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19134000 | Injury to the lung parenchyma is a constitutional feature shared by many lung diseases. The protein, phosphatase and tensin homologue deleted on chromosome Ten (PTEN) is a major suppressor of phosphoinositide-3 kinase/Akt signalling, a vital survival pathway in lung parenchymal cells. Based on this, we hypothesized that PTEN inhibition in vivo would enhance cell tolerance to stress thereby preventing acute lung injury.
We evaluated the ability of a PTEN inhibitor, potassium bisperoxo (1,10-phenanthroline) oxovanadate [bpV(phen)], to prevent acute lung injury induced by oleic acid (OA) in adult C57BL/6 mice. Lung assessments included bronchoalveolar lavage, tissue morphology, immunostaining for markers of cell death, cell identity, phospho-Akt and phospho-ERK levels and oximetry.
OA induced acute lung injury in a dose- and time-dependent manner. No injury was observed in the vehicle control or bpV(phen) treatment groups. PTEN inhibition by bpV(phen) increased lung tissue levels of phospho-Akt and ERK and but not focal adhesion kinase. This occurred in conjunction with a statistically significant reduction in protein content, lactate dehydrogenase, as well as tumour necrosis factor-alpha and chemokines in bronchoalveolar lavage fluid when compared with OA treatment alone. The incidence of alveolar lesions, consistent with acute lung injury, and terminal uridine deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive cells was also significantly reduced. Importantly, PTEN suppression maintained pulmonary function. | Does inhibition of the phosphatase PTEN protect mice against oleic acid-induced acute lung injury? | Yes. Treatment with bpV(phen) significantly reduced the severity of acute lung injury in mice indicating that additional investigation is warranted to understand the important role that this phosphatase may play in the lung. | PASS | pubmedQA | 1 |
23897505 | Femoral continuous peripheral nerve blocks (CPNBs) provide effective analgesia after TKA but have been associated with quadriceps weakness and delayed ambulation. A promising alternative is adductor canal CPNB that delivers a primarily sensory blockade; however, the differential effects of these two techniques on functional outcomes after TKA are not well established.
We determined whether, after TKA, patients with adductor canal CPNB versus patients with femoral CPNB demonstrated (1) greater total ambulation distance on Postoperative Day (POD) 1 and 2 and (2) decreased daily opioid consumption, pain scores, and hospital length of stay.
Between October 2011 and October 2012, 180 patients underwent primary TKA at our practice site, of whom 93% (n = 168) had CPNBs. In this sequential series, the first 102 patients had femoral CPNBs, and the next 66 had adductor canal CPNBs. The change resulted from a modification to our clinical pathway, which involved only a change to the block. An evaluator not involved in the patients' care reviewed their medical records to record the parameters noted above.
Ambulation distances were higher in the adductor canal group than in the femoral group on POD 1 (median [10(th)-90(th) percentiles]: 37 m [0-90 m] versus 6 m [0-51 m]; p < 0.001) and POD 2 (60 m [0-120 m] versus 21 m [0-78 m]; p = 0.003). Adjusted linear regression confirmed the association between adductor canal catheter use and ambulation distance on POD 1 (B = 23; 95% CI = 14-33; p < 0.001) and POD 2 (B = 19; 95% CI = 5-33; p = 0.008). Pain scores, daily opioid consumption, and hospital length of stay were similar between groups. | Are continuous adductor canal blocks superior to continuous femoral nerve blocks in promoting early ambulation after TKA? | Yes. Adductor canal CPNB may promote greater early postoperative ambulation compared to femoral CPNB after TKA without a reduction in analgesia. Future randomized studies are needed to validate our major findings. | PASS | pubmedQA | 1 |
16442035 | Mohs micrographic surgery (MMS) is an outpatient procedure that has become the treatment of choice for certain cutaneous malignancies. Although the major steps in this procedure are relatively standardized, one difference involves the use of sterile or nonsterile, clean gloves during the tumor removal phase.
This retrospective chart review study was performed to evaluate whether infection rates are affected by the use of sterile versus nonsterile gloves in the tumor extirpation phase of MMS.
This study evaluated the surgical records of 1,810 consecutive Mohs patients, of which 1,239 Mohs patients (1,400 Mohs procedures) met inclusion criteria. Age, sex, tumor diagnosis, anatomic location, number of Mohs stages, area of the defect, closure type, cartilage exposure, and sterile versus nonsterile glove use were recorded and evaluated.
Twenty-five infections were identified. Statistically significant infection rates were discovered for patients with cartilage fenestration with secondary healing and malignant melanoma diagnosis only. There was no statistical difference in infection rates with all other measured variables to include the use of sterile or clean, nonsterile gloves. | Is sterile versus nonsterile gloves during Mohs micrographic surgery : infection rate affected? | No. Our study lends support to the contention that clean, nonsterile gloves are safe and effective for use in the tumor extirpation phase of MMS, at a significant cost savings. | PASS | pubmedQA | 1 |
12048081 | With the evolution of anesthesia and surgical procedures, fast track extubation has gained an increased interest, mainly based on the possibility of reducing health costs seemingly without compromising patient care.
To compare two groups of patients submitted to a non-fast track extubation and a fast track extubation protocol after coronary artery bypass graft surgery with cardiopulmonary bypass, regarding their times of ventilation and intubation and their complication rates in the postoperative period.
During the year of 1998, 323 sequential patients scheduled for isolated coronary artery bypass graft surgery with cardiopulmonary bypass were enrolled in the study. Fifty-nine patients were excluded due to preoperative use of emergent mechanical and/or inotropic hemodynamic support, low body mass index (< or =18-20 kg/m(2)), reoperations for acute surgical complications, off-pump coronary artery bypass graft surgery, severe respiratory disease, recent myocardial infarction (< or =7 days) and absence of relevant data. Previous myocardial infarction (> or =7 days), prophylactic intraaortic balloon pump and use of postoperative vasoactive drugs were not exclusion criteria. We compared 76 patients sequentially submitted to anesthesia by one of the authors with a fast track extubation protocol and 188 patients sequentially submitted to anesthesia by others in the same period and using a conventional anesthetic protocol.
Demographic data, previous medical and cardiac history, preoperative medication and operative data were all similar between the two groups. The mean ventilation and intubation times were significantly shorter in the fast track extubation group than in the non-fast track extubation patients (30 min vs. 7 h and 50 min vs. 8 h, respectively). Forty-two percent of patients in the fast track extubation group were extubated on arrival at the intensive care unit. Morbidity and mortality were similar in both groups. | Does early extubation increase complication rates after coronary artery bypass graft surgery with cardiopulmonary bypass? | No. The study shows that a very fast track extubation protocol may be safely implemented in patients submitted to coronary artery bypass graft surgery with cardiopulmonary bypass. | PASS | pubmedQA | 1 |
22648653 | Vitamin D plays a key role in maintaining bone health, but evidence for its nonskeletal effects is inconsistent. This study aims to examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and all-cause mortality in a large general population cohort.
Using the computerized database of the largest health care provider in Israel, we identified a cohort of subjects 20 years old or older with serum 25(OH)D levels measured between January 2008 and December 2009. Vital status was ascertained through August 2011.
Median follow-up was 28.5 months (interquartile range 23.8-33.5 months); 7,247 of 182,152 participants (4.0%) died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8 ± 24.2 nmol/liter) than those alive at the end of follow-up (51.0 ± 23.2 nmol/liter), P < 0.001. After adjustment for age, gender, ethnicity, and seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 [95% confidence interval (CI) 1.89-2.15] for the lowest serum 25(OH)D quartile (<33.8 nmol/liter) compared with the highest. After further adjustment for comorbidity, use of vitamin D supplements and statins, smoking, socioeconomic status, and body mass index, the HR was 1.81 (95% CI 1.69-1.95). This remained, even after adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium level (corrected for serum albumin levels), and glomerular filtration rate, 1.85 (95% CI 1.70-2.01). The fully adjusted HR associated with being in the second 25(OH)D quartile (33.8-49.4 nmol/liter) was 1.25 (95% CI 1.16-1.34). | Is the risk of all-cause mortality inversely related to serum 25 ( OH ) D levels? | Yes. All-cause mortality is independently and inversely associated with serum 25(OH)D levels at levels less than 50 nmol/liter. | PASS | pubmedQA | 1 |
14600003 | self-reported disability reflects physical, environmental and attitudinal factors. We have previously reported the empirical identification of three simple tests to provide an index of (ambulatory) mobility-related physiological limitations (MOBLI). Evidence of the MOBLI 's responsiveness over time has been presented. Evidence of the predictive validity of the index is needed.
we aimed to measure the predictive validity for future mortality of the MOBLI and of self-reported mobility disability in a longitudinal cohort study.
data are from the sixth annual interview for two sites in the Established Populations for Epidemiologic Studies of the Elderly study. Included were 3,040 people, with information about self-reported walking difficulties, walking speed, time to complete five chair stands and peak expiratory flow. Age- and sex-adjusted death rates over a 4-year follow-up were computed, and proportional hazards regression models were used in the analysis.
the MOBLI score is associated with subsequent mortality over 4 years, with evidence of a 'dose-response' relationship. The predictive value for mortality of the MOBLI score is similar to that of self-reported mobility disability in the studied population. | Does the predictive validity for mortality of the index of mobility-related limitation -- result from the EPESE study? | Yes. the 'objective' MOBLI index has predictive validity as a continuous or dichotomised measure of the physiological component of mobility limitation in older populations. Given its empirical basis and face validity, predictive validity and responsiveness to change, MOBLI should be considered for local validation and use in epidemiological comparisons of older populations across countries or over longer periods of time. | PASS | pubmedQA | 1 |
20472097 | Although the most commonly recognized symptoms of gastroparesis (GP) are nausea and vomiting, patients also report abdominal pain. We aimed to define the prevalence, severity, and quality of abdominal pain in GP and to correlate abdominal pain with gastric emptying (GE) and quality of life.
Patients presumed to have GP underwent 4-hour GE scintigraphy and upper endoscopy examinations and completed the following: patient assessments of gastrointestinal symptoms (Patient Assessment of Upper Gastrointestinal Symptom Severity Index), abdominal pain questionnaires (Short-Form of the McGill Pain Questionnaire), and quality-of-life questionnaires.
The study group consisted of 68 patients (58 female; 10 male) with delayed GE (18 diabetic gastroparesis [DG] and 50 idiopathic gastroparesis [IG]). Abdominal pain was present in 90% of patients (89% DG, 90% IG) and nausea was present in 96% (100% DG, 94% IG). Abdominal pain was epigastric in 43% and umbilical in 13%. Pain occurred daily in 43% and was constant in 38%. Pain often was induced by eating (72%), was nocturnal (74%), and interfered with sleep (66%). Severity ranking of symptoms based on the Patient Assessment of Upper Gastrointestinal Symptom Severity Index was as follows: abdominal fullness (3.8 +/- 0.2), bloating (3.6 +/- 0.2), nausea (3.6 +/- 0.2), upper abdominal discomfort (3.3 +/- 0.2), upper abdominal pain (3.0 +/- 0.2), and vomiting (2.2 +/- 0.2). Abdominal pain severity did not correlate with GE, but had moderate correlation with quality of life. | Is abdominal pain a frequent symptom of gastroparesis? | Yes. Abdominal pain is a frequent symptom in patients with GP, comparable with nausea and vomiting. Abdominal pain correlates with impaired quality of life but not with GE. | PASS | pubmedQA | 1 |
25244167 | We believe this to be the first documented report of multiple endocrine neoplasia type-1 (MEN-1) in which the diagnosis was suspected based purely on cutaneous findings. The patient was initially referred to the dermatology department for cosmetic concerns and had no overt symptoms, laboratory abnormalities, or known family history of MEN-1.
The patient is a 28-year-old man who was referred to the dermatology department for evaluation and removal of skins lesions, later confirmed by biopsy to be facial angiofibromas and a truncal collagenoma. This combination of cutaneous findings was suspicious for a genodermatosis and genetic testing subsequently confirmed the diagnosis of MEN-1. The patient was referred for appropriate follow up and surveillance. | Do incidental angiofibromas prompt a diagnosis of multiple endocrine neoplasia type-1 ( MEN-1 )? | Yes. This case highlights the importance of vigilance on the part of dermatologists to be aware of subtle skin findings that may be characteristic of rare disorders and may have gone unrecognized by other providers and the patients themselves. In this respect, dermatologists are in a unique position given their specialized training in the recognition of inherited skin disorders. An early diagnosis of an inherited disorder, especially one with increased risk of malignancy, can allow for appropriate surveillance and potentially alter the course of the disease. | PASS | pubmedQA | 1 |
18780322 | Physician-reported performance status (PS) is an important prognostic factor and frequently influences treatment decisions. To the authors' knowledge, the extent, prognostic importance, and predictors of disagreements in PS assessment between physicians and patients have not been adequately examined.
Using North Central Cancer Treatment Group (NCCTG) clinical trial data from 1987 through 1990, the authors compared PS (Eastern Cooperative Oncology Group [ECOG] and Karnofsky [KPS]) and nutrition scores reported by physicians and patients individually. Differences were analyzed using a Student t test for paired data and degree of disagreement by kappa statistic. The effect of disagreement on overall survival was determined by the Kaplan-Meier method and Cox regression analysis. Predictors of disagreement were identified by logistic regression.
In all, 1636 patients with advanced lung and colorectal cancer had a median survival of 9.8 months (95% confidence interval [95% CI], 9.4-10.4 months). Percent disagreement between patients and physicians regarding KPS, ECOG PS, and nutrition score were 67.1%, 56.6%, and 58.0%, respectively. Physicians were more likely to rate patients better than individual patients were to rate themselves: ECOG (mean 0.91 vs 1.30; P < .0001), KPS (mean 83.3 vs 81.7; P < .0001), and nutrition score (mean 1.6 vs 2.1; P < .0001). Disagreement between patients and their physicians was associated with increased risk of death: KPS (hazards ratio [HR] of 1.16; 95% CI, 1.04-1.30 [P = .008]) and nutrition scores (HR of 1.44; 95% CI, 1.29-1.61 [P < .0001]) after adjustment for covariates. Patient sociodemographic factors that predict disagreement were identified. | Is patient-physician disagreement regarding performance status associated with worse survivorship in patients with advanced cancer? | Yes. Physicians and patients frequently disagree regarding PS and nutritional status. Disagreement is associated with an increased risk of death in patients with advanced malignancies. These findings illustrate the limitations of physician-only assessed PS. | PASS | pubmedQA | 1 |
24668496 | Previous animal studies demonstrated that hepatocyte growth factor (HGF) has the potential to regenerate scarred vocal folds. In addition, HGF is now produced under a good manufacturing practice (GMP) procedure. Therefore, human clinical trials of HGF are warranted in patients with vocal fold scarring. In the current study, we investigated the pharmacokinetics and the local tissue responses of HGF administered to rat vocal folds.
Prospective animal experiment.
Five μg of recombinant human HGF was administered to the vocal folds of Sprague-Dawley rats (n = 60) using a microsyringe. The concentration of HGF in larynges and blood was investigated by enzyme-linked immunosorbent assay. To evaluate the local tissue responses caused by HGF administration, endoscopic and histological examinations were performed.
HGF concentration in the larynges was 50.1 μg/g tissue 5 minutes after administration. The concentration decreased rapidly to 1.71 μg/g tissue at 12 hours after administration and to 0.29 ng/g tissue at 24 hours after administration. Seven days after administration, HGF concentration was minimal in one-half of the cases and was not detected in the other cases. Transmission of HGF to blood was detected in two of six cases at 5 minutes after administration, but was no longer detected 12 hours later. Endoscopic and histological examinations revealed no edema or erythema of the vocal folds in any of the cases. | Does pharmacokinetics and safety of human recombinant hepatocyte growth factor administered to vocal fold? | Yes. The current results contribute to the safety and pharmacokinetic management of future clinical trials using HGF administered to vocal folds. | PASS | pubmedQA | 1 |
16556668 | Limited data are available on intestinal MALT lymphoma owing to its relatively rare occurrence. The frequency of associated genetic changes was therefore analysed in intestinal MALT lymphoma to determine whether primary and secondary examples may be distinguished by their genetic profile.
Patients diagnosed with MALT lymphoma involving the intestine were evaluated and compared with 71 cases with localised gastric MALT lymphoma. Paraffin embedded samples were evaluated for t(11;18)(q21;q21) by reverse transcription polymerase chain reaction, and by fluorescence in situ hybridisation for t(14;18)(q32;q21), t(1;14)(p22;q32), and trisomies 3 and 18.
30 consecutive patients with MALT lymphoma involving the intestine were identified: 16 had primary intestinal lymphoma and 14 had secondary MALT lymphoma. t(11;18)(q21;q21) was found in one third of the patients, but there was a significant difference between the secondary MALT lymphomas and the primary intestinal and gastric MALT lymphoma groups (57% v 12.5%, p = 0.019, and 57% v 24%, p = 0.022). Two patients with primary intestinal MALT lymphomas were positive for t(1;14)(p22;q32) and none was positive for t(14;18)(q32;q21). Primary intestinal MALT lymphoma had a significantly higher frequency of trisomies 3 or 18 (81% v 36%, p = 0.024; 81% v 14%, p<0.001), in contrast to secondary intestinal MALT lymphomas and localised gastric MALT lymphomas. | Do mALT lymphoma associated genetic aberrations occur at different frequencies in primary and secondary intestinal MALT lymphomas? | Yes. The genetic profile of primary intestinal MALT lymphomas appears to be different from that of secondary intestinal or local gastric MALT lymphomas. Because of the high prevalence of trisomy 3 or 18, or both, in primary intestinal lymphoma, these numerical aberrations might be regarded as a genetic hallmark of the disease. | PASS | pubmedQA | 1 |
26452389 | Body mass index (BMI) in childhood predicts obesity in adults, but it is unknown whether rapid increase and variability in BMI during childhood are independent predictors of adult obesity.
The study cohort consisted of 1622 Bogalusa Heart Study participants (aged 20 to 51 years at follow-up) who had been screened at least four times during childhood (aged 4-19 years). BMI rate of change during childhood for each individual was assessed by mixed models; BMI residual standard deviation (RSD) during childhoodwas used as a measure of variability. The average follow-up period was 20.9 years.
One standard deviation increase in rate of change in BMI during childhood was associated with 1.39 [95% confidence interval (CI): 1.17-1.61] kg/m(2) increase in adult BMI and 2.98 (95% CI: 2.42-3.56) cm increase in adult waist circumference, independently of childhood mean BMI. Similarly, one standard deviation increase in RSD in BMI during childhood was associated with 0.46 (95% CI: 0.23-0.69) kg/m(2) increase in adult BMI and 1.42 (95% CI: 0.82-2.02) cm increase in adult waist circumference. Odds ratio for adult obesity progressively increased from the lowest to the highest quartile of BMI rate of change or RSD during childhood (P for trend < 0.05 for both). | Are variability and rapid increase in body mass index during childhood associated with adult obesity? | Yes. Rapid increase and greater variability in BMI during childhood appear to be independent risk factors for adult obesity. Our findings have implications for understanding body weight regulation and obesity development from childhood to adulthood. | PASS | pubmedQA | 1 |
16351738 | Structure prediction of membrane proteins is still a challenging computational problem. Hidden Markov models (HMM) have been successfully applied to the problem of predicting membrane protein topology. In a predictive task, the HMM is endowed with a decoding algorithm in order to assign the most probable state path, and in turn the labels, to an unknown sequence. The Viterbi and the posterior decoding algorithms are the most common. The former is very efficient when one path dominates, while the latter, even though does not guarantee to preserve the HMM grammar, is more effective when several concurring paths have similar probabilities. A third good alternative is 1-best, which was shown to perform equal or better than Viterbi.
In this paper we introduce the posterior-Viterbi (PV) a new decoding which combines the posterior and Viterbi algorithms. PV is a two step process: first the posterior probability of each state is computed and then the best posterior allowed path through the model is evaluated by a Viterbi algorithm. | Does a new decoding algorithm for hidden Markov models improve the prediction of the topology of all-beta membrane proteins? | Yes. We show that PV decoding performs better than other algorithms when tested on the problem of the prediction of the topology of beta-barrel membrane proteins. | PASS | pubmedQA | 1 |
21113014 | The inversa type of recessive dystrophic epidermolysis bullosa (RDEB-I) is a rare variant of dystrophic epidermolysis bullosa, characterised by blistering in the body flexures, trunk, and mucosa. The cause of this specific distribution is unknown. So far, 20 COL7A1 genotypes have been described in RDEB-I and genotype-phenotype correlations have not been studied extensively. The aim of the study was to gain more insight into the pathophysiology of this intriguing RDEB-I phenotype.
Twenty Dutch and British RDEB-I patients, and full genotypes in 18 of them, were identified. The literature on RDEB-I genotypes was reviewed and an extensive genotype-phenotype correlation study for RDEB-I was conducted.
All 20 patients had generalised blistering at birth and during early infancy. In most patients, the age of transition from generalised to inversa distribution was before the age of 4 years. A spectrum of disease severity, ranging from the mildest 'mucosal only' phenotype to the severest phenotype with limited acral involvement, was noted. The 29 genotypes of these RDEB-I patients and those reported in the literature revealed that RDEB-I is associated with specific recessive arginine and glycine substitutions in the triple helix domain of type VII collagen. | Is the inversa type of recessive dystrophic epidermolysis bullosa caused by specific arginine and glycine substitutions in type VII collagen? | Yes. Why these specific arginine and glycine substitutions cause the inversa distribution remains unknown. It was not possible to identify clear differences in location and nature of substituting amino acids between these mutations and missense mutations causing other RDEB phenotypes. It is hypothesised that the higher skin temperature in the affected areas plays an important role in the pathophysiology of RDEB-I. | PASS | pubmedQA | 1 |
17762289 | Quantitative study of elastin content in nondegenerate and degenerate human intervertebral discs.
To measure the site-specific changes in elastin content that accompany disc degeneration using a quantitative, dye-binding assay to assess elastin levels.
Recently, an abundant and organized network of elastic fibers was observed in nondegenerated human disc using immunostaining histochemistry, suggesting a functional role for elastin. While degenerative changes in the disc extracellular matrix composition are well known, changes in elastin content that may accompany degeneration have not been reported.
Human discs were assigned a degenerative grade by 3 independent orthopedic surgeons based on gross morphology. Samples were taken from the outer anulus fibrosus (OAF), inner AF (IAF) and nucleus pulposus (NP). Elastin content was measured using a specific, dye-binding assay and normalized to dry weight and collagen content, which was measured via a hydroxyproline assay. Samples were divided into 2 groups: nondegenerate (Grades 1-2.5) and degenerate (Grades 2.6-4.0). A 2-way analysis of variance was used to test for statistical significance where the 2 factors were disc location and degeneration. Correlations of composition with degeneration and age were analyzed.
In nondegenerate tissue, elastin by dry weight was on average 2.0% +/- 0.3%, and there were no differences in elastin content among the locations of OAF, IAF, or NP. With degeneration, there was a significant increase in total disc elastin per dry weight at each location. The degenerate IAF had the largest amount of elastin (9.3% +/- 2.3%), significantly greater than the NP and OAF. Elastin content correlated with degenerative grade and age at each site. | Does elastin content correlate with human disc degeneration in the anulus fibrosus and nucleus pulposus? | Yes. Based on the location-dependent degenerative changes, with highest increases in the IAF, elastin may function to restore lamellar structure under radial loads that potentially cause delamination. Future work will focus on distinguishing the changes in elastin orientation with degeneration and understanding the mechanical functional role of elastin in the disc. | PASS | pubmedQA | 1 |
26103960 | Environmental enteropathy is subclinical inflammation of the upper gastrointestinal tract associated with reduced linear growth in developing countries. Usually investigators have used biopsy or a dual sugar absorption test to assess environmental enteropathy. Such tests are time and resource intensive, restricting their utility as screening methods. Serum endotoxin core antibody (EndoCab) concentration is a potential indicator of intestinal inflammation and integrity, and thus may be useful to predict environmental enteropathy. We analyzed the association of serum EndoCab levels versus linear growth and lactulose-mannitol assay results in 2-5 year old rural Malawian children.
This was an observational study of 388 rural, asymptomatic Malawian children who had anthropometric measurements taken at least every 3 months since birth. In June and July 2011, dual sugar permeability tests were performed and serum samples were drawn for EndoCab assays. Pearson correlation, Student's t test and multivariable linear regression were used to compare ln EndoCab concentrations with height-for-age z scores (HAZ) at time of sampling and 3 months later. Identical analysis was also performed for ln EndoCab versus measurements from dual sugar permeability testing performed in conjunction with serum sampling. In a subgroup of children with anthropometric data in the months prior to serum sampling, Pearson correlation was used to estimate the relationship between ln EndoCab and recent linear growth.
Ln EndoCab concentrations were not correlated with HAZ at time of measurement (B = -0.078, P = 0.14) nor change in HAZ over the subsequent 3 months HAZ (B = -0.018, P = 0.27). EndoCab concentration was not associated with %lactulose excretion (B < 0.001, P = 0.98) nor the lactulose:mannitol ratio (B = 0.021, P = 0.62). Subgroup analysis also did not reveal any significant association between EndoCab and recent growth. | Are plasma endotoxin core antibody concentration and linear growth unrelated in rural Malawian children aged 2-5 years? | Yes. EndoCab titers were not correlated with measurements of growth or intestinal permeability in rural pre-school aged Malawian children. | PASS | pubmedQA | 1 |
18451223 | Recent studies of cancer metastasis have focused on the role of premetastatic gene expression and circulating tumor cells. We did a blind prospective study in gastric cancer to assess the significance of isolated tumor cells (ITC) and to test the hypothesis that vascular endothelial growth factor receptor-1 (VEGFR-1) is expressed within the bone marrow at tumor-specific, premetastatic sites.
Both bone marrow and peripheral blood samples from 810 gastric cancer patients were collected at the Central Hospital, National Cancer Center (Tokyo, Japan). The samples were transferred to Kyushu University Hospital (Beppu, Japan) where they were analyzed by quantitative real-time reverse transcription-PCR for three epithelial cell markers, carcinoembryonic antigen, cytokeratin-19, and cytokeratin-7, as well as VEGFR-1.
ITCs were observed in peripheral blood and bone marrow even in early stages of gastric cancer. The frequency of ITC in bone marrow was significantly associated with the stage of disease by ANOVA (P < 0.01). Gastric cancer metastasized when ITCs were observed in the presence of VEGFR-1. In the 380 patients who were ITC negative and showed low VEGFR-1 expression, synchronous (at the time of surgery) and heterochronous (recurrent) metastases were not observed. | Does hematogenous metastasis in gastric cancer require isolated tumor cells and expression of vascular endothelial growth factor receptor-1? | Yes. ITCs circulate even in early stages of disease. Furthermore, elevated expression of VEGFR-1 facilitates the establishment of hematogenous metastases in gastric cancer. This study indicates that the simultaneous presence of ITC and VEGFR-1 expression at premetastatic sites is clinically significant for disease progression. | PASS | pubmedQA | 1 |
22483414 | Helicobacter pylori is known to affect the host's nutritional status. This study was performed to elucidate the relationship between H. pylori status and the dynamics of the ghrelin system, in the context of ghrelin O-acyltransferase (GOAT) expression.
We conducted a clinical study of 30 subjects focusing on the following points: 1) the effects of H. pylori infection on the concentrations of circulating ghrelin isoforms and on ghrelin and GOAT mRNA expression in the gastric mucosa, and 2) the effects of H. pylori eradication on the same parameters.
The plasma acyl-ghrelin and desacyl-ghrelin concentrations of 16 H. pylori positive participants were significantly lower than those of 14 H. pylori negative controls. The acyl-ghrelin/desacyl-ghrelin ratio was not significantly different between the H. pylori positive and H. pylori negative participants. The levels of ghrelin and GOAT mRNA in the gastric mucosa were significantly lower in the H. pylori positive participants than in the H. pylori negative controls. In 11 subjects in whom H. pylori eradication was successful, their plasma acyl-ghrelin levels tended to increase after H. pylori eradication, but the difference was not significant; however, their plasma desacyl-ghrelin levels were significantly reduced. Although gastric ghrelin mRNA expression increased significantly after H. pylori eradication, gastric GOAT mRNA expression tended to increase but was not significantly altered. | Are plasma ghrelin isoforms and gastric ghrelin O-acyltransferase expression influenced by Helicobacter pylori status? | Yes. H. pylori status might affect the host's nutritional status through changes in the plasma levels of ghrelin isoforms and the gastric expression levels of ghrelin and GOAT mRNA. | PASS | pubmedQA | 1 |
23994111 | HIV rapid testing programs in New York State (NYS) are required to collect a specimen for confirmation of a preliminary positive result; however, some venues have limited capacity to collect venous blood, and confirmation using oral fluid is restricted by cost and availability.
To evaluate the feasibility of using dried blood spots (DBS) at non-clinical HIV rapid testing sites for Western blot testing.
The New York State Department of Health facilitated registration of 48 non-clinical HIV test sites and provided training on DBS procedures. Following a reactive rapid test, DBS were collected by fingerstick onto filter paper cards, dried and mailed to the NYS public health laboratory for Western blot testing.
From October 2010 to December 2012, 280 DBS specimens were submitted for confirmation. Four (1.4%) were unsatisfactory for testing and 276 (98.6%) DBS were tested. Of these, 235 (85.1%) were positive, 37 (13.4%) were negative and 4 (1.4%) were indeterminate. During this period, the laboratory also received 1033 venous blood specimens for rapid test confirmation, and 35 (3.4%) were unsatisfactory. Of the 998 tested by Western blot, 784 (78.6%) were positive, 197 (19.7%) were negative and 17 (1.7%) were indeterminate. | Is expansion of HIV screening to non-clinical venues aided by the use of dried blood spots for Western blot confirmation? | Yes. Compared to venous blood, the percentage of rapid test referral specimens with a positive Western blot was significantly greater for DBS specimens and the frequency of unsatisfactory specimens did not differ significantly. These results indicate that DBS are a suitable alternative to venous blood for confirmation of HIV rapid tests conducted at non-clinical sites. | PASS | pubmedQA | 1 |
25246784 | Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD), which has been related to systemic inflammation. It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion.
To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD.
Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients. Systemic inflammation was assessed from serum C reactive protein (CRP) and circulating total and differential leukocyte counts. Nutritional depletion was defined as a body mass index (BMI) less than 21 kg/m(2) and/or fat-free mass index (FFMI) less than 15 or 17 kg/m(2) in women and men, respectively. FFMI was calculated as the fat-free mass (FFM) corrected for body surface area. Measurements were repeated in 94 patients after a median 16-month follow-up. Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation.
Nutritional depletion occurred in 37% of patients. Lung function was worsened in patients with nutritional depletion compared to those without (forced expiratory volume in 1 second 1.17 L versus 1.41 L, mean difference 0.24, 95% confidence interval 0.10 to 0.38, P<0.01). There were no differences in airway inflammation and bacterial colonization in patients with and without nutritional depletion. At baseline, BMI correlated positively with serum CRP (rs=0.14, P=0.04). Change in weight and change in FFM over time could not be predicted from baseline patient characteristics. | Is systemic and pulmonary inflammation independent of skeletal muscle changes in patients with chronic obstructive pulmonary disease? | Yes. Nutritional depletion and progressive muscle atrophy are not related to airway inflammation or bacterial colonization. Overspill of pulmonary inflammation is not a key driver of muscle atrophy in COPD. | PASS | pubmedQA | 1 |
11450018 | Spreading depression (SD) is known to go along with temporary breakdown of ion gradients and cell swelling which spontaneously normalizes. Here, the effects of SD at reduced flow conditions as encountered in the ischemic penumbra are examined.
In rats the right carotid artery was permanently occluded. MABP was lowered to 50 mmHg for 30 min. This is sufficient to reduce CBF to penumbra-like conditions in the right hemisphere. The following parameters were assessed: rCBF, DC potential, and tissue impedance. 5 or 15 min after onset of flow reduction one SD wave was initiated by microinjection of KCl. Histology was performed after 7 days.
In animals with hypotension there was depolarization resembling anoxic depolarization after SD induction and an uncoupling of CBF and metabolism only in the right hemisphere. Impedance increased with SD but did not recover spontaneously as long as rCBF remained reduced. 15 min of SD-induced cell swelling was tolerated without permanent damage, whereas 25 min were followed by severe neuron loss in the affected cortex after 7 days. | Does spreading depression induce permanent cell swelling under penumbra conditions? | Yes. The study demonstrates the induction of penumbra conditions in the cortex of one hemisphere. SD is followed by cell swelling which persists as long as flow is critically reduced. The experiments illustrate how peri-infarct depolarizations may detrimentally affect the penumbra. | PASS | pubmedQA | 1 |
27433903 | To determine the role of the aryl hydrocarbon receptor (AHR) in colitis-associated colorectal tumorigenesis.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in United States. Chronic intestinal inflammation increases the risk for the development of CRC. We investigated the involvement of AHR, a ligand-activated transcriptional regulator, in colitis-associated colorectal tumorigenesis.
We used a mouse model of colitis-associated colorectal tumorigenesis that employs treatment with azoxymethane and dextran sodium sulfate. We examined the role of AHR using both an Ahr-deletion mouse model (Ahr) and treatment with the AHR pro-agonist indole-3-carbinol (I3C). Incidence, multiplicity, and location of tumors were visually counted. Tumors were defined as neoplasms. Intestinal inflammation was assessed by quantitative PCR for proinflammatory markers and colon length. Data were evaluated and compared using GraphPad Prism software (version 6, La Jolla, CA).
Tumor incidence was increased 32% in Ahr null mice and tumor multiplicity was approximately increased 3-fold compared with wild-type mice (2.4 vs 7; P < 0.05). Furthermore, tumor multiplicity was reduced 92% by treatment of I3C in wild-type mice, whereas the suppressor effect of I3C was not observed in Ahr null mice (P < 0.05). | Is the Aryl Hydrocarbon Receptor a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse? | Yes. We found that AHR plays a protective role in colitis-associated colorectal tumorigenesis. This conclusion is based on the observations that Ahr null mice showed increased number of colorectal tumors, and mice treated with I3C exhibited fewer tumors. This study supports the use of AHR agonists such as I3C as a chemopreventive therapy for IBD-associated CRC in human patients. | PASS | pubmedQA | 1 |
25182570 | In patients, an association exists between pulmonary diseases and diastolic dysfunction of the left ventricle (LV). We have previously shown that alveolar hypoxia in mice induces LV diastolic dysfunction and that mice exposed to hypoxia have increased levels of circulating interleukin-18 (IL-18), suggesting involvement of IL-18 in development of diastolic dysfunction. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. In this study, we hypothesized that neutralization of IL-18 during alveolar hypoxia would improve LV diastolic function.
Mice were exposed to 10% oxygen for 2 weeks while treated with IL-18BP or vehicle. Cardiac function and morphology were measured using echocardiography, intraventricular pressure measurements and magnetic resonance imaging (MRI). For characterization of molecular changes in the heart, both real-time PCR and Western blotting were performed. ELISA technique was used to measure levels of circulating cytokines.
As expected, exposure to hypoxia-induced LV diastolic dysfunction, as shown by prolonged time constant of isovolumic relaxation (τ). Improved relaxation with IL-18BP treatment was demonstrated by a significant reduction towards control τ values. Decreased levels of phosphorylated phospholamban (P-PLB) in hypoxia, but normalization by IL-18BP treatment suggest a role for IL-18 in regulation of calcium-handling proteins in hypoxia-induced diastolic dysfunction. In addition, MRI showed less increase in right ventricular (RV) wall thickness in IL-18BP-treated animals exposed to hypoxia, indicating an effect on RV hypertrophy. | Does iL-18 neutralization during alveolar hypoxia improve left ventricular diastolic function in mice? | Yes. Neutralization of IL-18 during alveolar hypoxia improves LV diastolic function and partly prevents RV hypertrophy. | PASS | pubmedQA | 1 |
23290291 | Even though fever is a common symptom in childhood, it often worries parents and they may try to reduce discomfort by giving the child paracetamol, which is currently the most commonly sold over-the-counter medicine. The objective of this study was to investigate parent-administered paracetamol in toddlers during a winter-period in relation to symptoms, doctor contacts and severity-rated illness.
The study was conducted as a prospective diary study covering a three-month winter-period. It comprised a cohort of 183 infants born in February 2001 in a district of the capital area in Denmark.
According to the parents, a total of 119 toddlers (65%) received paracetamol at least once during the study period; 9.3% of the toddlers received paracetamol for more than ten days. The administration of paracetamol rose as the number of symptoms increased. Paracetamol was given in 37% of days with fever. The most frequent combinations of symptoms to trigger paracetamol administration were fever and earache with a probability of 64%. For the symptoms of vomiting and earache, the probability was 60%. In the rare cases with monosymptomatic fever, some 23% used paracetamol. | Do the majority of sick children receive paracetamol during the winter? | Yes. The majority of ill toddlers received paracetamol if they had several symptoms. However, paracetamol was administrated in 37% of days with fever. This use of paracetamol seems reasonable as the parents differentiate between degrees of illness and withhold paracetamol until the second day of the illness episode. | PASS | pubmedQA | 1 |
8633627 | Nitric oxide is a potent vasorelaxant produced by endothelial cells. We tested the hypothesis that urinary and perhaps plasma nitric oxide metabolites would be reduced in women with preeclampsia.
Plasma and urine from 14 women meeting strict clinical criteria for the diagnosis of preeclampsia and 20 normal nulliparous women were assayed for the stable metabolites of nitric oxide, nitrate and nitrite.
There was no significant difference of plasma concentrations of nitrate and nitrite between women with preeclampsia and women with normal pregnancies (32.7 +/- 3.1 vs 25.8 +/- 2.4 micromol/L). Plasma creatinine levels were elevated in women with preeclampsia (0.85 +/- 0.09 vs 0.66 +/- 0.02 mg/dl, p<0.01), indicating a reduced glomerular filtration rate. Urine concentrations of nitrate and nitrite normalized by creatinine excretion were significantly lower in women with preeclampsia compared with normal pregnant women (0.37 +/- 0.06 vs 0.69 +/- 0.11 micromol of nitrite per milligram creatinine, p. <0.05). | Are urine but not plasma nitric oxide metabolites decreased in women with preeclampsia? | Yes. Our study using concomitant measurement of plasma and urine nitrate and nitrite suggests a reduced production of nitric oxide in women with preeclampsia compared with normal pregnant women. | PASS | pubmedQA | 1 |
24456863 | Opiates are widely used for postoperative pain relief. Unfortunately, their side effects such as inhibited gastrointestinal motility and respiratory depression may compromise or delay postoperative recovery after laparotomy. We used paraincisional subcutaneous catheters (PSCs) and applied 0.25% ropivacaine infusion to improve pain relief and decrease postoperative morphine consumption in patients after open surgery for aortic aneurysm.
A retrospective single-center study including 58 patients treated by open surgery for aortic aneurysm between October 2006 and June 2012. Overall, 28 patients (control group) received standard postoperative pain management including opiates, and 30 patients (PSC group) were treated with paraincisional continuous local analgesia with 0.25% ropivacaine administrated via bilateral subcutaneous catheters along with additional ad libitum opiates administration, at first intravenously and then orally.
Patients characteristics as well as perioperative and postoperative outcomes were comparable between the groups during the first 5 days after surgery. Patients of the PSC group received significantly less morphine, although the patients in both groups reported a similar pain intensity. Neither wound-healing disorder nor catheter-associated subcutaneous infection was reported. High serum concentration of ropivacaine was detected in 2 patients (6%) with end-stage renal disease, who developed temporary neurologic symptoms. Length of intensive care unit (ICU) stay was significantly shorter in the PSC group (2 [0-23] vs. 4.5 [0-32] ICU days). | Does paraincisional subcutaneous infusion of ropivacaine after open abdominal vascular surgery show significant advantages? | Yes. This is the first report about PSCs for analgesia after laparotomy. This case/control study shows that continuous paraincisional subcutaneous infusion of 0.25% ropivacaine after open surgery for aortic aneurysm repair is a feasible method of postoperative analgesia. This technique allows sustained pain relief with significant reduction of opiate requirement and faster recovery after surgery. Prospective randomized controlled trial is necessary for the assessment of safety and efficacy of this method. | PASS | pubmedQA | 1 |
27562865 | The tumor-suppressive microRNAs miR-26a and miR-138 are significantly down-regulated in prostate cancer (PCa) and have been identified as direct regulators of enhancer of zeste homolog 2 (EZH2), which is a known oncogene in PCa. In the present study, the influence of miR-26a and miR-138 on EZH2 and cellular function including the impact on the cell cycle regulating network was evaluated in PCa cells.
PC-3 and DU-145 PCa cells were transfected with 100 nM of miRNA mimics, siRNA against EZH2 (siR-EZH2) or control constructs for 4 h. Analyses of gene expression and cellular function were conducted 48 h after transfection.
Both miRNAs influenced the EZH2 expression and activity only marginally, whereas siR-EZH2 led to a notable decrease of the EZH2 expression and activity. Both miRNAs inhibited short- and/or long-term proliferation of PCa cells but showed no effect on viability and apoptosis. In PC-3 cells, miR-26a and miR-138 caused a significant surplus of cells in the G0/G1 phase of 6 and 12 %, respectively, thus blocking the G1/S-phase transition. Treatment with siR-EZH2 was without substantial influence on cellular function and cell cycle. Therefore, alternative target genes involved in cell cycle regulation were identified in silico. MiR-26a significantly diminished the expression of its targets CCNE1, CCNE2 and CDK6, whereas CCND1, CCND3 and CDK6 were suppressed by their regulator miR-138. | Do miR-26a and miR-138 block the G1/S transition by targeting the cell cycle regulating network in prostate cancer cells? | Yes. The present findings suggest an anti-proliferative role for miR-26a and miR-138 in PCa by blocking the G1/S-phase transition independent of EZH2 but via a concerted inhibition of crucial cell cycle regulators. | PASS | pubmedQA | 1 |
26804311 | Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25-44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air-liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense-epithelial cells, alveolar macrophages, and neutrophils-had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up-regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. | Does electronic cigarette inhalation alter innate immunity and airway cytokines while increasing the virulence of colonizing bacteria? | Yes. Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro. Acute exposure to EV decreases macrophage and neutrophil antimicrobial function. Inhalation of EV alters immunomodulating cytokines in the airways of mice. Inhalation of EV leads to increased markers of inflammation in BAL and serum. Staphylococcus aureus become more virulent when exposed to EV. | PASS | pubmedQA | 1 |
21442579 | Intra-aortic balloon pump (IABP) is an established therapy to support patients with heart failure during coronary artery bypass grafting (CABG). The impact of the timing of IABP on the hospital course and on follow-up is of particular clinical interest. The purpose of this study was to analyze the relationship between the time of IABP implantation and its impact on early, mid- and long-term survival in patients with acute myocardial infarction (AMI) who underwent emergent CABG for NSTEMI and STEMI.
A total of 472 patients with AMI (NSTEMI and STEMI) underwent emergency CABG at our institution; 158 of them additionally received IABP support. Fifty-seven (36 %) patients received preoperative and 101 (64 %) patients underwent intraoperative IABP implantation. Endpoints were in-hospital und follow-up (mean duration 37 ± 28 months) survival.
Overall in-hospital mortality was 17.1 % (n = 27): 17.6 % (n = 10) in the preoperative group and 16.8 % (n = 17) in the intraoperative group ( P = ns). Mid- and long-term survival rates were comparable for both groups 78.6 % vs. 73.7 %, 71.4 % vs. 68.7 % and 64.3 % vs. 54.6 % at 1, 3 and 5 years, respectively ( P = ns). | Does intra-aortic balloon pump implantation affect long-term survival after isolated CABG in patients with acute myocardial infarction? | No. This study demonstrates that CABG with IABP support in high-risk patients with AMI can be performed with acceptable in-hospital and long-term survival rates. The decision for IABP placement should consider the preoperative clinical condition and the intraoperative course of each patient. IABP placement does not appear to affect the long-term outcome after isolated CABG in patients with AMI. | PASS | pubmedQA | 1 |
26705411 | Remote sensing products can provide regular and consistent observations of the Earth´s surface to monitor and understand the condition and change of forest ecosystems and to inform estimates of terrestrial carbon dynamics. Yet, challenges remain to select the appropriate satellite data source for ecosystem carbon monitoring. In this study we examine the impacts of three attributes of four remote sensing products derived from Landsat, Landsat-SPOT, and MODIS satellite imagery on estimates of greenhouse gas emissions and removals: (1) the spatial resolution (30 vs. 250 m), (2) the temporal resolution (annual vs. multi-year observations), and (3) the attribution of forest cover changes to disturbance types using supplementary data.
With a spatially-explicit version of the Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3), we produced annual estimates of carbon fluxes from 2002 to 2010 over a 3.2 million ha forested region in the Yucatan Peninsula, Mexico. The cumulative carbon balance for the 9-year period differed by 30.7 million MgC (112.5 million Mg CO | Does choice of satellite imagery and attribution of changes to disturbance type strongly affect forest carbon balance estimates? | Yes. Uncertainty arising from activity data (rates of land-cover changes) can be reduced by, in order of priority, increasing spatial resolution from 250 to 30 m, obtaining annual observations of forest disturbances, and by attributing land-cover changes by disturbance type. Even missing a single year in the land-cover observations can lead to substantial errors in ecosystems with rapid forest regrowth, such as the Yucatan Peninsula. | PASS | pubmedQA | 1 |
23337935 | Little research has been conducted regarding the implications of Sirt1 (a classic III HDAC) in neuropathic pain. The aim of this study was to investigate the variation in the expressions of spinal Sirt1 and acetyl-histone H3 in a rat model of chronic constriction injury.
A neuropathic pain model of chronic constriction injury (CCI) was established in a unilateral hind limb in Sprague-Dawley rats.
Western blot analysis and immunohistochemistry revealed that Sirt1 (silent information regulator) expression decreased, whereas acetyl-histone H3 increased in the spinal cord following CCI surgery. The intrathecal administration of resveratrol, an activator of Sirt1, attenuated CCI-induced mechanical allodynia and thermal hyperalgesia, increased Sirt1 expression, and decreased acetyl-histone H3 in the spine. Resveratrol induced no obvious histopathological changes in the spinal cord. | Does resveratrol facilitate pain attenuation in a rat model of neuropathic pain through the activation of spinal Sirt1? | Yes. Our data provide new evidence for the contribution of spinal Sirt1 to the initiation and maintenance of neuropathic pain. The antinociceptive effects of resveratrol may be mediated through the activation of spinal Sirt1 in CCI rats. | PASS | pubmedQA | 1 |
27141151 | The present study investigated the effect of different surface treatments on shear bond strength (SBS) of resin cement to zirconia.
Ninety zirconia blocks were prepared and divided into 6 groups of 15 by treatment. Group 1 served as the control group, whereas groups 2 and 3 were treated with air abrasion and a universal primer (Monobond plus), respectively. The remaining zirconia copings were treated with a fractional CO2 laser for 10 seconds using 10 W/10 mJ (group 4), 10 w/14 mJ (group 5) or 20 W/10 mJ (group 6). A luting cement (Clearfil SA) was bonded to the treated zirconia surfaces and cured for 40 seconds. SBS was measured with a universal testing machine and the type of bond failure was determined.
There was a statistically significant difference in SBS among the study groups (p<0.001). The highest SBS values were observed in the groups treated with the fractional CO2 laser at settings of 20 W/10 mJ (28.1 MPa) or 10 W/14 mJ (27.4 MPa), followed by the specimens treated with the universal primer (22.8 MPa). The control specimens exhibited the lowest SBS (9.4 MPa) among the study groups (p<0.05). There was no significant difference in the distribution of failure modes among the groups (p=0.871). | Does surface treatment with a fractional CO2 laser enhance shear bond strength of resin cement to zirconia? | Yes. The application of fractional CO2 laser can improve bond strength of resin cement to zirconia ceramic, and thus it could be considered as an appropriate alternative to conventional methods of zirconia surface treatment. | PASS | pubmedQA | 1 |
24066107 | Nociceptin/orphanin FQ and its receptor (NOP) are involved in immune responses, inflammation and pain processing. The aim of this study was to investigate the modulation of NOP and prepro-nociceptin (PNoc), the precursor of nociceptin, by inflammatory mediators in human whole blood.
Peripheral blood from healthy volunteers was cultured for 0, 3, 6 and 24 hrs with or without lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10 or interferon (IFN)-γ. NOP and PNoc mRNA of peripheral white blood cells were detected by quantitative RT-PCR. Cytokine concentrations in supernatants of whole blood cultures were measured using ELISA. In addition, an intervention experiment using anti-cytokine antibodies was conducted to evaluate possible mechanisms involved in the modulation of NOP and PNoc by LPS. The primary goal was to investigate NOP and PNoc mRNA expression in human peripheral blood under inflammatory conditions.
LPS significantly suppressed NOP (median area under the mRNA-expression-time curve (1(st)/3(rd) quartile): 5.4 (4.6/6.6) normalized ratio · hr) and PNoc expression (40.8 (34.4/49.5)) compared to baseline measures (NOP: 22.7 (17.1/25.3); PNoc: 69.9 (58.4/89.2), both p<0.001). LPS incubation induced cytokine concentrations (TNF-α, IL-1β, IL-10 and IFN-γ) in whole blood cultures. Incubation with TNF-α, IL-1β, IL-10 or IFN-γ decreased NOP mRNA levels to varying extents (p<0.05 for all). In contrast, PNoc mRNA expression was decreased by IL-10 only (p = 0.018). The LPS effect on NOP expression could be antagonized by anti-TNF-α and anti-IL-1β, whereas anti-IL-10 and anti-INF-γ had no effect. There was no change of PNoc expression when LPS induced cytokines were antagonized by the respective antibodies. | Do inflammatory mediators influence the expression of nociceptin and its receptor in human whole blood cultures? | Yes. LPS as well as cytokines suppress mainly NOP and, in part, PNoc mRNA expression in human whole blood cultures. This may represent a negative feedback loop to the previously described upregulation of cytokines by PNoc. | PASS | pubmedQA | 1 |
22298725 | In 2 landmark publications, the Institute of Medicine reported on significant deficiencies in our current health care system. In response, an area of research examining the role of the physical environment in influencing outcomes for patients and staff gained momentum. The concept of evidence-based design has evolved, and the development of structural guidelines for new hospital construction was instituted by the American Institute of Architects in 2006.
To determine perceptions of patients and their families of evidence-based design features in a new heart center.
Hospitalized patients and their families, most of whom were in intensive care and step-down units, were surveyed and data from the Hospital Consumer Assessment of Healthcare Providers and Systems were reviewed to determine perceptions of evidence-based design features incorporated into a new heart center and to assess patients' satisfaction with the environment. Results Responses were reviewed and categorized descriptively. Five general environment topics of focus emerged: privacy, space, noise, light, and overall atmosphere. Characteristics perceived as being dissatisfying and satisfying are discussed. | Do patients and their families weigh in on evidence-based hospital design? | Yes. Critical care nurses must be aware of the current need to recognize how much the physical environment influences care delivery and take steps to maximize patients' safety, satisfaction, and quality of care. | PASS | pubmedQA | 1 |
9817368 | Hypospadias is a common urogenital malformation in boys. The etiology is unknown but genetic and environmental factors are involved. Because monozygotic twins have the same genetic constitution, we studied disease discordant twin pairs to evaluate environmental risk factors while controlling for genetic effects.
We used questionnaires to identify 28 male twins discordant for hypospadias at 4 pediatric surgical clinics in Sweden. Using deoxyribonucleic acid fingerprinting, and histopathological examination of the placenta and fetal membranes 18 twin pairs were diagnosed as monozygotic.
In 16 of the 18 monozygotic pairs discordant for hypospadias the twin with the lowest birth weight has hypospadias. Mean difference in birth weight was 498 gm. (t = 3.8, p <0.01). | Is hypospadias related to birth weight in discordant monozygotic twins? | Yes. Environmental factors associated with low birth weight are involved in the etiology of hypospadias. | PASS | pubmedQA | 1 |
12515417 | To determine if chefs' and student chefs' attitudes, knowledge, and practices regarding healthful food preparation are consistent with the Dietary Guidelines for Americans.
An analytical survey questionnaire was distributed to 4 chef groups. Sections 1 and 2 of the survey measured chefs' food science knowledge (13 questions) and likelihood of using food preparation practices (15 questions) necessary to meet the 1990 Dietary Guidelines for Americans. Section 3 (22 questions) measured chefs' attitudes toward nutrition in general, toward the importance of healthful food preparation practices, and toward the US Dietary Guidelines.
Of 512 surveys distributed by mail, at culinary meetings, and in classes at 2 culinary schools, 447 (86%) were returned (158 from practicing chefs and 289 from student chefs). Practicing chefs included chef educators, foodservice chefs from a national corporation, and independent chef members of the American Culinary Federation of New York City.
Descriptive statistics included frequencies, means, and standard deviations of survey items and of individual survey sections. Reliability and validity were determined using alpha coefficients and principal components analysis. Analysis of variance was used to examine differences in practice, attitudes, and knowledge among chef groups.
Both practicing chefs and student chefs answered more than 70% of the food science questions correctly; independent chefs scored significantly lower than educator and corporate chefs. More than two thirds of the chefs and student chefs correctly responded to questions about the nutrient composition of food and how cooking affects the nutrient content of food. All chef groups were confused about fat and cholesterol in food and in the body. Few healthful food preparation practices were likely to be used by any chef group more than two thirds of the time, although the subscale of the attitude toward the importance of these practices was very positive. The majority of practicing chefs thought that customers do not care about the US Dietary Guidelines and nutrition; student chefs thought that customers do care. Both groups strongly agreed that, as chefs, they are responsible for the nutritional content of the food they prepared. | Are chefs ' attitudes toward healthful food preparation more positive than their food science knowledge and practices? | Yes. Both chefs and student chefs are willing to learn about food science and recipe modification principles as they apply to healthful cooking practices. The opportunities are clear: Dietitians have the expertise to teach chefs healthful food preparation techniques, recipe modification, and food composition information. | PASS | pubmedQA | 1 |
22922655 | Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli.
We tested whether prophylaxis with colchicine , an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD.
Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels.
Colchicine significantly decreased lung damage as determined by the MLI in the hyperoxia groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-α and IL-1β levels compared with the hyperoxia group (p < 0.05). | Does colchicine protect against hyperoxic lung injury in neonatal rats? | Yes. Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD. | PASS | pubmedQA | 1 |
23731651 | Calcitonin gene-related peptide (CGRP) is a potent arterial and venous vasodilator. Increased airway epithelial cell expression of CGRP, together with increased CCL17 expression, was previously observed in a model of provoked asthma in atopic human subjects.
We sought to determine whether CCL17 induces CCR4-dependent CGRP synthesis and secretion by human airway epithelial cells.
Human airway epithelial cell lines (BEAS-2B and A549) and human primary airway cells were cultured with CCL17 or various other cytokines, and CGRP expression was measured by using RT-PCR, quantitative immunofluorescence, and enzyme immunoassay. CCR4 expression was determined in cultured cells by using flow cytometry and in bronchial biopsy specimens by using immunohistochemistry.
CCL17 induced a several thousand-fold increase in CGRP mRNA expression and released peptide product from BEAS-2B and A549 cells in a time- and concentration-dependent fashion. Concentration-dependent CCL17-induced release of CGRP by primary human airway epithelial cells was also observed. Under comparable conditions, CCL17 induced greater CGRP release from BEAS-2B cells than either IL-13, a cytokine mixture (TNF-α, GM-CSF, and IL-1), or CCL22. CCR4 was expressed by BEAS-2B and A549 cells and internalized after ligation with CCL17. CCL17-induced CGRP release was inhibited by a specific anti-CCR4 blocking antibody. Bronchial biopsy specimens obtained from healthy volunteers and asthmatic patients before and after provoked asthma all exhibited CCR4 staining of equivalent intensity, indicating that the receptor is constitutively expressed. | Does cCL17/thymus and activation-regulated chemokine induce calcitonin gene-related peptide in human airway epithelial cells through CCR4? | Yes. CCL17-induced, CCR4-dependent release of CGRP by human airway epithelial cells represents a novel inflammatory pathway and a possible target in patients with asthma and allergic disease. | PASS | pubmedQA | 1 |
24549772 | Age, sex, and medical comorbidities may be associated with differences in patient-reported outcome scores after THA. Highest level of education may be a surrogate for socioeconomic status, but the degree to which this is associated with patient-reported outcomes after THA is not known.
We investigated the national Swedish Hip Arthroplasty Register for the association of education attainment on patient-reported outcomes 1 year after THA; specifically, we evaluated level of education attainment against health-related quality of life (HRQoL), pain reduction, and satisfaction with treatment 1 year after THA.
All THAs for osteoarthritis performed from 2005 through 2007 with complete patient-reported outcome measures (representing 49% of the THAs performed for this diagnosis) were selected from the Swedish Hip Arthroplasty Register. These cases were merged with national databases containing education attainment, marital status, and comorbidities (n = 11,464; mean age of patients, 64 years). The patient-reported outcome measure protocol included the HRQoL measure EuroQol five-dimension scale (EQ-5D), a VAS for pain, the Charnley classification survey, and a VAS addressing THA satisfaction. Linear regression analyses determined the association of preoperative patient factors with patient-reported outcomes.
High education attainment was associated with higher HRQoL (EQ-5D index ß(high) = 0.03 ± 0.01; EQ VAS ß(high) = 2.6 ± 0.5) after THA, whereas those with low and medium education were at risk for lower HRQoL. High education was associated with less pain after treatment (ß(high) = -3.3 ± 0.05). Individuals with low or medium education were at risk for less satisfaction with THA (p < 0.001). | Is education attainment associated with patient-reported outcomes : findings from the Swedish Hip Arthroplasty Register? | Yes. Our results suggest clinicians should support patients with low and medium education to a greater extent. Identification of patients who will benefit most from THA and educating those at risk for poorer outcomes, like patients with low and medium education, ultimately may improve patient satisfaction, HRQoL, pain, and the cost utility of THA. | PASS | pubmedQA | 1 |
10837391 | Nitric oxide donors reduce intraocular pressure. Human trabecular cells in culture were examined for their nitric oxide production in response to hydraulic pressure.
Human trabecular cells were cultured from trabeculum tissue fragments excised during trabeculectomy and exposed to hydraulic pressure change in a culture flask connected to a glass syringe. The pressure was exerted by automatic infusion of the piston of the syringe and monitored by a pressure gauge. The intracellular nitric oxide level was measured in real time with a nitric oxide binding fluorescent dye, diaminofluorescein-2.
Intracellular nitric oxide levels in cultured trabecular cells showed spontaneous fluctuation during 400 seconds of observation. Peak levels of intracellular nitric oxide were significantly higher at hydraulic pressure of 30, 40, and 50 mm Hg, compared with 0 and 25 mm Hg (p<0.0001, one way ANOVA, and p<0.05, Tukey-Kramer test). The fluctuation was completely abolished by the presence of N-methyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor. The cultured trabecular cells were shown by immunohistochemistry to express brain nitric oxide synthase (bNOS). | Is basal nitric oxide production enhanced by hydraulic pressure in cultured human trabecular cells? | Yes. Higher levels of hydraulic pressure enhanced basal production of nitric oxide in human trabecular cells. Nitric oxide would be a physiological mediator in the regulation of intraocular pressure. | PASS | pubmedQA | 1 |
22248422 | Vascular risk factors (VRFs) are known to cause cerebral microvascular disease, but evidence supporting an effect of VRFs on regional brain atrophy is mixed. We investigate whether an aggregation of VRFs is associated with volume of hippocampus and entorhinal cortex in elderly people living in the community.
This cross-sectional study consists of 523 participants (age ≥60 years, 59.3% women) of the SNAC-K Study in central Stockholm, Sweden, who were free of clinical stroke and cognitive impairment. We collected data on VRFs through interviews, clinical examination and inpatient register system. Hippocampal and entorhinal cortex volume was manually measured on magnetic resonance images. Data were analysed with general linear regression models controlling for demographics and total intracranial volume.
In men, high total cholesterol and diabetes were significantly or marginally associated with smaller hippocampus and entorhinal cortex; when current smoking, binge alcohol drinking, high cholesterol and diabetes were aggregated, an increasing number of VRFs were significantly associated with decreasing volume of hippocampus and entorhinal cortex (P for linear trend <0.01). In women, none of individual VRFs or their aggregation was significantly associated with the volume of these brain regions, except former smoking that was significantly associated with a larger volume of these regions. | Is medial temporal lobe vulnerable to vascular risk factors in men : a population-based study? | Yes. Aggregation of VRFs is associated with reduced hippocampal and entorhinal cortex volume in apparently healthy elderly men, but not in women. This implies that in men, the medial temporal lobe is vulnerable to cardiovascular risk factors. | PASS | pubmedQA | 1 |
23463625 | This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC).
Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m(2)/day 1 plus capecitabine 1000 mg/m(2) bid/days 1-14 or with irinotecan 200 mg/m(2)/day 1 plus capecitabine 800 mg/m(2) bid/days 1-14 both every 21 days. The primary end point was 6 months progression-free survival (PFS).
A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx-bevacizumab: n = 127; mCapIri-bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%-84%) and 84% (95% CI, 77%-90%). Median PFS and OS were 10.4 months (95% CI, 9.0-12.0) and 24.4 months (95% CI, 19.3-30.7) with CapOx-bevacizumab, and 12.1 months (95% CI, 10.8-13.2) and 25.5 months (95% CI, 21.0-31.0) with mCapIri-bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab. | Is capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab effective and safe as first-line therapy for metastatic colorectal cancer : a randomized phase II study of the AIO colorectal study group? | Yes. Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri. | PASS | pubmedQA | 1 |
23803600 | Connective tissue growth factor (CTGF) is a key mediator of tissue fibrogenesis in kidney disease. Its involvement in renal allograft fibrosis was recently demonstrated in a mouse model.
We prospectively studied the association between urinary CTGF (CTGFu) levels and renal allograft fibrosis during the first 2 years after transplantation. Histologic and biochemical data were collected from 315 kidney transplant recipients enrolled in a protocol biopsy-based clinical program.
At 3, 12, and 24 months after transplantation, CTGFu levels were independently associated with the degree of interstitial fibrosis in protocol biopsies, scored according to the revised 1997 Banff criteria. In a subgroup of 164 patients with pristine biopsies at 3 months, higher CTGFu levels at 3 months were associated with moderate and severe interstitial fibrosis developed at 24 months after transplantation. | Is urinary connective tissue growth factor associated with human renal allograft fibrogenesis? | Yes. As it is readily quantifiable in urine, a role for CTGFu as a noninvasive candidate biomarker and predictor of human renal allograft fibrogenesis deserves further study. | PASS | pubmedQA | 1 |
25901973 | Macrophages are key players in inflammatory bowel diseases (IBD). This study aimed to determine site-specific effects of defined macrophage subtypes on the integrity of the intestinal epithelial barrier.
Macrophage subtypes in situ in intestinal specimens of patients with IBD were visualized by immunohistochemistry. In vitro polarization of human peripheral CD14 cells yielded M1 or M2 macrophages. The influence of primary monocytes or macrophage subtypes on epithelial barrier integrity was analyzed by transepithelial resistance measurements, Western blot analysis, confocal laser scanning microscopy, and cytometric bead array in a coculture model of primary human macrophages and layers of intestinal epithelial cell lines.
The lamina propria of the inflamed intestine in patients with IBD, predominantly in Crohn's disease, is massively infiltrated by CD68 cells also positive for inducible nitric oxide synthase and tumor necrosis factor (TNF) α. The presence of M1 macrophage shifted the balance in the local macrophage compartment towards a proinflammatory state. In the coculture model, monocytes and M1 macrophages reduced transepithelial resistance as a marker for epithelial barrier integrity. The mechanisms for paracellular leakage included intracellular relocalization of tight junction proteins like claudin-2 and epithelial cell apoptosis. Determined by specific cytokine blockade, M1 macrophages exerted their deleterious effect mainly through TNF-α, whereas monocyte-mediated damage was driven by the inflammasome effector cytokines, interleukin-1β and interleukin-18. | Does monocyte and M1 Macrophage-induced Barrier Defect contribute to Chronic Intestinal Inflammation in IBD? | Yes. Lamina propria monocytes and M1 macrophages invading intestinal tissues directly contribute to disrupting the epithelial barrier through deregulation of tight junction proteins and induction of epithelial cell apoptosis, thus driving intestinal inflammation in IBD. | PASS | pubmedQA | 1 |
23212294 | To investigate whether cluster headache (CH) was a risk factor for depression in a nationwide population-based follow-up study. Background There are few studies about the relationship between CH and depression, and prior research has been limited by cross-sectional studies or small sample sizes.
We identified 673 CH patients from the Taiwan National Health Insurance database between 2005 and 2009. The two comparison cohorts included age-, sex- and Charlson's score-matched migraine patients (n = 2692) and controls (patients free from migraine or CH, n = 2692). The cumulative incidence of depression was compared among these three cohorts until the end of 2009. We also calculated predictors of depression in the CH cohort.
After the median 2.5-year follow-up duration, the CH cohort had a greater risk for developing depression compared to the control cohort (adjusted hazard ratio; aHR = 5.6, 95% CI 3.0-10.6, p < 0.001) but not the migraine cohort (aHR = 1.1, 95% CI 0.7-1.7, p = 0.77). Of the CH patients, the number of cluster bout periods per year was a risk factor for depression (aHR = 3.8, 95% CI 2.6-5.4, p < 0.001). | Is cluster headache associated with an increased risk of depression : a nationwide population-based cohort study? | Yes. Our results showed that CH is associated with an increased risk for depression. The strength of this association is similar to that of migraine. | PASS | pubmedQA | 1 |
25876638 | To explore the influence of hydrogen sulfide on the intestinal biological barrier, by applying exogenous hydrogen sulfide and hydrogen sulfide synthase inhibitor for the treatment of rats with severe burn injury.
One hundred and four SD rats were divided into sham injury (SI, n = 8), burn control (BC, n = 32), sodium hydrosulfide (SH, n = 32), and propargylglycine groups (PPG, n = 32) according to the random number table. Rats in group SI were sham injured without fluid resuscitation. Rats in the latter 3 groups were inflicted with 30% TBSA full-thickness scald (referred to as burn below) on the back and intraperitoneally injected with 40 mL/kg balanced salt solution immediately after injury. Rats in groups SH and PPG were respectively intraperitoneally injected with SH (56 µmol/kg) and PPG (45 mg/kg) within 1 hour post injury. From post injury day (PID) 2, SH (56 µmol/kg) and PPG (45 mg/kg) were respectively intraperitoneally injected once a day to rats in groups SH and PPG. Eight rats from groups BC, SH, and PPG were sacrificed on PID 2, 7, 14 and 21, and ceca samples were collected. Ceca samples were added to the appropriate culture medium after being homogenized and diluted, for the culture of Bifidobacterium, Lactobacillus, Enterococcus, Enterobacter, and Candida albicans. The content of bacteria was calculated after the bacteria number was counted. The same procedure was performed for rats in group SI. Data were processed with logarithmic function, one-way analysis of variance, analysis of variance of factorial design, and SNK-q test.
On each PID, the content of Bifidobacterium and Lactobacillus in the ceca of each group with burned rats was less than that of group SI (with q values from 4.12 to 20.74, P values below 0.05); while the content of Enterococcus, Enterobacter, and Candida albicans was more than that of group SI (with q values from 2.84 to 68.29, P values below 0.05). Compared with that of group BC, the content of Bifidobacterium and Lactobacillus in the ceca of rats in group SH were increased on each PID (with q values from 2.88 to 17.57, P values below 0.05). In group SH, the content of Bifidobacterium peaked as (6.54 ± 0.35) lg (CFU/g) on PID 7, the content of Lactobacillus peaked as (7.25 ± 0.71) lg (CFU/g) on PID 21. Compared with that of group BC, the content of Enterococcus, Enterobacter, and Candida albicans in the ceca of rats in group SH was reduced on each PID (with q values from 2.79 to 29.59, P values below 0.05). Compared with that of group BC, the content of Bifidobacterium and Lactobacillus in the ceca of rats in group PPG was decreased on each PID (with q values from 2.82 to 46.56, P values below 0.05); while the content of Enterococcus, Enterobacter, and Candida albicans was significantly increased on each PID (with q values from 2.93 to 41.42, P values below 0.05). In group PPG, the content of Enterococcus peaked as (9.41 ± 0.22) lg (CFU/g) on PID 21, the content of Enterobacter peaked as (9.96 ± 0.24) lg (CFU/g) on PID 14, and that of Candida albicans peaked as (3.94 ± 0.84) lg (CFU/g) on PID 14. | Do [ Influence of hydrogen sulfide on the intestinal biological barrier of rats with severe burn injury ]? | Yes. Exogenous hydrogen sulfide can subdue the growth of pathogenic bacteria while promote that of probiotics, thus helping maintain the integrity of intestinal biological barrier of rats with burn injury. | PASS | pubmedQA | 1 |
24117047 | Loop diuretics are widely used to inhibit the Na(+), K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.
Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR.
When added to the intracellular solution, loop diuretics inhibited CFTR Cl(-) currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl(-) channels with 'very fast' speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with 'intermediate' speed and drug-induced blocking events were distinct from channel closures. | Are loop diuretics open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics? | Yes. Structure-activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity. | PASS | pubmedQA | 1 |
26927248 | Poor ovarian response to ovarian hyperstimulation is one of the biggest challenges in assisted reproduction technology. Although many stimulation protocols have been established to improve clinical outcomes in poor ovarian responders (PORs), which protocol is the most effective remains controversial. Luteal-phase ovarian stimulation (LPOS) has been used in normal ovarian responders with satisfactory outcomes. However, the efficacy of LPOS in PORs is unclear. This study aimed to compare the efficacy of LPOS and GnRH antagonist (GnRH-ant) in PORs.
The clinical parameters in PORs who received LPOS (50 cycles in 39 patients) or GnRH-ant (158 cycles in 123 patients) were compared.
Compared with those in the GnRH-ant group, the PORs in the LPOS group showed significantly fewer basal antral follicles (3.1 ± 2.2 vs. 4.1 ± 1.6, p < 0.001) and a higher in vitro fertilization rate. There were no significant differences in the numbers of retrieved oocytes and D3 transferable embryos between the two groups. However, the pregnancy rate in the LPOS group (46.4%) was significantly higher than that in the GnRH-ant group (25.8% overall; 22.9% from fresh embryos and 29.6% from frozen embryos). Moreover, 23 PORs in the LPOS group underwent oocyte retrieval twice in one cycle, and the numbers of retrieved oocytes and transferable embryos from the luteal phase were significantly higher than those from the follicular phase in the same menstrual cycle. | Is luteal-phase ovarian stimulation a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol : A retrospective study? | Yes. Compared with the GnRH-ant protocol, the LPOS protocol may be a better regime for PORs that can increase the numbers of retrieved oocytes and transferable embryos as well as the pregnancy rate. | PASS | pubmedQA | 1 |
11208455 | We examined previously the genomic structure of the human natriuretic peptide receptor type B (hNPRB) gene and reported a C2077T polymorphism located in exon 11 of the gene. We now have studied the C2077T polymorphism in myocardial infarction [MI] patients and non-MI [control] subjects to evaluate the value of this polymorphism as a marker for MI.
302 subjects (163 MI patients and 139 non-MI age-matched control subjects) were studied. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition.
The distribution of C2077T polymorphism genotypes in the MI patients (CC:CT:TT, 47.2%:41.1%:11.7%) was not significantly different from that in the control patients (CC:CT:TT, 53.2%:40.3%:6.5%) (chi 2 = 2.73, p = NS). Allele frequencies of the C2077T polymorphism were f(C/T) 68.2%/31.8% in the MI group and 73.4%/26.6% in the control group. However, no association was found between this polymorphism and clinical diagnosis of MI. | Is a C2077T polymorphism of the type B human natriuretic peptide receptor gene associated with myocardial infarction? | No. Our data indicate that the C2077T polymorphism is not a useful marker of the relation between the hNPRB gene and MI in the Japanese and variations of the hNPRB gene that may be in linkage disequilibrium with this polymorphism do not play a causative role in MI. | PASS | pubmedQA | 1 |
23456798 | MicroRNAs (miRNAs) play critical roles in tumor development and progression. The finding that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. For the current study, the authors investigated the miRNA expression profile of gastric adenocarcinomas and compared it with esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma.
miRNA expression profiles were obtained using 2 different proprietary microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated miRNAs and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time polymerase chain reaction was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas compared with normal gastric mucosa or esophageal mucosa, respectively.
The deregulation of miR-146b-5p, miR-375, miR-148a, miR-31, and miR-451 was associated significantly with gastric adenocarcinomas. Conversely, deregulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. It was noteworthy that miR-200a was significantly down-regulated in gastric adenocarcinoma samples (P = .04) but was up-regulated in esophageal adenocarcinoma samples (P = .001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor stage of gastric cancer. | Does gastric adenocarcinoma have a unique microRNA signature not present in esophageal adenocarcinoma? | Yes. Gastric adenocarcinoma displayed a unique miRNA signature that distinguished it from esophageal adenocarcinoma. This specific signature may reflect differences in the etiology and/or molecular signaling in these 2 closely related cancers. The current findings suggest important miRNA candidates that can be investigated for their biological functions and for their possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma. | PASS | pubmedQA | 1 |
14970115 | Secretoneurin is an abundant neuropeptide of the central, peripheral, and autonomic nervous systems, located in nerve fibers characterized by a close interaction with blood vessels and known to stimulate endothelial cell migration.
We hypothesized that secretoneurin might act as an angiogenic cytokine and tested for these effects in vivo using a mouse cornea neovascularization model and in vitro by assessing capillary tube formation in a matrigel assay. In vivo, secretoneurin-induced neovasculature is characterized by a distinct pattern of arterial and venous vessels of large diameter and length. Immunohistochemical staining for CD-31 revealed endothelial lining of the inner surface of these vessels, and recruitment of alpha-smooth muscle actin-positive perivascular cells suggests vessel maturation. In vitro, secretoneurin-induced capillary tube formation was dose dependent and specific, confirming that effects of secretoneurin occur directly on endothelial cells. Secretoneurin also stimulated proliferation and exerted antiapoptotic effects on endothelial cells and activated intracellular phosphatidylinositol 3' kinase/Akt and mitogen-activated protein kinase pathways, as demonstrated by increased phosphorylation of Akt and extracellular signal-regulated kinase. | Does the neuropeptide secretoneurin act as a direct angiogenic cytokine in vitro and in vivo? | Yes. These data show that secretoneurin represents a novel direct angiogenic cytokine and reiterate the coordinated relationship between nervous and vascular systems. | PASS | pubmedQA | 1 |
21912616 | Severe malaria is difficult to differentiate from other forms of malaria or other infections with similar symptoms. Any parameter associated to malaria-attributable severe disease could help to improve severe malaria diagnosis.
This study assessed the relation between erythropoietin (EPO) and malaria-attributable severe disease in an area of Mozambique with moderate malaria transmission. 211 children <5 years, recruited at Manhiça District Hospital or in the surrounding villages, were included in one of the following groups: severe malaria (SM, n = 44), hospital malaria without severity (HM, n = 49), uncomplicated malaria (UM, n = 47), invasive bacterial infection without malaria parasites (IBI, n = 39) and healthy community controls (C, n = 32). Malaria was diagnosed by microscopy and IBI by blood/cerebrospinal fluid culture.
Mean EPO concentration in the control group was 20.95 U/l (SD = 2.96 U/l). Values in this group were lower when compared to each of the clinical groups (p = 0.026 C versus UM, p<0.001 C vs HM, p<0.001 C vs SM and p<0.001 C vs IBI). In the 3 malaria groups, values increased with severity [mean = 40.82 U/l (SD = 4.07 U/l), 125.91 U/l (SD = 4.99U/l) and 320.87 U/l (SD = 5.91U/l) for UM, HM and SM, respectively, p<0.001]. The IBI group [mean = 101.75 U/l (SD = 4.12 U/l)] presented lower values than the SM one (p = 0.002). In spite of the differences, values overlapped between study groups and EPO levels were only associated to hemoglobin. Hemoglobin means of the clinical groups were 93.98 g/dl (SD = 14.77 g/dl) for UM, 75.96 g/dl (SD = 16.48 g/dl) for HM, 64.34 g/dl (SD = 22.99 g/dl) for SM and 75.67 g/dl (SD = 16.58 g/dl) for IBI. | Are erythropoietin levels independently associated with malaria-attributable severe disease in Mozambican children? | No. Although EPO levels increase according to malaria severity and are higher in severe malaria than in bacteremia, the utility of EPO to distinguish malaria-attributable severe disease is limited due to the overlap of values between the study groups and the main role of hemoglobin in the expression of EPO. | PASS | pubmedQA | 1 |
10985887 | Little is known about the impact of neoadjuvant chemotherapy on cell-mediated immunity in patients with advanced cervical cancers.
We have studied 24 patients with advanced cervical cancer submitted to neoadjuvant chemotherapy (CT) using cis-platinum (100 mg/m(2)/cycle) and bleomycin (30 mg/cycle). The cell-mediated immunity parameters available before and after CT were NK cells, CD4(+)/CD28 and CD8(+)/CD28 T-lymphocyte numbers, PBMC cytotoxicity, and modification of this parameter with "in vitro" addition of IL-12.
The number of NK cells was higher before CT (P < 0.008) in 13 patients who presented a good clinical response to treatment, compared to 11 patients with a poor clinical response. In addition, PBMC cytotoxicity (P < 0.001), CD4(+) and CD8(+) T-lymphocyte values (P < 0.0047), and CD8(+)/CD28(+) cells were also higher in the group with a good response compared with the group with a poor response. Addition of IL-12 to the medium increased the lytic capacity of PBMC after CT only in the group with a good clinical response (P < 0.05). | Is nK cell activity in the presence of IL-12 a prognostic assay to neoadjuvant chemotherapy in cervical cancer? | Yes. NK cell numbers, CD8(+) T-cell levels, and CD8(+)/CD28(+) cell levels can be used as prognostic factors before CT. Our results suggest that patients with a poor response have lower lytic activity per NK cell and are refractory to IL-12 stimulation, probably as a result of the reduced expression of IL-12 receptors or of an intracellular defect in the mechanism of transduction. These observations also provide support for human clinical trials of IL-12 and neoadjuvant CT in patients with cervical cancer. | PASS | pubmedQA | 1 |
22632167 | Previous studies reported that social phobia is associated with a history of child maltreatment. However, most of these studies focused on physical and sexual maltreatment whilst little is known about the specific impact of emotional abuse and neglect on social anxiety. We examined the association between emotional maltreatment, including parental emotional maltreatment as well as emotional peer victimization, and social anxiety symptoms in subjects with various degrees of social anxiety.
The study was conducted as a web-based Internet survey of participants (N = 995) who had social anxiety symptoms falling within the high range, and including many respondents who had scores in the clinical range. The assessment included measures of child maltreatment, emotional peer victimization, social anxiety symptoms and general psychopathology.
Regression and mediation analyses revealed that parental emotional maltreatment and emotional peer victimization were independently related to social anxiety and mediated the impact of physical and sexual maltreatment. Subjects with a history of childhood emotional maltreatment showed higher rates of psychopathology than subjects with a history of physical maltreatment. | Is emotional but not physical maltreatment independently related to psychopathology in subjects with various degrees of social anxiety : a web-based internet survey? | Yes. Although our findings are limited by the use of an Internet survey and retrospective self-report measures, data indicated that social anxiety symptoms are mainly predicted by emotional rather than physical or sexual types of victimization. | PASS | pubmedQA | 1 |
20476566 | Try to observe the plasticity of neuron in primary cortex of rat evoked by conditioned stimulus of different sound level.
Applying conventional electrophysiological technique of extracellular recording to investigate the plasticity of characteristic frequency (CF) and frequency turning curve (FIC) of neurons in rat auditory cortex (AC) by determining CF shifts of neurons caused by sound stimulus of different sound level.
When the frequency difference between conditioned stimulus (CS) frequency and the CF of neuron was in 1.0 kHz, the plasticity of CF induced by CS was associated with sound level. The probability of the plasticity of CF evoked by CS of higher sound lever was more than the lower. And the probability was dependent on frequency turning curve (FTC) and almost independent on the sound level of conditioned signal. | Does [ Sound level of conditioned stimulus differ the plasticity of characteristic frequency in the rat cortical neurons ]? | Yes. Sound level of conditioned stimulus differs the plasticity of characteristic frequency of neurons in rat auditory cortex. | PASS | pubmedQA | 1 |
11426979 | The correlation between the gene expression of various angiogenic factors and in vitro invasive activity in 16 human gynecological cancer cell lines was investigated.
Semiquantitative reverse transcription polymerase chain reaction analysis was performed to investigate the mRNA expression levels of vascular endothelial growth factors (VEGF-A, -B, -C, and -D), basic fibroblast growth factor (bFGF), and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay.
Expression of VEGF-A mRNA was detected in all 16 cell lines, whereas the relative expression levels of other VEGF family members and bFGF, differed markedly among the cell lines. There was a statistical correlation between VEGF-C gene expression and the number of cells that migrated and invaded (P < 0.01). However, expression of mRNAs of other angiogenic factors did not correlate with motility and invasive activity of the cells. Moreover, there was a close correlation between VEGF-C and MMP-2 gene expression levels (P < 0.05). | Is vascular endothelial growth factor C gene expression closely related to invasion phenotype in gynecological tumor cells? | Yes. Tumor cells that produce VEGF-C may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers. | PASS | pubmedQA | 1 |
25613127 | Diabetic macular ischaemia (DMI) is an important cause of visual loss in patients with diabetes, but its relationship to the larger retinal vessels is unknown. We examined whether retinal vessel calibre is related to DMI.
Clinic-based case-control study of patients with type 2 diabetes. The presence and severity of DMI was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols from fundus fluorescein angiographic (FFA) images. Custom software was used to quantify the greatest linear dimension and area of the foveal avascular zone (FAZ). Retinal vessel calibre was measured using a semi-automated software on fundus fluorescein images.
Of 53 patients examined, 18 (34%), 18 (34%) and 17 (32%) had no/mild, moderate and severe DMI, respectively. Persons with moderate or severe DMI had narrower mean retinal arteriolar calibre than persons with no/mild DMI (140.6 μm 95% confidence interval (CI) 134.7, 146.4 versus 150.7 μm, 95% CI 142.5, 158, p = 0.04). The association remained after multivariate adjustment for age, gender, previous panretinal photocoagulation, neovascularization at the disc and elsewhere and diabetic retinopathy severity. Increased FAZ size was also associated with narrower arteriolar calibre. Retinal venular calibre and arteriole to venule ratio (AVR) were not associated with DMI. | Is diabetic macular ischaemia associated with narrower retinal arterioles in patients with type 2 diabetes? | Yes. Retinal arteriolar narrowing was associated with moderate-to-severe macular ischaemia in eyes with diabetic retinopathy. This suggests that larger vessels other than capillaries may also be associated with DMI. | PASS | pubmedQA | 1 |
24366505 | The relationship of cerebral saturation measured by near-infrared spectroscopy with serum biomarker of brain injury S100B was investigated in infants undergoing cardiac surgery with cardiopulmonary bypass.
Prospective cohort study.
Single-center children's hospital.
Forty infants between 1 and 12 months old weighing greater than or equal to 4 kg with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass were enrolled.
None.
Serum S100B was measured at eight time points over 72 hours using enzyme-linked immunosorbent assay. Physiologic data including arterial, cerebral, and somatic regional oxygen saturations measured by near-infrared spectroscopy were synchronously recorded at 1-minute intervals from anesthesia induction through 72 postoperative hours. The arterial-cerebral oxygen saturation difference was calculated as the difference between arterial saturation and cerebral regional saturation. Thirty-eight patients, 5.4 ± 2.5 months old, were included in the analysis; two were excluded due to the use of postoperative extracorporeal membrane oxygenation. Seventeen patients (44.7%) had preoperative cyanosis. S100B increased during cardiopulmonary bypass in all patients, from a median preoperative baseline of mean ± SE: 0.055 ± 0.038 to a peak of 0.610 ± 0.038 ng/mL, p less than 0.0001. Patients without preoperative cyanosis had a higher S100B peak at the end of cardiopulmonary bypass. Although the absolute cerebral regional saturation on cardiopulmonary bypass was not associated with S100B elevation, patients who had arterial-cerebral oxygen saturation difference greater than 50 at any time during cardiopulmonary bypass had a higher S100B peak (mean ± SE: 1.053 ± 0.080 vs 0.504 ± 0.039 ng/mL; p < 0.0001). | Do changes in cerebral oxygen saturation correlate with S100B in infants undergoing cardiac surgery with cardiopulmonary bypass? | Yes. A wide cerebral arteriovenous difference measured by near-infrared spectroscopy during cardiopulmonary bypass is associated with increased serum S100B in the perioperative period and may be a modifiable risk factor for neurological injury. | PASS | pubmedQA | 1 |
24998254 | Aliskiren (ALK) is a renin inhibitor that has been used in the treatment of hypertension. The aim of this study was to determine whether ALK could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.
Transverse aortic constriction (TAC) was performed in mice to induce heart pressure overload. ALK (150 mg·kg(-1)·d(-1), po), the autophagy inhibitor 3-methyladenine (10 mg·kg(-1) per week, ip) or the PKCβI inhibitor LY333531 (1 mg·kg(-1)·d-(1), po) was administered to the mice for 4 weeks. Heart hypertrophy, fibrosis and function were evaluated based on echocardiography, histological and biochemical measurements. Mechanically stretched cardiomyocytes of rats were used for in vitro experiments. The levels of signaling proteins were measured using Western blotting, while the expression of the relevant genes was analyzed using real-time QRT-PCR.
TAC induced marked heart hypertrophy and fibrosis, accompanied by high levels of Ang II in plasma and heart, and by PKCβI/α and ERK1/2 phosphorylation in heart. Meanwhile, TAC induced autophagic responses in heart, i.e. increases in autophagic structures, expression of Atg5 and Atg16 L1 mRNAs and LC3-II and Beclin-1 proteins. These pathological alterations in TAC-mice were significantly ameliorated or blocked by ALK administration. In TAC-mice, 3-methyladenine administration also ameliorated heart hypertrophy, fibrosis and dysfunction, while LY333531 administration inhibited ERK phosphorylation and autophagy in heart. In mechanically stretched cardiomyocytes, CGP53353 (a PKCβI inhibitor) prevented ERK phosphorylation and autophagic responses, while U0126 (an ERK inhibitor) blocked autophagic responses. | Does aliskiren ameliorate pressure overload-induced heart hypertrophy and fibrosis in mice? | Yes. ALK ameliorates heart hypertrophy, fibrosis and dysfunction in the mouse model in setting of chronic pressure overload, via suppressing Ang II-PKCβI-ERK1/2-regulated autophagy. | PASS | pubmedQA | 1 |
19284557 | Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA.
A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined.
The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001). | Is rheumatoid cachexia associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis : a cross-sectional study? | Yes. About one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD. | PASS | pubmedQA | 1 |
27033675 | Tip-apex distance (TAD) is reported as a good predictor for cut-outs of lag screws and spiral blades in the treatment of intertrochanteric fractures, and surgeons are advised to strive for TAD within 20 mm. However, the femoral neck axis and the position of the lower limb in the lateral radiograph are not clearly defined and can lead to measurement errors. We propose a refined TAD by defining these factors. The objective of this study was to analyze the reliability of this refined TAD.
The radiographs of 130 prospective cases with unstable trochanteric fractures were used for the analysis of the refined TAD. The refined TAD was independently measured by 2 raters with clinical experience of more than 10 years (rater 1, 2) and 2 raters with much less clinical experience (rater 3, 4) after they received a training about the new measurement method. Intraclass correlation coefficient (ICC [2,4]) was calculated to assess the interrater reliability.
The mean refined TADs were 18.2:18.4:18.2:18.2 mm for rater 1:2:3:4. There was a strong correlation among all four raters (ICC 0.998, (95% CI: 0.998, 0.999). | Does a refined definition improve the measurement reliability of the tip-apex distance? | Yes. Regardless of the clinical experience of raters, the refined TAD is a reliable tool and can be used to develop new TAD recommendations for predicting failure of fixation. Future studies with larger samples are needed to evaluate the predictive value of the refined TAD. | PASS | pubmedQA | 1 |
21134374 | Liver X receptors (LXRs) are lipid-activated nuclear receptors with important roles in cholesterol transport, lipogenesis, and anti-inflammatory signaling. Hepatic stellate cells activate during chronic liver injury and mediate the fibrotic response. These cells are also major repositories for lipids, but the role of lipid metabolism during stellate cell activation remains unclear. We investigated the role of LXR signaling stellate cell activation and susceptibility to fibrotic liver disease.
Immortalized and primary stellate cells purified from mice were treated with highly specific LXR ligands. Carbon tetrachloride and methionine/choline deficiency were used as chronic liver injury models. Reciprocal bone marrow transplants were performed to test the importance of hematopoietically derived cells to the fibrotic response.
LXR ligands suppressed markers of fibrosis and stellate cell activation in primary mouse stellate cells. Lxrαβ(-/-) stellate cells produce increased levels of inflammatory mediators, and conditioned media from Lxrαβ(-/-) cells increases the fibrogenic program of wild-type cells. Furthermore, Lxrαβ(-/-) stellate cells exhibit altered lipid morphology and increased expression of fibrogenic genes, suggesting they are primed for activation. In vivo, Lxrαβ(-/-) mice have marked susceptibility to fibrosis in 2 injury models. Bone marrow transplants point to altered stellate cell function, rather than hematopoietic cell inflammation, as the primary basis for the Lxrαβ(-/-) phenotype. | Is liver X receptor signaling a determinant of stellate cell activation and susceptibility to fibrotic liver disease? | Yes. These results reveal an unexpected role for LXR signaling and lipid metabolism in the modulation of hepatic stellate cell function. | PASS | pubmedQA | 1 |
18193068 | ZP120 (Ac-RYYRWKKKKKKK-NH(2)), is a new partial nociceptin/orphanin FQ (NOP) receptor agonist with sodium-potassium sparing aquaretic effects. The mechanisms of vasodilatation of ZP120 were examined in rat mesenteric resistance arteries.
Arterial segments (internal diameters 206+/-4 microm, n=224) were mounted in microvascular myographs for isometric tension recordings and electrical field stimulation (EFS).
ZP120 and the endogenous NOP receptor ligand, N/OFQ, did not relax arteries contracted with noradrenaline or adenosine-triphosphate. EFS-evoked contractions were inhibited by a purinoceptor antagonist, suramin, and the alpha(1)-adrenoceptor antagonist prazosin. N/OFQ inhibited, concentration-dependently, EFS-evoked contractions with a maximal effect of 52+/-3% (n=8) at 1 microM. The maximal effect of 1 microM ZP120 was lower (27+/-5%, P<0.05, n=9) than for N/OFQ. Endothelial removal or pretreatment with capsaicin did not influence the vasodilator effects of ZP120 and N/OFQ. ZP120 and N/OFQ responses were preserved in the presence of suramin. The alpha(2)-adrenoceptor antagonist, rauwolscine, antagonized the effect of clonidine and brimonidine, but ZP120 and N/OFQ inhibition of EFS-evoked contraction was unaltered. The competitive NOP receptor antagonist, UFP-101 (10 microM), prevented the inhibitory effect of N/OFQ, but not ZP120 suggesting that N/OFQ and ZP120 have distinct modes of interaction with the NOP receptor. | Does zP120 cause relaxation by pre-junctional inhibition of noradrenergic neurotransmission in rat mesenteric resistance arteries? | Yes. Our findings suggest that the vasodilator effect of ZP120 and N/OFQ in rat mesenteric resistance arteries is mediated by prejunctional inhibition of adrenergic neurotransmission. These properties, that promote diuresis and attenuate the cardiovascular consequences of increased sympathetic nerve activity, make ZP120 a promising drug candidate. | PASS | pubmedQA | 1 |
18699941 | The Th2 cytokine interleukin-13 (IL-13) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands.
Interleukin-13 was measured in sputum samples from subjects with COPD (n = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2-4) and controls (n = 14) using ELISA. IL-13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD (n = 10), smoking (n = 10) and nonsmoking controls (n = 8).
Sputum IL-13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL-13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3(+) lymphocytes within bronchial glands in COPD (P = 0.04). | Is induced sputum and bronchial mucosal expression of interleukin-13 increased in chronic obstructive pulmonary disease? | No. Our findings do not support a role for IL-13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease. | PASS | pubmedQA | 1 |
20543553 | Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described.
The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL- 5).
The experimental setup was designed in order to expose samples to a radiofrequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800-900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured.
The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL- 5 cells with respect to basal conditions. | Do electric and magnetic fields modify the biochemical properties of FRTL-5 cells? | No. In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro. | PASS | pubmedQA | 1 |
8822660 | The development of advanced endoscopic instrumentation in recent years has demonstrated the superiority of direct visual examination over radiographic demonstration of various body cavities. Just as laparoscopy has gradually taken a primary role in the surgical investigation of the ovulatory infertile patient, the role of intrauterine endoscopy in comparison to hysterosalpingography (HSG) needs to be reevaluated.
Four hundred and sixty-four infertile women had undergone both hysterosalpingography and a diagnostic hysteroscopy and the findings were analysed.
Compared to hysteroscopy the sensitivity of HSG was 98%, but its specificity only 15%, the positive predictive value 45%, and negative predictive value 95%. On hysteroscopy a normal uterine cavity was found in 53% of the cases with a filling defect and in 56% of those with uterine wall irregularity on HSG. | Is hysteroscopy superior to hysterosalpingography in infertility investigation? | Yes. Hysteroscopy, a safe and rapid direct visualisation of the uterine cavity, is superior to HSG in the identification of intrauterine pathology. In view of the low positive predictive value and the low specificity of the HSG, we believe it should be replaced by the diagnostic hysteroscopy as a first line infertility investigation. | PASS | pubmedQA | 1 |
27342050 | West Nile virus (WNV) is an emerging zoonotic pathogen which is harmful to human and animal health. Effective vaccination in susceptible hosts should protect against WNV infection and significantly reduce viral transmission between animals and from animals to humans. A versatile vaccine suitable for different species that can be delivered via flexible routes remains an essential unmet medical need. In this study, we developed a recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing WNV premembrane/envelope (PrM/E) proteins (designated rLa-WNV-PrM/E) and evaluated its immunogenicity in mice, horses, chickens, ducks and geese.
Mouse immunization experiments disclosed that rLa-WNV-PrM/E induces significant levels of WNV-neutralizing antibodies and E protein-specific CD4+ and CD8+ T-cell responses. Moreover, recombinant rLa-WNV-PrM/E elicited significant levels of WNV-specific IgG in horses upon delivery via intramuscular immunization, and in chickens, ducks and geese via intramuscular, oral or intranasal immunization. | Is newcastle disease virus-vectored West Nile fever vaccine immunogenic in mammals and poultry? | Yes. Our results collectively support the utility of rLa-WNV-PrM/E as a promising WNV veterinary vaccine candidate for mammals and poultry. | PASS | pubmedQA | 1 |
27284688 | Neuroimaging and electrophysiological research have revealed a range of neural abnormalities in autism spectrum disorder (ASD), but a comprehensive understanding remains elusive. We utilized a novel methodology among individuals with ASD and matched controls, combining transcranial magnetic stimulation (TMS) with concurrent electroencephalogram (EEG) recording (TMS-EEG) to explore cortical function and connectivity in three sites implicated in the neuropathophysiology of ASD (dorsolateral prefrontal cortex, primary motor cortex, and temporoparietal junction). As there is evidence for neurobiological gender differences in ASD, we also examined the influence of biological sex.
TMS pulses were applied to each of the three sites (right lateralized) during 20-channel EEG recording.
We did not identify any differences in the EEG response to TMS between ASD and control groups. This finding remained when data were stratified by sex. Nevertheless, traits and characteristics associated with ASD were correlated with the neurophysiological response to TMS. | Does single Pulse Transcranial Magnetic Stimulation-Electroencephalogram reveal No Electrophysiological Abnormality in Adults with High-Functioning Autism Spectrum Disorder? | Yes. While TMS-EEG did not appear to clarify the neuropathophysiology of ASD, the relationships identified between the neurophysiological response to TMS and clinical characteristics warrant further investigation. | PASS | pubmedQA | 1 |
24923251 | The opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception.
We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception.
Etorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg(-1) ), unmasked etorphine (3 mg·kg(-1) ) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg(-1) ) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg(-1) ) and diazepam (1 mg·kg(-1) ). | Is anti-nociception mediated by a κ opioid receptor agonist blocked by a δ receptor agonist? | Yes. Systemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation. | PASS | pubmedQA | 1 |
25216916 | Human bitter taste receptors are encoded by a gene family consisting of 25 functional TAS2R loci. In addition, humans carry 11 TAS2R pseudogenes, some of which display evidence for substantial diversification among species, showing lineage-specific loss of function. Since bitter taste is thought to help prevent the intake of toxic substances, diversity at TAS2R genes could reflect the action of natural selection on the ability to recognize some bitter compounds rather than others. Whether species-specific variation in TAS2R pseudogenes is solely the result of genetic drift or whether it may have been influenced by selection due to different feeding behaviors has been an open question.
In this study, we analyzed patterns of variation at human TAS2R pseudogenes in both African and non-African populations, and compared them to those observable in nonhuman primates and archaic human species. Our results showed a similar worldwide distribution of allelic variation for most of the pseudogenes, with the exception of the TAS2R6P and TAS2R18P loci, both of which presented an unexpected higher frequency of derived alleles outside Africa. At the TAS2R6P locus, two SNPs were found in strong linkage disequilibrium (r2 > 0.9) with variants in the functional TAS2R5 gene, which showed signatures of selection. The human TAS2R18P carried a species-specific stop-codon upstream of four polymorphic insertions in the reading frame. SNPs at this locus showed significant positive values in a number of neutrality statistics, and age estimates indicated that they arose after the homo-chimp divergence. | Does genetic variation in taste receptor pseudogenes provide evidence for a dynamic role in human evolution? | Yes. The similar distribution of variation of many human bitter receptor pseudogenes among human populations suggests that they arose from the ancestral forms by a unidirectional loss of function. However we explain the higher frequency of TAS2R6P derived alleles outside Africa as the effect of the balancing selection acting on the closely linked TAS2R5 gene. In contrast, TAS2R18P displayed a more complex history, suggesting an acquired function followed by a recent pseudogenization that predated the divergence of human modern and archaic species, which we hypothesize was associated with adaptions to dietary changes. | PASS | pubmedQA | 1 |
9551677 | Whether mutations in the putative haemochromatosis gene (HFE) and hepatitis C virus act independently to precipitate porphyria cutanea tarda is unknown. The aim of the study was to investigate the relationship between mutations in HFE, hepatitis C and porphyria cutanea tarda.
The frequencies of the C282Y and H63D mutations in HFE were determined in 27 patients with porphyria cutanea tarda and compared with the reported control frequencies. In addition, the presence of hepatitis C virus infection was identified and related to the patients' HFE status.
The C282Y mutation was found in 44.4% of patients compared with the control frequency of 12% (p<0.001). Three patients were homozygous for the C282Y mutation, two of whom did not meet current clinical diagnostic criteria for expressed haemochromatosis. The proportion of patients with the H63D mutation did not differ from the reported control frequency. The mean transferrin saturation and serum ferritin concentration were similar in porphyria cutanea tarda patients who were homozygous normal and heterozygous for the C282Y mutation, but greater in both groups than previously reported in healthy controls. Seven (25.9%) patients were anti-HCV IgG positive. None of these patients carried the C282Y mutation. Porphyria cutanea tarda patients heterozygous for the C282Y mutation and patients with anti-HCV antibodies had elevated transferrin saturations and serum ferritin concentrations. | Are the C282Y mutation in the haemochromatosis gene ( HFE ) and hepatitis C virus infection independent cofactors for porphyria cutanea tarda in Australian patients? | Yes. The raised frequency of the C282Y mutation in porphyria cutanea tarda indicates that this mutation is likely to be a predisposing factor. However, abnormalities of iron indices also exist in porphyria cutanea tarda patients without mutations in HFE. Hepatitis C virus infection is likely to be another common precipitating factor for porphyria cutanea tarda which acts independently of the C282Y mutation. | PASS | pubmedQA | 1 |
23574883 | Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent.
We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays.
LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did not differ significantly between MS patients and controls. The minor allele frequencies for rs9652490 were 0.171 (95% CI = 0.140-0.201) and 0.167 (95% CI = 0.138-0.196 for cases and controls respectively (p = 0.853). For rs11856808 the minor allele frequencies were 0.317 (95% CI = 0.280-0.355) and 0.310 (95% CI = 0.274-0.346) for cases and controls, respectively (p = 0.773). Allele and genotype frequencies were unrelated with the age of onset of MS, gender, and clinical course of MS. In addition, haplotype analyses did not reveal any putative risk related to haplotypes. | Are lINGO1 rs9652490 and rs11856808 polymorphisms associated with risk for multiple sclerosis? | No. These results suggest that LINGO1 rs9652490 and rs11856808 polymorphisms are not related with risk for MS. This study adds to other published evidence indicating that, to date, the LINGO1 SNPs studied here could be useful risk biomarkers of developing essential tremor, but not other movement disorders. | PASS | pubmedQA | 1 |
20890680 | To date, common therapy in patients with intracranial hemorrhage (ICH) includes prophylaxis of seizure using antiepileptic drugs, commonly phenytoin. Phenytoin therapy is associated with a high incidence of cognitive disturbance. Levetiracetam is known to cause less cognitive disruption and may be a suitable alternative for seizure prophylaxis. Cognitive outcomes in ICH patients receiving seizure prophylaxis with levetiracetam or phenytoin are compared.
A retrospective chart review was conducted with 269 patients who received prophylactic levetiracetam or phenytoin between August 2005 and May 2008. A total of 85 reviewed patients met inclusion criteria (phenytoin n = 25, levetiracetam n = 60).
Statistically significant results included higher Glasgow Coma Scores (GCS) at dismissal (median, 14 vs. 11, P = 0.023), lower seizure incidence (0.0 vs. 8%, P = 0.03) for patients receiving levetiracetam than those treated with phenytoin and patients being discharged home (21.7% vs. 16%, P = 0.03). Observed trends included greater cognitive function retention rate (56.7% vs. 36%, P = 0.08). | Is levetiracetam associated with improved cognitive outcome for patients with intracranial hemorrhage? | Yes. Despite similarities in hemorrhage type and severity at onset, patients receiving levetiracetam had better cognition at discharge and fewer seizures than patients receiving phenytoin. These data suggest that levetiracetam is more effective than phenytoin for seizure prophylaxis without suppression of cognitive abilities in patients with ICH. | PASS | pubmedQA | 1 |
16481245 | Rats with nitrofen-induced congenital diaphragmatic hernia (CDH) have hypoplasia and malformations of the heart. The mechanism of action of nitrofen involves changes in neural crest signaling. Pax3 function is required for cardiac neural crest cells to complete their migration to the developing heart. Vitamin A improves heart hypoplasia. The aims of this study were to examine whether Pax3 expression is decreased in the heart of E13 E15 and E21 rats exposed to nitrofen and if vitamin A reverts this effect.
Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into 2 subgroups according to the subsequent treatment with intragastric vitamin A (15000 IU) or vehicle on E10.5 to E11.5. The pups were recovered on E13, E15 and E21 and the hearts were dissected out. Pax3 mRNA expression was determined by quantitative real time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P < .05.
Pax3 mRNA expression was significantly decreased on E13 and E15 in the hearts of nitrofen-treated embryos and it remained decreased although not significantly on E21. Vitamin A recovered this expression on E13, partially on E15 and above normal levels on E21. | Does vitamin A improve Pax3 expression that is decreased in the heart of rats with experimental diaphragmatic hernia? | Yes. Pax3 is underexpressed in the hearts of nitrofen exposed embryonal rats on days 13th and 15th of gestation and tends to be lower than normal near term. Vitamin A up-regulates this expression on the 3 end points. The mechanism of action of Pax3 should be further investigated because it could be one of the targets for future prenatal transplacental intervention. | PASS | pubmedQA | 1 |
24106773 | Cataract is among the major causes of vision impairment and blindness worldwide. Epidemiological studies support the role of antioxidants in the etiology of cataract, but the evidence for one specific antioxidant over another is inconsistent. Few studies have examined the association of cataract with fruit and vegetable intake with inconclusive results. In the present study, the relationship between cataract and fruit and vegetable intake and dietary and blood levels of carotenoids, vitamins C and E were examined in a Spanish Mediterranean population.
The present work is an analysis of data from 599 elderly ( ≥ 65 years) participants from the Spanish segment of the EUREYE study. This is a European multi-center cross-sectional population-based study. Cataract was diagnosed using a slit-lamp examination and defined as any lens opacity in either eye or evidence of its removal (cataract extraction). Energy-adjusted intake of fruit and vegetables and antioxidant vitamins was estimated using a semi-quantitative food frequency questionnaire. Plasma concentrations of vitamin C were analyzed by a colorimetric method and carotenoids and α-tocopherol by a HPLC method. The associations between cataract and quartiles of fruit and vegetable intake and plasma antioxidants were investigated using logistic regression models.
Of the 599 elderly recruited, 433 (73%) had cataract or cataract extraction, 54% were women and 46% were men. After adjustments, increasing quartiles of combined fruit and vegetable intake were associated with decreasing reduction of odds of cataract or cataract extraction, (P for trend = 0.008). Increasing quartiles of dietary intakes from 107 mg/d of vitamin C showed a significant decreasing association with prevalence of cataract or cataract extraction (P for trend = 0.047). For vitamin E, a protective association was found from intakes from 8 mg/d, but no linear trend was observed across quartiles of intake (P for trend = 0.944). | Are fruit and vegetable intake and vitamins C and E associated with a reduced prevalence of cataract in a Spanish Mediterranean population? | Yes. High daily intakes of fruit and vegetables and vitamins C and E were associated with a significantly decreased of the prevalence of cataract or cataract surgery. This study reinforces the WHO recommendations on the benefits of diets rich in fruit and vegetables. | PASS | pubmedQA | 1 |
17854601 | The retinoblastoma (RB) tumor suppressor is functionally inactivated in most hepatocellular carcinomas (HCC), although the mechanisms by which RB suppresses liver tumorigenesis are poorly defined. We investigated the impact of RB loss on carcinogen-induced liver tumorigenesis.
Mice harboring liver-specific RB ablation and normal littermates were exposed to the hepatocarcinogen diethylnitrosamine (DEN). The influence of RB loss on liver tumorigenesis was assessed by evaluating tumor multiplicity, proliferation, and genome integrity within tumors arising in RB-deficient and wild-type livers. In silico analyses were used to probe the association between gene expression signatures for RB loss and chromosomal instability and the ability of genes up-regulated by RB loss to predict the survival of human HCC patients.
RB deficiency significantly increased tumor multiplicity in livers exposed to DEN. Although hepatocytes in nontumor regions of DEN-exposed livers were quiescent regardless of RB status, tumors arising in RB-deficient livers were significantly more proliferative than those in normal livers and expressed high levels of RB/E2F target genes. Analysis of genes up-regulated by RB loss demonstrated significant overlap with a gene expression signature associated with chromosomal instability. Correspondingly, tumors arising in RB-deficient livers were significantly more likely to harbor hepatocytes exhibiting altered ploidy. Finally, gene expression analysis of human HCCs demonstrated that elevated expression of RB-regulated genes independently predicts poor survival. | Does rB loss abrogate cell cycle control and genome integrity to promote liver tumorigenesis? | Yes. RB deletion in the mouse liver enhances DEN-induced tumorigenesis, associated with increased hepatocyte proliferation and compromised genome integrity. Evaluation of RB status may be a useful prognostic factor in human HCC. | PASS | pubmedQA | 1 |
21892586 | Ageing induces changes in gut microbiota that may affect the quality of life. In this work we analyze the effect of Lactobacillus plantarum CECT 7315/7316 on the regulation of intestinal transit and on nutritional status.
We carried out a double-blind, randomized and controlled by placebo clinical trial. We evaluated the evolution of the weekly defecation frequency and blood levels of total proteins, albumin, cholesterol and reactive C-protein.
Lactobacillus plantarum CECT 7315/7316 helps to regulate intestinal transit and improves the nutritional status in elderly. | Does [ Consumption of the probiotic Lactobacillus planctarum CECT 7315/7316 improve general health in the elderly subjects ]? | Yes. Consumption of functional foods containing L. plantarum CECT 7315/7316 improves the quality of life in elderly subjects. | PASS | pubmedQA | 1 |
21963958 | The Study of Biologic and Immunomodulator-Naïve Patients With Crohn's Disease (SONIC) showed that combination therapy with infliximab and azathioprine (IFX/AZA) is more effective than treatment with IFX alone. Numbers and types of adverse events were roughly equivalent among groups, although enrollment was limited, so it was not clear how rare adverse events might affect overall outcomes in practice. We sought to define the frequency at which a rare adverse event would have to occur for the risks of combination therapy to outweigh the benefits of treatment.
We constructed a decision model to compare the risks and benefits of IFX/AZA with IFX monotherapy. Model parameters were taken from SONIC and other published literature. The base-case analysis was patients with active Crohn's disease who are naïve to both medications (similar to those in SONIC) who were treated for 1 year. We used sensitivity analyses to determine the thresholds at which the risks of side effects from IFX/AZA outweigh its benefits.
During 1 year, the benefits of IFX/AZA would outweigh the risks, unless serious infections occurred in 20% or more of the population or lymphoma in 3.9% or more. These thresholds are 5-fold and 65-fold higher than base-case estimates, respectively. | Do adverse events outweigh benefits of combination therapy for Crohn 's disease in a decision analytic model? | No. On the basis of data from 1 year of SONIC, the combination of IFX/AZA was more effective than IFX alone in patients with Crohn's disease who are naïve to either drug. For the risks of combination therapy to outweigh the benefits in this time frame, the incidence of serious adverse events would have to be higher than seems clinically realistic. | PASS | pubmedQA | 1 |
16483579 | To investigate whether serum gamma-glutamyltransferase (GGT) is an independent predictor for incident coronary events in initially healthy men from the general population.
The study was based on 1878 men (aged 25-64 years) who participated in the first MONICA Augsburg survey 1984/1985, and who were free of coronary heart disease at baseline. Up to 2002 a total of 150 incident acute coronary events occurred. Baseline levels of GGT were higher in men who experienced an event than in event-free men (28.4+/-2.0 units/l versus 22.4+/-2.1 units/l, p 0.0002). GGT was highly correlated with other cardiovascular risk factors. In a Cox proportional hazards model after age adjustment hazard ratios (HR) for incident myocardial infarction across GGT quartiles (<13, 13 to <20, 20 to <35, and >/=35 units/l) were 1.0, 1.84, 2.02, and 3.08 (p for trend 0.0001). Further adjustment for hypertension, TC/HDL ratio, diabetes, smoking, physical activity, alcohol intake, education years and BMI attenuated the association; comparing the highest versus lowest quartile of GGT the HR for a first-ever coronary event was then 2.34 (95% CI, 1.23-4.44). | Is serum gamma-glutamyltransferase a predictor of incident coronary events in apparently healthy men from the general population? | Yes. Serum GGT is a strong predictor of acute coronary events in apparently healthy men from the general population, independent of other risk factors for cardiovascular disease. | PASS | pubmedQA | 1 |
16174723 | Hypospadias is one of the most common malformations in man, with an incidence of 1:300 in newborn boys. No gene has been identified that causes isolated hypospadias, but the androgenic influence is important during male genital development.
A key enzyme for the androgenic function is steroid 5-alpha-reductase (SRD5A2). The V89L polymorphism in the SRD5A2 gene has been studied and found to be of functional importance. The leucine version of the enzyme is 30% less efficient than the valine variant. DESIGN, SETTING, PATIENTS, AND RESULTS: We have genotyped 158 hypospadias cases and 96 unaffected controls for this polymorphism and found a significant negative association for the V89 allele in hypospadias (odds ratio, 0.24; 95% confidence interval, 0.14-0.41 for homozygous individuals). This indicates that a fully functional 5-alpha-reductase enzyme (homozygous for V89) protects the male urethral development. This association is shown regardless of heredity, ethnicity, and severity of phenotype. We have also sequenced a selected material of 37 sporadic cases of more severe hypospadias for mutations in the androgen receptor AR, SRD5A2, and 17beta-hydroxysteroid dehydrogenase HSD17B3 genes and found only two previously described mutations, one in the AR and one in the SRD5A2 gene. | Does the valine allele of the V89L polymorphism in the 5-alpha-reductase gene confer a reduced risk for hypospadias? | Yes. This finding is in accordance with the assumption that functional polymorphisms may play an important role in complex disorders such as hypospadias when several genes as well as environmental factors contribute to the etiology. | PASS | pubmedQA | 1 |
15136629 | This study was performed to prospectively evaluate fast PET/CT imaging protocols using lutetium oxyorthosilicate (LSO) detector technology and 3-dimensional (3D) image-acquisition protocols.
Fifty-seven consecutive patients (30 male, 27 female; mean age, 58.6 +/- 15.7 y) were enrolled in the study. After intravenous injection of 7.77 MBq (0.21 mCi) of (18)F-FDG per kilogram, a standard whole-body CT study (80-110 s) and PET emission scan were acquired for 4 min/bed position in 49 patients and 3 min/bed position in 8 patients. One-minute-per-bed-position data were then extracted from the 3- or 4-min/bed position scans to reconstruct single-minute/bed position scans for each patient. Patients were subgrouped according to weight as follows: <59 kg (<130 lb; n = 15), 59-81 kg (130-179 lb; n = 33), and >or=82 kg (>or=180 lb; n = 9). Three experienced observers recorded numbers and locations of lesion by consensus and independently rated image quality as good, moderate, poor, or nondiagnostic.
The observers analyzed 220 reconstructed whole-body PET images from 57 patients. They identified 114 lesions ranging in size from 0.7 to 7.0 cm on the 3- (n = 8) and 4-min/bed position images (n = 49). Of these, only 4 were missed on the 1-min/bed position scans, and all lesions were identified on the corresponding 2-min/bed position images. One- and 2-min/bed position image quality differed significantly from the 4-min/bed position image reference (P < 0.05). | Do impact of patient weight and emission scan duration on PET/CT image quality and lesion detectability? | Yes. LSO PET detector technology permits fast 3D imaging protocols whereby weight-based emission scan durations ranging from 1 to 3 min/bed position provide similar lesion detectability when compared with 4-min/bed position images. | PASS | pubmedQA | 1 |
7943112 | We investigated the participation of the cellular arm of the immune system in adaptation to pregnancy by assessing plasma and amniotic fluid levels of the cytokine tumor necrosis factor-alpha.
Fifty-five healthy pregnant women who underwent second-trimester genetic amniocentesis at a mean gestational age of 17.0 +/- 1.4 weeks composed study group A. Blood was drawn from each patient before amniocentesis, and an aliquot of amniotic fluid was obtained for this study. Twenty-one healthy patients at a mean gestational age of 35.5 +/- 4.8 weeks composed study group B, and blood was obtained from each patient at an outpatient prenatal visit. Twenty-two healthy, nonpregnant women of reproductive age composed the control group (C). All specimens were stored at -70 degrees C and collectively assayed for tumor necrosis factor-alpha by a specific enzyme-linked immunoassay.
All patients in group A had a normal karyotype and all patients in groups A and B had uneventful pregnancies. Tumor necrosis factor-alpha was detected in the plasma of 43 of 55 (78.2%) patients in group A compared with 7 of 21 (33.3%) patients in group B (p < 0.001); tumor necrosis factor-alpha was not detected in any of the 22 women in group C. The median plasma tumor necrosis factor-alpha level for group A was 135 pg/ml (range 0 to 625 pg/ml) compared with 0 pg/ml (range 0 to 110 pg/ml) in group B (p < 0.001). Tumor necrosis factor-alpha was not detected in any of the amniotic fluid specimens studied. | Is immunoreactive tumor necrosis factor-alpha elevated in maternal plasma but undetected in amniotic fluid in the second trimester? | Yes. Levels of tumor necrosis factor-alpha were elevated in the plasma but not detected in the amniotic fluid of normal pregnant patients in the second trimester. These findings suggest involvement of the cellular branch of the immune system and its products, the cytokines, in the normal adaptation of the mother to the fetal allograft, with a possible role in regulating trophoblast growth and invasion. | PASS | pubmedQA | 1 |
24397850 | Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism's reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).
To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16(INK4a) and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.
Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs. | Does donor age negatively impact adipose tissue-derived mesenchymal stem cell expansion and differentiation? | Yes. In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies. | PASS | pubmedQA | 1 |
21544513 | Oxidized fats are known to induce oxidative stress resulting in the up-regulation of antioxidant enzymes, with the underlying mechanism being unclear. It is known, however, that the response of tissues to oxidative stress is mediated by redox-sensitive transcription factors such as NF-κB and Nrf2. The aim of this study, therefore, was to test the hypothesis that ingestion of an oxidized fat causes activation of these transcription factors in the small intestinal mucosa.
Female mice were randomly assigned to 2 groups of 12 mice each and administered orally by gavage either oxidized or fresh fat once per day.
After 6 days of treatment, mice were killed, intestinal mucosa was isolated, and nuclear concentration of NF-κB and Nrf2 and expression of NF-κB- and Nrf2-regulated oxidative stress-responsive genes were determined. Oxidized fat markedly increased nuclear concentration of NF-κB and Nrf2 and transcript levels of oxidative stress-responsive genes, like aldo-keto reductase 1B8, vanin-1, glutathione peroxidase 1, and superoxide dismutase-1. In addition, oxidized fat increased the concentrations of PPAR-regulated genes. | Does dietary oxidized fat activate the oxidative stress-responsive transcription factors NF-κB and Nrf2 in intestinal mucosa of mice? | Yes. The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa. | PASS | pubmedQA | 1 |
22798288 | Kinase inhibitors are accepted treatment for metastatic melanomas that harbor specific driver mutations in BRAF or KIT, but only 40% to 50% of cases are positive. To uncover other potential targetable mutations, we conducted whole-genome sequencing of a highly aggressive BRAF (V600) and KIT (W557, V559, L576, K642, and D816) wild-type melanoma. Surprisingly, we found a somatic BRAF(L597R) mutation in exon 15. Analysis of BRAF exon 15 in 49 tumors negative for BRAF(V600) mutations as well as driver mutations in KIT, NRAS, GNAQ, and GNA11, showed that two (4%) harbored L597 mutations and another two involved BRAF D594 and K601 mutations. In vitro signaling induced by L597R/S/Q mutants was suppressed by mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition. A patient with BRAF(L597S) mutant metastatic melanoma responded significantly to treatment with the MEK inhibitor, TAK-733. Collectively, these data show clinical significance to BRAF(L597) mutations in melanoma. | Are bRAF ( L597 ) mutations in melanoma associated with sensitivity to MEK inhibitors? | Yes. This study shows that cells harboring BRAF(L597R) mutants are sensitive to MEK inhibitor treatment, providing a rationale for routine screening and therapy of BRAF(L597R)-mutant melanoma. | PASS | pubmedQA | 1 |
18053021 | Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe.
In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed.
The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). | Is the socio-economic burden of asthma substantial in Europe? | Yes. The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females. | PASS | pubmedQA | 1 |
21039404 | Serum and IgG isolated from patients with the autoimmune blistering disease pemphigus vulgaris (PV) trigger complex intracellular pathways in keratinocytes, including alterations of the cell cycle and metabolism, which ultimately lead to cell-cell detachment (acantholysis). We have shown previously that one of the earliest pathogenic events in PV is the activation of protein kinases, including the PKR-like endoplasmic reticulum (ER) kinase PERK.
In the present study we investigated in more detail the role of PERK in the pathogenesis of PV.
PERK levels were assessed by Western blotting and in-cell enzyme-linked immunosorbent assay, and PERK expression was silenced by siRNA technology. The effects of PV sera/IgG on keratinocyte cultures were investigated by flow cytometry, MTT and adhesion assays.
We show that PERK is activated in keratinocytes exposed to PV serum, as demonstrated by an increase in phosphorylated PERK levels and phosphorylation of eIF2α. Decreased expression of PERK by siRNA reduced the effects of PV serum on the cell cycle and keratinocyte viability, two key events in PV pathophysiology. As impairment of metabolic activity in PV is partially due to non-IgG serum factors, we then investigated the activation of PERK in keratinocytes incubated with whole PV serum, purified PV IgG and IgG-depleted PV serum. The data demonstrated that PV sera depleted of IgG, but not PV IgG, triggered PERK phosphorylation and this correlated with a marked reduction of metabolic activity in keratinocytes exposed to IgG-free serum. Knockdown of PERK by siRNA abrogated the changes in the cell cycle and apoptosis induced by IgG-depleted PV serum. Finally, the reduction of metabolic activity observed in keratinocytes exposed to IgG-depleted PV serum was almost absent in PERK-deficient cells. | Does deregulation of PERK in the autoimmune disease pemphigus vulgaris occur via IgG-independent mechanisms? | Yes. Taken together, the results demonstrate that activation of PERK participates in the reduction of metabolic activity and cell viability seen in PV and that this phenomenon depends on non-IgG factors. PERK activation may represent a novel signalling mechanism linking ER stress and acantholysis in PV. | PASS | pubmedQA | 1 |
27765658 | Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures.
Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS
613 unique named metabolites were identified. Of these, 189 metabolites were increased in the VC exposure group while 94 metabolites were decreased. Random Forest analysis indicated that the metabolite signature could separate the groups with 94% accuracy. VC exposures were associated with increased long chain (including arachidonic acid) and essential (including linoleic acid) fatty acids. Occupational exposure increased lipid peroxidation products including monohydroxy fatty acids (including 13-HODE); fatty acid dicarboxylates; and oxidized arachidonic acid products (including 5,9, and 15-HETE). Carnitine and carnitine esters were decreased, suggesting peroxisomal/mitochondrial dysfunction and alternate modes of lipid oxidation. Differentially regulated metabolites were shown to interact with extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, AMP-activated protein kinase (AMPK), and the N-Methyl-d-aspartate (NMDA) receptor. The top canonical pathways affected by occupational exposure included tRNA charging, nucleotide degradation, amino acid synthesis/degradation and urea cycle. Methionine and homocysteine was increased with decreased cysteine, suggesting altered 1-carbon metabolism. | Are occupational exposures at a polyvinyl chloride production facility associated with significant changes to the plasma metabolome? | Yes. Occupational exposure generated a distinct plasma metabolome with markedly altered lipid and amino acid metabolites. ERK1/2, Akt, AMPK, and NMDA were identified as protein targets for vinyl chloride toxicity. | PASS | pubmedQA | 1 |
21129944 | Continuous positive airways pressure (CPAP) for treatment of obstructive sleep apnea (OSA) can produce troublesome nasal symptoms (i.e. congestion, rhinorrhea) that may reduce the compliance of CPAP. Topical nasal steroids are often prescribed to reduce these side effects, although scientific data are scarce supporting any benefits of this treatment for CPAP-induced nasal side effects.
To study whether a topical nasal steroid can reduce CPAP-induced nasal symptoms and improve CPAP adherence during the initial phase of OSA treatment.
A randomized, double-blinded, placebo-controlled study with fluticasone propionate 100 μg/nasal cavity twice daily Treatment was started 10 days prior to and continued throughout the first 4 weeks of CPAP. 63 patients who were selected for CPAP treatment participated. Nasal symptoms were recorded, nasal patency was assessed and lung function was measured with a peak flow meter. The patients' adherence to CPAP was recorded by the CPAP device.
Total nasal symptoms increased from baseline to 4 wks after CPAP use for both nasal treatments (p < 0.05). No differences in total nasal symptoms between treatments were seen (p = 1), and no differences in nasal peak flow values after treatment were seen (p = 0.11). Moreover, there were no differences in CPAP use between the treatments. | Does topical nasal steroid treatment improve CPAP compliance in unselected patients with OSAS? | No. Fluticasone propionate as a nasal topical steroid does not reduce CPAP-induced unwanted nasal side effects, and has no beneficial effect on CPAP compliance during the first four weeks of treatment in unselected patients with OSAS. | PASS | pubmedQA | 1 |
9341589 | To investigate the effect of smoking on serum ionized magnesium concentration ([Mg2+]) determined by the NOVA and AVL Mg ion-selective electrodes (Mg ISEs).
Subjects were apparently healthy smokers (n = 30) and nonsmokers (n = 30). We determined NOVA and AVL [Mg2+] in their serum and in test solutions containing compounds increased by smoking. We also determined subjects' white blood cell and differential counts.
For smokers, the mean values for NOVA and AVL [Mg2+] differed significantly (0.41 vs 0.52 mmol/L, respectively). We found a significant intramethod difference in NOVA [Mg2+] (0.11 mmol/L, P < .0001) between smokers and nonsmokers. A dose-dependent decrease in NOVA [Mg2+] was observed with an increase in cigarettes/day. NOVA [Mg2+] inversely correlated with white blood cell counts. There was no interference by the test compounds with either Mg ISE. | Is the effect of smoking on the serum ionized magnesium concentration method-dependent? | Yes. Smoking may induce a serum factor, possibly related to white blood cells, that negatively interferes with the response of the NOVA Mg ISE. | PASS | pubmedQA | 1 |
25862596 | To examine the association between early menarche and risk of post-menarcheal asthma.
Using data from two multidisciplinary questionnaire surveys, conducted eight years apart, we prospectively studied 10,648 female twins, 12-41 years of age, from the nationwide Danish Twin Registry. Early menarche was defined as menarche before 12 years of age. We performed a cohort analysis and a co-twin control analysis including twin pairs discordant for incident asthma.
Early menarche was observed in 9.3% of the individuals. The eight-year cumulative incidence of asthma was higher in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p < 0.001; also after adjustment for BMI, current age, physical activity, education, and smoking, OR = 1.53 (1.15-2.04), p = 0.003. The unadjusted risk of asthma was increased by 8% (1-15%), p = 0.041 per year earlier menarche occurred. Among 167 twin pairs discordant for incident asthma, there was a non-significant tendency towards early menarche being more common in the asthmatic than the non-asthmatic co-twin (12.0 vs. 9.6%), OR = 1.57 (0.61-4.05), p = 0.350. The risk of asthma was not uniform in discordant monozygotic and dizygotic twins. | Is early menarche associated with increased risk of asthma : Prospective population-based study of twins? | Yes. Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non-genetic effects. | PASS | pubmedQA | 1 |
25223540 | The goal of the current study was to investigate the effect of aging on the development of endothelial dysfunction in a murine model of sepsis, and to compare it with the effect of genetic deficiency of the endothelial isoform of nitric oxide synthase (eNOS).
Cecal ligation and puncture (CLP) was used to induce sepsis in mice. Survival rates were monitored and plasma indices of organ function were measured. Ex vivo studies included the measurement of vascular function in thoracic aortic rings, assessment of oxidative stress/cellular injury in various organs and the measurement of mitochondrial function in isolated liver mitochondria.
eNOS deficiency and aging both exacerbated the mortality of sepsis. Both eNOS-deficient and aged mice exhibited a higher degree of sepsis-associated multiple organ dysfunction syndrome (MODS), infiltration of tissues with mononuclear cells and oxidative stress. A high degree of sepsis-induced vascular oxidative damage and endothelial dysfunction (evidenced by functional assays and multiple plasma markers of endothelial dysfunction) was detected in aortae isolated from both eNOS(-/-) and aged mice. There was a significant worsening of sepsis-induced mitochondrial dysfunction, both in eNOS-deficient mice and in aged mice. Comparison of the surviving and non-surviving groups of animals indicated that the severity of endothelial dysfunction may be a predictor of mortality of mice subjected to CLP-induced sepsis. | Is endothelial dysfunction a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock : preclinical studies in a murine model of cecal ligation and puncture? | Yes. Based on the studies in eNOS mice, we conclude that the lack of endothelial nitric oxide production, on its own, may be sufficient to markedly exacerbate the severity of septic shock. Aging markedly worsens the degree of endothelial dysfunction in sepsis, yielding a significant worsening of the overall outcome. Thus, endothelial dysfunction may constitute an early predictor and independent contributor to sepsis-associated MODS and mortality in aged mice. | PASS | pubmedQA | 1 |
22059850 | Short-chain fatty acids (SCFAs), produced at relatively high levels by anaerobic bacteria in bacterial vaginosis (BV), are believed to be anti-inflammatory. BV, a common alteration in the genital microbiota associated with increased susceptibility to HIV infection, is characterized by increased levels of both pro-inflammatory cytokines and SCFAs. We investigated how SCFAs alone or together with Toll-like receptor (TLR) ligands affected pro-inflammatory cytokine secretion.
Cytokines were measured by ELISA. Flow was used for phenotyping and reactive oxygen species (ROS) measurement.
Short-chain fatty acids, at 20 mM, induced interleukin (IL)-8, IL-6, and IL-1β release, while lower levels (0.02-2 mM) did not induce cytokine secretion. Levels >20 mM were toxic to cells. Interestingly, lower levels of SCFAs significantly enhanced TLR2 ligand- and TLR7 ligand-induced production of IL-8 and TNFα in a time- and dose-dependent manner, but had little effect on lipopolysaccharide-induced cytokine release. SCFAs mediated their effects on pro-inflammatory cytokine production at least in part by inducing the generation of ROS. | Do short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands? | Yes. Our data suggest that SCFAs, especially when combined with specific TLR ligands, contribute to a pro-inflammatory milieu in the lower genital tract and help further our understanding of how BV affects susceptibility to microbial infections. | PASS | pubmedQA | 1 |
27261559 | Congenital diaphragmatic hernia (CDH) is associated with high postnatal mortality because of pulmonary hypoplasia. The prognostic utility of serial lung-to-head circumference measurements as a marker of lung growth has not been described. Our objective was to examine the relationship between the rate of interval increase of LHR and postnatal survival in left-sided CDH.
We retrospectively reviewed charts of all left-sided CDH patients from January 2004 to July 2014. All ultrasound studies performed at our institution (n=473) were reviewed. Categorical and continuous data were analyzed by chi-square and Mann-Whitney t-test, respectively, and slope analysis was performed by linear regression analysis (p<0.05).
A total of 226 patients were studied, with 154 long-term survivors and 72 non-survivors. Established markers of CDH severity, including intrathoracic liver position and requirement for patch repair, were significantly increased in non-survivors (p<0.0001). The rate of LHR increase as measured by linear regression and slope analysis was significantly increased in long-term survivors (p=0.0175). | Is rate of increase of lung-to-head ratio over the course of gestation predictive of survival in left-sided congenital diaphragmatic hernia? | Yes. Our findings indicate that the interval increase in LHR levels over the course of gestation correlate with survival in left-sided CDH patients. Regular ultrasonographic re-evaluation of LHR throughout gestation following diagnosis of CDH may provide prognostic insight and help guide patient management. | PASS | pubmedQA | 1 |
24690247 | Conventional clinical staging for prostate cancer has many limitations. This study evaluates the impact of adding MRI scans to conventional clinical staging for guiding decisions about radiotherapy target coverage.
This was a retrospective review of 115 patients who were treated between February 2002 and September 2005 with radical radiotherapy for prostate cancer. All patients had MRI scans approximately 2 weeks before the initiation of radiotherapy. The T stage was assessed by both conventional clinical methods (cT-staging) as well as by MRI (mT-staging). The radiotherapy target volumes were determined first based on cT-staging and then taking the additional mT staging into account. The number of times extracapsular extension or seminal vesicle invasion was incorporated into target volumes was quantified based on both cT-staging and the additional mT-staging.
Extracapsular extension was incorporated into target volumes significantly more often with the addition of mT-staging (46 patients (40%) ) compared with cT-staging alone (37 patients (32%) ) (P = 0.002). Seminal vesicle invasion was incorporated into target volumes significantly more often with the addition of mT-staging (21 patients (18%) ) compared with cT-staging alone (three patients (3%) ) (P < 0.001). A total of 23 patients (20%) had changes to their target coverage based on the mT-staging. | Does mRI scan significantly change target coverage decisions in radical radiotherapy for prostate cancer? | Yes. MRI scans can significantly change decisions about target coverage in radical radiotherapy for prostate cancer. | PASS | pubmedQA | 1 |
24775184 | Serotonin (5-HT) neurons mediate the ectopic release of dopamine (DA) induced by L-DOPA in the Parkinsonian brain. We hypothesized that the participation of noradrenalin transporters (NET) in the clearance of DA may account for the lower effect of L-DOPA in extrastriatal regions compared with the striatum.
Using a multisite intracerebral microdialysis approach, we tested the influence of the pharmacological blockade of NET and/or the destruction of noradrenalin (NE) fibers on DA and 5-HT release in the striatum, hippocampus (HIPP), substantia nigra pars reticulata (SNr) and prefrontal cortex (PFC) of 6-hydroxydopamine-lesioned rats.
L-DOPA (12 mg/kg, i.p.) increased DA extracellular levels to a lesser extent in the SNr, PFC and HIPP compared with the striatum. The NET blockers desipramine (10 mg/kg, i.p.) and reboxetine (3 mg/kg, i.p.) potentiated L-DOPA effect in the PFC, SNr and HIPP but not in the striatum. The NE neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg, i.p. 1 week before dialysis experiment) potentiated L-DOPA effect in the SNr and HIPP. 5-HT extracellular levels were enhanced only when L-DOPA was combined to NET blockers. | Do noradrenergic terminals regulate L-DOPA-derived dopamine extracellular levels in a region-dependent manner in Parkinsonian rats? | Yes. Noradrenalin neurons are indirectly involved in the mechanism of action of L-DOPA in part through the heterologous reuptake of DA in extrastriatal regions. | PASS | pubmedQA | 1 |
20573805 | Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation.
Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications.
All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). | Does pre-emptive liver transplantation for primary hyperoxaluria ( PH-I ) arrest long-term renal function deterioration? | Yes. Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal transplantation. | PASS | pubmedQA | 1 |
25887553 | Group B Sox proteins are a highly conserved group of transcription factors that act extensively to coordinate nervous system development in higher metazoans while showing both co-expression and functional redundancy across a broad group of taxa. In Drosophila melanogaster, the two group B Sox proteins Dichaete and SoxNeuro show widespread common binding across the genome. While some instances of functional compensation have been observed in Drosophila, the function of common binding and the extent of its evolutionary conservation is not known.
We used DamID-seq to examine the genome-wide binding patterns of Dichaete and SoxNeuro in four species of Drosophila. Through a quantitative comparison of Dichaete binding, we evaluated the rate of binding site turnover across the genome as well as at specific functional sites. We also examined the presence of Sox motifs within binding intervals and the correlation between sequence conservation and binding conservation. To determine whether common binding between Dichaete and SoxNeuro is conserved, we performed a detailed analysis of the binding patterns of both factors in two species. | Is common binding by redundant group B Sox proteins evolutionarily conserved in Drosophila? | Yes. We find that, while the regulatory networks driven by Dichaete and SoxNeuro are largely conserved across the drosophilids studied, binding site turnover is widespread and correlated with phylogenetic distance. Nonetheless, binding is preferentially conserved at known cis-regulatory modules and core, independently verified binding sites. We observed the strongest binding conservation at sites that are commonly bound by Dichaete and SoxNeuro, suggesting that these sites are functionally important. Our analysis provides insights into the evolution of group B Sox function, highlighting the specific conservation of shared binding sites and suggesting alternative sources of neofunctionalisation between paralogous family members. | PASS | pubmedQA | 1 |
25249235 | Developing beta cells are vulnerable to nutrient environmental signals. Early developmental processes that alter the number of pancreatic progenitors can determine the number of beta cells present at birth. Metformin, the most widely used oral agent for treating diabetes, alters intracellular energy status in part by increasing AMP-activated protein kinase (AMPK) signalling. This study examined the effect of metformin on developing pancreas and beta cells.
Pancreatic rudiments from CD-1 mice at embryonic day 13.0 (E13.0) were cultured with metformin, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an AMPK activator) or vehicle control in vitro. In another set of studies, pregnant C57BL/6 mice were treated with metformin throughout gestation. Embryonic (E14.0) and neonatal pancreases were then analysed for their morphometry.
In vitro metformin treatment led to an increase in the proliferation and number of pancreatic duodenal homeobox 1-positive (PDX1(+)) progenitors. These results were reproduced by in vitro culture of embryonic pancreas rudiments with AICAR, suggesting that AMPK activation was involved. Similarly, metformin administration to pregnant dams induced an increase in both PDX1(+) and neurogenin 3-positive progenitors in the embryonic pancreas at E14.0 and these changes resulted in an increased beta cell fraction in neonates. | Does exposure of mouse embryonic pancreas to metformin enhance the number of pancreatic progenitors? | Yes. These results indicate that exposure to metformin during gestation modulates the early steps of beta cell development (prior to E14.0) towards an increase in the number of pancreatic and endocrine progenitors. These changes ultimately result in a higher beta cell fraction at birth. These findings are of clinical importance given that metformin is currently used for the treatment of gestational diabetes. | PASS | pubmedQA | 1 |
9403530 | To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection.
Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43 degrees C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, bax, and bcl-2 expression was analyzed at various times by the Western blot method.
Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T-cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly up-regulated bax. The expression of p53 peaked at 4 hours and preceded maximal bax induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased bax levels. Levels of bcl-2 were unaffected. | Does induction of heat shock protein 70 protect thymocytes against radiation-induced apoptosis? | Yes. Our data show that HSP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and bax expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized. | PASS | pubmedQA | 1 |