town administrations (Bahirdar and Dessie).Sampling: five zones and two town administrations were purposively sampled and visited for the review based on recent surveillance performances and risk of wild or vaccine derived polio virus importations .We included those areas owing to the sub-optimal AFP surveillance performances during the two years prior to the review and zone bordering Sudan with history of imported circulation of wild polio virus in the past. Zone and woreda health offices, health facilities, and a holy water site were selected for review. Three to five woreda health offices and two to three health facilities in each of the woredas were included for the review in most of the areas. One holy water site was also visited. We tried to include both good and poor performing woredas in the selected zones. Health facility selection considered representation of all types of facilities in the level of care and geography .Measurements/variables: the following variables were considered for both health offices and health facilities: availability of focal persons and their training status in the last two years, terms of reference for surveillance and availability of formats and guidelines, supervisory support from higher levels, and documentation status of cases and outbreaks. The following variables were considered for woreda and zonal health offices: availability of surveillance work plan, written supervision plan, supervisory checklist that adequately addresses surveillance, records for active surveillance visits, review meetings on surveillance, availability of coordinating committees and rapid response teams, availability of line lists of reported AFP, measles and neonatal tetanus cases, and monitoring of selected AFP and measles surveillance indicators. Prioritization of sites and written schedule for active surveillance were assessed for woredas and town administrations only. Clinician sensitization during last 6 months and availability of standard case definitions or reminders were variables considered for only health facilities.Data collection: the primary tool for data collection was a structured questionnaire adapted from the standard WHO - AFRO tool for external surveillance review. The tool consisted of two sets of questions: the first set can only be administered to zonal and woreda health offices and the second set only apply to health facilities. Generally, the questionnaire was designed to assess the organization of surveillance at each level, active surveillance system, case-based surveillance performance and documentations [ntations . The tooData analysis: primary and secondary data were entered, cleaned, and analyzed in MicrosoftTM Excel 2010. Proportions were calculated for selected variables and key indicators.Peer WHO Medical Surveillance Officers and regional and zonal PHEM officers reviewed a total of 82 reporting units consisting of five zones, two town administrations, 21 woredas, and 54 health facilities. One holy water was visited but excluded from the analyses because of incomplete information.Written surveillance work plan was available for 26 (93%) of the 28 zonal and woreda health offices reviewed. There was a written supervision plan and supervisory checklist that covers surveillance in 23 (82%) and 26(93%) of health offices visited, respectively. Of the reviewed offices and health facilities, 71 (87%) had a designated surveillance focal person. About three-fourth (76%) of these surveillance focal persons had a refresher training in the last two years. Only 36(44%) of the offices and health facilities have written terms of reference for surveillance. Out of the reviewed health offices and facilities, 71 (87%) have operational surveillance guidelines. Standard case definitions on AFP, measles and NNT were available and posted in outpatient departments of 50 (93%) of the 54 health facilities visited .Availability of prioritization of reporting sites was assessed in 21 woreda and two town administration levels and it was found that only 17 (81%) of them had potential reporting sites prioritized in to high, medium and low during the last one year. Private health facilities, holy water sites and traditional practitioners included in the prioritization of surveillance units by 21 (70%) of woreda and town health offices visited. Only nine (39%) of woredas and town administrations have written schedule for visiting priority reporting sites. Only four (17%) of woredas and town administration health offices have made regular active surveillance visits based on their plan during the last 6 months. There was a written evidence of regular active case search within health facilities  in more than two thirds (70%) of health facilities visited. Almost all (96%) of 23 woreda and town administration health offices had made one or more independent active surveillance visits to reporting sites during the six months prior to the visit. But, only 15 (65%) had documented records (e.g. filled management tool or integrated checklist) for the active case search visits to these reporting sites. Both health offices and health facilities were inquired if a supervisor from higher level visited them for surveillance, and it was found that 75 (91%) of the sites were visited during the past 6 months. The supervisory visit was followed by written feedback in 58 (78%) of supervised sites. About two-thirds (63%) of visited health facilities have received clinician sensitizations on surveillance during six months prior to the assessment. Surveillance review and/or monitoring meetings mostly integrated with review of other health programs were conducted in all of the 28 health offices and town administrations during the past 12 month. Of the health offices and health facilities with laboratory services, 55 (72%) of them had laboratory staff actively involved in surveillance activities. Almost all (96%) of health offices have coordinating committees for surveillance activities either in the form of health emergency taskforce or rapid response team .Three years (2012-2014) trend analyses of AFP detection rates for the zones reviewed showed that Awi and Bahir Dar had non-polio AFP rates below 2 per 100,000 under-15 years of age population for two of the three years reviewed. Detection was also low  in 2014 for South Gondar. Stool adequacy rate was below the target 80% during two of the three years in both Awi and West Gojjam zones . MajoritPHEM activities are being implemented at all, 82 (100%), sites reviewed. Of all sites visited, 64(78%) have integrated case definitions of IDSR priority diseases. The national PHEM guidelines were available in 69 (84%) of the sites. A line graph was available and used for trend analysis in 55 (67%) of the 82 sites . Of the A designated Expanded Program of Immunization (EPI) focal person was available in 78 (95%) of sites and there was a trained cold chain technician in 37(48%). EPI monitoring tools  were available in 93% and EPI coverage performance monitored on a monthly basis in 77 (94%) of sites. There had been vaccine stock out in the 3 months before assessment in 28 (34%) of sites .This study addresses an important peer exchange surveillance and immunization review in selected zones and woredas of Amhara regional state. The main finding from this evaluation was that there were still some challenges to the functioning of the disease surveillance and immunization systems in some of the visited woredas \u20137In the majority of reviewed woredas and health facilities, we found that 71 (87%) visited sites have designated surveillance focal persons. However, less than half 36 (44%) of the health offices and health facilities have clearly written and communicated surveillance terms of reference and standard operating procedures for their focal persons. Though not well-structured and not detailed with measurable indicators, almost all, 26 (93%), of the health offices reviewed have written surveillance work-plans, mostly as a section of annual integrated health plan.Though officers were aware of the number, type and location of their reporting sites, not all surveillance focal persons have exhaustively listed reporting sites organized into high, medium, and low priorities. Conducting active case search by surveillance focal persons is one of the major activities for diseases targeted for eradication and elimination but this activity hardily seen in the reviewed sites. Woreda surveillance focal persons were key persons to ensuring of active surveillance in the reporting sites. Except irregular integrated supportive supervisions, these personnel were not performing independent active case search on regular basis due to financial limitations and multiple responsibilities they had. The results of surveillance performance analysis were not being used at all levels to stimulate activities to improve surveillance performance . All levWe have found that there was measles and other priority diseases outbreaks in the visited areas but not all outbreaks were laboratory confirmed. The involvement of laboratories in surveillance activities  at all levels is very limited (8). The biggest concern we found from our review was that not all outbreaks specifically measles were properly investigated, lab confirmed and appropriately responded . The majFinally, we found that polio related resources were used to strengthen other health programs particularly through integrated trainings, review meetings and supervisions, technical supports from polio funded WHO staff, and budgetary supports for other PHEM and routine immunization activities,Limitations of the study: the main limitations include the selection of poor performing zones, inclusion of small number of woredas and health facilities due to financial and time constraint. Thus, the current findings cannot be generalized for the whole region. Despite these limitations, however, the study revealed challenges and successes of disease surveillance in the study areas with viable recommendations. Moreover, experiences shared among World Health Organization surveillance officers and their government counter parts. This exercise enabled WHO medical surveillance officers as well as the government surveillance focal person to independently identify strength and weakness of the system.In conclusion, disease surveillance system is better organized, planned, implemented and monitored at all levels of Amhara region. However, there are major gaps in following the nationally adopted standards and guidelines both in routine surveillance and outbreak managements. Immunization program is constrained by high rates of vaccine stock outs and inadequate numbers of cold chain technicians. Furthermore, particular gaps exist in Awi, Bahir Dar Town and South Gondar Zones of the region. Hence, woreda and health facility focal persons should properly formulate operational plans for strengthening active case search with realistic prioritization of reporting sites to be visited; the planned schedules should be strictly adhered to. The regional or zonal or Woreda level should analyze data and closely monitor surveillance performance indicators, properly investigate and respond to outbreaks. Overall surveillance documentations should be improved. A system should be in place to ensure sustainable supply of vaccines for the region.In 1998 the World Health Organization Regional office for Africa (WHO-AFRO), following the resolution of the 48th assembly, started promoting Integrated;Disease Surveillance and Response (IDSR) for all Members States to adopt as the main strategy to strengthen national disease surveillance systems;Ethiopia as a Member State adopted the IDSR strategy, which is district centered and outcome-oriented.It builds the capacity of zonal and woreda (district) Government focal person who participated in the assessment;It will also be an input for surveillance planning for the study areas.The authors declare no competing interests. The views expressed in the perspective articles are those of the authors alone and do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated and the position of World Health Organization."}
+{"text": "Cassava mosaic virus species associated with CMD have been isolated and characterized over the years, several new super virulent strains of these viruses have evolved due to genetic recombination between diverse species. In this data article, field survey data collected from 184 cassava farms in 12 South Western and North Central States of Nigeria in 2015 are presented and extensively explored. In each State, one cassava farm was randomly selected as the first farm and subsequent farms were selected at 10\u202fkm intervals, except in locations were cassava farms are sporadically located. In each selected farm, 30 cassava plants were sampled along two diagonals and all selected plant was scored for the presence or absence of CMD symptoms. Cassava mosaic disease incidence and associated whitefly vectors in South West and North Central Nigeria are explored using relevant descriptive statistics, box plots, bar charts, line graphs, and pie charts. In addition, correlation analysis, Analysis of Variance (ANOVA), and multiple comparison post-hoc tests are performed to understand the relationship between the numbers of whiteflies counted, uninfected farms, infected farms, and the mean of symptom severity in and across the States under investigation. The data exploration provided in this data article is considered adequate for objective assessment of the incidence and symptom severity of cassava mosaic disease and associated whitefly vectors in farmers\u2019 fields in these parts of Nigeria where cassava is heavily cultivated.Cassava mosaic disease (CMD) is one of the most economically important viral diseases of cassava, an important staple food for over 800 million people in the tropics. Although several  Specifications TableValue of the data\u2022In addition to its significance as source of food and animal feed, cassava is increasingly becoming an important raw material for several industries including biofuel producing industries \u2022Nigeria is the highest producer of cassava globally and the plant is heavily cultivated in the South Western and North Central States of Nigeria \u2022The data exploration and the statistical analyses provided in this data article are considered adequate for objective assessment of the incidence and symptom severity of cassava mosaic disease and associated whitefly vectors in farmers\u2019 fields in these parts of Nigeria where cassava is heavily cultivated \u2022The data presented in this article will encourage reproducible research and open new doors of research collaborations towards finding effective solutions to deal with the evolution of new super virulent strains of cassava mosaic viruses.1Cassava is a major staple food for millions of people in Nigeria and Africa at large. The plant is drought tolerant, grows in all agro-ecological zones in Nigeria and is one of the highest producing crops in terms of carbohydrate produced per hectare 2Cassava farms located along major and intermediate roads in all the State in the South West and North Central Nigeria were surveyed. The distribution of 184 cassava farms surveyed in 12 South Western and North Central States of Nigeria in 2015 is shown in 3Boxplot representations of the numbers of whiteflies counted, uninfected cassava plants, infected cassava plants, and mean of symptom severity in 184 cassava farms across the 12 States of Nigeria are shown in Correlation analysis, ANOVA, and multiple comparison post-hoc tests were performed to understand the relationship between the numbers of whiteflies counted, uninfected cassava plants, infected cassava plants, and the mean of symptom severity in and across the States under investigation. Correlation coefficient matrix and the p-value computed using the field data are presented in"}
+{"text": "Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx), through an interaction with its globotriaosylceramide (Gb"}
+{"text": "Scientific Reports6: Article number: 2186810.1038/srep21868; published online: 02232016; updated: 05142018The Acknowledgements section in this Article is incomplete.\u201cWe thank Torsten Mayr and Josef Ehgartner  for providing oxygen sensors. We are grateful to the excellent technical work of Maria Franke, Margot Voigt and Daniela Remane. We thank the team of the Placenta Laboratory of the Jena University Hospital for supplying umbilical cords for HUVEC isolation. The authors would further like to acknowledge support of this work by 2011 VF 0005 grant of the Th\u00fcringer Aufbaubank. This work was further supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1002.\u201dshould read:\u201cWe thank Torsten Mayr and Josef Ehgartner  for providing oxygen sensors. We are grateful to the excellent technical work of Maria Franke, Margot Voigt and Daniela Remane. We thank the team of the Placenta Laboratory of the Jena University Hospital for supplying umbilical cords for HUVEC isolation. The authors would further like to acknowledge support of this work by 2011 VF 0005 grant of the Th\u00fcringer Aufbaubank. This work was further supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1002. The authors further acknowledge support of this work by a grant from the German Federal Institute for Risk Assessment (grant no. 1328-511).\u201d"}
+{"text": "Unfortunately, the original version of this article  containeThe title was incorrectly published as:The effectiveness of the peer-delivered Thinking Healthy PLUS (THPP+) Program for maternal depression and child socioemotional development in Pakistan: study protocol for a randomized controlled trialThe correct title is below:The effectiveness of the peer delivered Thinking Healthy Plus (THPP+) Programme for maternal depression and child socio-emotional development in Pakistan: study protocol for a three-year cluster randomized controlled trial."}
+{"text": "The Topical Collection on Invasive Species includes 50 articles addressing many tenets of marine invasion ecology. The collection covers important topics relating to propagule pressure associated with transport vectors, species characteristics, attributes of recipient ecosystems, invasion genetics, biotic interactions, testing of invasion hypotheses, invasion dynamics and spread, and impacts of nonindigenous species. This article summarizes some of the collection\u2019s highlights. The introduction and establishment of nonindigenous species (NIS) beyond their natural distributional range is a key component of global environmental change  and the number of introduction events (propagule number)\u2014is the most consistent predictor of invasion success  and aquaculture. Casas-Monroy et al.  presenteUndaria pinnatifida and two native kelps, Lessonia variegata and Ecklonia radiata, from Tauranga Harbour, New Zealand found that the NIS generally exhibited broader tolerance to the treatments than the native ones  and introduced  ranges suggest that the nonindigenous populations are more tolerant to heat stress than the native ones  for NIS establishment . Interestingly, results of the study suggest that the native range of H. dianthus might be the Mediterranean, rather than the east coast of USA as previously assumed  can strongly influence whether invading NIS can persist and proliferate in introduced environments  was positively related to the density of the native canopy-forming species Zostera marina  may occasionally outcompete nonindigenous Tubastraea corals in Ilha Grande Bay, Brazil by overgrowing them, though the most common competitive interaction among the species is contact without dominance.Biotic interactions may promote or impede the establishment and spread of NIS in recipient environments via mechanisms such as competition, exploitation, facilitation, and mutualism  had negative effects on whelks, whereas no significant impact on whelks was detected for crab scavenging  (Quinn and Boudreau Naso unicornis), on the growth and distribution of the nonindigenous Gracilaria salicornia in the Hawaii Marine Laboratory Refuge reported that the unicornfish might serve as both a control agent and a natural transport vector for G. salicornia  and a number of native competitors in pair-wise and multiple-choice feeding assays found that the grazers generally preferred native algae over the nonindigenous ones because they were deterred by the chemical properties  of the invaders  over the ones from the native range (Japan) could indicate a resource allocation from chemical defense to reproduction and growth, which is in line with the EICA hypothesis  in the Mediterranean Sea found no evident decrease of parasite richness and levels of infection in the fish  in the Gulf of Mexico identified the Campeche Bank as an important source of lionfish recruits to the north-eastern Gulf of Mexico  significantly altered the community structure of local invertebrates in muddy habitats of Prince Edward Island, Canada by creating feeding pits in sediments , and the native seagrass Posidonia oceanica in the eastern Adriatic coast suggested that the invader altered the structure of meiofauna assemblages and caused a decline in meiofauna density  could disrupt benthic-pelagic coupling by reducing the 13C-uptake by the native clam Ruditapes decussatus and thus the availability of phytoplankton-derived C for deposit feeders  in Bahamian reefs found losses of 26.67 and 21.67 discounted service unit years (DSUY) per km2 owing to reductions in recruitment and biomass of lionfish prey fishes  in the Bah\u00eda Blanca estuary, Argentina. The potential effectiveness of individual approach is expected to vary depending on the location, though all approaches would offer risk reduction to some degree (Fiori et al. Negative impacts of NIS; however, may be mitigated by effective prevention and management efforts (Simberloff Biological invasion is a major driver of global environmental change (Simberloff et al."}
+{"text": "In the above-mentioned article, the authors would like to revise (changes are in bold) the acknowledgement section as follows:They acknowledge Generation Scotland for providing control samples and thank Shona Kerr and Archie Campbell for assistance in provision of Generation Scotland samples. The authors acknowledge Cat Graham for providing statistical guidance and also thank David Parry and Sophie Marion de Proce for providing helpful comments on the manuscript.\u201cThe authors thank the patients for consenting to research. In addition, they acknowledge Alona Sosinsky and the Imperial College BRC Genomics facility for bioinformatics support. Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6 and CZB/4/285) and the Scottish Funding Council, HR03006.The authors acknowledge the MRC funding awarded to Timothy J. Aitman for translational support, the Euan MacDonald Centre for Motor Neurone Disease Research and MND Scotland. Danielle J. Leighton also receives funding from the Chief Scientist Office, Scotland and the MND Association. Peter Connick is funded by the Wellcome Trust. Ethical approval for the GS:3D study was obtained from the Tayside Committee on Medical Research Ethics , held by the NHS Lothian NRS BioResource (REC ref: 13/ES/0126).\u201dEthical approvals were obtained for the SMNDR , the Scottish MND DNA bank  and the Scottish Regenerative Neurology Tissue Bank ."}
+{"text": "Visual Hallucinations (VH) are a common non-motor symptom of Parkinson\u2019s Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance.More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks  and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery.Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH.We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH."}
+{"text": "In addition, we delineate how continuous CysLT1 receptor activation and signaling can increase cell survival and proliferation as important early steps toward oncogenicity.Leukotrienes (LTs) and prostaglandins (PGs) are metabolites of arachidonic acid that play major roles in various inflammatory conditions. The release of these mediators, by cells recruited to or present at the site of inflammation, modulate/influence the magnitude of the inflammatory response. A better understanding of eicosanoids and how their receptors trigger intracellular signaling during inflammatory conditions is helping to elucidate the well-known connection between chronic inflammatory disease and neoplastic transformation. In the current review, we summarize the role of LTs and PGs in chronic inflammation and, in particular, we focus on recent insights into the role of CysLT"}
+{"text": "The goal of this study is to determine the efficacy of bone marrow-derived mononuclear cell fraction (MNC) and multipotent mesenchymal stromal cells (MMSC) in the treatment of destructive inflammatory joint diseases.The treatment of destructive inflammatory joint diseases (arthropathies) is one of the issues of current interest in modern medicine. In destructive inflammatory diseases, the regenerative ability of The study subjects consisted of 15 male rabbits weighing 3\u20134 kg with experimental destructive inflammatory knee joint disease. The test animals were divided into 3 groups: reference group without treatment, first test group \u2013 introduction of autologous MNC from rabbit bone marrow into the affected joint, and second test group \u2013 introduction of cultured MMSC from rabbit bone marrow into the joint.A morphological examination of the synovial membranes in the reference group on the 40th day of the experiment revealed chronic synovitis with destruction of synoviocytes, thickening and inflammatory infiltration of the underlying connective tissue (subintima). During examination of synovial membranes in the first test group the patches of thickened regenerating inner layer (intima) made up by large proliferating synoviocytes were observed. The layer of loose connective tissue (subintima) contained a large number of small blood vessels and was only slightly infiltrated by inflammatory cells. The morphological examination of synovial membranes in the second test group discovered thickened regenerating intimal layer sitting on hypertrophied subintima with dense vascular network. Elastic collagenous layers of synovial membrane adjoined proliferating elements in cartilage plates.Both autologous MNC fraction and MMSC from bone marrow proved effectiveness in the treatment of destructive inflammatory joint diseases which stimulate neoangiogenesis. At the same time, it must be noted that the introduction of MMSC diminished destructive changes and accelerated proliferative process."}
+{"text": "The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS), and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids), have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs), a major family of pattern recognition receptors (PRRs) that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands."}
+{"text": "Determining the neurobiological substrates of working memory is of major clinical significance yet has proven to be a complex undertaking. The dorsolateral prefrontal cortex (dlPFC) is a key site for working memory  improves behavioral performance in both aged monkeys who have naturally occurring low norepinephrine and in young animals with experimental depletion of catecholamines (Arnsten and Goldman-Rakic, 2A receptor agonism increases delay cell firing for preferred directions and modestly decreases firing for non-preferred directions (Williams et al., 2A decreases firing for preferred directions and modestly increases firing for non-preferred directions (Williams et al., Compared to the other neuromodulators, significantly less is known about the role of serotonin in working memory. The dlPFC receives serotonergic innervation from the dorsal raphe nucleus (Porrino and Goldman-Rakic, The complex and varied effects of neuromodulation on dlPFC cellular activity and working memory performance are summarized in Table Although many studies have investigated the role of neuromodulation on delay cell firing, the neuromodulation of other dlPFC cell types remains vastly understudied. Local \u03b14\u03b22 agonism increases fixation cell firing for both preferred and non-preferred directions but has no effect on cue or response cells (Sun et al., A number of studies use delay cell firing as a proxy for working memory performance. It bears mentioning that there are alternative hypotheses for the significance of persistent delay cell firing other than the maintenance of task-relevant information (Rowe et al., The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor is currently co-hosting a Research Topic with the reviewer SR, and confirms the absence of any other collaboration."}
+{"text": "Apoptotic index values were significantly increased within the epithelium lining noncystic and cystic structures (p < 0.001). In the interstitium, increased proliferation and apoptosis rates were also noted. Interstitial infiltrates were dense and consisted mainly of CD 68\u2013positive macrophages and CD 45\u2013positive lymphocytes. The present study demonstrated that changes in cell turnover are early events in cyst formation. The observation of mild proportionate elevation of both proliferation and apoptosis values of the epithelium lining cysts explains the lack of increase risk of renal cell carcinoma in ADPKD. The development of heavy interstitial inflammation could contribute to progressive tubulointerstitial scarring, leading to progressive renal failure.Previous studies have highlighted epithelial proliferation and apoptosis in the cyst lining as common features in animal models of cystic disease. In this study, we sought to evaluate the timing and extent of these changes in renal tissue obtained from patients with autosomal-dominant, polycystic kidney disease (ADPKD) subjected for nephrectomy for a variety of clinical indications. Cell proliferation was assessed using an antibody to proliferating cell nuclear antigen (PCNA), and apoptosis was evaluated by the use of terminal deoxynucleotidyl transferase (TdT) digoxigenin-deoxyuridine (dUTP) nick end-labeling technique (ApopTag). The origin of cystic structures was evaluated using antibodies to epithelial membrane antigen (EMA). The lineage of interstitial mononuclear cells was assessed by anti CD 45 and CD 68 monoclonal antibodies. We found an increased rate of proliferation within the epithelium, not only of cystic, but also of noncystic, tubules that was significantly higher than the corresponding values from normal kidney ("}
+{"text": "Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK.A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures.Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups.A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. Rheumatology key messagesWe report development of a national clinical audit tool for children with JIA.Staged implementation of national audit will inform future quality improvement interventions in JIA.We propose future development of an electronic data collection tool integrated into electronic patient records.et al. [JIA is an umbrella term for a heterogeneous group of conditions characterized by chronic arthritis and categorized into sub-types according to clinical features at onset , 2. JIA et al.  in 1996.et al. , 5.Appropriately tailored interventions are central to minimizing the adverse impact of JIA on physical, psychological and visual function, health-related quality of life and social/educational attainments . HoweverThe British Society for Paediatric and Adolescent Rheumatology (BSPAR)/Arthritis and Musculoskeletal Alliance Standards of Care (SOC) for Children and Young People (CYP) with JIA 2009) are consensus-derived minimum standards for clinical services delivering paediatric rheumatology (PRh) care . The SOC are consThis paper describes the development of a nationally agreed tool and dataset for prospective national clinical audit of JIA. The audit tool will identify key service delivery measures necessary to benchmark current practice, and set future standards and targets for improvement; ultimately the aim is to reduce variations in delivery of care and improve health outcomes for CYP with JIA. To address the outcomes-based commissioning of National Health Service (NHS) services, a national clinical audit tool for JIA must include the UK NHS Specialist Commissioning for PRh specifications  and also patient and carer reported outcome measures (PROMs) and patient and carer reported experience measures (PREMs).In parallel to the development of this national audit tool for JIA, the UK PRh community has derived a standardized JIA-specific core dataset called Consensus derived, Accessible (information), Patient-focused, Team-focused, Universally collected (UK), Relevant to all and containing Essential data items (CAPTURE-JIA), to facilitate comparative clinical studies and research collaborations between providers of care . The ultThe aim was to develop a national clinical audit tool for JIA that would enable evaluation of current clinical practice against both clinical outcomes and PROM/PREM. A secondary goal was to set future quality standards and to ensure these could be regularly assessed by standardized data collection with CAPTURE-JIA.To ensure engagement with all relevant stakeholders , a robust governance structure comprising three expert groups was established as follows. A complex and consultative methodology underpins the development of this JIA audit tool .The committee was responsible for overall operational management and final decision making. Membership was open to individuals engaged with development of BSPAR SOC, CAPTURE-JIA and/or HQIP application.The group provided expert guidance with powers to recommend actions. The expert group invited expressions of interest from all NHS England PRh providers (identified through the NHS Providers List) and PRh representatives from Scotland and Wales. A purposeful sample of respondents was invited to participate in the study, with >80% of all UK sites represented. The sample included a range of service delivery models and geographic locations, a spectrum of track records of research from the National Institute for Health Research (and other research involvement), PRh national training centres (termed \u2018grid centres\u2019) and other paediatric rheumatology centres (termed \u2018non-grid\u2019).This group was responsible for development of novel PROM and PREM questionnaires suitable for national audit. The BSPAR National Parents Group was established in 2013 to identify and represent the experiences of families affected by musculoskeletal diagnoses, most commonly JIA. The PROM/PREM development group included the BSPAR Parents Group (with representatives from across England and Scotland), invited consumer representatives from the National Institute for Health Research, Clinical Research Network Children and Arthritis Research UK Clinical Studies Group and young people with JIA.The ScSC established four domains for the audit, namely inclusion criteria and patient eligibility, service delivery quality measures and two aspects of impact, physician reported outcome measures and PROM/PREMs.The ScSC agreed inclusion criteria and eligibility. Discussion focused on the time window for collection of audit data, follow-up time per patient and decision to include only new patients or all patients attending rheumatology outpatients within a given audit time frame. Advice was taken from the Chair of the British Society for Rheumatology (BSR) Clinical Affairs Committee, which is responsible for the National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (BSR EIA) .An iterative approach between the ScSC and expert group was taken. The ScSC derived a preliminary long list of possible questions addressing key quality measures based on the BSPAR Standards of Care, the Scottish Paediatric and Adolescent Rheumatology Network Quality Standards, clinical commissioning requirements in England (NHS England dashboard for PRh) and additional suggestions from the wider ScSC. The specific data items required for each quality measure were listed and duplicate data items were removed to form a single list.The feasibility of collecting the proposed list of data items was discussed with the expert group, highlighting the need for further prioritization. The ScSC prioritized the quality measures on the basis of perceived importance, inclusion in the commissioning dashboard and audibility (i.e. ease of collection of the necessary data items or overlap with CAPTURE-JIA). The expert group were asked to approve the final list.To understand the impact of variation in service delivery, the quality measures will need to be assessed against the most important clinician reported outcomes and PROMs/PREMs.The ScSC agreed that the primary outcome measure would be a measure of disease activity and worked in consultation with the Clinical Studies Group JIA Topic Specific Group to develop a list of candidate disease activity measures informed by a literature review of disease activity assessment tools  and an aAt a facilitated meeting of the expert group, a three-round nominal group voting exercise was used to achieve consensus (majority agreement of \u2a7e70%) on the primary disease activity measure for inclusion. A consensus definition of 70% was selected to align our work with consensus definitions favoured by the OMERACT collaboration  and the Inclusion of PROMs and PREMs was a core requirement of the project. The PROM/PREM development group led the development and selection process, using a staged approach.Patients and parents attended a facilitated workshop in which key outcomes and experiences for CYP with JIA were identified. The open exchange workshop was moderated by a PRh Consultant (N.W.). Key messages were brought together during and after the workshop by one of the consumer members of the BSPAR Parents Group (S.D.).Similar items were collapsed into a single item and grouped into broad themes and sub-themes by a sub-group of the ScSC. These were approved by the BSPAR Parents Group.Any pre-existing validated questionnaires capturing any of the broad themes or sub-themes prioritized by the patient/parent group were considered for the audit. Factors considered included length of questionnaire, ease of scoring and the time referent period used.A simple Yes/No online consultation exercise was undertaken with all members of the PROM/PREM development group to determine whether they would prefer one broad question capturing several aspects of a theme, or one specific question addressing just one sub-theme.A second facilitated workshop was held to finalize the development of the PROMs and PREMs. The goals for this final workshop were to agree the number of patient outcome and patient experience questions for inclusion, agree the time reference period for questions  and develop wording for the questions and the format for the answers, ensuring that the questions were (i) generic , (ii) relevant and valuable to all patients/parents and (iii) suitable for inclusion in CAPTURE-JIA to facilitate clinical adoption.Following the meeting, a further online exercise with all members of the patient/parent group was undertaken for refinement and final approval of the HQIP audit PROM/PREM questionnaires.Two additional groups of parents attending one of two JIA family days in April 2016  were asked to complete the PROM/PREM questionnaires and an additional brief questionnaire including questions on completion time, ease of completion and ease of understanding. A group discussion to highlight any key issues was facilitated by one of the research team. A full list of data items and an associated data dictionary were prepared.Rheumatology Online).Membership of each of the three expert groups is provided online  be included.The ScSC identified 14 potential quality measures requiring the collection of 40 data items. Overall the expert group felt that the data required for this would be too extensive in the absence of an electronic data capture system. The ScSC therefore agreed to prioritize 11 quality measures requiring 32 data items, including all those that map to the commissioning questions . The expA literature review informed the identification of 19 candidate disease activity measures (12 single and 7 composite measures) by the ScSC in collaboration with the JIA Topic Specific Group. A subsequent audit of current practice was completed by 10/14 invited PRh providers (71%), with data available for 153 children . Although there was widespread agreement around important single measures of disease activity , collection and documentation of these measures was inconsistent and unreliable, ranging from 87% (active joint count) to 43% (presence/absence of active uveitis) [This information informed the expert group workshop. Although some members of the expert group had completed the audit, the expert group included a wider spectrum of centres and non-clinician stakeholders. The expert group achieved consensus (>70% agreement) on the three- or four-variable Juvenile Arthritis DAS as the primary outcome measure , 21 and The ScSC approved the choice of outcome measures but following some discussion, a simple yes/no consultation process with the expert group led to two modifications; documentation of presence/absence of sacroiliitis in enthesitis related arthritis and inclusion of the systemic Juvenile Arthritis DAS composite measure when published. The final list of clinical outcome measures is given in The initial PROM/PREM development group workshop initially identified 40 outcomes and 63 experiences. The outcomes and experiences were subsequently collapsed into three broad themes with 13 sub-themes for PROMs and six broad themes with 17 sub-themes for PREMs .Table 3For PROMs, some existing questionnaires were identified that captured many of the same themes, for example, Child Health Utility 9D Index (CHU-9D) . HoweverFor PREMs, just two pre-existing tools were identified: The Friends and Family questionnaire  and the A prioritization exercise was sent to the PROM/PREM development group to identify broad themes and sub-themes for inclusion and there was an 88% (15 people) response rate. At the start of the second workshop, those attending (n = 8) agreed a cut-off of 11/15 (73%) to be the minimum requirement for inclusion of each theme in the audit. On initial review, no single broad theme or sub-theme met these criteria. Discussion continued and the group achieved consensus (>73%) within the meeting, enabling development of appropriate question and response options for each theme. Once finalized, the questions were sent to the wider parent/young person group , and consensus was once again achieved.Given that JIA is a relapsing and remitting condition that can vary widely over relatively short time periods, a referent period of 1 month was agreed as sufficient to capture variability but short enough to minimize recall bias.Following the workshop, the final set of questions was sent to all members of the PROM/PREM development group and minor modifications made based on feedback. The final PROM and PREM against which the quality measures will be assessed are shown in s.d. 1.49) min for group 1 and 3.45 (s.d. 1.51) min for group 2; 75% and 100% of groups 1 and 2, respectively, reported the questionnaire to be \u2018easy\u2019 or \u2018very easy\u2019 to complete and 85% and 91%, respectively, were \u2018happy\u2019 with the wording used.Feedback from the two additional family groups  was very similar. Average time to complete the questionnaire was 3.44 (Rheumatology Online).The full list of data items (n = 32) plus the PROM/PREM questionnaire (n = 7) is shown in This report describes the highly consultative consensus-based methodology underpinning development of a JIA-specific national audit tool including identification of key quality measures for inclusion, and selection of optimal clinician and patient/parent reported outcome tools to understand the impact of variations in service delivery.National audit programmes aim to improve disease outcome for patients. In the UK, the Royal College of Paediatrics and Child Health supports national audit programmes in paediatric diabetes, neonatal care and epilepsy . Such prImplementation of a national audit programme for JIA will require a staged approach. The first step will be an initial data collection exercise generating benchmarking data against which robust and validated quality standards can be set. This will facilitate effective quality assessment for NHS England commissioning of specialized services. The second data collection phase will assess how well the standards are being met in terms of the quality, safety, outcome and experience of care for CYP with JIA.Future participation of all PRh NHS Providers in a national clinical audit process evaluating the care of CYP with JIA will capture a more complete impression of what is happening at local (Trust), regional and national levels. The completion of the audit tool could in itself be considered a quality measure for the delivery of care in JIA. Collecting audit data in itself  is simply not enough\u2014the data must be utilized to actually deliver the change required to drive quality improvements and this requires concerted effort and commitment from all stakeholders\u2019 services and access to fit-for-purpose IT systems.Describing and understanding current clinical practice through national clinical audit will enable the development of robust and meaningful quality standards that will be used to drive improvements in clinical care and outcomes for JIA. Important national audit questions and quality measures may change over time. In particular, the current audit tool does not include an assessment of damage. Clinical and radiological evidence of damage occurs relatively late in JIA and damage assessment tools are not currently used routinely in clinical practice. Although a valid and meaningful assessment of damage could not be included in the audit tool at this time, damage may merit inclusion in future iterations, as damage assessment tools evolve further.The active participation of the wider PRh clinical and research communities across the UK is an important strength of this study. It demonstrates the widespread support for projects informing best practice, the need for greater collaboration between centres, and support for a consensus process to agree and define a feasible dataset (i.e. set of data items to be collected) to encompass the needs of patients and families, clinical teams, research teams, service providers and commissioners. Although we acknowledge that our primary aim of assessing all patients with new onset JIA may be aspirational, the active participation of the wider PRh community in this and other national projects suggests that identification of all new patients could be a realistic expectation.Patient experience and outcomes are key quality indicators but few condition-specific paediatric PREMs are available. A further strength of the study is the methodologically sound development of novel PROM/PREM tools specific to JIA and developed in consultation with the BSPAR Parents Group.A major challenge for the PROM/PREM development group was achieving agreement on which broad themes and sub-themes to include. While agreement was achieved, a number of important sub-themes have been excluded. Future development of an electronic data collection tool may enable inclusion of further data items. The PROM/PREM tools require further validation and piloting prior to incorporation into standard clinical practice.A consensus agreed core dataset for JIA (CAPTURE-JIA), which incorporates the audit data items, has been developed and is currently being piloted. Once finalized, embedding the collection of CAPTURE-JIA data items into routine clinical care would facilitate a national audit programme.The longer-term goal is development of an electronic data collection tool with routine integration of data collection into electronic patient records. Improved documentation (and auditing) of service delivery at local (trust), regional  and national level against these important clinical and consumer reported outcomes will likely identify potential areas for healthcare quality improvement, key to improving clinical outcomes for this vulnerable group of patients.Implementation of the proposed national audit tool should facilitate investigation of variability between services and across networks, identify current levels of care and drive a long-term quality improvement programme for children and young people with JIA. Healthcare providers designated as providing paediatric rheumatology services should be held accountable to address inadequacies in care and recommendations when demonstrated using the validated audit tool.Supplementary TablesClick here for additional data file.Supplementary DataClick here for additional data file."}
+{"text": "Hand gestures are an integral part of social interactions and are involved in nonverbal and verbal communication. The convey language that is expressed by motor actions, and thus depend on the interplay of various brain regions. Several functional magnetic resonance imaging studies in healthy subjects suggest the praxis network for gesture production, involving distinct frontal, parietal and temporal regions. Lesions studies in subjects with apraxia, following left brain damage corroborate these findings. However, little is known about the structural connectivity underlying gesture production. We aimed to provide novel insights into the structural connectivity of the praxis network and how it is related to gesture production.Our sample consisted of 41 healthy subjects and of 40 patients with schizophrenia, demonstrating gesture impairments and structural network abnormalities. All participants performed a gesture production test, the test of upper limb apraxia and underwent diffusion weighted magnetic resonance imaging. Finsler geometry was used to investigate structural connectivity and graph theory to estimate global and local efficiency of the praxis network, which consists of 13 bilateral regions of interest.Our findings showed an association of gesture production with network attributes and specific connections within the praxis network. Thus, global and local efficiency and most of the intra- and interhemispheric connections within the gesture network predicted gesture production across groups. Global efficiency of the praxis network further predicted gesture production only in the patient group. Local efficiency of many ROIs and connections of interest predicted production in patients at trend-level. In contrast, there were no significant or trend-level associations of gesture production with network attributes in controls.The results revealed an association of impaired gesture performance with structural alterations of the praxis network, including global and local efficiency and many connections of interest. Our findings are of great importance in the understanding of the structural correlates of gesture production and shed further light on the neural underpinnings of gesture deficits in a patient group with severe social deficits."}
+{"text": "Heat shock proteins (HSPs) are evolutionarily conserved molecules and play important roles in fundamental cellular processes. They serve as molecular chaperones and hence provide a protective function in ensuring cell survival and repair of cellular damage after a stressful stimulus. This paper summarizes the current knowledge about the different roles of HSPs in aging and disease, focusing on the neurodegenerative disorders of Alzheimer's disease, Parkinson's disease, Huntington's disease, and prion disease."}
+{"text": "Natural products (NPs) are superior starting point for the major antimicrobials used in clinical trials  precursor directed biosynthesis  chemical transformation or (2) chemoenzymatic biosynthesis. In the first approach, the biological product is processed through single/multiple chemical reaction and decorated with the desired chemical scaffold. In latter approach, the microbial product is processed through iterative modes of biosynthetic mechanism along with chemical reactions, thus multiplexing the parent compounds with novel functionalities and delivering chemical libraries as new leads (Yan et al., The integration and interaction of synthetic chemistry with biological processes has definitely broadened the scope of the development of antimicrobial agents, such as:The combination/conjugation of NPs with the chemically or biologically generated nanoparticles has proven to be very popular (Singh et al., The pathogenic bacteria frequently release small molecules commonly called as virulence factors. The study of such virulence factor or other signaling molecules can assist in understanding bases of pathogenicity and designing inhibitor molecules (Anthouard and DiRita, The chemistry directed evolution in NPs discovery has provided diversified bioactive molecules or chemical modulators. But the traditional chemical processes are limited in diversity generated through \u201cone-synthesis/one-scaffold\u201d approach Hong, , whereasDD and JS made substantial, direct and intellectual contribution to the work, and approved it for publication with full consent.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Most investigations into the pharmacology of schizophrenia have revolved around dopaminergic and glutamatergic neurotransmission; however, one neurotransmitter that has not received adequate attention is the cholinergic system. Indeed, several post-mortem, genetic and epidemiologic studies link specifically the alpha7 nicotinic receptor (nAChR) to schizophrenia, and the potential use of alpha7 modulators as a treatment strategy is an active field of research. Nevertheless, studies to date have been limited to normal animals rather than on a validated neurodevelopmental model of schizophrenia. Moreover, knowledge about the differential impact of orthosteric and allosteric modulators in vivo is lacking. Thus, we investigated the effects of alpha7 nAChR modulation on dopamine (DA) neuron activity in the ventral tegmental area (VTA) in the methylazoxymethanol acetate (MAM) animal model of schizophrenia.All experimental procedures were conducted according to NIH guidelines and were approved by University of Pittsburgh Institutional Animal Care and Use Committee. Sprague-Dawley pregnant dams were treated with MAM or saline on gestational day 17. Recordings of VTA dopamine neuron activity was performed on the male offspring at adulthood. The effects of four different drugs were evaluated: PNU282987 (full agonist), SSR180711  NS1738  and PNU120596 (PAM type II).Intravenous administration of alpha7 selective ligands did not induce a major change in the firing profile of spontaneously active DA neurons when dosed during dopamine neuron recording. PNU120596 increased in the number of active DA neurons found in the VTA of normal rats, their mean firing rate and percentage of spikes in bursts. In contrast, the full agonist PNU282987 and the partial agonist SSR180711 reduced the hyperdopaminergic tone in MAM rats, with a more prominent decrease in the number of DA neurons recorded in the lateral VTA. In order to investigate the drug site of action, both PNU282987 and SSR1800711 were infused into the ventral hippocampus (vHipp) and basolateral amygdala (BLA). After vHipp infusion, the alpha7 nAChR agonists significantly decreased the number of active DA neurons in MAM rats, with no significant impact in control rats. Once more, the effects were more robust in the lateral VTA. In contrast, the same drugs when infused directly into the BLA increased the number of spontaneously active DA neurons in the VTA of normal rats, but not in the MAM model.In summary, our results show that alpha7 nAChR positive modulators can affect midbrain dopaminergic neuronal activity in vivo in a state-dependent manner. Interestingly, alpha7 nAChR agonists counterbalanced the hyperdopaminergic state of MAM rats and this effect is partially mediated by their action in the vHipp. This effect is consistent with the potential use of alpha7 nAChR agonists for schizophrenia treatment and fits the current search for drugs able to control dopaminergic function acting in structures upstream from the dopamine receptor. The predominant inhibition of the lateral VTA points to a lower propensity to produce unwanted side effects in comparison to current employed antipsychotic agents. Our data show that drug effects can vary according to the basal level of activity of specific brain circuits and highlights the importance of using appropriated animal models to make inferences about potential therapeutic use of new neuropsychiatric drug candidates."}
+{"text": "Empirical measurement, monitoring, analysis, and reporting of learning outcomes in higher institutions of developing countries may lead to sustainable education in the region. In this data article, data about the academic performances of undergraduates that studied engineering programs at Covenant University, Nigeria are presented and analyzed. A total population sample of 1841 undergraduates that studied Chemical Engineering (CHE), Civil Engineering (CVE), Computer Engineering (CEN), Electrical and Electronics Engineering (EEE), Information and Communication Engineering (ICE), Mechanical Engineering (MEE), and Petroleum Engineering (PET) within the year range of 2002\u20132014 are randomly selected. For the five-year study period of engineering program, Grade Point Average (GPA) and its cumulative value of each of the sample were obtained from the Department of Student Records and Academic Affairs. In order to encourage evidence-based research in learning analytics, detailed datasets are made publicly available in a Microsoft Excel spreadsheet file attached to this article. Descriptive statistics and frequency distributions of the academic performance data are presented in tables and graphs for easy data interpretations. In addition, one-way Analysis of Variance (ANOVA) and multiple comparison post-hoc tests are performed to determine whether the variations in the academic performances are significant across the seven engineering programs. The data provided in this article will assist the global educational research community and regional policy makers to understand and optimize the learning environment towards the realization of smart campuses and sustainable education. Specifications TableValue of the data\u2022Comprehensive academic performance datasets provided in this article will promote evidence-based research in the emerging field of learning analytics in developing countries \u2022Easy access to this data will assist the global educational research community and regional policy makers to understand and optimize the learning environment towards the realization of smart campuses and sustainable education \u2022With the growing adoption of machine learning and artificial intelligence techniques in different fields, empirical data provided in this article will help in the development of predictive models for learning outcomes in engineering undergraduates \u2022Descriptive statistics, frequency distributions, one-way ANOVA and multiple comparison post-hoc tests that are presented in tables, plots, and graphs will make data interpretation much easier for useful insights and logical conclusions.\u2022Detailed datasets that are made publicly available in a Microsoft Excel spreadsheet file attached to this article will encourage further explorative studies in this field of research.1. It is a private Christian university affiliated with Living Faith Church Worldwide and a member of the Association of Commonwealth Universities (ACU), Association of African Universities (AAU), and National Universities Commission (NUC).The emerging field of learning analytics may be exploited to improve learning outcomes of engineering undergraduates in higher institutions of developing countries towards attaining sustainable education in the region A total population sample of 1841 undergraduates that studied Chemical Engineering (CHE), Civil Engineering (CVE), Computer Engineering (CEN), Electrical and Electronics Engineering (EEE), Information and Communication Engineering (ICE), Mechanical Engineering (MEE), and Petroleum Engineering (PET) within the year range of 2002\u20132014 are randomly selected. The earliest year of entry and the latest year of graduation are 2002 and 2014 respectively. Having excluded undergraduates with incomplete academic records, 198, 152, 374, 407, 349, 166, 195 undergraduates were pooled from CHE, CVE, CEN, EEE, ICE, MEE, and PET respectively. The descriptive statistics of the academic performances of undergraduates in each of the seven engineering programs at Covenant University are presented in The academic performances of engineering undergraduates vary as the students proceed from one level to another yearly. 2For the five-year study period of engineering program, Grade Point Average (GPA) and its cumulative value of each of the sample were obtained from the Department of Student Records and Academic Affairs. In order to encourage evidence-based research in learning analytics, detailed datasets are made publicly available in a Microsoft Excel spreadsheet file attached to this article. Descriptive statistics and frequency distributions of the academic performance data are presented in tables and graphs for easy data interpretations. In addition, one-way Analysis of Variance (ANOVA) and multiple comparison post-hoc tests are performed to determine whether the variations in the academic performances are significant across the seven engineering programs. Data showing whether there are significant differences in the GPA data of the engineering undergraduates throughout their five-year study period are presented in"}
+{"text": "Action Plan for the Prevention, Care, and Treatment of Viral Hepatitis  infection and the estimated 3 million persons living with hepatitis C virus (HCV) infection are unaware of their infection and are not receiving necessary care and treatment (The first report examines projects (based on the Project ECHO model of videoconference and case-based learning) to strengthen HCV primary care capacity in Arizona and Utah. In the second report, programs in three sites  targeted HBV testing for persons born in countries where HBV infection is endemic . Both programs were successful in reaching persons in underserved populations  and linking them to appropriate care and treatment. Broader expansion of programs like these will help prevent HBV and HCV transmission and disease."}
+{"text": "Recently, Raymond Reif and colleagues from the Leibniz Research Center in Dortmund have published a technical article about two-photon based intravital imaging (Reif et al., 2016[The presented intravital technique has major implications for three fields of research. First, pharmacokinetic modelling can be improved by intravital imaging. PBPK modelling is of high relevance for simulation of compound concentrations in blood or organs (Golubovskaya et al., 2015; Stamyr In conclusion, the two-photon based imaging technique presented by Reif and colleagues will support spatio-temporal modelling studies of physiological and pathophysiological processes in all organs of interest."}
+{"text": "Natural cytotoxicity receptors (NCRs), expressed by natural killer (NK) cells, trigger NK lysis of tumor and virus-infected cells on interaction with cell-surface ligands of these target cells. We have determined that viral hemagglutinins expressed on the surface of virus-infected cells are involved in the recognition by the NCRs, NKp44 and NKp46. Recognition of tumor cells by the NCRs NKp30 and NKp46 involves heparan sulfate epitopes expressed on the tumor cell membrane. Our studies provide new evidence for the identity of the ligands for NCRs and indicate that a broader definition should be applied to pathological patterns recognized by innate immune receptors. Since nonmicrobial endogenous carbohydrate structures contribute significantly to this recognition, there is an imperative need to develop appropriate tools for the facile sequencing of carbohydrate moieties."}
+{"text": "Internet addiction behavior was examined in 6,121 Chinese primary and secondary school students in Hong Kong based on the assessment frameworks of Ivan Goldberg and Kimberly Young. Results showed that scales derived from both frameworks  were internally consistent and evidence supporting their validity was found. Descriptive statistical analyses revealed that roughly one-fifth of the respondents could be classified as Internet addicted based on either scale. Further analyses showed that Internet-addicted and -nonaddicted respondents differed in their Internet use and related behavior. Logistic regression analyses showed that engagement in certain on-line activities (such as playing on-line games and downloading software) and replacement of pastimes activities (such as watching TV and going out with friends) with Internet activities predicted a higher probability of Internet addiction."}
+{"text": "Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole . This prDevelopment of consensus is required around a set of well-defined, relevant and feasible outcomes for all trials concerning particular obstetric and gynaecologic health conditions, such as preterm birth, incontinence, infertility and menstrual problems. With so many subspecialties involved, this is no easy task. Duplication of effort can be avoided by working with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, which is working towards core data sets for all medical specialties . ProductJournal editors now invite researchers to take the lead in beginning this work. What will we do as editors to support them and their colleagues? First, we are drawing wide attention to The CROWN Initiative by publishing this editorial in the journals listed below. We shall ensure that the global research community, which includes our many reviewers, is aware of the need for core outcome sets. Submissions which describe development of core outcome sets, if deemed acceptable after peer review, will be effectively disseminated.http://www.comet-initiative.org): \u201cThe existence or use of a core outcome set does not imply that outcomes in a particular trial should be restricted to those in the relevant core outcome set. Rather, there is an expectation that the core outcomes will be collected and reported, making it easier for the results of trials to be compared, contrasted and combined as appropriate; while researchers continue to explore other outcomes as well.\u201d We also expect that as new or superior ways of capturing outcomes emerge, core outcome sets will themselves need updating.Our collaboration is not for enforcing harmony at the expense of innovation. To quote from the COMET home page  Initiative by Professor Khalid Khan with permission from the Royal College of Obstetricians and Gynaecologists and John Wiley & Sons Ltd.Reproduced from th May 2014, up to date list available at http://www.crown-initiative.org):Acta Obstetricia et Gynecologica ScandinavicaAmerican Journal of Obstetrics & GynecologyAmerican Journal of PerinatologyArchives of Gynecology and ObstetricsAustralian and New Zealand Journal of Obstetrics and GynaecologyBest Practice & Research: Clinical Obstetrics & GynaecologyBirth: Issues in Perinatal CareBJOG: An International Journal of Obstetrics and GynaecologyBMC Pregnancy and ChildbirthBMC Women's HealthClimactericClinical Obstetrics and GynecologyClinics in PerinatologyCochrane Menstrual Disorders and Subfertility GroupCochrane Pregnancy and Childbirth GroupContraceptionContraception and Reproductive MedicineCurrent Opinion in Obstetrics and GynecologyEuropean Journal of Obstetrics & Gynecology and Reproductive BiologyFertility and SterilityFertility Research and PracticeFetal Diagnosis and TherapyGinekologia PolskaGynecological SurgeryGynecologic OncologyGynecologic Oncology ReportsHuman FertilityHuman ReproductionHuman Reproduction UpdateHypertension in PregnancyInternational Journal of Fertility and SterilityInternational Breastfeeding JournalInternational Journal of Gynecology & ObstetricsInternational Urogynecology JournalJournal of Family Planning and Reproductive Health CareJournal of Gynecologic OncologyJournal of Lower Genital Tract DiseaseJournal of Midwifery & Women's HealthJournal of Obstetrics & GynaecologyJournal of Obstetrics and Gynaecology CanadaJournal of Obstetric, Gynecologic & Neonatal NursingJournal of Ovarian ResearchJournal of Perinatal & Neonatal NursingJournal of Perinatal MedicineMaternal Health, Neonatology, and PerinatologyMaturitasMCN The American Journal of Maternal Child NursingMenopause Review Menopause: The Journal of The North American Menopause SocietyNeurourology and UrodynamicsObstetrics & GynecologyPaediatric and Perinatal EpidemiologyPlacentaPrenatal DiagnosisReproductive HealthThe Breast JournalThe European Journal of Contraception and Reproductive Health CareThe Obstetrician & Gynaecologist (TOG)Twin Research and Human GeneticsUltrasound in Obstetrics & GynecologyWomen\u2019s Midlife HealthThe CROWN Initiative includes the following journals, in alphabetical order (correct on 13"}
+{"text": "We especially thank the CRBIP for the provision of these highly valuable historical strains.S1 TableThe geographic origin and year of isolation are indicated when known, together with the SNP lineage assignment (canSNP), accession numbers, sequencing level, and links to the corresponding data.(XLSX)Click here for additional data file."}
+{"text": "The meeting, held in Jaipur  from 24 to 26 February 2017, assembled 600 participants from India and worldwide. It was organised by the Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC), Jaipur. BMCHRC Jaipur is one of the largest superspeciality oncology research and treatment centres in north India. The vision of BMCHRC has been to foster collaboration between oncologists, encouraging dialogue in an open forum that improves the care and outcomes of patients with cancer using the latest advances in cancer treatment. IGSHNO 2017 was part of this aim and vision.The organising team, including Dr Anil Gupta (Organising Secretary), Dr Lalit Mohan Sharma (Organising Secretary), Dr Pawan Singhal , Dr Tej Prakash Soni , Dr Umesh Bansal and Dr Dinesh Yadav (Joint Organising Secretary), Dr Anjum Khan , Dr Gaurav Pal Singh  and Dr (Maj Gen) SC Pareek  worked hard for the previous 6 months to make this conference a successful academic event.IGSHNO 2017, held over three days, is a chance for oncologists from different parts of India to come together and discuss ongoing research, recent announcements and introduce new developments in head and neck cancer. It consisted of 51 lectures, seven debates, 10 panel discussions, oral paper presentations, e-poster sessions, a quiz for postgraduate students, a live surgery workshop, a prosthodentics workshop for dentists, a radiotherapy contouring workshop for radiation oncologists, a pain and palliative care workshop and a meet the expert session\u2014all focusing on the multidisciplinary treatment of head and neck cancer.Special highlights from IGSHNO 2017 included the radiotherapy contouring workshop, the live surgery workshop by internationally renowned head and neck oncosurgeons, the dental and prosthodontics workshop and the pain and palliative care workshop. The conference started on 24 February 2017 at 8.00 am with a \u2018Meet the Expert\u2019 session where 6\u20137 pre-registered and selected postgraduate students and junior consultants got the opportunity to meet and express their queries directly with eminent members of faculty such as Prof Dr Peter G Cordeiro , Dr Peter Clarke , and Dr Bhagwat Mathur .Simultaneously, in another hall, senior head and neck oncosurgeons and plastic surgeons started pre-recorded video sessions displaying the different head and neck surgeries on screen with a demonstration of their surgical skills.Following a welcome from the IGSHNO Organising Secretary  the first session, titled \u2018Recent advances and Role of imaging in Head and Neck tumours,\u2019 focused on anatomy, diagnosis, response evaluation and treatment planning by CT scan and MRI for head and neck Cancer by Prof Dr Supreeta Arya . It was very useful for postgraduate students. Despite the session being in the early morning as well as being the first session of the day, the auditorium was filled by the delegates. Dr BA Krishna  also described the clinical utility of PET-CT scan for head and neck cancer management. He reported that PET-CT scan improves the staging and radiotherapy treatment planning for locally advanced head and neck cancers . F-18] 8 1].Dr DD Patel  explained the \u2018Journey of Head and Neck Cancer in the last six decades\u2019 with an outstanding and comprehensive talk on the evolution of head and neck cancer treatment from the past to the present. He described the developments of various surgical techniques from neck dissection to excision of primary head and neck tumours, along with recent advances in pathology and radiology. Dr PB Desai  reported on the importance of neck node metastasis as one of the most important prognostic and therapeutic factors in head and neck cancer along with management options.et al revealed 63 randomised trials on nearly 11,000 patients assessing the impact on survival of adding chemotherapy to locoregional treatment, revealed that adding chemotherapy to locoregional treatment was associated with an absolute survival benefit of 4% at both 2 years and 5 years, compared with locoregional treatment alone. However, the benefit was statistically significant only with the addition of concomitant chemotherapy to radiotherapy.   were als< 0.001) .Prof Dr Peter G Cordeiro  explained the classification system for defect of the mandible and a reconstructive algorithm. Dr James Adam  described the role of 3D reconstruction image in complex mandibular reconstruction. Dr Sankalp Mittal  explained the methods of post-ablative maxillary mandibular rehabilitation with dental implants and prosthesis.In an interesting debate \u2018Marginal v/s Segmental Mandibulectomy for GBS lesions without gross bone invasion\u2019, Dr Shamit Chopra  supported the marginal mandibulectomy for gingivo-buccal lesions without gross bone invasion along with evidence. Dr Rajeev Kapila  opposed him and presented the evidence for the advantages of segmental mandibulectomy.Dr Pankaj Chaturvedi  moderated the interesting panel on \u201cControversies in the management of Head and Neck Cancer\u2019 along with panelists which were senior oncosurgeons, pathologists, radiologists, medical oncologists, radiation oncologist and plastic surgeons. Dr Naresh Soni, Dr Sandeep Gupta, Dr Deepa Nair, Dr Pradeep Goil, Dr KK Mangal, Dr Chirag Desai, Dr Munish Gairola, Dr Rajesh Pasricha and Dr Supreeta Arya shared their opinions regarding the very relevant issues related to head and neck cancer management, such as the indications of various neck dissection methods, indications of adjuvant radiotherapy with or without chemotherapy, organ preservation and nonsurgical methods and how to interpret the histopathology.Prof Dr Subramania Iyer  delivered the oration on \u2018Beyond basics in mandibular and maxillary reconstruction\u2019 and shared his experience and techniques of reconstruction of maxilla.Dr Vinay Kant Shankdhar  reported the techniques of reconstruction of complex post-oncologic maxillectomy defects using the free fibula osteocutaneous flap. Dr Peter Cordeiro explained the classification system for defects to the midface and a reconstructive algorithm. Dr Naguib-El Mutardi  described the techniques and indications of loco-regional flaps in head and neck reconstruction. Dr Bhagwat Mathur reported the techniques, indications and role of Submental Artery Perforator (SAP) in head and neck reconstruction. Dr Harikrishna M described the role of ICG Dye-based imaging and its role in head and neck oncosurgery. Optical imaging using ICG has the potential of traversing the gap between radiology and surgery by providing real-time visualisation of the tumour, thereby allowing for image-guided surgery. The use of the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background ratio of contrast agents.Dr Pradeep Goil  reported the techniques and indications of the double paddle-free fibular flap in oncological reconstruction. Dr Sandeep Mehta (Sr Consultant and Plastic Surgeon) and Dr Satyabodh Guttal  explained the rehabilitation methods as well as role of prostodontists after head and neck oncosurgery.In an interesting debate about the optimum management of medically fit old age patients of head and neck cancer management, Dr Pankaj Chaturvedi reported that elderly patients should be treated as younger patients with radical intent if they are medically fit and have good performance status. Dr Gagan Saini  opposed him stating that the treatment of elderly patients should be discussed in a multidiscipilanary tumour board and it should be optimised for individual patients as old age is associated with many medical comorbidities and even after radical treatment, survival may be inferior compared to younger patients.Dr Sridhar PS  explained the emerging evidence supporting the role of stereotactic radiotherapy for recurrent head neck cancer. The consensus appears to be that SBRT is a viable option with good control rates and modest acute toxicity due to increased precision and decreased duration of treatment .Dr Sunil Kumar Gupta  described the optimum chemotherapy for recurrent head neck cancer. Prof Dr DN Sharma  described the technique and indications of brachytherapy for early oral cancers and oropharynx cancer as well as recurrent head neck cancers.et al found the similar three-year survival and recurrence rate between both the groups (p > 0.05) but in subgroup analysis, oropharyngeal primary tumours exhibited improved results by cetuximab with a pooled HR of 1.56  for PFS. Additionally, the HPV+ status was a significant factor in positive outcomes with cetuximab with a pooled HR of 1.12  for OS [In an interesting debate, Dr Anish Maru  presented the evidence supporting the use of monoclonal antibodies (cetuximab and nimotuzumab) replacing cisplatin for locally advanced head and neck cancer in selected patient populations. Cetuximab plus radiotherapy significantly improves overall survival at 5 years compared with radiotherapy alone. In a recently published meta-analysis on cetuximab versus cisplatin, Jingwen Huang et al in a phase-II trial comparing radiotherapy with concomitant cisplatin versus concomitant cetuximab reported that discontinuation for more than 10 days occurred in 13% of patients given cituximab and 0% given CDDP (p = 0.05). Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the cituximab arm  [Dr Chirag Desai  opposed him with evidence suggesting that cisplatin has been the standard chemotherapy for many decades up until now. Magrini SM = 0.044) .Dr Daniel Saleh  delivered a talk on incidence, treatment and outcomes in head and neck sarcomas. In another presentation, he described the technique and methods along with indications of primary oncological reconstruction of facial nerves.HPV is one of the most important prognostic and predictive factors for head and neck cancer management. Prof Dr Arvind Krishnamurthy  reported the HPV as a prognostic factor shifting paradigm in the staging of head and neck cancers. Human papillomavirus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancers. HPV-positive HNSCC carries a better prognosis than HPV-negative HNSCC. HPV-positive oropharyngeal cancers are more responsive to treatment and have better rates of disease-specific survival than those with HPV-negative oropharyngeal cancers .Dr Naguib EL Mutardi explained the dermal scaffolding technique in soft-tissue defect reconstruction. A full-thickness soft-tissue defect closure often needs complex procedures. In soft-tissue defects, a wound closure often is possible by transplants or flaps. In other cases, the use of dermal templates has become an alternative. The use of dermal templates can be helpful in improving the outcome; it is a simple, reliable and fast method with excellent safety.The palliative care and pain management workshop was attended by 65 participants. Dr MR Rajagopal  reported the importance of palliative care and pain management in cancer treatment centres as most of the patients in India present in very advanced stages and they require palliative care during the course of the treatment. Dr Jayita  delivered the importance of psychological counselling of cancer patients during and after the treatment. Dr DD Patel shared the importance of nursing services and care during the cancer treatment. Dr Pushplata Gupta  reported the role of dietary counselling and nutrition as a vital part of the treatment. Dr Mrinal Joshi  delivered the talk on rehabilitation of cancer patients with disabilities. Dr Shikha Jain  demonstrated the wound and non-healing ulcer care.On 25th February, during the video session, recorded video clips of superficial parotidectomy by Dr Sowrabh Arora , lateral skull base approaches for the petrous apex by Dr Amit Goyal , Free fibular flap by Dr Pradeep Goil, Bilateral parotidectomy by Dr Shamit Chopra and submandibular gland excision by Dr Rajeev Kapila were demonstrated. In the \u2018meet the expert session\u2019, Dr Jonathan Pollok , Dr James Adam, Dr Daniel Saleh, Dr Sampat Rao , Dr Hasu D Patel , and Dr Naguib El Mutardi interacted with the few selective and pre-registered postgraduate students and shared their experiences and opinion.There was an interesting panel discussion on standard management and recent advances in surgery, imaging and pathology for well-differentiated thyroid carcinoma by Prof Dr Pawan Singhal  along with panelists Dr Raj Govind Sharma , Dr Ashish Varghese (Sr Head Neck Oncosurgeon), Dr Naresh Ledwani (Sr Head Neck Oncosurgeon), DrKiran Kothari (Sr Head Neck Oncosurgeon), Dr Rishabh Jain (Sr Head Neck Oncosurgeon), Dr Arpita Jindal , Dr Tripti Shah (Radiologist), Dr C S Bal and Dr B Venkat Ratnam  and Dr Brig. JK Bhagat . They discussed the role and indication of Radioiodine for low risk well differentiated thyroid cancer.Dr Ashish Varghese reported the indications for neck node dissection for differentiated thyroid cancer. Dr Subramania Iyer in a comprehensive manner reported the optimum selection criteria to choose the flap for head and neck reconstruction. Dr Deepak Sarin  moderated the panel discussion on the role and importance of depth of invasion and cut margins for oral malignancy. Dr Tarun Ojha , Dr Mahendra Hada , Dr J D Patel , Dr Peter Clarke, Dr Anjali Sharma , Dr Poonam , Dr Ruchir Bhandari and Dr Nidhi Patni  discussed the importance of depth of invasion and cut margin status as important therapeutic, prognostic and predictive factors. Dr Prafull B Desai explained the developments and progress made by medical science in the last decade, but he emphasised the importance of the bond between patients and doctors. He expressed his concerns over the strengthening of machines and technology in medical science in the last few years while weakening the confidence value between patients and physicians. Prof Dr Ashok Shenoy  reported that morbidity and disability of head and neck oncosurgery affects quality of life as an independent factor. Dr Jonathan Pollok, Dr Peter Clarke, Dr GD Kalra , Dr Moni Abraham , Dr Pankaj Gupta and Dr Rashim Kataria  and Dr Sampat Rao reported the indications and techniques of anterior, central, and lateral skull base lesion surgery.Dr Kiran Kothari  presented a comprehensive talk on indications of surgery or chemo-radiotherapy as organ preservation for carcinoma larynx. Dr Alok Thakar  reported the emerging role of robotic surgery for head and neck cancers. Dr Hasu D Patel reported the role of GI tract in microsurgical reconstruction. In another presentation, she reported the importance of tubed pectoralis major flap as a salvage procedure after radiotherapy in head and neck reconstruction. Dr Ashok Shenoy described the recent advances for speech restoration after larynx surgery. Dr Peter Clarke along with senior surgical oncologists , Dr Tejpal Gupta  and Dr BK Smruti  in a panel discussion covered all the aspects of carcinoma larynx management.This was followed by a hot debate between Prof Dr Alok Thakar and Dr Deepak Gupta . Dr Alok Thakar reported that primary surgery has been the standard treatment for locally advanced carcinoma larynx for many years. Dr Deepak Gupta opposed him and presented the evidence suggesting that there is no randomised controlled trial to prove the superiority of surgery over chemoradiotherapy for advanced carcinoma larynx. He presented the evidence and results of larynx preservation studies with chemoradiotherapy or neoadjuvant chemotherapy followed by chemoradiotherapy for locally advanced carcinoma larynx. There have been major changes in treatment paradigms for advanced laryngeal cancer. The result has been a major increase in the number of patients with advanced larynx cancer treated by chemoradiotherapy. The major driver for these changes has been the publication of clinical trials reporting high rates of larynx preservation after using chemoradiotherapy protocols to treat advanced laryngeal cancer. Dr Rakesh Gupta  discussed the progress of the National Tobacco Control Program of India along with the importance and role of NGOs (non-Govt. Organisations) for the cessation of tobacco. Dr BK Smruti reported the results of landmark trials published recently on head and neck cancer chemotherapy, monoclonal antibodies and immunotherapy. Dr Tejpal in a comprehensive manner presented the results and evidence of altered fractionation radiotherapy in head and neck cancer. The take-home message after his presentation was that hyper-fractionation definitely gives very good overall survival benefit for locally advanced head and neck patients equivalent to survival benefit to that of concurrent chemoradiotherapy. Dr Srinivas Chilukuri  emphasised that conformal radiotherapy as IMRT has significant impact on long-term toxicities such as xerostomia and subcutaneous fibrosis, osteoradionecrosis and chronic dysphagia. Dr V Kaushal  reported in his talk on challenges in head and neck cancer control in India that head and neck cancer is one of the most common cancers in India. Weaker implementation of tobacco control policies, lack of awareness among patients, lack of medical facilities for treatment, lack of radiotherapy machines and the high cost of the treatment are major challenges to control head and neck cancer in India.Dr Munish Gairola  along with panel members including Dr Hemant Shukla and Dr Varsha Mahadeo Bundele (Head Neck Surgeon), Dr Sandeep Mehta (Plastic Surgeon), Dr BK Smruti , Dr Shikha Goyal , and Dr RK Vyas, Talib Khan  discussed the various aspects of recurrent head and neck cancer management.Dr Sheh Rawat  and panel members including Dr Tejpal Gupta, Dr Srinivas Chilkuri, Dr Vaibhav Choudhary , Peter Clarke, Alok Thakar, Dr Karun Sethi , and Dr Jyoti P Dabholkar  discussed the role of surgery, chemoradiotherapy and PET-CT/MRI/CT scans in the management of unknown primary with secondary neck nodes.Dr Purvish Parikh  reported the emerging role of molecular oncology for treatment of head neck cancer. He reported that targeted therapies and predictive biomarkers are needed to improve the outcomes and reduce the treatment toxicities and to allow selection of patients who are likely to benefit from both nonselective and targeted therapies. The main molecular determinants for head neck cancer are the abrogation of p53 and retinoblastoma (pRb) pathways and mutations in EGFR-MEK, NOTCH, PI3K, PTEN and AKT pathways that lead to uncontrolled cell replication.Dr Purvish Parikh, along with panelists including Dr Vivek Kaushal, Dr Chirag Desai, Dr Sandeep Jasuja, Dr BK Smruti, Dr Praveen Aswal , Dr Anjum Khan , Dr Praful B Desai, Dr Deepak Sarin discussed head and neck cancer treatment perspectives in the Indian scenario. They discussed the quality of training and education of oncologists, the lack of cancer treatment centres and medical staff and facility, the high number of patients taking incomplete treatment mainly because cancer centres are very far away from their homes, significant treatment toxicity, high cost of the treatment, lack of awareness, etc.In the live surgery workshop, senior and renowned oncosurgeons operated the cases of carcinoma thyroid, carcinoma buccal mucosa, carcinoma parotid, carcinoma larynx, carcinoma parapharyngeal space at BMCHRC with a live telecast at the conference venue. It was an interactive session as delegates, the moderator at the conference hall and the operating surgeon team were sharing their opinion and queries.On the last day of the conference, a workshop on prosthodentics for dentists was conducted. In this workshop, Dr B Srinivasan  and Dr Manu Rathi explained the role of prosthetics in head and neck cancer management. Dr Manish Chomal  reported the importance of dental prophylaxis and treatment of post radiotherapy dental complications with management. Dr Sunil Gupta  explained the optimum approach of maxillary and mandibular tumour resection.A radiotherapy contouring workshop was also conducted on the last day of the conference. It was a successful event and 60 radiation oncologists from different states in India and Nepal participated in the workshop. The workshop was conducted by Dr Vincent Gregoire . Eclipse treatment planning systems were granted by Varian Medical System, India as an educational support for this academic event. Dr Sheh Rawat, Dr Parveen Ahalawat , and Dr Anjali K Pahuja  described the anatomical and radiological boundaries of the neck node levels, CTV-node selection for involved and uninvolved nodes levels according to primary and radiotherapy dose prescription etc. Dr Vincent Gregoire presented the clinical history and investigatory reports, namely CT, MRI, and PET of two patients, one of whom was diagnosed with carcinoma oropharynx and the other with carcinoma nasopharynx. Participants were asked for contouring and delineation of CTV primary and CTV node for both of the cases on treatment planning systems. Then, Dr Vincent Gregoire carried out an analysis of each contour done by the delegates for both of the cases and highlighted the mistakes in contouring or shared his expert opinion. Radiotherapy contouring workshops are a new concept in India. They provide the opportunity of hands-on training in contouring to delegates. Radiation oncologists are encouraged to attend contouring workshops to ensure maintenance of professional standards. Attending these workshops offers the opportunity for radiation oncologists to validate their contouring practice during live workshops by comparing them with those from experts and other participants.Twenty-two delegates presented their research work in head and neck oncology during an oral paper presentation session. Seventy delegates displayed their research work with eposters. Teams of judges evaluated their research and presentations and gave scores accordingly.Head and neck cancer is one of the most common cancers in India. Each site including buccal mucosa, oropharynx, larynx, nasopharynx, base of skull and tongue has unique and different tumour characteristics that require multidisciplinary discussion and treatment. Surgical oncologists, radiation oncologists, medical oncologists, plastic surgeons, radiologists, nuclear medicine experts, pathologists, dentists, physiotherapists, palliative care professionals, nursing staff and NGOs are essential and important parts of the multidisciplinary team to get better outcomes. Multidisciplinary meetings such as IGSHNO 2017 for head and neck cancer management are essential especially in India as head and neck cancer patients make up the major load in cancer centres in this country."}
+{"text": "Multivariate neuroimaging studies of schizophrenia have revealed a generalizable neuroanatomical signature of the illness which however does not fully explain the variance of ist clinical phenotyps. A potential strategy to improve the mapping between the psychopathology and brain pathology of the disorder is to decipher the dictionary of symptom pattern and their neuroanatomical fingerprints. If successful, such a strategy could support a biologically informed revision of the taxonomy of psychosis.176 patients with first episode to chronic stages of schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and scanned using T1-weighted magnetic resonance imaging (MRI). The patients`PANSS scores, sociodemographic data and disease course variables, as well as their grey matter volume maps (GMV) entered a multivariate Partial Least Square (PLS) analysis that decomposed unique patterns of brain-behavior covariance between these data domains into latent variales (LV). We tested the LVs for significance using nonparametric- permutation and bootstrap resampling techniques.Three LVs showed significant brain-behavioral constellations. The first pattern linked hippocampal and medial frontal cortex volume with negative symptoms, age and age of onset. The second pattern consisted of opposite correlation between positive and negative symptoms associated with positive loadings in the subcortical structures such as the thalamus, the caudate nucleus and negative loadings in the auditory, insular and medial prefrontal cortices. The third LV presented a pattern involving negative symptoms, illness duration and age of onset as well as volume reductions in the anterior insular and orbitofrotal cortices.Our results indicate that the heterogeneity of schizophrenia can be decomposed into clinically relevant brain-behavioral phenotyps of the disorder, suggesting a biologically-informed and disease stage-sensitive stratification of schizophrenic patients. This might provide a neurobiological basis for future stratified investigations of treatment effects and prognosis both in early and advanced stages of schizophrenia."}
+{"text": "The burden of trauma and injuries in Uganda is substantial and growing. Two important gaps that need addressing are the shortage of trained people and a lack of national data on noncommunicable diseases and their risk factors in Uganda.We developed and implemented a new track within an existing master of public health programme, aimed at developing graduate-level capacity and promoting research on key national priorities for trauma and injuries. We also offered training opportunities to a wider audience and set up a high-level national injury forum to foster national dialogue on addressing the burden of trauma, injuries and disability.The Chronic Consequences of Trauma, Injuries and Disability in Uganda programme was implemented in 2012 at Makerere University School of Public Health in Kampala, Uganda, in conjunction with Johns Hopkins Bloomberg School of Public Health in Baltimore, United States of America.Over the years 2012 to 2017 we supported four cohorts of master\u2019s students, with a total of 14 students . Over 1300 individuals participated in workshops and seminars of the short-term training component of the programme. The forum hosted three research symposia and two national injury forums.Institutional support and collaborative engagement is important for developing and implementing successful capacity development programmes. Integration of training components within existing academic structures is key to sustainability. Appropriate mentorship for highly motivated and talented students is valuable for guiding students through the programme. Injuries are a leading cause of death in the African Region, where they claim over 900\u2009000 lives annually,As is the case in many low- and middle-income countries, Uganda faces challenges in addressing this burden, due to a shortage of trained people and a lack of national data on noncommunicable diseases and injuries and their risk factors.The Chronic Consequences of Trauma, Injuries and Disability Across the Lifespan in Uganda programme was implemented at Makerere University School of Public Health in Kampala, Uganda, in collaboration with Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America. The programme was funded by the Fogarty International Center of the United States National Institutes of Health in 2012.The programme was designed to integrate within the existing academic structures at Makerere University School of Public Health, so as to enhance its sustainability beyond the funding period. The programme comprised three main domains: long-term training; short-term training and national engagement.We introduced a new track within the master of public health programme at Makerere University School of Public Health, focused on trauma, injuries and disability. The master programme lasts two years, covering 78 weeks of study, and has both academic and field components. Each credit unit was 15 contact hours, which included lectures, practical work and fieldwork hours. The academic part of the master programme consisted of introductory and specialized courses in public health and included both core courses  and elective courses (3 credit units). In addition, students were required to take track-specific courses (9 credit units) and deliver a seminar series during year 2 (4 credit units). The field component of the programme consisted of two field studies with an output of two field reports (6 credit units), one of which converted into a dissertation research project (9 credit units). Overall, students accumulated a total of 61 credit units before graduating from the programme.For the track-specific component, three new courses were developed: Chronic consequences of trauma, injuries and disability; Interventions for trauma, injury and disability; and Surveillance and data systems for trauma, injury and disability. Students participated in a two-month advanced training at the Johns Hopkins Bloomberg School of Public Health in Baltimore, United States of America during the recess term of the first year of their master study. This consisted of taught courses in advanced epidemiology and biostatistics and mentoring to help students develop research proposals for their dissertations. Each student was assigned two mentors, one each from Johns Hopkins Bloomberg School of Public Health and Makerere University School of Public Health. The mentors monitored students\u2019 progress in the coursework, identified suitable research projects and gave professional development guidance in the field of injury prevention.We introduced a two-year postgraduate fellowship, which provided funds for tuition and travel. This kick-started the master programme, generated interest and raised awareness within the student community of the new track and research opportunities in the field of trauma and injuries. Students had to have a degree in health sciences, biological sciences or social sciences or humanities and were recruited from among junior faculty, residents, fellows and staff members in various departments of Makerere University. Applicants were selected based on their academic performance, personal commitment to research on trauma and injury, professional background and previous research experience.The short-term training aimed to supplement and enhance the long-term training component. This domain was open to a larger audience of postgraduate students and faculty members in Makerere University and externally to staff of other academic institutions, research and private sector organizations working on injuries and disability, and nongovernmental and governmental organizations. Activities included workshops (basic and advanced), symposia and seminars that assisted in training scientists at Makerere University and provided more in-depth, targeted research training to both the master students and other scientists in Uganda. The activities also raised awareness and stimulated dialogue among health and other professionals about the importance of research on trauma and injuries, and fostered collaboration among trauma and injury researchers both within Uganda and internationally.As part of the national engagement domain the programme team established a high-level national injury forum, which led research-to-policy dialogue on trauma and injury in Uganda. The aim was to facilitate the uptake of research into policy and to influence research that would respond to key policy issues. Attendees were university fellows, researchers and faculty, other health and public health professionals, policy-makers and public-sector officials.Over the five years of the programme (2012\u20122017), we were able to support four cohorts of students in the master in public health, totalling 14 fellows . The programme also supported five independent research projects through a small-grants programme to further stimulate research around key national priorities. The three new master courses in trauma, injuries and disability were co-instructed by faculty from the Makerere University School of Public Health, and Johns Hopkins Bloomberg School of Public Health for three consecutive years, before being taken over by faculty members from the Makerere University School of Public Health. The dissertation research projects of the master students and small-grant recipients covered a variety of injury-related topics and contributed to promotion of research around key national priorities for trauma and injuries in Uganda .Box\u00a01International Journal of Injury Control and Safety Promotion January 2018) Estimating road traffic injuries in Jinja district using capture\u2013recapture method Knowledge, attitudes and practices of commercial motorcyclists on helmet use in Makindye division, Kampala district (Jul\u2013Aug 2014)Annals of Global Health in autumn 2017)Quality of life of persons with physical disabilities receiving community based rehabilitation care in Kayunga district, Uganda Emergency department patient waiting times and its determinants at Mulago national referral hospital (Jul\u2013Aug 2015)Household coping mechanisms and economic consequences of motorcycle injuries among victims and their households for patients admitted at Mulago hospital (Oct\u2013Nov 2015)International Journal of Injury Control and Safety Promotion; submitted to BMC Public Health July 2017) Mobile phone use and the risk of road crashes among commuter taxi drivers in Kampala, Uganda Outcomes and cost estimates of unintentional injuries among children in a slum community in Kampala  Pre-hospital care time intervals and associated factors among victims of road traffic injuries in Kampala, Uganda boda boda drivers, related injuries and health costs at Mulago national referral hospital (Jul\u2013Aug 2016)Alcohol intoxication among Assessment of pre-hospital care provided to road traffic injury patients reporting at Mulago national referral hospital (Jul\u2013Aug 2016) Determinants of occupational injuries: a case\u2013control study among building construction workers in Kampala city, Uganda (Jul\u2013Aug 2016)Percutaneous injuries and splash blood exposures among health-care workers in Kampala: knowledge and utilization of HIV and hepatitis B prophylaxis (Jul\u2013Aug 2016)Utilization of rehabilitation services by human immunodeficiency virus (HIV) patients attending Mulago HIV clinic (Jul\u2012Aug 2016)Factors influencing utilization of physical rehabilitation services among injured patients in rural Uganda (Jul\u2013Aug 2017)Accident Analysis & Prevention February 2018)Geospacial distribution of pedestrian injuries and associated factors in urban Uganda: a case of Kampala metropolitan Notes: Text in brackets shows the date of completion of the dissertation and any scientific publications based on the research. There were 14 students in the trauma, injuries and disability track of the master of public health programme at Makerere University School of Public Health. The small-grants programme supported five independent research projects to further stimulate research around key national priorities in trauma, injury and disability.During the five years, over 1300 individuals participated in the symposia and seminars in the short-term training component of the main programme. The programme hosted three research symposia  and two Uganda national injury forums .The Chronic Consequences of Trauma, Injuries and Disability Across the Lifespan in Uganda programme was developed to respond to needs and priorities for research and training to reduce the burden of trauma and injuries in Uganda. The programme was successful in establishing and running a two-year postgraduate fellowship programme. The main strengths of this component were the highly motivated and talented students chosen through a rigorous selection process; the excellence in teaching and research at both institutions; and the individual mentoring by mentors with a diverse range of interests and experience . ThroughBox\u00a02Institutional support and collaborative engagement was important for developing and implementing a successful capacity development programme in trauma, injuries and disability.Integration of training components within existing academic structures was key to sustainability of the new master of public health programme.Appropriate mentorship for highly motivated and talented students was valuable for guiding students through the master programme.The founding and incorporation of the trauma, injuries and disability track in the master curriculum was designed to enhance the sustainability of the main programme. Such a model for capacity development had the advantage of making the training programme more accessible and tailored to meet local needs. Furthermore, it enhanced institutional capacity to create a locus for focused research and practice in the field, supporting the interests of both students and faculty members.The development and successful delivery of three new courses was essential in providing students with a foundation of knowledge in injury research and served as a strong base for the speciality in trauma, injuries and disability. After the initial collaboration with Johns Hopkins Bloomberg School of Public Health faculty members, Makerere University School of Public Health faculty now deliver the courses independently. This demonstrates strengthened capacity for injury research and training at Makerere University School of Public Health and further enhances the programme\u2019s sustainability and impact.To respond to the need for enhancing writing skills, the programme team implemented a seminar series on scientific writing. We assisted both current students and alumni of the master programme in converting their research projects in scientific publications . ThroughBuilding the skills for conducting, managing and delivering injury and trauma research is important for tackling the growing burden of injuries; yet it is not enough."}
+{"text": "Apis mellifera) are principal insect pollinators, whose worldwide distribution and abundance is known to largely depend on climatic conditions. However, the presence records dataset on potential distribution of honeybees in Indian Ocean Islands remain less documented. Presence records in shape format and probability of occurrence of honeybees with different temperature change scenarios is provided in this article across Zanzibar Island. Maximum entropy (Maxent) package was used to analyse the potential distribution of honeybees. The dataset provides information on the current and future distribution of the honey bees in Zanzibar Island. The dataset is of great importance for improving stakeholders understanding of the role of temperature change on the spatial distribution of honeybees.Honeybees ( Specifications TableValue of the data\u2022The data provide information on the potential spatial distribution of honeybees in both Unguja and Pemba Islands in Zanzibar and which is accessible for reuse.\u2022The data provide interesting and important information on future honeybee's distribution expansion in both Unguja and Pemba Islands in Zanzibar.\u2022The data can be used for modeling the effect of climate change and land use/ cover on honeybee's distribution in Indian Ocean Islands, in particular Zanzibar Island.\u2022The data can be useful for study genetic diversity of honeybees in Zanzibar Island.\u2022The data are important to different stakeholder include beekeeper communities, policy makers, international and local non-government organization engaged in apiculture intervention, researchers, scholars and academics.12htt://www.york.ac.uk) of the Representative Concentration Pathways Scenarios, Fifth Assessment Report (RCPs-AR5) The dataset collected in this study is located in Zanzibar Island in Eastern and South Eastern coast of Africa"}
+{"text": "Editorial on the Research TopicTertiary Lymphoid Organs (TLOs): Powerhouses of Disease Immunityantigen-driven TLO hypothesis. However, for many TLO-associated diseases, the presence of antigen-triggered immune responses\u2014let alone antigen-triggered disease-causing immunity\u2014has not been demonstrated  as the potential driving forces of TLO-dependent autoimmunity continue. New approaches and technologies including single-cell transcriptome analyses (Tertiary lymphoid organs (TLOs) arise in peripheral tissues  of adultnstrated . We theranalyses , next-geanalyses , improveanalyses , tissue analyses , and tra+ T cells  without compromising the systemic immune response and the integrity of the surrounding tissue. While identification of shared mechanisms has made major advances in recent years, disease-specific alterations of TLO immunity are less well understood. Studies on the peripheral plasticity of TLO characteristics should focus on CD4 T cells ; microgl T cells ; the bio T cells ; immunog T cells ; innate  T cells ; immune  T cells ; B-cell  T cells ; identif T cells ; identif T cells ; meninge T cells ; intesti T cells ; the var T cells , and lym T cells . AdvanceThe recent surge of interest in the TLO microcosm of disease immunity is remarkable as very little is known about the impact of these lymphocyte aggregates on disease progression: How and when TLOs are triggered? What distinct tasks do they have\u2014located so close to diseased tissues when compared to the more distant secondary lymphoid organs? Are they critically important for disease progression and\u2014if they are\u2014what are the underlying mechanisms? How do they connect to the tissue-draining lymph nodes and lymphatics? Are they beneficial, injurious, or both, depending on the context and stage of disease, anatomical location, and other factors? Can they be exploited or even artificially constructed for therapeutic purposes? Are there ways to disrupt them or enhance their activity without interfering with the systemic immune response? These are only a few of the questions that are being addressed in various disciplines. Until these fundamental issues will have been resolved, the interest in TLOs will most likely intensify. Hence, this research topic assembles scientists who agree on the premise that it is time to study these enigmatic lymphocyte aggregates over a broad range of angles.This research topic is organized into two major sections as follows.Section 1 covers the structures and cellular composition of TLOs and their development and function. It is introduced by Nancy Ruddle  who provides an overview on functional and regulatory features of high endothelial venules (HEVs) and the lymphatic system in TLOs; Nancy emphasizes the importance of HEVs in the recruitment of na\u00efve and central memory lymphocytes and of lymph vessels to transport antigen and serve as an entry site for antigen-presenting cells and lymphocytes. Ann Ager (Cardiff University) also discusses blood vessels and HEVs as critical regulators of lymphoid organ development and function. In particular, this review focuses on the role of vascular addressins in the regulation of lymphocyte trafficking and stresses the role of CD11c+ dendritic cells to regulate addressin expression in HEVs. Francesca Barone et al. (University of Birmingham and University of Lausanne) discuss the complex issue of stromal fibroblasts in shaping TLOs; Francesca proposes that these cells may represent a novel therapeutic target in chronic inflammation. Jan Kranich (Ludwig-Maximilians-University Munich) and Nike Julia Krautler (ETH Zurich) cover the area of follicular dendritic cells in shaping the B-cell antigenome. Jan and Nike highlight the origin and role of follicular dendritic cells in the capture and retention of antigen, thereby allowing B cells to undergo affinity maturation in germinal centers. Catherine Hughes et al. (University of Glasgow) assess the area of TLO antigen presentation and antigen-presenting cells. Gareth Wyn Jones et al. (Cardiff University) evaluate and discuss the complex interaction of immune cells as drivers in TLO development. James A. Butler et al. (University of York) provide an overview on their unconventional approach of model-driven experimentation to understand TLO neogenesis and function. Finally, Katrijn Neyt et al. (Ghent University) complement this section by providing original data on the role of interleukin 1 in TLO neogenesis.Section 2 covers prototypical examples of an expanding number of clinically significant diseases in which TLOs have been observed. Alice Koenig and Olivier Thaunat (University of Lyon) discuss TLOs in chronic transplant rejection; Alice and Olivier challenge the traditional view that TLOs may contribute to transplant rejection by pointing out the recent finding that TLOs have been described in stably accepted organ grafts. Elisa Corsiero et al. (Queen Mary University of London) review ectopic lymphoid structures as powerhouses of autoimmunity, and Meike Mitsdoerffer and Anneli Peters  focus attention on central nervous system autoimmunity. Changjun Yin et al. (Ludwig-Maximilians-University Munich) discuss the structures and possible impacts of artery TLOs in atherosclerosis. Manuela Buettner and Matthias Lochner (University of Hannover) summarize the special features, development, and function of TLOs in the small intestine and colon; Nobuyoshi Hiraoka et al.  cover the expanding area of TLOs in cancer tissues. Eoin Neil McNamee and Jesus Rivera-Nieves  discuss the roles of TLOs in inflammatory bowel disease as potentially protective or disease-promoting immune cell aggregates. Aliyah M. Weinstein and Walter J. Storkus (University of Pittsburg) summarize what is currently known on the biosynthesis and functional significance of peripheral node addressin in cancer-associated TLOs. Ji Young Hwang et al. (University of Alabama at Birmingham) point out the unique features of inducible bronchus-associated lymphoid tissue as protective immune aggregates in the lung. Jorge Caama\u00f1o and Sara Cruz-Migoni (University of Birmingham) summarize the recent discovery of fat-associated lymphoid clusters and their potential role in bridging metabolism and inflammation in adipose tissue. Marc Clement et al. (University of Paris Diderot) provide original observations on TLOs in Takayasu Arteritis. The section on TLOs in diseases is complemented by Catherine Sautes-Fridman et al. (Cordeliers Research Center Paris) on the epidemiology of tertiary lymphoid structures in cancers. The research topic ends with an original contribution by Yuka Kobayashi and Takeshi Watanabe  on their work on the in vivo generation of artificially constructed TLOs and their function in attempts to exploit TLOs for future therapeutic purposes.start spreading the news on TLOs to accelerate information on and interest in the important issue of the functional impacts of these still largely enigmatic disease-restricted lymphocyte aggregates.We hope that this research topic and E-book will help to All authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "In the explanatory background section a lot has been said about the structural reforms of the national health system. These reforms were to a large extent led by the external consultancies provided by the World Bank through the Health Project SerbiaThroughout that period, the accessibility of physicians, nurses, and midwives per 10 000 population has increased by 14 % but with significant inequity across districts.\u201d However, they miss to mention the scale of geographical inequality in density of staff distribution. Most of this pool of physicians, nursing and associated medical staff is concentrated in four largest cities with heavily neglected rural periphery. Heavy migration of skilled labor force toward rich urban cores happens due to higher living standards and stronger employment prospects (Stilwell et al., In the section entitled \u201cDrivers of health expenditure in the Republic of Serbia\u201d little has been said about the microeconomic drivers of local medical spending. Mostly top-down national health reports were cited in this chapter. However, there is a strong body of quantified, bottom-up assessments on real-world costs of care in Serbian health system. Over the past 15 years academic health economists have identified core drivers of high costs of inpatient and outpatient medical care. Innovative pharmaceuticals imaging diagnostics, interventional radiology procedures, dental care and radiotherapy in oncology are among the highest impact ones (Jakovljevic et al., In conclusion, authors noticed the role of the growing size of an aging population coupled with strong emigration net rates (Santric-Milicevic et al., MJ and MV have jointly designed the research question, prepared the manuscript and revised it for important intellectual content. They share equal authorship responsibility.We acknowledge the Ministry of Education Science and Technological Development of the Republic of Serbia for Grant ON 175 014 supporting the underlying studies laying grounds for this Commentary article. Publication was not contingent upon Ministry's approval or cenzorship.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Scientific Reports6: Article number: 3900010.1038/srep39000; published online 12192016; updated on 04242017The original version of this Article contained a typographic error in the spelling of Golam Jalal Ahammed, which was incorrectly given as Golam JalalAhammed, This error has now been fixed in the HTML and PDF versions of this Article."}
+{"text": "Interactions among endothelial cells (EC) forming blood vessels and their surrounding cell types are essential to establish the blood-brain barrier (BBB), an integral part of the neurovascular unit (NVU). Research on the NVU has recently seen a renaissance to especially understand the neurobiology of vascular and brain pathologies and their frequently occurring comorbidities. Diverse signaling molecules activated in the near proximity of blood vessels trigger paracellular pathways which regulate the formation and stabilization of tight junctions (TJ) between EC and thereby influence BBB permeability. Among regulatory molecules, the erythropoietin-producing-hepatocellular carcinoma receptors (EphR) and their Eph receptor-interacting signals (ephrins) play a pivotal role in EC differentiation, angiogenesis and BBB integrity. Multiple EphR-ligand interactions between EC and other cell types influence different aspects of angiogenesis and BBB formation. Such interactions additionally control BBB sealing properties and thus the penetration of substances into the brain parenchyma. Thus, they play critical roles in the healthy brain and during the pathogenesis of brain disorders. In this mini-review article, we aim at integrating the constantly growing literature about the functional roles of the EphR/ephrin system for the development of the vascular system and the BBB and in the pathogenesis of neurovascular and neuropsychiatric disorders. We suggest the hypothesis that a disrupted EphR/ephrin signaling at the BBB might represent an underappreciated molecular hub of disease comorbidity. Finally, we propose the possibility that the EphR/ephrin system bears the potential of becoming a novel target for the development of alternative therapeutic treatments, focusing on such comorbidities. Structural integrity of the blood-brain barrier (BBB) is essential for the establishment and maintenance of brain homeostasis. Any disruption in its cellular or structural components may exert devastating effects on mental health. During the past couple of years, research on the neurovascular unit (NVU) has experienced a second revival. This highlighted the BBB as a potential novel target for the development of alternative treatment strategies for brain and vascular pathologies.The BBB is a multicellular vascular structure separating the central nervous system from peripheral blood circulation , which lack fenestrations and undergo extremely low rates of transcytosis Figure . This liThe TJ are key regulators of paracellular permeability and transendothelial electrical resistance. Major constituents of the TJ are transmembrane molecules like occludin /Eph receptor-interacting signals (ephrin) system was first discovered in 1990, when ephrinA1 was characterized as a tumor necrosis factor (TNF)-inducible protein in human umbilical vein EC . Eph receptors and ephrins can be divided into subclasses A and B. In humans, nine EphA and five EphB receptors are known. They consist of an extracellular part including a globular ligand-binding domain, a cysteine rich region two fibronectin type 3 repeats and a cytoplasmic domain comprised of a short juxtamembrane region with several conserved tyrosine residues, a sterile alpha motive protein-protein interaction domain and a C-terminal PDZ binding motif. Additionally, several alternatively spliced forms have been identified with distinct functions -2 internalization, which is necessary for receptor activation and VEGF-induced filopodial extension in EC during angiogenesis (Bochenek et al., BBB leakiness is a hallmark of neurovascular pathologies comorbid with neuroinflammatory processes (Lee et al., Preclinical studies indicated that, among \u201cA\u201d members of the EphR/ephrin system, especially the EphA2 receptor mediates inflammation during injury, ischemia and other chronic inflammatory conditions in various murine models of neurovascular disorders (Jellinghaus et al., Regarding the \u201cB\u201d members, a link between TNF and EphB2 has also been suggested to be relevant to induce inflammatory pathways (Pozniak et al., A proof-of-principle that the EphR/ephrin system might represent a highly relevant therapeutic target for comorbid neurovascular and neuropsychiatric disorders has been provided by the controlled reactivation of EphB4/ephrinB2 in cardiovascular disorders, which enhanced BBB repair mechanisms (Ghori et al., Although several studies provide evidence for a compromised BBB integrity in a broad variety of psychopathologies, it is still unknown whether the BBB disruption is a cause or a consequence of the disease. Depending on the circumstances, a transient opening of the BBB might even be beneficial, e.g., during inflammation, it may allow the passage of growth factors or antibodies to hinder the inflammatory process. On the other hand, tightening of the BBB appears necessary during periods of stress or hypoxia (Abbott et al., Investigating the expression of EphR/ephrin system in the single components of the BBB during vasculogenesis and barriergenesis as well as their interplays in health and in the pathogenesis of brain and neurovascular disorders might open new avenues to understand neurobiological underpinnings of pathological comorbidities. This may help to identify novel therapeutic targets especially beneficial for comorbid patients.VAM and BDB contributed to literature screening and drafting the manuscript; both authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "A dual network hydrogel made up of polyvinylalcohol (PVA) crosslinked by borax and polyvinylpyrrolidone (PVP) was prepared by means of freezing-thawing circles. Here PVP was incorporated by linking with PVA to form a network structure, while the introduction of borax played the role of crosslinking PVA chains to accelerate the formation of a dual network structure in PVA/PVP composite hydrogel, thus endowing the hydrogel with high mechanical properties. The effects of both PVP and borax on the hydrogels were evaluated by comparing the two systems of PVA/PVP/borax and PVA/borax hydrogels. In the former system, adding 4.0% PVP not only increased the water content and the storage modulus but also enhanced the mechanical strength of the final hydrogel. But an overdose of PVP just as more than 4.0% tended to undermine the structure of hydrogels, and thus deteriorated hydrogels\u2019 properties because of the weakened secondary interaction between PVP and PVA. Likewise, increasing borax could promote the gel crosslinking degree, thus making gels show a decrease in water content and swelling ratio, meanwhile shrinking the pores inside the hydrogels and finally enhancing the mechanical strength of hydrogels prominently. The developed hydrogel with high performances holds great potential for applications in biomedical and industrial fields. Nowaday\u2019 in the lactam ring ; Project of Science and Technology Department of Sichuan Province [grant number 2016FZ0081]; Provincial Academic and Technical Leaders Foundation of Sichuan Province [grant number 2016-183-29]."}
+{"text": "Nature Communications7: Article number:1254910.1038/ncomms12549 (2016); Published 09162016; Updated 10252016The original version of this Article contained an error in the spelling of a member of the University of Michigan students Consortium, Sam Lee, which was incorrectly given as Sam Lewe. This has now been corrected in both the PDF and HTML versions of the Article."}
+{"text": "Aging of the central nervous system (CNS) is one of the major risk factors for the development of neurodegenerative pathologies such as Parkinson\u2019s disease (PD) and Alzheimer\u2019s disease (AD). The molecular mechanisms underlying the onset of AD and especially PD are not well understood. However, neuroinflammatory responses mediated by microglia as the resident immune cells of the CNS have been reported for both diseases. The unique nature and developmental origin of microglia causing microglial self-renewal and telomere shortening led to the hypothesis that these CNS-specific innate immune cells become senescent. Age-dependent and senescence-driven impairments of microglia functions and responses have been suggested to play essential roles during onset and progression of neurodegenerative diseases. This review article summarizes the current knowledge of microglia phenotypes and functions in the aging CNS and further discusses the implications of these age-dependent microglia changes for the development and progression of AD and PD as the most common neurodegenerative diseases. Microglia are the resident immune cells of the central nervous system (CNS) and are involved in a multifaceted range of physiological as well as pathophysiological functions , microglia undergo a constant self-renewal in order to maintain their population and it has been shown that no progenitor recruitment from blood circulation is contributing to this maintenance of microglia numbers throughout the lifetime  and danger-associated molecular patterns (DAMPs) have been categorized and are detected by microglial receptors including Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), AIM2-like receptors (ALRs) as well as C-type lectins , both of which being previously associated with age-related macular degeneration (AMD), increased during aging suggesting that senescent retinal microglia may contribute to complement dysregulation during disease pathogenesis and progression -[(11)C]PK11195 and positron emission tomography revealed that activated microglia appear in several cortical and subcortical areas during healthy aging  hotspots around amyloid plaques (Condello et al., In PD, marked microglia reactions in the human SN have been observed, which are associated with extraneuronal neuromelanin deposits (Beach et al., in vitro and in vivo and it further appears that the unique nature of microglia contributes to their age-dependent functional impairment. Moreover, the onset, severity and progression of neurodegenerative diseases such as AD and PD are influenced by aging and aging-associated changes in microglia functions (Figure Aging has been clearly demonstrated to affect microglia functions and activation states s Figure . HoweverBS wrote the manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Development of an implementation intervention is often based on the available evidence base and practical issues, i.e. feasibility and acceptability. The aim of this study was to describe the development of an implementation intervention for the TA stepped method for developing complex interventions based on theory, evidence and practical issues was adapted using the following steps: (1) Who needs to do what, differently? (2) Using a theoretical framework, which barriers and enablers need to be addressed? (3) Which intervention components (behaviour change techniques and mode(s) of delivery) could overcome the modifiable barriers and enhance the enablers? A researcher panel was convened to review the list of BCTs recommended for use and to identify the most feasible and acceptable techniques to adopt.3 Trial clinical intervention were identified by the researchers; step 2: the researcher panellists then selected one third of the BCTs recommended for use as appropriate for the clinical context of the ED and, using the enabler workshop data, devised enabling strategies for each of the selected BCTs; and step 3: the final implementation intervention consisted of 27 BCTs).Seventy-six barriers were reported by hospital staff who attended the workshops  is used to develop highly reportable implementation interventions. The classifying of BCTs using recognised implementation intervention components will facilitate generalisability and sharing across different conditions and clinical settings.The TDF was successfully applied in all steps of developing an implementation intervention for the TThe online version of this article (doi:10.1186/s13012-017-0616-6) contains supplementary material, which is available to authorized users."}
+{"text": "Differentiating between clear cell neuroendocrine tumor (NET) of the pancreas and renal cell carcinoma (RCC) metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL). The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies."}
+{"text": "The goal of this work was to determine the molecular basis for the induction of tumour vascularization and progression by injury. Magnetic resonance imaging (MRI) studies demonstrated that administration of wound fluid derived from cutaneous injuries in pigs reduced the lag for vascularization and initiation of growth of C6 glioma spheroids, implanted in nude mice, and accelerated tumour doubling time. The former effect can be attributed to the angiogenic capacity of wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial cell proliferation. The latter effect, namely the induced rate of tumour growth, is consistent with the angiogenic activity of wound fluid as well as with the finding that wound fluid was directly mitogenic to the tumour cells, and accelerated growth of C6 glioma in spheroid culture. Of the multiple growth factors present in wound fluid, two key factors, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of their activity using specific neutralizing antibodies suppressed the mitogenic effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the stimulatory effect of injury on tumour progression can possibly be attenuated by therapeutic targeting directed against a limited number of specific growth factors. \u00a9 1999 Cancer Research Campaign"}
+{"text": "The paper describes an integrated luminometer able to perform fluorescence (FL), room temperature phosphorescence (RTP) and chemiluminescence (CL) measurements on seawater samples. The technical details of the instrumentation are presented together with flow injection (FI) manifolds for the determination of cadmium and zinc (by FL), lead (RTP) and cobalt (CL). The analytical figures of merit are given for each manifold and results are presented for the determination of the four trace metals in seawater reference materials  and Scheldt estuarine water samples."}
+{"text": "To analyse the effect of ethylenediamine tetraacetate (EDTA) on tumour cell adhesiveness, fine structure of intercellular junctions of rat ascites hepatoma cells AH136B and AH7974 (both forming cell islands in vivo) was first compared. The close contact of the apical portion of both cell islands was composed of tight junctions with a narrow gap. The close contact of the inner portion of AH136B cell islands was largely by simple apposition, while that of AH7974 cell islands had many intermediate junctions and desmosomes. Treatment with EDTA (2 mM) induced morphological alteration of simple apposition, intermediate junctions and desmosomes, but tight junctions remained intact. The effect of EDTA on such junctional complexes seemed to be partially reversible on readministration of Ca ions. Changes in desmosomes, as confirmed on AH7974 cells, were initiated by disappearance of the central disc of electron-dense materials, followed by marked opening of intercellular space and disappearance of endoplasmic laminar plaque. These results suggest that Ca ions may be concerned with maintaining the integrity of junctional complexes other than tight junctions."}
+{"text": "The identification of endogenous avian leukosis virus (ALV) and endogenous avian retrovirus (EAV) in chick cell-derived measles and mumps vaccines in current use has raised concern about transmission of these retroviruses to vaccine recipients. We used serologic and molecular methods to analyze specimens from 206 recipients of measles, mumps, and rubella (MMR) vaccine for evidence of infection with ALV and EAV. A Western blot assay for detecting antibodies to endogenous ALV was developed and validated. All serum samples were negative for antibodies to endogenous ALV by Western blot analysis. Peripheral blood lymphocyte samples from 100 vaccinees were further tested by polymerase chain reaction for both ALV and EAV proviral sequences; all were negative. Matching serum samples were tested by reverse transcriptase polymerase chain reaction for ALV and EAV RNA, and all 100 samples were negative, providing no evidence of viremia. These findings do not indicate the presence of either ALV or EAV infection in MMR vaccine recipients and provide support for current immunization policies."}
+{"text": "Malaria interventions are usually prioritized using efficacy estimates from intervention trials, without considering the context of existing intervention packages or long-term dynamics. We use numerical simulation of mathematical models of malaria in humans and mosquitoes to provide robust quantitative predictions of effectiveness of different strategies in reducing transmission, morbidity and mortality.We can simulate indoor residual spraying (IRS) and insecticide-treated nets (ITNs), used singly and in combination with each other and with other interventions such as improved case management, intermittent preventive treatment (IPT). We can estimate reductions in entomological inoculation rate (EIR), clinical cases, prevalence and malaria deaths from simulations of different coverage levels ITNs and IRS with different properties, and at different transmission and health system settings.Our results suggest that sustained coverage of one or two interventions reduces malaria prevalence in two to three years but does not lead to further gains Figure . However"}
+{"text": "Sera from patients with nasopharyngeal carcinoma (NPC), a disease associated with Epstein-Barr virus (EBV), were found to be cytotoxic at 15% degrees C in the presence of complement for a panel of human lymphocytes, with a higher frequency than those of matched controls. The cold lymphocytotoxic antibodies (LTA) responsible for this activity have the same properties as those described in sera from individuals with acute viral infections. The frequency and geometric mean titres (GMT) of LTA varied with the origin of the patient (Chinese larger than North African larger than Caucasian) and the stage of the disease (Stage IV larger than Stage I). A positive correlation between LTA and anti-EBV titres was found with regard to antibodies to the viral capsid antigen (VCA) and the EBV-specified nuclear antigen (EBNA). The absence of correlation between LTA and anti-early antigen (EA) titres probable reflects the complex relationships existing between viral infection and LTA production, but is compatible with the hypothesis that LTA acts as an immune regulatory mechanism in viral infections."}
+{"text": "This paper is aimed at investigating how metastatic tumour growth influenced the haemostatic system of the host. Blood platelet count, blood fibrinogen level, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) were determined at various intervals during growth and metastasis of a murine fibrosarcoma (mFS6) or one of its sublines with different metastatic capacity. Progressive thrombocytopenia and increase in fibrinogen level were observed during development of the tumour in all the animal groups studied, irrespective of the metastatic potential of the various sublines. No significant changes were observed in the PT or APTT values. These data support the concept that primary rather than metastatic growth influences the haemostatic system of tumour-bearing animals."}
+{"text": "Intact cells of various human tumours and tumour cell lines, and acid extracts of various human tumours and normal tissues, each of which react with the lymphocytes of cancer patients as detected by the macrophage electrophoretic mobility (MEM) test, have been subjected to proteolysis. Activity was destroyed by some enzymes, and the apparent molecular size of the active material was reduced by others. An active low-mol.-wt fragment has been partially purified from papain digests of several tumours. Peptides with normal tissue and tumour-characteristic activities have been separated chromatographically from tryptic digests of tumour extracts."}
+{"text": "An overview of the use of immobilized enzymes in flow-injection analysis (FIA) is presented. The joint use of FIA and immobilized enzymes means that analytical procedures are easily automated, analytical costs are reduced and methods are faster. The future possibilities for this combination are discussed."}
+{"text": "The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes  and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient."}
+{"text": "Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus and the title studies have proved a definative role of anions in increasing the biological activityMixed ligands biologically active complexes of cobalt(II), copper(II) and nickel(II) withnicotinoylhydrazine-derived ONO, NNO and SNO donor schiff-base ligands having thesame metal ion but different anions such as sulphate, nitrate, oxalate and acetate have beensynthesised and characterised on the basis of their physical, analytical and spectral data. Inorder to evaluate the role of anions on their bioability, these ligands and their synthesisedmetal complexes with various anions have been screened against bacterial species such as"}
+{"text": "In a clinical investigation of postoperative survival after primary surgery for stomach cancer, 390 patients were registered since 1974. The potential prognostic parameters examined within the first days of hospitalization for primary resection included age of the patients, operability, tumour extension (TNM classification) and tumour stages I-IV (UICC). Statistical treatment of the data revealed that each of the clinical parameters covers critical ranges associated with highly significant differences in patient survival. The preoperative serum CEA concentration exhibited prognostic significance in addition to the criteria of operability and tumour extension. In selected subgroups of patients with distinct resectability and tumour extension, ranges of preoperative CEA concentration could be specified which were associated with statistically significant differences in the patient survival. The results indicate that the preoperative serum CEA level can be an independent prognostic parameter in stomach cancer."}
+{"text": "Cognitive function items are increasingly included in quality of life measures, and complaints of concentration and memory difficulties are often reported by cancer patients. The aim of this study was to examine the factors influencing patients' level of complaint by comparing subjective reports with objective test performance of a sample of adult lymphoma patients, disease-free and > or = 6 months after treatment. There was no significant difference between complainers and non-complainers in sociodemographic or clinical characteristics or in their performance on standard neuropsychometric tests of concentration and memory. Those reporting concentration and memory difficulties had significantly higher scores on measures of anxiety, depression and fatigue. This calls into question the validity of including cognitive function items in self-report quality of life measures. Patients who report concentration and memory difficulties should be screened for clinically significant and potentially remediable mood disorder. Objective testing remains the method of choice for assessing higher mental function."}
+{"text": "Conception, design, and implementation of cDNA microarray experiments present avariety of bioinformatics challenges for biologists and computational scientists. The multiplestages of data acquisition and analysis have motivated the design of Expresso, asystem for microarray experiment management. Salient aspects of Expresso includesupport for clone replication and randomized placement; automatic gridding, extraction ofexpression data from each spot, and quality monitoring; flexible methods of combiningdata from individual spots into information about clones and functional categories; and theuse of inductive logic programming for higher-level data analysis and mining. Thedevelopment of Expresso is occurring in parallel with several generations of microarrayexperiments aimed at elucidating genomic responses to drought stress in loblolly pineseedlings. The current experimental design incorporates 384 pine cDNAs replicated andrandomly placed in two specific microarray layouts. We describe the design of Expresso aswell as results of analysis with Expresso that suggest the importance of molecularchaperones and membrane transport proteins in mechanisms conferring successfuladaptation to long-term drought stress."}
+{"text": "The indirect immunofluorescence technique demonstrated that human alpha fetoprotein (AFP) was present in a focal pattern in the cytoplasm of malignant liver cells of patients whose sera contained AFP. A few fibroblastlike cells in tissue culture of liver biopsies from patients with hepato-cellular carcinoma and AFP in their sera also had the protein. The intracellular localisation of human AFP was confirmed by centrifugation of washed, homogenised and ultra-sonically disrupted neonatal liver cells. Examination of livers of fetuses and neonates showed that AFP was present predominantly in the periportal parenchymal cells."}
+{"text": "Wound site infections are a major source of postoperative illness, accounting for approximately a quarter of all nosocomial infections. National studies have defined the patients at highest risk for infection in general and in many specific operative procedures. Advances in risk assessment comparison may involve use of the standardized infection ratio, procedure-specific risk factor collection, and logistic regression models. Adherence to recommendations in the 1999 Centers for Disease Control and Prevention guidelines should reduce the incidence of infection in surgical patients."}
+{"text": "Risk of death and risk of recurrence in 108 potentially curable non-small-cell lung cancer patients were analysed with respect of TNM stage, histological type and carcinoembryonic antigen (CEA), CA125 antigen and squamous cell carcinoma antigen (SCC) levels in serum and cytosol. CA125 and CEA levels were closely related to outcome figures. Multivariate analyses indicated that TNM stage and histological type had the best predictive power, but serum and cytosolic CA125 and serum CEA contained additional, independent prognostic information. Predictive information drawn from serum and cytosolic levels proved mutually complementary. We conclude that CA125 and CEA complement TNM classification and histological type for the purpose of quantifying risk of death or recurrence."}
+{"text": "Systems biology research and applications require creation, validation, extensive usage of mathematical models and visualization of simulation results by end-users. Our goal is to develop novel method for visualization of simulation results and implement it in simulation software package equipped with the sophisticated mathematical and computational techniques for model development, verification and parameter fitting.We present mathematical simulation workbench DBSolve Optimum which is significantly improved and extended successor of well known simulation software DBSolve5. Concept of \"dynamic visualization\" of simulation results has been developed and implemented in DBSolve Optimum. In framework of the concept graphical objects representing metabolite concentrations and reactions change their volume and shape in accordance to simulation results. This technique is applied to visualize both kinetic response of the model and dependence of its steady state on parameter. The use of the dynamic visualization is illustrated with kinetic model of the Krebs cycle.http://www.insysbio.ru.DBSolve Optimum is a user friendly simulation software package that enables to simplify the construction, verification, analysis and visualization of kinetic models. Dynamic visualization tool implemented in the software allows user to animate simulation results and, thereby, present them in more comprehensible mode. DBSolve Optimum and built-in dynamic visualization module is free for both academic and commercial use. It can be downloaded directly from  Kinetic modeling is one of the main tools of computational systems biology aimed at quantitative description of intracellular dynamic processes. The term kinetic model refers to a system of algebra-, integral- or delay- differential equations that determine the temporal and steady state of the corresponding biological system. The model of a particular system of biochemical reactions is usually represented by a system of mechanistic differential equations and includes multiple parameters which values must be estimated on the basis of experimental data. There are, at least, three stages in study of a biochemical system by means of kinetic modeling . The firDBSolve Optimum is significantly improved and extended successor of well known simulation software DBSolve5 ). BelTo describe dynamics of the kinetic models DBSolve Optimum uses a popular LSODE  algorithm . These mUsers may have their own particular equation which they require solving and wish to be applied to a set of experimental data. DBSolve Optimum offers the facility to encode and solve such \"explicitly stated\" formulae. They should be typed at the bottom of the RHS window in the section \"Explicit Function\" and then solved by turning to the \"Explicit Solver\" tabbed page, where the appropriate variable, interval of variation of parameters and an initial step can be entered. In additional file This method allows the user to trace the changes in the steady state of the system as a result of variation of one or more of its parameters. This procedure is very useful for determining any functional dependencies  against any external (substrate concentrations) or internal (enzyme concentrations) or some model parameter. It is especially useful in the case of non-linear algebraic systems which have no explicit solution or have multiple or unstable solutions. DBSolve Optimum includes a general continuation procedure, based on a tangent predictor continuation scheme . A modifBifurcation theory is a more systematic and general theory of non-linear systems than the standard, steady-state analysis of metabolic networks. Computation of one or two-parameter bifurcation diagrams can quickly inform the user about what is possible for, or prohibited by, a particular type of non-linear model . To calcThis method can be used to fit a model to experimental data .The fitting/optimization can exploit either a zero-order  or firstwhere Yti and Yei are the theoretical and experimental values, respectively and F0 is discrepancy.In additional file Simulation results and schematic representation of biochemical system of the model can be visualized by DBSolve Optimum in two possible ways.Each calculation module can either save calculation results as text file of CSV  format or plot them as a graph. The second option has been implemented in DODE on the basis of TeeChart package . In compTo understand behavior of the biological system as a whole we have developed special visualization technique allowing to animate simulation results  and implemented it in DBsolve Optimum. The main idea of the technique consists of 1) construction of visual map of the biological system (and corresponding model) and 2) animation of the visual map, i.e. reproducing dynamic changes in concentrations and fluxes by altering shapes and volumes of geometrical objects corresponding to these model variables. Graphical objects corresponding to biological entities and reactions of the model can change their volume and shape in accordance to the calculated values of corresponding concentrations and fluxes. Dynamic Visualization (animation) can be used to represent both kinetic (time dependent) response of the model to any perturbations and dependences of steady state concentrations and fluxes to any model parameters. This Dynamic Visualization technique has been implemented in DBSolve Optimum Framework in following manner. Initial construction of the static visual map (pathway) for kinetic model and generation of data file with simulation results has been implemented in DODE as Dynamic Visualization Module (DVM)  and calculation results produced by DODE solvers and saved as special plain text file with \"PLT\" (PLain Text) extension . XML (eXtensible Markup Language) file is designed to store geometry of basic graphic objects. The XSD (XML Schema Definition Language) schema of this XML file can be found on our website . The PLTStatic scheme of the biochemical system  and simulation results (saved as PLT file) are input data for DOP. On the basis of the input data DOP is able to animate visual map and save the animation as video file. Indeed, to reproduce the animation corresponding to the selected model, the user should download in DOP the XML file with the constructed visual map and corresponding PLT file generated in DVM see Fig. . Before iC, is represented by change in circle radius, ir, around the corresponding node in such a way that the concentration is directly proportional to circle radius:DBSolve Optimum allows visualization of simulation results in two different ways: \"Bar animation\" and \"Arrow animation\" ;7. Automatic search of optimal values of the parameters of a system based on the experimental data (fitting);8. Analysis of stability of the dynamic system (bifurcation) and calculation of the control coefficients as defined in metabolic control analysis.DBSolve Optimum belongs to the family of software packages designed for creation, analysis and simulation of kinetic models of biological systems. More than 50 different programs able to assist in quantitative description and visualization of biological systems are presented in web site . These pAs follows from the comparison Table  DBSolve in silico simulations.DBSolve Optimum Visualization Module allows user (1) to create visual map using stoichiometric matrix, (2) to create stoichiometric matrix from visual map, (3) to export of the visual map to raster or vector graphical format files and (4) to animate visual map. Automatic construction of the basis of the visual map (clause 1) allows modeler to facilitate substantially process of creation of metabolic map corresponding to the model developed. In framework of this option DBSolve Optimum creates set of graphical objects which are interconnected by reactions in accordance to stoichiometric matrix. To create the appropriate map, user should drag these objects in appropriate places on the canvas. Other option of Visualization (2) allows to solve inverse problem, namely to construct automatically the stoichiometric matrix from the visual map. The export of the visual map to raster or vector graphical format (3) allows modeler to use maps for presentations and reports. Animation of the visual map (4) is dynamic representation of To create Dynamic Visualization (animation) of simulation results in DODE, user should open \"Visualization\" tabbed page of DBSolve Optimum see Fig. . Then, cWhen static visual map (XML file) and simulation results (PLT file) are generated user can download them to DOP see Fig. . The basTable In this article we present DBSolve Optimum. The software package has been successfully employed for dynamic modeling and visualization of microbial central metabolism and gene regulation, signal transduction pathways and mitochondrial oxidative phosphorylation. Broad functionalities of DBSolve Optimum are able to address most problems arising in systems biology. Implementation of dynamic visualization tool in DBSolve Optimum has been described in details. This tool allows user to animate simulation results and, thereby, present them in more comprehensible mode. The visualization module of DBSolve Optimum is an important feature which provides essential functionality for presentation of modeling results and communication to biologists and medics.DBSolve Optimum runs on Windows platforms. Also it can be run under Linux platform using Wine: free Win32 implementation . DBsolveDODE: DBSolve Optimum Developer Environment; DOP: DBSolve Optimum player; SLV: (SoLVe) is internal format of DBSolve Optimum; RCT: (ReaCTions) file; SBML: Systems Biology Markup Language; ASCII: American Standard Code for Information Interchange; ODE: Ordinary Differential Equation; RHS: Right Hand Side; IV: Initial Values; LSODE: Livermore Solver for Ordinary Differential Equations; NADH: Nicotinamide Adenine Dinucleotide (reduced form); CSV: Comma Separated Value format; DVM: Dynamic Visualization Module; PLT: PLain Text extension; XML: eXtensible Markup Language file; XSD: XML Schema Definition Language.IG, NG, OD designed and NG programmed the DBSolve Optimum. OD, NG, EuM wrote software documentation. KP, EuM prepared web site materials. OD, KP, EuM, EkM, NG tested DBSolve Optimum. All co-authors contributed to the conception and design of the manuscript as well as drafted and revised the manuscript. All authors read and approved the final manuscript.supplementary materials. file contains supplementary materials describing in details (1) main features of DBSolve Optimum (2) kinetic model of Krebs cycle as an example of DBSolve implementation to model biochemical system.Click here for filekinetic model of TCA cycle. DBSolve Optimum kinetic model file. file contains kinetic model of TCA cycle in internal DBSolve language.Click here for fileSchematic representation of TCA cycle kinetic model in bars animation. DBSolve Optimum schema file. file contains scheme of kinetic model of TCA cycle in xml format designed for bar animation.Click here for fileSchematic representation of TCA cycle kinetic model in arrows animation. DBSolve Optimum schema file. file contains scheme of kinetic model of TCA cycle in xml format designed for arrows animation.Click here for filenumerical data for bars animation. DBSolve Optimum Player animation data. file contains numerical data designed for bar animation of simulation results of the kinetic model of TCA cycle.Click here for filenumerical data for arrows animation. DBSolve Optimum Player animation data. file contains numerical data designed for arrow animation of simulation results of the kinetic model of TCA cycle.Click here for file"}
+{"text": "An interesting and not previously reported parallel has been observed between the known pattern of ABO (H) blood group isoantigen expression in normal and neoplastic colonic epithelium and that in the thyroid. Epithelial expression of blood group isoantigens was not observed in 16 specimens of normal or non-neoplastic thyroid tissue. This contrasts with the progressive re-expression of these antigens in neoplastic thyroid tissue. Blood group isoantigens were detected in two of eight papillary adenomas and 13 of 17 papillary carcinomas. Antigen expression was in part related to differentiation, and stained cells were less readily detected in follicular tumours, only one of five adenomas and two of seven carcinomas displaying blood group antigens while three medullary and two anaplastic carcinomas were antigen-deficient."}
+{"text": "A computational program which compares the effciencies of different experimental designs with those of maximum precision (D-optimized designs) is described. The program produces confidence interval plots for a calibration curve and provides information about the number of standard solutions, concentration levels and suitable concentration ranges to achieve an optimum calibration. Some examples of the application of this novel computational program are given, using both simulated and real data."}
+{"text": "It provides comprehensive dosimetric comparisons of different radiotherapy systems and sources and precise dosimetric methods and data for modern radiotherapy systems and sources which are of immense importance during clinical applications of these devices. The thesis also deals with the development of quality audit methods and programs for both beam and brachytherapy modalities which can be used for routine external audit of dosimetry data generated for patient dosimetry at radiotherapy centers.The above thesis by Sunil Dutt Sharma deals with the dosimetric aspects of beam therapy systems and brachytherapy sources Detailed experimental data of Siemens secondary multileaf collimator (MLC)\u2013shaped high energy X-ray beams and a comparison with scatter factors of conventional jaw collimator (JC)\u2013shaped X-ray beams of the same medical linear accelerator are presented. On the basis of these studies, it is demonstrated that the patient dosimetry formalism based on 10-cm reference depth gives better accuracy over depth-of-dose maximum formalism. The use of a suitable beam coaxial mini phantom for the measurement of collimator scatter factor is recommended to eliminate the unwanted contribution of contaminated electrons. Collimator and phantom scatter factors of high-energy X-ray beams are important parameters used for monitor unit calculations for patient treatment using a medical linear accelerator. The effect of contamination electrons and collimator exchange effects on the magnitude of these parameters are topics of current interest.The advent and introduction of MLC in clinical practice has made it possible to adopt the technique of conformal radiotherapy. The method of shaping the conformal treatment portals depends on the type and technical aspects of the MLC. Accordingly, the degree of irregularity of the treatment field plays an important role in determining the magnitude of related dosimetry parameters. The author investigated the effect of degree of irregularity on the dosimetry parameters for conformal field shaped by Varian tertiary MLC and observed a significant change in the absolute output of the beam for the conformal field of very high degree of irregularity. This is an important observation which needs to be accounted for either mechanically or dosimetrically while using Varian tertiary MLC for conformal beam therapy. The quantification of percentage under dosing effect at the junction of MLC-shaped adjacent fields using radiochromic and radiographic films for the Varian tertiary MLC needs special mention as data presented is relevant to both conventional and intensity-modulated radiotherapy.in vivo dosimetry diode (Victroreen VeriDose), micro cubes and powder grains of LiF:Mg, Ti thermoluminescence dosimeter (TLD), radiochromic film and radiographic film for dosimetry of X-Knife (Cone- as well as MLC-based) and Gamma Knife beams, the author studied the intricacies and made specific recommendations on the choice of dosimeter for small-field dosimetry. The work demonstrates that the practice of measuring output by PTW Markus plane parallel chamber and PTW Pinpoint chamber and using the average values of these two measurements is erroneous for SRS cone of diameter smaller than 12.5 mm.The steep dose gradient of very narrow photon beams used in stereotactic radiosurgery/radiotherapy (SRS/SRT) requires dosimeters with spatial resolution better than 1.0 mm. The lack of lateral electronic equilibrium further complicates the dosimetry. By using three different types of ionization chambers , an Measured helmet output factors (HOF) of four different gamma knife units are also presented, indicating the unit-specific character of HOF.192Ir source, indigenously developed low-energy photon-emitting 125I seed source and different gamma- and beta-emitting intravascular sources used for brachytherapy applications. Radiochromic film\u2013based dosimetry methods are presented for in-water dosimetry of HDR 192Ir gamma ray source. It also demonstrates that radiochromic film can be used to generate dosimetry data at a high resolution suitable for comparison with the values obtained by Monte Carlo calculations. Accurate and precise methods using TLD micro rods and in-house fabricated PMMA phantoms are presented for generation of American Association of Physicists in Medicine (AAPM) TG-43\u2013recommended dosimetry data of 125I seed source and for comparison with the Monte Carlo\u2013calculated values. Simple dose rate tables presented for patient dosimetry while using 125I seed source for interstitial and ocular brachytherapy applications may be useful.The thesis also deals with dosimetry aspects of high\u2013dose-rate (HDR) 32P-coated stents, 186Re/188Re liquid\u2013filled balloons, 90Sr/90Y seed trains and 192Ir seed ribbons used for intracoronary brachytherapy applications.In the thesis, the author has also included the experimentally measured and Monte Carlo\u2013calculated dosimetry features of Quality audit (QAu) by mailed dosimeters is an alternative to fulfill partially the requirements stipulated under audit programs by various national/international agencies. TLD is a reliable, well-tested dosimeter and is in use from the last three decades for postal audit purposes. However, it is laborious and time consuming. Gafchromic EBT film\u2013based comprehensive postal dosimetry method is demonstrated by the author for audit of important dosimetry parameters, both in reference and nonreference conditions of high-energy photon beams. The postal QAu method presented for measuring brachytherapy source strength and verifying dose to point \u2018A\u2019 and point \u2018B\u2019 delivered during intracavitary brachytherapy treatment also appears useful.The work for Ph.D. degree carried out by S. D. Sharma at Radiological Physics & Advisory Division (RP&AD), Bhabha Atomic Research Centre (BARC), Mumbai, under the guidance of Dr. B. C. Bhatt  (as a research guide) at the University of Mumbai, Mumbai, India, is of significant relevance to clinical dosimetry and quality audit of several parameters of radiotherapy systems and sources of modern technology used for the treatment of cancer patients."}
+{"text": "The relationships between DNA damage from UV radiation, alkylating drugs and the methylated xanthines (MX) have been studied in normal and malignant rodent and human cells. A comparison of the level of DNA excision repair (repair replication and unscheduled DNA synthesis) confirms that some forms of alkylating-agent damage (probably mono-filar DNA adducts) are less completely removed by both normal and malignant rodent cells than by their human counterparts, rendering rodent cells more susceptible to the toxic potential of unexcised lesions. The toxicity of alkylating agents can be increased by the presence of several MXs during the period of DNA replication which follows infliction of the damage. Human cells appear capable of excising more DNA damage, rendering them somewhat less susceptible to enhancement of cytotoxicity by MX. This resistance of human cells is only quantitative, however, since 2 human cancer cell lines (HeLa and HT-29) could be sensitized to a variety of alkylating agents by appropriate concentrations of MX. Trimethylxanthine (caffeine) and the 2 clinically useful dimethylxanthines (theophylline and theobromine) appeared equally effective in sensitizing cells. The sensitization was dependent upon a slightly cytotoxic concentration of the MX and a suitably prolonged period of post-damage MX exposure. Of these 3 classic MXs, only theobromine might be clinically useful. The levels required for alkylating-agent sensitization exceed the clinically tolerable level of theophylline, and probably approach the tolerance of man to caffeine. The most likely mechanism by which MX sensitization is achieved is reversal of the inhibition of DNA replicon initiation which follows the infliction of significant DNA damage. Through the selection of suitable clinically useful alkylating agents (those dependent on active cellular transport for cell penetration) and appropriate MX scheduling, an enhanced therapeutic ratio might be achieved, potentially increasing the clinical usefulness of these alkylating agents. MX would thus form a useful class of agents adjuvant to conventional anti-cancer drugs."}
+{"text": "Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria-endemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides."}
+{"text": "Abscission is the cell separation process by which plants are able to shed organs. It has a great impact on the yield of most crop plants. At the same time, the process itself also constitutes an excellent model to study cell separation processes, since it occurs in concrete areas known as abscission zones (AZs) which are composed of a specific cell type. However, molecular approaches are generally hampered by the limited area and cell number constituting the AZ. Therefore, detailed studies at the resolution of cell type are of great relevance in order to accurately describe the process and to identify potential candidate genes for biotechnological applications.in-vitro 24 h ethylene treatment was performed utilising microarray hybridization and analysis. Our analyses of gene functional classes differentially represented in ethylene-treated LAZ revealed an activation program dominated by the expression of genes associated with protein synthesis, protein fate, cell type differentiation, development and transcription. The extensive repertoire of genes associated with cell wall biosynthesis and metabolism strongly suggests that LAZ layers activate both catabolic and anabolic wall modification pathways during the abscission program. In addition, over-representation of particular members of different transcription factor families suggests important roles for these genes in the differentiation of the effective cell separation layer within the many layers contained in the citrus LAZ. Preferential expression of stress-related and defensive genes in Pet reveals that this tissue is likely to be reprogrammed to prevent pathogen attacks and general abiotic stresses after organ shedding.Efficient protocols for the isolation of specific citrus cell types, namely laminar abscission zone (LAZ) and petiolar cortical (Pet) cells based on laser capture microdissection (LCM) and for RNA microextraction and amplification have been developed. A comparative transcriptome analysis between LAZ and Pet from citrus leaf explants subjected to an The LCM-based data generated in this survey represent the most accurate description of the main biological processes and genes involved in organ abscission in citrus. This study provides novel molecular insight into ethylene-promoted leaf abscission and identifies new putative target genes for characterization and manipulation of organ abscission in citrus. Abscission of plant organs takes place through a highly coordinated sequence of biochemical events that occur in a discrete group of cells located in predictable positions in the plant, known as abscission zones (AZs) . SheddinArabidopsis ) show transcripts involved in pyruvate metabolism, glycolysis or nucleotide-sugar interconversions preferentially expressed in LAZ and negative values those preferentially expressed in Pet. Each bar represents the expression ratio of a singleton or of different ESTs assembled in the same contig. Data are the average of two dye-swap comparisons and error bars show SE.Click here for fileList od citrus ESTs associated to protein biosynthesis and metabolism. Expressed sequence tags (ESTs) and the corresponding genes associated with protein biosynthesis and metabolism expressed preferentially in the laminar abscission zone cells (M>1) or in the petiolar cortical cells (M<1).Click here for fileList of citrus ESTs associated with defense and interaction with the environment. Expressed sequence tags (ESTs) and the corresponding genes associated with defense and interaction with the environment expressed preferentially in the laminar abscission zone cells (M>1) or in the petiolar cortical cells (M<1).Click here for fileList of citrus ESTs associated with protein phosphorylation and signal transduction. Expressed sequence tags (ESTs) and the corresponding genes associated with protein phosphorylation and signal transduction expressed preferentially in the laminar abscission zone cells (M>1) or in the petiolar cortical cells (M<1).Click here for fileList of citrus ESTs asociated with transcriptional regulation. Expressed sequence tags (ESTs) and the corresponding genes associated with transcriptional regulation expressed preferentially in the laminar abscission zone cells (M>1) or in the petiolar cortical cells (M<1).Click here for fileGenes tested with sqRT-PCR and qRT-PCR and primers used.Click here for file"}
+{"text": "The Evaluation of Processes and Indicators in Infection Control (EPIC) study assesses the relationship between hospital care and rates of central venous catheter-associated primary bacteremia in 54 intensive-care units (ICUs) in the United States and 14 other countries. Using ICU rather than the patient as the primary unit of statistical analysis permits evaluation of factors that vary at the ICU level. The design of EPIC can serve as a template for studies investigating the relationship between process and event rates across health-care institutions."}
+{"text": "Flow-injection manifolds are described which allow the preconcentrationof lead for flame atomic absorption determinations, usingcolumns contained within the sample loop of an injection valve. Aninterface was designed which allowed the valves and pump in thesystem to be controlled by an autosampler which enabled precisetiming of preconcentration and elution steps. The effects of sampleflow rate, buffer pH and buffer type for preconcentration andeluent concentration and flow rate were investigated in order toobtain optimum performance of the system. A 50-times improvementin detection limits over conventional sample introduction wasobtained for a sample volume of approximately 12 ml, preconcentrated for150 s. The injection of eluent, as opposed to the use of acontinuously flowing eluent stream, enabled this reagent to beconserved."}
+{"text": "This article describes photometric flow injection (FI) methods forthe determination of ammonia and nitrite in aquaculture. Themethods are based on the use of normal and reversed FI approachesand show the potential of this technique for monitoring the inputand output streams of small tanks at young fish-breeding farms.The methods meet the requirements of fish hatcheries, particularly interms of the high sampling rate allowable (40/h)."}
+{"text": "The thymus is a complex organ with an epithelium formed by two main cell types, the cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs), referred to as stroma. Immature thymocytes arising from the bone marrow, macrophages and dendritic cells also populate the thymus. Thymocytes evolve to mature T cells featuring cell differentiation antigens (CDs), which characterize the phenotypically distinct stages, defined as double-negative (DN), double positive (DP) and single positive (SP), based on expression of the coreceptors CD4 and CD8. The thymus is therefore implicated in T cell differentiation and during development into T cells thymocytes are in close association with the stroma. Recent evidence showed that mTECs express a diverse set of genes coding for parenchymal organ specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has led to the reconsideration of the role of the thymus in central T cell tolerance to self-antigens, which prevents autoimmunity. The evidence of PGE is causing a reanalysis in the scope of central tolerance understanding. We summarize the evidence of PGE in the thymus, focusing particularly the use of cDNA microarray technology for the broad characterization of gene expression and demarcation of PGE emergence during thymus ontogeny."}
+{"text": "There is evidence of a clustering of healthy dietary patterns and physical activity among young people and also of unhealthy behaviours. The identification of influences on children's health behaviors, particularly clustered health behaviors, at the time at which they develop is imperative for the design of interventions. This study examines associations between parental modelling and support and children's physical activity (PA) and consumption of fruit and vegetables (FV), and combinations of these behaviours.In 2002/3 parents of 775 Australian children aged 10\u201312 years reported how frequently their child ate a variety of fruits and vegetables in the last week. Children wore accelerometers for eight days during waking hours. Parental modelling and parental support  were self-reported. Binary logistic and multinomial logistic regression analyses examined the likelihood of achieving \u2265 2 hours of PA per day (high PA) and of consuming \u2265 5 portions of FV per day (high FV) and combinations of these behaviors (e.g. high PA/low FV), according to parental modelling and support.Items of parental modelling and support were differentially associated with child behaviours. For example, girls whose parents reported high PA modelling had higher odds of consuming \u2265 5 portions of FV/day . Boys whose parents reported high financial support for snacks/fast foods had higher odds of having 'high PA/low FV' .Parental modelling of and support for physical activity and fruit and vegetable consumption were differentially associated with these behaviours in children across behavioural domains and with combinations of these behaviours. Promoting parents' own healthy eating and physical activity behaviours as well encouraging parental modelling and support of these behaviours in their children may be important strategies to test in future research. The importance of examining influences on children's physical activity and fruit and vegetable consumption is underpinned by the recognition that lifestyles including adequate levels of physical activity and high intakes of fruit and vegetables have positive health benefits and important health-protective effects ,2. DespiGiven such evidence, the identification of influences on children's health behaviours, particularly clustered health behaviours, at the time at which they develop is imperative for the design of interventions. Socialization of health-related behaviours occurs within the family, with parents' beliefs, attitudes and behaviours substantially affecting children's health behaviours . PreviouStudies examining correlates of children's physical activity and fruit and vegetable intake tend to focus on associations within the same behavioural domains. For example, recent reviews have shown that parental support for physical activity was consistently positively associated with children's physical activity  and thatTo our knowledge there is currently no published research examining associations between parental modelling and support and children's combined physical activity and fruit and vegetable consumption . The aim of the present study, therefore, is to examine cross-sectional associations between a) parental modelling and support and children's physical activity and fruit and vegetable consumption individually, and b) between parental modelling and support and children's combined physical activity and fruit and vegetable consumption.Cross-sectional data was collected between November 2002 and December 2003 as part of the Health, Eating and Play Study: a study investigating family environmental influences on changes in children's eating, physical activity and obesity throughout childhood and adolescence. The parent responsible for the daily care of the child completed a questionnaire and the children each wore an accelerometer to provide an objective measure of physical activity. Ethical approval was received from Deakin University, the Department of Education and Training Victoria, and the Catholic Education Office.Children aged 10\u201312 years were recruited from 17 State or Catholic primary schools within the Greater Melbourne and Geelong areas in Victoria, Australia . SchoolsParents provided demographic information including their age, sex, language usually spoken at home, marital status, education level and employment status. In addition, parents provided the date of birth and sex of their child enrolled in the study.Parents were asked seven questions about the frequency with which they modelled physical activity or healthy eating, or provided transport or financial support to their child for physical activity and dietary behaviours. For example, 'how often did you and/or the co-carer do physical activity, sport or exercise together with the child in the past week?' Question wording and response scales are presented in Additional file Children's physical activity was assessed using accelerometers . Except for during water-based activities and while sleeping, children were asked to wear the accelerometer on their right hip for eight days. Average duration of moderate- and vigorous-intensity physical activity per day was computed only for children who wore the accelerometer for a minimum of four days including a weekend day , defineTo estimate the time spent per day in moderate intensity physical activity  and vigorous intensity physical activity (6.0+ METs), age-specific movement count thresholds  were appParents were asked how often their child ate 14 different fruits  or types of fruit  and 13 different vegetables  or types of vegetables  in the last week, excluding potatoes. These items were adapted from the most recent Australian National Nutrition Survey (NNS)  and show2) tests of significance. As there were significant differences by gender and by maternal education, all further analyses were conducted separately for boys and girls, and adjusted for maternal education.Initial analyses were undertaken using SPSS statistical software version 14.0. Descriptive statistics were used to describe parent characteristics and the distribution of predictor and outcome variables. The proportion of children achieving \u22652 hours/day of MVPA and the proportion consuming fruit and vegetables \u22655 times/day were compared by gender and maternal education using Pearson Chi-square , and of consuming fruit and vegetables \u22655 times/day (high), respectively, with measures of parental modelling and support entered as independent variables. Four categories were created combining physical activity and fruit and vegetable consumption: high PA/high FV; high PA/low FV; low PA/high FV; low PA/low FV. Multinomial logistic regression analyses were conducted to examine the likelihood of being in each of these categories according to parent modelling and support variables. The 'low PA/low FV' category was used as the referent category. All regression analyses were undertaken using Stata 8  to allow for potential clustering by schools. Parental modelling and parental support items that were significantly associated with combinations of physical activity and fruit and vegetable consumption in the multinomial logistic regression analyses were entered into multivariate multinomial logistic regression models.Active consent was received for 947 children (46% response rate). Due to incomplete physical activity and FFQ data, 172 children were excluded from analyses. The analyses presented here are based on 775 children: 354 boys  and 421 girls . Responding parents were most commonly female (84%), reported speaking English at home (87%) and were married or co-habiting (86%). In addition, 24% of mothers had not completed secondary school, 30% were secondary school educated, 10% had a technical/trade school certificate/diploma and 36% were university/tertiary educated.Table Additional file Logistic regression analyses showed that several of the parental modelling and support items were significantly associated with children's physical activity and fruit and vegetable consumption  for fast food had lower odds of having high levels of MVPA compared to those whose parents reported low support.Several parental modelling and support items were associated with combinations of MVPA and fruit and vegetable consumption in the multivariate multinomial logistic regression analyses shown in Additional file This study examined associations between parental modelling and support and children's physical activity, frequency of consumption of fruit and vegetables and combinations of these behaviours. Current research tends to focus on examining associations between parent and child behaviours in the same behavioural domain , and on single health behaviours. Findings of the present study justify further research examining associations between parental and child behaviours across different domains, and between parental behaviour and clustered health behaviours of children. Such research will provide a better understanding of the transferability of behavioural correlates to different health behaviours, as well as provide a greater depth of understanding about the dynamics of the relationship between parent and child behaviour. Our findings give weight to the importance of addressing parental behaviours in interventions aimed at promoting healthy behaviours among children. They revealed several significant associations that were not always in the expected direction and in most cases differed for boys and girls, suggesting that intervention strategies may need to be tailored according to the child's gender.Parental modelling appears to be a consistent correlate of positive health behaviours for boys and girls. Results of the present study suggest that parents who engage in healthy behaviours with their children are more likely to have children who also exhibit positive health behaviours and not necessarily in the same behavioural domain. For example, we found that parental physical activity modelling was positively associated with high FV consumption among girls and with 'High PA/High FV' among boys and girls in this study. In addition, parental modelling during breakfast was positively associated with high FV consumption among boys and girls. This finding supports previous research of positive associations between parental modelling and children's fruit and vegetable consumption . Eating Parental support for physical activity appears to be an important correlate of girls' health behaviours. Financial support for physical activity was positively associated with girl's MVPA and transport-related support for physical activity was positively associated with girl's 'High PA/High FV'. Such findings support previous research showing that parents who support and facilitate their child's physical activity are more likely to have children who are active . Among bStrengths of the study include the sample of children from a range of socioeconomic and family environment backgrounds, the objective assessment of physical activity, and the use of health guidelines to determine combinations of groups. This study is limited by its cross-sectional design and the generalisability of the results is limited because our sample was drawn from urban schools in Victoria, Australia and so does not represent the population at large. In addition, research has shown weak to moderate associations between parent and child reports of fruit and vegetable intake . HoweverThis study found that parental modelling of and support for physical activity and fruit and vegetable consumption were differentially associated with these behaviours in children across behavioural domains and with combinations of these behaviours. Promoting parents' own healthy eating and physical activity behaviours as well encouraging parental modelling and support of these behaviours in their children may be important strategies to test in future research.The authors declare that they have no competing interests.NP analyzed the data and conceived and drafted the original manuscript. DC designed the overall Health Eating and Play study (HEAPs) project, and provided critical feedback on drafts. AT, JS and SJHB provided critical feedback on drafts. All authors read and approved the final manuscript.Table S1. Description and distribution of parental modelling and support items. The data provided describe the distribution of the modelling and support items used in the study.Click here for fileTable S2. Parental modelling and support items and the odds of achieving \u2265 2 hours/day MVPA and \u2265 5 fruit and vegetables/day among boys and girls. The data provided present results from the binary logistic regression analysis examining the odds of children achieving \u2265 2 hours/day MVPA and \u2265 5 fruit and vegetables/day according to parental modelling and support items.Click here for fileTable S3. Parental modelling and support items and the likelihood of combinations of physical activity and fruit and vegetable consumption among boys. The data provided present results from the multivariate multinomial logistic regression analyses examining the likelihood of combinations of physical activity and fruit and vegetable consumption among boys according to parental modelling and support items.Click here for fileTable S4. Parental modelling and support items and the likelihood of combinations of physical activity and fruit and vegetable consumption among girls. The data provided present results from the multivariate multinomial logistic regression analyses examining the likelihood of combinations of physical activity and fruit and vegetable consumption among girls according to parental modelling and support items.Click here for file"}
+{"text": "Dr. Boaz Zissu was mistakenly omitted from the author byline. He should be listed as the ninth author and is affiliated with Martin (Szusz) Department of Land of Israel Studies and Archaeology, Bar Ilan University, Israel. His contribution included excavating materials for analysis."}
+{"text": "There is limited epidemiological research that provides insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes. This study explores the relationship between housing conditions  and common childhood illness in remote Australian Aboriginal communities for the purpose of informing development of housing interventions to improve child health.Hierarchical multi-level analysis of association between carer report of common childhood illnesses and functional and hygienic state of housing infrastructure, socio-economic, psychosocial and health related behaviours using baseline survey data from a housing intervention study.Multivariate analysis showed a strong independent association between report of respiratory infection and overall functional condition of the house (Odds Ratio (OR) 3.00; 95%CI 1.36-6.63), but no significant association between report of other illnesses and the overall functional condition or the functional condition of infrastructure required for specific healthy living practices. Associations between report of child illness and secondary explanatory variables which showed an OR of 2 or more included: for skin infection - evidence of poor temperature control in the house , evidence of pests and vermin in the house ; for respiratory infection - breastfeeding in infancy ; for diarrhoea/vomiting - hygienic state of food preparation and storage areas ; for ear infection - child care attendance .These findings add to other evidence that building programs need to be supported by a range of other social and behavioural interventions for potential health gains to be more fully realised. Children in remote Australian Aboriginal communities experience exceptionally high rates of common childhood infections including otitis media, skin and respiratory infections and gastroenteritis -4. ThesePoor housing conditions are widely regarded as being an important underlying factor for these poor Indigenous child health outcomes  Housing There is limited previous epidemiological research that has aimed to gain insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes ,23. In rThe construction of additional housing in remote communities has been a priority strategy of Government to improve Aboriginal child health for some years . EffortsA complex mix of political, economic, social and physical factors underlies the poor living conditions and subsequent poor health of children in remote communities . This miThis paper reports on baseline data from a study which aims to assess the impact of building programs on the occurrence of common childhood illness in remote Australian Aboriginal communities. The purpose of the paper is to provide insight into the social and environmental correlates, with a primary interest in the functional state of household infrastructure and carers' reports of a number of common childhood illnesses. The reason for the emphasis in this study on the functional state of infrastructure is that this has been the strongly predominant focus of housing programs,27. The There are several hundred discrete Aboriginal communities in the Northern Territory (NT) that range in size from a single family group to 2500 people. Indigenous people make up almost 30% of the approximately 200,000 people living in the NT, and over 70% of these people  live in locations which are isolated by distance and terrain from the type of modern-day economic activity and services to be found in rural and regional Australian towns . These rThe Housing Infrastructure and Child Health (HICH) study is built around the conceptual framework depicted in Figure has [the child's name] had a [illness]in the last 2 weeks?\" For skin infection, the question was asked separately for scabies, skin sores and boils with two outcome measures coded post-survey. Questions about these outcomes were asked using the colloquial terms used by local community residents to describe these illnesses. Appropriate interpretation of these and all other survey questions was supported by employment of local community residents to assist the survey teams, and by piloting, standardisation and training of surveyors [These were obtained for five childhood illnesses ; and vi. skin infection (includes boils) with no scabies) that are common in remote communities by asking the primary carer if the child had an illness in the last 2 weeks. Specifically, the primary carer of the child was asked \"urveyors .Composite variables reflecting the functional state of items of housing infrastructure that enabled residents to carry out healthy living practices (HLPs) were based on the approach used in previous housing development and research work -40. The These variables reflect measurable indicators of constructs in our conceptual framework Figure . The 'soCrowding is included among the 'socio-demographic variables'  was developed by the Australian Bureau of Statistics (ABS) in consultation with peak Aboriginal health bodies  to measuThe Brief Screen for Depression (BSD)  produces\u00a9.Carer report data on each child health outcome provides a dichotomous measure which is suited to logistic regression modelling. The analysis was carried out in a hierarchical process due to the large number of explanatory variables and follows a broadly similar process to that used in the pilot study  and otheEthics approval for the study was obtained from the Top End and Central Australia Human Research Ethics Committees in-line with the requirements of the National Health and Medical Research Council of Australia.The median reported population for the ten participating communities was 588 (range 250-1450), with 328 houses identified as being home to at least one child in the eligible age range. In 12 (4%) of these houses the householder declined any involvement, in 19 (6%) the householder was not available on at least three repeated visits and in 18 (5%) the householder agreed to be interviewed but refused the house survey. Interview and survey data were available from 279 (85%) houses with children in the eligible age range, and we obtained data on 618 individual children aged seven years or less who were living in these houses - i.e. 85% of the estimated total of 727 children in the eligible age range in these communities (based on surveys of 85% of houses of children in the eligible age range and assuming the same number of children on average in participating and non-participating households).For the 618 children, carers reported each of the conditions of interest to have occurred within the two weeks preceding the survey as follows: skin infection (with no scabies) in 19.7%, scabies (with or without skin infection) in 17.1%; respiratory infection in 28.8%, diarrhoea and/or vomiting in 30.6%, and ear infection in 28.0% (percentages add up to more than 100% because some children had more than one condition reported). Complete data were available for all children for the outcome variables, while for the primary explanatory variables between 5% and 8% of children had missing data. Only a small proportion of children (<10%) had missing data for specific secondary explanatory variables  are seen between ear infection and child age (highest reporting in 1-2 year age group); skin infections and large numbers of adults in the house; scabies and larger numbers of people smoking indoors; ear infection and poor hygienic condition of bedding and sleeping areas; and skin infections and intermediate scores for evidence of adequate temperature control.The results of multivariable models for each of the reported illnesses are presented in Additional file skin infection were a poor score for evidence of pests and vermin in the house, and an intermediate score for evidence that the house had adequate temperature control facilities; for scabies: a poor score for evidence of pests and vermin, and a protective effect of the carer living with her/his spouse; for respiratory infection: a poor overall score for the functional state of house infrastructure, younger age of child (<1 year vs. 3-7 years), carer positive screen for depression, and a protective effect for breastfeeding; for diarrhoea and/or vomiting: younger age of child (<1 year and age 1-2 years vs. 3-7 years), male sex, carer report of negative life events (factor 2), absence of soap in the house, and an intermediate score for food preparation and storage facilities; and for ear infection: age of child (age 1-2 years vs. <1 year), and day care attendance . The strongest associations of reported illnesses and the explanatory variables  are seen between respiratory infection and overall functional condition of the house and breastfeeding; diarrhoea and/or vomiting and ear infection and child age (highest reporting in 1-2 year age group); skin infections and intermediate scores for evidence of adequate temperature control  [Indicators of the socio-demographic environment, carer's psychosocial status and of health related behaviour showed associations with reported occurrence of a number of the childhood illnesses, although these associations were in general not as strong as the association with the measure of functional state of infrastructure. These findings point to the potential importance of interventions which target factors which impact negatively on the psychosocial status of carers and which target health related behaviour, including maintenance of household and personal hygiene. Interestingly, crowding was not independently associated with any of the child health outcomes, possibly due to almost universally high levels of crowding (90% of study houses had 3 or more  people) . With re people) ,49-51. T people) -56, and This study aimed to address one of the major recognised limitations of previous housing and health research - namely the measurement and assessment of the concurrent influence of a range of other related factors with the potential to confound or modify the association between housing condition and health. We also aimed to follow the principles of the MEME model by measuring a range of important exposures as well as a range of outcomes . This waA major strength of this study is the detailed assessment of the functional state of a wide range of items of housing infrastructure and of the hygienic condition of the household environment. Furthermore, the inclusion of multiple communities spread across a wide geographic area enhances the potential generalisability of the findings, at least within the context of remote Australian Aboriginal communities.The study is subject to a number of limitations. First, the cross sectional design limits the potential to discern causative relationships, as the direction of influence between the factors is not clear. Second, some of the constructs represented in the conceptual framework are complex and may not be adequately represented by the indicators used in this study. Furthermore, potential important factors such as the quality of parenting  were notThis study addresses an important gap in housing and health research, including in the specific context of remote Australian Aboriginal communities. The findings are relevant to current efforts to improve health through provision of improved housing  and confBSD: Brief Screen for Depression; CDEP: Community Development Employment Program; CI: Confidence Interval; CRCAH: Co-operative Research Centre for Aboriginal Health; HICH study: Housing Improvement and Child Health study; HLPs: Healthy Living Practices; IHANT: Indigenous Housing Association of the Northern Territory; MEME: Multiple Exposure Multiple Effects; NHMRC: National Health and Medical Research Council; NLES: Negative Life Events Scale; OR: Odds Ratio.The authors declare that they have no competing interests.RB developed the study design and managed the implementation of the study. He developed the data analysis plan and played a primary role in the interpretation of study results and preparation of the manuscript. MS was responsible for data management and data analysis and contributed to preparation of the manuscript. EM developed and implemented the pilot study on which this study is based. She provided expert advice and support in contextualising study findings and assisted with manuscript preparation. DB and SG provided expert advice on data analysis and child health and participated in editing the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/147/prepubTable 2a Socio-demographic variables unadjusted odds ratios  with carer report of child illness in previous two weeks. N = 618 children. Socio-demographic variables and categories are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for fileTable 2b Socio-economic status and financial stress variables and unadjusted odds ratios  for carer report of child illness in previous two weeks. N = 618 children. Socio-economic and financial stress variables and categories are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for fileTable 2c Psychosocial variables and unadjusted odds ratios  for carer report of child illness in previous two weeks. N = 618 children. Psychosocial variables and categories are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for fileTable 2d Health-related behaviour and hygienic state of environment variables and unadjusted odds ratios  for carer report of child illness in previous two weeks. N = 618 children. Health-related behaviour and hygienic state of environment variables and categories are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for fileTable 3 Primary explanatory variables unadjusted odds ratios  with carer report of child illness in previous two weeks. N = 618 children. Primary explanatory variables (FHLP measure) are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for fileTable 4 Multivariable adjusted models for carer report of child illness in previous two weeks. Primary explanatory variables and categories (Specific HLP failed) and secondary explanatory variables (socio-demographic characteristics) are listed and results provided according to illness categories: skin infection - no scabies; scabies w/wo infection; respiratory infection; diarrhoea and vomiting; ear infection.Click here for file"}
+{"text": "In this study it is reported that: (1) the levels of bloodplatelet-activating factor and serum tumour necrosis factorsignificantly increased after coronary ligation and reperfusion,compared with sham-ligated controls, in an anaesthetized rat model;(2) compared with vehicle controls, pretreatment with the PAFantagonist BN 50739  produced significantdecreases in infarct size  and the level of serum TNF ; and (3) a significan positive correlation was found between thelevel of blood PAF or serum TNF and infarct size. The presentresults indicate that PAF and TNF may be important mediatorsinvolved in myocardial ischaemia and reperfusion injury, and thatPAF antagonists may exert a protective effect on ischaemic orreperfused myocardium by inhibiting the interaction of PAF and TNF."}
+{"text": "Knowledge of the appearances of normal bone marrow, metastases involving marrow,            and therapy-related marrow changes shown by MR imaging is necessary in order to avoid            misdiagnosis. This article reviews MR imaging techniques and the findings that allow            distinction of normal yellow (fatty) marrow and red marrow from tumor in marrow,            as well as the identification of marrow changes resulting from radiation therapy or            treatment with marrow-stimulating drugs in patients with musculoskeletal tumors."}
+{"text": "The blood-brain barrier (BBB) is composed of a continuous endothelial layer with pericytes and astrocytes in close proximity to offer homeostatic control to the neurovasculature. The human demyelinating disease multiple sclerosis and the animal counterpart experimental allergic encephalomyelitis (EAE) are characterized by enhanced permeability of the BBB facilitating oedema formation and recruitment of systemically derived inflammatory-type cells into target tissues to mediate eventual myelin loss and neuronal dysfunction. EAE is considered a useful model for examining the pathology which culminates in loss of BBB integrity and the disease is now proving valuable in assessing compounds for efficacy in limiting damage at neurovascular sites. The precise mechanisms culminating in EAE-induced BBB breakdown are unclear although several potentially disruptive mediators have been implicated and have been previously identified as potent effectors of cerebrovascular damage in non-disease related conditions of the central nervous system. The review considers evidence that common mechanisms may mediate cerebrovascular permeability changes irrespective of the initial insult and discusses therapeutic approaches for the control of BBB leakage in the demyelinating diseases."}
+{"text": "Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front."}
+{"text": "In patients with traumatic injury of an upper limb it is often necessary to both secure intravenous (IV) access and record blood pressure noninvasively in the other upper limb. This may cause intermittent obstruction to the flow of IV fluids during cuff inflation. Also backflow of blood into the IV tubing when the cuff is inflated and the temporary stasis which occurs predisposes to clotting of blood in the IV tubing/catheter. Overenthusiastic efforts to push IV fluids without disconnection and flushing of IV line may pose a possible risk of embolizing the clotted blood thrombus into circulation. We describe a simple technique to prevent backflow of blood into the IV tubing when both intravenous fluid infusion and non-invasive blood pressure cuff are in the same limb. This may prevent clot formation and eliminate the risk of an iatrogenic thrombo-embolism. Patients presenting to the emergency department with multiple trauma often require aggressive fluid resuscitation and constant monitoring of their arterial blood pressure. In patients in whom one upper limb is already compromised as a result of trauma both intravenous (IV) fluid infusion and non-invasive blood pressure (NIBP) monitoring have to be done in the other upper limb. IV line placement in the lower limbs is generally avoided because of associated increased risk of thrombophlebitis. Also, the appropriate size thigh cuff for NIBP may not be available especially in the emergency department where such cases often present.Venous stasis and hypercoagulabilty state have been documented to predispose to thrombus formation (Virchow's triad). Stasis of blood  resultinWe have found that if the IV tubing is passed between the NIBP cuff and upper arm (the \"KAPLIT\" technique) it gets compressed whenever the cuff inflates to measure BP Figure . This isNIBP monitoring has long been considered to be a safe monitoring method. Underreporting of the complications associated with NIBP monitoring has lead to limited awareness among clinicians of its potential complications . The repIV: intravenous; NIBP: non invasive blood pressure.The authors declare that they have no competing interests.KC conceived of the technique and participated in its design and coordination, observing the efficacy and drafted the manuscript. LG helped in observing the efficacy of technique and preparation of manuscript. RA helped to draft the manuscript and gave final approval to submit manuscript. All authors have read and approved the final manuscript.KC- Senior Resident, Department Of Anaesthesia and Intensive Care, Maulana Azad Medical College & associated Lok Nayak Hospital, New Delhi, IndiaLG- Ex-DNB Student, Department Of Anaesthesia and Intensive Care, Maulana Azad Medical College & associated Lok Nayak Hospital, New Delhi, IndiaRA- Director, Professor and Head, Department Of Anaesthesia and Intensive Care, Maulana Azad Medical College & associated Lok Nayak Hospital, New Delhi, India"}
+{"text": "The precision and validationof the method have been established using both types of samplesand the results obtained compare well with those of the methodused for routine analysis in official agricultural laboratories.A fully automatic method for the determination of organic matterhas been implemented using a robotic station. The overall processinvolves weighing, dilution, oxidation in very harsh workingconditions (K"}
+{"text": "Primary care providers (PCPs) can perform a central role in bridging mental health and public health. This role was recognized by the Mental Health/Mental Illness Expert Panel convened by the Centers for Disease Control and Prevention's Division of Adult and Community Health. PCPs, who form the backbone of the US health workforce, can serve a critical role in all stages of mental health delivery, from prevention through early detection, and effective ongoing care.PCPs (in their practices) have a unique opportunity to reduce the risk for onset of mental disorders. Approximately 70% of Americans see a general practitioner in any given year , making Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Primary Care Version (DSM-IV PC) includes tools for differential diagnosis of psychiatric disorders in general medical settings (PCPs are ideally poised to provide effective secondary prevention through the early detection and treatment of common mental disorders. Diagnostic tools designed for the primary care setting have been developed to facilitate the identification of common mental disorders in primary care. One example is the Primary Care Evaluation of Mental Disorders diagnostic system , which fsettings .Primary care clinics are increasingly becoming critical sites for tertiary prevention, the ongoing treatment of common mental disorders to reduce disease. During the past 20 years, the locus of mental health treatment in the United States has shifted from specialty mental health to primary care medical settings, and more than half of treatment for mental disorders now occurs in general medical settings . HoweverPolicy initiatives such as the patient-centered medical home movement  are work"}
+{"text": "Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and the results are reported.Some acylhydrazine derived ONO donor Schiff bases and their Co(II) and Ni(II) complexes have been prepared having the same metal ion (cation) but different anions. These synthesized metal(II) complexes have been characterized on the basis of their elemental analyses, magnetic moment, molar conductance, and IR and electronic spectral data. All of the Schiff base ligands function as tridentates and the deprotonated enolic form is preferred for coordination. In order to evaluate the effect of anions on the bactericidal activity, these synthesized complexes, in comparison to the uncomplexed Schiff bases have been screened against bacterial species.,"}
+{"text": "To the Editor: Recently, the directors of Biosafety Level 4 (BSL-4) laboratories in the United States published their views of the requirement of having \u22652 persons present at all times while biological work is undertaken in a BSL-4 laboratory (Surveillance video monitoring and data storing have their place in protecting laboratory facilities from unauthorized access and theft of materials, but their effectiveness for ensuring proper handling of pathogens is quite limited. Finally, we agree with the authors that both biosafety and biosecurity must be founded on careful selection and monitoring of staff, without which even the most sophisticated of control systems would fail."}
+{"text": "Background: Disseminated cytomegalovirus (CMV) infection is relatively uncommon, occurring primarily in immunocompromised hosts and neonates. Patients with acquired immunodeficiency syndrome (AIDS) are the most common hosts, with symptoms secondary to lung and eye involvement. There have been no reports of symptomatic CMV infection of the pelvis in women.Case report: This case is the first described of acute symptomatic CMV infection of the genital tract in a woman with AIDS. Her presenting symptoms were the result of acute CMV oophoritis. In addition, CMV was found in the endometrium and endosalpinx (an infected structure heretofore unreported).Conclusion: The increasing prevalence and incidence of AIDS in women should make us aware of the possibility of opportunistic, symptomatic CMV pelvic infection."}
+{"text": "We describe the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance system. Elements of the system critical for successful reduction of nosocomial infection rates include voluntary participation and confidentiality; standard definitions and protocols; identification of populations at high risk; site-specific, risk- adjusted infection rates comparable across institutions; adequate numbers of trained infection control professionals; dissemination of data to health-care providers; and a link between monitored rates and prevention efforts."}
+{"text": "That finding prompted a systematic investigation that links phthalate-containing medications with high internal exposure to these chemicals .Until recently, most of the concern surrounding the health risks of phthalates has focused on the use of these plasticizers in toys, personal care products, food packaging, and medical equipment such as intravenous tubing. A case report in 2004 raised the possibility that certain prescription medications may also be a source of phthalate exposure for some people The 2004 case study pinpointed Asacol\u00ae, a medication for treating ulcerative colitis, as a probable source of phthalate exposure. Asacol is covered with an enteric coating of dibutyl phthalate (DBP) that prevents the medication from degrading before it reaches the small intestine. Concentrations of the main metabolite of DBP in the urine of the case study subject corresponded to an uptake of DBP exceeding by two orders of magnitude the 95th percentile reported by the Centers for Disease Control and Prevention in the general population. The concentrations also surpassed the reference dose established for DBP by the U.S. Environmental Protection Agency (EPA) on the basis of animal testing.To assess possible links between phthalate-containing prescription medication usage and excreted metabolites, the investigators searched National Health and Nutrition Examination Survey (NHANES) data from survey periods between 1999 and 2004 when urine samples were tested for phthalate metabolites and participants were asked about their use of prescription medications. Various enteric-coated medications identified as likely to contain phthalates included mesalamine (the generic form of Asacol), didanosine , omeprazole (which inhibits gastric acid secretion), and theophylline (used to treat asthma and other lung diseases).Among the 6 documented mesalamine users, average urine concentrations of DBP metabolites were 50 times higher than those of nonusers. For 2 of the 6 mesalamine users, the DBP metabolite concentrations pointed to uptake exceeding the EPA\u2019s reference dose. Users of the other phthalate-containing medications also had significantly higher concentrations of some metabolites than did nonusers, though the gaps between users and nonusers were considerably smaller than for mesalamine. The NHANES data also showed that at least 3 women who reported taking phthalate-containing medications were pregnant.[EHP113:1056\u20131061 (2005)]. The authors of the new study write that phthalate-containing medications are among some of the most widely prescribed drugs in the United States, which implies that many people, including pregnant women, may be exposed to high concentrations of phthalates.These findings call for more investigation, the authors write, particularly because some phthalates cross the placenta and cause reproductive and developmental effects in laboratory animals. In one study of male infants, increasing prenatal exposure to background levels of phthalates was associated with a decrease in the distance between the anus and base of the penis, indicating incomplete male reproductive development"}
+{"text": "This special issue of PPAR Research is dedicated to \u201cPPARs, RXRs and Drug Metabolizing Enzymes\u201d. Knowledge of PPAR biology, over the past five years, has dramatically increased our understanding of the potential therapeutic usefulness of these receptors in metabolic alterations associated with disease process of alcoholic and non-alcoholic fatty liver disease and metabolic syndrome. In addition, the utility of PPAR agonist in the treatment of liver disease by normalizing hypertriglyceridemia, dyslipidemia, and the toxic effects of bile acids has a sound scientific basis in the ability of PPAR receptors to control lipid oxidation and disposal as well as regulators of hepatic inflammation. Further insight into both the indirect and direct effects of dual and pan PPAR agonist may potentiate the development of new therapeutic modalities to treat fatty acid oxidation disorders, dyslipidemia, inflammation, and bile acid accumulation associated with several liver diseases and metabolic syndrome. \u03b1 regulates bile acid synthesis, conjugation, and transport by phase II and III enzymes. This review also provides an updated report on how PPARs regulate cholesterol synthesis, absorption, and reverse cholesterol transport, and how PPAR agonist may be used to treat cholestatic liver disease. This review also raises important questions concerning the use of PPAR agonist in treating bile acid accumulation in several liver diseases, which leads to hepatocyte injury, impaired liver metabolic function, progressing to liver fibrosis and cirrhosis. Further research needs to focus on how selective PPAR agonist and isoforms regulated bile acid conjugation and thereby prevent bile acid toxicity observed in cholestastic disease. The conjugation of bile acids by UDP-glucuronosyltransferase, a PPAR target gene further emphasizes the importance of PPAR in bile acid toxicity. In addition, induction of the sulfotransferase genes by PPAR and sulfonation of cholesterol in keratinocyte differentiation suggests that these phase II genes have an important role in epidermal wound healing. Finally, although numerous studies in animal models of disease have dramatically increased our understanding of how PPARs not only regulate drug metabolism and the elimination of drugs and toxic endogenous metabolities in disease progression, the application of these results to human in the design of effective PPAR agonist has all too often led to adverse drug interactions and unacceptable drug toxicity. A fourth review in this series details the exciting possibility of using a human hepatocyte chimeric mouse model to predict metabolism and possible effectiveness of new PPAR agonist in humans. The investigators clearly show the utility of this model system by the increased phosphatidylcholine transport into bile canaliculi through induction of human ABCB4 transporter by benzafibrate activation of PPAR. There are marked species differences in genes and proteins associated with the absorption, distribution, metabolism, and excretion (ADME) of xenobiotics and drugs, thus the human hepatocyte chimeric mice may not only be used for increasing the safety and effectiveness of lead drugs, but may also serve as a model system to study human liver disease and assess the potency and efficacy of dual and pan PPAR agonist in preventing or delaying disease progression. The final review in these series details how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and explores how medium chain fatty acid (MCFA) CYP4A and long chain fatty acid (LCFA) CYP4F\u03c9-hydroxylase genes are regulated in fatty liver. The authors propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis. Articles included in this special issue highlight the importance of PPARs and RXR in drug metabolism and hepatic diseases associated with metabolic disorders. Alterations in drug metabolizing gene expression in different disease states due to the differential expression of PPAR isoforms highlights the importance of PPAR in disease progression and as therapeutic target in the amelioration of disease progression. The first review summarizes past and new developments in alcoholic fatty liver disease (ALD) and how PPAR/RXR regulates phase I enzymes in alcohol metabolism and the redox balance of cells. The direct impairment of PPAR by acetaldehyde results in reduction of NAD+ pool leading to alterations in lipid metabolism, increased oxidative stress, and increased pro-inflammatory cytokines, chemokines and acute phase proteins, which may be central in the onset and perpetuation of mechanism in the clinical progression of alcoholic liver disease (ALD). A second review focuses on the role of PPAR isoforms in the regulation of bile acid and cholesterol metabolism, with specific insight into how PPARWe thank the editors for the opportunity to share with other investigators these interesting reviews on drug metabolizing genes regulated by PPAR/RXR. It is apparent that drug metabolizing genes not only play a pivotal role in drug efficacy, drug toxicity, and adverse drug reactions, but also a critical and crucial role in the development and progression liver disease. Therefore, understanding how the PPAR genes and other hormone nuclear receptors are regulated during disease processes will provide us the opportunity to design effective therapeutic modalities to treat disease by the inactivation, conjugation, and transport of toxic endogenous metabolities. James P. HardwickJames P. HardwickJohn Y. L. ChiangJohn Y. L. Chiang"}
+{"text": "Medical histories of themselves and their first-degree relatives were obtained from parents of 82 leukaemic children (54 acute lymphoblastic (ALL), 28 acute myeloblastic (AML)) and from control couples matched for age. The possibility of a primary familial immunological abnormality as an aetiological factor in childhood leukaemia was suggested by binding some infections significantly more frequently reported in parents than in controls, but more strongly supported by the finding of a significantly (P less than 0.02) increased prevalence of disorders associated with autoimmunity  amongst members of ALL families compared to those of controls. Analogy with Down's syndrome and the strain of NZB mice, in which diminished T-cell function is associated with autoimmune disease and lymphoid neoplasia, is discussed. Varicella and herpes zoster occurred respectively in 2 ALL mothers during their pregnancies involving the patients and in none of the other 388 pregnancies here reported. This supports previous evidence that antenatal varicella infections may be of aetiological importance in some cases of ALL."}
+{"text": "We examined 26 gastric carcinomas from British patients for mutations of the APC gene using a single-strand conformation polymorphism (SSCP) and heteroduplex assay in conjunction with the protein truncation test (PTT). In addition, we performed loss of heterozygosity (LOH) analysis of the APC and MCC genes. We detected an inactivating somatic mutation in one gastric tumour. LOH of APC was observed in one of 12 informative cases (8%) and of MCC in two of 20 cases (10%). We thus find that alteration of the APC and MCC genes are infrequent in gastric cancers from the British population. Tumour-suppressor genes on other chromosomes must play a more significant role in the development of these tumours."}
+{"text": "Gallus gallus) is the premier avian model for biological research; however, only a limited number of studies have compared chicken and mammalian aquaporins. The identification of aquaporins that share functional motifs or are expressed in the same tissues in human and chicken could allow the further functional analyses of homologous aquaporins in both species. We hypothesize that integrative analyses of protein sequences and body site expression of human, mouse, rat and chicken aquaporins has the potential to yield novel biological hypotheses about the unexpected cellular roles of aquaporins beyond transmembrane water transport.Proteins that selectively transport water across the membranes of cells are recognized as important in the normal functioning of the body systems of vertebrates. There are 13 known mammalian aquaporins (AQP0 to AQP12), some of which have been shown to have unexpected cellular roles beyond transmembrane water transport. The availability of non-mammalian vertebrate animal models has the potential to provide insight into the emergence of diverse function in the aquaporins. The domesticated chicken  were identified in which there is suggested expression of at least one mammalian and one chicken aquaporin. This study demonstrates that modern on-line analysis tools, a novel matrix integration technique, and the availability of the chicken genome for comparative genomics and expression analysis enables hypothesis generation in several important areas including: (i) alternative transcription and speciation effects on the conservation of functional motifs in vertebrate aquaporins; (ii) the emergence of basolateral targeting in mammalian species; (iii) the potential of the cysteine-rich AQP11 as a possible target in the pathophysiology of neurodegenerative disorders such as autism that involve Purkinje cells; and (iv) possible impairment of function of pancreas-expressed AQP12 during pancreatotropic necrosis in avian influenza virus infection.The investigation of aquaporin function in chicken and mammalian species has the potential to accelerate the discovery of novel knowledge of aquaporins in both avian and mammalian species. Proteins that selectively transport water across the membranes of cells are recognized as important in normal functioning of the body systems of vertebrates. These homologous proteins are collectively referred to as aquaporins and include a subset called aquaglyceroporins that are able to transport glycerol, urea and other small solutes in addition to water . There aGallus gallus is the premier avian model for biological research [The domesticated chicken research -10. Furtresearch . This brresearch .Apart from transmembrane/epithelial water transport, recently suggested unexpected cellular roles of mammalian aquaporins include cell migration, cell volume regulation, mitochondria metabolism, neural signal transduction, renal glycerol clearance and vesicular swelling ,13. The There are a limited numbers of reports that have compared the body site expression of chicken and mammalian aquaporins. Comparison of nucleotide sequences of chicken AQP2, AQP4 and AQP5 to their rat and human orthologs has revealed an overall identity of 75\u201390% and similarity in tissue distribution . In addiThe objectives of the investigation reported in this article were to (1) determine the impact of alternative transcription and speciation on functional motifs of aquaporin gene transcript models predicted from the genomes of human, mouse, rat and chicken; and (2) determine body sites common to human, mouse, rat and chicken with suggested aquaporin expression. We hypothesize that integrative analyses of protein sequences and body site expression of human, mouse, rat and chicken aquaporins has the potential to yield novel biological hypotheses about the unexpected cellular roles of aquaporins beyond transmembrane water transport. Our high-throughput comparative sequence analysis revealed the potential impact of alternative transcription and speciation on the conservation of functional motifs in human, mouse, rat and chicken aquaporins. Furthermore, by using controlled vocabulary of terms describing body sites in the UniGene database, an integrated view of suggested tissue expression of aquaporins for these four organisms was generated.The integrative analyses of protein sequences and tissue expression profiles presented in this article provides novel insights into the potential function of cysteine-rich AQP11 in the pathophysiology of autism and evidence for involvement of pancreas-expressed AQP12 in the pathology of highly pathogenic avian influenza virus infections. The investigation of aquaporin function in chicken could accelerate the discovery of novel knowledge on human aquaporins especially during early development.In order to determine the impact of alternative transcription as well as speciation on the conservation of functional motifs in aquaporins, we first compiled the aquaporin types with entries in the Entrez Gene  and EnseOrnithorhynchus anatinus) had a YKLL motif aligned to the NKLV motif of the chicken sequence  in all the isoforms examined. Only three protein isoforms from transcripts ENSRNOT00000018091, ENSMUST00000084986 and ENST00000313578 contained the second NPA motif. AQP11 sequences had a high number of cysteine residues compared to other aquaporin types including a triplet CCC present in the N-terminal of protein sequences produced by transcripts ENSMUST00000055379, ENSMUST00000084986 and ENST00000313578. The two rat sequences had a CYC motif while chicken had a CAC motif. Cysteine residues are known to interact with sulfhydryl-reactive metals such as mercury, cadmium, lead, and arsenic . A totalA total of 44 UniGene aquaporin entries from human (13), mouse 12), rat (10) and chicken (9) were identified has having suggested expression in at least one of 57 body sites based on Expressed Sequence Tags (EST) counts  and an amphibian , the ancestral motifs of the sorting motifs found in human may be NKLL or NMLM  tool , the NKLM Figure . Thus, t genomes ,32. ThesWe have used a binary encoding integration strategy to gain a comprehensive view of suggested tissue expression of aquaporins for four organisms. Higher-order patterns in a binary vector space that encodes the presence (1) or absence (0) of feature of interest is an approach for integrating genome-wide numerical datasets -35. SeveThe functions of AQP11 and AQP12 in vertebrate physiology are not completely understood . We obseIn the case of AQP12, there was suggested expression in the pancreas of human, mouse and chicken Table  with chiThis study demonstrates that the chicken genome combined with a comprehensive controlled vocabulary-facilitated integration of UniGene suggested body site expression can drive generation of hypotheses related to the function of avian and mammalian aquaporins. We describe the generation of hypotheses related to (i) the impact of alternative transcription and speciation on the conservation of functional motifs in human, mouse, rat and chicken aquaporins; (ii) identification of the emergence of basolateral targeting in mammalian species (iii) possibility of cysteine-rich AQP11 as target in the pathophysiology of neurodegenerative disorders; and (iv) impact on the function of pancreas-expressed AQP12 during pancreatotropic necrosis associated with avian influenza virus infection.Predictions of genes encoding aquaporins from human, mouse, rat and chicken genomes were obtained from the Ensembl project (Release 50 July 2008)  and the Each NCBI UniGene Cluster contains set of transcript sequences that appear to come from the same transcription locus (gene or expressed pseudogene) as well as other information including expression profile in body sites and developmental stages . The UniThere was need to identify chicken and mammalian aquaporins that were expressed in the same body site based on controlled vocabulary term used in UniGene. Therefore, a 4-digit binary signature was constructed to encode the presence or absence of species aquaporin expression. Thus a matrix consisting of 52-digit binary signature and the number of body sites was constructed and visualized using matrix2png .The authors declare that they have no competing interests.RDI, RVR and HHPC conceived and designed the study. RDI wrote scripts to retrieve compare and integrate datasets and drafted the manuscript. RVR carried out sequence alignment and motif analysis and helped to draft the manuscript. CDJ assembled the aquaporin datasets from multiple organisms, evaluated binary matrix integration and helped to draft the manuscript. TOO developed scripts and computational pipelines to facilitate literature extraction, search and visualization of binary matrices; and helped to draft the manuscript. HHPC helped to interpret the study results, coordinated the study and helped to draft the manuscript. All authors read and approved the final manuscript.Multiple sequence alignment of aquaporins isoforms from human, mouse, rat and chicken. ClustalW multiple sequence alignment of aquaporin types from human, mouse, rat and chicken. Identifiers preceded by ENST, ENSMUST, ENSRNOT, and ENSGALT are for human, mouse, rat and chicken transcripts respectively.Click here for fileUniGene Transcripts per million and spot intensity of human, mouse and chicken AQP12 expressed in pancreas.Click here for file"}
+{"text": "These agents loweredthe activity of rat hepatic rate limiting enzymes for the synthesis of cholesterol and triglycerides. The effectsof these agnets on cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase and HMG-CoAreductase activities were reduced by a magnitude to explain the reduction of serum cholesterol levelsafforded by the compounds. The reduction of acetyl CoA carboxylase,"}
+{"text": "The marine biogeochemistries of carbon and nitrogen have come under increased scrutiny because of their close involvement in climate change and coastal eutrophication. Recent studies have shown that the high-temperature combustion (HTC) technique is suitable for routine analyses of dissolved organic matter due to its good oxidation efficiency, high sensitivity, and precision. In our laboratory, a coupled HTC TOC-NCD system with a sample changer was used for the automated and simultaneous determination of dissolved organic carbon (DOC) and total dissolved nitrogen (TDN)in seawater samples. TOC control software was used for TOC instrument control, DOC data acquisition, and data analysis. TDN data acquisition and manipulation was undertaken under LabVIEW. The combined system allowed simultaneous determination of DOC and TDN in the same sample using a single injection and provided low detection limits and excellent linear ranges for both DOC and TDN. The risk of contamination has been remarkably reduced due to the minimal sample manipulation and automated analyses. The optimised system provided a reliable tool for the routine determination ofDOC and TDN in marine waters."}
+{"text": "Crocidolite asbestos fibres, suspended in physiological saline, were injected subcutaneously into one or both flanks of 95 CBA/Lac female mice; 75 control mice received injections of saline only. Most animals were killed at chosen intervals of between 2 and 42 days after injection but some were left for longer periods of up to 623 days. At autopsy, many lymphoid and non-lymphoid structures were removed and examined for the presence of asbestos by the following techniques: haematoxylin and eosin staining followed by conventional and polarized light microscopy; Perl's stain; microincineration followed by phase-contrast microscopy; maceration with KOH followed by phase-contrast microscopy; and electron microscopy.A combination of haematoxylin and eosin staining and microincineration was found to be the most convenient and reliable method for demonstrating asbestos fibres in the tissues. Electron microscopy was essential for detecting very small fibres and for locating them to specific intracellular structures.The morphological findings indicate that some migration of asbestos fibres away from the initial site of injection takes place. Dissemination is usually along lymphatic pathways and fibres tend to accumulate in the lymphoid tissues, particularly in the regional (axillary) lymph nodes; smaller amounts were found in inguinal, mediastinal and lumbar nodes. The fibres were usually intracellular, lying inside the phagosomes of macrophages, but larger fibres weresometimes encountered lying free. Small numbers of fibres were seen in the spleen and also in non-lymphoid organs such as the liver, kidneys and brain\u2014suggesting that some asbestos may enter the blood stream. There was no evidence of massive or selective spread to subserosal tissues in the thorax or abdomen, though trapping of asbestos fibres was observed in pleural \u201cmilky spots\u201d in long-term survivors. The possible role of milky spots in the development of pleural plaques and mesotheliomata is discussed."}
+{"text": "The vascularisation of rectal and oesophageal carcinomas and of normal mucosa was studied using histochemical and immunohistochemical methods. Endothelial cells were stained for alkaline phosphatase (AP) using an azo-dye procedure. Histochemical results were compared with the immunohistochemical identification of endothelial cells using the monoclonal antibody BW 200 recognising an epitope restricted to human endothelial cells. In the AP experiments the simultaneous reactivity of stromal tissue often precluded the exact evaluation of tumour blood vessels. Immunohistochemistry facilitated the identification of vessels in neoplastic tissues and allowed a quantitative analysis of vascular volume by means of point-counting. Vascular volumes of normal tissues exceeded those of tumours by a factor of 1.6. This immunohistochemical technique has potential application in studying the importance of tumour blood supply in man, especially in relation to radiotherapy."}
+{"text": "This inhibition was reversed (blocked) by the addition of the patients' own sera. Both LAI and blocking were tumour-type specific, but showed complete cross-reactivity within each type of tumour .The leucocyte adherence inhibition (LAI) test, previously described for the detection of cell mediated immunity and serum blocking factors associated with murine tumours, has now been adapted for use with human cancer patients. Blood leucocytes from these patients, mixed The LAI test could be of great value in diagnosis and evaluation of treatment, since it seems to reproduce consistently the findings made by more elaborate techniques but has the advantage of being simple, rapid and inexpensive."}
+{"text": "The kinetics of development and subsequent growth of a C3H mouse mammary tumour after implantation of 10(6) cells was quantified by observation and statistical analysis of latent period and growth rate for different categories of tumour. These comprised control tumours, tumours recurring after large single doses of X-rays alone and in combination with misonidazole, tumours developing from cells implanted both outside and within the sites of tumours previously cured by irradiation, tumours developing from cells implanted in heavily irradiated skin, and tumours developing from cells taken from tumours recurring after irradiation and re-implanted in untreated skin. The kinetics of development and growth of tumours in host animals previously treated by i.p. injection of killed tumour cells was also quantified. The results confirm that tumour development and growth is significantly perturbed by irradiation of host tissues both before and after tumour transplantation, and that this perturbation involves an extended latent period, a slower average rate of growth and a less uniform pattern of growth. These effects result from localized radiation damage to host tissues, are not attributable to residual damage to irradiated tumour cells, and are not markedly dose-dependent within the dose range 25--80 Gy. These results are consistent with the complete sterilization of host endothelial cells by doses of 25 or more. In marked contrast to the growth-slowing effect of irradiation, the treatment of host animals by previous injection of radiation-killed tumour cells led to a reduced latent period and a faster average rate of growth."}
+{"text": "Sir,Mastroianni et al.  report hWe agree with the speculation of the authors, as this was also our experience. Indeed, children who received surgical intervention for esophageal atresia have high incidence of respiratory function abnormalities  and bronTreatment of underlying respiratory disease instead of anti-reflux therapy may be warranted in children with a history of surgical repair of esophageal atresia and tracheoesophageal fistula, especially when lung function studies confirm respiratory involvement."}
+{"text": "The clinical, pathological and immunological features in 5 cases of T-cell lymphoma without overt marrow involvement are described. Classification of this distinct sub-group of lymphoma on morphological and clinical criteria alone has been shown to be unreliable, and precise recognitionr equires additional information from cytochemical and immunological marker studies of peripheral blood and lymph nodes. Valuable information may also be obtained from analysis of pleural fluid. The accurate identification of this sub-group assumes new clinical relevance in the light of the considerable improvement in prognosis reported with treatment schedules that are effective in acute lymphoblastic leukaemia."}
+{"text": "Suppression subtractive hybridization (SSH) is frequently used to unearth differentially expressed genes on a whole-genome scale. Its versatility is based on combiningcDNA library subtraction and normalization, which allows the isolation of sequencesof varying degrees of abundance and differential expression. SSH is a complex processwith many adjustable parameters that affect the outcome of gene isolation.We presenta mathematical model of SSH based on DNA hybridization kinetics for assessing theeffect of various parameters to facilitate its optimization. We derive an equationfor the probability that a particular differentially expressed species is successfullyisolated and use this to quantify the effect of the following parameters related tothe cDNA sample: (a) mRNA abundance; (b) partial sequence complementarity toother species; and (3) degree of differential expression. We also evaluate the effectof parameters related to the process, including: (a) reaction times; and (b) extentof driver excess used in the two hybridization reactions. The optimum set of processparameters for successful isolation of differentially expressed species dependson transcript abundance. We show that the reaction conditions have a significanteffect on the occurrence of false-positives and formulate strategies to isolate specificsubsets of differentially expressed genes. We also quantify the effect of non-specifichybridization on the false-positive results and present strategies for spiking cDNAsequences to address this problem."}
+{"text": "The induction of chromosome damage by the Platinum complex CHIP in Chinese hamster ovary (CHO) cells has been studied, together with the relationship between cell survival and aberration frequency. The type and frequency of chromosome aberrations observed in asynchronous and G1 phase treated cells indicated a similar mode of action to that of bifunctional alkylating agents. A log-linear relationship was observed between the frequency of chromatid aberrations (excluding gaps) and the level of survival after CHIP treatment, with approximately one aberration per cell corresponding to 37% survival."}
+{"text": "Characteristics of a panel of seven human ovarian tumour cell lines are presented. Positive staining with HMFG2 and ultrastructural identification of desmosomes confirmed the epithelial nature of the cell lines. The lines showed wide variations in ploidy, doubling times and clonogenicity in soft agar. Both vimentin and keratin were equally expressed in five lines, one line showed strong preferential expression of keratin and one line showed preferential expression of vimentin. Karyotypic changes associated with ovarian cancer were identified in all the lines. Four of the seven cell lines showed loss of chromosome material distal to 11p13-15. These cell lines offer considerable potential for research into the biology and genetics of ovarian cancer."}
+{"text": "Explants of fresh biopsy specimens from non-neoplastic nasopharyngeal (NP) mucosa, nasopharyngeal carcinoma (NPC), other tumours (OT) of the head and neck and freshly removed tonsils were treated with an Epstein-Barr virus (EBV) preparation from B95-8 cells and cultured. The mainly epitheloid outgrowths from these infected explants were then compared with those from their respective uninfected controls at 14 days. Growth stimulation occurred with a significantly higher frequency, and the degree of stimulation was generally higher with the infected NP explants than those of the similarly infected explants of other origins. Furthermore, after treatment with the virus preparation, several of the outgrowths from the NP explants showed growth characteristics and cellular morphology typical of those of transformed cells. Light microscopy has shown the changed NP cells to have epithelial characteristics. This is now being verified by electron microscopy, which has so far shown the presence of keratin fibrils and desmosomes in one specimen examined. They are also being examined for the presence of EBV-DNA and EBNA, and other features of transformation, including malignant tendency, by passage through athymic nude mice."}
+{"text": "This review higlghts key aspects of corticotropin releasing hormone (CRH) biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h) CRH gene: (1) a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2) a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system."}
+{"text": "We evaluated colony formation in soft agar by cells obtained after mechanical and/or enzymatic disaggregation of 455 malignant human tumours. Counting and assessment of cell colonies in the agar plates were done by inverted microscopy, computerized image analysis, and inspection of serial photomicrographs of the agar plates. Our results indicate that standard methods of tumour disaggregation did not usually produce single-cell suspensions and that aggregates of tumour cells varying greatly in size were placed in the agar. Most groupings of cells identified as colonies 1-3 weeks after plating arose from enlargement of preexisting aggregates of cells."}
+{"text": "The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine leukocyte antigen (SLA) complex jointly determine risk of SSCM in pedigreed animals. These loci also influence severity of affection, accounting for approximately 20% of the phenotypic variation in quantitative tumour burden."}
+{"text": "The blood, spleen and liver of RFM/Un mice were examined by means of electron spin resonance (ESR) throughout the course of myeloid leukaemia induced by i.v. injection of leukaemic spleen cells. Marked changes in the concentration of iron transferrin and caeruloplasmin were observed in the blood 1 day after injection. As the disease progressed, changes occurred in the concentrations of the ascorbyl radical and of paramagnetic metal complexes in both spleen and liver. These changes are compared with those induced in RF/J mice injected with normal and leukaemic spleen cells from RFM/Un mice."}
+{"text": "Principal component analysis and evolving factor analysis wereapplied to the study of the speciation of Cu (II)/ethylenediamine/ oxalate. Two programs were designed, based on mathematical algorithms. Error functions were calculated for evaluating the number of species. Submatrix analysis plots were constructed toestimate the species present in the system. The method should proveuseful in studies of complex systems in environmental samples."}
+{"text": "Competitive polymerase chain reaction assays have been developed for the quantitation of oestrogen receptor mRNA and two oestrogen-regulated mRNAs (progesterone receptor and pNR-2/pS2) in breast cancer cells. These assays are more sensitive than traditional hybridisation techniques, do not require the use of radioisotopes, measure absolute amounts of messenger RNAs and can be used to measure the expression of mRNAs in small numbers of tumour cells obtained by fine-needle aspiration (FNA). These assays should prove useful for predicting the hormone responsiveness of breast cancer from tumour cells obtained by FNA at diagnosis and could be particularly useful in the management of elderly/frail patients who receive primary tamoxifen, or in other patients for whom tumour tissue for standard biochemical measurements is not available."}
+{"text": "The objective of this study was to determine the putative neuropathological effects in young chickens after administration of a single dose of 55 mg/kg bw chlorpyrifos. The gross lesions of the nervous system comprised of congestions in the brain. Microscopic examination of brain showed mild congestion of cerebral blood vessels and mild perivascular cuffing of lymphomononuclear cells in the cerebral cortex and necrosis of the neurons. The interesting findings were the presence of cytoplasmic vacuolations of cerebral neurons and swelling of the endothelial cell of the cerebral capillaries. Cerebellum showed congestion and hemorrhages in the granular layer and necrosis of Purkinje cell. Sciatic nerve exhibited mild edema, swelling and degeneration of axons, and swelling of Schwann cells. There was a significant inhibition of plasma cholinesterase enzyme activity in chickens administered with chlorpyrifos compared to chickens of control group. The study revealed that administration of chlorpyrifos produces neuropathological lesions in chickens shortly after exposure. It is us periods.The present study was undertaken to determine the neuropathological effects of a single dose of CPF in young chickens other than delayed neuropathy. The neuropathologic lesions in the central and peripheral nerves systems are documented.A total of thirty 50-day-old layer chickens were randomly divided into two groups of 15 each. Chickens in group 1 were fasted for six hours before insecticide administration and received single dose of 55 mg/kg bw CPF orally. Group 2 served as a control. The chickens were closely watched for the presence of clinical signs. The experiment was performed after getting the permission from Institutional Animal Ethics Committee (IAEC), GADVASU, Ludhiana, India. The regulations addressing animal use and proper attention and care have been given to the chickens used in this experiment.Blood samples were collected from all chickens of control group (n = 15) and from eight birds of CPF group immediately before death. Plasma was separated and immediately used for the analysis of acetylcholinesterase enzyme (AChE), using commercial kits  on Biotron BTR-830 analyzer.\u03bc paraffin sections were cut and stained with hematoxylin and eosin as per the method of Luna.[Representative samples from brain and sciatic nerve were collected in 10% neutral formalin. After washing in running water followed by dehydration in alcohol, tissues were embedded and 5  of Luna.CPF at the dose of 55 mg/kg orally produced cholinergic signs commencing two hours after administration which included excitation followed by sluggishness, watery diarrhea, excessive salivation changing to drooling, and rigid stance with dropping of wings. The chickens were unable to stand and showed paralysis and convulsions before death.Eobania vermiculata revealed highly vacuolated neuronal cytoplasm. Such vacuoles were regarded as a cellular defense mechanism against injurious substances that segregated in the vacuoles.[et al.[The chickens were necropsied immediately after blood collection and after death. The sacrificed chicks were subjected to gross examination and tissues collected were used for histopathological findings. The gross lesions of the nervous system comprised of congestions in the brain. Microscopic examination of brain showed mild perivascular cuffing of lymphomononuclear cells in the cerebral cortex . Interesvacuoles. The secovacuoles.. Higher s.[et al. reporteds.[et al. Similar s.[et al. Cerebells.[et al. and deges.[et al.. It is cs.[et al..In the present study, the neuropathological changes were associated with significant inhibition of plasma cholinesterase enzyme activity in chickens administered with CPF compared with chickens of control group. The insecticidal action of CPF stems from inhibition of AChE by CPF -oxon, resulting in acute cholinergic toxicity.50 in hens resulted in OPIDN, but at doses that required extensive and aggressive antidote treatment to keep the birds alive, both before treatment and throughout the treatment and recovery periods.[Usually, single neurotoxic doses of organophosphates in chicken give rise to nerve fiber degeneration after a latent period of one week or more. However  periods.In conclusion, CPF produced neuropathological lesions in chickens shortly after administration. However, the neuropathogenesis of CPF toxicity in chickens needs to be elucidated."}
+{"text": "The histone, neutral and acidic nuclear-protein content of BR6 mouse mammary tumours have been measured and related to growth rate and hormone responsiveness. In unresponsive tumours, histone and neutral nuclear-protein content was inversely correlated with growth rate while acidic nuclear-proteins were directly correlated with growth rate. The histone content of these tumours was low when compared to pregnancy dependent tumours growing at the same rate under the same physiological conditions.In vitro incorporation of labelled amino acids into total protein and the nuclear proteins was also measured. Pregnancy independent tumours had higher rates of total protein synthesis than pregnancy dependent tumours The rates of incorporation of amino acids into the nuclear proteins also tended to be higher in independent tumours."}
+{"text": "The structural types are assigned to the prepared compounds and the influence of (i) carboxylate chain length, (ii) substitution of hydrogen atom of carboxylate by halogen and (iii) presence of N-donor organic ligands on the biological activity is discussed.The antibacterial and antifungal activity of zinc(II) carboxylates with composition Zn(RCOO)"}
+{"text": "Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen (REc) and progesterone (RPc) receptors. Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade, lymphocytic infiltration and tumour elastosis. There were significant associations between epithelial cellularity, stromal fibrosis and the value of REc in those tumours in which the receptor was present. Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor. By contrast, neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis. The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy. Overall relapse-free survival (RFS) was no different for those patients with receptors compared to those without them . There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account."}
+{"text": "A study of 953 invasive cutaneous malignant melanomas of the head and neck was performed to determine differences between lentigo maligna melanoma and other histogenetic types with regard to patients and sites affected; prognosis was analysed in 595 of these cases. The cases studied comprised all head and neck melanomas registered with the Scottish Melanoma Group between 1979 and 1992, apart from the 3% of cases that were unclassifiable or rare histogenetic types. The histogenetic types of melanoma were 498 (52%) lentigo maligna melanoma (LMM), 237 (25%) superficial spreading melanoma (SSM) and 218 (23%) nodular melanoma (NM). All types increased in incidence throughout the study period. Patients with LMM (mean age 73 years) and NM (mean 68 years) were significantly older than those with SSM (mean 57 years). There were significant anatomical subsite differences related to sex of patients and histogenetic type of melanoma; melanomas on the face were more frequent in females and 90% of LMM occurred at this site, whereas melanomas on the scalp, neck and ears were more frequent in men. Kaplan-Meier estimates of the probability of survival were produced for the 595 of these 953 patients with 5 year follow-up details. In this group of patients the prognostic significance of tumour thickness, Clark level of invasion, ulceration, histogenetic type of melanoma and number of mitoses were studied using stepwise variable selection of procedures. Each of these possible prognostic factors attained individual significance but the tumour thickness was the dominant risk factor in the proportional hazards analysis. When patients were divided into four sex/ulceration subgroups  and analysed by proportional hazards analysis, no variable other than the tumour thickness had any further prognostic effect. Histogenetic type did not remain an independent prognostic variable at this stage. Despite sex and subsite differences, the prognosis for invasive lentigo maligna melanoma does not differ from that for other histogenetic types after controlling for tumour thickness."}
+{"text": "Since 1986, approximately 170,000 cases of bovine spongiform encephalopathy (BSE) have occurred among approximately one million animals infected by contaminated feed in the United Kingdom. A ruminant feed ban in 1988 resulted in the rapid decline of the epidemic. Transmissible spongiform encephalopathies due to agents indistinguishable from BSE have appeared in small numbers of exotic zoo animals; a small outbreak among domestic cats is declining. Creutzfeldt-Jakob disease (CJD) has been intensively monitored since 1990 because of the risk BSE could pose to public health. In 1995, two adolescents in the United Kingdom died of CJD, and through the early part of 1996, other relatively young people had cases of what became known as new variant CJD, whose transmissible agent (indistinguishable from that of BSE) is responsible for 26 cases in the United Kingdom and one in France. Areas of concern include how many cases will appear in the future and whether or not use of human blood and blood products may cause a second cycle of human infections."}
+{"text": "We compile over 270 wildlife counts of Kenya's wildlife populations conducted over the last 30 years to compare trends in national parks and reserves with adjacent ecosystems and country-wide trends. The study shows the importance of discriminating human-induced changes from natural population oscillations related to rainfall and ecological factors. National park and reserve populations have declined sharply over the last 30 years, at a rate similar to non-protected areas and country-wide trends. The protected area losses reflect in part their poor coverage of seasonal ungulate migrations. The losses vary among parks. The largest parks, Tsavo East, Tsavo West and Meru, account for a disproportionate share of the losses due to habitat change and the difficulty of protecting large remote parks. The losses in Kenya's parks add to growing evidence for wildlife declines inside as well as outside African parks. The losses point to the need to quantify the performance of conservation policies and promote integrated landscape practices that combine parks with private and community-based measures. The need for ecosystem-wide monitoring has become more pressing as the goals of conservation have expanded from saving endangered species and national parks to sustaining biological diversity, ecosystem function and ecological services Despite the need to quantify conservation programs, few studies have looked at the success of protected areas, which now cover 10% of the earth's land surface Lamenting the lack of quantitative data, Struhsaker et al. Despite a lack of systematic monitoring, there has been a large number of individual wildlife censuses conducted in eastern and southern Africa since the 1960s. Scholte and Caro Caro and Scholte Here we assemble continuous multi-species ungulate censuses of sufficient duration and on a large enough scale to transcend climatic cycles and to compare protected areas with matching non-protected areas of Kenya. We also compare the importance of Kenya's protected area system relative to country-wide wildlife numbers and trends.2 land surface and all but a small proportion of its large herbivore populations Wildlife audits of the rangelands have been conducted by the government's Department of Remote Sensing and Resource Surveys (DRSRS) since 1977. The rangelands cover three quarters of Kenya's 440,000 kmHere we assemble over 270 counts conducted over the last 25 years or more to assess wildlife trends in national parks relative to countrywide trends. The counts include published censuses and formal reports where possible, but most are drawn from unpublished counts from public institutions, individual researchers and volunteer groups.Kenya has 23 terrestrial national parks under the administration of the Kenya Wildlife Service and 26 national reserves under district administration. Collectively, the parks and reserves cover 8% of the national land surface of Kenya. Many parks and reserves have too few counts to assess long-term trends. We have therefore included in our study all parks that had a baseline count by 1977 and have been counted repeatedly until at least 1997, giving 20 years of contemporaneous data.The study includes 73% of the area covered by national parks and an estimated 95% of the national wildlife population Our audit of Kenya's protected areas was analyzed using standard methodologies with four objectives in mind. First, we assess wildlife numbers and trends in one of Africa's premier protected area systems. Second, we compare trends in protected and non-protected areas similar in setting. We did so by matching contemporaneous counts inside and outside the park within the same ecosystem. Third, we compare wildlife trends in parks with nation-wide trends. Fourth, we compare the wildlife coverage given by protected areas as a proportion of national totals. We look at the numbers of all species combined rather than individual species in order to compare the trends and overall contribution of wildlife in parks to national trends and to the country-wide population. A more detailed study underway looks at species trends and changes in guild and community structure.Linear regression models were fitted using the Prais-Winsten Generalised Least Squares method, assuming errors have a first-order autocorrelation structure. The assumption of first-order autoregression was verified by partial autocorrelation of the raw data. Analyses were performed using SPSS 12.0 for Windows. All values were log10 transformed prior to analysis. Data for any missing years were estimated by linear interpolation.Highly significant declines have occurred in three of the seven parks. These include Tsavo East and Tsavo West National Parks (combined) and Meru National Park. Nairobi National Park shows a negative but non-significant downward trend. Mara also shows a negative but insignificant decline. However, an earlier study The combined wildlife population change for all national parks listed in A comparison of wildlife trends in nationally protected areas and adjacent ecosystems is given in In The combined wildlife populations show considerable fluctuation in parks and adjoining areas, with numbers rising in the late 1970s, falling through to the mid-1980s, rising again more slowly in the late 1980s and falling steeply in the 1990s. The large fluctuations outside protected areas is likely due to their greater proportion of wet season range than parks and their more episodic use, especially with increasing settlement The fluctuations of populations outside and inside parks are closely correlated  and not significantly different in slope . Although it is not possible to relate the national wildlife trends to rainfall, the oscillations correspond to drought cycles recorded for southern Kenya Despite the large inter-annual populations, the counts show a steep decline in wildlife populations in parks and adjacent ecosystems transcending drought cycles. The decline in parks is highly significant . Aggregated wildlife populations in parks declined by 48%, from 90,691 to 47,599 between 1977 and 1997. Adjoining area populations declined by 45%, from 133,758 in 1977 to 73,394 in 1997.A meta-analysis of the DRSRS censuses of the Kenya rangelands counts between 1977 and 1997 showed a highly significantly decline in numbers The importance of Kenya's protected areas can be gauged by comparing the proportion of wildlife found in parks and reserves with the national total .Based on the national audit for the 1990s, national parks account for approximately 10% of all Kenya's wildlife and national parks and national reserves for 35%. Maasai Mara accounts for 25% of the national total, underscoring its singular importance in Kenya's protected area system.Our results have specific and general implications for conservation. Specifically, the decline in Kenya's park populations is not surprising, given the inherent shortcomings in their design. Only a modest portion of the annual migratory range of large herbivores is included in Kenya's parks. Most parks differentially cover dry season rather than wet season ranges of the dominant migratory species such as wildebeest and zebra Big parks in Kenya are no more insulated from the wildlife decline than small parks. The three largest protected areas, Tsavo (East and West), Meru and Maasai Mara Two of the smallest parks, Nakuru and Amboseli, showed non-significant upward trends in population between 1977 and 1997 , but sigMore generally, long-term monitoring in Kenya adds to growing evidence of wildlife declines in many African parks The evidence of park losses points to the need for systematic monitoring of ecological trends and biological criteria for auditing conservation policies and practices. The results show sufficient variation in conservation areas and approaches to begin weighing the relative importance of various policies, strategies and management practices in conservation The value of large-scale long-term trend analysis is highlighted in a recent study showing that wildlife on private and community sanctuaries is stable or increasing The count data were obtained from the Department of Remote Sensing and Resource Surveys (DRSRS) for Tsavo East and West and the Kitengela, from DRSRS and Ottichilo Loxidonta Africana), buffalo (Syncerus caffer), Burchell's zebra (Equus burchelli), giraffe , wildebeest (Connochaetes taurinus), eland (Taurotragus oryx), waterbuck , warthog (Phacochoerus africanus), Grant's gazelle (Gazelle granti), Thomson's gazelle (Gazelle thomsonii), impala (Aepyceros melampus), lesser kudu (Tragelaphus imberbis) oryx (Oryx gazella), black rhinoceros (Diceros bicornis), topi  and hartebeest (Alcelaphus buselaphus),Species covered by the surveys include: elephant ("}
+{"text": "The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting. The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting.A representative group of Canadian rectal cancer experts from the key disciplines  involved in managing resectable rectal cancer were invited .Health care professionals involved in the care of patients with potentially curable rectal cancerStakeholders  responsible for program and funding decisions related to the management of potentially resectable cancerPatient advocacy and education groups such as the Colorectal Cancer Association of CanadaAll recommendations are based on a structured presentation and discussion of the best available evidence.These standards provide the basis for a discussion with patients regarding management options. Treatment plans will depend on a more complete discussion of the risks and benefits of proposed therapies with individual patients.Significant progress has been made in improving outcomes for patients with potentially resectable rectal cancer; however, further improvement is necessary. Offering patients the option of participating in clinical trials should be a priority.Optimally, the approach for assessing and managing patients with rectal cancer should involve a collaborative, multidisciplinary team . For example, optimal rectal cancer management is predicated on open communication and quality assurance between the surgeon and the pathologist describing the extent of disease of the surgical specimen for optimal postsurgical treatment choices.Radiologic assessment and imaging should be completed within 2\u20133 weeks to ensure that the appropriate information is available to make timely management decisions.For complete clinical staging of rectal cancer, what should the standard diagnostics and reporting be (preoperative assessment)?timely period , starting from the date of biopsy.All diagnostics should be completed within a Services should include:ColonoscopyImagingmri)Computed axial tomography of thorax, abdomen, and pelvis AND magnetic resonance imaging (Slices of 3\u20134 mm should be routinecrm) with tumour distance should be reportedMesorectal margin measurements or circumferential resection margin  protocol for the examination of specimens from patients with primary carcinomas of colon and rectum, based on the American Joint Committee on Cancer and International Union Against Cancer TNM, to include these points:For complete clinical staging of rectal cancer, synoptic reporting in accordance with the College of American Pathologists (tme) qualityTotal mesorectal excision crm statuscrm or if a lymph node with metastasis is at 1 mm or less from the crmPositive if tumour is at 1 mm or less from the If neoadjuvant therapy was received, pathologic tumour response grading should be recordedcap template  with fluoropyrimidine chemotherapy or short-course radiation without chemotherapy can be considered. A multidisciplinary team approach (with or without a tumour board) is important to review individual cases and reach consensus on the appropriate course of treatment (short- vs. long-course radiation).Preoperative neoadjuvant radiotherapy is the standard of care for clinically staged et al. 2004 et al. 2003 et al. 2006 et al. 2006 et al. 2004 This statement utilizes Bujko Which neoadjuvant chemotherapy protocol or protocols should be standard when combined with long-course radiation?int 0144) The optimal fluoropyrimidine-based chemotherapy is based on extrapolation of data from randomized trials of combined-modality chemoradiation used in the postoperative setting. Use fluoropyrimidine-based chemotherapy with long-course radiation. Protracted fluoropyrimidine is preferable to bolus 5-fluorouracil because of improved tolerability and similar efficacy, as seen in the largest and most recent randomized trial  of the surgical specimen immediately after removal of the rectum. The pathologist receiving the specimen should also grade the macroscopic quality of the excision, independently of grading by the surgeon. Optimal management is predicated on productive, open communication between the surgeon and the pathologist so that quality assurance and appropriate mechanisms for evaluation and improvement can be achieved . Collaboration is mandatory for optimal evaluation; that is, margin assessment, surgical difficulty encountered, neoadjuvant treatment given to the patient must be communicated. et al. 2008 This statement takes account of Nagtegaal and van Krieken 2002 What is the standard adjuvant chemotherapy post neoadjuvant treatment and surgery?All patients should be considered for 4\u20136 months of fluoropyrimidine-based therapy. Based on extrapolation of phase III trials for adjuvant treatment of colon cancer, adjuvant oxaliplatin-based therapy should be considered for patients at high risk for recurrence, including, but not limited to those who areypN-positive.crm-positive.et al. 2004 et al. 2008 et al. 2009 et al. 2007 This statement utilizes Sauer Participants disclosed potential conflicts of interest within the past 2 years:Scott Berry: Advisory boards for Sanofi\u2013AventisCelia Marginean: NoneCarole Richard: NoneAndrew Smith: NoneTe Vuong: Work as a consultant for Sanofi\u2013AventisThe Colorectal Cancer Association of Canada and the authors acknowledge the sponsors who provided unrestricted grants: Sanofi\u2013Aventis, Bristol\u2013Myers Squibb, and Amgen."}
+{"text": "DNA/cell distributions were recorded by automated cytofluorometry (=pulse cytophotometry) in bone-marrow aspirates of leukaemia and lymphosarcoma patients subjected to chemotherapy. In most cases, early perturbations in DNA/cell histographs were observed, characteristically reflecting the known mode of action of the drugs. These changes in general preceded the clinical observation of drug response. In a series of 23 measurements in 19 patients, a positive correlation between early cytophotometric changes and clinical effects of chemotherapy was observed in 17 patients. Five patients were negative for both cytophotometric and clinical reactions and one patient was probably false-positive. The validity of the assay for early detection of drug resistance in acute leukaemia and related diseases is discussed."}
+{"text": "We describe refinements to and new experimental applications of the Data Mining Surveillance System (DMSS), which uses a large electronic health-care database for monitoring emerging infections and antimicrobial resistance. For example, information from DMSS can indicate potentially important shifts in infection and antimicrobial resistance patterns in the intensive care units of a single health-care facility."}
+{"text": "Escherichia coil,Pseudomonas aeruginosa and Staphylococcus aureus. The title studies have proved a definitive role of anions in increasing the antibacterial properties.A number of biologically active complexes of cobalt(II) and nickel(II) with pyrazinedicarboxaimido derivedthienyl and furanyl compounds having the same metal ion but different anions such as sulphate, nitrate,oxalate and acetate have been synthesized and characterized on the basis of their physical, spectral andanalytical data. In order to evaluate the role of anions on their antibacterial properties, these ligands andtheir synthesized metal complexes with various anions have been screened against bacterial species"}
+{"text": "The peptidergic/aminergic innervation of normal liver and tumour blood vessels was investigated in order to determine vascular control with a view to improving the efficacy of hepatic arterial cytotoxic infusion in the treatment of colorectal liver metastases. Selected areas of liver metastases and macroscopically normal liver from resection specimens (n = 13) were studied using light microscope immunohistochemistry for the presence of protein gene product 9.5 (PGP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and tyrosine hydroxylase (TH). The ultrastructure of blood vessels supplying liver metastases and their perivascular innervation were also examined by transmission electron microscopy. In the normal liver, perivascular immunoreactive nerve fibres containing PGP, NPY and TH were observed around the interlobular blood vessels and along the sinusoids and the central vein of the hepatic lobule. The greatest density of immunoreactive nerve fibres was seen for PGP, followed (in decreasing order) by NPY and TH. VIP, SP and CGRP immunoreactivity was observed only in nerve bundles associated with the large interlobular blood vessels. In contrast, no perivascular immunoreactive nerves were observed in colorectal liver metastases. Electron microscopy confirmed the absence of perivascular nerves in liver metastases. In addition, it showed that the walls of these blood vessels were composed of a layer of endothelial cells surrounded by an incomplete or, very rarely in the periphery of the tumour, a complete, layer of synthetic phenotype of smooth muscle-like cells. These results imply that the blood vessels supplying liver metastases are bereft of normal neuronal regulation; whether there is a role for endothelial cell control of blood flow in these vessels is not yet known."}
+{"text": "To the Editor: In August 2006, several northern European countries including Belgium reported cases of bluetongue (BT) (Bluetongue virus (BTV), genus Orbivirus, family Reoviridae. The genome of BTV consists of 10 segments of double-stranded RNA; 24 serotypes have been reported (Bos grunniens grunniens).Yaks living in captivity in a Belgian animal park showed clinical signs of BT. A clinical examination performed on 1 yak showed loss of weight associated with a progressive weakness linked to anorexia, ulcerative and necrotic lesions on the muzzle with some crusts and mucopurulent nasal discharge, and udder erythema with papules and crusts. The tongue was severely swollen and cyanotic and protruded from the mouth . The aniSamples of spleen and bone marrow were taken and prepared according to the method of Parsonson and McColl (Culicoides vectors. Antibodies against BTV have been found in many wild ruminants (The yak species in its natural biotope is usually rarely exposed to competent In the epidemiology of BT in African countries, cattle and wild ruminant species such as antelopes play a role as asymptomatic reservoir hosts of the virus ("}
+{"text": "The repeated intratracheal instillation of cigarette smoke condensate (SWS) in rats at close to maximum tolerated dose levels failed to induce squamous neoplasms in the lungs although such treatment was associated with an increased incidence of cuboidal/columnar metaplasia (CCM) and squamous metaplasia (Sq.M) of alveolar epithelium. With one exception, various fractions of SWS had no effect on lung tumour incidence though some were more effective than SWS in increasing the incidence of CCM and Sq.M. The exceptional fraction, Fraction P, which contains most of the polycyclic aromatic hydrocarbons of smoke and is the most effective of the fractions tested in producing tumours in mouse skin, gave rise to 4 squamous tumours of doubtful malignancy and one metastasizing squanmous carcinoma among 3 groups of 18 animals exposed at 3 different dose levels. The results are discussed in relation to the possible development of a method for comparing condensates for relative lung carcinogenicity."}
+{"text": "Sir,An investigation of anti-BK virus antibodies among immunosuppressed patients with BK-related nephropathy was beyond the scope of the EPIC-Oxford cohort study , cancer of the uterine cervix (human papillomaviruses) or endemic African Burkitt lymphoma (Epstein Barr virus), elevated titres of antibodies against the relevant viral antigens have been found both in prospective and in retrospective studies , but this was an unusual case in an immunosuppressed transplant recipient (A common morphological sign of active polyoma virus infection is the presence in urine of bladder epithelial cells with typical intranuclear viral inclusions. These \u2018decoy cells\u2019 are so named because they mimic the nuclear enlargement and atypia of urothelial carcinomas and can easily be mistaken for malignant cells. Weinreb draws attention to his recent report ("}
+{"text": "The relation between reproductive factors and cervical neoplasia was evaluated in a case-control study of 528 cases of invasive cancer compared with 456 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 335 cases of cervical intraepithelial neoplasia compared with 262 outpatient controls. The risk of invasive cervical cancer increased with number of livebirths, the estimated multivariate relative risk (RR) being 4.39 in women with five or more births compared with nulliparous women. There was also an inverse relation with age at first livebirth  which, however, disappeared after inclusion of parity in multiple logistic regression analysis. Likewise, cases of invasive cervical cancer tended more frequently to report induced abortions. However, this association was not statistically significant after allowance for confounding factors, including parity. No relation emerged with number of spontaneous abortion and age at last pregnancy. When the interaction between parity and sexual habits was analysed, the relative risk increased in subsequent strata of parity with increasing number of sexual partners or decreasing age at first intercourse, thus suggesting an independent effect of sexual and reproductive factors, and hence multiplicative on the relative risk of invasive cervical cancer. No consistent association emerged between the risk of intraepithelial cervical neoplasm and parity, number of abortions and age at first or last birth."}
+{"text": "The cytotoxic activity of metronidazole (Flagyl) and misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells suspended in standard medium in sealed vials and in gassed spinner flasks has been investigated. Flagyl (5 mM) was only cytotoxic at high initial cell densities. However, when lactate (20 mM) was included in the medium the cytotoxicity of Flagyl at low cell densities was considerable, and similar to that of misonidazole under the same conditions. The relevance of this \"lactate effect\" to in vivo systems, and the possible mechanisms involved, are discussed."}
+{"text": "Gerry Killeen and colleagues argue that malaria eradication efforts will not be successful until a better understanding of the ecology and evolution of the mosquito vectors is gained. Plasmodium falciparum in the most intensely endemic parts of Africa and the PacificExisting front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malariaPriority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmissionGlobal commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecologyeradication was often nervously referred to as \u201cthe E-word\u201d by a disillusioned community that had learned from bitter experience that optimistic forecasts The Global Malaria Eradication Program, launched in the middle of the last century, over-promised and under-delivered By definition, eradication of human malaria parasites globally Anopheles gambiae and An. funestus behaviours of feeding and resting almost exclusively indoors An. arabiensis, which dominates transmission in much of Africa All front-line vector control methods used in Africa today  are based on the stereotyped view that vectors bite and rest primarily inside houses. This assumption is based on the early characterization of The ability of vectors to evolve diverse resistance mechanisms to insecticides has been well documented The emergence of new vector behavioural phenotypes is a less-recognized phenomenon than insecticide resistance, but it has the potential to similarly diminish the effectiveness of current interventions. Documented examples of adaptable vector behaviours that could impact interventions such as ITNs and IRS include changes in host-species preferences Plasmodium spp. in human populations de facto primary vectors following the successful implementation of interventions aimed at current priority vector species Over 30 different primary vectors dominate transmission in various parts of the world An. funestus by An. rivolurumAn. parensisAn. funestus.Mosquito vectors are embedded within ecological communities where they act as predators, prey, and competitors. Consequently the reduction of one target vector may trigger a cascade of ecological effects that could impede or enhance transmission by another. Studies have reported that suppression of one vector species through habitat change or control was followed by an increase in another. Notable examples include the apparent replacement of Virtually nothing is known about the role of vectors in regulating, or being regulated by, their prey or predators. Consequently the potential use of biological control to manage vector populations is vastly underexplored. Perhaps the best-described biological regulator of vector populations is themselves. Several studies have shown that traits such as the larval development, fecundity, survival, and population growth rates of mosquito vectors is negatively correlated with their population size Knowledge of mosquito dispersal range is essential for accurate predictions of the optimal spatial implementation of more conventional control methods such as ITNs, IRS, and larviciding An. aquasalis to switch its feeding from livestock to humans. This change initiated the return of transmission into the area after 16 years of absence Climate and environmental change are driving the expansion of numerous vector species and the intensification of pathogen transmission in many locations The ecological hurdles detailed in Historically, vector biologists have focused primarily on evaluating specific control interventions and less on fundamental studies of vector ecology. Now that the gap between currently achievable levels of control and the ultimate goal of eradication is becoming clear, new intervention options for integrated vector management Our understanding of the ecology of mosquitoes that transmit malaria lags decades behind that of agricultural pests, endangered species, and model organisms. The reasons are multifaceted The paucity of national funding schemes for ecological research within impoverished malarious countries, and limited access to relevant overseas funding, have restricted the conversion of indigenous talent into an adequate expertise base. Furthermore, the primary focus of malaria control on developing countries with limited infrastructure or research capacity may deter the engagement of ecologists from the developed world who have a myriad of more convenient, accessible, and tractable organisms at their disposal. Until the inherent challenges of working in these more demanding settings is recognized and valued by mainstream ecology, researchers may have little incentive to build their careers in this area. Sponsors of fundamental biological research have typically undersupported vector ecology, on the basis of the assumption that public health and medical donors with often substantially larger budgets will fill this gap. Unfortunately this has rarely been the case in practice because donors generally prioritize applied research focusing on the development and delivery of interventions which have more obvious and immediate potential benefits Most funding for ecological studies of malaria vectors in recent years has been driven by the needs of specific biotechnological interventions Aedes aegypti, the primary vector of Dengue, to distribute insecticides to their own larval habitats As a result of these various funding deficiencies, huge knowledge gaps exist in relation to most components of the mosquito life cycle that occur outside of houses, including larval growth and sugar feeding, oviposition, and adult dispersal  [26],[31The overarching strategic priority for increased investment should therefore be to improve the quantitative understanding of mosquito life history, fitness, genetics, and behavioural processes as determinants of their population stability and malaria transmission intensity. Support should be directed towards delivering key outcomes, without which malaria eradication is difficult to envisage . As such(1) Identification of specific vulnerabilities of vector and sporogonic-stage parasite populations that can be prioritized for intervention development and delivery(2) Estimation of threshold values of vector population parameters required to achieve pathogen elimination(3) Quantification of the strength of selection pressures imposed on vectors by particular interventions so that the likelihood and rate at which physiological and behavioural resistance traits emerge can be predicted and managed(4) Avoidance of the mistakes of the previous eradication drive through biologically realistic understanding of the scale of the challenge(5) Estimation of achievable endpoints for single and multiple interventions and synergies and redundancies associated with particular combinations(6) Stimulation of creative, \u201cblue skies\u201d scientific investigation resulting in identification of unforeseen novel intervention targets and strategies(1) Development of new field measurement tools for surveying diverse primary and secondary vector populations and the environmental conditions and resources they rely upon through all phases of their life cycles(2) Establishment of comprehensive, long-term data collection systems spanning individual to landscape scales from diverse and representative field sites(3) Creation and maintenance of public data repositories with standardized, simplified data storage formats for mosquito ecology data combined with policies and incentive systems that facilitate data sharing and synergy between laboratory- and field-based investigators(4) Application of cutting-edge mathematical modelling approaches to understand vector populations dynamics, pathogen transmission, and optimal intervention strategies(5) Development and application of enclosed, pathogen-free, semi-field mesocosms in which vector populations can be experimentally manipulated 6) Exploitation of the perturbations of vector populations and parasite transmission processes resulting from ongoing scale-up of existing intervention measures so that the population dynamics, behavioural specialization, and competitive relationships between mosquito species can be lucidly understood(7) Engagement and recruitment of leading theoretical and empirical ecologists into malaria vector research, control, and capacity strengtheningDirect research investment will be required to develop new field measurement tools, establish a network of longitudinal population monitoring sites with complementary semi-field facilities"}
+{"text": "Several studies of breast tumour histology and oestrogen receptor (ER) contents report an inverse correlation between the density of the stromal lymphoid cell infiltrate and the presence or concentration of ER. Using monoclonal antibodies to lymphoid cell surface markers we have examined the immunophenotype of the infiltrating lymphoid cells and related this to the tumour ER content. There is a significant inverse correlation between the presence of Leu7-positive cells, which includes a subpopulation of natural killer (NK) cells, and tumour ER content; this is possibly superimposed on the dilutional effect of macrophages and other infiltrating cells."}
+{"text": "Leukocyte extravasation into perivascular tissue during inflammation and lymphocyte homingto lymphoid organs involve transient adhesion to the vessel endothelium, followed by transmigrationthrough the endothelial cell (EC) layer and establishment of residency at the tissue sitefor a period of time. In these processes, leukocytes undergo multiple attachments to, and detachmentsfrom, the vessel-lining endothelial cells, prior to transendothelial cell migration. Transmigratingleukocytes must traverse a subendothelial basement membrane en route to perivasculartissues and utilize enzymes known as matrix metalloproteinases to make selective clips in theextracellular matrix components of the basement membrane. This review will focus on the evidencefor a link between adhesion of leukocytes to endothelial cells, the induction of matrixmetalloproteinases mediated by engagement of adhesion receptors on leukocytes, and the abilityto utilize these matrix metalloproteinases to facilitate leukocyte invasion of tissues. Leukocyteswith invasive phenotypes express high levels of MMPs, and expression of MMPsenhances the migratory and invasive properties of these cells. Furthermore, MMPs may be usedby lymphocytes to proteolytically cleave molecules such as adhesion receptors and membranebound cytokines, increasing their efficiency in the immune response. Engagement of leukocyteadhesion receptors may modulate adhesive (modulation of integrin affinities and expression),synthetic (proteinase induction and activation), and surface organization (clustering of proteolyriccomplexes) behaviors of invasive leukocytes. Elucidation of these pathways will lead tobetter understanding of controlling mechanisms in order to develop rational therapeuticapproaches in the areas of inflammation and autoimmunity."}
+{"text": "The initial events (virus adsorption and fusion with the cells) in the replicative cycle ofhuman immunodeficiency virus (HIV) can serve as targets for the antiviral action of metal-bindingcompounds such as polyanionic compounds , bicyclams and G-octet-forming oligonucleotides. The adsorption and fusion of HIV with its target cells depends on the interaction of the viral envelope glycoproteins (gp 120) with the receptors  at theouter cell membrane. We are currently investigating how the aforementioned compounds interferewith these viral glycoproteins and/or cell receptor."}
+{"text": "Early detection of testicular leukaemia and the identification of residual leukaemic cells in treated patients are important aims in the management of males with acute lymphoblastic leukaemia (ALL). In most cases of ALL ( greater than 95%) the blast cells express terminal deoxynucleotidyl transferase (TdT), a nuclear enzyme. We have therefore standardized the immuno-fluorescence and -peroxidase techniques (using anti-Tdt antibodies) for identifying TdT cells in the normal thymus, as well as in samples of testis with heavy leukaemic infiltrates (positive controls). TdT cells can be identified in formalin (but not in Bouin's or Carnoy's) fixed paraffin-embedded tissues, and the preservation of morphological details is excellent. The method is nevertheless difficult to standardize and also requires the use of deoxyribonuclease (DNase) for the digestion of sections. However, in frozen tissue sections, stronger staining of TdT cells was found, even without DNase treatment. Good morphology was preserved when cut sections were fixed immediately in the cryostat. In the second part of the study 15 samples from treated boys were analysed to see whether the technique is suitable to identify residual minimal leukaemic infiltrates. In 5 patients scanty disseminated TdT cells were detected, and in 2 patients small clumps of TdT cells were seen. The results indicate that the immunohistological identification of TdT ALL blasts may be the method of choice."}
+{"text": "Similarly, such information is available for urinary bladder cell types.Public databases are crucial for analysis of high-dimensional gene and protein expression data. The Urologic Epithelial Stem Cells (UESC) database Two major data types were archived in the database, protein abundance localization data from immunohistochemistry images, and transcript abundance data principally from DNA microarray analysis. Data results were organized in modules that were made to operate independently but built upon a core functionality. Gene array data and immunostaining images for human and mouse prostate and bladder were made available for interrogation. Data analysis capabilities include: (1) CD (cluster designation) cell surface protein data. For each cluster designation molecule, a data summary allows easy retrieval of images (at multiple magnifications). (2) Microarray data. Single gene or batch search can be initiated with Affymetrix Probeset ID, Gene Name, or Accession Number together with options of coalescing probesets and/or replicates.Databases are invaluable for biomedical research, and their utility depends on data quality and user friendliness. UESC provides for database queries and tools to examine cell type-specific gene expression , whereas most other databases contain only whole tissue expression datasets. The UESC database provides a valuable tool in the analysis of differential gene expression in prostate cancer genes in cancer progression. Public databases for the storage and retrieval of genomic and proteomic data have become an integral component of biomedical research. These databases can aid in the identification of genes and proteins responsible for disease and health and defining their function by enabling investigators in diverse research areas and interests with a range of computer expertise to have ready access to the stored information through one user interface. Previously, the Prostate Expression Database (PEDB) established a centralized archive of gene expression information for human prostate . This daThe Stem Cell Genome Anatomy Project (SCGAP) initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) included seven organ-specific groups that were funded to form a research consortium. The aims of this consortium were to collectively develop necessary biological procedures and reagents for characterization of tissue specific progenitor cells and to characterize gene expression patterns in these cells using advanced technologies and bioinformatic techniques. The official web portal for SCGAP  was desi+ endothelial cells, CD26+ luminal secretory and CD104+ basal cells of the epithelium, and CD49a+ fibromuscular cells of the interglandular stroma for transcriptome profiling . Fig. UESC data types were organized in separate modules to afford a good balance between flexibility and consistency. The management system was designed to allow efficient data access to all levels of users, with both easy web and scriptable, sophisticated interfaces, and to be reusable so that a new project may be built on a previous one . The database will therefore continuously expand as more cell type-specific information becomes available. The UESC database will be a valuable tool in the analysis of differential gene expression in prostate cancer genes in cancer progression.Strategies for the analysis of the interface between gene expression and protein information involve a variety of computational methods that require the storage and retrieval of large datasets. These databases become perforce an integral component of biomedical research. The UESC database is a unique, web-accessible, searchable compilation of published data concerning the identification and characterization of genes and proteins in specific cell types of the urologic organs where cancer is a major disease. These cell populations retain to a high degree their CD phenotype as determined by immunostaining in intact tissue; concordance between gene expression measured by DNA array and immunohistochemistry was good and will be published separately. These cell type transcriptomes allow us to pursue many studies which are not possible with whole tissue transcriptomes.. It has been tested to work with Mozilla Firefox and Internet Explorer.The UESC database is freely accessible at BPH: Benign prostatic hyperplasiaCD: Cluster designationEST: Expressed sequence tagMACS: Magnetic cell sortingMISFISHIE: Minimum Information Specification For In Situ Hybridization and Immunohistochemistry ExperimentsMPSS: Massively Parallel Signature SequencingNIDDK: National Institute of Diabetes and Digestive and Kidney DiseasesPEDB: Prostate Expression DatabasePGDB: Prostate Gene DatabasePIN: Prostatic intraepithelial neoplasiaRDBMS: Relational database management systemRMA: Robust multi-array averageSBEAMS: Systems Biology Experiment Analysis Management SystemSCGAP: Stem Cell Genome Anatomy ProjectTPM: Transcripts per millionUESC: Urologic Epithelial Stem CellThe author(s) declare that they have no competing interests.LEP drafted the manuscript with input from DSC, EWD and AYL. Database design and programming was performed by EWD, DSC and MK with input from AYL, LEP and LDT. LDT provided immunohistochemistry data annotation and staining summaries. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:"}
+{"text": "The effect of 10% glucose solution and narcosis upon the blood borne cancer cells was studied on Wistar rats, with Walker 256 carcinosarcoma inoculated intravenously.Our experiment reveals obvious differences between the control group and the groups treated with glucose concerning incidence, localization and tumour extension, differences which suggest that there is a risk in using glucose in the intra- and post-surgical resuscitation of patients with cancer."}
+{"text": "The effect of an antiserum containing antibodies against cell surface components of PyBHK cells on the action of certain anticancer agents has been studied using a colony formation inhibition assay. The effects of x-rays, chlorambucil, CCNU and possibly ICRF 159 are augmented by the antiserum whereas methotrexate and vinblastine are not."}
+{"text": "Permanent changes in the endocrine status of female SJL/J and CR mice were induced by masculinization, ablation of endocrine glands, inoculation of hormones, or feeding of the chemical carcinogen DMBA. All these procedures resulted in modification of the host hormonal milieu, as shown by blood hormone determination. Masculinization reduced drastically the onset of lymphosarcoma and increased the incidence of systemic neoplasms respectively in DMBA-treated female SJL/J and CR mice. Continued administration of gonadotrophins increased the incidence of systemic neoplasia in CR mice. A direct correlation is suggested between onset of lymphosarcoma or other tumours in mice and a specific shift to an abnormal hormonal environment."}
+{"text": "The profiles of 4 acute-phase reactant proteins (APRPs) (haptoglobin (HPT), alpha1 antitrypsin (AAT), alpha1 acid glycoprotein (AGP) and prealbumin (PALB)) have been studied during the evolution of bowel cancer. Serial measurements of these APRPs can add to the information obtained from measurements of the level of CEA and hepatic enzymes during the monitoring of postoperative patients. There is considerable stability in the profile in a given individual in health, Rises of AAT and AGP are associated with metastases. High levels of HPT may suggest involvement of the bowel wall by recurrent cancer. PALB levels tend to reflect the nutritional status. A discriminant function based on the log CEA, AAT and AGP preoperative blood levels can considerably improve on the predictive value attained using CEA levels alone."}
+{"text": "The levels of VEGF and VEGF165 and VEGF121 mRNAs were remarkably higher in some stage II and III/IV adenocarcinomas of the cervix than in other cases, including normal cervices. Therefore, the elevation of VEGF165 and VEGF121 might contribute to the relatively late advancing via angiogenic activity in some adenocarcinomas of the cervix. \u00a9 1999 Cancer Research CampaignTo know the potential of growth, invasion and metastasis of uterine cervical cancer associated with neovascularization, localization of vascular endothelial growth factor (VEGF) and microvessel density in tumours were determined by immunohistochemical staining, the levels of VEGF subtypes were determined by Western blot analysis and by a sandwich enzyme immunoassay, and the levels of VEGF subtype mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR) \u2013 Southern blot analysis in uterine cervical cancers. The relation between VEGF subtype expressions and microvessel density, histological types and clinical stages of uterine cervical cancers was analysed. The expression of VEGF was seen dominantly in the cancer cells, and correlated with microvessel density in uterine cervical cancers. Among the four subtypes of VEGF, the populations of VEGF"}
+{"text": "The joint application of separation and spectroscopic techniques provides valuable information on the nature and the properties of the resulting ruthenium/protein adducts. Recent work carried out in our laboratory points out that, under physiological conditions, some selected ruthenium(III) complexes bind plasma proteins tightly with a marked preference for surface imidazole groups. Representative examples of interactions of antitumor ruthenium(III) complexes with plasma proteins such as albumin and transferrin are given. Notably the antitumor ruthenium(III) complexes considered here bind proteins much tighter than DNA; it is proposed that protein binding of ruthenium(III) complexes will have a large impact on the biodistribution, the pharmacokinetics and the mechanism of action of these experimental drugs.Presently, there is large interest in analysing the interactions"}
+{"text": "Patient decision aids are increasingly regarded as important components of clinical practice that enable shared decision making (SDM) and evidence based patient choice. Despite broad acceptance of their value, there remains little evidence of their successful implementation in primary care settings.Health care practitioners from five general practice surgeries in northern England participated in focus group sessions around the themes of patient decision aids, patient and practitioner preferences and SDM. Participants included general practitioners (n = 19), practice nurses (n = 5) and auxiliary staff (n = 3). Transcripts were analysed using a framework approach.We report a) practitioners' discussion of the current impetus towards sharing decisions and their perspectives on barriers to SDM, and b) the implementation of patient decision aids in practice and impediments such as lack of an evidence base and time available in consultations.in practice for the implementation of SDM.We demonstrate two orientations to sharing decisions: practitioner-centred and patient-centred with the former predominating. We argue that it is necessary to rethink the changes required  Engaging patients in clinical decision making has become a guiding ethical principle underpinning much contemporary and routine clinical practice -5. DevelDespite broad acceptance of the use of patient decision aids in improving patient based outcomes and health, evidence for their successful implementation and use in extending SDM in routine practice remains scarce -10. SDM Five general practice surgeries in northern England were invited to participate in the study. The selection of practices built on the recruitment in our earlier study. Within each of the participating practices information sheets were circulated and participants invited to attend a presentation. A one hour presentation was given by RGT to introduce the study, the concept of SDM and current developments concerning patient decision aids. The presentation included a brief overview of different approaches to decision making and gave examples of different patient decision aids and modes of implementation. It also introduced the work and resources of organisations involved in the development and use of patient decision aids such as the Ottawa Health Research Institute (OHRI) and International Patient Decision Aids Standards Collaboration (IPDAS) . ParticiA framework approach was used (by DBW and MJM) in the analysis of transcripts . The frapractices adopted approaches variably consistent with the principles of SDM. The transcripts from FG1 demonstrated the least familiarity with principles of SDM, and FG2 the most. In this section we demonstrate practitioner-centred  and a Framingham derived computerised risk assessment for cardiovascular risk (by practice nurses and GPs). In both situations practitioners recognised that derivation of patient values were not incorporated in the use of the tools. Moreover, the presentation of risk was used to \"reinforce what you are saying  declare that they have no competing interests.RGT led the presentation to practitioners, DBW organised and conducted the focus groups and participated in the data analysis sessions with MJM. All authors approved the final manuscript.Focus group participationFG1: GPs ; Nurse practitioners FG2: GPs ; Nurse practitioner ; Health visitor FG3: GPs FG4: GPs ; Nurse practitioner ; Health visitor FG5: GPs The pre-publication history for this paper can be accessed here:A table of the thematic frameworks.Click here for file"}
+{"text": "This paper describes the results of analytical applications of electrochemical biosensors based on bilayer lipid membranes (BLMs) for the automated rapid and sensitive flow monitoring of substrates of hydrolytic enzymes, antigens and triazine herbicides.BLMs, composed of mixtures of egg phosphatidylcholine (egg PC) and dipalmitoylphosphatidic acid (DPPA), were supported on ultrafiltration membranes (glass microfibre or polycarbonate filters) which were found to enhance their stability for flow experiments. The proteins  were incorporated into a floating lipid matrix at an air-electrolyte interface, and then a casting procedure was used to deliver thelipid onto the filter supports for BLM formation. Injections of the analyte were made into flowing streams of the carrier electrolyte solution and a current transient signal was obtained with a magnitude related to the analyte concentration. Substrates of hydrolytic enzyme reactions  could be determined at the micromolar level with a maximum rate of 220 samples/h, whereas antigens (thyroxin) and triazine herbicides  could be monitored at the nanomolar level in less than 2 min. The time of appearance of the transient response obtained for herbicides was increased to the order of simazine, atrazine and propazine which has permitted analysis of these triazines in mixtures."}
+{"text": "From July to September 1999, a widespread outbreak of meningoencephalitis associated with West Nile virus  occurred in southern Russia, with hundreds of cases and dozens of deaths. Two strains of West Nile virus isolated from patient serum and brain-tissue samples reacted in hemagglutination-inhibition and neutralization tests with patients' convalescent-phase sera and immune ascites fluid from other strains of West Nile virus."}
+{"text": "This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous  forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis."}
+{"text": "Profound changes in the level of certain dehydrogenase enzymes were observed in lymphoid tissues of rats involved by erythroblastic stem cell leukaemia. In lymphoid tissues free of leukaemic involvement, activity of malate dehydrogenase (MDH) always exceeded that of lactate dehydrogenase (LDH). In those which contained substantial infiltrates of leukaemic cells, activity of LDH was increased while MDH activity was reduced. In leukaemic spleen significant changes were observed in the molecular forms of LDH; the proportion of LDH-5 (muscle-type LDH) was greatly increased while the other molecular forms were reduced. The spleen of rats with leukaemia exhibited a marked increase in the normal level of aerobic and anaerobic glycolysis but the rate of respiration was unchanged.The terminal stages of stem cell leukaemia in the rat are characterized by wide-spread leukaemic infiltration of liver and other tissues. Lymph node involvement, however, was found to be selective. Coeliac lymph nodes greatly exceeded other lymph node groups in their incidence of leukaemic involvement. It is considered that the selective nature of lymph node involvement in stem cell leukaemia derives from topographical considerations."}
+{"text": "The copper and platinumcomplexes of this steroid derivative were synthesized and characterized by spectroscopy and electrochemiatry.The in vitro activity of these compounds against human breast cancer cell line MCF-7 was tested. Thehighest activity was found for the [Pt(TATSC)Cl"}
+{"text": "To the Editor: Sin Nombre virus (SNV) is a highly virulent strain of hantavirus associated with rodent hosts in North America (Peromyscus maniculatus) that inhabit the Channel Islands off the California coast often have rates of SNV that greatly exceed values on the mainland (P. maniculatus.Coreopsis gigantea), a shrub native to California, to provide a standardized habitat for comparisons across islands. The number of sampling areas depended largely upon the distribution of C. gigantea habitat and logistical considerations during each island visit (P. maniculatus serum samples were examined for immunoglobulin (Ig) G antibodies to the SNV nucleocapsid protein by ELISA with Centers for Disease Control and Prevention reagents . Overall, 36 male and 42 female mice were captured; the sex of captured animals was independent of SNV infection . We captured only 2 subadult mice on islands where we also detected antibodies to SNV; 1 mouse tested positive, the other tested negative. Although our sample sizes precluded detecting very low rates of SNV infection with confidence on Santa Barbara and East Anacapa Islands, the consistency of our results with those of Jay et al. (There was no significant difference in prevalence of SNV antibodies between our 2007 results and the prevalence found by Jay et al. (P. maniculatus and seroprevalence for SNV (P. maniculatus on the Channel Islands, despite considerable variation in host population density between earlier studies and ours (P. maniculatus on the Channel Islands in periods between the studies by Jay et al. (Several studies now indicate the importance of long-term surveillance of SNV prevalence in wild rodent populations for understanding the factors that may contribute to outbreaks of human disease, e.g (P. maniculatus is found on the islands to more completely characterize within-island risk.Future studies comparing long-term dynamics on islands and related mainlands are needed to examine the possibility that insular systems provide unique opportunities to understand the factors affecting pathogen dynamics and human risk. Given the substantial variation in mouse population density among different habitats within these islands and variation in prevalence among trapping areas in our study  and othe"}
+{"text": "Normal fibroblasts, mouse peritoneal cells and cells of low tumorigenicity infiltrated poorly and slowly whereas most tumours infiltrated rapidly. Some cells of the more invasive tumours achieved minimum rates of migration through the normal tissue of 2-3 \u03bcm/h. One tumour line which tended to form aggregates on the chorioallantoic membrane elicited a pronounced rejection response from the ectoderm of the membrane. Colcemid, which inhibits the formation of cell processes and the directional migration of cells, and dibutyryl cyclic AMP, which restores certain aspects of normal behaviour to tumour cells"}
+{"text": "Tumours of the head and neck were examined for gene amplification and expression of the epidermal growth factor (EGF) receptor by Southern blot and Western blot analyses. The EGF receptor gene was found to be amplified in four (19%) of 21 squamous cell carcinomas. The EGF receptor was overexpressed in eight (53%) of 15 squamous cell carcinomas examined, including all four tumours showing gene amplification. No amplification or overexpression of the EGF receptor gene was detected in any of nine malignant or eight benign tumours of other types of the head and neck. The tumours showing amplification and/or overexpression of the EGF receptor gene (8/15) were all identified histologically as well differentiated squamous cell carcinomas, whereas none of the histologically less differentiated squamous cell carcinomas (0/9) showed amplification and/or overexpression of the EGF receptor gene. Within our sample set, no correlation was evident between amplification and/or overexpression and the clinical stage or tumour site. Our results support the possible involvement of gene amplification and overexpression of the EGF receptor in a subclass of squamous cell carcinomas of the head and neck."}
+{"text": "The objective of this study was to determine the role of endoscopic Nd:YAG laser treatmentin the preoperative or postoperative management of tracheobronchoplasty.Eighteen patients with severe stenotic lesions of the trachea or bronchus underwentNd:YAG laser treatment. Nd:YAG laser treatment was performed in the preoperativeperiod in 14 patients and in the postoperative period in 4 patients. The indications forNd:YAG laser treatment included emergency airway dilatation, confirmation of the distalmargin of tumor, and safe tracheal intubation in patients with severe tracheal stenosis.The indications for Nd:YAG laser treatment in patients with severe stenosis of themainstem bronchus were confirmation of the distal margin of tumor and recovery oflung ventilation during the preoperative period and reopening of the bronchial lumen toprevent obstructive pneumonia in the postoperative period. Among patients treated withNd:YAG laser preoperatively, the indications were completely achieved in all 14patients, except for 1 patient with adenoid cystic carcinoma who underwent treatment ofthe right mainstem bronchus. Among patients treated with Nd:YAG laser postoperativelythe indications also were achieved in all 4 patients with severe granulomatousstenosis of the bronchial end-to-end anastomosis following sleeve lobectomy. In conclusion,endoscopic Nd:YAG laser treatment played an important role in the perioperativemanagement of patients undergoing tracheobronchoplasty."}
+{"text": "A fully automated flow system for on-line monitoring ofanalytes/parameters of interest in aquaculture is described. Theapproach has been optimized for the photometric determination ofnitrite and ammonia and the continuous monitoring of pH,conductivity and dissolved oxygen, but these analytes/parametersare readily changeable as required. The system has been tested bymonitoring these species in the input and output sea water streamsof tanks at a fish breeding farm and also by monitoring watercontaining high concentrations of fish feed."}
+{"text": "The longer survival of neoplastic patients achieved through improvements of therapeutic regimens has increased the relative risk of developing a second primary tumour (SPT). In this context, conventional cytopathology can define tumour histotype only in a small fraction of cases. In this study, we have evaluated whether selected combinations of monoclonal antibodies (MAbs) to tumour-associated antigens (TAAs) can increase the accuracy of conventional morphology in detecting second primary tumours (SPTs) in two particularly difficult areas of cytodiagnosis, namely that of effusions and pulmonary fine-needle aspirates (FNAs). The immunocytochemical (ICC) analysis of 334 cytological specimens demonstrated that the use of our selected panel of MAbs could allow a more efficient identification of SPTs in comparison with conventional morphology. This diagnostic improvement was statistically significant (P < 0.0001). The present findings show that the immunophenotyping of effusions and FNAs, providing a more accurate and objective identification of SPTs, may have significant therapeutic and epidemiological relevance."}
+{"text": "Congenital abnormalities of the coronary arteries are uncommon but can be associated with important cardiac events depending on their location and the course of the aberrant artery. Conventional angiography has been the gold standard for the diagnosis of these anomalies. The recent development of cardiac CT has allowed accurate and non-invasive depiction of coronary artery anomalies in terms of their origin, course and termination. We describe the case of a patient presenting with acute inferior myocardial infarction who was found to have a very rare congenital abnormality consisting of an anomalous origin of the right coronary artery from the mid-segment of the left anterior descending. Coronary angiography and cardiac CT angiographic images are shown and discussed. On examination, she had pulmonary oedema with symmetrical and equal pulses in both upper and lower limbs. She was given intravenous furosemide 100\u2009mg, and an electrocardiogram (ECG) was obtained showing sinus rhythm with right bundle branch block (RBBB) and ST segment elevation in leads II, III and AVF  was obtained from the patient(s) for publication of this case report, including accompanying images."}
+{"text": "Population aging has brought about a number of challenges to public health and primary health care systems due to increases in the prevalence of non-communicable diseases (NCDs). As a country with one of the largest populations globally, China is confronting a rising number of chronic NCDs including cardiometabolic related conditions. This mini-review investigates the link between NCDs and cognitive impairment through common risk factors. Identifying risk factors is important for the prevention and management of these chronic conditions. In addition, this review also identifies the role of primary health care services in reducing behavioral risk factors for NCDs and cognitive impairment. Addressing shared determinants and pathways is important in the design of public health interventions and primary health care services in China. Monitoring and management of NCD biomarkers and behavioral risk factors may also be beneficial for cognitive health among older Chinese. As China's population ages, the country is confronted with rapidly changing health profiles. According to the Global Burden of Diseases, the pattern of causes of deaths has also changed significantly away from communicable diseases and as of 2016, the main causes of death were cardiovascular diseases (41%), cancers (25%), chronic respiratory diseases (10%), and diabetes (4%)  compared to Western China (14.7%) . A more There is increasing evidence on the significant relationship between type 2 diabetes mellitus and CI/MCI among older adults in China , 15, 33.Cardiovascular diseases and cognitive decline share common risk factors including high blood pressure, which was found to be a predictor for CI/MCI among older adults , 34. A cThere is evidence documenting the relationships between chronic obstructive pulmonary disease and cognitive impairment among older Chinese. A nationally representative Chronic Disease and Risk Factor Surveillance study covering 31 provinces across China reported chronic cough, chronic phlegm, and self-reported symptoms in urban areas, but only chronic phlegm in rural areas was associated with cognitive impairment . In addiSmoking and alcohol consumption have been found to be major behavioral risk factors for cognitive impairment among older Chinese , 25. ForThe benefits of being physically active has been widely documented among older Chinese with direct effects across multiple domains of cognitive functions from engaging in modern aerobic and traditional Chinese exercise such as Tai Chi and Qigong \u201337. A syLow socioeconomic status has been commonly linked to disparity in mild cognitive impairment , 19, 39.The role of demographic characteristics, particularly old age and being female is associated with cognitive impairment among older persons across China , 19. TheMultiple epidemiological studies have determined that geographical disparities result in an increase in cognitive impairment among older Chinese in rural areas , 44. ResThis mini review brings together recent evidence on cognitive and mild cognitive impairment among older Chinese highlighting the link to shared behavioral lifestyle risk factors of cardio-metabolic conditions. The strength of this mini review draws upon many large epidemiological studies across China including longitudinal studies where possible. Notably, the mini review focuses on observational population-based data with less evidence from clinical studies. Because of the smaller scope of the mini review, which is primarily based on international databases, relevant articles in Chinese may be omitted. This could potentially result in under reporting bias in some geographical areas that have limited exposure to English publications.The definition and severity of cognitive impairment vary across studies, however, most of these studies use international standardized measures. It has been argued that these measures should have differing cut-offs for older and less educated respondents within the Chinese context . Care shUnder the national Healthy China Initiative, the Chinese government has put in place the plan toward 2025 for the prevention and treatment of chronic non-communicable diseases . The firSince the health system reforms in 2009, achieving essential public health services and community-based non-communicable disease management has been rolled out nationwide to improve availability and accessibility of health services . PrimaryFrontiers Special Topic Chronic Illness and Aging in China present a strong argument for the training of general practitioners in China in behavior change and chronic illness management in order to prevent and manage behavioral risk factors in chronic illness. Wang et al. (In order to implement these reforms in primary health care settings the health care workforce needs to be upskilled , 56. Theg et al.  in an anThe recent World Bank China Joint Study Partnership Health Policy Summary \u201cDeepening health reform in China\u201d  advocateAs well as training the healthcare workforce in people-centered care, risk factor and chronic disease management; and the empowerment of patients in the management of their illness, system level changes are also needed. In addition to workforce strengthening and engaging citizens in their health care, the Deepening Health Reform in China policy statement identifies another six levers of reform including shaping a tiered health care delivery system, improving quality of care, reforming public hospitals, realigning purchaser and provider payment incentives; strengthening the health care private sector and modernizing health service planning [ p. xviiiGiven our current knowledge about the relationships between NCDs and cognitive impairment it is important that early public health interventions and primary health care services address risk factors across the lifecourse and that these interventions and services are well-targeted. We argue that attention to prevention through reducing behavioral risk factors such as excess tobacco and alcohol consumption and physical inactivity and the management of abnormal blood pressure and blood glucose all have the potential to impact positively on cognitive and mild cognitive impairment and non-communicable diseases in China.VY and CB conceptualized the study, drafted the manuscript, and finalized revisions for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The emergence and rapid development of dementia friendly initiatives (DFIs) represents growing global awareness of needs of persons living with dementia (PWD). Policy and practice efforts across regions and countries made to make physical and social environments more friendly, inclusive, and capable for PWD vary. When designing, implementing and evaluating DFIs, countries at different socioeconomic development stages need to set priorities based upon their local needs and cultural norms. This East Meets West symposium aims to understand the variability and progress of the DFI in the global context, highlighting experiences from two countries: U.S.A. and China, where about one third of the world\u2019s total estimated 47 million PWD live. The first study from Shanghai emphasizes efforts by local health care professionals to promote dementia screening and improve diagnosis, with the ultimate goal to improve dementia literacy and build a dementia friendly city. The second paper describes a community-based participatory approach to develop dementia friendly communities in Beijing, highlighting the significance of non-governmental and governmental collaboration. The DFI in Florida underscores the partnership among multiple sectors with an emphasis of the involvement of PWD, while the DFI in rural Michigan stresses care system coordination. The last paper based upon an online survey of DFI stakeholders from six WHO regions echoes successful features of DFIs  identified in Chinese and U.S. examples, and identifies variations in strategies used to modify physical and social environments across countries. Invited panelists from different sectors will share comments in the end."}
+{"text": "According to the World Health Organization, in 2015 dementia affected 47 million people worldwide (or roughly 5% of the world's elderly population), a figure that is predicted to increase to 75 million in 2030 and 132 million by 2050  and current consensus has established the need for early recognition.An intensive research effort is being devoted to the development of novel neuroimaging biomarkers that can provide an alert even before the cognitive decline appears. Structural and functional magnetic resonance imaging (MRI) and functional and molecular nuclear medicine neuroimaging techniques including single-photon emission computed tomography (SPECT) and positron emission tomography (PET), are widely used in combination with other blood, cerebrospinal fluid (CSF), and genetic biomarkers for early diagnosis of dementia.Large multicenter studies are currently investigating the value of existing and novel multimodal and longitudinal neurodegeneration biomarkers. The vast amount of data available represents an opportunity for the development of more accurate statistical models of neurodegeneration enabling the early recognition as well as the characterization of the progressive course of dementia.The aim of the Research Topic \u201cMultimodal and Longitudinal Bioimaging Methods for Characterizing the Progressive Course of Dementia,\u201d published in Frontiers in Aging Neuroscience, was to present the current state of the art in the theory and practice of multimodal and longitudinal neuroimaging analysis approaches for characterizing the progressive course of dementia. The Research Topic features 14 research articles. Most of the contributions analyzed disease progression and the relationships among underlying pathological changes.. Ten healthy controls, 20 IPD, 39 PSP, and 41 MSA patients were studied using MRI and Structural Imaging Evaluation with Normalization of Atrophy (SIENA)  and atypical parkinsonian syndromes (APS) is still a challenge, specially at early stages when the patients show similar symptoms. During last years, several computational approaches have been proposed in order to improve the diagnosis of PD, but their accuracy is still limited  tract integrity between AD and LOBD cases, and their correlation with systemic inflammatory, neurotrophic factors, and oxidative stress blood plasma biomarkers. Differences in WM tract integrity reflected greater behavioral and mood clinical features of LOBD and together with alterations of neuroinflammatory blood markers, different impact of neuroinflammation in both diseases.Bipolar disorders such as the Late Onset Bipolar Disorder (LOBD) is often difficult to be differentiated from neurodegenerative dementias due to common cognitive and behavioral impairment symptoms. In a multimodal study Yap et al. focuses on visualization of hyperactivation in neurodegeneration based on prefrontal oxygenation showing a comparative study of mild AD dementia, mild cognitive impairment, and healthy controls. Functional near-infrared spectroscopy (fNIRS) signals were analyzed together with a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC). It was shown that the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms, and hypoactivation in mild AD dementia could reflect an inability to compensate.The paper by H\u00f6ller et al. showed that combining quantitative markers from SPECT and EEG increased discrimination of MCI and AD cases from people with depression, and that the resulting diagnostic accuracies were higher than the diagnostic accuracy of each single modality alone.Several works have suggested that multimodal data analysis has the potential to improve the diagnosis of dementia  was analyzed and cortical surface based measurements were computed from longitudinal and cross-sectional MRI scans. Their results using feature selection and a voting classifier suggested that longitudinal features were not superior to the cross-sectional features for MCI subtype classifications.The paper by Sarica et al. provides a systematic review of random forests  by examining postsynaptic dopamine D2/3 receptors. Segovia et al. proposed a novel methodology to preprocess 18F-DMFP-PET data that improves the accuracy of computer aided diagnosis systems for PD. PET data were segmented into 4 maps according to the intensity and the neighborhood of the voxels using an algorithm based on Hidden Markov Random Field. Then, the maps were individually normalized so that the shape of their histograms could be modeled by a template Gaussian distribution. The results outperformed those reported by previous approaches.Emerging imaging modalities are also covered in this Research Topic. Simultaneous EEG-fMRI acquisitions allow combining the spatial resolution of fMRI with the temporal resolution of EEG. The paper by Alderson et al. used a multimodal approach to assess white matter integrity between thalamus and default mode network (DMN) components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Their methodology enabled the DMN of each subject to be identified using independent component analysis (ICA) and resting state effective connectivity that was calculated between thalamus and DMN nodes. Significant changes in the diffusivity metrics of thalamic white matter projection tracts to hippocampus, posterior cingulate cortex and lateral inferior parietal lobe were identified.The article by Mueller and Weiner developed a graph and cluster analysis on a sample of Florbetapir-F18 PET and task-free 3T functional and structural MRI and found distinct pattern of hypersynchrony with underlying white matter connectivity in amyloid positive vs. negative cognitively normal older subjects.Based on the notion that amyloid may induce neuronal network hypersynchony in eary AD stages the work by Sch\u00f6necker et al. aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic FTD and ALS patients or healthy controls.Mutation carriers may exhibit distinct neuropathological features of neurodegenerative diseases. As an example, patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation are characterized by two distinct types of characteristic protein depositions. The study by Salvatore et al. analyzed progression of AD using a machine learning method in a cohort of 200 subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Subjects were followed-up for 24 months, and grouped as AD, progressive-MCI to AD, stable-MCI, and cognitively normal (CN). Structural T1-weighted MRI and neuropsychological measures were used to train a classifier to distinguish mild-AD patients (AD + progressive MCI) from subjects with a benign cognitive course (stable-MCI + CN). Principal component analysis (PCA) and partial Least squares (PLS) were used as feature extraction methods similar to previous studies  in 2014. Based on the broad availability of PET-CT scanners, the work by Segovia et al. proposed to include in the analysis the information about gray matter neurodegeneration provided by CT images in order to improve the diagnosis of AD. Specifically, standardized uptake values (SUVs) from 18F-FBB PET data were obtained using only voxels belonging to gray matter in CT images. The results suggested that SUVs calculated according to the proposed method allowed AD and non-AD subjects to be more accurately differentiated. This agrees with previous studies on the use of structural MRI scans to correct amyloid PET data for spill out effect of signal from gray matter to CSF and for spill in effect from white to gray matter  (Lehmann et al., In summary, the Research Topic provides a transnosological, transdisciplinary view on current developments in neuroimaging techniques and their application to neurodegenerative dementias. It depicts a dynamic landscape of emerging acquisition and analyses techniques that share, however, three key features:The combination of modalities within and beyond imaging techniques to improve group separation and modeling of longitudinal declineThe combination of data driven and model driven analysis approaches to get the best from both worlds: full exploitation of available data and top down restriction of the outcome space based on a priori assumptions on disease pathogenesisRelated to these features, the ability to test assumptions of underlying disease mechanisms in combinatorial multimodal imaging analyses, crossing even the boundaries of single disease entities.Such highly interdisciplinary approach serves as blueprint not only for future research in neurodegenerative dementias but in other neuropsychiatric diseases as well.JR, JG, and ST equally participate in the preparation of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The Age Friendly Health Systems initiative is a culture change movement funded by the John A. Hartford Foundation in collaboration with the Institute for Health Care Improvement. Transforming clinical training environments into integrated geriatrics and primary care systems to become Age-Friendly Health Systems must incorporate the principles of value-based care and alternative-payment models. This symposium will discuss how the implementation of the Geriatric Interprofessional Team Transformation in Primary Care (GITT-PC) model and the Reducing Avoidable Facility Transfer Model (RAFT) in primary care will improve patient outcomes focused on the 4M\u2019s of the Age Friendly Health System. The success of the GITT-PC model focuses on 4 Medicare reimbursable services including the Annual Wellness Visit, Transitional Care Management, Chronic Care Management and Advance Care Planning. The RAFT model focuses on What Matters Most to residents of long term care facilities and reduces ED visits and hospital transfers through elicitation of goals of care and 24 hour virtual support from an interprofessional geriatric team."}
+{"text": "Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well as development of new biomarkers; drugs targets and therapies. In this review; we argue that the recent; successful advances in MS technologies towards cancer omics studies provides a strong rationale for its implementation in biomedicine as a whole. One of the most important aspects of medical research is the establishment and development of better therapeutic options for patients. Because of the individual variation of the human proteome; precision and personalized medical strategies are of relevance; based on the specific protein or molecular signatures and cellular context . Due to The \u201cOmics\u201d represent a set of complex technologies used to study the roles; relations; and activities of the different types of molecules that compose the cells of an organism. The aim for any biological sample is the detection of patterns or specific genes (genomics); mRNAs (transcriptomics); proteins (proteomics) and metabolites (metabolomics) . The genGenomics relies on the studies of the structure; function and relative expression of a gene in an organism ,3. TotalFunctional genomic analysis comprises both genomics and transcriptomics; using DNA-seq and RNA-seq to describe genes and transcripts with relevance to protein prediction and their functionalization or interconnection to different patients ,12. TranHigh-throughput RNA sequencing (RNASeq) has appeared as an attractive and cost-effective technique for transcriptome profiling ,19. RNASProteomics refers to all proteins present in a specific cell; a pattern that is highly dynamic between cell types and environment response. The proteome is controlled by a wide range of factors; such as the complexity of protein synthesis; degradation and modification; which effects protein localization; function and connection between partners. Proteomics links our understandings of complex biological systems through the expressible; identifiable; modifiable intermediary because proteins represent quantifiable specific characteristics of disease . MoreoveProteomic analysis is considered a useful approach to identify the targets of bioactive compounds; drugs; chemotherapy ,27 and tThere are two major strategies applied to proteomics: top-down based on intact protein level analysis or bottom-up based on peptide level analysis. Bottom-up proteomics is distinguished by proteolytic digestion before mass spectrometric analysis; which allows for identification of proteins and determining amino acid sequences or post-translational modifications. This strategy combines MS with techniques like gel electrophoresis for protein purification or liquid chromatography for proteolytic peptides or protein fragments separation . It comePost-translational modifications can be widely defined as covalent processing events that change the properties of a protein by proteolytic cleavage or by addition of a modifying group to one or more aminoacids . Thus; tMetabolomics is the study of global metabolites profile in the cell; tissue or organisms; setting specific conditions for research experiments ,37,38. MIt is important to achieve qualitative and quantitative information regarding metabolites that occur under normal conditions to be able to detect abnormalities due to changes in environmental factors ,42. The The simplified representative relationship between omics and corresponding analysis are presented in Genomics; transcriptomics; proteomics and metabolomics are interdisciplinary research areas and together can accelerate studies for early diagnosis of many diseases such as cancer; diabetes ; cardiovIn the future; omics technologies may offer us the possibility to improve approaches that intend to be predictive; preventive and personalized ,58. SpecIn order to achieve this new vision for personalized medicine; an important role is attained by mass spectrometry which allows a rapid and early diagnosis; specific therapies for patients and real-time therapeutic drug monitoring .The purpose of this paper is to present the successful applications of mass spectrometry in cancer research to emphasize the impact mass spectrometry-based techniques can have for the future of personalized care.m/z) ratio; of analytes at concentrations in the attomolar range (10\u201318). This is an important feature of the technology; which ensures the ability to accurately measure an analyte in the presence of other interfering products (such as degraded products that may be present in the processed sample matrix). Despite the difficulty of studying proteins from biological systems  due to the dynamic nature of protein expression; this system obtains unique fingerprints correlated to proteins/peptides from known databases facilitating identification of unknown compounds  peaks significantly differentially expressed in the patient training set; of these; only two were the peptide sequences and proteins were known; uridylate kinase and Glucosamine--fructose-6-phosphate aminotransferase [In another experiment; Wang et al. used MB-WCX coupled with MALDI-TOF MS to compare the serum peptidome profiles of advanced lung adenocarcinoma patients treated using first-line platinum-based pemetrexed chemotherapy . Using tnsferase .Akpinar et al. evaluate the differentially expressed proteins between parathyroid adenomas (PA) and parathyroid hyperplasia (PH). In terms of methodology; they combined 2D gel electrophoresis (2DE) with MALDI TOF-TOF MS. According to their expression levels; they identified a total of 40 proteins whose levels have changed: fourteen overexpressed in PH and 26 overexpressed in PA. The results particularly suggest that proteins overexpressed in PH were mitochondrial. Thus; this emphasizes the demand for more research into the role mitochondrial activity plays in disease and perhaps the discovery of novel mitochondrial marker used for differentiating PH from PA .Mass spectrometry imaging (MSI); the newest technique; is used to investigate the molecular distribution of metabolites; proteins and lipids without labeling. This novel ionization technique allows to analyze the tissue by desorption electrospray ionization (DESI); where the corresponding steps in sample preparation are reduced. Most interestingly; this technique has a great applicability in intraoperative tumor assessment. Meanwhile; it facilitates characterizing the differences between cancer and non-cancer tissue based on lipidomic information and the correlation of lipid distribution with tissue morphology. Distinctive lipid profiles that are associated with different forms of cancer have been investigated with this technique and the results correlate with histopathological examination . InevitaTo best characterize the variations within the same protein structure and; in essence; to investigate post-translational modifications; the protein ideally needs to remain intact meaning not digested or fragmented. This requires top-down proteomic strategies for analysis. Using electrospray ionization (ESI) and quadrupole (Q) mass analyzer is one such alternative for serum biomarker identification using liquid chromatography for sample fractionation and ESI-Q technology . To analm/z ratio of each ion can be determined from the length of the tube; the kinetic energy given by the electric field and the time travelling the length of the tube. Some examples of modified surfaces used in SELDI are: CM10 (weak-positive ion exchange); H50 ; IMAC30 ; and Q10 (strong anion exchanger) [m/z reports; has data difficult to analyze and interpret; and lastly; does not produce identities. Consequently; it has been replaced with MALDI in most applications.Surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) is a top-down proteomics approach; introduced in 1993 and used for the quantification of small peptides and proteins relative to large proteins. SELDI-TOF MS is an older alternative to MALDI-TOF MS . In thischanger) . RealistThis comprehensive section is a roadmap of MS applications in medicine; focusing on diagnosis and prognosis in cancer; immunotherapy; investigation of proteins in laboratory; and clinical trials.Early diagnosis ensures possibilities of eliminating malignant tissues before metastasis to other organ systems. In 2000; National Cancer Institute established the Early Detection Research Network that relies on the development of biomarkers and technologies for the early diagnosis of cancer . The proMolecular diagnostic development represents the key in individualized medicine. Current diagnosis and prognosis classification based on anatomical; clinical methods do not highlight the heterogeneity of complex diseases; and cannot predict the therapy response or clinical outcome ,131. BasNowadays; many studies strive to diagnose and treat different type of cancers at an early developmental stage. An important technique used in cancer diagnostics is proteomics that facilitates protein biomarker identification from blood samples  ,137,138.A diagnostic assay relies on the development of antibodies; which involve important steps such as target-specific antigen discovery and identification; sensitive in vitro assay to detect antigen-specific antibodies; in vivo detection of antibodies from accessible body fluids ; and assay validation for clinical use ,136. ThuIn recent decades; an intense effort was directed toward the development of new therapies to enhance the survival rate of cancer patients. Unfortunately; the majority of patients with cancer are diagnosed in the late stages of the disease with regional or distant dissemination of cancer cells. However; when clinicians try to diagnose the cancer in the early stage when the tumor is limited; the survival rate can exceed 85% . Mass spm/z reports and is limited in that it does not produce identities.First up; Surface-enhanced Laser Desorption/Ionization (SELDI), a technique extending the base technology of mass spectrometry using a time-of-flight (TOF) analyzer to calculate the mass-to-charge ratio. SELDI-TOF-MS has great clinical diagnostic potential as a technology for detection or disease screening; as demonstrated for prostatic adenocarcinoma ,149. HowTo determine the metabolic profiles for diagnostic purposes; ultra-performance liquid chromatography coupled with a quadrupole time-of-flight (UPLC-QTOF) mass spectrometer could be used. Matos Do Canto et al. utilized UPLC-QTOF to compare metabolic profiles in the ductal fluid from breast cancer patients with non-affected contralateral controls from the same subjects. In this way; they were able to differentiate the metabolites from tumor microenvironment where breast cancer forms. Moreover; they identified different metabolites with significant changes in the cellular microenvironment offering information about tumor evolution. Thus; this MS-based technique for metabolomic profiling aims is to distinguish early stage from advanced metastatic cancer and to develop a model for the early detection of breast cancer . For oraMoreover; Chen Y et al.; using the same technique GC-MS in their study; were able to differentiate the metabolite profiles of urinary samples from patients with gastric cancer. They distinguished a group of cancer metabolites; which exposed a diagnostic value for gastric cancer as important biomarkers for gastric cancer screening . Lastly;Despite an increased worldwide life expectancy; the percentage of deaths caused by so-called non-communicable diseases; respectively cancer; heart disease and stroke; is increasing. Based on these statistics; the collective of researchers are sparking major efforts in discovery of novel and efficient biomarkers which could serve as better prognostic predictors of cancer. The rapid evolution and promising results from human proteome  and metaUsing mass spectrometry as a method of analysis provides high and consistent percentages of prognostic biomarker values achieved for the following types of cancers: breast; lung; colon; prostate; liver; pancreas; melanoma; thyroid; gastric and oral. In conducting these types of studies; various types of biological samples were analyzed; among which: plasma; serum; tissue; cultured cell lines; urine; saliva or seminal plasma . A briefThe applicability of mass spectrometry in gynecological oncology has been a real success; where the outcome of prognosis is now over 90% in the evaluation of some patients diagnosed with ovarian cancer versus healthy subjects . It was Depending on the different type of cancer; there is only a quantifiable patient response to immunotherapy in about 10\u201340% of the cases due to the fact that there are no accurate predictive biomarkers in routine use. The identification and development of predictive immune biomarkers can bring clear advantages to patients such as enhancement of the response rates in immunotherapy; decreased cost and toxicity caused by the chemotherapeutic agents ; improveImmunotherapy used for cancer treatment generally involves a wide range of concepts designed to activate the immune system or restore the anticancer immune response. Thus; recognition and elimination of cancer cells and the tumor microenvironment through an endogenous defense mechanism can be used to determine the stabilization and remission of the disease. In this way; cancer immunotherapy can enhance treatment efficiency through the combination of external treatments such as chemo-; radio-therapy or surgery with the internal defense . SeveralFor different oncologic diseases there are some therapeutic antibodies; such as antibody-drug conjugates; that present a higher binding specificity and good pharmacokinetic for drug delivery targeting the cancer cells. Thus; the investigation into the primary structure of the antibodies is known as peptide mapping. This concept for mapping represents an important tool in understanding the primary structure of any therapeutic protein; amino acid composition; sequence variants; glycosylation heterogeneity and post translational modifications .Cell-surface proteins play a fundamental role in signal transduction; ion transport; cell adhesion and cancer pathogenesis. Their profile could offer a better understanding about cell-surface proteome; more explicitly how regulation occurs and their active response to different intracellular or extracellular signals. Consequently; cell-surface proteins could be exploited as targets for diagnosis; prognosis and therapy. A major drawback is the lack of characterization and quantification of tumor cell proteins that are critical for marker identification during clinical diagnosis and prognosis; or of drug targets for therapy. Regarding this aspect; the mass spectrometry technology has been developed as a specific platform that integrates cell-surface protein capture in vitro and intact protein fractionation for tumor cell protein analysis . This maClinical classification of these protein molecules is measured as tumor markers; risk or prognostic markers; acute or chronic disease markers or hormone markers. Immunoassays are a common method used to detect protein analytes. In most cases; this method does not distinguish the different proteo-forms from the protein variants present in clinical sample . ConversA recent article describes an immunoaffinity-based methodology of removing interfering high-abundant blood-derived proteins from human plasma and tissue samples . Prieto To conclude this section; mass spectrometry encompasses all of the analytic laboratory demands for a fully integrated analysis from proteome profiling; biomarker discovery; protein degradation study; protein-protein interactions; protein-ligand interactions; and lastly; biological regulation through post-translational modifications .www.clinicaltrials.gov; it was determined that mass spectrometry is used in various ways for clinical trials; starting with the development of the drug and continuing with clinical trials in diagnosed patients vs. healthy volunteers (where is applicable).Through the literature study conducted on website m/z ratio of components; has the following qualifications for use. Firstly, and simply; biological sample analysis of tissues meaning sampling and comparing of cancer tissue to normal adjacent tissue. Secondly; biological sample analysis to determine substances/compounds of interest; which entails bioavailability/bioequivalence studies of analytes; evaluation of the relationship between oxidative DNA damage and use of antioxidants or mineral supplements; or determination of percentage of volatile organic compounds in the exhaled breath through advanced techniques like MALDI-TOF analysis  or rapid evaporative ionization.Based on information obtained from approved clinical trial protocols; mass spectrometry; due to the accurate mass measurements based on ionic forms of samples which are separated according to It has been widely used in the evaluation of various types of cancer diagnoses; in different stages  such as: brain; breast; colon; endometrial; head and neck; lung; melanoma; ovarian; etc.At present; even if the observational clinical trial is in the recruitment stage; the appropriate activities are being implemented to determine the advantages and disadvantages for the treated patients following therapies concordant with GPS Cancer test; offered by NantHealth. This revolutionary molecular test is integrating the most relevant quantitative measurements; respectively, the targeted proteomics detected by whole genome (DNA); mass spectrometry and whole transcriptome (RNA) sequencing; of both normal and cancer tissue. The results will greatly support oncology specialists in providing treatment; as a continuous promotion of personalized medicine and; last but not least; in decreasing costs associated with the care of cancer patients. The inclusion criteria for the study population; as per protocol requirements; contains full eligibility enrolment for metastatic pancreatic cancer; breast cancer patients; advanced stage lung cancer; metastatic colon cancer or metastatic non-resectable malignant melanoma at any time in their treatment history.The types of MS analysis correlated with clinical trials are grouped into the following categories: dosage and purity analysis of the interest active substance; quantitative and qualitative analysis of the compound where evaluation occurs during the clinical study; routine analysis  for patients enrollment; or proper response evaluation corresponding to the approved clinical trial protocol .However; researchers conducting the observational clinical trials still lament that patient recruitment remains a great challenge due to low percentage of participation ; 40% of studies failed to achieve minimum patient enrollment; fear of patients to reduce the quality of life; concerns involved receiving placebo; possible side effects; no-active encouragements from physicians; budgetary constraints of trial participation; the difficulty of eligibility according to inclusion/exclusion criteria; or lack of public education on emphasizing the importance of clinical trials.Mass spectrometry has the potential to become a multi-platform analysis for all small molecules from biological samples; especially when coupled with other techniques like liquid chromatography to enhance sensitivity; selectivity; speed; molecular specificity and high-throughput chemical information. It is a tool for the identification and quantification of expression; modifications and interactions of proteins; powerful in offering understanding in cellular signaling pathways; detection of drug metabolites; diagnostics and drug discovery.Using mass spectrometry; analyses which rely on the identification of cellular proteins and pathways causing DNA damage under the influence of chemotherapeutic agents; can be performed. Through this method; the protein; drug and metabolites from human serum or plasma can be detected and quantified. The advantages of this method include its enhanced sensitivity and selectivity while; concurrently; decreasing run time; elution time and consumption of solvent or sample. MS provides a more complete profile of regular and reactive metabolites; providing a great lead in drug metabolism monitoring and treatment streamline. All of this demonstrates that MS based techniques have been successfully implemented for omics studies; in particular for cancer research; meaning they could be extended to encompass broader medical studies as we adopt the concept of personalized medicine."}
+{"text": "Vulnerable older adults needing surrogate decision makers typically rely upon others for care and are unable to advocate for themselves. The issue of EFFE perpetrated by family members designated as surrogates has become highly visible nationally, yet no reliable, empirical documentation exists on the nature or extent of exploitation by surrogate perpetrators. In collaboration with the National Adult Protective Services Association (NAPSA), we prospectively gathered APS data from six geographically diverse counties on 450 substantiated cases of abuse by POAs, representative payees, and guardians of vulnerable adults 65+ living in community settings. This presentation will highlight how family member surrogates perpetuated abuse and the outcomes on elder victims. These findings elucidate person and process-level factors  within the context of the APS system and can inform practice and policy recommendations for better prevention, detection, investigation, and intervention in these challenging cases."}
+{"text": "Biosensor-based devices are pioneering in the modern biomedical applications and will be the future of cardiac health care. The coupling of artificial intelligence (AI) for cardiac monitoring-based biosensors for the point of care (POC) diagnostics is prominently reviewed here. This review deciphers the most significant machine-learning algorithms for the futuristic biosensors along with the internet of things, computational techniques and microchip-based essential cardiac biomarkers for real-time health monitoring and improving patient compliance. The present review also discusses the recently developed cardiac biosensors along with technical strategies involved in their mechanism of working and their applications in healthcare. Additionally, it provides a key for the ontogeny of an effective and supportive hierarchical protocol for clinical decision-making about personalized medicine through combinatory information analysis, and integrated multidisciplinary AI approaches. Cardiovascular diseases (CVDs) and stroke are at the top causing death globally. World Health Organization (WHO), approximate death of 17.7\u00a0million people due to CVDs in 2015 which represented 31% of all global deaths WHO . Among tRecent advances in the field of artificial intelligence (AI) using machine learning and its successful use in biomedical sciences have cast new areas and tools in creating novel modeling and predictive methods for clinical use including cardiac diseases  microscopy can be used for real-time visualization of second messengers in living cells and detection of alkaline phosphatase in human serum  can be briefed as a fast, cheap and effective process, which is carried out near the patient ambiance. Integration of biosensors with the wireless capabilities through Bluetooth, Wi-Fi, and GPS has eased the closeness of professional health expert and the home patient  is the simultaneous testing of the various analyte for diseases from a single specimen  based device being used for regular check up of patients with chronic disorders. It includes biosensors, machine-learning traits and telemedicine that connects the patients automatically to its clinicians upon noticing the threshold symptoms of disorder -based application integrated with AI along with biosensors for cardiac care can act as a virtual assistant. Real-time monitoring of a patient specific makes the diagnosis of the patient easier and well in time. It is understood that composing the result interpretation via machine learning and data analysis approaches are quite efficient and supports clinical decision-making (Wu et al."}
+{"text": "With the promise of better care coordination, better member outcomes, and lower costs, Medicare and state Medicaid programs are implementing population-based payment systems for older adults. Medicare Advantage (MA) plans are responsible for Medicare services for their members, Medicaid managed long-term services and supports (MLTSS) programs cover a broad span of Medicaid benefits, and some state initiatives enroll beneficiaries dually eligible for both Medicaid and Medicare and integrate benefits from the two programs. Simultaneously, Medicaid programs are attempting to shift LTSS utilization away from nursing homes and toward home and community based services (HCBS). The presentations for this symposium address aspects of this changing landscape using Medicare and Medicaid claims and other data and causal econometric models. The first paper considers the effect of MA utilization on SNF staffing, quality, and financial health. The second paper compares medical care utilization outcomes, specifically risk of hospitalization, for Medicaid nursing home residents to outcomes for similar Medicaid members receiving HCBS. The third paper presents an MLTSS initiative in one state in the context of national developments and considers the challenges of evaluating its impact. The fourth paper compares hospitalization rates for MLTSS populations to rates for dually eligible-beneficiaries not enrolled in MLTSS. The discussion will bring findings together to assess early gains and costs as these systems of care evolve."}
+{"text": "Applications and limitations of pre-clinical PK/PD models and future alternatives are reviewed in the context of HIV prevention.Prevention strategies against sexual transmission of human immunodeficiency virus (HIV) are essential to curb the rate of new infections. In the absence of a correlate of protection against HIV infection, pre-clinical evaluation is fundamental to facilitate and accelerate prioritization of prevention candidates and their formulations in a rapidly evolving clinical landscape. Characterization of pharmacokinetic (PK) and pharmacodynamic (PD) properties for candidate inhibitors is the main objective of pre-clinical evaluation.  The majority of HIV transmissions currently occur via the genital and the colorectal tracts. Following infection of the initial mucosal founder population  for PrEP and post-exposure prophylaxis (PEP), broadly neutralizing antibodies (bNAbs) delivered by passive immunization ; AUC (area under the curve for drug concentration during a period of time); Tmax (time to achieve maximum concentration); t1/2 ; kel (elimination rate over time); MIC ; MEC ; T (time the concentration remains over the MIC or MEC); IC50 (50% inhibitory concentration); EC50 (50% effective concentration), extent of viral replication at the last time point of the assay or during a period of time ; cytotoxicity and immunological toxicity. The two main read-outs required to calculate these parameters are drug concentration and level of infection after treatment of the model with candidate inhibitors. Drug concentration can be measured as cell-free drug  or intracellularly (in cells or tissues) and new analytical methods are constantly being developed to measure the concentration of candidate inhibitors in these different matrixes. Intracellular measurements are necessary for inhibitors that require metabolization for activation such as some reverse transcriptase inhibitors. Evaluation of viral replication is specific for each pre-clinical model and can be done through measurement of a reporter signal, of gag protein (p24 for HIV and p27 for SIV) by ELISA, or of viral RNA/DNA by PCR or qRT-PCR ; Cmax ; CAssays that provide data to calculate PK/PD will be defined by multiple factors including, among others, the candidate inhibitor, the dosing route, the formulation and the anatomical site of action. ARVs and modulators of mucosal immunity can be formulated for oral or topical dosing, as injectables or as implants; bNAbs can be delivered topically, intravenously or intramuscularly for passive immunization. For mucosal prevention, independently of the dosing route, concentrations measured in the genital and colorectal tracts will need to be sufficient to inhibit viral infection, and these concentrations will be tissue-specific.in vitro models such as cell lines susceptible to HIV infection that allow calculation of PK parameters and evaluation of cellular toxicity. Compounds or Abs are then tested in ex vivo cellular models such as PBMCs, which in addition to PK/PD parameters can provide toxicity and immunological safety information.Inhibitory potency of candidate HIV inhibitors is initially screened in +T cell lines and non-lymphocytic cells that are transfected to express CD4 and CCR5 and/or CXCR4. Among the CD4\u2212 parental cell lines there are human glioblastoma cells, U87MG, which stably express human CD4 and CCR5 (U87 CD4+ CCR5+ cells) or CXCR4 (U87 CD4+ CXCR4+ cells)  CXCR4+ and GHOST (3) CXCR4+ CCR5+ cells] and that express green fluorescent protein (GFP) upon production of the viral trans-activator of transcription (Tat)  or luciferase expression when using reporter viral plasmids. CD4+T cell lines have also been used to study the mechanism of drug cellular transport and the implications of the PK profile of drug candidates for HIV prevention  cleavage into a blue-colored product (formazan) in viable cells  allowing multiple viral replication cycles and therefore, tend to be used after initial assessment in immortalized cell lines. Inhibitory activity, concentration and safety of drugs and Abs have been measured in activated PBMCs following ex vivo dosing or in cells obtained from animal studies  as well as cells derived from PBMCs, including monocyte-derived macrophages and immature dendritic cells (iDCs), provide more physiologically relevant cellular models for anti-viral activity measurements. These in vivo dosing of NHPs  and TZM-bl cells or autologous CD4+ T cells (Sagar et al., Another important model is based on co-cultures of different cell types. This model can be set up with cell lines and/or primary cells directly in contact to replicate the interaction between DCs and CD4+ cell lines such as TZM-bl cells (Pasetto et al., + cells for several days after dosing (Shen et al., Co-cultures of epithelial cells with target cells in a dual-chamber model mimicking trans-epithelial migration of drugs, Abs and virus have been successfully used to assess safety and allow studies of HIV transmission and efficacy of candidate inhibitors. Epithelial cell lines have been co-cultured with target CD4ex vivo culture of mucosal tissue explants (Grivel and Margolis, ex vivo dosing with candidate inhibitor and then with virus for ex vivo challenge. After incubation and depending on the type of tissue, explants are transferred either to new plates in submerged conditions for culture of cervicovaginal and penile tissue, or onto gelatin sponge rafts presoaked in media to help maintain the structure of colorectal explants by culturing them at the air-media interface. Non-polarized culture reduces the protective function of the epithelial barrier by exposing target cells on the edges of the explant directly to the virus, and therefore allows PD evaluation in what could be considered the \u201cworst-case scenario,\u201d however it also represents the \u201cbest-case scenario\u201d of drug or Ab availability to prevent infection of the target cell.The next phase in PK/PD evaluation often utilizes tissue models such as TM or surgical glue. These models have been prioritized for evaluation of formulated inhibitors to evaluate the ability of the formulation to deliver drugs or Abs to the target cells across the epithelial barrier and to assess the safety profile of the formulation toward the epithelium. Polarized systems require larger tissue explants for an increased surface exposure to the candidate inhibitor, for a correct orientation of the epithelium and to avoid incorrect sealing of the explant edges.In polarized models the tissue epithelium is oriented upwards on the apical chamber of a trans-well system and the edges are sealed using agarose, Matrigelin vivo is replicated in the tissue explant model with lower read out values of infection in cervicovaginal explants after challenge with a normalized viral input titer (Lapenta et al., The different mucosal portals of HIV entry have histological and immunological specificities such as epithelium type, abundance of activated HIV-target cells, drug transporter profile, Ab isotype expression, and pH, among others (Fischetti et al., Viability of explants has been questioned. However, despite progressive decay in structure, CD4/CD8 cell ratios remain constant and viral replication is sustained (Fletcher et al., +T cells, such as PM-1 cells, to assess anti-viral activity of a drug against dissemination by migratory cells (Hu et al., In cervical and penile tissue models, cells emigrating from the tissue have been described and these can be cultured separately from the explant and in the presence of CD4To further model the PK/PD profile of a candidate inhibitor in a mucosal compartment and during intercourse, mucosal secretions can be added to the tissue explants. Addition of semen or seminal fluid does not affect the activity of reverse transcriptase inhibitors (Neurath et al., Safety of candidate inhibitors and their formulations can also be pre-clinically evaluated in tissue explants. Clinical trials testing the first generation of topical inhibitors revealed the importance of mucosal safety following enhancement of infection Honey, . CytotoxEx vivo modeling of the mucosal compartment provides efficacy, concentration, and safety data. Additionally, tissue explants recapitulate the viral replication fitness of wild type and resistant isolates observed in vivo in patients (Abraha et al., ex vivo challenge of tissue resections obtained from NHPs topically dosed in vivo (Cranage et al., ex vivo challenge of mucosal biopsies is increasingly being used as an endpoint of ex vivo efficacy of PrEP (Anton et al., ex vivo challenge (Gupta et al., Studies in NHPs delivered proof of principle that efficacy of topical dosing with tenofovir against rectal challenge could be replicated by Despite the variety of explant models, it has been shown that consistent results of anti-viral efficacy can be obtained among different laboratories through protocol standardization for a same model (Richardson-Harman et al., The tissue explant model will need to be further developed to assess the PK/PD profiles of new inhibitors and their formulations designed to provide long term efficacy. This will require the model to be adapted physically with protocols that will mimic, for example, mucosal efficacy of injectables; and define new biomarkers of safety and activity. New models should also be able to evaluate broad spectrum anti-viral drugs and compounds designed to maintain mucosal health.TM or silk (Chen et al., in vivo tissue could be resolved using three-dimensional bioprinting techniques (Mittal et al., The development of engineered human tissues as a model to study physiological functions and pathologies could lead to new systems for safety and PK evaluation of candidate HIV-inhibitors and ideally for efficacy studies. Initial models mimicking the intestinal epithelium were based on the culture of isolated intestinal crypts with human adult stem cells (Sato et al., These and future models will need to fully recapitulate the cellular diversity of mucosal tissues, the immune responsiveness and the donor-to-donor variation to provide pre-clinical PK and PD information on candidate HIV inhibitors.in vitro drug potency, animal efficacy data, stage of product development, cost of goods, existing safety data, and ability to measure PK/PD parameters in clinical trials. New PK/PD parameters or correlations might need to be defined to pre-clinically predict the outcome of clinical trials. This will require further development of existing models, which have not significantly changed in the last decade, and introduction of new models in the pre-clinical toolbox. Ultimately, validation of in vitro and ex vivo models will require in vivo studies in humans.Pre-clinical assays for HIV prevention remain critical to understanding the relative potential of new compounds and combinations and for selecting the best candidates, their formulation and dosing regimen. Furthermore, in an era where HIV cure research has been prioritized, pre-clinical models developed for prevention might be applicable for the evaluation of cure strategies. However, all pre-clinical assays have their limitations and their value in predicting clinical efficacy has yet to be established. Hence, the process of product prioritization needs to be based on a range of criteria that include: The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Background: The Project ECHO model utilizes a hub and spoke approach through which a team of experts co-mentors local providers in the management of complex cases while disseminating information about best practices and evidence-based care. Project ECHO is a promising model for improving patient care through transformation of the care delivery system. The UW ECHO in Rural and Frontier Care Transitions created an online community of practice comprised of local care coalitions dedicated to improving care transitions in Wyoming and Montana. This ECHO network provided a unique opportunity to support system- and provider-level implementation of best practices in care transitions. Methods: Semi-structured interviews were conducted with thirty ECHO attendees following participation in an ECHO session as either a participant or case presenter. Thematic analysis was used to analyze interview data. Results: Two overarching themes emerged 1) impact of the ECHO on the provider or healthcare team and 2) impact on the system. Participants indicated that the impact on the provider/healthcare team included an increased sense of community, increased awareness of community resources, increased knowledge of care transition strategies, and increased confidence in implementing best practices. Additionally, providers indicated increased utilization of community resources. Systemic impacts included increased involvement of interprofessional team members in patient care and utilization of ECHO recommendations to present systemic interventions and changes to colleagues, administration, and leadership. Conclusions: This ECHO network had a particularly strong impact on the provider and healthcare team as participants increased their knowledge, confidence, and use of best practices in care transitions."}
+{"text": "We read with interest the article by Tsutsui et al.  comparison of actual NEMA phantom image and digital reference object (DRO) developed by the Quantitative Imaging Biomarker Alliance (QIBA) FDG PET technical committee, and (b) use of the root mean squared error (RMSE) for evaluation of appropriate harmonization. The formula and figure of RMSE in their article were quite similar to ours.Of key importance, the use of the DRO was firstly published in 2015 , only anGiven this, we believe that the authors should have cited our work. None declared."}
+{"text": "Enterocytozoon group Microsporidia (EGM), includes parasites that infect the cells (and sometimes the nuclei) of invertebrates and fish hosts from aquatic habitats, terrestrial birds and mammals, and human patients with underlying immune-suppressive conditions such as HIV/AIDS  [The universal emergence of EGM is suggestive of multifactorial intestinal barrier dysfunction across susceptible host groups. Epithelial cells of the intestine form both metabolic and physical barriers to invasion by microbes and maintain an immunoregulatory function by influencing stasis of gut mucosal cells . Direct an hosts ). In add [AHPND] ). We hav [AHPND] . We pred"}
+{"text": "Climate change exerts adverse effects on crop production. Plant researchers have therefore focused on the identification of solutions that minimize the negative impacts of climate change on crops. This Special Issue comprises 23 articles that celebrate the 2020 International Year of Plant Health, highlighting the processes, mechanisms, and traits that will underpin future sustainability of crop quality and yield. These articles critically evaluate recent advances in our understanding of climate change impacts on plants, within the context of climate-smart agriculture.Global agriculture is dependent on a relatively small number of crop species, which have been bred to optimize productivity within a relatively narrow range of environmental variations . MoreoveOn top of the uncertainty regarding the future environmental impact of agriculture comes the looming threat to yield sustainability caused by climate change-induced fluctuations in weather patterns , nitrogen oxides (NOx), and ozone (O3).Respiratory pathways are crucially important determinants of plant defences against abiotic stresses and climate change. The importance of the alternative oxidase (AOX) in preventing the respiratory production of ROS and reactive nitrogen species (RNS) is discussed in the review by Arabidopsis thaliana. Reporter lines expressing the redox-sensitive green fluorescent protein (roGFP2) were used to measure the glutathione redox state of cells in each part of the flower. This study reveals that the ungerminated pollen resides in a highly oxidized state that is commensurate with quiescence. Moreover, analysis of the glutathione-deficient cad2-1 (cad2-1/roGFP2) mutants revealed that the pollen achieves high GSH/GSSG ratios upon germination and that this highly reduced state is required to sustain pollen tube growth (Glutathione (GSH) is the key redox molecule in all living cells and is directly involved in the maintenance of intracellular redox homeostasis. GSH is involved in numerous cellular processes such as detoxification of heavy metals and metalloids (The compartmentation of proteins is a fundamental concept in cellular regulation, but it has long been known that the location of many proteins is not totally fixed and that some proteins can relocate between different intracellular compartments, particularly between the cytosol and nucleus. The proteins and processes involved in redox-dependent intercompartmental switching is expertly discussed in the review by Finally, our current knowledge of the impacts of climate and related stresses on physiological processes in woody tree species and vine crops remains poor. The study reported by"}
+{"text": "This study considers the role of adult children in the core networks of older adults undergoing mental health change. Taking a multidimensional perspective of the network system, I consider (a) presence of child(ren), (b) contact with children network members, and (c) embeddedness of children within the network using longitudinal data from the United States. Parameters were estimated with generalized estimating equations from the pooled panel data. There was no evidence that mental health transitions lead to systematic forms of child reshuffling or increased contact with child ties. Children that remained in networks, however, showed increased contact with other members of the network when the parent underwent depression onset, but became less embedded when their parents had chronically high levels of depression. These patterns may have far-reaching consequences for older people and their children, which could include increased feelings of loneliness and social isolation for parent and child alike."}
+{"text": "The Ammonia Recovery Process (ARP) is an award-winning, low-cost, environmentally responsible method of recovering nitrogen, in the form of ammonia, from various dilute waste streams and converting it into concentrated ammonium sulfate. The ThermoEnergy Biogas System utilizes the new chemisorption-based ARP to recover ammonia from anaerobically digested wastes. The process provides for optimal biogas production and significantly reduced nitrogen levels in the treated water discharge. Process flows for the ammonia recovery and ThermoEnergy biogas processes are presented and discussed. A comparison with other techniques such as biological nitrogen removal is made. The ARP technology uses reversible chemisorption and double salt crystal precipitation to recover and concentrate the ammonia. The ARP technology was successfully proven in a recent large-scale field demonstration at New York City\u2019s Oakwood Beach Wastewater Treatment Plant, located on Staten Island. This project was a joint effort with Foster Wheeler Environmental Corporation, the Civil Engineering Research Foundation, and New York City Department of Environmental Protection. Independent validated plant data show that ARP consistently recovers up to 99.9% of the ammonia from the city\u2019s centrate waste stream (derived from dewatering of sewage sludge), as ammonium sulfate. ARP technology can reduce the nitrogen (ammonia) discharged daily into local bodies of water by municipalities, concentrated animal farming operations, and industry. Recent advances to ARP enhance its performance and economic competitiveness in comparison to stripping or ammonia destruction technologies."}
+{"text": "The World Health Organization (WHO) estimates that 79% suicides occur in low- and middle-income countries (LMICs) in 2016  putting a spotlight on the topic of suicide in these countries. While the rates are highest among individuals ages 15 to 29 years, suicide affects individuals, families, and communities throughout the lifespan. The topic of suicide among older adults, especially those living in LMICs, has unfortunately received limited attention. Using a sample of 228 women with depression from the first wave of the WHO\u2019s Study on global AGEing and adult health , the present study sought to identify predictors of suicide ideation among aging African women. Binominal logistic regression results revealed that wealth (negatively) and health (negatively) were associated with suicide ideation in the sample; indicating that the women who were poor and unhealthy were more likely to have suicidal thoughts. Implications of the findings for aging Ghanaian women will be addressed."}
+{"text": "Currently, the earth is undergoing rapid and major environmental changes mostly because of anthropogenic activities . The bioTypically, the ecological understanding of the response to environmental conditions and changes rely on three approaches: (i) manipulative experiments, (ii) long-term observational records by monitoring the response to ambient environmental fluctuations using repeat sampling of plots, and (iii) space-for-time substitutions derived from sampling along environmental gradients and across time scales. The three approaches are valuable but sometimes produce inconsistent estimates of the magnitude of plant community response to environmental changes . There iMahajan et al.; Wang et al; Li et al.) and nutrient addition . Mahajan et al. quantified the impact of moisture stress on the physiological changes and reproductive capacity of emerging problematic weed species (Sisymbrium thellungii) to understand reasons for its spread and develop appropriate management strategies. Wang et al. measured the performance of root systems of two contrasting plant species  under different soil moisture regimes to understand interactions between the shrub\u2013grass species. Cui et al. measured the N response of two temperate desert plant species  to understand their aboveground and belowground growth performance and N retention, thus helping understand the relative competitiveness and species composition under different environmental conditions. Li et al. conducted experiments to understand the interaction between endophytes isolated from desert plants on the performance of Hedysarum scoparium under different soil water conditions. They observed that endophytes established a positive symbiosis and further enhanced the biomass and antioxidant activities of the host plant particularly under water-deficit conditions.Six of the 12 articles in the issue deal with manipulative experiments, an ongoing commonly used approach in ecology research. They address a variety of topics, notably the responses of a vast range of dryland plant species to experimental drought  and the National Natural Sciences Foundation of China (31570438) toZY, Chinese Academy of Sciences\u2019 \u201c100 Talent\u201d Program to ZY and YC.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The 2018 Political Declaration of the Third High-level Meeting on Noncommunicable Diseases notes that progress and investment on noncommunicable diseases have been insufficient to meet the health-related targets of the sustainable development goals.The United Nations (UN) Inter-Agency Task Force on the Prevention and Control of Non-communicable Diseases has undertaken joint missions to over 25 countries to support government responses to these challenges.These missions have identified priorities for an effective national response on noncommunicable diseases. The first priority is developing national frameworks comprising an investment case; a prioritized and costed national plan with sustainable financing; maximized domestic resources; and coordination and accountability structures. The second priority is achieving greater policy coherence across government to effectively deliver national multisectoral action plans on noncommunicable diseases, including stronger legislation and regulation to reduce levels of risk factors, and to build enabling environments for health-promoting behaviours.While the responsibility for addressing these priorities lies with countries, the UN system has a key role in catalysing these responses. The United Nations Development Programme and the World Health Organization (WHO) are already providing support for developing noncommunicable disease investment cases in 15 countries.The 2017 ECOSOC resolution urged governments, the private sector and donors to explore financing for noncommunicable disease prevention and control, and to mobilize adequate, predictable and sustained resources for the programmatic work of the task force.The 2015 Addis Ababa Action Agenda was clear that noncommunicable disease responses should be financed from domestic resources."}
+{"text": "Patient Priorities Care (PPC) is an approach to clinical conversations that focuses on aligning care with patient priorities. This approach involves identifying and incorporating patient values, goals, and preferences into care for patients with multiple comorbid conditions. We have previously described how this clinically feasible and sustainable approach has been implemented in VA and private healthcare settings, and how this approach results in documented care aligned with patient goals. In this paper, we describe the way PPC has been adapted and implemented in a VA geriatrics clinic for Veterans with dementia and their caregivers. We discuss results from a funded pilot project in which we investigated the role of caregivers in patient goal setting; assessed patient functioning using self-reported and sensor measures; and examined clinical conversations and interviews. We use these results to discuss implementation strategies targeting: (1) caregiver activation and involvement in clinical conversation and decision-making, (2) patient and caregiver education about the disease trajectory of dementia, (3) life space function and using physical sensor data in dementia care, (4) measures of community integration for patients and caregivers, and (5) features of successful clinical conversations in this context."}
+{"text": "Heavy metals find their way into surface and groundwater due to degrading environmental conditions, and as such consistent monitoring to avoid the adverse health implications associated with the consumption of polluted water is required. This study examined the concentrations for Lead (Pb), Nickel (Ni), Zinc (Zn), Chromium (Cr), Cadmium (Cd), Copper (Cu) and Arsenic (As) in the Surface water of River Balogun in Ota, Ogun State, Nigeria during the wet season and estimated the human health risk resulting from prolonged consumption by children and adult of dissimilar age groups without treatment. Although there were persistent occurrence of Nickel (Ni), Copper (Cu), Zinc (Zn) and Arsenic (As) in all stations sampled, the health risk assessment conducted revealed that both population groups are more likely to be affected by high concentration levels of Arsenic than any other Heavy metal present. Specifications TableValue of the data\u25cfThe presence of Heavy Metals in surface water is unavoidable especially with the growing concerns of indiscriminate release of untreated effluent by industries within the study area. To this end, there are likelihood of adverse effects on Humans when consumed either in little or large quantities. This data obtained revealed the contamination levels of some selected Heavy Metals.\u25cfThe associated health risk is pertinent considering various means by which these Heavy Metals find their way into the body.\u25cfThe associated health risk for different age groups and population is required to estimate the at-risk groups among them for proper intervention from both Governmental and non-Governmental Organizations.\u25cfThe data is required for the design and implementation of essential and accurate treatment technique(s) for industrial effluents as well as agrochemicals that might have polluted the river.12The data presented showed the concentration levels of selected surface water quality obtained from River Balogun in Adodo-Ota, Ogun State and the associated health risk due to oral consumption only. The presence of these heavy metals emerged due to presence of many industries situated close to the river and consistently discharged untreated liquid waste into the river under study which affected the water quality adversely 2Seventeen (17) sampling points were assessed and a total of fifty-one samples were collected. The samples were preserved with acid and kept in a cooler to prevent speciation of the inherent metals. Thereafter, the mean values obtained from each sampling stations were used to calculate the associated health risk and comparison with standard values to ascertain whether or not these values were in concentrations below or above limits set by World Health Organization In this study, samples collected were obtained from sections of the river where inhabitants of the locality get water for various uses especially farmers. Additionally, some essential physicochemical properties of water such as pH, Total dissolved solids (TDS), Electrical Conductivity (EC) and Temperature were measured using HANNA \u2013 HI2030 device before taking collected samples for heavy metal analysis. Other heavy metals reported in this study were achieved using the Inductively coupled plasma optical emission spectrophotometer (ICP-OES). The raw values obtained from the analysis of the sampled surface water are presented in Consequently, these values obtained  can be u[9]Specifically, In addition, the"}
+{"text": "The scientific interest in plant phenolics as chemopreventive and therapeutic agents against chronic and degenerative diseases has been increasing since the late 1990s, when the French paradox was associated with the high intake of phenolics present in red wine [Twenty-one contributions (17 research and four review articles) in this special issue show some of the most recent advances in plant phenolics research. The information published includes: the chemical characterization of phenolic profiles from different plant species and the evaluation of their bioactivity; the effect of processing conditions on the phenolic composition of foods; methods for the purification of phenolics; methods for the evaluation of phenolics in blood samples; functional characterization of enzymes involved on the biosynthesis of flavonoids; and the evaluation of pre- and postharvest treatments to increase the phenolic content of different horticultural crops.Uncaria tomentosa L. (cat\u2019s claw) from different regions of Costa Rica. Furthermore, the phenolic composition accompanied with the antiviral and antimicrobial activity of Bombax malabaricum [Rhoeo discolor [In this special issue, Navarro Hoyos et al.  evaluateabaricum  and Rhoediscolor  were repdiscolor  comparedJuniperus communis L. and Cotinus coggy methanol extracts showed marked cytotoxic effect, affecting cell morphology and growth [Rhodiola crenula and reported their antioxidant and inducing INF-\u03b3 activities.Regarding the chemical characterization of phenolic compounds and the evaluation of their bioactivity, Pollio et al.  evaluated growth . Likewisd growth  elucidatRegarding the effect of processing on the phenolic content and bioactivity of plant foods, Yu and Beta  identifiSalvia miltiorrhiza roots metabolites. Salvia miltiorrhiza roots are broadly used as herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.An emerging topic that is presented in this special issue is the development of methods to increase and/or modify the phenolic profile of horticultural crops. A review article on this topic was presented by Kaushik et al. . In thiso-quinones (produced from chlorogenic acid) with nucleophiles present in proteins.Other research articles published in this special issue include the functional characterization of a dihydroflavanol 4- reductase (DFR) from fiber of upland cotton . DFR is In relation with the purification of phenolic compounds and their further applications as food additives, Aguilar and Hern\u00e1ndez-Brenes  exploredOther review articles published in this special issue include a contribution about insoluble-bound phenolics, explaining their localization and biosynthesis in plant cells, as well as their metabolism in human digestive system and corresponding bioactivity . LikewisFinally, Santana-G\u00e1lvez et al.  reviewed"}
+{"text": "Nobel Prize announcements dominated science news this week. The Nature news section led with three Prize-winner stories: medicine, physics, and chemistry. Science saved the Nobel details for next week and instead led with an announced $58 million non-profit effort to sequence the mouse genome and distribute the results free of charge."}
+{"text": "A 29-year-old non-smoker male with a history of chronic cough, and recurrent pneumonia, sinusitis and otomastoiditis was admitted to the emergency room with a 3-day history of headache, cough productive and dyspnea. Positive findings on physical examination included heart sounds in the right side of his chest and pain on palpation and percussion of the sinus areas. Laboratory testing was unremarkable. Chest radiography showed dextrocardia (A); computed tomography (CT) of the face showed mucosal thickening and material with soft tissue density in the paranasal sinuses, mastoid cells and in the middle and external ear cavities ; chest CT showed bronchiectasis and centrilobular nodules (tree-in-bud pattern) ; liver on the left and spleen on the right (F). The diagnosis of Kartagener's syndrome (KS) was made. KS is a subset of primary ciliary dyskinesia, an autosomal recessive condition characterised by bronchiectasis, paranasal sinusitis and situs inversus totalis (SIT). Patients with KS often have multiple episodes of respiratory tract infection and exacerbation of bronchiectasis due to poor mucociliary clearance and some male patients with KS also have sterility due to dyskinesia of the spermatozoa. Clinicians and mainly emergency physicians should be aware of this rare disorder once failure to recognize this syndrome can be potentially hazardous, especially in surgical conditions."}
+{"text": "The diagnosis of adult-onset Niemann\u2013Pick disease type C (NPC) could be difficult because its primary symptoms [dementia and vertical supranuclear gaze palsy (VSGP)] are mainly seen in neurodegenerative dementias and progressive supranuclear palsy (PSP). Our patient with dementia and asymmetric parkinsonism resembled corticobasal syndrome and after the appearance of VSGP, the criteria of PSP were fulfilled too. Cerebellar symptoms appeared late during the course of the disease, leading to the diagnosis of NPC at the age of 59\u00a0years. Niemann\u2013Pick disease type C (NPC) is a rare genetic disorder belonging to the lysosomal storage diseases. It is mainly diagnosed in children, while adult-onset forms of the disease are even rarer. Diagnosis of late-onset NPC is complicated by the heterogeneous symptomatology of the disease, especially in adults, where its neuropsychiatric consequences (mainly psychosis and dementia) are frequent symptoms in degenerative dementias and the red flag sign of NPC, the vertical supranuclear gaze palsy (VSGP), is usually seen in patients with progressive supranuclear palsy (PSP)  disease is a rare neurovisceral disorder with autosomal recessive inheritance. NP has two distinct forms. The first is due to complete or partial deficiency of acid sphingomyelinase, resulting from mutations in the SMPD1 gene with the clinical phenotypes of NP type A and B. NPC is characterized by unique abnormalities of intracellular transport of endocytosed cholesterol with sequestration of unesterified cholesterol in lysosomes and late endosomes, but the function of the affected proteins  are not precisely elucidated Ory . Age of The manifestations of NPC are classified in visceral, neurological and psychiatric categories. While visceral manifestations tend to predominate during the perinatal and infantile period, neurological and psychiatric signs are more prominent in juvenile and adult patients. Neurological manifestations of NPC include non-disease-specific and more pathognomonic neurological signs such as VSGP especially when it occurs in combination with other manifestations, e.g., ataxia or splenomegaly , as seen in our patient who had dementia with asymmetric parkinsonism as the initial manifestation of NPC.Based upon the predominant early feature of the disease, FTD can be categorized into three main syndromes: behavioral variant (bvFTD), semantic variant (svPPA) and non-fluent variant of primary progressive aphasia (nfvPPA). Motor neuron signs and parkinsonism are frequent accompanying symptoms (FTD with motor neuron disease (FTD-MND), PSP and CBS are being the corresponding clinical syndromes) . In case of high likelihood of NPC there are available biochemical and genetic tests to prove the diagnosis. A sensitive and specific biomarker is oxysterol, a cholesterol oxidation product, which level is significantly associated with the age of initial presentation and severity of the disease (Papandreou and Gissen Neurological manifestations in combination with frequently asymptomatic visceral symptoms raise the suspicion of NPC. In patients with adolescent/adult-onset form, splenomegaly can only be occasionally detected by routine ultrasound assessments. Score systems aid clinicians to estimate the probability of NPC (such as Genetic tests are requested to support suspicious biochemical results. NPC1 gene mutations are present in 95% of cases, while NPC2 mutations in approximately 4%; the remaining patients are biochemically proven cases who do not have identified mutations (Papandreou and Gissen Only one study was found in the literature where a limited number of PSP and FTD patients had been screened for NPC1 and NPC2 gene mutations, but no carriers were found in these patient groups (Papandreou and Gissen NPC may be under-diagnosed due to its highly heterogeneous clinical presentation. The neurological manifestations of NPC can mimic FTD syndromes leading to significant delays in the diagnosis especially in dementia and movement disorders units, where vertical gaze palsy is a red flag symptom for PSP. In case of familial aggregation of the phenotype and presence of otherwise inexplicable visceral symptoms, clinicians should think about late-onset NPC, where treatment with miglustat is able to slow the progression of the disease (Papandreou and Gissen"}
+{"text": "As more Americans approach retirement age and eligibility for Medicare coverage, many face difficult decisions about their health insurance and health care. This session explores how adults age 50-64 are navigating these choices following implementation of the Affordable Care Act (ACA), presenting data from two nationally representative surveys: The University of Michigan\u2019s National Poll on Healthy Aging (NPHA) and the Health and Retirement Study (HRS). Erica Solway, Associate Director of the NPHA, will begin by presenting background information about the NPHA and an overview of critical health policy issues for adults age 50-64. Jamie Luster, Research Area Specialist at the University of Michigan, will then provide NPHA findings linking concerns about health insurance affordability with delayed/forgone health care. Next, Aaron Scherer, Associate of Internal Medicine at the University of Iowa Carver College of Medicine, will discuss NPHA findings on factors associated with adults\u2019 concern about affordability of health insurance in retirement but before Medicare eligibility begins at age 65. Finally, Renuka Tipirneni, Assistant Professor of Internal Medicine at the University of Michigan, will present findings based on the HRS on changes in health care utilization for adults age 55-64 since implementation of the ACA\u2019s Medicaid expansion. To conclude, Erica Solway will discuss current federal health care policy proposals for adults age 50-64, including the recent introduction of the Medicare at 50 bill, and how the perspectives and experiences of adults in this age group can help inform those policies."}
+{"text": "The advent of Information and Communications Technology (ICT) in the new age has led to the digitalization of business processes including banking. For performance measurement among other usefulness, the dataset for these adopted electronic banking channels\u00a0\u2013 Automated Teller Machines, Internet (Web) Transactions, Mobile Payments, Instant Payments, Electronic Fund Transfer, Point of Sales (POS), Automated Cheque Clearing and e-BillsPay was sourced. This dataset gives a trend analysis of e-payment performance of transactions both in value and volumes on each channel as consummated on the platform of Nigeria Inter-Bank Settlement System (NIBSS) in the last six years covering 2012\u20132017. This dataset gives a breakdown of transactions both in volume and values for eight different e-payment channels authorized and adopted for settlement by all banks in Nigeria. Data was derived from the repositories of Nigeria Inter-Bank Settlement System (NIBSS) and the Central Bank of Nigeria (CBN). The dataset has been analyzed using table and pictorial presentations.In This dataset is useful for defining the existing relationship among e-payment channels in mathematical form for further research work.2The dataset is a raw data for a six year period starting from 2012 to 2017 pooled from the online repositories of the apex regulatory body, the Central Bank of Nigeria (CBN) and the Nigeria Inter-Bank Settlement System (NIBSS). The Nigeria banking system has undergone series of reform agenda like consolidation, universal banking and cashless policy but had stability and confidence restored within the last six years hence the choice of dataset collection period. The dataset was analyzed using Microsoft excel applying sum total and simple average formula. Since NIBSS is jointly owned by all the listed banks and CBN, the dataset gives a good degree of reliability level for the analysis. Details of similar research work that have analyzed dataset in a descriptive form are"}
+{"text": "This article examined the personal and household characteristics influencing the quality of life (QoL) of grandparents caring for grandchildren in Skipped Generation Households in Nigeria with a sample of 2, 144 grandparents in Imo, Lagos and Kano. Chi square and multinomial logistic regression were employed to understand the relationship between the dependent variable (QoL) and independent variables . The level of the QoL of the grandparents almost spread evenly among low (34.3%), average (34.3%) and high (31.4%). Five domains of QoL were examined including level of independence (LI), psychological well-being (PW), social relation (SR), physical health (PH), environment (ENV) and engagement in income generating activities (IGA). Personal characteristics including; state of residence was significantly associated with all the domains except LI and PW, age was associated with IGA, LI and ENV, sex was associated with SR and ENV and level of education was associated with all the domains except IGA and ENV while religious affiliation was associated with IGA. Household characteristics including; sex of household head was significantly associated with PH, SR and ENV, age of household head was associated with IGA and LI and wealth index was associated with all the domains while the number of household members was significantly associated with ENV. The regression analysis shows that only state of residence and wealth index significantly influence the QoL of the grandparents (P\u22640.05). The state of residence and wealth index are therefore important in any policy intervention for this category of elderly persons in Nigeria."}
+{"text": "Increasing numbers of people are aging in place and dying in assisted living (AL) and AL is increasingly becoming a site of end-of-life care in the US. Consequently, AL staff frequently experience death and decline of the residents they care for. Using data from ethnographic observations and in-depth qualitative interviews with 14 direct care workers and 16 administrators participating in a 5-year NIA-funded study (R01AG047048) examining end-of-life care in four diverse ALs, we used thematic analysis to examine how AL administrators and staff implement and understand policies and norms around death and dying . We found there is limited training regarding death and bereavement and limited formal grief support for staff. These findings identify gaps in communication between administrators and direct care workers with implications for increasing communication about death and dying and improving support for direct care workers experiencing grief and bereavement."}
+{"text": "The data presented herein relates to the article entitled \u201cWillingness to pay for management and preservation of natural, semi-urban and urban beaches in Italy\u201d [1].Data of several Italian beaches are collected considering shape, anthropogenic characteristics, use, activity and urbanization levels. Descriptive statistics of beach characteristics and beach users are presented, on the basis of about 5000 interviews. Beach characteristics are used as variables in a multivariate model of WTP From 2Researchers collected these data by in-person collection of questionnaires from visitors and residents to Italian beaches (Interactive map data). A questionnaire was used to elicit visitor preferences and willingness to pay for coastal preservation. The questionnaire was based on those used by Refs. Statistical and descriptive analyses of WTP surveys were performed using the Statistical Package for Social Sciences (SPSS) version 20 (Statistics Solutions) and Microsoft Excel version 2017 ."}
+{"text": "OBJECTIVES/SPECIFIC AIMS: Acute care research is a unique area of clinical research that demands specialized skills, knowledge, and talents from empathetic professionals working in the field. Building off existing competencies for clinical research professionals, the Cincinnati Acute Care Research Council (ACRC) developed additional areas of competency for professionals working in the acute care research discipline. METHODS/STUDY POPULATION: Qualitative data obtained from job shadowing, clinical observations, and interviews were analyzed to understand the educational needs and desires of the acute care research workforce. We then utilized Bloom\u2019s Taxonomy to build acute care research competencies that are measurable for job performance and build off of foundational clinical research professionals\u2019 domains and competencies developed by the Joint Task Force of Clinical Trial Competency. RESULTS/ANTICIPATED RESULTS: Results suggest 35 special interest competencies for acute care clinical research professionals under 8 common domains set by the Joint Task Force of Clinical Trial Competency. Additionally an approved ACRC tactic, from actionable learnings through community assessments throughout 2017, is the creation of a Task Force made up of acute care research Principal Investigators and Clinical Research Directors to focus on the identified training and professional development obstacles in the clinical research enterprise. DISCUSSION/SIGNIFICANCE OF IMPACT: The competencies developed for acute care research should serve as guidelines for training a workforce prepared for the challenges of conducting research with each acute audience, as its own vulnerable population. These competencies will guide development of a multi-pronged program of professional development that will include new hire onboarding, new hire on-job training, and ongoing on-job training."}
+{"text": "This article presents unrevealed details of the systematic review process of the article \u201cThe number of FoxP3 regulatory T cells in the circulation may be a predictive biomarker for kidney transplant recipients: A multistage systematic review\u201d . Eligibility criteria guiding searches and study selection, the risk of bias assessment, the assessment of medicine-test codependency , and meta-analytic calculations are provided. The data allows other researchers, particularly those involved in experiments on Translational Epidemiology applied to Pharmacology, to corroborate and extend our assessments. Specifications tableValue of the data\u2022In the field of Translational Pharmacology, sharing systematic review process details is very important.\u2022This data allows other researchers to corroborate and extend our assessments.\u2022The main aim of sharing this data is to improve the qualification of potential predictive biomarkers.1In addition to links to the four systematic review protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO) /exposure(s), comparators, outcomes and study design)"}
+{"text": "The biological origin of impressive accuracy of DNA methylation clocks, the most precise currently available biological markers of aging in humans and model animals, remains largely unclear. In addition, they sometimes suffer from uncontrollable precision loss out of sample. To address these two issues, we develop a novel method for constructing robust molecular markers of age based on network analysis of age-dependent omics data. The newly developed robust markers of aging in yeast, fruit fly, mouse and human are nearly free of batch effects and have a transparent biological nature related to tight control of translation-related processes and their disregulation associated with aging."}
+{"text": "Multiple factors influence decision-making of family caregivers of African American older adults with dementia about participation in end-of-life care research. Existing literature on best practices for research recruitment includes little on recruitment strategies for this specific population. The purpose of this presentation is to analyze successful recruitment strategies used with family caregivers of African American older adults with dementia. Sixty-five caregivers of African American older adults with dementia were recruited over 11 months throughout a southeastern state from local communities and Program of All-Inclusive Care for the Elderly. Community partnership strategies such as community-based networking, purposively-targeted presentations, and leveraging of existing social networks provided a strong basis for successful recruitment. These strategies were credible to the participant population and effective in engaging both research participants and community partner stakeholders in working on shared goals of improving older adult and caregiver outcomes near the end of life."}
+{"text": "The last decade has witnessed an increasing interest in exploring the network connectivity of brain areas and communities. The disruption of brain networks has been linked to variable levels of neuropsychological dysfunctions observed in individual patients with brain disorders  in Wilson's disease (WD) associated with mild cognitive impairments (MCI). They found that the CBF-FCS correlations of patients with WD were significantly decreased in the basal ganglia and the cerebellum and slightly increased in the prefrontal cortex and thalamus. Qi et al. evaluated the pattern of activity in the cerebral limbic network from the perspective of the cerebellum. Results indicated that the cerebellum was not compromised by Alzheimer pathology in the early stages of AD, and this pattern indicates that the sub-scale ventral attention network may play a pivotal role in functional compensation through the coupled cerebro-cerebellar limbic network in MCI, and the cerebellum may be a key node in the modulation of social cognition. Moreover, patients with cerebral vascular diseases exhibit widespread differences in functional connectivity across multiple cortical networks. Leukoaraiosis (LA) is associated with cognitive impairment in older people and associated with dysfunctional communications between the three basic brain networks, consisting of the default-mode network (DMN), salience networks (SNs), and the central executive network (CEN). Chen et al. presented the diminished negative correlations between the SN and DMN while positive correlation between the SN and CEN were enhanced as the cognitive impairment loads increased in patients with LA.Neurovascular imbalance is generally noted in the aging population and Alzheimer's disease (AD). It has been shown that regional cerebral blood flow (rCBF) is closely coupled with cerebral metabolism, and the relationship between network measures and rCBF provides insights into the mechanisms of connectivity disruptions in brain disorders. Wang et al. aimed to investigate the sex difference on whole-brain functional connectivity at the network level from a cohort of acute mild TBI patients since there were differential cognitive outcome by sex. Ye et al. investigated the changes of \u03b1-synuclein in blood serum and its relationship with default mode network (DMN) connectivity after acute mild TBI. The chronic consequences of TBI may contribute to the increased risk for early cognitive decline and dementia, primarily due to diffusion axonal injury. Yin et al. investigated longitudinal changes of white matter (WM) using diffusion tensor imaging (DTI) and their correlations with neuropsychological tests following mild TBI. They reported that increased fractional anisotropy values in some tracts at 1 month post-injury were positively associated with better performance on cognitive information processing speed at initial assessment.Traumatic brain injury (TBI) is a substantial public health problem, and can accelerate the aging process, leading to long-term structural and functional alterations to the brain. Budak and Zochowski systematically analyzed how two types of synaptic failure  affect two complementary (incoming and outgoing) scale-free network structures. Williams and Sun explored the layer and spectrotemporal architecture and laminar distribution of high-frequency oscillations (HFOs) in a neonatal freeze lesion model of focal cortical dysplasia (FCD). They provided the evidence that HFOs, particularly fast ripples, is a biomarker to help define the cortical seizure zone and understand cellular level changes underlying the HFOs. Infarction or aging in regions project to the pyramidal tract (PyT) would result in incomplete transmission of information to the PyT and concomitant decreases in motor planning and coordination abilities. Using the large population data of the HCP and high magnet gradient HARDI data, Wang et al. visualized the existence of the PyT in humans.Synaptic failure may critically impair information processing in the brain and may underlie many neurodegenerative diseases. Samuel et al. examined the neural compensation from a fatigue paradigm and reflect neural activities typically associated with aging-related cognitive impairment. In the young cohort, they found that both behavioral performance and neural activity declined as the experiment progressed, reflecting the deleterious effects of cognitive fatigue. Both behavioral performance and neural activity did not decline as the experiment progressed in the older cohort, in contrast to the young. Pelzer et al. reviewed the literature regarding quantitative susceptibility mapping (QSM), MEG, and rs-fMRI detected changes in motor and non-motor symptoms in Parkinson's disease (PD).Cognitive aging research has identified several general patterns of compensatory neural activity. Most studies of neural compensation limited to a between-subject design, Yang et al. explored the temporal variability of cortical gyral-sulcal resting state functional activity and its association with fluid intelligence measures on the Human Connectome Project dataset, which provided novel insights to understand the functional relevance of gyri and sulci. Social anxiety and risk of mental disorders have increased in the left-behind children (LBC). Fu et al. provided empirical evidence of altered brain structure in LBC compared to non-LBC, responsible for emotion regulation and processing, which may account for mental disorders and negative life outcome of LBC.Finally, the morphological features of gyri and sulci change during aging and development-related psychiatric disorders such as schizophrenia, reflecting a potential of gyral-sulcal indices as a biomarker for developmental and aging related disorders. Fluid intelligence, as a measure of higher-order relational reasoning, has been argued to be linked to specific functional outcomes and to variations in human neuronal structure and function. LB and TZ drafted the work and revised it critically for important intellectual content. All of the authors provide approval for publication of the content, agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved, and made substantial contributions to the conception and design of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Families often remain unaware of long-term services and supports (LTSS) that could help to mitigate the negative effects of Alzheimer\u2019s disease and related dementias (ADRDs). Approaches that: a) identify community-residing older persons with potential memory impairment; b) assist their families in navigating the healthcare system; and c) facilitate the identification of appropriate community-based LTSS could result in more effective management of ADRD. The Porchlight Project is a multicomponent training approach for lay volunteers in Minnesota  that enhances their capability to deliver dementia care and support to underserved older persons in need. Mixed methods analysis of qualitative and quantitative data among 20 Senior Companions and up to 25 persons with ADRD and their family caregivers suggest the potential success of the Porchlight Project, as well as areas to refine and enhance prior to large-scale evaluation throughout Minnesota."}
+{"text": "The authors wish to make the following correction to their paper :pksCT and ctnA) and up-regulation of the Monascus pigments (MPs) synthesis genes (pksPT and pigR).\u201dIn the Abstract section, the fifth sentence should be replaced with, \u201cIt was verified through the transcriptional down-regulation of citrinin synthesis genes (Toxins by this change.We apologize for any inconvenience caused to readers of"}
+{"text": "We examined the effects of sustained levels of happiness on dementia incidence among Japanese elderly from the Japan Gerontological Evaluation Study. Data were from 12,051 community-dwelling participants aged 65 and over, free from dementia or other chronic conditions at baseline (2010). A survey was conducted in 31 administrative districts from Japan. Participants were followed-up for six years, and the incidence of dementia or death was assessed through National Public Long-Term Care Insurance and Resident Registry, Japan. We conducted survival analysis using the Cox proportional hazard model with a competing risk analysis accounting for death. The adjusted differences in days for dementia onset were estimated using Laplace regression models. In this analytical sample, we observed 520 men and 693 women with dementia and found that higher levels of sustained happiness were associated with reduced risks of onset of dementia among Japanese elderly. These findings suggest a protective role of psychological mood."}
+{"text": "We present the output data of Robust Principal Component Analysis (RPCA) applied to global crop yield variability of maize, rice, sorghum and soybean (MRSS) as presented in the publication \u201cClimate drives variability and joint variability of global crop yields\u201d . Global maps of the correlation between all the principal components (PCs) acquired from the low rank matrix (L) of MRSS and Palmer Drought Severity Index (PDSI), air temperature anomalies (ATa) and sea surface temperature anomalies (SSTa) are provided in this article. We present co-varying countries, impacted cropland areas across global countries, and 10 global regions by climate and the association between PCs and multiple atmospheric and oceanic indices. Moreover, the joint dependency between PCs of MRSS yields are presented using two different approaches. In all the maps, significant correlations (95% confidence) over croplands of MRSS are marked with small black dots. The first few PCs explain a large portion of the crop yield variability, and succeeding PCs account for the remaining variability. The variability explained by each PC is shown at the top of each map. The boundary of the countries with large loading values are highlighted in orange  and blue . These countries co-vary similarly/oppositely , and they explain the variance of that PC the most.Nine tables in the Microsoft Excel Worksheets are included in the supplementary. MRSS producer countries with complete yield dataset from 1961 to 2013 that are used as input for RPCA are presented in 2RPCA"}
+{"text": "This paper describes the rationale, development and final protocol of the Healthy Diets Australian Standardised Affordability and Pricing (ASAP) method which aims to assess, compare and monitor the price, price differential and affordability of healthy (recommended) and current  diets in Australia. The protocol is consistent with the International Network for Food and Obesity / non-communicable Diseases Research, Monitoring and Action Support\u2019s (INFORMAS) optimal approach to monitor food price and affordability globally.The Healthy Diets ASAP protocol was developed based on literature review, drafting, piloting and revising, with key stakeholder consultation at all stages, including at a national forum.The protocol was developed in five parts. Firstly, for the healthy (recommended) and current  diet pricing tools; secondly for calculation of median and low-income household incomes; thirdly for store location and sampling; fourthly for price data collection, and; finally for analysis and reporting. The Healthy Diets ASAP protocol constitutes a standardised approach to assess diet price and affordability to inform development of nutrition policy actions to reduce rates of diet-related chronic disease in Australia. It demonstrates application of the INFORMAS optimum food price and affordability methods at country level. Its wide application would enhance monitoring and utility of dietary price and affordability data from a health perspective in Australia. The protocol could be adapted in other countries to monitor the price, price differential and affordability of current and healthy diets.The online version of this article (10.1186/s12937-018-0396-0) contains supplementary material, which is available to authorized users. Poor diet is now the major preventable disease risk factor contributing to burden of disease, globally and in Australia . Less thdiets have been assessed rarely, as opposed to the relative price of selected pairs of \u2018healthy\u2019 and \u2018less healthy\u2019 foods [The expense of healthy foods has been reported as a key barrier to consumption in Australia, particularly among low socioeconomic groups \u201311. Howey\u2019 foods .Various methods have been utilised to assess food prices in Australia, such as Consumer Price Indexes (CPI) , 19 and A recent systematic review of food pricing methods used in Australia since 1995, identified 59 discrete surveys using five major food basket pricing tools (used in multiple survey areas and multiple time periods) and six minor food basket pricing tools (used in a single survey area or time period) . No natiSince 1995, the vast majority of \u2018healthy\u2019 food pricing surveys in Australia have confirmed that: food prices in rural and remote areas are up to 40% higher than those in capital cities; lower socioeconomic households need to spend a higher proportion of their income to procure healthy diets than other Australians, and food prices generally increase over time , 21. Reltaxing \u2018unhealthy foods\u2019 (\u201cfat taxes\u201d) e.g. on sugar sweetened beverages;exempting \u2018healthy foods\u2019 from goods and service tax (GST) or value added tax; andsubsidising \u2018healthy foods,\u2019 such as through agricultural and transport subsidies, retail price reductions, or voucher systems targeted to vulnerable population groups .The aim of relevant nutrition policy actions is to help shift the current intake of the whole population to a healthier diet consistent with dietary recommendations. Governments can manipulate food prices through a range of complex policy approaches . Three cTherefore, to inform relevant policy decisions, robust data are required for both current  and healthy (recommended) diets . With reWhile the potential effects of specific changes to fiscal policy have been modelled , 28, recThere is a lack of such data globally; the current research helps to address this, within the food price module of the International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support (INFORMAS) , 30. UndBased on the \u2018optimal\u2019 approach of the INFORMAS diet price and affordability framework, we developed a standardised method to assess and compare the price and affordability of healthy and current diets in Australia, provide more robust, meaningful data to inform health and fiscal policy in Australia, and develop national data benchmarks with the potential for international comparisons .This paper presents the resultant protocol for Healthy Diets ASAP methods in Australia.The aim of this paper is to describe the development and final protocol of the Healthy Diets ASAP methods, based on the INFORMAS optimal price and affordability approach. It details tools and methods to assist others to apply the approach in a standard manner, in order to enable comparison of the price, price differential and affordability of healthy (recommended) and current  diets in Australia.In November 2013, all key Australian stakeholders gave in-principle support at a national teleconference for the development of national food price and affordability monitoring methods based on the INFORMAS \u2018optimal\u2019 approach. The development and pilot testing of the methods using readily available dietary data for five household structures in high socio-economic (SES) and low SES areas is reported elsewhere . The finDevelopment of accepted, standardised diet pricing methods also required agreement from all key stakeholders on the final approach, including accord on systematic arbitrary decisions points around application of the tools . There was also a desire to simplify methods to optimise uptake and utility.The final Healthy Diets ASAP protocols were developed in two phases.The food pricing tools were revised based on the pilot outcomes  and feedThe revised unhealthy (current) diet pricing tools reflected dietary data at the five-digit level by age and gender groupings  in the CThe revised Healthy Diets ASAP diet pricing tools and methods were applied to assess the price, price differential and affordability of current and healthy diets in six randomly selected locations in two major cities  in November and December 2015. The preliminary reports of these studies were provided to NSW Health and ACT Health in early 2016. Colleagues in these government departments provided feedback on the revised methods early March 2016.At the national Healthy Diets ASAP Methods Forum (the Forum) held in Brisbane on 10 March 2016, 25 expert stakeholders from academia, government jurisdictions and non-government organisations (see Acknowledgements) worked together to finalise the Healthy Diets ASAP tools and methods for national application in Australia. De-identified preliminary data from and feedback on the reports provided to NSW Health and ACT Health were used to highlight methodological challenges and arbitrary decision points during the Forum.Generally, the revised tools and methods applied in Sydney and Canberra were confirmed at the Forum. However, some simplifications around arbitrary decision points were recommended Table\u00a0.Table 2AThe revised tools and methods were finalised according to the recommendations from the Forum. The resultant Healthy Diets ASAP protocol is described in detail in the results.Following the Forum, the food price data collected in Sydney and Canberra in late 2015 were reanalysed according to the Healthy Diets ASAP protocol and the preliminary reports to NSW Health and ACT Health were finalised in May 2016.There are five parts to the Healthy Diets ASAP protocol.There are two diet pricing survey tools: the current  diet pricing tool; and the healthy (recommended) diet pricing tool Table\u00a0. The dieThe current  diet pricing tool constitutes the sum of the mean intake of specific foods and drinks, expressed in grams or millilitres, in each age/gender group corresponding to the four individuals comprising the reference household, as reported in the AHS 2011\u201312 . Foods aThe healthy diet pricing tool reflects the recommended amounts and types of foods and drinks for the reference household for a fortnight, consistent with the Australian Guide to Healthy Eating and the Australian Dietary Guidelines . The amoTo ensure the most commonly consumed healthy foods in Australia are used, food categories in the healthy diet pricing tool are the same as those in the current diet pricing tool (but differ in quantity). A variety of fresh, canned, frozen and dried foods is included. For example, representative categories of fresh produce reflect common fruit and vegetables available all year round in Australia. Luxury products, such as imported fruit and vegetables (particularly those out of season) and foods with very high cost per kilogram  are excluded. Some \u2018convenience\u2019 foods are included in the healthy diet pricing tool as per stakeholder decisions Table .Consistent with Australian recommendations , the heaThe amounts of foods and drinks comprising the Healthy Diets ASAP healthy (recommended) diet for the reference household per fortnight are presented in Table Several stakeholders requested Table  that theConvergent validity of the constructed healthy and current diet pricing survey tools for each age/gender group was assessed by energy and macronutrient analysis using FoodWorks 7 Professional  computerInternal validity indicators, such as the ratio of fruit and vegetables content between the healthy and current diet pricing tools (approximately 2:1) are consistent with available published data  and recoA random sample of the Statistical Area Level 2 (SA2) locations in each town is selected to achieve a representative sample. SA2 locations are stratified by the Index of Relative Socio-Economic Disadvantage for Areas (SEIFA) quintile using information and maps available on the ABS website \u201338 FolloThe Healthy Diets ASAP diet price survey data collection form Table  combinesPermission to participate is sought from each store manager prior to data collection.Data entry and analysis sheets have been developed using Excel\u2122 spreadsheets . Double Household income is determined by either of three methods, depending on the purpose of the study and the granularity of available data.In Australia, national census data is the only source of SA2 level household income data and is provided only at total (gross) level. Median gross household income is determined per week  in each SA2 area by entering relevant post codes into the Community Profile data calculator  that is Indicative low (minimum) income of the reference household (and other households of interest to specific stakeholders) is calculated based on the level of minimum wages  and detehe Survey of Income and Housing [.For assessment of diet affordability at the national level, median equivalised disposable household income for the reference family composition is sourced from t Housing .The price of the healthy (recommended) and current diets in each store and the mean price for each SEIFA quintile is calculated for the reference household composition in each of areas surveyed in each city. Results can be presented in a range of metrics, including the cost of the total diets per household per fortnight, and the cost of purchasing specific five food group and discretionary foods and drinks . The results for the current  diet and healthy (recommended) diet are compared to determine the differential.Affordability of the healthy and current diets for the reference household is determined by comparing the cost of each diet with the median gross household income  and healthy (recommended) diets for the reference household. The price of the relevant foods and drinks can be modified readily to highlight the likely \u2018real-world\u2019 impacts of different scenarios, for example, to investigate the potential extension of the Goods and Services Tax (GST) on basic healthy foods , or the There are several methodological limitations inherent in the Healthy Diets ASAP protocols. Given that it is based on national reported mean dietary intakes, the cost of the current  diet is unlikely to be the same as actual expenditure on food and drinks in specific areas and among specific groups . Other aIdeally, the specific foods included in both diet pricing tools are culturally acceptable, commonly consumed, widely available, accessible and considered \u2018every day\u2019 rather than luxury items. As the foods and drinks included in the current diet pricing survey tool reflect actual consumption data, it was presumed that they were deemed by the population as a whole as meeting these requirements. No adjustments were made for costs such as transport, time, cooking equipment and utilities; as these apply to both current and healthy diets, assessment of the price differential between the two can help control for some of these hidden costs to some extent. However, these hidden costs would increase actual diet costs and decrease affordability of the diets.No adjustments were made to account for the marked under-reporting in the AHS 2011\u201312 , reporteNo attempt was made to control the price of the healthy diet pricing tool or the current diet pricing tool for energy, as the diets are constructed on recommended energy levels and actual reported levels of energy respectively. Further, the energy content of each tool is a determinant variable that directly affects diet-related health outcomes , 49. As While a benchmark of 30% of income has been used to indicate affordability of diet internationally and in Australia , 9, 10 iArbitrary decision points occur around sampling frameworks, data collection protocols , analysis and presentation of results, data sources and definitions of family and household income and composition. Such methodological limitations are common to other food price studies. In order for final methods to be replicable, agreement among key stakeholders including end users on each of these decision points at the Healthy Diets ASAP Forum was invaluable. Publication of detailed protocols is essential to support uptake, replicability, fidelity and transparency of the method.The detailed dietary survey data required to produce the current  diet pricing tool and the modelling data required to produce the healthy (recommended) diet pricing tool are not easily accessible in all countries and technical capacity to analyse individual records may be limited. Therefore, this optimal approach may be too complex for application to assess and monitor the price of diets from a health perspective globally. However, there is potential for the diet pricing tools to be adapted for use in other countries by substitution of food components with commonly-consumed local equivalents, dietary analysis and testing.The development of standardised Healthy Diets ASAP method protocols provides an example of how the INFORMAS optimal food price and affordability methods can be adapted at country level to help develop standardised, policy relevant diet price assessment, monitoring tools and benchmarks. The approach can be used to assess the price, price differential and relative affordability of current  and healthy (recommended) diets and inform scenario modelling of potential fiscal and nutrition policy actions.The Healthy Diets ASAP method satisfies long-standing calls for the development of a nationally standardised approach to assess food prices from a health perspective, supporting comparison of results from different locations and over time, in Australia.The protocol could be adapted in other countries to benchmark and monitor the price, price differential and affordability of current and healthy diets globally.Additional file 1:Current  Diets: Mean daily intake of representative categories of foods and drinks for individuals (age/gender) comprising the reference household, and other common households. (DOCX 43 kb)Additional file 2:A. Foundation diet recommended serves of foods per week for individuals (NHMRC 2011) comprising the reference household and other common households. B. Healthy (recommended) Diets: Recommended serves per day of food groups and amounts of composite foods and drinks for individuals comprising the reference household, consistent with Foundation Diets (NHMRC 2011) including commonly-consumed brands. (DOCX 55 kb)Additional file 3:1 per fortnight. (DOC 188 kb)Composition of the current  diet and healthy (recommended) diet for four additional households Additional file 4:Energy and nutrient analysis of individual current and healthy diet baskets compared to results of the AHS and Foundation Diet modelling. (DOCX 36 kb)Additional file 5:Median income determination by SA2 Example- Median income data from the 2011 Census, ABS Community Profiles of SA2 areas for six SA2 locations in Sydney, NSW*. (DOCX 36 kb)Additional file 6:Calculations of low (minimum) disposable household income data from welfare data \u2013 Example. (DOCX 34 kb)"}
+{"text": "Lyme disease is a tickborne zoonosis for which serologic testing is the principal means of laboratory diagnosis. In 1994, the Association of State and Territorial Public Health Laboratory Directors, CDC, the Food and Drug Administration (FDA), the National Institutes of Health (NIH), the Council of State and Territorial Epidemiologists, and the National Committee for Clinical Laboratory Standards convened the Second National Conference on Serologic Diagnosis of Lyme Disease (The conference proceedings recommended a two-test methodology using a sensitive enzyme immunoassay (EIA) or immunofluorescence assay as a first test, followed by a western immunoblot assay for specimens yielding positive or equivocal results  or immunofluorescence assay, followed by a western immunoblot assay for specimens yielding positive or equivocal results.On July 29, 2019, the Food and Drug Administration (FDA) cleared several Lyme disease serologic assays with new indications for use, allowing for an EIA rather than western immunoblot assay as the second test in a Lyme disease testing algorithm.When cleared by FDA for this purpose, serologic assays that utilize a second EIA in place of western immunoblot assay are acceptable alternatives for the serologic diagnosis of Lyme disease."}
+{"text": "The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions. Open Forum Infect Dis 2019; 6(7);In addition to study support from the National Institutes of Health, the publication was also supported by the Centers for Disease Control and Prevention under Award Number U54CK000481 to MKH.The authors regret this omission."}
+{"text": "Relationships between land-use and river water quality assessed by means of biological and physical-chemical variables and habitat characteristics were analysed for the Zwalm River basin in Flanders (Belgium). The research focussed on three zones within this river basin, each characterized by different land uses, and consequently, different types of pollution, mainly of diffuse origin. Environmental data have been integrated within a Geographic Information System. Possible relationships between aquatic ecosystem and land-use variables were searched for by means of multivariate analysis."}
+{"text": "Mycoplasma genitalium infection, and lymphogranuloma venereum add further weight to these estimates `Sexually transmitted infections (STI) exact an astounding yet preventable toll on the health and lives of men and women worldwide. The World Health Organization (WHO) estimated 376 million new curable STI occurred in 2016, including chlamydia (127 million), gonorrhoea 87 million), syphilis (6.3 million) and trichomoniasis 156 million) 6 million7 millionSTI have been associated with increased HIV transmission In 2016, three linked WHO strategies for HIV, hepatitis and STIs were endorsed by the World Health Assembly Treponema pallidum incidence globally .90% reduction in Neisseria gonorrhoeae incidence globally .90% reduction in \u226450 cases of congenital syphilis per 100,000 live births in 80% of countriesSustain 90% national coverage and at least 80% in every district  in countries with the human papillomavirus vaccine in their national immunization programme.The WHO strategy on STIs (2016 to 2021) identified four targets for 2030 Robust national\u2010level strategic information systems that incorporate STI case reporting, prevalence surveys, assessment of the aetiology of STI syndromes, and monitoring for antimicrobial resistance to gonorrhoea are needed to guide programming and clinical service delivery Box 1Strengthen and integrate sexually transmitted infection surveillance into the national health information system as a part of health system strengthening, using standardized indicators and methodologies as guided by WHO; ensure that data collection methods yield high\u2010quality information, meet ethical standards, and do not pose risks for communities or the health care workers involved. Increase the \u201cgranularity\u201d of data including through: enhanced sexually transmitted infection\u2010related disaggregated data collection based on different stratifiers that include age, sex, population and location; involve affected communities and specific populations to achieve high\u2010quality data and analysis. Identify specific populations who are most at risk for sexually transmitted infections and places where most of the transmission is occurring; establish mechanisms to promote the participation of affected communities; conduct routine case reporting and periodic prevalence assessments of core sexually transmitted infections to assess the magnitude of the sexually transmitted infection problem in target populations, including by disaggregating the data; describe the sexually transmitted infection epidemics and measure the impact in terms of sequelae and cost. Include data on the risk factors and determinants of sexually transmitted infections in order to understand and address these determinants. Include a focus on pre\u2010exposure prophylaxis as appropriate. Use both standard and innovative participatory survey methodologies to develop accurate estimates of key population sizes and detailed understandings of subnational epidemics; integrate biological surveillance with other programmes, such as a behavioural surveillance survey in the HIV files \u2013 include contact tracing and treatment of partners. Strengthen national laboratory capacity through quality assurance and the introduction of point\u2010of\u2010care diagnostics to ensure routine monitoring of sexually transmitted infections and antimicrobial resistance to Neisseria gonorrhoeae. Provide global leadership and assistance to countries in strengthening sexually transmitted infection surveillance and in using standard methodologies for such surveillance and estimation of the burden and impact; support the development of strategic information systems and sexually transmitted infection epidemics and response mapping, including the analysis of disaggregated data for monitoring inequities; support countries in strengthening case reporting, prevalence assessment, aetiologic assessment and antimicrobial resistance monitoring; strengthen global systems for collecting and sharing national surveillance data on sexually transmitted infections, including disaggregated data and analysis for monitoring equity. Provide guidance on the collection and analysis of disaggregated data based on different stratifiers and the involvement of affected communities and specific populations, including key populations for HIV, in efforts to obtain high\u2010quality data and achieve high\u2010quality analysis; use internationally endorsed methods for estimating the sizes of key populations for HIV and on setting programme targets for services for key populations for HIV. Ensure linkages of some components of sexually transmitted infection surveillance to existing mechanisms including HIV and antimicrobial resistance surveillance.WHO has developed frameworks, targets and priority actions for STI surveillance at national and global levels High\u2010income and low\u2010middle income countries with STI surveillance systems frequently rely on case reporting of STI cases or STI syndromes to estimate national incidence It is evident from recent global and regional estimates of STIs that the necessary stakeholder support, advocacy and investment \u2013 both national and international \u2013 to support STI programme and surveillance efforts has not been realized. While the burden of prevalent and incident STI cases increases, advocacy for control of these infections has waned. Transforming and strengthening STI surveillance and clinical services can serve as a cornerstone for advocacy and investment in STI prevention and control. Alignment of STI control programmes alongside HIV and hepatitis prevention through linked WHO strategies has offered frameworks for integration yet clinical services and surveillance of STIs continue to lag behind As part of a transformation process taking place at WHO, set in motion by the Director General in 2018, the global STI surveillance and STI programme support activities will be moved from the WHO Department of Reproductive Health and Research (WHO RHR) to the Department of HIV and Hepatitis, to be duly renamed the WHO Department of HIV, Hepatitis and STIs. STI research will remain with (WHO RHR) ensuring that research continues to inform STI programming. The move of the STI programme will set an example at the global level of the opportunity to integrate these surveillance and country support activities recognizing similar modes of transmission, populations at risk and currently existing health care platforms. This transition is expected to herald a renewed global focus on the importance of STIs as indicators of HIV and hepatitis risk and as opportunities for prevention and control of all STIs while ensuring continued inclusion within the broader framework of sexual and reproductive health and rights The authors have no competing interests to declare.MT and TW conceived of the paper and provided content and references. MT drafted the paper. MT and TW reviewed and revised drafts prior to submission"}
+{"text": "Voice first technology offers older adults with dementia support that may maintain independence, reduce social isolation and improve quality of life (QoL). This study investigates the impact of a voice-controlled technology customized to the needs of participants living with dementia and their caregivers. A mixed methods design focused on psychosocial factors and usability characteristics. The purposive sample consisted of older adults with dementia (n=12) and their care partners (n=12)) living independently in the community. Validated measures for cognition, depression, caregiver burden, quality of life and usability were included. Qualitative in-home interviews were conducted to assess impact on social connections and independence. Results indicate that voice first technology can reduce caregiver burden and can support the independence and QoL of older adults with dementia. The discussion considers the value of low cost voice first technology as a way to support older adults with dementia and their caregivers."}
+{"text": "In existence for nearly 25 years, the Healthcare Systems Research Network (HCSRN) is an established and sustainable network of health care systems that serves as a \u201creal world\u201d laboratory to enable the integration of research findings into practice. The objective of this paper is to demonstrate how the HCSRN serves as an ideal environment for studying dissemination and implementation of evidence-based practices into health care systems through the example of developing a multi-site study on the implementation of evidence-based precision medicine practices.The \u201cImplementing Universal Lynch Syndrome Screening (IMPULSS)\u201d study (NIH R01CA211723) involves seven HCSRN health care systems and two external health care systems. The IMPULSS study will describe and explain organizational variability around Lynch syndrome (LS) screening to identify which factors in different organizational contexts are important for successful implementation of LS screening programs and will create a toolkit to facilitate organizational decision making around implementation and improvement of precision medicine programs in health care systems.The strengths of the HCSRN that facilitate D&I research include: 1) a culture of collaboration, 2) standardization of data and processes across systems, and 3) researchers embedded in diverse health care systems. We describe how these strengths contributed to developing the IMPULSS study.Given the importance of conducting research in real world settings to improve patient outcomes, the unique strengths of the HCSRN are of vital importance. The IMPULSS study is one case example of how the strengths of the HCSRN make it an excellent environment for research on implementing evidence-based precision medicine practices in health care systems. Established in 1994, the Healthcare Systems Research Network (HCSRN) is a network of over 1,900 researchers across 19 health care systems who regularly collaborate and serve as a research laboratory based in \u201creal-world\u201d health care populations and environments and to enable the rapid integration of research findings into practice [The implementation of effective technologies and evidence-based precision medicine strategies into clinical practice is challenging and slow and contributes to variability and deficiencies in quality of care 3. Contex45Dissemination and implementation (D&I) science bridges the gap between research and clinical practice by generating evidence to: 1) understand how evidence spreads to different stakeholders in the health care system (dissemination) and 2) characterize how the behavior and perspectives of clinical stakeholders, health care organizations, and patients influence the adoption, adaptation, and sustainability of evidence-based practices in real world settings (implementation) 7.th year of embedded research in health care systems in 2019; therefore is also an established and sustainable network in which to conduct D&I research. The \u201creal-world\u201d health care organizational infrastructure, clinical infrastructure, providers, and patient populations within the HCSRN represent diverse contextual factors to better understand the factors influencing dissemination and implementation of evidence-based practices.The HCSRN provides an optimal environment to conduct D&I studies. The HCSRN will celebrate its 25Overall, the HCSRN member systems provide care for over 28 million individuals based in diverse geographic regions across 13 states .Benefits of conducting D&I science within the HCSRN can be illustrated through the example of the newly-funded study, \u201cImplementing Universal Lynch Syndrome Screening (IMPULSS)\u201d . The IMPThe health care systems participating in IMPULSS were identified through collaborations facilitated by the HCSRN, the HCSRN Genomics Scientific Interest Group (SIG), and the Cancer Research Network (CRN). Seven HCSRN health care systems are participating in the IMPULSS study , KP Colorado (KPCO), HealthPartners, Harvard Pilgrim Health Care, Sutter Health-Palo Alto Medical Foundation, and Meyers Primary Care Institute). Two non-HCSRN organizations  are also collaborating in the IMPULSS study Figure .Both non-HCSRN organizations were identified through existing collaborations with the HCSRN: the IMPULSS site principal investigator (PI) from Weill Cornell Medicine has an established record of collaboration within the HCSRN related to Lynch Syndrome through the CRN Scholar program . An IMPUPreliminary data for the IMPULSS project were gathered by surveying the two non-HCSRN organizations and all HCSRN organizations about their respective Lynch Syndrome screening practices in general. The application for funding was developed through a collaborative process which included the overall PI presenting the IMPULSS project concept in multiple HCSRN venues to identify researchers interested in collaboration. The administrative requirements  were efficiently facilitated through processes developed through the long-standing collaborations within the HCSRN to gather and share such materials for grant applications. This familiarity of administrative processes enabled the application process to run efficiently with the seven HCSRN sites so that administrative staff at the prime institution could focus on any procedural needs that arose with the non-HCSRN sites.Lynch Syndrome (LS) is the most common form of inherited colorectal cancer and is also associated with significant risk for endometrial, ovarian, gastric, small bowel, and renal cancers, among others 11. LS is1215141020212223Implementing LS screening in health care systems, however, involves multiple stakeholders and customization to local contextual factors, including integrating LS screening into individual organizational processes, communicating with different patient populations, and determining the costs of LS screening to systems and patients 28. BecauCapitalizing on the variability and complexity of individual organizational structures and differences in the implementation of LS screening programs across health care systems, the IMPULSS study will describe and explain individual organizational variability. As shown in Table The HCSRN is a unique environment for studying the dissemination and implementation of evidence-based practices, such as LS screening, because of the number of health care systems in various stages of implementing programs to adhere to guidelines. Here we further describe the strengths of the HCSRN for D&I through the themes of 1) a culture of collaboration over more than twenty years 31, 2) st301http://www.hcsrn.org/en/Collaboration/SIG/) to foster collaboration and facilitate project development between HCSRN annual research meetings. There are also qualitative, quantitative, and mixed-methods experts collaborating across the HCSRN, as well as senior scientists collaborating to mentor junior researchers through formal and informal programs [The HCSRN has a long-standing culture of collaboration at the organization, researcher, staff, and research methodology levels . Over thprograms 31. SpeciCollaboration to build on prior studies: The collaborative culture facilitates the ability of researchers to build on studies conducted at one site to inform and contribute to the design of subsequent studies at other sites. This is crucial in D&I research to facilitate the adoption of evidence-based practices. For example, a prior study of LS screening implementation at KPNW assessed patient and provider perspectives of LS screening but was limited to individuals newly diagnosed with CRC who had agreed to undergo screening for LS as part of a study protocol at a single site [gle site 34. The IMethodologic expertise and collaboration: The robust sharing of research methodology and experiences that has been established over time in the HCSRN also enables leveraging expertise and institutional memory of the researchers and staff at various sites in the development of new studies within the real-world environment of the health care systems. Multiple prior HCSRN studies established the methodology proposed in the IMPULSS study to conduct key organizational stakeholder interviews across all participating systems centrally from one site (Geisinger) [36isinger) 3637. Metinger) 36. CapitalThe longevity of the HCSRN provides a wealth of experience in the understanding of data infrastructures and reliability and has resulted in robust streamlining of research administrative processes over time. Specific to IMPULSS, this familiarity with data infrastructure and existing administrative protocols are another strength of the HCSRN that made developing a study of this size possible within the limited research resources available in a funded study.Data standardization: The common data model utilized by the HCSRN is the Virtual Data Warehouse (VDW) [se (VDW) . The VDWse (VDW) . For datAdministrative process streamlining: Over the years, the HCSRN has worked diligently to streamline administrative processes by developing and adopting pre-negotiated sub-award and DUA templates, as well as constructing standardized IRB templates. These data and organizational standardizations have made it possible to execute DUAs across the 7 HCSRN sites and the 2 non-HCSRN sites in the first year of the IMPULSS project. For IRB processes and to facilitate movement towards the single IRB process, standard operating procedures (SOPs) for ceding and an Inter-institutional authorization agreement (IIA) template for ceding within the HCSRN have existed for some time [ome time . Within Standardization of data and processes are happening elsewhere and single IRB for multi-site projects funded by the NIH is required for projects funded after January 25, 2018 . The HCSHCSRN organizations have researchers who are embedded within their respective health care systems and conduct research in \u201creal-world\u201d settings critically important to D&I research. These researchers have access to and established collaborations with their local clinical enterprises and a deep understanding of the contextual complexity of their organization\u2019s data, business model, and organizational and leadership structure.D&I research in general and the IMPULSS study specifically seeks to understand organizational complexity around implementation of evidence-based recommendations. For IMPULSS, the embedded researchers (the site PIs) were able to quickly assess specifics related to their organization\u2019s process (or lack thereof) towards implementing universal tumor screening for LS (see above Table Another challenge with D&I studies is that health care systems are rarely static. Because HCSRN investigators are embedded in their health care systems, they can notify the larger research team when changes that may impact the study happen. Based on experience from other implementation studies conducted by the PI 41, the IFor IMPULSS, a database is used to track changes to LS screening programs specifically and to clinical and organizational leadership for each health care system within the IMPULSS study. Information is entered into a database as reported by site PIs during regular study meetings. Data corresponding to change over time will contribute to study results as we identify those contextual factors needed for implementing effective LS screening and other precision medicine programs.Given the importance of conducting research in real world settings to improve patient outcomes, the unique strengths of the HCSRN are relevant now more than ever. The development and successful funding of the IMPULSS study is one case example of how the strengths of the HCSRN make it an important environment for research on implementing evidence-based practices in health care systems. Key strengths of the HCSRN important to D&I research include a culture of collaboration with high levels of productivity and experience, standardization of data collection and research procedures across systems, and researchers embedded in diverse health care systems. These strengths individually are not unique to the HCSRN; and in fact, are important to conducting D&I research in any network. Based on the case example of the newly-funded IMPULSS precision medicine study, we demonstrate it is the combination of these elements \u2013 collaboration, standardized data and processes \u2013 and embedded researchers that make the HCSRN one such environment to successfully design and conduct D&I research."}
+{"text": "Among older cancer patients, cancer-related fatigue is a common chronic problem that may result in functional dependence and decreased quality of life. Currently, there exists no standard of care for managing fatigue among cancer patients, pressing the need for further research and the development of novel interventions. Our research followed the validated DIPEx (Database of Patient Experiences) methodology, which utilizes in-depth, narrative interviews to create a rich and broad archival resource of patient stories to highlight commonalities and differences in illness experiences. We interviewed 9 older women (aged 60+ years) who have been diagnosed with and treated for breast cancer . Interviews were audio and/or video-recorded and transcribed for analysis of emergent themes using MAXQDA qualitative software. Four primary themes have emerged from the data: (1) fatigue is a distressing side effect of treatment for which patients do not feel adequately prepared; (2) information about fatigue and how to deal with it is not systematically provided within the oncology setting; (3) patients develop their own systems for managing fatigue and general energy levels ; and (4) social support for fatigue varies. Education about cancer-related fatigue and its management represents an unmet need among older breast cancer survivors. The development and implementation of both clinician training initiatives and patient-facing educational and engagement interventions represent important next steps in supporting the care needs of cancer patients and survivors."}
+{"text": "This data article features a figure and tables that show the correlations among brand value by Brand Valuation , market capitalization, and the consolidated overseas sales ratios of Japanese companies. The figure shows the scatter plot for market capitalization vs. brand value for Japanese companies. The lines in the plot show the regression fits for two groups of companies  with consolidated overseas sales ratios below or above 30%, respectively. The Pearson's correlation coefficients between brand value and market capitalization are calculated for global and domestic companies separately. Additionally, cross-tabulation statistics and Chi-square test of independence for brand values and consolidated overseas sales ratios were performed to assess their correlation. The companies with brand value, consolidated overseas sales ratio and market capitalizations were listed in The brand value and consolidated overseas sales ratios for 80 Japanese companies  for 2017 were collected from the website of Interbrand Japan Ltd 2.3https://www.r-project.org) We present the correlation between brand value and market capitalization in a scatter plot and in regression statistics using Pearson's correlation coefficient. Cross-tabulation statistics and Chi-square test of independence were employed to assess the correlation between brand value and consolidated overseas sales ratios of Japanese companies listed in"}
+{"text": "OBJECTIVES/SPECIFIC AIMS: To review the multiple differences between traditional research design and on the ground pragmatic trials. To review two pragmatic projects, identify core assumptions and to contrast assumptions with the reality of conducting T3 and T4 research. METHODS/STUDY POPULATION: Observational mixed methods multi trial review of large multi site implementations. RESULTS/ANTICIPATED RESULTS: The complexities of implementation on the ground were consistently greater than anticipated and required changing assumptions and research design elements. DISCUSSION/SIGNIFICANCE OF IMPACT: Research findings are tremendously influenced by design and design implementation decisions. Anticipating the scope and breadth of the challenges will assist potential of successful implementation."}
+{"text": "Social integration of neighborhoods and social network properties are associated with better cognitive function but the two factors are often investigated separately. This study examines the interaction between neighborhood social integration and quantity and composition of social network on cognitive domains by analyzing Population Study of Chinese Elderly, a population-based epidemiological study of over 3000 US Chinese older adults aged 60 and above in Chicago metropolitan. Regression results show that larger network size, volume of contact and smaller proportion kin and proportion co-resident were associated with higher level of global cognition. Higher sense of community was associated with higher level of global cognition. The interaction term of volume of contact and neighborhood cohesion was negative and statistically significant, suggesting the protective effect of volume of contact may decrease in high cohesion neighborhoods. Similar moderation effects were observed in specific cognitive domains, including episodic memory, working memory and executive function."}
+{"text": "Parkia biglobosa cuttings. The investigated data are related to the research article \u201cEffects of alternative hormones on the rootability of Parkia biglobosa.\u201d  [1]. In the experimental data, number of rooted cuttings, number of cuttings with callus, number of cuttings with mortality, total number of roots, total root length of cuttings and length of longest root of cuttings data employing alternative hormone  on the semi-hardwood stem cutting of Parkia biglobosa have been exhibited. The data would be useful to researchers finding alternate growth and rooting hormones that are cost friendly and for vegetative propagation during enrichment planting program of important tree crops that are difficult to propagate via seeds.The data article contains the experimental data and figures on the number of rooted cuttings, number of cuttings with callus, cutting mortality and root length of  The stem cuttings were treated with the alternative hormones for 3\u2009min and air dried for 5\u2009min after each basal end treatments. The design of the experiment was a Randomized Complete Block Design (RCBD) where five cuttings of Parkia biglobosa were subjected to four treatments (control included) and replicated three times to give a total of 60 cuttings. At the end of the experiment, the following observations were made and data collected were; Number of rooted cuttings, Number of cuttings with callus, Number of cuttings with mortality, Total number of roots, Total root length of cuttings and Length of longest root of cuttings.An experiment was carried out at Landmark University Teaching and Research Farm Omu-aran, Kwara inside a three polypropagator rooting chambers fabricated following the design described by Leakey et al. 2.2The data collected was analyzed using Analysis of Variance (ANOVA) and the means were separated using Least Significant Difference (LSD)."}
+{"text": "This study investigates the effects of childhood misfortune and adult physical activity on later-life body mass index (BMI) and waist circumference. We use ordinary least squares regression to examine the impact of childhood misfortune (30 indicators), and adult physical activity (frequency and intensity) on waist circumference and BMI (kg/m\u00b2) using data from the Health and Retirement Study . Results emphasize that experiencing childhood misfortune is associated with a larger waist circumference and BMI in later life, while adjusting for social status and lifestyle variables. Adjusting for adult physical activity decreases the effect of childhood misfortune on waist circumference, suggesting mediation. The analysis reveals that the effects of childhood misfortune on BMI and abdominal adiposity are remediable. Although childhood misfortune is associated with larger waist circumference and BMI in later life, regular physical activity reduces the risk on both indicators of obesity."}
+{"text": "The scope of AGHE\u02bbs responsibility to gerontology and geriatrics extends worldwide, as reflected in its tag line, \u201cGlobal Leaders in Education on Aging.\u201d Optimal responses to worldwide demographic transitions can only come from persons well-versed in the dimensions of aging and trained and globally situated to translate that knowledge into effective and culturally-appropriate solutions. This presentation reviews the evolution of AGHE\u2019s role in initiating and fostering global networks of educators in gerontology and geriatrics, including collaborative efforts with major international organizations  to increase the visibility and appreciation of aging-related issues among world leaders; sponsoring national and international meetings to promote exchange of ideas and refinement of teaching methodologies; initiating and adapting new models of gerontological training enhanced by advances in information and communication technology; and supporting world-wide cohorts of emerging scholars to assume leadership roles within the organization. Recommendations for next steps are considered."}
+{"text": "In recent years, the knowledge generated by decoding the human genome has allowed groundbreaking genetic research to better understand genomic architecture and heritability in healthy and disease states. The vast amount of data generated over time and yet to be generated provides the basis for translational research towards the development of preventive and therapeutic strategies for many conditions. In this special issue, we highlight the discoveries of disease-associated and protective DNA variations in common human diseases and developmental disorders. Sequencing of the whole genome of many organisms has provided the scientific community with a tremendous amount of information to determine which part of the mammalian genome is under constraint or undergoing rapid turnover. Based on DNA conservation, evolutionary studies have shown that DNA changes are taking place at a higher rate in noncoding regulatory regions and at a much lower rate within gene coding sequences . Each huTo emphasize the importance of gene regulation, genome-wide association studies (GWAS) of human common diseases demonstrate that ~10% of the disease-related single nucleotide polymorphisms (SNPs) are located in amino acid coding sequences, whereas around 90% of the disease-associated SNPs fall outside of protein coding regions ,3,9. IdeThis Special Issue on DNA Variations in Evolution and Human Diseases features a series of studies that identify new pathological and protective DNA variations in common human diseases and conditions including chronic periodontitis , familia"}
+{"text": "Healthy diet is essential to the management of chronic conditions such as cardiovascular disease and diabetes. Research suggests an association between social support and dietary behavior, yet the relationship is not fully explored. The role of social support in nutrition consumption was examined among older participants in a group-based lifestyle enhancement program (Texercise Select) designed to improve dietary behaviors and physical activity and related supports. Factor analysis and structural equation modeling were performed using secondary data from a quasi-experimental study of participants who completed a baseline survey and three-month follow-up . The majority of participants were age 70 years or older , female (82.1%), and had at least two chronic conditions (63.5%). The two groups did not differ in baseline levels of nutrition intake or social support. Program participants improved in terms of intake of water and fruits/vegetables as well as social support. Structural equation models adjusting for the effect of baseline scores indicated that the intervention effect on fruits/vegetable intake  was partially mediated  by social support for planning and keeping dietary goals and reducing barriers to healthy eating . Findings suggest that programs designed to enhance social support may be effective in improving dietary behaviors among older adults. Future research should investigate various types of social support for promoting healthy diets."}
+{"text": "As two of the most common geriatric conditions, frailty and cognitive impairment often coexist, and are known to predict poor health outcomes separately and jointly. The link between frailty and cognitive impairment may result from the fact that many of the aging processes underlying frailty may also be responsible for brain aging and cognitive decline. What is unknown is: (1) whether frailty as a measure of physiological resilience is predictive of dementia above and beyond neuropathology and cognitive decline; (2) whether there are individual characteristics that uniquely identify separate vs. joint presence of physical frailty and cognitive impairment. To begin to address these questions, Talk 1 reviews concept of frailty in relationship to reserve and resilience and discusses theoretical underpinnings of three integrated phenotypes of physical and cognitive impairment; Talk 2 uses data from two epidemiological cohorts to study the relationship between frailty and dementia after accounting for neuropathology. Talk 3 uses data from the Gait & Brain Study to compare the strength of associations of cognitive impairment alone vs. cognitive impairment plus physical frailty (or gait performance) with incident dementia. Talk 4 uses data from the National Health and Aging Trends Study to develop a U.S. national profile on the intersection between physical frailty and cognitive impairment in community-dwelling older adults. Together, findings from this study help elucidate the interconnection between physical frailty and cognitive impairment, as well as clinical utility of joint consideration of cognitive decline and physical frailty for predicting risk of dementia."}
+{"text": "A growing body of literature shows that health promotion and disease prevention strategies and messages may not be effective in reaching racially and ethnically diverse communities, unless those strategies are culturally and linguistically adapted for target communities . The Rachttps://millionhearts.hhs.gov/) blood pressure medication adherence resources at faith-based sites, community-based pharmacies, and health care providers\u2019 offices  with the locations of implementation sites and participants. A desire lines (or spider diagram) approach was used to visualize KOT program participation. Mapping provides a visual means of evaluating program reach and is a concise way of communicating the role of implementation sites in delivering culturally, linguistically, and geographically targeted health prevention strategies.z scores, determined by the ArcGIS Hot Spot Analysis (Getis-Ord Gi*) tool (Esri) with the Contiguity Edges Corner and Apply False Discovery Rate correction parameters; the shading indicates intensity of clustering with darker shading indicating more clustering of high values (larger z scores). Overlaps in population clusters were found by using the ArcMap Intersect tool, version 10.3 (Esri).We geocoded the addresses of 12 implementation sites active as of 2016 and residential addresses of KOT program participants reported in baseline surveys from 2015 and 2016 \u20136. All rAn overarching objective of REACH FAR is delivery of targeted strategies for 4 Asian American communities. The map demonstrates that program implementation sites are located in population clusters of targeted Asian American subgroup populations, as intended at program inception: Asian Indian in Middlesex and Queens counties, Bangladeshi in Kings and Queens counties, Filipino in Queens county, and Korean in Queens and Bergen counties. By mapping KOT program participants, we found that large concentrations of congregants residing in areas neighboring each faith-based site are reached by the KOT program. However, the maps also demonstrate that the programs also reached community members residing outside of immediate or neighboring ethnic enclaves. We suspect that people attending these events prefer or need culturally and linguistically adapted resources that are unavailable in the neighborhoods in which they reside. Culturally and linguistically adapted materials regarding healthy eating and blood pressure control developed for limited English-proficient Asian Americans were disseminated at implementation sites , reachinOur map provides a visual illustration of the network of faith-based organizations and community-based organizations coordinating to promote healthy eating and heart health and the progress of implementation as illustrated with the KOT program. To this end, mapping products are being used in the following ways to enhance future coordination and collaboration between partners:The map is being presented to the NYC DOHMH to demonstrate the need for reaching Asian American populations. Before our coalition efforts, the KOT program had not been implemented in any faith-based organizations serving Asian Americans. Our results demonstrate both success and potential for future NYC DOHMH engagement efforts with Asian American communities.The map is being reviewed at coalition meetings to discuss opportunities for scaling the program to expand program reach. For example, the map suggests that partnering with community-based organizations serving the Asian Indian and Filipino communities in Hudson County or the Bangladeshi community in Bronx County may expand reach."}
+{"text": "Recent advances in computational and bioimaging techniques have greatly enhanced the ability of engineers and scientists to better understand the dynamics of the human body and functions of living organisms. Specifically, progressive computational, mathematical, and physics-based approaches have helped researchers to develop sophisticated novel techniques that can solve the problems encountered in the fields of bionics and biomechanics with improved visualization of biological systems and design of new medical devices. These advances in imaging and visualization methods are helping to identify, classify, and quantify patterns in bionics and biomechanical investigations.The theme of this Special Issue is to explore the state of the art of bionics and biomechanical research using bioimaging technology. The Special Issue consists of original contributions addressing challenges in understanding the mechanics and functions of biological systems and living organisms solved by innovative bioimaging methods. The scope of the Special Issue includes the bioimaging analysis in biomechanics, investigation of the functions of living organisms through imaging techniques, inventions of biomedical devices, and evaluation of surgical treatments. These original research studies provided the biomedical research community an insight into novel biomedical imaging techniques and algorithms on bionics and biomechanics.This Special Issue accepted 6 papers out of 15 through careful review by editors and peer review, which led to an acceptance ratio of 40%. These 6 original research articles investigated the radiography system improvement, radiographic image analysis, medical image modeling, and imaging technique evaluation.Y. Liu et al. proposed a novel data-driven decomposition model to decompose the conventional chest radiograph into both soft tissue and bone images and compared the results with virtual dual-energy subtraction (DES) imaging. The proposed approach markedly reduced the visibility of bony structures in chest radiographs and produced soft tissue and bone contrast similar to those produced by the actual DES system. Their work shows potential to enhance diagnosis of lung diseases.Y.-H. Chang et al. constructed a finite element mandible model  from high-resolution computed tomography (CT) images to investigate the biomechanical structures of four common occlusion conditions after bilateral sagittal split osteotomy surgical treatment. They observed high stress on the miniplate for all four occlusion conditions, and the screws on the proximal segment near the bone gap experienced high stress. This platform provides more information on the biomechanics of mandible implantation.W.-E. Hsu et al. compared 15 vertebral measurements on radiographic images of 18 patients with single-level vertebral compression fracture to access the degree of vertebral body height loss and kyphotic angle. The evaluation of these measurements could help to determine the probability of intravertebral clef, and this study could provide a reference for surgeons when using imaging modalities to access the degree of vertebral body collapse.C.-W. Liao et al. developed a high-frame-rate intraoral periapical sensor with a senor imaging speed of up to 15\u2009Hz for a 2.5D periapical radiography system, which could be used to capture images at different depths of an object. The developed sensor could be combined with tomosynthesis to obtain reconstructed slice images of different depths and has the potential for clinical dentistry applications.K. Oberhofer et al. fit a generic musculoskeletal model of the lower limbs of an adult female subject to 3D body surface data of children with and without cerebral palsy. They compared the fitted lengths and volumes of six muscle-tendon structures with the subject-specific muscle-tendon lengths and volumes derived from magnetic resonance images. High accuracies were obtained in the fitted lower limbs in both study groups for 3D body surface data, but the accuracies of muscle volumes contained large variations.S. Shimawaki et al. performed CT imaging on the fingers of 10 male adults gripping cylinders of three different diameters  and constructed 3D computational bone models based on these CT images to measure the flexion angle of each finger joint. Results showed that smaller cylinder diameters were associated with significant increases in the flexion angle of the all joints of four fingers. Consistent results were observed when comparing to the flexion angles of joints using other published methods."}
+{"text": "Educational attainment is one of the strongest social determinants of adult health. However, recent studies show that it is a stronger determinant in some areas of the country than others. This study investigates geographic and life course contexts that may explain the pattern. We merge data on adults aged 50+ in the Health and Retirement Study (1998-2014) with contextual data on their state(s) of birth and residence. We examine: (1) how the education-health association varies across regions, and (2) how childhood  and adulthood experiences  explain the variation. Findings reveal that the education-health association varies across regions and is more pronounced for outcomes further along in the disablement process. Poor childhood health, adult behaviors, and states\u2019 economic policies partly explain why the association varies across regions. The findings underscore the importance of geographic and life course contexts for understanding educational disparities in health."}
+{"text": "Dear Editor,We read the study \u201cEpidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients\u201dThe utility of PCT for sepsis determination has been largely established in burn patients.Thus, we believe that day 0 PCT levels should be considered as an independent prognostic marker for SJS/TEN in addition to the validated parameters of SCORTEN. Further, we encourage trials specifically evaluating the role of PCT in the management of SJS/TEN.None declared.Ananta Khurana: Approval of the final version of the manuscript; critical literature review; effective participation in research orientation; critical manuscript review; preparation and writing of the manuscript.Mukesh Kumar Sharma: Approval of the final version of the manuscript; critical literature review; critical manuscript review; preparation and writing of the manuscript.Kabir Sardana: Approval of the final version of the manuscript; critical literature review; effective participation in research orientation; critical manuscript review; preparation and writing of the manuscript.None declared."}
+{"text": "We conducted analysis to test if health disparities in cognitive aging were parallel to or different from health disparities in patterns of aging in other systems in the body, and if race/ethnicity-related disparities could be accounted for by differences in socioeconomic circumstances across the life-course. We analyzed data from more than 10,000 adults participating in the US NHANES and US Health and Retirement Study. We measured cognitive aging using neuropsychological tests of processing speed and memory. We measured aging in other systems using composite indices of biological aging based on organ-system function tests and blood chemistries. We conducted analysis to (i) quantify and compare health disparities in cognitive aging and biological aging; (ii) test if individuals exhibiting accelerated cognitive aging were also exhibiting accelerated biological aging; and (iii) test if race/ethnic disparities in cognitive and biological aging could be explained by measured socioeconomic resource differences in childhood and later life."}
+{"text": "Older adults living in Asia or of Asian origin have unique preferences for information that require special attention. This symposium focuses on the health information preferences and behaviors of Asian older adults. Song et al. investigated the relationship between Internet use and perceived loneliness among Older Chinese using from survey data collected in the 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS), a national study involving 12,400 households in Mainland China. Multiple regression results suggest that older Chinese Internet users perceived significantly less loneliness compared with their age peers who were non-Internet users. Zhang et al. investigated the role of information and communication technologies in supporting antiretroviral therapy (ART)-related knowledge seeking among older Chinese with HIV. Their cross-sectional survey data were collected from 2012 to 2013 in Guangxi, China. The results suggest that less than 5% of the participants sought HIV-related information via computers. Patients less knowledgeable about ART were more likely than those more knowledgeable to consult medical professionals about the disease via cell phones. Shiroma et al. report findings of a systematic literature review conducted in spring 2019 that examined Asian ethnic minority older adults\u2019 preferences for end-of-Life (EOL) information seeking and decision making. The results suggest Asian ethnic minority older adults are understudied in the literature on EOL information and decision making, especially in terms of their unique cultural contexts. Du et al. examined how health information obtained from different types of social networks affect osteoporosis self-management behaviors among older White and Asian women."}
+{"text": "People with Alzheimer\u2019s disease use more medical services  and are admitted to inpatient facilities at higher rates  than normal controls. In addition, social services provide support for caregivers and are associated with positive outcomes for care-recipients and their caregivers . Despite high level of need, utilization of mental health services and social agencies for caregiver support remains low . Following the Andersen and Newman model (1973), we examined whether predisposing factors , needs , and enabling factors  differentially predicted the presence of medical, social, and mental health service use. A total of 228 dyads (PWD and the caregiver) were included. We examined each PWD and caregiver characteristic individually (univariate models) and then as a unique predictor of each of the three service use outcomes (multivariate models). A greater number of medications uniquely predicted higher medical service use, greater pain severity and PWD income were uniquely associated with higher social service use, and a greater number of medications and increased memory impairment predicted more mental health service use. These results show that distinct factors predict use of different types of service use among PWD and their caregivers."}
+{"text": "Stress and resilience are two factors that are receiving attention as key determinants that can provide insights that underlie the deleterious effects on the overall health and well-being of individuals by influencing behavioral and biological processes. This symposium contains a collection of papers seeking to address the influence of resilience and coping on health outcomes in middle to late life adults. Tobin and Thorpe identified profiles of psychosocial resilience and examined their association with allostatic load (AL) among 283 Black men in the Nashville Stress and Health Study. Using Latent class analysis (LCA), individuals in the high resilience class had the greatest odds of high AL; high resilience worsened physical health for older but not younger Black men. Tan and colleagues explored satisfaction across life domains and correlates of satisfaction across domains in 93 Black adults. The authors report that higher satisfaction was associated with less education, less financial strain, lower depressive symptoms, and better self-rated physical health. Nguyen examined the association between everyday discrimination and generalized anxiety disorder (GAD) and whether church-based relationships buffer the negative effects of everyday discrimination on GAD among older African Americans. Using data from 670 African American respondents age 55 and older from the NSAL, the author reports, that significant interactions indicated that frequent contact with church members and high levels of subjective closeness to church members buffered against the negative effects of discrimination on GAD. These presentations collectively will bolster our knowledge of how stress and resilience impacts health disparities."}
+{"text": "Objective: To culturally and linguistically validate PROMIS Cognitive Functions and Concerns Scales in American Sign Language (PROMIS-ASL) for use with deaf older adults over 50. Methods: We used the standard procedures developed at the U.S. National Center for Health Statistics Cognitive Survey Laboratory to culturally adapt and translate items from the cognitive scales of the Patient Reported Outcomes Measurement Information System (PROMIS). We describe cultural adaptation and linguistic translation procedures led by a team of primarily deaf investigators. Using multidimensional exploratory or confirmatory factor analyses, we identify or confirm the items most likely to comprise each subset. Once the PROMIS-ASL version is finalized, we will compute test-retest reliability using ICC (intraclass correlation coefficient) from two-way random effects ANOVA models. Results: We produced an accessible patient reported outcomes cognitive measure in American Sign Language and a culturally appropriate set of items that are relevant to the experiences of deaf older adult over 50 users of accessible technology and services. Conclusions: The final PROMIS-ASL product with cognitive domain will be distributed for public use."}
+{"text": "This paper presents an innovative conceptual framework for designing a Comprehensive Digital Self-care Support System (CDSSS) to meet the health needs -physical, mental and social health needs of older adults and their caregivers. Older adults deal with multiple co-morbidities, medications and their side effects, fragmented care and often have poor understanding of their own health and treatments. These challenges call for solutions that lead to better empowerment and pro-active engagement and for support systems that focus on wellness and preventive care. The conceptual model we offer draws on diverse disciplines including health care management and medicine, information systems, communication, consumer behavior, and sociology to identify a set of key design principles for CDSSS. A review and analysis of the literature in the different fields led to the identification of 6 CDSSS design principles: (1) Systems approach; (2) User experience; (3) Ecosystem perspective for shared resources 4) Social and contextual learning; (5) Accessible design; (6) Designing for trust and empathy. The model clarifies how these design principles (or approaches) inform the development of the three main components of a CDSSS  and enable the key CDSSS deliverables . The conceptual model also helps to lay out an agenda for future research on self-care support systems for older adults."}
+{"text": "We present the effect of racial/ethnic group difference on the impact of REACH TX on measures of quality of life as implemented by the Alzheimer\u2019s Association North Central Texas Chapter. Five dimensions of quality of life  were assessed at baseline and 6-month follow-up among three racial/ethnic groups of caregivers . Generalized estimating equations (GEEs) were used to assess racial/ethnic differences in the changes of quality of life after adjusting covariates. Significant interaction effects between racial/ethnic group and time (from baseline to follow-up) were found in burden, depression, and social support. White and Hispanic caregivers showed significant improvements, while the improvement among African American Caregivers was not statistically significant. The disparity in outcomes among diverse racial/ethnic groups in the program suggests the REACH TX intervention would benefit from tailoring interventions for African American caregivers."}
+{"text": "Prevalence of marine biotoxins in seafood has been associated with increasing frequency, intensity, and duration of harmful algal blooms, and an increase of the geographical and temporal distribution of harmful algae. New and emerging biotoxins have been recurrently detected in regions where they were previously absent, raising challenges to the economic sustainability of seafood production in coastal areas and to consumer health safety. The economic burden to seafood producers caused by the closure of production areas and a possible feeling of insecurity from consumers urges researchers to improve available knowledge on toxin dynamics in marine organisms and the environment. Epidemiological studies are scarce and risk characterization is needed, particularly for emerging toxins. It is critical to enhance collaborative multi- and trans-disciplinary actions to introduce eco-innovative sustainable strategies to improve shellfish and fish safety. Strengthening industrial competitiveness is achievable by developing fast and reliable methods for marine biotoxin detection, and by implementing mitigation strategies. Innovative toxicological approaches for seafood safety evaluation are also required. The seven articles of this special issue address such research needs and are organized into three groups: (i) toxin dynamics and effects in marine organisms, (ii) development of detection methods for marine toxins, and (iii) toxin exposure and risks associated with the consumption of contaminated seafood.Alexandrium catenella that caused mass mortality of several marine invertebrate species, and resulted in accumulation of high levels (exceeding 100 times the regulatory limit for human consumption) of paralytic shellfish poisoning (PSP) toxins in clams. This study highlights the need for assessing toxin dynamics in shellfish under controlled conditions to better understand and foresee the impacts of harmful algal blooms. Andres et al. [Perna viridis) with the toxic dinoflagellate Alexandrium minutum under controlled laboratory conditions to assess the dynamics of PSP toxin levels during accumulation and elimination phases. Barbosa et al. [Sparus aurata) exposure to PSP toxins through contaminated mussels to assess physiological responses and changes in toxin accumulation. Tetrodotoxin (TTX), which has a mode of action comparable to PSP toxins, was characterized in the greater blue-ringed octopus Hapalochlaena lunulata from Okinawa, Japan [Within the first group of articles, Alvarez et al.  reporteds et al.  fed greea et al.  investiga, Japan .Regarding the development and optimization of methods for toxin detection, Chen and colleagues  optimize"}
+{"text": "The 2019 GSA Fellows Symposium includes GSA members who were recently granted GSA Fellow status. They represent each of the GSA sections: Biological Sciences (BS), Health Sciences (HS), Behavioral & Social Sciences (BSS), Social Research, Policy & Practice (SRPP), and the Academy for Gerontology in Higher Education (AGHE). The theme of the 2019 GSA Fellows Symposium is focusing on the power of networks and will highlight the importance of neuroendocrine networks (Christian Sell), the role of social support for refugees in Canada (Esme Fuller-Thomson), the importance of professional partnerships to promote health (Heather Young), aging-friendly communities (Emily Greenfield), and the role of networks in teaching gerontology (Tina Kruger). The importance of networks across disciplinary boundaries will be discussed."}
+{"text": "Rapid containment (RC) is one of the five priority interventions of the World Health Organization (WHO) Strategic Action Plan for Pandemic Influenza;  update national pandemic preparedness plans; (2) clarify specific sector roles during both RC and pandemic response efforts; (3) emphasize concepts to senior officials from different government agencies that may be involved in pandemic response; and (4) allow stakeholders to identify knowledge and planning gaps, such as lack of standardized operating procedures for RC initiation and availability of trained staff to execute the plans. A lesson learnt from the exercise at the regional level in 2014 was the need to improve Emergency Operations Centre activation plans. As a result, the improved plans were developed, implemented and successfully tested in the 2015 PanStop exercise (Many national governments within the Western Pacific Region have developed national pandemic response plans for RC to prepare for the next influenza pandemic. ("}
+{"text": "Long-term services and supports (LTSS) are services provided to individuals with functional limitations and chronic conditions who need assistance to perform daily activities such as bathing, dressing, preparing meals, and administering medications, and can be provided in community settings via services such as home health, as well as institutions such as nursing homes. Racial disparities are persistent across systems of LTSS, with older adults of color receiving lower quality care and experiencing worse health outcomes than their white counterparts. Given the increasing diversity of the aging population, and the need to ensure equity in quality and health outcomes in LTSS, there is a greater need for more understanding of how experiences of care vary across multiple settings for diverse groups of older adults and the people who help them. This symposium will feature 5 presentations that provide novel insight regarding racial disparities in community- and institution-based LTSS. We focus on racial differences in functional needs and disparities among those receiving home health services and living in nursing homes. Individual presentations will describe 1) race and gender differences in physical functioning needs of older adults; 2) disparities in home health quality across racially diverse and low income geographic areas; 3) racial disparities in nursing home residents overtime; 4) racial and ethnic disparities in rates of 30-day rehospitalization from skilled nursing facilities among Medicare Fee-For-Service and Medicare Advantage patients; and 5) the impact of the unequal burden of care provided to minority nursing home residents by staff of color."}
+{"text": "This first truly global conference on the use of zygomatic implants for the oral reconstruction of patients with compromised or deficient maxillae was held at the Museum of London from 1 to 2 March 2019. It attracted over 200 clinicians and academics from 24 nations and reviewed over 25 years\u2019 experience and research in this field. This conference presented concepts heralding new opportunities for the oro-facial rehabilitation of doctor-induced osteonecrosis of the jaw (ONJ), both osteonecrosis radiation-induced (ORN) and medication-induced ONJ (MRONJ) in oncology patients. He detailed their development from Professor Branemark et al\u2019s  seminal Dr Claudio Brenner from The National Cancer Institute, Chile, considered the placement of zygomatic implants in the postoperative head and neck cancer patient. He discussed the role of careful zygoma assessment via CT, to gain a quantitative and qualitative understanding of available bone for zygomatic implant stability and osseointegration. The shape of the lateral maxillary air sinus wall in relation to implant trajectory was considered along with the question of whether the lateral bone was necessary for long-term implant success.The relationship of a zygomatic implant to the lateral sinus wall, and indeed the Schneiderian membrane itself was the topic presented in detail by Dr Carlos Aparicio (Universities of Gothenburg and Barcelona). He introduced the concept and classification system of the zygoma anatomy-guided approach (ZAGA)  method oDr Ulf Nannmark  explored the range of biomaterials for reconstruction of the challenging edentulous maxilla, including the role of ceramic \u2018membranes\u2019 to promote filler-less osseous regeneration prior to zygomatic implant treatment. He has developed novel materials, which release bioactive molecules to upregulate bone formation, and he hoped to bring these to market.The role of the ENT surgeon in pre-assessment of the maxillary sinuses was considered by Mr Samuel Leong of the Skull Base Team at Aintree University Hospital NHS Foundation Trust, Liverpool, UK. He recommended that pre-assessment patient questionnaires, such as the Sino-Nasal Outcome Test (SNOT-22) , should Day 1 was rounded off by clinical technique presentations by Mr Guy McLellan  and Dr Andrea Tedesco . Mr McLellan introduced the role and methodology of the extended maxillary sinus lift approach with simultaneous zygomatic implant placement. He advocated in-fracturing the lateral maxillary sinus wall and placing osteogenic filler and an autologous fibrin membrane harvested from the patient\u2019s blood (PRGF-Endoret). Dr Tedesco presented an alternative approach, where piezosurgical site preparation of the lateral sinus wall and zygoma was developed before implant placement. Early clinical preliminary results were promising but research was needed.Day 2 had a distinct emphasis on prosthodontic rehabilitation of zygomatic implants. Professor Dale Howes  considered the prosthodontic implications of fixture head position and the issues for both maintenance and prosthesis construction. The role of 55\u00b0 abutment angulation was explored, providing screw access within the prosthodontic envelope. Removal versus fixed restoration was also considered, in terms of patient quality of life and function. Challenges to the chewing cycle of a lingualised occlusion were discussed in great depth.Dr Luc Vrielinck (Belgium) presented a very honest and candid lecture on what he\u2019s learned over the past 25 years in terms of complications . ComplicProfessor Dale Howes maintained this theme of honesty by considering the issues with long-term prosthodontic failure and maintenance. Cement versus screw retention of prostheses was discussed, and the evidence basis presented. He advocated screw retention, given its retrievable nature and ease of repair. Poor implant head position and the effect on prosthodontic outcome over the long-term was highlighted, giving a salutary lesson to the surgeons in the audience.Finally, treatment planning in maxillectomy patients and the role of combining zygomatic implants with soft tissue and composite grafts in oncology patients were considered by Mr Andrew Dawood , Mr Chris Butterworth   and Dr CZygomatic 2019 was an enlightening and aspirational meeting, where the historical context of care was considered alongside contemporary advances. The benefits to head and neck oncology patients were immense, in their rehabilitation back into meaningful society. The role of zygomatic implants in the oro-facial rehabilitation of head and neck cancer patients was explored, and the benefits of their use in ONJ cases was highlighted, where most forms of dentoalveolar osseointegrated implants would be contraindicated. For both ORN and MRONJ cancer survivors, zygomatic implants provide a lifeline for oral functional and aesthetic rehabilitation."}
+{"text": "Elder family financial exploitation (EFFE) is widespread and increasing. The effect is devastating, causing significant financial losses, reducing health and well-being of elders, and disrupting family systems. Research reveals that most (90%) perpetrators are family members or trusted others and researchers typically focus on identification of the problem, rather than understanding how and why exploitation occurs within the family unit. Furthermore, limited consensus exists regarding a theoretical understanding of the complexities of EFFE. Theory-driven, empirical explanations of how and why EFFE transpires are urgently needed to enhance and deepen intervention and prevention efforts. In this symposium, we extend both theory and research by using a common theoretical lens to present research findings from three distinct EFFE studies. The first paper reviews the current literature on EFFE and theory and introduces Bronfennbrenner\u2019s bioecological Process-Person-Context-Time (PPCT) model as an under-utilized, but useful framework for understanding EFFE. The second paper reports on findings from in-depth interviews with non-perpetrator family members who experienced EFFE and will highlight complex intergenerational family systems processes in PPCT. The third paper highlights findings from a national study of substantiated and investigated cases of EFFE in which family member perpetrators were designated as surrogate decision makers. The fourth paper shares results from a qualitative study of family member POAs and how components of the PPCT model can be interpreted for use by helping professionals assisting families. We will also focus on the opportunities and challenges of developing theoretically sound EFFE research and the implications for improving practice and policy."}
+{"text": "While prior research has found associations between chronic pain and cognition and genetic risk of cognitive decline, little research examined moderating effects of genetic risk on the association between chronic pain and cognition. This study investigate whether genetic risk of accelerated cognitive decline, assessed by polygenic risk score (PRS) of Alzheimer disease (AD), moderates the association between severe chronic pain and cognitive decline. The data are drawn from Midlife in the US (MIDUS), a survey of a nationally representative sample of US adults. The analytic sample consists of two groups: 201 individuals who reported severe chronic pain  and 404 individuals without severe chronic pain  who completed MIDUS 2 (2004-06) and MIDUS 3 (2013-14) surveys and participated in biomarker data collection. The findings showed that men who suffered from severe chronic pain were more vulnerable to genetic risk of cognitive decline than men who did not experience severe chronic pain. Specifically, men who suffered from severe chronic pain and had higher level of PRS of AD experienced a greater decline of episodic memory than men who experienced chronic pain with lower level of PRS of AD. This association was not found in women sufferers. For both men and women who did not have chronic pain, cognitive change was not a function of the level of genetic risk of cognitive decline. Findings suggest that genetic risk of cognitive decline would be manifested contingent on life circumstances as well as gender of individuals."}
+{"text": "Salmonella enterica serovar Typhi and S. enterica serovar Paratyphi A occurs in South and Southeast Asia and in sub-Saharan Africa. In the last 2 decades, significant contributions to our overall understanding of typhoid fever and paratyphoid fever (collectively enteric fever) have been achieved through key population-based disease burden studies. Of particular note, the landmark Diseases of the Most Impoverished (DOMI) project, conducted between 2000 and 2008, documented the high incidence of blood culture\u2013confirmed typhoid and several epidemiological aspects of the disease in 7 Asian countries [Salmonella disease in that geographic region [Salmonella diseases that will make major contributions to their effective control [The highest burden of morbidity and mortality associated with ountries . Similar control .In this supplement, the Surveillance for Enteric Fever in Asia Project (SEAP), a multicountry study covering Bangladesh, India, Nepal, and Pakistan, reports data from a retrospective records review of enteric fever in Phase I of the study . The sitAndrews et al report a low blood culture positivity rate of 4.1% among clinically diagnosed enteric fever cases , reinforSalmonella Typhi strain that caused a typhoid fever outbreak in Sindh Province, Pakistan. The emergence of that XDR strain, which has been described as encoding resistance to all the major antimicrobials that have been routinely used for treating typhoid fever over the last 7 decades, amplifies the urgent concerns about narrowing therapeutic options for treatment and control of typhoid fever, and a real need for culture and antimicrobial sensitivity to guide treatment of typhoid fever [All participating sites report data on antimicrobial resistance, which are key considerations for countries conducting enteric fever surveillance given the alarming trends in antibiotic resistance, including the recent discovery of an extensively drug-resistant (XDR) id fever , 13.Kaljee et al provide critical insights on community and patient perceptions and other socioeconomic factors underlying healthcare utilization patterns in Nepal . We encoCollectively the SEAP Phase I data help to fill the knowledge gaps in Asia that existed despite the valuable data generated from the DOMI project and other key studies in the last 2 decades. The World Health Organization (WHO) recently issued recommendations for the programmatic use of typhoid conjugate vaccine (TCV) for the control of typhoid fever in both endemic and epidemic settings , supportAnother limitation of SEAP and the other burden studies is that the use of sentinel sites does not permit full understanding of the heterogeneity of typhoid and paratyphoid fever across large geographic regions and especially between urban and rural settings. This reemphasizes the critical need for investments in good-quality prospective surveillance in endemic countries. Blood culture is the mainstay for the confirmation of enteric fever for the foreseeable future but remains inaccessible (or unsustainable) in many of the countries that need it most. The resulting inadequate diagnostic capacity and lack of alternative reliable and inexpensive diagnostic tools remain threats to typhoid control.On a more positive note, the long-awaited realization of opportunities for routine vaccination with TCV could ensure rapid reductions in typhoid burden, leading to elimination of typhoid fever in critical geographic areas if the vaccine performs as expected. Today, with these new vaccines, we are on the cusp of the turning point in typhoid history, but we must ensure that the time bought by vaccination leads to long-term investments in sustainable WASH improvements so that typhoid becomes of only historical interest."}
+{"text": "A majority of United States Veterans are older adults, compelling healthcare systems such as Veterans Health Administration to attend to their unique needs when designing and implementing programs for workforce development and service delivery. In this symposium authors will present findings from four studies examining how older Veterans\u2019 needs and preferences affect implementation and sustainment in a variety of settings. Presenters demonstrate how: 1) understanding Veterans\u2019 perspectives and preferences for measuring functional status may inform the improvement of care coordination in the primary care setting; 2) the role of population characteristics in implementation of geriatric patient centered medical home teams ; 3) the interaction of patient, provider, and delivery system information needs in limiting sustainment of diverse initiatives to improve osteoporosis screening and management for Veterans; and 4) the factors affecting transferability and sustainment of rural and geriatrics-focused quality improvement initiatives beyond local settings. Beyond their focus on how older adults\u2019 needs are reflected or shape implementation, the studies illustrate the application of qualitative data to clinical practice and workforce development."}
+{"text": "OBJECTIVES/SPECIFIC AIMS: Translational science supports the continuum of activities from early-stage bench research to implementation of discoveries for better and faster treatments to more patients. Past studies have attempted to clarify our understanding of the spectrum of translational research by categorizing the activities into stages ranging from T0 to T4 using explanatory definitions. Unfortunately, this approach is often vague and relies on a process of manual classification and binning of research publications into predetermined categories. This study aims to provide a big-picture analysis of clinical and translational science (CTS) based on an in-depth analysis of the entire corpus of publications resulting from research funded by Clinical and Translational Science Awards (CTSA) U54 awards (through 2016). METHODS/STUDY POPULATION: We harvested bibliographic metadata from all papers that cited any of the U54 award numbers since the inception of the CTSA program to the most recent award announcement. Natural language processing techniques were used to create term co-occurrence networks based on English-language textual data. Relevant and nonrelevant terms were distinguished algorithmically and processed accordingly to provide the clustered visualization. RESULTS/ANTICIPATED RESULTS: With this approach, we uncovered 6 natural clustered areas of emphasis of published CTS research, the evolution of specific concepts through time, and gained a better understanding of their relative impact as demonstrated by citations. We performed additional analyses including discipline-specific impact assessment; identification of categories of excellence relating to both productivity and citations; characteristics of collaborative networks such as organizational, industry, and international collaborations and network dynamics; and resulting global impact of the CTSA program. DISCUSSION/SIGNIFICANCE OF IMPACT: Ultimately we gained a clearer understanding of the CTSA program, its evolution through scholarly publications, and key areas of impact of the program using computational, data-driven evaluation methods."}
+{"text": "The following information is missing from the Funding section: Publication costs were funded by the Diabetes prevention and management by lay health workers in Nepal project-Nepal Development Society (NEDS) and World Diabetes Foundation, Denmark."}
+{"text": "Life-span perspectives on adult development and aging highlight the processes of understanding and acting to support one\u2019s own health and well-being. Within this framework, subjective measures offer insight into the experience of objective measures of health. This symposium brings together four papers that highlight the overlap and discrepancy between subjective and objective measures of health and how these are shaped by individual development in different contexts and phases of adult development over various timescales. Mej\u00eda and colleagues consider the intraindividual dynamics of older adults\u2019 perceived and actual fall risk. Using 30 days of subjective and objective balance assessment, they illustrate individual differences in how awareness of fall-risk relates to physical activity on that day. Koffer and Kamarck use data from the Pittsburgh Healthy Heart Project to examine how reactivity of cardiovascular response and affective experience to daily experiences of stress changes with age. Drewelies and colleagues consider how objective aging feels. Using data from the Berlin Aging Study II, they examine how chronological and subjective age are linked to biological age in older adults. Gonzalez and colleagues use self-reported and behavioral data from an in-context biosocial research lab to comment on the theoretical and methodological implications of integrating objective and subjective measures of experience. The discussion by Berg integrates the four papers, highlights their theoretical and methodological contributions, and considers challenges and opportunities for subjective and objective inquiries of older adults\u2019 experiences of health."}
+{"text": "There is significant literature on the importance of addressing social determinants of health (SDOH) in order to improve health care outcomes. In response, the Centers for Medicare and Medicaid Services (CMS) has expanded Medicare Advantage plans ability to cover SDOH-related services. Medicare home health does not cover SDOH-related services. A literature review indicates no studies on the nature, significance, or impacts of the lack of SDOH coverage in Medicare home health. This article summarizes an initial, exploratory study to address the literature gap, based on interviews of a convenience sample of 29 home care social workers between January 2013 and May 2014 in the New York City metropolitan area. Results indicate social workers believe the lack of SDOH coverage in Medicare home health results in exacerbation of existing patient conditions; creation of new, additional patient conditions; increased home care readmissions and re-hospitalizations; increased caregiver burden; and exacerbation of patients\u2019 mental health and substance abuse needs. Policymakers are urged to consider adding coverage of SDOH to Medicare home health primarily through expanded social work coverage."}
+{"text": "This data article reports the global datasets of land surface state changes including daily maximum and minimum temperature, diurnal temperature range, surface precipitation, snow cover, soil moisture and outgoing longwave radiation associated with the Madden-Julian Oscillation (MJO), which are related to the research article entitled \u201cVariation of Global Diurnal Temperature Range Associated with the Madden-Julian Oscillation\u201d published in the Journal of Atmospheric and Solar-Terrestrial Physics by Lin and Qian (2019). The changes of surface air temperature and diurnal temperature range are calculated from two datasets: the Berkeley surface air temperature and the National Oceanic and Atmospheric Administration (NOAA) Climate Prediction Center (CPC) surface air temperature. The change of surface precipitation is derived from the NOAA CPC daily surface precipitation. The change of snow cover is calculated from the MODIS satellite data. The change of soil moisture is derived from the European Space Agency combined satellite data. The change of outgoing longwave radiation is calculated from NOAA satellite measurements. All of the data are stored in separate netcdf files and deposited at PANGAEA. These datasets can be used as observational benchmarks for evaluating the MJO simulations in global climate models, and in studies of MJO's impacts on global physical systems, public health, and ecosystems. Low fre"}
+{"text": "The purpose of this study was to investigate 1) rural patients\u2019 perceptions of their own rurality and its effects on experience of head and neck cancer survivorship, and 2) potential barriers and facilitators to survivorship care within an integrated health care delivery system of the Veterans Health Administration (VHA). Data from qualitative interviews with Veterans who have a history of head and neck cancer are presented to understand the complex ways that rurality impacts cancer survivorship. Head and neck cancer survivors must contend with specific challenges resulting from their risk factors and treatment, including access to complex medical follow up, long-term physical and psychological effects of treatment, and tobacco- and alcohol-related comorbidities. While integration within the VHA facilitates coordination of specialty and primary care and the transfer of medical information, the use of community care in rural areas presents coordination challenges, especially for survivors with comorbidities."}
+{"text": "Recent advances in data acquisition and various monitoring modalities have resulted in generating and collecting a growing volume of biological and medical data at unprecedented speed and scale . These aMedical decision support systems help clinicians to best exploit these overwhelming amount of data by providing a computerized platform for integrating evidence-based knowledge and patient-specific information into an enhanced and cost-effective health care . Over thWith that scope in mind, this special issue focuses on the applications of pattern recognition for clinical decision support. For this purpose, we selected five research articles that discussed the design and clinical applications of feature extraction and/or classification of large-scale or high-dimensional biomedical data including biomedical signals and images.S. Long et al. developed and evaluated an automatic retinal image processing algorithm to detect hard exudates (HE). Their algorithm consisted of four main stages: (i) image preprocessing; (ii) localization of optic disc; (iii) identification of potential HE region using dynamic threshold and fuzzy C-means clustering; and (iv) extraction of texture features from the HE region being fed into a support vector machine classifier. The proposed algorithm was trained and cross-validated on a publicly available e-ophtha EX database, achieving the overall average sensitivity of 76% and positive predictive value of 83%. Testing their algorithm on DIARETDB1 database resulted in better sensitivity (97%) and specificity (98%).Z. Luo et al. developed and tested a machine learning approach to detect hypertension by automatic processing of radial artery blood pressure signals collected from healthy and hypertensive subjects by a noninvasive measurement device designed and built in house. They applied K-means clustering to exclude the noisy pulses from the data. Then they identified a subset of features that helped the most in detecting the hypertensive cases and applied various pattern classification algorithms such as AdaBoost and random forest. The authors were able to achieve the highest accuracy of 86% using AdaBoost.K. Y. Win et al. proposed a novel methodology for the detection of cancer cells in cytological pleural effusion (CPE) images. Following some image intensity adjustment and application of median filtering to improve the image quality, cell nuclei were extracted by a hybrid segmentation method based on the fusion of simple linear iterative clustering and K-means clustering. Shape and contour concavity analyses were carried out to detect and split any overlapped nuclei into individual ones. Then several morphometric, colorimetric, and texture features were extracted. A novel hybrid feature selection method was developed using an artificial neural network to select the most discriminant and biologically interpretable features. Finally, an ensemble classifier of bagged decision trees was utilized to classify cells into being either benign or malignant. The proposed method achieved sensitivity of 88% and specificity of 99% on a dataset of 125 images containing more than 10,000 cells.J. Jaworek-Korjakowska employed analysis of vascular structures in dermoscopy color images to distinguish benign and malignant pigmented skin lesions using a segmentation technique and convolutional neural network. The proposed method achieved sensitivity of 85% and specificity of 81%. The author concluded that small size and similarity of vascular structures to other local structures makes the segmentation and classification of dermoscopy color images challenging.H. Tang et al. proposed employment of various features (from time/frequency domains) of phonocardiogram data and support vector machine for classifying normal and abnormal heart sound data. They applied correlation analysis to quantify discrimination level of the features and used support vector machine with radial basis kernel function for classification of phonocardiogram data from publicly available PhysioNet database. Their methodology achieved an average sensitivity of 88% and a specificity of 87%.With upcoming technology upgrades in clinical measurement and monitoring systems, it is reasonable to assume that the cost of acquiring and storing biomedical data will decrease dramatically in the near future , 7. This"}
+{"text": "Adult protective services (APS) workers regularly engage in advanced care planning (ACP). This qualitative content analysis of 21 APS cases sought to extend knowledge and uncover characteristics that influenced the ACP process and increased vulnerability of older adults in cases of neglect. The case narratives were examined to identify themes of vulnerability and risk related to ACP. Vulnerabilities of the older adults included multimorbidities, geriatric syndromes, and functional limitations. Risks involving caregivers included health problems and cognitive impairment. Caregivers were overwhelmed or lacked insight into the older adults\u2019 needs. Involvement of other family members was detrimental or non-existent while some advocated for improvements where the caregiver refused assistance. Findings support the development of methods of ACP, including the facilitation of difficult conversations, that would respect the autonomy and dignity of the older adult while meeting the multiple needs of caregivers and family members."}
+{"text": "Over the last decade, the number of older adults (people over the age of 50) who misuse opioids doubled and continues to increase. People over the age of 50 also represent one of the fastest growing groups entering into and sustaining medication assisted treatment (MAT)  for opioid use disorder (OUD). Despite increasing awareness of this growing at-risk population, significant knowledge gaps regarding their support and care needs persist. To begin to address these gaps, we conducted interviews with 20 treatment staff, focus groups with 18 patients and surveys with 100 patients over the age of 50 at eight diverse Opioid Treatment Programs (OTPs) participating in a 1-year pilot study  funded by the Georgia Clinical and Translation Science Alliance supported by the National Center Advancing Translational Sciences. Patients in this study do not always disclose their use of MAT to non-OTP providers. When they do, participants reported numerous negative experiences with non-OTP providers, including perceived discrimination, stigma, and misunderstanding by providers about MAT. These negative experiences potentially contribute to an over reliance on OTP providers to manage age-related health conditions . Providers report minimal training about aging and varied levels of confidence to manage these conditions. We present the experiences of patients and providers with suggestions for improving care coordination. We conclude with recommendations to improve communication among providers working with older adults in recovery from OUD."}
+{"text": "The following information is missing from the Competing Interests statement:JMT has consulted and received speaker honoraria from organizations  based on her research exploring generational differences. These include honoraria from religiously affiliated colleges and universities including Calvin College, California Lutheran University, Geneva College, and the University of the Incarnate Word, though these honoraria were independent of the reported study."}
+{"text": "Beilstein Journal of Organic Chemistry covers novel phosphorescent and TADF materials design and their inclusion as emitters in OLEDs.Organic light emitting diodes (OLEDs) are at the cusp of becoming the dominant technology for the mobile device and display markets. This is largely due to the concerted efforts over the past thirty years to improve the material design, beginning with the first demonstrated viability of this technology in 1987 by Tang and VanSlyke [Some highlights in this issue include the work of Thanh-Tu\u00e2n Bui et al., who provide a welcome perspective on blue TADF materials for OLEDs in the form of a review article . CristinThe articles in this thematic issue provide a window into the design principles used towards the development of next-generation emitter and host materials for OLEDs. I hope these articles will provide inspiration for further research in this exciting area.Eli Zysman-ColmanSt Andrews, June 2018Eli Zysman-Colman obtained his Ph.D. from McGill University in 2003. He then completed two postdoctoral fellowships, one in supramolecular chemistry at the Organic Chemistry Institute, University of Zurich and the other in inorganic materials chemistry at Princeton University. After beginning his career in Canada, he moved to the University of St Andrews where he is presently Reader in Optoelectronic Materials and Fellow of the Royal Society of Chemistry. His research program focuses on the rational design of: (i) luminophores for use in organic light emitting diodes (OLEDs) and light-emitting electrochemical cells (LEECs), two types of electroluminescent devices; (ii) sensing materials employed in electro-chemiluminescence; and (iii) photocatalysts employed in photoredox catalytic reactions."}
+{"text": "Every culture has its own tradition of intergenerational exchange based on accepted norms, while the meanings of traditional filial values have evolved over time. This paper aims to identify the various forms of filial care, support and respect for older people in Maori and Korean cultures, and reconceptualise current ways of intergenerational exchanges in both physical and virtual contexts. Data were collected through a qualitative inquiry framework consisting of 32 individual interviews and 5 ethnographic observations in New Zealand and South Korea. Thematic analysis of the data was used to identify themes and patterns from the participants\u2019 perspectives and experiences in the multilingual research context. In this cross-cultural study, for M\u0101ori participants, whanaungatanga (family relationships) was recognised as a core value that places whanau (family) at the centre of whakapapa (human and non-human relations). For Korean participants, their tradition of filial piety has continued to constitute a major component of familism mindsets and practices, while their ability to support their parents and maintain connections to their ancestors varied. Being knowledgeable about the traditional values of intergenerational solidarity helped generations feel connected and supported by each other, although both monetary and non-monetary support for one\u2019s elders has come under strain due to the impact of changes in family ties and social dynamics. Technological developments have reshaped traditional filial practices, offering new ways of intergenerational exchanges. Redefining whanaungatanga and filial piety can provide a theoretical basis for developing the concept of extended social work through avoiding excessive individualism and culture-blind approaches."}
+{"text": "AbstractNeuroptera of Canada consists of 101 extant species, an increase of 26 (35%) since the previous assessment of the fauna in 1979. More than 48 additional species are believed to occur in Canada based largely on recent DNA evidence and new distribution records. The Barcode Of Life Data System (BOLD) currently includes 141 Barcode Index Numbers (BINs) for Canadian Neuroptera. Canadian fossils have thus far yielded 15 species in three families of Neuroptera.The  Neuroptera, including the lacewings, antlions, owlflies and relatives, contains approximately 6400 extant species worldwide  (Ratnasingham and Hebert 2013) associated with them  (Dilaridae) and Ululodesquadripuntatus (Burmeister)  (Dicromantispasayi (Banks) (Mantispidae) is another species that was expected by Ninetagravida (Banks) was rediscovered on Canada\u2019s Pacific coast after 90 years (Polystoechotespunctatus (Fabricius) appears to be extirpated from the eastern half of North America having not been recorded there since 1952  revised the family   and eastern Nearctic. One species, Wesmaeliuslongipennis (Banks), was listed by W.longipennis in the Canadian National Collection, collected from coastal and interior locations in British Columbia, and one from Quebec, in the 1920s and 1930s, were recently identified (J Klimaszewski pers. comm.). This is a significant extension of the known range and implies that the California records may represent the southern extent of a more widely distributed northern species.a) Table . Kevan aNeuroptera in Canada are considered to be exotic species. These introductions include three Coniopterygidae (Conwentziapsociformis (Curtis), Semidalisvicina (Hagen), S.pseudouncinata Meinander), three Hemerobiidae (Psectradiptera (Burmeister), Wesmaeliussubnebulosus (Stephens), Micromusvariegatus (Fabricius), and the chrysopid, Chrysoperlacarnea (Stephens)  (a North American species) and no C.carnea were present (Few tephens) . Chrysop America  is mass- America . Chrysopon songs  and anal present .Neuroptera is likely to yield some new species and range extensions in the more diverse families (Table http://fossilworks.org) indicates that the fossil record has thus far yielded 15 species from three families for Canada, and 68 species in five families for North America, and research on Canadian fossil deposits may reveal additional species. Other interesting avenues of research include the application of native Neuroptera as control agents in agricultural settings, the mating songs of Chrysoperla and the existence of this phenomenon and other mate selection methods in related taxa and systematic revisions of the Myrmeleontidae and Coniopterygidae.Future research on Canadian es Table . The Pal"}
+{"text": "A study to determine the effects of entrainment by the Diablo Canyon Power Plant (DCPP) was conducted between 1996 and 1999 as required under Section 316(b) of the Clean Water Act. The goal of this study was to present the U.S. Environmental Protection Agency (EPA) and Central Coast Regional Water Quality Control Board (CCRWQCB) with results that could be used to determine if any adverse environmental impacts (AEIs) were caused by the operation of the plant\u2019s cooling-water intake structure (CWIS). To this end we chose, under guidance of the CCRWQCB and their entrainment technical working group, a unique approach combining three different models for estimating power plant effects: fecundity hindcasting (FH), adult equivalent loss (AEL), and the empirical transport model (ETM). Comparisons of the results from these three approaches provided us a relative measure of confidence in our estimates of effects. A total of 14 target larval fish taxa were assessed as part of the DCPP 316(b). Example results are presented here for the kelp, gopher, and black-and-yellow (KGB) rockfish complex and clinid kelpfish. Estimates of larval entrainment losses for KGB rockfish were in close agreement . The similar results from the three models provided confidence in the estimated effects for this group. Due to lack of life history information needed to parameterize the FH and AEL models, effects on clinid kelpfish could only be assessed using the ETM model. Results from this model plus ancillary information about local populations of adult kelpfish suggest that the CWIS might be causing an AEI in the vicinity of DCPP."}
+{"text": "Historically, a diagnosis of Alzheimer\u2019s disease and related dementias (ADRDs) created a sense of hopelessness among those diagnosed, their families, and physicians. The misperception that there is no available medical treatment or interventions inhibited patients from receiving cognitive assessments or exploring home- and community-based interventions that could improve quality of life. Today, researchers have developed evidence-based pathways to improve brain health, reduce dementia risk, and enhance lifelong cognitive function. This report highlights recent scientific advancements focused on medical and lifestyle interventions that reduce the risk of ADRDs and slow the disease progression. To improve the current system and reduce the risk of dementia and improve brain health, the following policy areas are recommended: 1) promote brain health strategies to delay onset and reduce the stigma associated with cognitive decline; 2) increase early detection and cognitive screening efforts; 3) build a dementia-capable workforce; 4) create seamless transitions from health systems to community-based services to better support those with dementia; 5) improve caregiver training and support; and 6) increase funding for research related to ADRDs. Understanding that ADRDs disproportionately impact certain populations, these policy recommendations include strategies to narrow health disparities. Previous Milken Institute research highlighted the disproportionate health impacts of dementia on women, which costs the economy trillions of dollars. This report expands on that analyses and stratifies the data by race and income as well. Ensuring that these policy recommendations address disproportionately impacted groups will benefit the broader healthcare system and alleviate the burden felt by all patients and families."}
+{"text": "Although prior researchers have decried the lack of research on racial/ethnic minority older adults, they have been less vocal about the gaps in research concerning the ways in which immigrant status and race/ethnicity affect their well-being. Thus, we examined the role of immigrant status on the stress coping process by race/ethnicity using the Transactional Model of Stress and Coping. The multi-group analysis function in structural equation modeling was used to determine whether the stress coping process was equivalent across three racial/ethnic groups (Non-Hispanic White (NHW), Non-Hispanic Black(NHB), and Hispanic) by immigrant status using the Round 1 of the National Health and Aging Trends Study ). We found that immigrant status and race/ethnicity may have complex effects on the stress coping process. For example, the total effects of being an immigrant were significantly associated with more stressors, less resources, and worse physical health. Except NHW, the total effects of being immigrant were associated with higher levels of depression and anxiety. With respect to the direct and indirect effect of immigrant status in the three groups, the Hispanic group has a larger effect of immigrant status on stressors, resources, depression/anxiety and physical health than their NHW and NHB counterparts. The results indicated that immigrant racial/ethnic minority older adults were more likely to have higher levels of depression and anxiety than the U.S.-born except for NHW. Immigrant status will require special attention in both assessment and management of depression/anxiety among racial/ethnicity minority older adults."}
+{"text": "Ma et al.). Research on PGPM  have shown great potential in the management of various agricultural and environmental problems, however, to date, a collective database on the role of PGPM in alleviating various climatic stresses in plants is not available. Therefore, this research topic was launched to advance the knowledge of the mechanisms underlying plant-microbe interactions, review recent progress and address some of the challenges, thus providing the opportunities to translate basic knowledge into sustainable applications.Global climate change accelerates the concurrence of a variety of abiotic  and biotic stresses , thus considerably affecting agricultural productivity and bioremediation efficiency, even forest ecosystems. In this scenario, plant growth promoting microorganisms (PGPM) are receiving increasing attention of agronomists and environmentalists as candidates to develop an effective, eco-friendly, and sustainable alternative to conventional agricultural  and remediation  methods employed to deal with these climate change-induced stresses  improvement of water and nutrient uptake, photosynthesis, and source-sink relationships; (2) activation of antioxidant activity, osmolyte accumulation, proton transport machinery, salt compartmentalization, and nutrient status; (3) modulation of phytohormone status, gene expression, protein function, metabolite synthesis, and secretion of signaling molecules and initiation of stress-responsive pathways. The systems biology perspective on plant-microbe interactions in response to salinity opens up new prospects of understanding the regulatory networks of PGPR induced plant salt tolerance, suggesting application of PGPR could serve as a promising measure to alleviate salt stress and improve global food production.Salinity is a major abiotic stress limiting the growth and productivity of plants worldwide. It has been proved that harnessing the potential of plant growth promoting rhizobacteria (PGPR) is an alternative strategy to improve plant stress tolerance. Egamberdieva et al.Among the mechanisms involved in plant-microbe interactions, microbial phytohormone production plays a crucial role in the stimulation of plant defense response against abiotic stress. A comprehensive review of the function, aspects and production of microbial phytohormones  involved in the improvement of abiotic stress tolerance and defense response in crop plants under hostile environments  was provided by Zhao et al. performed a field trial in a mixed deciduous forest of China with canopy addition of N and water for 4 years and found that the effect of increased N deposition and precipitation on AMF community composition was time-dependent, mediated by soil factors, and possibly related to the sensitivity and resilience of forest ecosystem to global changes.As an important component of global climate change, increasing nitrogen (N) deposition and its ecological consequences are of serious concern, since it may profoundly influence the structure and function of the forest ecosystem. Jha and Singh exemplified to us in a study of the potential of PGPR Stenotrophomonas maltophilia SBP-9 to promote the growth of Triticum aestivum under biotic (Fusarium graminearum) and abiotic  stresses.The further understanding of how successful PGPR colonization can improve the growth and defense response of the plants against fungal pathogens under salinity stress implies the diverse physiological and biochemical mechanisms used by PGPR to confer both abiotic and biotic stress tolerance of host plants. This was what Egamberdieva et al. described a detailed study of the functional role of endophytic PGPB colonizing root tissues in enhancing the growth performance and controlling root rot in Cicer arietinum under saline soil conditions. They demonstrated the importance of endophytic bacterial colonization for the improved symbiotic performance of legume host plants with rhizobia, with increased root growth, nutrient bioavailability and faster osmotic adjustment, and reduction in H2O2 production and pathogen infection under saline soil conditions.Additionally, Rybakova et al. combined in vitro and in planta methods with the study of the mode of interaction between PGPB and phytopathogens via their VOCs. They highlighted the identification of several antimicrobial and plant growth promoting VOCs and several other antimicrobial volatile substances that were produced by both Paenibacillus polymyxa and Verticillium longisporum as a reaction to one another's VOCs, and the regulation of their general metabolic activities. The findings contribute to a better understanding of the mechanisms of VOCs underlying the interaction between pathogens and their natural antagonists.The emission of volatile organic substances (VOCs) of microorganism can increase disease resistance and abiotic stress tolerance, and thereby helping plants control a wide range of pathogens. Notably, Rez\u00e1\u010dov\u00e1 et al. established an intercropping experiment of two similar Panicum species with contrasting carbon (C3 and C4) metabolism. The plants were subjected to two different temperature regimes and inoculated with or without a consortium of AMF. A root-free compartment (RFC), but AMF-accessible, was added that was comprised of 15N-labeled clover residues, which could allow direct assessment of the benefit of AMF on the plants in term of N derived from the organic biomass. Also, the isotopic C signature of the plants enabled the determination of which plant species were the main donor of C to the AMF. The authors found that the C3 species continued feeding the CMNs by using the specific C signature of the plant, AMF biomass/specific lipids in the root compartments and in the RFC. Other important results are that the inoculation of AMF reduced the plant biomass production, but increased plant phosphorus uptake under both temperature regimes.Common mycorrhizal networks (CMNs) by AMF interconnect plants, which play a crucial role in redistributing nutrients and draining carbon (C) from the different plant partners at different rates  on leaf water potential, whole-plant water use, and stomatal responses of Oryza sativa under CO2 enrichment and water deficit. They found that the ABA production by endophytes contributed significantly to the stomatal reactions and the resulting plant physiological benefits.One example of novel applications for the sustainable use of diazotrophic bacterial and yeast endophytes in modulating stomatal behavior and increasing plant water relations was shown by Scientists from different fields of research, from basic science to applied science, are indeed contributing to the understanding of the molecular, cellular and physicochemical mechanisms underlying plant-microbe interactions under various environmental stresses, which will certainly contribute to generating novel solutions for the development of PGPM-based sustainable applications in agricultural and forestry systems.YM draft the editorial text. YM, MV, and HF revised and approved the final version of the editorial text.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "A 33-year-old primigravida at 32-week gestation was admitted to labor and delivery complaining of severe right upper quadrant pain and worsening coagulopathy. We report the anesthetic and obstetrical management of a complex case of a parturient with a mixed picture of hemolysis, elevated liver enzymes and low platelets who was delivered under general anesthesia further complicated by Disseminated Intravascular Coagulopathy (DIC) and placental abruption. Both thIn conclusion, preeclampsia, HELLP syndrome, and AFLP are all on the spectrum of end organ disease processes that can result in perinatal mortality. Rapid disease recognition and proactive anesthetic and obstetric multidisciplinary treatment can result in a good outcome for both the mother and baby."}
+{"text": "Available data on science is constantly gleaned for gathering valuable information to create concise yet precise knowledge on specific subjects  for service in the society. These sacrifices surmounts as success stories for scientists worldwide. Data in the form of known literature plays a radicalrole in serving the society with improved infrastructure and facilities making associated resources available, accessible and affordable. This is possible by making known literatureavailable and accessible for application in a modern economy dominant with features of democratic socialism. The public investment from tax payers coupled with the privately propelledcommercial factions involved in the gathering, archiving and distribution of known literature data is complex in its current status quo in the context of creating a harmonious societywith optimal social benefits. It should be noted that the role played by indirect, unorganized, unskilled and unaccounted farmers, farm laborers and service men in different layers ofthe supply chain in accordance with demand and supply is highly imperative. Therefore, it is of interest for a comprehensive discussion on issues in making known literature availableand accessible for application towards the benefit of the society through open access publishing models within the acceptable ethical frameworks of Creative Commons (CC) and Committeeon Publication Ethics (COPE). The world is passing through a difficult crossroad with multiple issues of concern with heated debates on Inflation (price rise), Fiscal  deficit (shortage) and import dependency world-wide . We needThe access to known scientific literature through available resources such as the products of Routledge , SpringeThe biology-oriented agriculture , food prIt is of interest for a comprehensive discussion on issues to make known literature available and accessible for social application through open access publishing models within the ethical guidelines of Creative Commons (CC)  and CommPandjassarame Kangueane  is a sciSenkuttuvan Pavithra received her Bachelor of Commerce (2016) and Master of Commerce (2018) from Pondicherry University, Union Territory of Pondicherry (a French colony of pre independence India), India. She is an alumni of the alma mater Saradha Gangadharan College, Pondicherry 600 5004 which is affiliated with Pondicherry University. She serves as production director at Biomedical Informatics (P) Ltd since 2018."}
+{"text": "Correction to: Trials (2019) 20:499https://doi.org/10.1186/s13063-019-3571-5Initially published title:Trial of healthy relationship initiatives for the very early years (THRIVE), evaluating Enhanced Triple P for Baby and Mellow Bumps additional social and care needs during pregnancy and their infants who are at higher risk of maltreatment: study protocol for a randomised controlled trialCorrected title:for those with additional social and care needs during pregnancy and their infants who are at higher risk of maltreatment: study protocol for a randomised controlled trialTrial of healthy relationship initiatives for the very early years (THRIVE), evaluating Enhanced Triple P for Baby and Mellow Bumps Following publication of the original article , it has The original article has been corrected."}
+{"text": "Sharing Opinions and Advice about Research (Project SOAR), funded by PCORI, trained individuals living in under-resourced and underserved communities how to evaluate and provide advice to scientists about recruitment procedures, survey items, and intervention components for implementation in their communities. In partnership with the HELLO Project , Project SOAR community partners recruited 50 rural African American adults to consider their values, plans, and treatment preferences near the end of life while playing the HELLO game. Community and research partners along with a HELLO Project representative facilitated questionnaire completion and the process of the HELLO game to promote advance care planning. Tables of 10 participants held facilitated discussions for each HELLO game item and recorded their individual wishes and plans in HELLO booklets. Community participants had difficulty completing questionnaires without assistance; however, all were engaged and accepting of game-like discussions regarding advance care planning."}
+{"text": "Oxidative stress is the most frequent cause of female infertility disorders including polycystic ovary syndrome (PCOS). Genistein as a major component of soybean isoflavone scavenges free radicals by antioxidant activities.The present study examines the antioxidant effects of genistein on ovarian tissue following experimental PCOS in rats.n=5 each group): (I) control group (no treatment); (II) induced PCOS ; (III) genistein-treated non-PCOS (received genistein); and (IV) genistein-treated PCOS groups. The weight of rats were measured and the blood samples collected and centrifuged. The oxidant and antioxidant activity of plasma and ovaries were measured. All rats were sacrificed under anesthesia, and ovaries were collected and weighted. Histological examination and follicular quality were assessed by staining.Twenty female Wistar rat were randomly divided into the following groups (In histological observation, the induced PCOS rats displayed more number of atretic follicles and the follicular quality in genistein-treated rats was similar to the control groups. The plasma and ovaries malondialdehyde levels significantly increased in PCOS rats (p Treatment with genistein preserved follicular quality by increasing antioxidant activities and scavenging oxidant levels in PCOS rats. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that characterized by hyperandrogenism, an ovulation, menstrual irregularity and metabolic syndrome . However, several genetic and environmental factors interface in PCOS condition (3).Rezvanfar and colleagues demonstrated that oxidative and nitrosative stress have critical role in the pathogenesis of PCOS (4). In normal condition, the low concentrations of reactive oxygen species (ROS) are essential for the physiological functions of female reproductive tract including oocyte maturation, ovulation, fertilization, and implantation (5). High concentration of the ROS or oxidative stress is a common pathological process involved in the process of cell injury (6). It is seen in the elementary phases of most PCOS patients, which disrupts the follicular development in the ovaries and leads to the development of PCOS.Although all organisms need to make a balance between ROS production and antioxidant system including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In the overproduction of ROS such as PCOS conditions, these protective systems are insufficient to entirely scavenge of free radicals and prevent follicular damages.Zhang and colleagues' studies also support the hypothesis that the oxidant levels were increased in PCOS patients, whereas the antioxidants level was decreased (7).Currently, studies are still being conducted to find better natural antioxidants for improving all the clinical features of PCOS. Therefore, antioxidant supplementation may be a goal strategy for restricting oxidative stress damages in PCOS patients and thereby improving the quality of ovarian follicles and restoration of reproductive cycle (8).Genistein is the predominant isoflavones phytoestrogen in soybeans and is a major source of xenoestrogen exposure in both humans and animals (9). Recently, it has been shown that genistein has potential anticarcinogenic activity and could diminish menopause-associated cognitive deficits through antioxidant function and scavenging free radicals . Additionally, genistein exhibits both proliferative (estrogenic) and antiproliferative (antiestrogenic) properties (11), and currently dietary supplements of genistein are widely used for menopausal symptoms by women as a potential alternative therapy (12). Previous studies revealed that genistein could activate antioxidant defense systems/pathways which would diminish the oxidative stress activity .The potential mechanisms for the antioxidant effects of genistein on induced PCOS are poorly understood. The effects of genistein on ovarian tissue structure still need further investigation.We hypothesized that low dose of genistein treatment would exert its antioxidative effect in ovarian follicles, which may partially alleviate the toxic effects induced by PCOS.In this research study, we tried to investigate the beneficial effect of genistein against induced PCOS as well as the number and quality of ovarian follicles. We also investigated the body and ovary weight of PCOS rats in response to the treatment with genistein.All media and chemicals were purchased from Sigma-Aldrich unless otherwise mentioned.Twenty female Wistar albino rats (8-weeks old) with an average weight of 200n = 5/each) as follows:The animals were randomly divided into four groups (\u2022Group (I) rats were not injected and did not receive any treatment (control group).\u2022Group (II) PCOS rats were induced by EV for 60 days (induced PCOS group).\u2022Group (III) rats received genistein for 14 days (genistein-treated non-PCOS group).\u2022Group (IV) PCOS rats were induced by EV (60 days) and then treated with genistein for 14 days (genistein-treated PCOS group).The injection site was sterilized and 2mg/kg body weight (BW) single dose of EV  was injected subcutaneously for 60 days. At the end of the treatment, the body and ovary weights of PCOS rats were measured. The induction of PCOS was verified by vaginal smears and was examined histologically and serologically for a period of 60 days. In this procedure, estrous cycles were monitored under a light microscope for the relative abundance of leukocytes, epithelial, and cornified cells.Genistein was obtained from Santa Cruz Company in America. About 0.2 mg of genistein was dissolved in Dimethyl sulfoxide under standard conditions  and then stored at a temperature of \u201320\u00baC. The equivalent dietary intakes of phytoestrogens/BW was estimated in humans and rodents by this theory:The PCOS/non-PCOS rats received 1 mg/kg BW genistein subcutaneously for 14 days at 10 am because of an average 60\u201370 mg adult would consume phytoestrogen approximately 60\u201375 mg per day .n=20) were sacrificed under anesthesia, their ovaries were collected and measured. The left ovaries were immediately fixed in 4% (w/v) paraformaldehyde for histological analysis and the right ovaries were immediately frozen at \u201370\u00baC for determining oxidant-antioxidant markers .After the last treatment, the BW of rats were measured and then anesthetized, and 5 mL blood samples were directly taken from the heart. Blood samples were centrifuged at 3000 The collected ovaries were fixed in 10% buffer formalin, dehydrated by using ethanol, clarified with xylene, embedded by using paraffin wax, and prepared serially sectioned (5 \u03bcm). The slides were stained with hematoxylins and eosin (H&E) and visualized under a light microscope with 400 magnification.Ovarian follicles were categorized according to granulosa cells and layers around the oocyte:\u2022Primordial follicles (one layer of flattened granulosa cells)\u2022Primary follicles \u2022Preantral follicles ,\u2022Antral follicles All follicles were numbered when the nucleus of the oocyte was observed . Follicular quality was evaluated as normal (if they had an intact oocyte and surrounded by a complete layer of granulosa cells) and atretic Free radical (lipid peroxidation) levels were measured in plasma and ovarian tissue samples using a commercial kit  by measuring MDA levels based on thiobarbituric acid reacting substance method. The LPO level was detected spectrophotometrically at 535 nm and evaluated in The TAC, GPx, and SOD activities in plasma and ovaries of control and experimental groups was measured spectrophotometric using a commercial kit . The TAC (mmol/L) assay was based on reducing the tripiridyltriazine (TPTZ)\u2013Fe3+ complex to TPTZ\u2013Fe2+ complex with a blue color and maximum absorbance at 593. The GPx activity (units/mg protein) was determined based on coupling the oxidation of glutathione and nicotine adenosine dinucleotide phosphate using glutathione reductase. The SOD activity (units/mg protein) was assessed colorimetrically at 420 nm by the conversion of superoxide anion to hydrogen peroxide and oxygen.All experiments were carried out in compliance with the guideline developed by the Medical Ethics Committee of Tabriz University of Medical Sciences (1395.249).Data were analyzed using statistical SPSS software . The distribution of data was evaluated by Anderson darling test. All data were normally distributed. The variables with normal distribution results were expressed as meanBW and ovary weight of rats in the control and experimental groups are shown in Figure 2. The BW and ovary weight increased significantly in PCOS rats in comparison to the control rats .The ovarian tissue of induced PCOS rats displayed more signs of follicular cysts in various sizes. Some antral follicles appeared to be moderately atretic with nuclear pyknosis, fragmentation of granulosa cell layer, disruption of the zona pellucida, and hyperplasia of theca layer . The ovary of genistein-treated groups was similar to the control groups .In contrast to the PCOS group, the ovarian tissue showed well-developed antral follicles in the genistein-treated rats including substantial reductions in total populations of ovarian atretic follicles, normal granulosa cell layer, a defined theca layer, and few corpus lutea .As shown in Table I, a significantly higher level of MDA were detected in plasma and ovaries (Table I) of PCOS groups when compared to the control groups  and antioxidant  levels in PCOS model. Also, this study is an attempt to examine the effect of genistein on oxidant level, antioxidant activity, and morphology of ovarian tissue in the induced PCOS rats.The results of this study clearly revealed that 2mg/kg EV injection induced some changes including multisize cysts, irregular estrous cycle, follicular atresia, and increased BW and ovary weight. This result is in accordance with the Walters and colleagues' results that suggested that clinical characteristics of PCOS were induced in rat models by EV (17).BW and ovary weight increased in PCOS rats during EV supplementation. March and colleagues reported that about 42% of PCOS patients have the complication of obesity (18). The increased body and ovarian weight may be due to the accumulation of fatty tissue, formation of follicular cysts, and accumulation of follicular fluid in the cystic follicles. Our results show that the exposure to genistein significantly decreased BW and ovary weight in PCOS rats that may be responsible for decreasing the fatty formation, decreasing follicular cysts (follicular fluid), and scavenging oxidative stress due to the potential antioxidant capacity. A positive correlations between oxidative stress levels and obesity indexes in the PCOS women were reported in previous studies (19). The present study indicated two types of histologic changes in the ovaries in PCOS rats. The first type was characterized by a high number of atretic and poly-cystic follicles. Such changes are probably associated with the consequence of the accumulation of follicular fluid in the cystic follicles and high levels of estrogens in follicular fluid (20).The other changes were increasing the thickness of stroma and ovarian capsule, hyperplasia of internal theca cells and anovulation. These changes could be directly related to oxidative stress or indirectly associated with the inhibition of gonadotropins hormones (21). Our study demonstrated more sign of cystic antral follicles during EV injection, suggesting an anovulatory condition in PCOS rats. Pandey and colleagues suggested that high level of androgens in accordance with antioxidants\u2013oxidant imbalance may be responsible for the induction of degenerating follicles, which are the major causes of PCOS induction (22).Our results demonstrated that genistein-treated ovaries appeared to be healthy with regular granulosa and theca cell layers and well-developed antral follicles. Thus, our histological investigation in accordance with biochemical analysis indicated that genistein can exert beneficial effects in the PCOS condition through decreasing the oxidative stress production or by estrogen pathways. Our study affirmed that low concentration of genistein (1mg/kg BW) was the effective doses in female reproductive function by increasing antioxidant activity and thereby decreasing ROS production.ROS have important roles in modulating many reproductive physiological functions including folliculogenesis, oocyte maturation, ovulation, fertilization, implantation, ovarian steroidogenesis, progesterone production, and luteolysis . This function improved by making a suitable balance between oxidant and antioxidant mechanism. In contrast, the overproduction of ROS or oxidative stress interferes with many pathological conditions of reproduction such as infertility, abortion, preeclampsia, endometriosis, and PCOS (23).In a previous meta-analysis, the MDA level, a direct oxidant marker, was Our results in accordance with Pandey and colleagues indicated that the MDA levels as a marker of lipid peroxidation increased in within the plasma and ovaries of PCOS rats, while antioxidant activities  decreased in contrasts to Daneasa and colleagues results (22).It is seen that oxidant\u2013antioxidant balance was disrupted in the PCOS rats and thereby could damage biologic molecules and cell membrane and resulted in increasing the MDA level and thereby failed the antioxidants activities.In addition, the extension of oxidative stress production or inadequate removal of ROS resulted in Ca2+ influx into cells that induced further cell injury and increased DNA strand breakage . Therefore, the histological examinations affirmed that both evaluation and protection of oxidative stress are very important in PCOS models.Antioxidants supplementation as a therapeutic method implement critical role in three approaches: minimize or prevent, repair and remove oxidative damage (27). Antioxidants are categorized as enzymatic and non-enzymatic. The enzymatic antioxidants include SOD, GPx, and CAT (23). SOD is the important oxidant scavengers with antioxidant effect against superoxide anion that reduces the superoxide anion radicals and catalyzes convert them to H2O2 (28). GPx plays an effective role in the peroxyl scavenging mechanism that converts H2O2 (produced by SOD) into water .Genistein is a phytoestrogen that is similar to the chemical structure of 17\u03b2-estradiol. It has been known as a powerful antioxidant and oxidant scavenger that inhibits oxygen radicals and hydrogen peroxide production through the activation of SOD and GPx enzymes in several organs (12).The elevation of antioxidant activity strongly suggests that ovarian tissue was protected against oxidative damages in PCOS conditions. Therefore, antioxidants supplementation in PCOS condition positively contributes to the management of PCOS and its complications.et al. showed four-weeks treatment with genistein improving the development and viability of rat ovarian follicles (29). Genistein may exert its protective effects through many biochemical and multidirectional pathways. Genistein may decrease the pool of ROS and act as free radical scavengers in the ovary due to their polyphenolic structures and hydroxyl group (28). Moreover, genistein exerts antioxidant effects through the modulation of transcription factors such as nuclear respiratory factor (Nrf), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) , and anti-inflammatory effects (32).However, Zhuang The previous studies indicated that inappropriate levels of gonadotropins and sex hormones induced polycystic ovaries . On the other hand, follicle-stimulating hormone (FSH) levels decreased and Luteinizing hormone (LH) levels increased in PCOS patients. The imbalances levels of FSH and LH impair follicular growth and lead to anovulation in PCOS (31). Moreover, high levels of LH lead to excessive secretion of estrogen and testosterone by suppressing aromatase activity (conversion of androgen hormones into estrogens) and thereby resulting to the disruption of sexual cycle and ovulation in PCOS .Kafali and colleagues demonstrated that the inappropriate secretion of FSH and LH is due to an inadequate interaction between granulosa and theca cells in PCOS ovaries (35). The damaged granulosa and theca cells in our histological observation affirmed the abnormal secretion of gonadotropins in PCOS rats.The protective effects of genistein may be mediated not only through antioxidant activity but also by retaining follicular steroidogenesis and ovarian cycle, which is disrupted by PCOS conditions (36). Genistein is a natural inhibitor of ovarian estrogenic activity by binding to the estrogen receptor (ER) with the polyphenolic structure  and decrease testosterone by stimulation of aromatase activity (34).In addition, genistein may affect the hypothalamic pituitary axis and increase the gonadotrophin-releasing hormone (GnRH) production and lead to reducing the secretion of gonadotropins (3). Moreover, the level of FSH increased and affect the follicular growth and subsequently stimulated granulosa cells for the production of estrogen and preserve follicular reserve (30).Our study revealed that there is an increased oxidative stress and decreased antioxidant activity in rat PCOS model, and suggests that oxidative stress as an important pathological feature of PCOS could induce formation of cystic follicles and disrupt follicular structure. Thus, these physical, biochemical and histological results clearly demonstrated that treatment with genistein promotes follicular growth by achieving an adequate antioxidant defense system and scavenging free radicals, thereby reducing the harmful effects of excess of oxidative stress on follicular structure in the PCOS model. Further researches are recommended to clarify the effects of genistein on oxidative stress in the PCOS model.The authors have no conflicts of interest to declare."}
+{"text": "Sci., 2019, DOI: ; 10.1039/c9sc01496a.Correction for \u2018Unraveling the structural and chemical features of biological short hydrogen bonds\u2019 by Shengmin Zhou  The authors regret that in the original article funding information was inadvertently omitted in the Acknowledgements. The authors gratefully acknowledge the National Science Foundation through the award CHE-1904800.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."}
+{"text": "The present qualitative study examined the reconciliation of trauma experienced by 55 World War II veterans  demonstrated via testimonial language within a semi-structured interview. The research team considered themes of language coherence as they relate to veteran experiences of trauma and reconciliation. Trauma literature documents the importance of personal narratives in both identifying and reconciling traumatic experiences. This study examined morals and values of participants, traumatic experiences either lived or witnessed, and reconciliation of trauma as demonstrated by the coherence of participants\u2019 linguistic and paralinguistic communication. Linguistic analysis included the use of evaluative and emotional language; linguistic devices such as crowding, topic maintenance, and humor; and lessons learned from trauma and the reconciliation process. Prosody was analyzed as a paralinguistic indicator of trauma and reconciliation using audio recordings of semi-structured interviews. The primary findings revealed that highly coherent language is present among participants with distinct content when comparing episodes from youth and reflections of experience in old age. The unique differences demonstrated overall strength of veterans\u2019 narrative identity throughout their lives. Strength of identity and coherence of language indicated adequate reconciliation of traumatic events. Reconciliation of trauma was also evident in veterans\u2019 participation in the study and generative behavior described in testimonial language."}
+{"text": "Strong and fulfilling relationships are important components of men\u2019s health and well-being across the life course; however, social isolation and loneliness are important but under-assessed conditions among older men. This is important to note because older men often subscribe to common masculinity themes regarding independence and self-sufficiency which places them at greater risk for social isolation and loneliness in comparison to older women. The purpose of this presentation is to review the social isolation and loneliness literature specifically among older men by 1) discussing gender differences, and the potential mechanisms behind these differences, in social isolation and loneliness, 2) examining health, behavioral and physiological effects of social isolation and loneliness specifically among older men, and 3) providing future research directions for understanding social isolation and loneliness among older men including understanding social isolation and loneliness and their associative outcomes among diverse samples of older men."}
+{"text": "The associations between smoking and health are well documented. Using the Healthy Ageing In Scotland (HAGIS) survey linked to the administrative Scottish National Health Service (NHS) records this study analyses health service resource usage by older people according to self-reported smoking status. Individual level smoking status , socio-demographic characteristics  and subjective health are sourced from people aged 50+ across Scotland using HAGIS. These responses are then linked to NHS Scottish Morbidity Records to analyse variation in health service usage as measured by the total number of days spent in hospital (daycases and inpatient stays), number of stays, and mean length of stay. Costs are then assigned by medical speciality. We use a two-part model to analyse the i) the probability of having been hospitalised at all, and ii) the quantum of resource usage and its associated cost for those who have been in hospital. Our study provides a conceptual and empirical framework for the associative relationship between smoking status and actual (rather than self-reported) health service usage and expenditure. This study demonstrates the insights to be gained from the linkage of individual survey responses to administrative health service data on resource usage and costs, and discusses the implications for health policy."}
+{"text": "Coronary artery disease (CAD) is the first cause of mortality worldwide and the majority of individuals older than 60 years of age suffer from its consequences. It is ascertained that the epidemiology and social impact of ischemic heart disease (IHD) are huge and big efforts are mandatory in diagnostic and prognostic fields.Modern and thrilling technology such as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) has been emerging and offering the possibility to characterize both the coronary arteries and the myocardium at a very high level of detail.Our special issue, which had opened for 6 months in the first half of 2018, mainly focused on scientific evidences of advance in cardiac and coronary CT and CMR and included four narrative reviews and two original articles.Carrabba et al. critically analyzed the National Institute for Health and Care Excellence (NICE) guidelines on chest pain published in 2016 and underscored the key changes provided in comparison to the 2010 version [CT) as major advance in cardiovascular imaging, able to provide critical information of coronary tree without exposing the patient to added risk. According to authors' report, invasive FFR measurements represent a guide to percutaneous coronary revascularization and have demonstrated to reduce contrast use, cost, or care and improve outcomes [CT values are obtained using resting 3D CCTA images through computational fluid dynamics. Several multicenter clinical trials demonstrated the diagnostic superiority of FFRCT over traditional CCTA for the diagnosis of functionally significant CAD and put it in competition with refined diagnostic tools as stress CMR and coronary CT perfusion [CT offers the possibility to distinguish between patients who can safely avoid invasive coronary angiography and those patients who require revascularization.Ball et al. described the fractional flow reserve (FFR) derived from CCTA datasets  CT systems which allow an accurate assessment of both coronary epicardial stenosis and myocardial CT perfusion imaging at rest and during pharmacologic stress as \u201cone-stop-shop\u201d method [ slices Cormation . In theiCarit\u00e0 et al. considered in their review that primary prevention of major cardiac events needed a strong implementation for ethic and economic reasons. The authors took into consideration the prognostic value of CCTA in the first half of the manuscript and concluded with the description of the recent literature upon the therapeutic perspective. As well described by the authors, CCTA offers the possibility to study the coronary arteries beyond the assessment of coronary stenosis, evaluating the plaque composition and the presence of positive remodeling. This ability has opened a new scenario about the possibility of estimating the prognostic profile of the single patient . Indeed,Catalano et al. sought to evaluate the added prognostic value of CMR as compared to conventional risk profiling, including clinical history, atherosclerosis risk factors, electrocardiography, and echocardiography, in 465 patients affected by stable CAD who underwent a comprehensive CMR evaluation which consisted of left ventricle dimensions and functioning, late gadolinium enhancement (LGE) and stress perfusion sequences. The authors concluded that LGE and stress perfusion assessment independently predicted MACE beyond conventional risk stratification in this subset of patients. Moreover, authors discussed some critical insight of CMR partially explored from existing literature, such as the prognostic value of LGE in the middle-long term  and the Lin et al. aimed to explore the role of the CHADS2 score in the evaluation of carotid atherosclerosis in 109 patients with nonvalvular atrial fibrillation undergoing carotid artery ultrasonography and velocity vector imaging  , 13. Int"}
+{"text": "Agriculture is responsible for over half of the input of reactive nitrogen (N) to terrestrial systems; however improving N availability remains the primary management technique to increase crop yields in most regions. In the majority of agricultural soils, ammonium is rapidly converted to nitrate by nitrification, which increases the mobility of N through the soil matrix, strongly influencing N retention in the system. Decreasing nitrification through management is desirable to decrease N losses and increase N fertilizer use efficiency. We review the controlling factors on the rate and extent of nitrification in agricultural soils from temperate regions including substrate supply, environmental conditions, abundance and diversity of nitrifiers and plant and microbial interactions with nitrifiers. Approaches to the management of nitrification include those that control ammonium substrate availability and those that inhibit nitrifiers directly. Strategies for controlling ammonium substrate availability include timing of fertilization to coincide with rapid plant update, formulation of fertilizers for slow release or with inhibitors, keeping plant growing continuously to assimilate N, and intensify internal N cycling (immobilization). Another effective strategy is to inhibit nitrifiers directly with either synthetic or biological nitrification inhibitors. Commercial nitrification inhibitors are effective but their use is complicated by a changing climate and by organic management requirements. The interactions of the nitrifying organisms with plants or microbes producing biological nitrification inhibitors is a promising approach but just beginning to be critically examined. Climate smart agriculture will need to carefully consider optimized seasonal timing for these strategies to remain effective management tools. The antAgriculture is responsible for over half of the input of reactive N to terrestrial systems; however improving N availability through fertilization remains a primary management technique to increase crop yields in most regions. N fertility management is inherently complex because available N is temporally and spatially dynamic and subject to high rates of loss through diverse pathways. Mobility and availability of N from fertilizers and organic sources is the result of microbial enzymatic processes especially mineralization and nitrification operating within the physical and chemical constraints of the soil matrix . In many3) or ammonium  such as Nitrobacter or Nitrospira convert While the nitrite oxidizing bacteria (NOB) such as Nitrospira bacteria have been found that mediate the entire reaction from Oxidation to nitrate known as Comammox , 2 often limits both the rate of nitrification and the size of the resultant nitrifier populations  additions of urea and ammonical fertilizers, (2) deposition of animal wastes (urine and feces), (3) atmospheric deposition of 3 (The substrate supply for energy yielding reactions (Equations 1\u20133) are important factors controlling nitrification in agricultural soils. The availability of ammonia/ammonium  or using Michaelis-Menten equations  or product (The injection of anhydrous ammonia and banding of urea fertilizers in soils results in temporarily extremely high 3) may result in 3 levels in the application zone  may exceed the temperatures normally experienced at the site under consideration and may exceed the temperature optimum for growth of nitrifier biomass  and the contention that NH3 is the actual substrate for ammonia oxidizers  isolated from circum-neutral pH, fertilized soil in Scotland  that determines the community structure of nitrifiers in agricultural soils  may play an important role in mediating availability of Micavibrio that have been observed in wastewater systems to prey upon Nitrospira  and urease inhibitors (UI), higher splitting frequency of fertilizer N application, lower basal N fertilizer (BF) proportion, deep placement of N fertilizer, and optimizing N rate based on soil N test , growing greater diversity of crops (in rotation and as diverse mixtures of cover crops), maintaining living roots in the soil as much as possible (with crops and cover crops), and keeping the soil covered with residue at all times will increase the resiliency of agroecosystems and decrease N losses , and NO emission (\u221224%)  slow the microbial conversion of ammonium-N to nitrate-N (nitrification), reducing the risk of loss through leaching or denitrification and thereby increasing the NUE of fertilizers. Many synthetic NIs act on the ammonia monooxygenase enzyme often as competitive suicide subtrates (for example acetylene) McCarty, . SeveralBrachiaria spp. have high BNI-activity in root systems and among field crops, sorghum (Sorghum bicolor) has been observed to produce biological nitrification inhibitors  is the ability of certain plant roots to impede soil nitrification through the production of biological inhibitors  focus on enzymes involved in nitrification using proteomics\u2014direct extraction of enzymes or fluorescently labeling key enzymes, (2) link ecophysiology in soil to sequence variants for trait-based modeling, (3) discover novel nitrification inhibitors, survey rootzone microbes and cultivars of major crop plants for inhibitory compounds, and (4) improve nitrification management modeling, especially for changing climate scenarios.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Aging is a distinct part of the life cycle. College students enrolled in courses in gerontology often have difficulty relating to aging, that part of life not yet experienced. They may not fully appreciate that adults become more unique, not more similar, as they age. We describe courses in an undergraduate gerontology certificate program that incorporate experiential learning activities with older adults across a hierarchical sequence of courses. These courses feature service learning opportunities focused on increased understanding of course content, broader appreciation of the discipline and improved sense of civic responsibility. Much like the course content of the curriculum, the incorporated experiential learning opportunities for each course level fit a hierarchy leading to student competence and skills development needed for success in the final independent practicum. For the described courses, students provided community service, experienced direct contact with older adults and used reflective practices to integrate course content into service learning activities. We report on qualitative data obtained from students enrolled in the foundational course, Biophysical Aspects of Aging and the third level course, Aging and Mental Health. Content analyses of reflective essays identified five themes: (a) insights about the realities of aging in America (b) perceptions concerning personal negative stereotypes about older adults; (c) feelings of accomplishment/awareness of new skills in providing community services; (d) understandings related to the importance/value of community service; and (e) successes in integrating the course work on aging into service-learning experiences. Other experiential learning activities incorporated into this gerontology certificate program are highlighted."}
+{"text": "Person-centered collaborative care arrangements that empower residents, families, and care partners require supports for resident and their \u201ccare convoys\u201d\u2014the evolving collection of individuals who provide formal and informal care. Direct care workers (DCWs) are essential in supporting resident needs within the complex and dynamic environment of assisted living. The stability and preparedness of this workforce is central to improving quality of life for residents. This paper identifies key factors influencing the integration of DCWs in the convoys and explore supportive employment practices to strengthen the convoy. This analysis uses data from a 5-year mixed-method qualitative study of eight assisted living communities. Time pressures, AL policies and practices, work overload, lack of training, and turnover impact whether direct care workers are empowered as full members of the care convoy. Supportive employment practices  are discussed as potential solutions for building consensus and collaboration."}
+{"text": "Health disparities are differences in the incidence, prevalence and burden of diseases, mortality rates and causes of death that exist among population groups. Health disparities are associated with a broad, complex, and interrelated array of factors that influence health, accelerate aging and reduce life expectancy. NIA\u2019s health disparities research goals are to understand environmental and sociocultural factors and related behavioral and biological mechanisms that diminish health and reduce life expectancy for vulnerable populations, explore the biological mechanisms through which disparities influence age-related change, and identify where disparities emerge in diagnosis, prognosis or treatment in geriatric conditions. Presentations will focus on whether structural-level discrimination may be a key factor in potentiating well known race-related health disparities especially those with an accelerated onset and may be associated with MRI-indicators of subclinical brain pathology; identifying biomarkers for early detection of cognitive and functional decline in high risk subpopulations and how ethnicity influences cerebral spinal fluid and imaging biomarkers link to early identification of cognitive and functional impairment ; effects of medication management and deprescribing among African American and Hispanic older adults with Alzheimer\u2019s disease and related dementias and multiple chronic conditions; examine the use of multi-level factors and technology to overcome the barriers to urban-rural health disparities in managing many chronic diseases such as hepatitis C virus infection and delivery of appropriate medical services; and understanding the racial and ethnic differences in the link between environmental exposures and auto-immune comorbid asthma."}
+{"text": "Objective: Whereas prevalence of elder financial mistreatment has received increased attention over the past decade, health and mental health correlates are rarely studied. Thus, the potential relevance of financial abuse to mental health and perceived health is relatively unknown, and the objective of this article is to illustrate this relationship. Method: The second wave of the National Elder Mistreatment Study used random digit dialing telephone survey methodology to assess both recent financial mistreatment and its potential mental health correlates  in 774 older adults. Results: The study indicated that past-year Wave II financial mistreatment was associated with significantly increased likelihood of depression, PTSD, GAD, and poor self-rated health; and financial mistreatment perpetrated by family members was associated with particularly increased risk of depression. Discussion: Assessment of mental health is relevant and important in cases of financial abuse."}
+{"text": "This data examines the impact of personal  and contextual (university environment and knowledge about business) factors on entrepreneurial intentions of university students in two Turkish universities. University students are one of the important groups to analyse entrepreneurial intentions. There are a number of researches that tested the effects of different personal and contextual factors separately on students' entrepreneurial intentions. This data tests the impacts of two different personal and contextual factors on students\u2019 entrepreneurial intentions at the same time. Data collected using a questionnaire adapted from previous research. A quantitative research design is employed to test the data. The population of the data included 356 university students. Data was analysed running regression analyses with Statistical Package for Social Sciences (SPSS). Personal factors are confirmed stronger triggering factors than those of contextual. Total of five hundred (500) copies of surveys were distributed to two different universities, namely Gazi University and Baskent University located in city of Ankara, and totally three hundred and fifty-six (356) surveys were returned representing 71.2% response rate. Questionnaire and raw data are attached to the article as The data were designed to test the impacts of personal and contextual factors on the entrepreneurial intentions of university students. Personal factors in this data were entrepreneurial self-efficacy (ESE) and locus of control (LOC) while contextual factors were university environment (UE) and knowledge about the business (KAB). Entrepreneurial intention refers to the efforts of a student towards the behaviour of establishing his/her own business.To test the hypotheses, two different regression analyses were employed. As shown on 2The data was based on quantitative analysis. The method of analysing the data was regression analyses. The data was gathered from students in two selected Turkish universities. Five hundred questionnaires were distributed and three hundred and fifty-six were gathered. The data collecting instrument has been adapted from already used previous papers . Questio"}
+{"text": "The VA has invested in developing the skills of its primary care workforce through the longitudinal Geriatric Scholars Program. The program consists of core components --- intensive course in geriatrics, intensive workshop in quality improvement (QI) and initiation of a micro QI projects in the Scholar\u2019s clinic; electives allow learners to tailor the program to self-identified gaps in knowledge, skills and competencies. The program has demonstrated direct impacts of continuing education through a workforce development process that enhances skills and competencies at a pace and selection that meets clinicians\u2019 self-identified gaps in training. Now in its 11th year, the program has been shown to increase career satisfaction and job retention, standardize provider behaviors, improve clinical decision-making and reduce dispensing of potentially inappropriate medications. This symposium further explores the impact of the program on individual clinicians and on clinical teams."}
+{"text": "Racial disparities in quality of care (QoC) and quality of life (QoL) for nursing home (NH) residents persist even as the proportion of minorities is significantly increasing. Staff of color are a growing part of the long-term care workforce and staffing is a key component for delivering quality care. This study looks at staff (n=60) perspectives on resident QOL through semi-structured interviews, using thematic analysis in six Minnesota high proportion minority NHs. Key findings show that staff of color are concerned about the QoC and QoL residents of color experience, and take extra steps to provide care that goes beyond addressing their clinical needs. This agency of providing extra care is a factor in burnout among staff of color. More research on how this unequal burden of care impacts QoC/QoL is important to address the disproportionate role that staff of color play in reducing disparities in resident QoC and QoL."}
+{"text": "Direct cloning of metagenomes has proven to be a powerful tool for the exploration of the diverse sequence space of a microbial community leading to gene discovery and biocatalyst development. The key to such approach is the development of rapid, sensitive, and reliable functional screening of libraries. The majority of library screen have relied on the use of agar plates in petri dishes incorporating the target enzyme substrate for activity detection of positive clones (Iqbal et al. , Knietsc\u2022Novel substrate gel assay plates for activity screening with localized and intensified signals.\u2022Rapid and complete screening of library clones in split pools.\u2022Progressive enrichment scheme as a refining step for isolating target gene. Microbial diversity provides a vast genetic resource for the discovery of new genes, enzymes, natural products, and bioactives with impacts on industrial and biotechnological applications. However, only less than 1% of the microorganisms in the natural environment can be cultured in traditional laboratory conditions. For the last two decades, metagenomic research has demonstrated that direct cloning of collective genomic DNA provides a powerful tool for exploring the diverse sequence space of uncultured microbes . The genIn the general scheme, a metagenomic library was split into small pools (sub-libraries) for culturing in 96-well microplates (culture plates). The sub-libraries grown overnight in the culture plate were then transferred to premade substrate gel microtiter assay plates. The substrate gel was formulated to enable the localization and confinement of the reaction products, resulting in intensified signal for detection  . The minute quantity of the enzyme reaction product combined with its rapid diffusion through the agar medium rendered the screening unreliable in capturing the signal. Compartmentation of the substrate gel in microplate wells had the effect to contain and minimize signal diffusion, significantly increased the sensitivity of the assay, and allowed rapid measurement of the activity and unambiguous identification of positive clones even at very low activity level. (2) The incorporation of a detergent at sub-cytotoxic concentrations was to enhance the diffusion of substrate/enzyme across the cell membrane, and enzyme action on the substrate. The type of detergent and its concentration were used for optimum formulation to maximize permeability and minimize toxicity. A gel matrix platform containing both growth nutrients and enzyme substrates would then allow for simultaneous maintenance/growth of the clones and activity monitoring of gene expression. (3) The enrichment strategy contained two key steps: a stepwise reduction of the complexity of pool, and repeated dilution and sampling of the positive pool. This strategy enabled rapid isolation of individual positive clones in the sub-library pool. The serial dilution approach was derived in full extension of the efficacy of the substrate gel assay being able to detect the activity of a very few active clones.In the present example, screening by both types of FAE assay plates could be performed for extended periods of time with continuing signal accumulation up to 20\u202fh. The two screenings were conducted in parallel to confirm the activity and reduce false positives. A total of seven FAE genes (numbered C1\u2013C7) have been isolated from rumen microbial metagenomic library.Orpinomyces sp. PC-2 FAE  screening library of clones in split pools; (2) localizing and intensifying positive signals on substrate gel assay plates; and (3) progressive enrichment and isolation of positive clones. The method significantly enhances the success rate in gene discovery. The method has been developed and used successfully in our various projects to discover numerous hard-to-find novel genes/enzymes within a short time period."}
+{"text": "Geriatric Research Education and Clinical Centers (GRECCs) are centers of excellence funded by the Veterans Administration for the advancement and integration of research, education and clinical activities in geriatrics and gerontology to improve the health, and health care of, older Veterans. The GRECC Connect program expands access to care for rural-residing older Veterans and caregivers. Eastern Colorado GRECC Connect integrates Associated Health Trainees  and Geriatric Medicine Fellows into interdisciplinary tele-geriatric and tele-palliative care consultations provided to outlying community-based outpatient clinics. The formal telehealth training includes: (1) an initial didactic orientation to introduce skills, common challenges, and important tips when working with older patients and caregivers via telehealth; (2) direct observation and modeling by preceptors, followed by a structured opportunity to debrief what the trainee observed and address questions; and (3) opportunities to provide Geriatric telehealth services, supported by the interprofessional team and feedback and reflection. A formal competency assessment, standardized observation protocol and debriefing guide support the development and assessment of telehealth competencies. During exit interviews, trainees indicated that these experiences offered unique opportunities to develop their clinical skills, particularly related to active listening and communication. They identified their involvement with GRECC Connect as a highly valued aspect of their Geriatrics training. Rigorous training in telehealth is an essential aspect of workforce development in Geriatrics and Gerontology given the concentration of older adults in rural areas. During this session, we will highlight the value of telehealth training for workforce development in Geriatrics and Gerontology."}
+{"text": "Social isolation and loneliness are associated with poorer health status and poorer health outcomes. Little is known the impact on health service usage, and its inherent cost, although it is considered to be higher. Latent class analysis (LCA) was used to determine profiles (population groups) of loneliness and social isolation in older people  using model-fit criteria. Loneliness was measured using the UCLA Loneliness Scale and social isolation used a measure of social networks and social contact. We then analysed the socio-demographic, perceived health, and health behaviour of these profiles using descriptive statistics and logistic regression. The survey data  were linked to retrospective administrative health data to investigate patterns of repeat prescription use (from 2009) and health service usage (from 2005) and their associated costs. Our results highlight the distinction and inter-relation between social isolation and loneliness , and the variation in health service usage and costs between the population groups. LCA profiles may help focussed targeting of these groups for health interventions. Further, the data-driven approach of LCA may overcome some of the limitations of indices of social isolation and loneliness. As such, this will extend the existing methodological approaches to quantitative analyses of social isolation and loneliness and demonstrate the benefits of using linked administrative health data. Significantly, this study incorporates the social and financial cost of social isolation and loneliness on health and its implications for health services."}
+{"text": "There has been emerging evidence of non-pharmacologic therapeutics for psychiatric illnesses to modulate brain activity. These methodologies are often referred as \u201cneuromodulation,\u201d which is a broad term that could technically be considered to cover any medical, surgical, or physiologic therapy designed to alter the function of the nervous system in some manner. In the clinical neurosciences, however, neuromodulation is understood to refer specifically to therapies that involve targeted delivery of electrical current or magnetic field, which includes electroconvulsive therapy (ECT), one of the oldest treatments in psychiatry, and vagus nerve stimulation (VNS), approved by the Food and Drug Administration (FDA) in 2005 for severe depression, and repetitive transcranial magnetic stimulation (rTMS), approved by the FDA in 2008 for the treatment of major depression. Recently, studies using transcranial direct current stimulation (tDCS), electric trigeminal nerve stimulation (eTNS), deep brain stimulation (DBS), and neurofeedback have been also reported in a growing trend. To develop more effective treatments for psychiatric diseases, translational approaches bridging basic and clinical evidence deserve considerations.In this e-book, we tried to provide a forum for researchers interested in basic, translational, and clinical research of neuromodulation for psychiatric illnesses and aim to facilitate an integrative view of neuromodulation. It was our unexpected pleasure to have 16 papers in this topic which reported new exciting findings and cutting edge methodologies. The included papers were divided into four groups as follows: (1) the clinical application of tDCS, ECT, and rTMS for psychiatric diseases, (2) the brain function enhancement by tDCS, (3) new application of neurofeedback, and (4) translational research in neuromodulation.Takayima et al. analyzed resting 19-lead EEG data recorded from 13 depressed patients before and after a course of ECT by exact low resolution electromagnetic tomography (eLORETA). They found ECT modulation on resting-state EEG oscillatory patterns and phase synchronization in central nodes of the default mode network (DMN) and suggested that changes in beta synchronization in the left hemisphere might explain the ECT-related cognitive side effects. Nishida et al. evaluated the immediate impact on anxiety of tDCS to the left dorsolateral prefrontal cortex (DLPFC) or dorsomedial prefrontal cortex (DMPFC) in 14 patients with major depressive disorder (MDD) and 19 healthy controls (HCs) and its association with pre-stimulus brain activity by using eLORETA. They suggested that the association between pre-tDCS brain activity and the anxiety reduction effect of tDCS depends on psychopathology (depressed or non-depressed) as well as the site of stimulation (DMPFC or left DLPFC) and insomnia. To compare rTMS-induced cortical plasticity changes in patients with MDD and in healthy volunteers, Vignaud et al. used motor evoked potentials (MEPs) evoked by single-pulse TMS before and after a single and continuous intermittent theta-burst stimulation (TBS). They observed impaired TBS-induced neuroplasticity in patients with MDD compared to that in controls and suggested impaired long-term potentiation (LTP)-like mechanisms in MDD. Kazemi et al. reported the effects of bilateral rTMS of DLPFC on the activity of resting state network (RSN) as well as relevant cognitive function in patients with bipolar depression that responded to treatment. They suggested that bilateral rTMS of DLPFC changed the activity of RSN and consequently improves verbal memory and executive functions in patients with bipolar depression. Inagawa et al. assessed the safety and efficacy of tDCS during cognitive training on cognitive functioning in patients with mild or major neurocognitive disorders by adopting two-arm, parallel, randomized, and sham-controlled trial and reported tDCS is safe and tolerable but causes no statistically significant cognitive effects in patients with mild or major neurocognitive disorders. Cruz Gonzalez et al. conducted the systematic review on the literature about the efficacy of tDCS in improving cognitive outcomes in mild cognitive impairment (MCI) and dementia, including 12 studies with 195 patients with dementia and four studies with 53 patients with MCI. They concluded that tDCS improves memory in dementia in the short term and have a mild positive effect on memory and language in MCI. These studies showed clinical validity and usefulness of neuromodurational methodology with the effectiveness on brain activity and pathophysiology related to certain brain areas and connectivity related to various types of cognitive process and psychiatric symptoms.The clinical application of neuromodulation for psychiatric diseases, mainly mood disorders and cognitive impairments, was described in the papers of the first group. To examine the effects of ECT on neuronal oscillatory pattern and phase synchronization, and the relationship between clinical response or cognitive change and electroencephalogram (EEG) measurements, Ikeda et al. investigated the cortical oscillatory changes induced by anodal tDCS during a WM task. They elucidated no-correlation between stable WM capacity and increased gamma-band oscillation induced by tDCS. Gold and Ciorciari applied tDCS to \u201cflow states,\u201d considered a positive, subjective experience during an optimal balance between skills and task demands. Although they found the increased flow experience by real stimulation for both trained and untrained Tetris players compared to sham stimulation, improved performance effects were only seen with untrained groups. They concluded that tDCS may encourage flow experiences in complex real-life motor tasks that occur during sports, games, and everyday life. Steinberg et al. reviewed the literature about acute behavioral, neurophysiological, and neurochemical effects and the mechanistic pathways of tDCS and aerobic exercise (AE) and discusses potential interactions and synergies between tDCS and AE that might be provoked when directly combining both techniques. They suggested that a direct combination of tDCS and AE provides multiple beneficial opportunities for synergistic effects both within non-clinical settings in health and for treating several psychiatric and neurologic conditions. These papers proved quite wide and promising utility of tDCS on the brain function enhancement and augmentation which would provide huge markets for normal subjects.The second group of papers investigated the possibility of the enhancement of brain function of normal subjects by applying tDCS. To test whether anodal offline tDCS over the left prefrontal cortex (PFC) enhances working memory (WM) capacity by modulating the oscillatory activity in the left dorsolateral PFC (DLPFC) using magnetoencephalography (MEG), Karch et al. assessing the combination of real-time fMRI (rtfMRI) and neurofeedback (NF) to predict the outcome of NF training plus group psychotherapy at the beginning of the treatment for patients with tobacco use disorder. They reported that they could estimate a successful withdrawal in patients with tobacco use disorder by analyzing the first rtfMRI NF session: a pronounced reduction of frontal responses during NF training in patients might be the functional correlate of better therapeutic success. They suggested that the results of the first NF sessions could be useful as predictor whether a patient will be able to achieve success after the behavioral group therapy and NF training in quitting smoking or not. Chiba et al. conducted a systematic review to compare Decoded Neurofeedback (DecNef) effect with those of conventional EEG/fMRI-based neurofeedback on post-traumatic stress disorder (PTSD) amelioration. They suggested that DecNef could be a promising therapy that bypasses the unpleasantness of conscious exposure associated with conventional therapies for fear related disorders, including PTSD. The other types of neurofeedback studies, especially electrophysiological procedures, which have some advantages like cheaper running costs, smaller apparatus, and non-invasiveness without any exposure to radiation or strong magnetic fields, would be encouraged and provoked by these MRI neurofeedback studies.The third group contains the new application of neurofeedback from Zhou et al.), TMS and brain-derived neurotrophic factor (BDNF) in fibromyalgia and depression , acoustic startle response (ASR), and locomotor dynamics in autism spectrum disorder (ASD) , P300 and heart rate in emotional processing . The future translational approach bridging between clinical application on neuropsychiatric diseases and basic pathophysiological research about the mechanism of these neuromodurational methodologies will be expected.The fourth group of articles tried to expand the new frontiers for translational research of neuromodulation, combining electroacupuncture and neurogenesis in PTSD rats  from Merck & Co., VistaGen Therapeutics, Inc., and MECTA Corporation, the U.S. Department of Veterans Affairs, and August Biomedical Research Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "The data presented in this article characterizes the erring patterns intrinsic to manual contouring of PET positive tumor targets in the lung from twelve quantitative agreement measuring metrics, with categories related respectively to spatial overlap, pair counting, information theory, distance, and volume. The data holds the potential for the formation of new hypotheses towards improving the accuracy and precision of manual delineation of PET positive lung targets for radiation therapy. Conto"}
+{"text": "Although the impact of dementia on the health and well-being of those living with Alzheimer\u2019s Disease and related Disorders (ADRD) and their care partners has been widely studied, less attention has been paid to how the disease impacts individuals within the context of their larger social networks. This symposium presents findings from a series of integrated studies aimed at strengthening measurement of health and well-being among older adults with living with dementia and well-being among members of their social networks. Findings will be presented from five studies: (1) a scoping review of social network measurement in older adults in chronic illness, including dementia, that emphasizes the use of technology in measuring older adults\u2019 social networks; (2) a simulation study to evaluate the feasibility and reliability of sensor technology to measure social interaction among a person living with dementia and others in their immediate surroundings; (3) development of a web-based application that allows older adults to map and activate their social networks; (4) a qualitative analysis of interviews from persons living with dementia, their unpaid caregivers, and paid caregivers from an adult day health program concerning well-being focused outcomes; and (5) a mixed methods analysis of the feasibility of using both traditional and novel measures of health and well-being deployed among networks of people living with dementia. Emerging technologies for measuring social networks health and well-being hold promise for advancing the study of the relationship-based nature of care for people living with dementia."}
+{"text": "OBJECTIVES/SPECIFIC AIMS: To identify new ethical challenges in human subject research related to the use of cloud-based platforms for data collection. METHODS/STUDY POPULATION: Ethical analysis. RESULTS/ANTICIPATED RESULTS: The OHRP regulations protecting the data, privacy and confidentiality of human subjects and the Terms of Service regulations governing data use by cloud-based platforms are vastly different. The gap between these 2 sets of laws and regulations leaves human subjects vulnerable to harm during the data collection process via clod-based tools. DISCUSSION/SIGNIFICANCE OF IMPACT: Recognizing the risks related to data gathering via cloud-based platforms, and educating researchers and research subjects about these risks and how to minimize them will strengthen the protections of participants and will enhance the informed consent process resulting in increased trust and greater willingness to participate in human subject research."}
+{"text": "The African American church has played a major role in African American communities, and church relationships represent an important stress-coping resource for older African Americans. This study examined 1) the association between everyday discrimination and generalized anxiety disorder (GAD) and 2) whether church-based relationships buffer the negative effects of everyday discrimination on GAD among older African Americans. Logistic regression analyses were conducted using data from 670 African American respondents age 55 and older from the National Survey of American Life: Coping with Stress in the 21st Century. More frequent experiences of everyday discrimination was associated with higher odds of meeting criteria for GAD. Significant interactions indicated that frequent contact with church members and high levels of subjective closeness to church members buffered against the negative effects of discrimination on GAD. Interventions that focus on the use of church members for support capitalize on a major strength among older African Americans."}
+{"text": "Recent evidence suggests that inflammatory markers may reflect cerebral disease mechanisms related to dementia. However, whether and how inflammation is associated with cognitive function in older Chinese is unknown. The current study is to analyze the association between high-sensitivity C-reactive protein (CRP), an indicator of chronic inflammation, and domain-specific cognitive function  among older adults aged 65 years and over in China. Data of the study  were selected from the 2015 China Health and Retirement Longitudinal Study (CHARLS) and were analyzed using linear regression models. Results of the study show that for every 1.00 mg/L increase in CRP, the scores of mental status and overall cognition both decreases by 0.03 unit and higher levels of CRP are observed in men than women. The findings might be useful in interpreting the biological mechanisms of dementia and add value in dementia prevention and health promotion for the general older population."}
+{"text": "The data presents an examination of Islamic ethical work behavior of Malay Muslim teachers in Brunei through religiosity and theory of planned behavior. The total number of participants was 370 Bruneian Malay Muslim teachers. The participants were sampled from two different types of school systems being non-religious schools and religious schools, with five schools each. By documenting information of the data, this data article presented the demographic characteristics of participants, and reliability and correlation of measures involved. Analyses of the data can provide insights into determinants and in predicting Islamic ethical work behavior. Furthermore, the data will be useful for researchers and policymakers that are interested in knowing the current situation of religiosity and behavior in the country. It can also be used as references in developing interventions, promoting and facilitating Islamic ethical work behavior in the workplace. Islamic ethical work behavior in the dataset was labeled as IEWB and measured only with a single item. ATB has two sub-measures: instrumental (ATBI) and experiential (ATBE). SN has injunctive (SNI) and descriptive (SND). PBC has capacity (PBCC) and autonomy (PBCA). Each sub-measure had three items. Items were labeled with numbers . The process of developing the measures were done adhering to several guidelines ,5. ItemsIn order to measure religiosity, seven scales from Psychological Measures of Islamic Religiosity were used . The scaIn the dataset itself, all items for both measures of theory of planned behavior and religiosity were properly labeled. Ratings were also provided in the dataset. Furthermore, items were computed to conceive their respective measure's mean values, and then labeled as their composite counterpart .However, due to the dataset containing multiple measures and their items having varying ratings (even within measures), an annotated questionnaire is attached for a clearer picture of the data (see \u201cAnnotated Questionnaire\u201d file under Reliabilities of instruments see  and corr"}
+{"text": "Few studies on quality of life (QoL) in the mentally ill population of South Africa have been conducted, but none in community-dwelling individuals. This study examined the QoL of psychiatric patients at community mental health clinics in Gauteng province of South Africa.A cross-sectional interview-based study was conducted on 121 adult patients attending community psychiatric clinics. To reduce the impact of acute psychiatric symptoms on subjective QoL, only clinically stable patients were included. Instruments used included the World Health Organization Quality of Life BREF domains , the Brief Psychiatric Rating Scale (BPRS) for severity of illness and a socio-demographic and clinical questionnaire.Just under half of the sample rated their overall QoL as good or very good. The strongest predictor of a poor QoL in all four domains was residual psychiatric symptomatology. The most severe BPRS scores were for the symptoms of depression, anxiety and somatic concern. Perceived social support significantly predicted a better QoL in the psychological, social relationships and environmental domains.This study highlights the negative impact of residual psychiatric symptoms on subjective QoL, and the importance of social support and enhancing QoL. If better QoL is the goal of care, then our findings highlight the importance of managing residual symptoms and promoting social support."}
+{"text": "The treatment of drug-resistant tuberculosis has attracted intense debate over many years because of the limited number of available drugs and the uncertainties about the relative effectiveness of regimens used, especially those to treat rifampicin- or multidrug-resistant (MDR) tuberculosis. Many treatment options fail to achieve a lasting cure in a large proportion of patients with MDR tuberculosis and have a very unfavourable safety profile.Given the need to deliver life-saving treatment when choice of medicines is limited, patients and clinicians have had to work with toxicity of MDR tuberculosis regimens. Due to a lack of alternative medicines, treatment guidance from the World Health Organization (WHO), the American Thoracic Society, the United States Centers for Disease Control and Prevention and others, has historically featured injectable agents  among priority medicines for MDR tuberculosis regimens, largely based on limited available evidence and expert clinical opinion.Since 2011, WHO guidelines for drug-resistant tuberculosis have been developed using the Grading of Recommendations Assessment, Development and Evaluation evidence-based approach.Despite appeals by patients and carers for more effective and safer regimens, evidence-based patient care and public health policy development for MDR tuberculosis have been negatively impacted by the long-standing gaps in research investment.,This situation is, however, expected to improve as more evidence becomes available for safer and more effective treatment, newer medicines become accessible to more patients and monitoring and rapid management of drug adverse effects are intensified. WHO has repeatedly stressed the need to balance effectiveness and harms when choosing medicines in MDR tuberculosis regimens. Options to replace injectable agents when serious adverse events occur have been highlighted in WHO guidance.The landscape of MDR tuberculosis treatment has changed dramatically in the last 10 years. Among others, evidence for the composition and duration of regimens has evolved; new oral medicines have become accessible ; significant price reductions for key medicines have been achieved through the Global Drug Facility; access to molecular and phenotypic drug susceptibility testing has expanded; and better quality data with a global span on effectiveness and safety from ongoing trials, observational cohort studies and programmatic use of second-line tuberculosis medicines are increasingly available. New data from MDR tuberculosis patients treated with all-oral regimens lasting nine months or less are expected in 2019.The era when patients with drug-resistant tuberculosis had to endure injectable agents as a necessary evil to achieve a durable cure is ending. Accelerated innovation and increased investment in research should translate into a more personalized and tolerable pathway to cure for many more patients with drug-resistant tuberculosis."}
+{"text": "Children in slums are at high risk of acute malnutrition and death. Cost-effectiveness of community-based management of severe acute malnutrition programmes has been demonstrated previously, but there is limited evidence in the context of urban slums where programme cost structure is likely to vary tremendously.Anganwadi community health workers. The analysis used a decision tree model to compare the costs and effects of the two options: standard ICDS services with the intervention and prevention versus standard ICDS services alone. The model used outcome and cost data from the Society for Nutrition, Education & Health Action\u2019s Child Health and Nutrition programme in Mumbai slums, which delivered services to 12,362 children over one year from 2013 to 2014. An activity-based cost model was used, with calculated costs based on programme financial records and key informant interviews. Cost data were coupled with programme effectiveness data to estimate disability adjusted life years (DALYs) averted.This study assessed the cost-utility of adding a community based prevention and treatment for acute malnutrition intervention to Government of India Integrated Child Development Services (ICDS) standard care for children in Mumbai slums. The intervention is delivered by community health workers in collaboration with ICDS Anganwadi community health workers can work efficiently with community health workers to increase the prevention and treatment coverage in slums in India and can lead to policy recommendations at the state, and potentially the national level, to promote such programmes in Indian slums as a cost-effective approach to tackling moderate and severe acute malnutrition.The community based prevention and treatment programme averted 15,016 DALYs  at an estimated cost of $23 per DALY averted (95%UI:19\u201328) and was thus highly cost-effective. This study shows that ICDS  Aahar acute malnutrition programme\u2019, supported by the Society for Nutrition, Education and Health Action (SNEHA), to complement the ICDS scheme by providing community based prevention and treatment of acute malnutrition in children under 3 years old. The Aahar acute malnutrition programme approach is based on early screening of acute malnutrition through identification of all pregnant women and children younger than 3 years, growth monitoring, home-based counseling on feeding and care practices, referrals to public health-care facilities, treatment of malnourished children with provision of antibiotics and Medical Nutrition Therapy (MNT) . The Aahar acute malnutrition programme has demonstrated significant impact on wasting reduction; children in Aahar intervention areas were significantly less likely to be malnourished   denotes the applied age weighting constant (K) and discount rate (r).DALY[(DOCX)Click here for additional data file.S1 Database(XLSX)Click here for additional data file."}
+{"text": "Contribution of genetics to our understanding of pathomechanisms of complex pulmonary disease is undoubtable. Genetic Association Studies (GAS) with candidate genes, Genome-Wide Association Studies (GWAS), or Whole Exome Sequencing (WES) have collectively identified a spectrum of susceptibility loci in diseases such as COPD , IPF 2)2), or saThree review and three original articles were accepted by the editorial team  after passing interactive review with reviewers' names openly disclosed. The collection of these six contributions does not address solely the assessment of genetic background of given lung diseases but also determination of the etiologic factors using genetic methodologies or identification of new biomarkers. In wider sense, the articles in the collection cover also the aspects how to analyse, interpret, and utilize vast amount of data generated by experimental approaches and how to find ways for their practical utilization in clinical decision making.Newton et al. ideally fitting within the scope of this Research Topic, presents a concise overview of the state of the art in the application of genetics into the diagnosis and management of interstitial lung diseases. The authors do not focus only on idiopathic pulmonary fibrosis (IPF), a debilitating disease in which a number of gene variants was recently nominated and started to be investigated for their clinical relevance. Further, they discuss yet another disease with distinct immune features, hypersensitivity pneumonitis, in which the role of genetic factors is far from clarified and thus should be investigated . Besides the role of the most polymorphic genetic system in humans - HLA, the authors list other TB-associated genes with signaling, enzymatic and other  functions, e.g., Forkhead BoxP1 (FOXP1), C-terminal domain phosphatase, etc. The review emphasizes the importance of population (ethnicity) aspect of these associations with main focus on Asia.The second review by Kishore and Petrek). Here, the advent of a new technology of massive parallel sequencing  and its application to determination of extensive HLA polymorphism is described in context of investigations of another complex pulmonary disease with immune features, sarcoidosis. It is proposed that fine characterization of HLA at the allelic level will provide precise assessment of existing and identification of novel associations between HLA and sarcoidosis/its clinical phenotypes; the authors also discuss population aspects of sarcoidosis immunogenetic research.The author of this editorial himself has co-authored a minireview . In extension of their previous work, which characterized possible candidates for NA biomarkers by transcriptomic (mRNA) analysis, the authors have evaluated protein levels of seven nominated genes. Based on the current data including ROC analyses, Chitinase-3-like protein 1 (CHI3L1), elastase-specific protease inhibitor PI3, and namely their combination is proposed as plausible biomarkers of non-allergic asthma itself and possibly also of its severity. This paper may represent translation of gene expression studies to clinical practice.In the second original paper of this Research Topic, Hopp et al.) approaches common acquired pneumonia (CAP), namely its septic complication, from a perspective angle of bioinformatics. Analysis of patients' blood transcriptome showed that disease severity was associated with immune suppression due to disturbance in a number of functional immune components and functional processes such as T-cell exhaustion, receptor deactivation or metabolic conversion. The authors also demonstrate epigenetic alterations including chromatin remodeling and related methylation changes. Based on their data, they propose a novel stratification for CAP with possible impact on prognostication.The last original paper by a joint German and Armenian author team (The review and original articles in this collection do not and cannot address all issues pertinent to area of genetic applications to complex immune mediated lung disease. This area has been under constant progress as evidenced e.g., by most recent reports on new genetic signals for lung function in COPD  or curreThe author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
+{"text": "Owing to an unfortunate mistake in typesetting, in the original publication of this article (McKay & Mohamad, Figures citation errors and corrections:Figures legend errors and corrections:Anonymous information errors and corrections:The publisher apologizes to the readers and authors for the inconvenience.The original publication has been corrected."}
+{"text": "Generally, vibrational spectroscopy enjoys increasing popularity . One reaMiniaturization of spectrometers in size down to portable and handheld devices for all three vibrational modes makes them more popular even outside the spectroscopic community ,13,14. EThis special issue contains fifteen published papers, twelve research and three review articles. Let me first outline the principal content of the published research articles in chronological sequence: Eisenstecken, Oberhuber et al. described the potential of NIR spectroscopy for predicting quality parameters of Cripps Pink and Braeburn apples such as total soluble solids (TSS), acidity (TA), firmness, and individual sugars  .Baldassarre, Barth et al. described an approach for the simultaneous fitting of MIR absorption spectra for an improved analysis of proteins. The approach termed as \u201cco-fitting\u201d leads to a more reliable modeling of the experimental data because it uses more spectral information than the standard approach of fitting only the absorption spectrum and it also avoids that the fitting routine becomes trapped in local minima. The approach was tested with different mixtures of \u03b1/\u03b2 proteins containing ribonuclease A, pyruvate kinase and aconitase .\u22121) to gain new insights into structure and chemical composition of bovine fibro lamellar bone [Schuetz, Masic et al. investigated the anisotropy in bone demineralization by high intensity synchrotron-based far-IR spectroscopy  as a novel food processing technology on the composition of hia coli .Lutz, Huck et al. prepared an article about the vibrational self-consistent field (VSCF) treatment calculations and the effect of grid densities .Aydin published a comparative study about the structural and vibro-electronic properties of porphyrin and its derivatives employing density functional theory (DFT) and Raman spectroscopy .Lewis, Blake et al. investigated the dynamic light scattering and Raman spectroscopy approach for characterizing the aggregation of therapeutic proteins. The ability to differentiate between unfolding and aggregation that the combination of both dynamic light scattering (DLS) and Raman spectroscopy provides enables for the first time insights into underlying protein aggregation mechanisms .Campos, Stephani et al. investigated the quality of frankfurters by FT-Raman spectroscopy. A multivariate classification model was developed to identify the Frankfurter type, including chicken, turkey and mixed meat. The established PLS-DA models give sensitivity and specificity values on the test-set in the ranges of 88%\u2013100%, showing high performance .Farias and Carneiro described the application of a novel Raman spectroscopic method for the simultaneous quantification of three polymorphic forms of carbamazepine in the presence of excipients. This method was shown being highly useful because it can affect the bioavailability of the final product .Echinacea. Authors explained how this technique can be used to differentiate between the root and leaf samples of three different species and how this method can be applied for differentiation between different root species [Sandasi, Viljoen et al. introduced a novel hyperspectral imaging and chemometric modeling approach for the quality control of the herbal medicine  species .Furthermore, the special issue also contains three review articles providing an excellent overview about selected topics. The first review authored by Huck summarizes the recent development in solid-phase extraction (SPE) methods that can be used in combination with NIR and attenuated total reflection (ATR) spectroscopy . CozzoliIn summary, in this special issue on one side novel technical and theoretical attempts have been introduced including miniaturization of spectrometers and quantum mechanics, on the other side highly selective applications have been introduced in various fields of life science related research. From those articles and especially the three review articles the reader could build up not only his own mind upon the current state of the art, but also might get stimulated to get his own idea for new developments and approaches."}
+{"text": "This editorial describes the purposes and content of the Special Issue for the development of a national pediatric pharmacotherapy collaborative practice network. A collaborative practice network from a population health perspective is needed to better manage the medication-related needs of children with special health care needs and medical complexity (CSHCN-CMC). Over the last 25 years, the pharmacy profession has been engaged in organized efforts both to elevate practice and educational standards for pediatric pharmacy practice and to design medication management systems that benefit children and their families and caregivers. Moreover, alignment with pediatric clinical pharmacologists will aid in the development of new practice-based research paradigms that can be applied in the clinical setting. Formalized multi-disciplinary collaboration (CPAs) with new approaches to specialized electronic medication systems and comprehensive medication management (CMM) is necessary to improve the pharmacotherapy outcomes of pediatric patients. We are delighted that the pharmacy profession has created a board specialty for pediatric pharmacies. The opportunity for residency- and fellowship-trained clinical pharmacists to validate their knowledge base and patient care skills affords the clinical pharmacy a vital mechanism for self-directed life-long learning. In addition, Board-Certified Pediatric Pharmacy Specialists (BCPPS) can not only improve patient care but will also enhance the patient care experience for many children and their families with complex, life-long needs (CSHCN-CMC). With most of the recently boarded pharmacists practicing in the institutional environment, it is incumbent on national pediatric pharmacy leaders to ask several foundational questions in order to sustain and elevate professional practice: (1) where are the ambulatory care pediatric pharmacists; (2) where are the bridge-builders that might create sustainable relationships between the pediatric pharmacy, pediatric clinical pharmacology, and pediatrics; (3) where are the systems-thinkers that manage complicated medication management systems within the inpatient and outpatient environments; and (4) where are the collaborators that can create value for money through the direct care of pediatric patients?Pharmacy (Basel)  on major gaps in pediatric medication management systems, we identified the need for a separate medication management system for children, argued for a system designed for children and their families, suggested potential solutions to the lack of standardized formulations and electronic formulation identifiers, recommended the creation and placement of a validated electronic extemporaneous formulation repository within the National Library of Medicine\u2019s RxNorm database and structure, and proposed a system design for medication therapy management to address the unique needs of children [We believe that the pharmacy profession needs to better understand and estimate the need for pediatric pharmacists that would work in collaboration with pediatric clinical pharmacologists, pediatricians and pediatric sub-specialists. Moreover, to aid in global collaborative research efforts on behalf of children to develop child-friendly medicines, additional traineeships in pediatric clinical pharmacology should be developed to complement the 18 programs worldwide (8 in Europe and 10 in the US) [children ,3,4,5,6.This Special Issue will expand on the needs of further advancing the care of pediatric patients, including the following: (1) addressing the need for a multi-disciplinary national pediatric pharmacotherapy collaborative practice network; (2) exploring sub-specialty needs, processes, and models of care; and (3) describing examples of collaborative practice agreements (CPAs) between clinical pharmacists, clinical pharmacologists, and pediatricians for providing comprehensive medication management (CMM) for CSHCN-CMC. We hope to stimulate thought to generate answers to the above questions in order to project how many pediatric clinical pharmacists providing direct care and CMM through CPAs are needed for the ambulatory care setting . We hope"}
+{"text": "There are errors in the Funding statement. The correct Funding statement is as follows: The research reported in this article was supported by grants to KJV from Vlaams Instituut voor Biotechnologie (VIB), European Molecular Biology Organization Young Investigator Programme (EMBO YIP), and a European Research Council (ERC) Consolidator Grant CoG682009. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."}
+{"text": "The findings of the landmark Should we Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial significantly altered our treatment approach to patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) . With a In response to the absence of clear guidelines for the care of patients with this hemodynamically complex and multifactorial disease state, the Society for Cardiovascular Angiography and Interventions (SCAI) recently released a consensus statement on the classification of CS . A multiThe discipline of structural heart disease has embraced a model of multidisciplinary team- based care, known as the Heart Team, to provide collaborative and patient-centered care for patients with valvular heart disease. Despite clinical precedent for such an approach with other complex cardiac conditions, the management of CS has remained largely fragmented with widely disparate practice patterns for decades . DespiteTwenty years after the SHOCK Trial, we are now at an inflection point in acute cardiovascular care. Using population-based registries, clinicians and researchers are coming together to identify innovative ways to improve recognition and treatment of CS across the entire disease spectrum . Therefo"}
+{"text": "Telomeric repeats were present at both ends of all chromosomes in all species, while varying numbers of ITSs were also found on microchromosomes and in pericentromeric or centromeric regions on macrochromosomes in five lizard species examined. This suggests that chromosomal rearrangements from ancestral squamate reptiles to Iguania occurred mainly by fusion between ancestral types of acrocentric chromosomes and/or between microchromosomes, leading to appearance of bi-armed macrochromosomes, and in the reduction of microchromosome numbers. These results support the previously proposed hypothesis of karyotype evolution in squamate reptiles. In addition, we observed the presence of telomeric sequences in the similar regions to heterochromatin of the W microchromosome in Pogona barbata and Doporiphora nobbi, while sex chromosomes for the two species contained part of the nucleolar organiser regions (NORs). This likely implies that these ITSs are a part of the satellite DNA and not relics of chromosome fusions. Amplification of telomeric repeats may have involved heterochromatinisation of sex-specific W chromosomes and play a role in the organisation of the nucleolus.Telomeric sequences are generally located at the ends of chromosomes; however, they can also be found in non-terminal chromosomal regions when they are known as interstitial telomeric sequences (ITSs). Distribution of ITSs across closely related and divergent species elucidates karyotype evolution and speciation as ITSs provide evolutionary evidence for chromosome fusion. In this study, we performed physical mapping of telomeric repeats by fluorescence  Lacerta agilis) karyotype (2n = 38: 36 macrochromosomes and 2 microchromosomes) showed conserved synteny with ten chromosome pairs of the Hokou gecko (Gekko hokouensis) karyotype (no microchromosomes) and macrochromosomes and/or macrochromosome segments of Toxicofera species . Such ITSs showing co-localisation with NOR have also been reported in butterfly lizard chromosomes [Telomeric DNA can also contain repeat elements similar to centromeric repeat elements . This su barbata . Such am barbata ,35,37,38omosomes ,26). ThiThe karyotypic variability in Australian dragon lizards allowed examination of ITS relationships with chromosomal rearrangements, heterochromatin and NORs. Different patterns of ITSs may be due to the age of chromosomal rearrangements. Further studies involving chromosome mapping of telomeric repeats as well as satellite DNA in more representative species from divergent taxa are required to better understand evolutionary origins and distributions of ITS in squamate reptiles."}
+{"text": "Transportation is vital in the daily lives of older adults and provides access to health care services and health enhancing activities, such as social engagement. Disparities in mobility exist for older African American and Hispanic adults compared to non-Hispanic Whites, including higher likelihood of driving cessation at an earlier age and having a higher risk for reduced life space. This poster presents findings from a qualitative analysis of data from the Using Geo-Ethnography to Explore the Spatial Accessibility of Health Services for Aging Minorities Study (GeoSAS), a mixed methods study of older minority adults in Houston, TX. Using interpretive phenomenological analysis, the transcripts of semistructured interviews with 23 older adults  were analyzed to address the research question: What are the mobility experiences and perceptions of minority older adults regarding healthcare access and social engagement? Based on an ecological systems theoretical framework, we found reciprocal influences of (1) healthcare systems and transportation utilization and (2) participants\u2019 health and well-being, mobility, and social engagement. Support from family members and financial capacity were critical for participants\u2019 mobility. Implications of this research include educating health care providers about patients\u2019 transportation experiences and barriers, optimizing social support to increase mobility, and addressing systematic disparities in transportation access to enhance health and well-being for older minority adults."}
+{"text": "In order to speed up the availability of new drugs for diseases with unmet need, regulators around the world have created rapid review and approval pathways. For the US Food and Drug Administration (FDA), Fast Track, Priority Review and Breakthrough and Orphan Drug designations can allow for softening of evidentiary standards with rapid review and accelerated approval of some drugs without randomized data , 2. RandExpedited regulatory pathways have been associated with shorter time to market but also a higher prevalence of post-marketing safety related label modifications in a cohort of cancer and non-cancer drug approvals . Recent An additional consideration of cancer drug approval without supporting RCTs is the quality of the data which forms the basis for clinical decision making as well as for treatment guidelines. The combination of small sample size, lack of control group, surrogate endpoints and expedited approval pathways is concerning and results in uncertainty about whether data derived from non-randomized registration trials is clinically meaningful. While this might be appropriate for urgently needed drugs, the increasing prevalence of drugs approved through expedited regulatory pathways is noteworthy, perhaps driven by industry eager to approve drugs quickly and reduce costs of drug development . Many ofThere is an inherent trade-off between pre-approval scrutiny of the safety and efficacy of new drugs, and the desire to get potent new drugs to patients without delay Figure . Achievi"}
+{"text": "There is significant literature on the importance of addressing social determinants of health (SDOH) in order to improve health care outcomes. In response, the Centers for Medicare and Medicaid Services (CMS) has expanded Medicare Advantage plans ability to cover SDOH-related services. Medicare home health does not cover SDOH-related services. A literature review indicates no studies on the nature, significance, or impacts of the lack of SDOH coverage in Medicare home health. The current study is an initial, exploratory study to address the literature gap, based on interviews of a convenience sample of 37 home care nurses between January 2013 and May 2014 in the New York City metropolitan area. Results indicate nurses believe the lack of SDOH coverage in Medicare home health results in exacerbation of existing patient conditions; creation of new, additional patient conditions; increased home care readmissions and re-hospitalizations; increased caregiver burden; and exacerbation of patients\u2019 mental health and substance abuse needs."}
+{"text": "In 2017 over one million individuals of all ages were enrolled in approximately 260 self-directed long-term services and support programs nationwide. Research conducted by the National Resource Center for Participant-Directed Care (NRCPDS) and the Council for Social Work Education identified training gaps among current aging and disability network professionals and within social work education. Believing that both self-directing individuals and their family caregivers would benefit from a workforce that has the knowledge and skills to implement the principles of self-directed care, NRCPDS and CSWE working with national professional organizations and government agencies have identified workforce competency domains and developed a number of training resources that can be used in both academic and professionals settings. This presentation will review the work of NRCPDS and CSWE in workforce competencies, training resources, and recommendations for self-directed services training."}
+{"text": "Recently, Anne-Sophie Heimes and colleagues from the University Hospital of Mainz published a study to gain a better understanding of the association of specific immune responses with prognosis in breast cancer . AlthouThe positive prognostic influence of lymphocytic infiltrates has been known for decades (Di Paola et al., 1974; Aaltoma"}
+{"text": "Efficient broadband Internet access is required for optimal productivity in smart campuses. Besides access to broadband Internet, delivery of high speed and good Quality of Service (QoS) are pivotal to achieving a sustainable development in the area of education. In this data article, trends and patterns of the speed of broadband Internet provided in a Nigerian private university campus are largely explored. Data transmission speed and data reception speed were monitored and recorded on daily basis at Covenant University, Nigeria for a period of twelve months . The continuous data collection and logging were performed at the Network Operating Center (NOC) of the university using SolarWinds Orion software. Descriptive statistics, correlation and regression analyses, Probability Density Functions (PDFs), Cumulative Distribution Functions (CDFs), Analysis of Variance (ANOVA) test, and multiple comparison post-hoc test are performed using MATLAB 2016a. Extensive statistical visualizations of the results obtained are presented in tables, graphs, and plots. Availability of these data will help network administrators to determine optimal network latency towards efficient deployment of high-speed broadband communication networks in smart campuses. Specifications tableValue of the data\u2022The data provided in this data article include both peak and off-peak periods and these are valuable to the development of prediction or forecasting models for broadband communication networks in a smart campus environment \u2022Robust data exploration presented in this data article will facilitate effective bandwidth distribution and allocation based on need, priority, and desired Quality of Service \u2022Open access publication of these empirical data has an inherent ability to spur further evidence-based research on efficient bandwidth allocation and usage in computer networking \u2022Availability of these data will help network administrators to determine optimal network latency towards efficient deployment of high-speed broadband communication networks in smart campuses 1Quantitative data on broadband Internet access speed in Covenant University are presented in a reusable format. The data presented are further explored to reveal useful insights that are needed for productive decision making based on statistical parameters used in The scatter plot shown in The datasets were tested for statistical difference across the months of the year based on Analysis of Variance (ANOVA) and multiple post-hoc comparison tests. The results of the ANOVA and multiple post-hoc comparison tests for data transmission speed are presented in 2A smart campus relies on robust and efficient broadband internet access for optimal functionality Covenant University, an ICT-driven private university located in Nigeria, is serviced with high-speed broadband Internet by three ISPs through fiber optic communication links. Two of the ISPs utilize STM-1 with an equivalent maximum Internet speed of 310 Megabit per second (Mbps) while the third ISP provides three STM-1 with an equivalent maximum Internet speed of 465 Mbps. All fiber optic communication links terminated at the Network Operating Center (NOC), which distributes available broadband Internet access to all academic, administrative, and residential buildings in the university campus. The data transmission speed and the data reception speed were monitored and recorded on daily basis for a period of twelve months . The continuous data collection and logging were performed with the use of SolarWinds Orion software. The network monitoring tool was installed on the bare metal server in the NOC to ensure sufficient computing resources. To facilitate easy data reuse for reproducible research, empirical data obtained from the experimental process were properly sorted and preprocessed using Microsoft Excel (MS-Excel) 2013 version."}
+{"text": "Among many possible factors that are associated with increased risk for dementia, one important topic is the role of race and ethnicity. However, previous studies did not examine rates separately by racial/ethnic groups and by nativity status, and little of this research comes from nationally representative data. The current study investigated different predictors of dementia by race/ethnicity and nativity status using Round 1 of the National Health and Aging Trends Study . Our stratified log-binominal regression analyses by race/ethnicity (Non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and Other) show that the relationship of nativity status to dementia (Probable dementia vs Possible and no dementia) is likely determined by multiple factors  that may vary across race and ethnicity. The relative risks of Probable dementia were higher among immigrants in the Hispanic, and other groups, but lower among immigrants in NHBs, although the relative risk of dementia among NHBs was marginally significant. Gender was not a significant factor of Probable dementia across the four groups after adjustment for other variables including nativity status. Older age was significantly associated with the higher prevalence of Probable dementia across the four groups. However, other risk factors for dementia varied considerably between the four racial/ethnic groups after controlling for nativity status. Healthcare providers systems must be prepared to deliver culturally competent supports and services to diverse groups of older Americans and their family members."}
+{"text": "Background: Previous research using cross-sectional data shows widening inequalities in disability-free life expectancy (DFLE) by socioeconomic status (SES) in the UK. We aimed to understand the underlying transitions of DFLE and years dependency free (DepFLE) using longitudinal data from the Cognitive Function and Ageing Studies (CFAS I and CFAS II). Methods: Two large population based studies of those aged 65+ in three centres  interviewed at baseline in 1991 (CFAS I) and 2011 (CFAS II) with follow up two years later. Disability was measured using difficulty in activities of daily living (ADL), and dependency by time between help required for ADLs. SES was based on area deprivation categorised into study specific tertiles. Transitions between disability or dependency states and death were modelled using Interpolated Markov Chain software. Results: Between 1991 and 2011, DFLE and disabled life expectancy (DLE) at age 65 increased for men in every SES group, with men being less likely to become disabled or die, and more likely to recover, in 2011 than 1991 across SES groups. For the most disadvantaged women, DFLE was similar, and DLE increased, whilst for the remaining women DFLE increased and DLE was similar. For women probability of recovery increased and probability of death from disability decreased but probability of becoming disabled decreased only for the most advantaged. DepFLE patterns across time were similar but more pronounced. Conclusion: Preventive measures should focus on reducing the disability and dependency onset in the most disadvantaged to ensure inequalities do not widen further."}