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SomaticSignatures: inferring mutational signatures from single-nucleotide variants. UNLABELLED: Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes. The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data. It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows. AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. Its documentation provides additional details on the methods and demonstrates applications to biological datasets. CONTACT: [email protected], [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Which R packages have been developed for the discovery of mutational signatures in cancer?

5a7636d39e632bc066000004_009

SomaticSignatures: inferring mutational signatures from single-nucleotide variants. UNLABELLED: Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes. The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data. It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows. AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. Its documentation provides additional details on the methods and demonstrates applications to biological datasets. CONTACT: [email protected], [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Which R packages have been developed for the discovery of mutational signatures in cancer?

5a7636d39e632bc066000004_010

SomaticSignatures: inferring mutational signatures from single-nucleotide variants. UNLABELLED: Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes. The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data. It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows. AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. Its documentation provides additional details on the methods and demonstrates applications to biological datasets. CONTACT: [email protected], [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Which R packages have been developed for the discovery of mutational signatures in cancer?

5a7636d39e632bc066000004_012

signeR: an empirical Bayesian approach to mutational signature discovery. MOTIVATION: Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. Current methods based on optimization techniques are strongly sensitive to initial conditions due to high dimensionality and nonconvexity of the NMF paradigm. In this context, an important question consists in the determination of the actual number of signatures that best represent the data. The extraction of mutational signatures from high-throughput data still remains a daunting task. RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. While requiring minimal intervention from the user, our method addresses the determination of the number of signatures directly as a model selection problem. In addition, we introduce two new concepts of significant clinical relevance for evaluating the mutational profile. The advantages brought by our approach are shown by the analysis of real and synthetic data. The later is used to compare our approach against two alternative methods mostly used in the literature and with the same NMF parametrization as the one considered here. Our approach is robust to initial conditions and more accurate than competing alternatives. It also estimates the correct number of signatures even when other methods fail. Results on real data agree well with current knowledge. AVAILABILITY AND IMPLEMENTATION: signeR is implemented in R and C ++, and is available as a R package at http://bioconductor.org/packages/signeR CONTACT: [email protected] information: Supplementary data are available at Bioinformatics online.

Which R packages have been developed for the discovery of mutational signatures in cancer?

5a7636d39e632bc066000004_013

Prevalence of metabolic syndrome in patients undergoing total joint arthroplasty and relevance of biomarkers. BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA. METHODS: Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-α, IL-1a, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria. RESULTS: Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were significantly elevated in patients undergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNFα was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in TJA±MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal. CONCLUSIONS: Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFα in TJA-MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_001

Prevalence of metabolic syndrome in patients undergoing total joint arthroplasty and relevance of biomarkers. BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA. METHODS: Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-α, IL-1a, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria. RESULTS: Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were significantly elevated in patients undergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNFα was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in TJA±MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal. CONCLUSIONS: Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFα in TJA-MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_002

Prevalence and Correlates of Metabolic Syndrome in Chinese Children: The China Health and Nutrition Survey. Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity. During the past decades, MetS has become a major public health issue worldwide in both adults and children. In this study, data from the China Health and Nutrition Surveys (CHNS) was used to assess the prevalence of MetS based on both the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) guidelines and the International Diabetes Federation (IDF) criteria, and to evaluate its possible correlates. A total of 831 children aged 7-18 years were included in this study, and 28 children were classified as having MetS as defined by the modified NCEP-ATPIII definition, which yielded an overall prevalence of 3.37%. Elevated blood pressure was the most frequent MetS component. The results of logistic regression models revealed that increased body mass index (BMI), hyperuricemia, and insulin resistance (IR) were all associated with the presence of MetS. To conclude, our study revealed the prevalence of MetS in Chinese children at the national level. Further large-scale studies are still needed to identify better MetS criteria in the general paediatric population in China.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_003

Risk factor clusters for metabolic syndrome in coronary heart disease: state of the science. Metabolic syndrome, defined as a cluster of obesity, hypertension, dyslipidemia, and insulin resistance/glucose intolerance, has been identified as a major risk factor for coronary heart disease in women. Nurses should increase their awareness of metabolic syndrome to help identify and treat the current estimated 47 million US residents who have metabolic syndrome.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_004

Risk factor clusters for metabolic syndrome in coronary heart disease: state of the science. Metabolic syndrome, defined as a cluster of obesity, hypertension, dyslipidemia, and insulin resistance/glucose intolerance, has been identified as a major risk factor for coronary heart disease in women. Nurses should increase their awareness of metabolic syndrome to help identify and treat the current estimated 47 million US residents who have metabolic syndrome.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_005

Metabolic Syndrome: Insulin Resistance and Prediabetes. Metabolic syndrome is a cluster of conditions that synergistically increase the risk of cardiovascular disease, type 2 diabetes, and premature mortality. The components are abdominal obesity, impaired glucose metabolism, dyslipidemia, and hypertension. Prediabetes, which is a combination of excess body fat and insulin resistance, is considered an underlying etiology of metabolic syndrome. Prediabetes manifests as impaired fasting glucose and/or impaired glucose tolerance. Impaired fasting glucose is defined as a fasting blood glucose level of 100 to 125 mg/dL; impaired glucose tolerance requires a blood glucose level of 140 to 199 mg/dL 2 hours after a 75-g oral intake of glucose. In patients with prediabetes, the rate of progression to diabetes within 3 years can be decreased by approximately 58% with lifestyle modifications. These include weight loss through exercise (30 minutes or more of moderate physical activity on most, preferably all, days of the week) and dietary modifications. Recommended diets are high in fruits, vegetables, whole grains, and fish. Consumption of sweetened beverages, including diet soda, should be avoided. For patients who do not achieve goals with lifestyle modifications, metformin can be considered. Weight loss drugs and bariatric surgery are appropriate for select patients. Hypertension and dyslipidemia should be managed according to current guidelines.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_006

Metabolic Syndrome: Insulin Resistance and Prediabetes. Metabolic syndrome is a cluster of conditions that synergistically increase the risk of cardiovascular disease, type 2 diabetes, and premature mortality. The components are abdominal obesity, impaired glucose metabolism, dyslipidemia, and hypertension. Prediabetes, which is a combination of excess body fat and insulin resistance, is considered an underlying etiology of metabolic syndrome. Prediabetes manifests as impaired fasting glucose and/or impaired glucose tolerance. Impaired fasting glucose is defined as a fasting blood glucose level of 100 to 125 mg/dL; impaired glucose tolerance requires a blood glucose level of 140 to 199 mg/dL 2 hours after a 75-g oral intake of glucose. In patients with prediabetes, the rate of progression to diabetes within 3 years can be decreased by approximately 58% with lifestyle modifications. These include weight loss through exercise (30 minutes or more of moderate physical activity on most, preferably all, days of the week) and dietary modifications. Recommended diets are high in fruits, vegetables, whole grains, and fish. Consumption of sweetened beverages, including diet soda, should be avoided. For patients who do not achieve goals with lifestyle modifications, metformin can be considered. Weight loss drugs and bariatric surgery are appropriate for select patients. Hypertension and dyslipidemia should be managed according to current guidelines.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_007

Metabolic Syndrome and Nephrolithiasis Risk: Should the Medical Management of Nephrolithiasis Include the Treatment of Metabolic Syndrome? This article reviews the relationship between metabolic syndrome (MetS) and nephrolithiasis, as well as the clinical implications for patients with this dual diagnosis. MetS, estimated to affect 25% of adults in the United States, is associated with a fivefold increase in the risk of developing diabetes, a doubling of the risk of acquiring cardiovascular disease, and an increase in overall mortality. Defined as a syndrome, MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. Urologic complications of MetS include a 30% higher risk of nephrolithiasis, with an increased percentage of uric acid nephrolithiasis in the setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary volume. Current American Urological Association and European Association of Urology guidelines suggest investigating the etiology of nephrolithiasis in affected individuals; however, there is no specific goal of treating MetS as part of the medical management. Weight loss and exercise, the main lifestyle treatments of MetS, counter abdominal obesity and insulin resistance and reduce the incidence of cardiovascular events and the development of diabetes. These recommendations may offer a beneficial adjunctive treatment option for nephrolithiasis complicated by MetS. Although definitive therapeutic recommendations must await further studies, it seems both reasonable and justifiable for the urologist, as part of a multidisciplinary team, to recommend these important lifestyle changes to patients with both conditions. These recommendations should accompany the currently accepted management of nephrolithiasis.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_008

Metabolic Syndrome and Nephrolithiasis Risk: Should the Medical Management of Nephrolithiasis Include the Treatment of Metabolic Syndrome? This article reviews the relationship between metabolic syndrome (MetS) and nephrolithiasis, as well as the clinical implications for patients with this dual diagnosis. MetS, estimated to affect 25% of adults in the United States, is associated with a fivefold increase in the risk of developing diabetes, a doubling of the risk of acquiring cardiovascular disease, and an increase in overall mortality. Defined as a syndrome, MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. Urologic complications of MetS include a 30% higher risk of nephrolithiasis, with an increased percentage of uric acid nephrolithiasis in the setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary volume. Current American Urological Association and European Association of Urology guidelines suggest investigating the etiology of nephrolithiasis in affected individuals; however, there is no specific goal of treating MetS as part of the medical management. Weight loss and exercise, the main lifestyle treatments of MetS, counter abdominal obesity and insulin resistance and reduce the incidence of cardiovascular events and the development of diabetes. These recommendations may offer a beneficial adjunctive treatment option for nephrolithiasis complicated by MetS. Although definitive therapeutic recommendations must await further studies, it seems both reasonable and justifiable for the urologist, as part of a multidisciplinary team, to recommend these important lifestyle changes to patients with both conditions. These recommendations should accompany the currently accepted management of nephrolithiasis.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_009

Guidelines updates in the treatment of obesity or metabolic syndrome and hypertension. Obesity and overweight are nowadays very prevalent worldwide. They are known to be linked with an increased risk of developing cardiovascular comorbidities and mortality. Abdominal obesity is frequently associated with a collection of metabolic disorders that include elevated blood pressure, characteristic lipid abnormalities (low high-density lipoprotein cholesterol and high triglycerides) and increased fasting glucose, with an underlying situation of insulin resistance, which has been defined as metabolic syndrome, conferring a high cardiovascular risk profile to these subjects. A multidisciplinary approach is required, including lifestyle changes and pharmacological and surgical approaches. Intensive management of all the risk factors of the metabolic syndrome is also needed to reduce body weight and waist circumference, lessen insulin resistance and avoid the development of new-onset diabetes and cardiovascular disease associated with this entity. This article will review the recently published literature and guideline updates on this topic, although it is not yet included in the highlights.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_010

[Is it necessary to detect insulin resistance for diagnosis of metabolic syndrome in clinical practice?]. Metabolic syndrome is widely spread in population especially among subjects with risk factors of atherosclerosis related diseases. Since 1988 criteria of metabolic syndrome have undergone substantial transformation. Technical difficulties related to detection of insulin resistance created obstacles to application of the term "metabolic syndrome" in clinical practice. In 2001 experts of National Cholesterol Education Program in USA suggested new set of criteria. The presence of 3 or more of the following 5 components (abdominal obesity, hypertriglyceridemia, low level of high density lipoprotein cholesterol, hypertension and high fasting blood glucose) allows to diagnose metabolic syndrome. These worldwide used criteria do not imply detection of insulin resistance. Feasibility of this approach has been confirmed by analysis of correlation between presence of markers of insulin resistance and that of metabolic syndrome according to novel criteria. This analysis has shown that combination of 3 or more components is significantly associated with insulin resistance.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_011

[Is it necessary to detect insulin resistance for diagnosis of metabolic syndrome in clinical practice?]. Metabolic syndrome is widely spread in population especially among subjects with risk factors of atherosclerosis related diseases. Since 1988 criteria of metabolic syndrome have undergone substantial transformation. Technical difficulties related to detection of insulin resistance created obstacles to application of the term "metabolic syndrome" in clinical practice. In 2001 experts of National Cholesterol Education Program in USA suggested new set of criteria. The presence of 3 or more of the following 5 components (abdominal obesity, hypertriglyceridemia, low level of high density lipoprotein cholesterol, hypertension and high fasting blood glucose) allows to diagnose metabolic syndrome. These worldwide used criteria do not imply detection of insulin resistance. Feasibility of this approach has been confirmed by analysis of correlation between presence of markers of insulin resistance and that of metabolic syndrome according to novel criteria. This analysis has shown that combination of 3 or more components is significantly associated with insulin resistance.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_012

The relationship of body fat to metabolic disease: influence of sex and ethnicity. Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_013

The relationship of body fat to metabolic disease: influence of sex and ethnicity. Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_014

Challenges associated with metabolic syndrome. Approximately 2500 Americans die from cardiovascular disease (CVD) each day. Each year, CVD claims more lives than the next four leading causes of death combined. Direct and indirect costs of CVD are estimated to be Dollars 403.1 billion in 2006. Despite advancements in conventional therapy, the residual risk of CVD continues to rise. One component of the cardiometabolic risk is metabolic syndrome. Metabolic syndrome is a constellation of interrelated risk factors of metabolic origin including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, elevated plasma glucose level, and prothrombotic and proinflammatory states that promote atherosclerotic CVD and increase the risk of type 2 diabetes mellitus. Approximately 47 million residents of the United States have metabolic syndrome. Abdominal obesity and insulin resistance appear to be its predominant underlying risk factors. Abdominal adiposity is considered high-risk fat, and it is associated with insulin resistance, hyperglycemia, dyslipidemia, hypertension, and prothrombotic and/or proinflammatory states. Despite notable advances in cardiovascular risk management, the prevalence of cardiovascular events and type 2 diabetes remains high. First-line therapy for individuals with metabolic syndrome should be directed to the major CVD risk factors, namely, elevated low-density lipoprotein cholesterol levels, hypertension, and diabetes, and it should emphasize lifestyle modification. Until additional research better defines the most appropriate therapies, conventional cardiovascular risk factors, such as lipid levels, blood pressure, and diabetes, should be managed in individuals with metabolic syndrome according to nationally accepted clinical guidelines.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_015

The current waist circumference cut point used for the diagnosis of metabolic syndrome in sub-Saharan African women is not appropriate. The waist circumference cut point for diagnosing the metabolic syndrome in sub-Saharan African subjects is based on that obtained from studies in European populations. The aim of this study was to measure the prevalence of obesity and related metabolic disorders in an urban population of African females, a group at high risk for such diseases, and to determine the appropriate waist cut point for diagnosing the metabolic syndrome. Anthropometry and fasting lipid, glucose and insulin levels were measured in a cohort of 1251 African females participating in the Birth to Twenty cohort study in Soweto, Johannesburg. The waist circumference cut points for diagnosing metabolic syndrome (as defined using the new harmonised guidelines), insulin resistance, dysglycaemia, hypertension and dyslipidaemia were obtained using receiver operator characteristic curve analysis. The prevalence of obesity, type 2 diabetes and metabolic syndrome were 50.1%, 14.3% and 42.1%, respectively. The appropriate waist cut point for diagnosing metabolic syndrome was found to be 91.5 cm and was similar to the cuts points obtained for detecting increased risk of insulin resistance (89.0 cm), dysglycaemia (88.4 cm), hypertension (90.1 cm), hypo-high density lipoproteinaemia (87.6 cm) and hyper-low density lipoproteinaemia (90.5 cm). The present data demonstrates that urban, African females have a high prevalence of obesity and related disorders and the waist cut point currently recommended for the diagnosis of the metabolic syndrome (80.0 cm) in this population should be increased to 91.5 cm. This latter finding demonstrates a clear ethnic difference in the relationship between abdominal adiposity and metabolic disease risk. The similar waist cut points identified for the detection of the individual components of the metabolic syndrome and related cardiovascular risk factors demonstrates that the risk for different metabolic diseases increases at the same level of abdominal adiposity suggesting a common aetiological pathway.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_016

The metabolic syndrome and related cardiovascular risk. The metabolic syndrome is a complex association of several risk factors including insulin resistance, dyslipidemia, and essential hypertension. Insulin resistance has been associated with sympathetic activation and endothelial dysfunction, which are the main mechanisms involved in the pathophysiology of hypertension and its related cardiovascular risk. According to the Sixth Report of the Joint National Committee, and guidelines of the World Health Organization/International Society of Hypertension, the presence of multiple risk markers suggests that both hypertension and risk factors should be aggressively managed in order to obtain a better outcome. Primary prevention of obesity at different levels--individual, familial, and social-- starting early in childhood has proven to be cost effective, and will be mandatory to reduce the world epidemic of obesity and its severe consequences.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_017

Insulin resistance syndrome: interaction with coagulation and fibrinolysis. Insulin resistance represents a common metabolic abnormality leading to cardiovascular disease, the major cause of morbidity and mortality in most parts of the world. Insulin resistance is also associated with an increased risk of type 2 diabetes which is strongly associated with obesity. The insulin resistance of obese people and subjects with type 2 diabetes is characterised by defects at many levels, affecting insulin receptor concentration, glucose transport mechanisms and the activities of intracellular enzymes. Around 25% of western populations show some features of the insulin resistance syndrome (often referred to as syndrome X or the metabolic syndrome) ie, a clustering of metabolic, atheromatous risk factors, including hypertriglyceridaemia, hyperinsulinaemia, hyper-tension, hypercholesterinaemia and obesity. However, the known metabolic cardiovascular risk factors associated with the insulin resistance syndrome do not sufficiently explain the excess vascular risk attributed to this syndrome. The observation, that increased plasma plasminogen activator inhibitor 1 (PAI-1) levels were associated with insulin resistance and atherothrombosis added for the first time a pathological basis for an association of the insulin resistance syndrome not only with metabolic, atheromatous (atherosclerotic) risk but also with atherothrombotic risk. It is very likely that not only PAI-1, but also other abnormalities in haemostatic variables contribute to this excess vascular risk. Knowledge of how haemostatic variables cluster with classical metabolic risk factors associated with the insulin resistance syndrome could help to better understand the pathogenesis of cardiovascular diseases. Indeed, many coagulation and fibrinolytic proteins have been shown to be associated with features of the insulin resistance syndrome and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders, principally through an association with other established metabolic (atheromatous) risk factors in the presence of underlying insulin resistance. Interestingly, new therapeutic approaches in the prevention and treatment of insulin resistance do show some influence on coagulation and fibrinolysis. The newest drugs are the thiazolidinediones, a totally novel class of insulin sensitisers. They have the potential to offer improvements both in glycaemic control and in cardiovascular events.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_018

Metabolic syndrome, or What you will: definitions and epidemiology. The metabolic syndrome is a clustering of risk factors which predispose an individual to cardiovascular morbidity and mortality. There is general consensus regarding the main components of the syndrome (glucose intolerance, obesity, raised blood pressure and dyslipidaemia [elevated triglycerides, low levels of high-density lipoprotein cholesterol]) but different definitions require different cut points and have different mandatory inclusion criteria. Although insulin resistance is considered a major pathological influence, only the World Health Organization (WHO) and European Group for the study of Insulin Resistance (EGIR) definitions include it amongst the diagnostic criteria and only the International Diabetes Federation (IDF) definition has waist circumference as a mandatory component. The prevalence of metabolic syndrome within individual cohorts varies with the definition used. Within each definition, the prevalence of metabolic syndrome increases with age and varies with gender and ethnicity. There is a lack of diagnostic concordance between different definitions. Only about 30% of people could be given the diagnosis of metabolic syndrome using most definitions, and about 3540% of people diagnosed with metabolic syndrome are only classified as such using one definition. There is currently debate regarding the validity of the term metabolic syndrome, but the presence of one cardiovascular risk factor should raise suspicion that additional risk factors may also be present and encourage investigation. Individual risk factors should be treated.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_019

Revisiting the metabolic syndrome. Metabolic syndrome (MS) refers to the clustering of cardiometabolic risk factors - including abdominal obesity, hyperglycaemia, dyslipidaemia and elevated blood pressure - that are thought to be linked to insulin resistance. MS is associated with increased risk of cardiovascular disease and type 2 diabetes. MS is common, affecting a quarter to a third of adults, and its prevalence is rising, in parallel with increasing obesity and population ageing. Operational definitions of MS have been proposed by the World Health Organization and the National Cholesterol Education Program. Recently, the International Diabetes Federation proposed a global definition that emphasised the importance of central adiposity. In cardiovascular risk assessment, MS encapsulates the contribution of non-traditional risk factors and provides a clinically useful framework for early identification of people at increased long-term risk. It should be used in conjunction with standard algorithms based on conventional risk factors, which better predict short-term risk. Management of MS should emphasise lifestyle interventions (eg, physical activity, healthy diet and weight reduction) to reduce long-term risk of cardiovascular disease and diabetes. Those at increased short-term risk should also have individual risk factors treated according to established guidelines.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_020

Insulin resistance and the metabolic syndrome. The metabolic syndrome is a constellation of risk factors including glucose dysregulation, central obesity, dyslipidemia, and hypertension. There are multiple definitions that have been described by various health organizations. However, we do know that insulin resistance plays a major role as the underlying cause for the development and potentiation of the metabolic syndrome. At present, it is unclear if the diagnosis of metabolic syndrome is greater than the sum of its parts. However, the presence of more than one of the associated risk factors should indicate that a patient is at increased risk for developing diabetes, cardiovascular disease and death. Thus, the primary care physician should aggressively treat the metabolic risk factors in their patients to prevent the onset and progression to more severe disease.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_021

Insulin resistance and the metabolic syndrome. The metabolic syndrome is a constellation of risk factors including glucose dysregulation, central obesity, dyslipidemia, and hypertension. There are multiple definitions that have been described by various health organizations. However, we do know that insulin resistance plays a major role as the underlying cause for the development and potentiation of the metabolic syndrome. At present, it is unclear if the diagnosis of metabolic syndrome is greater than the sum of its parts. However, the presence of more than one of the associated risk factors should indicate that a patient is at increased risk for developing diabetes, cardiovascular disease and death. Thus, the primary care physician should aggressively treat the metabolic risk factors in their patients to prevent the onset and progression to more severe disease.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_022

Clinical implications of the insulin resistance syndrome. Insulin resistance syndrome (IRS), also termed syndrome X, is a distinctive constellation of risk factors for the development of type 2 diabetes mellitus and cardiovascular disease. The syndrome's hallmarks are glucose intolerance, hyperinsulinemia, a characteristic dyslipidemia (high triglycerides; low high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol), obesity, upper-body fat distribution, hypertension, and increased prothrombotic and antifibrinolytic factors. Insulin resistance, caused by a complex of genetic and environmental influences, is now recognized not just as a mechanism contributing to hyperglycemia in type 2 diabetes, but also as an early metabolic abnormality that precedes the development of overt diabetes. The clinical definition of insulin resistance is the impaired ability of insulin (either endogenous or exogenous) to lower blood glucose. In some insulin-resistant individuals, insulin secretion will begin to deteriorate under chronic stress (glucose toxicity) and overt diabetes will result. If not, individuals will remain hyperinsulinemic, with perhaps some degree of glucose intolerance, together with other hallmarks of the IRS. The statistical correlation between hypertension and impaired glucose tolerance is clear, although the mechanism is not yet fully understood. Epidemiologic evidence of insulin resistance as an independent risk factor for atherosclerosis and coronary heart disease (CHD) completed the evolving concept of IRS as the common soil for the development of both diabetes and CHD. No single laboratory test exists for diagnosis of IRS. Rather, IRS remains a clinically evident syndrome that can be suspected on the basis of physical and laboratory findings. This identifies individual patients whom the clinician should screen for associated comorbid conditions, aggressively control cardiovascular risk factors, and tailor drug therapy for optimal benefit. This article provides practical guidelines to achieve these goals and specific strategies to ameliorate cardiovascular and metabolic risk in the IRS.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_023

Clinical implications of the insulin resistance syndrome. Insulin resistance syndrome (IRS), also termed syndrome X, is a distinctive constellation of risk factors for the development of type 2 diabetes mellitus and cardiovascular disease. The syndrome's hallmarks are glucose intolerance, hyperinsulinemia, a characteristic dyslipidemia (high triglycerides; low high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol), obesity, upper-body fat distribution, hypertension, and increased prothrombotic and antifibrinolytic factors. Insulin resistance, caused by a complex of genetic and environmental influences, is now recognized not just as a mechanism contributing to hyperglycemia in type 2 diabetes, but also as an early metabolic abnormality that precedes the development of overt diabetes. The clinical definition of insulin resistance is the impaired ability of insulin (either endogenous or exogenous) to lower blood glucose. In some insulin-resistant individuals, insulin secretion will begin to deteriorate under chronic stress (glucose toxicity) and overt diabetes will result. If not, individuals will remain hyperinsulinemic, with perhaps some degree of glucose intolerance, together with other hallmarks of the IRS. The statistical correlation between hypertension and impaired glucose tolerance is clear, although the mechanism is not yet fully understood. Epidemiologic evidence of insulin resistance as an independent risk factor for atherosclerosis and coronary heart disease (CHD) completed the evolving concept of IRS as the common soil for the development of both diabetes and CHD. No single laboratory test exists for diagnosis of IRS. Rather, IRS remains a clinically evident syndrome that can be suspected on the basis of physical and laboratory findings. This identifies individual patients whom the clinician should screen for associated comorbid conditions, aggressively control cardiovascular risk factors, and tailor drug therapy for optimal benefit. This article provides practical guidelines to achieve these goals and specific strategies to ameliorate cardiovascular and metabolic risk in the IRS.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_024

Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications. Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_025

Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications. Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_026

Metabolic syndrome X: a review. Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_027

Metabolic syndrome X: a review. Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_028

Metabolic syndrome X: a review. Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.

According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.

5a981e66fcd1d6a10c00002f_029

Neuronally-directed effects of RXR activation in a mouse model of Alzheimer's disease. Alzheimer's disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age. Moreover, bexarotene treatment improved remote memory stabilization in fear conditioned mice and improved olfactory cross habituation. These improvements in neuron viability and function were correlated with significant increases in the levels of post-synaptic marker PSD95 and the pre-synaptic marker synaptophysin. Moreover, bexarotene pretreatment improved neuron survival in primary 5XFAD neurons in vitro in response to glutamate-induced excitotoxicity. The salutary effects of bexarotene were accompanied by reduced plaque burden, decreased astrogliosis, and suppression of inflammatory gene expression. Collectively, these data provide evidence that bexarotene treatment reduced neuron loss, elevated levels of markers of synaptic integrity that was linked to improved cognition and in an aggressive model of AD.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_001

Anesthesia/Surgery Induces Cognitive Impairment in Female Alzheimer's Disease Transgenic Mice. Anesthesia and/or surgery may promote Alzheimer's disease (AD) by accelerating its neuropathogenesis. Other studies showed different findings. However, the potential sex difference among these studies has not been well considered, and it is unknown whether male or female AD patients are more vulnerable to develop postoperative cognitive dysfunction. We therefore set out to perform a proof of concept study to determine whether anesthesia and surgery can have different effects in male and female AD transgenic (Tg) mice, and in female AD Tg plus Cyclophilin D knockout (CypD KO) mice. The mice received an abdominal surgery under sevoflurane anesthesia (anesthesia/surgery). Fear Conditioning System (FCS) was used to assess the cognitive function. Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis. Here we showed that the anesthesia/surgery decreased the freezing time in context test of FCS at 7 days after the anesthesia/surgery in female, but not male, mice. The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95 and SVP in female, but not male, mice. The anesthesia/surgery induced neither reduction in freezing time in FCS nor decreased hippocampus levels of PSD-95 and SVP in the AD Tg plus CypD KO mice. These data suggest that the anesthesia/surgery induced a sex-dependent cognitive impairment and reduction in hippocampus levels of synaptic markers in AD Tg mice, potentially via a mitochondria-associated mechanism. These findings could promote clinical investigations to determine whether female AD patients are more vulnerable to the development of postoperative cognitive dysfunction.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_002

Anesthesia/Surgery Induces Cognitive Impairment in Female Alzheimer's Disease Transgenic Mice. Anesthesia and/or surgery may promote Alzheimer's disease (AD) by accelerating its neuropathogenesis. Other studies showed different findings. However, the potential sex difference among these studies has not been well considered, and it is unknown whether male or female AD patients are more vulnerable to develop postoperative cognitive dysfunction. We therefore set out to perform a proof of concept study to determine whether anesthesia and surgery can have different effects in male and female AD transgenic (Tg) mice, and in female AD Tg plus Cyclophilin D knockout (CypD KO) mice. The mice received an abdominal surgery under sevoflurane anesthesia (anesthesia/surgery). Fear Conditioning System (FCS) was used to assess the cognitive function. Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis. Here we showed that the anesthesia/surgery decreased the freezing time in context test of FCS at 7 days after the anesthesia/surgery in female, but not male, mice. The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95 and SVP in female, but not male, mice. The anesthesia/surgery induced neither reduction in freezing time in FCS nor decreased hippocampus levels of PSD-95 and SVP in the AD Tg plus CypD KO mice. These data suggest that the anesthesia/surgery induced a sex-dependent cognitive impairment and reduction in hippocampus levels of synaptic markers in AD Tg mice, potentially via a mitochondria-associated mechanism. These findings could promote clinical investigations to determine whether female AD patients are more vulnerable to the development of postoperative cognitive dysfunction.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_004

Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy. Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (p<0.001), hippocampal (p<0.001) and cortical (p<0.05) IGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; p<0.001), and changes in neurotransmitters (VGLUT2, Tyrosine hydroxylase, GABA, ChAT). Furthermore, naïve stressed rats recorded a significant decrease in post-synaptic marker (PSD-95; p<0.01) and synaptic regulator (CaMKIIα; p<0.001). As part of the synaptic response to a decrease in brain CaMKIIα, small ion conductance channel (KCa2.2) was upregulated in the brain of naïve stressed rats (p<0.01). After a PET, an increase in IGF-1 (p<0.05) and IGF-1R was recorded in the Stress-PET group (p<0.001). As such, hippocampal (p<0.001), but not cortical (ns) synaptophysin expression increased in Stress-PET. Although PSD-95 was relatively unchanged in the hippocampus and PFC, CaMKIIα (p<0.001) and KCa2.2 (p<0.01) were upregulated in Stress-PET, and may be involved in extinction of fear memory-related synaptic potentials. These changes were also associated with a normalized neurotransmitter function, and a significant reduction in open space avoidance; when the animals were assessed in elevated plus maze (EPM). In addition to a decrease in IGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (p<0.05) and after a PET (Stress-PET; p<0.001). Furthermore, this was linked with a significant increase in HMGB1 (Hippocampus: p<0.001, PFC: p<0.05) and TLR4 expression (Hippocampus: p<0.01; PFC: ns) in the neurons. Taken together, this study showed that traumatic stress and subsequent PET involves an event-dependent alteration of IGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_006

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats. Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its ability to trigger different region-dependent changes in glutamate synapse and glial cells. The phenotype observed in males is mainly associated with marked dysregulations in the hippocampus, whereas the prevalence of alterations in the emotional sphere in females is associated with profound changes in the PFC.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_007

Cellular reactions of the central nervous system. Major cell types of the central nervous system comprise neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells, and microglia), choroid plexus cells, cells related to blood vessels and coverings. These cells show a wide range of reactions to various noxious agents, which can be detected in routine stainings. Some of these reactions are nonspecific to different injuries; however some, such as the appearance of inclusion bodies, can be highly disease-specific. Immunohistochemical markers are widely used in neuropathologic diagnostic practice and help to understand the pathogenesis of diseases. The most widely used neuronal markers comprise phosphorylated and nonphosphorylated neurofilaments, microtubule-associated protein-2, NeuN, or synaptic markers such as synaptophysin. The best antibody for the detection of astrocytes is anti-GFAP (glial fibrillar acidic protein); however, to support a glial origin, S100 or vimentin is also used in the diagnostic practice. Further astroglial markers include connexin-43, excitatory amino acid transporters, aquaporin-4, heat shock protein Hsp27, and α-B-crystallin. Depending whether the tissue is fixed or nonfixed, different oligodendroglial markers are available, such as myelin basic protein, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, proteolipid protein, Olig2, NG2, 2' 3'-cyclic nucleotide 3-phosphodiesterase (CNPase), and tubulin polymerization-promoting protein/p25 alpha (TPPP/p25). A wide range of microglia functions is recognized. Apart from a role in immune-mediated disorders, inflammation, and response to injury, microglia are important during the development and aging of the brain. The best markers include the clone CR3/43, Iba1, and CD68. Evaluation of cell reactions is the first step in the diagnostic procedure.

List the two most important synaptic markers.

5a8861eb8cb19eca6b000001_008

Diagnosing acute HIV infection at point of care: a retrospective analysis of the sensitivity and specificity of a fourth-generation point-of-care test for detection of HIV core protein p24. OBJECTIVES: Detection of acute HIV infection is vital in preventing onward transmission. HIV point-of-care testing (POCT) has improved uptake of HIV testing but has been limited to third-generation assays, which only detect chronic HIV infection. Previous evaluation of the fourth-generation Alere Determine HIV-1/2 Ag/Ab Combo POCT showed only 50% sensitivity for HIV core protein p24 (p24 antigen) detection, which is suboptimal for diagnosis of acute HIV infection with limited advantage over third-generation POCT. We aimed to assess the sensitivity of the new Alere HIV Combo POCT to detect acute HIV infection. METHODS: Stored samples in samples already identified as p24-positive using standard-of-care fourth-generation assays were randomly selected alongside groups of antibody-positive samples and HIV-negative samples. Each sample was tested using the new Alere POCT according to manufacturer's instructions. Sensitivity and specificity were then calculated. RESULTS: The Alere HIV Combo POCT test demonstrated 88% sensitivity 95% CI (78% to 98%) and 100% specificity 95% CI (99.7% to 100%) for detection of p24 antigen. CONCLUSIONS: This new POCT shows improved sensitivity for detection of p24 antigen and may be of value for clinical use in detecting acute HIV infection. Further evaluation of its use in a clinical setting is still required.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_001

Diagnosing acute HIV infection at point of care: a retrospective analysis of the sensitivity and specificity of a fourth-generation point-of-care test for detection of HIV core protein p24. OBJECTIVES: Detection of acute HIV infection is vital in preventing onward transmission. HIV point-of-care testing (POCT) has improved uptake of HIV testing but has been limited to third-generation assays, which only detect chronic HIV infection. Previous evaluation of the fourth-generation Alere Determine HIV-1/2 Ag/Ab Combo POCT showed only 50% sensitivity for HIV core protein p24 (p24 antigen) detection, which is suboptimal for diagnosis of acute HIV infection with limited advantage over third-generation POCT. We aimed to assess the sensitivity of the new Alere HIV Combo POCT to detect acute HIV infection. METHODS: Stored samples in samples already identified as p24-positive using standard-of-care fourth-generation assays were randomly selected alongside groups of antibody-positive samples and HIV-negative samples. Each sample was tested using the new Alere POCT according to manufacturer's instructions. Sensitivity and specificity were then calculated. RESULTS: The Alere HIV Combo POCT test demonstrated 88% sensitivity 95% CI (78% to 98%) and 100% specificity 95% CI (99.7% to 100%) for detection of p24 antigen. CONCLUSIONS: This new POCT shows improved sensitivity for detection of p24 antigen and may be of value for clinical use in detecting acute HIV infection. Further evaluation of its use in a clinical setting is still required.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_002

Evaluation of two 4th generation point-of-care assays for the detection of Human Immunodeficiency Virus infection. BACKGROUND: Fourth generation assays detect simultaneously antibodies for HIV and the p24 antigen, identifying HIV infection earlier than previous generation tests. Previous studies have shown that the Alere Determine HIV-1/2 Combo has lower than anticipated performance in detecting antibodies for HIV and the p24 antigen. Furthermore, there are currently very few studies evaluating the performance of Standard Diagnostics BIOLINE HIV Ag/Ab Combo. OBJECTIVE: To evaluate the performance of the Alere Determine HIV-1/2 Combo and the Standard Diagnostics BIOLINE HIV Ag/Ab Combo in a panel of frozen serum samples. STUDY DESIGN: The testing panel included 133 previously frozen serum specimens from the UCLA Clinical Microbiology & Immunoserology laboratory. Reference testing included testing for HIV antibodies by a 3rd generation enzyme immunoassay followed by HIV RNA detection. Antibody negative and RNA positive sera were also tested by a laboratory 4th generation HIV Ab/Ag enzyme immunoassay. RESULTS: Reference testing yielded 97 positives for HIV infection and 36 negative samples. Sensitivity of the Alere test was 95% (88-98%), while the SD Bioline sensitivity was 91% (83-96%). Both assays showed 100% (90-100%) specificity. No indeterminate or invalid results were recorded. Among 13 samples with acute infection (HIV RNA positive, HIV antibody negative), 12 were found positive by the first assay and 8 by the second. The antigen component of the Alere assay detected 10 acute samples, while the SD Bioline assay detected only one. CONCLUSIONS: Both rapid assays showed very good overall performance in detecting HIV infection in frozen serum samples, but further improvements are required to improve the performance in acute infection.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_003

Evaluation of two 4th generation point-of-care assays for the detection of Human Immunodeficiency Virus infection. BACKGROUND: Fourth generation assays detect simultaneously antibodies for HIV and the p24 antigen, identifying HIV infection earlier than previous generation tests. Previous studies have shown that the Alere Determine HIV-1/2 Combo has lower than anticipated performance in detecting antibodies for HIV and the p24 antigen. Furthermore, there are currently very few studies evaluating the performance of Standard Diagnostics BIOLINE HIV Ag/Ab Combo. OBJECTIVE: To evaluate the performance of the Alere Determine HIV-1/2 Combo and the Standard Diagnostics BIOLINE HIV Ag/Ab Combo in a panel of frozen serum samples. STUDY DESIGN: The testing panel included 133 previously frozen serum specimens from the UCLA Clinical Microbiology & Immunoserology laboratory. Reference testing included testing for HIV antibodies by a 3rd generation enzyme immunoassay followed by HIV RNA detection. Antibody negative and RNA positive sera were also tested by a laboratory 4th generation HIV Ab/Ag enzyme immunoassay. RESULTS: Reference testing yielded 97 positives for HIV infection and 36 negative samples. Sensitivity of the Alere test was 95% (88-98%), while the SD Bioline sensitivity was 91% (83-96%). Both assays showed 100% (90-100%) specificity. No indeterminate or invalid results were recorded. Among 13 samples with acute infection (HIV RNA positive, HIV antibody negative), 12 were found positive by the first assay and 8 by the second. The antigen component of the Alere assay detected 10 acute samples, while the SD Bioline assay detected only one. CONCLUSIONS: Both rapid assays showed very good overall performance in detecting HIV infection in frozen serum samples, but further improvements are required to improve the performance in acute infection.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_004

Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing. INTRODUCTION: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. METHODS: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. RESULTS: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19-31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5-99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5-93.7), 99.9% (95% CI 99.8-100), 99.3% (95% CI 97.4-99.8) and 99.1% (95% CI 98.8-99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01-0.24) and 8.9% (95% CI 6.3-12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. CONCLUSIONS: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_005

Evidence for a diagnostic window in fourth generation assays for HIV. BACKGROUND: The routine HIV screening essentially depends on the detection of HIV specific antibodies. However, HIV p24 antigen can be detected in individuals with recent HIV infection about 2-18 days prior to seroconversion. New fourth generation HIV screening assays combine the detection of anti-HIV antibodies with the simultaneous detection of HIV p24 antigen. This may result in a reduction of the diagnostic window after primary infection. OBJECTIVES: The performance of two novel fourth generation assays in routine diagnostic was evaluated. STUDY DESIGN: We compared two third generation, two fourth generation and one antigen HIV assays in a case with acute primary HIV infection. RESULTS: In our case, the HIV infection was detected 11 days earlier with the fourth generation assays compared to third generation assays. Interestingly, after the initial reactive results the fourth generation assays became negative resulting in a second diagnostic window. During this second diagnostic window neither third nor fourth generation HIV assays were reactive. This second diagnostic window was caused by the absence of HIV specific antibodies and the decline of HIV p24 antigen concentrations below the detection limits of the fourth generation assays. CONCLUSIONS: Fourth generation assays markedly improve the diagnosis of recent HIV infections but the possibility of a second diagnostic window must be considered.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_006

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was designed to screen blood products, not to diagnose AIDS. The first-generation assays detected IgG antibody and became positive 6 to 12 weeks postinfection. False-positive results occurred; thus, a two-test algorithm was developed using a Western blot or immunofluorescence test as a confirmatory procedure. The second-generation HIV test added recombinant antigens, and the third-generation HIV tests included IgM detection, reducing the test-negative window to approximately 3 weeks postinfection. Fourth- and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days. A new algorithm addressed the fourth-generation assay's ability to detect both antibody and antigen and yet not differentiate between them. The fifth-generation HIV assay provides separate antigen and antibody results and will require yet another algorithm. HIV infection may now be detected approximately 2 weeks postexposure, with a reduced number of false-positive results.

What is included in the fourth generation HIV test?

5a68fd01b750ff445500001b_007

The history of autonomy in medicine from antiquity to principlism. Respect for Autonomy (RFA) has been a mainstay of medical ethics since its enshrinement as one of the four principles of biomedical ethics by Beauchamp and Childress' in the late 1970s. This paper traces the development of this modern concept from Antiquity to the present day, paying attention to its Enlightenment origins in Kant and Rousseau. The rapid C20th developments of bioethics and RFA are then considered in the context of the post-war period and American socio-political thought. The validity and utility of the RFA are discussed in light of this philosophical-historical account. It is concluded that it is not necessary to embrace an ethic of autonomy in order to guard patients from coercion or paternalism, and that, on the contrary, the dominance of autonomy threatens to undermine those very things which have helped doctors come to view and respect their patients as persons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_001

An Ethical Issue in Medical Education of Obstetrics and Gynecology. There are four principles of medical ethics; Beneficence, Respect for autonomy, Non-maleficence, and Justice. It is not easy to apply to principles of medical ethics in the special circumstances of obstetrics and gynecology. Student doctors must learn to be familiar with principles of medical ethics tailored to the special circumstances while the obstetrics and gynecology practice.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_002

An Ethical Issue in Medical Education of Obstetrics and Gynecology. There are four principles of medical ethics; Beneficence, Respect for autonomy, Non-maleficence, and Justice. It is not easy to apply to principles of medical ethics in the special circumstances of obstetrics and gynecology. Student doctors must learn to be familiar with principles of medical ethics tailored to the special circumstances while the obstetrics and gynecology practice.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_003

An Ethical Issue in Medical Education of Obstetrics and Gynecology. There are four principles of medical ethics; Beneficence, Respect for autonomy, Non-maleficence, and Justice. It is not easy to apply to principles of medical ethics in the special circumstances of obstetrics and gynecology. Student doctors must learn to be familiar with principles of medical ethics tailored to the special circumstances while the obstetrics and gynecology practice.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_004

An Ethical Issue in Medical Education of Obstetrics and Gynecology. There are four principles of medical ethics; Beneficence, Respect for autonomy, Non-maleficence, and Justice. It is not easy to apply to principles of medical ethics in the special circumstances of obstetrics and gynecology. Student doctors must learn to be familiar with principles of medical ethics tailored to the special circumstances while the obstetrics and gynecology practice.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_005

Defending the four principles approach as a good basis for good medical practice and therefore for good medical ethics. This paper argues that the four prima facie principles-beneficence, non-maleficence, respect for autonomy and justice-afford a good and widely acceptable basis for 'doing good medical ethics'. It confronts objections that the approach is simplistic, incompatible with a virtue-based approach to medicine, that it requires respect for autonomy always to have priority when the principles clash at the expense of clinical obligations to benefit patients and global justice. It agrees that the approach does not provide universalisable methods either for resolving such moral dilemmas arising from conflict between the principles or their derivatives, or universalisable methods for resolving disagreements about the scope of these principles-long acknowledged lacunae but arguably to be found, in practice, with all other approaches to medical ethics. The value of the approach, when properly understood, is to provide a universalisable though prima facie set of moral commitments which all doctors can accept, a basic moral language and a basic moral analytic framework. These can underpin an intercultural 'moral mission statement' for the goals and practice of medicine.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_006

Defending the four principles approach as a good basis for good medical practice and therefore for good medical ethics. This paper argues that the four prima facie principles-beneficence, non-maleficence, respect for autonomy and justice-afford a good and widely acceptable basis for 'doing good medical ethics'. It confronts objections that the approach is simplistic, incompatible with a virtue-based approach to medicine, that it requires respect for autonomy always to have priority when the principles clash at the expense of clinical obligations to benefit patients and global justice. It agrees that the approach does not provide universalisable methods either for resolving such moral dilemmas arising from conflict between the principles or their derivatives, or universalisable methods for resolving disagreements about the scope of these principles-long acknowledged lacunae but arguably to be found, in practice, with all other approaches to medical ethics. The value of the approach, when properly understood, is to provide a universalisable though prima facie set of moral commitments which all doctors can accept, a basic moral language and a basic moral analytic framework. These can underpin an intercultural 'moral mission statement' for the goals and practice of medicine.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_007

Defending the four principles approach as a good basis for good medical practice and therefore for good medical ethics. This paper argues that the four prima facie principles-beneficence, non-maleficence, respect for autonomy and justice-afford a good and widely acceptable basis for 'doing good medical ethics'. It confronts objections that the approach is simplistic, incompatible with a virtue-based approach to medicine, that it requires respect for autonomy always to have priority when the principles clash at the expense of clinical obligations to benefit patients and global justice. It agrees that the approach does not provide universalisable methods either for resolving such moral dilemmas arising from conflict between the principles or their derivatives, or universalisable methods for resolving disagreements about the scope of these principles-long acknowledged lacunae but arguably to be found, in practice, with all other approaches to medical ethics. The value of the approach, when properly understood, is to provide a universalisable though prima facie set of moral commitments which all doctors can accept, a basic moral language and a basic moral analytic framework. These can underpin an intercultural 'moral mission statement' for the goals and practice of medicine.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_008

Defending the four principles approach as a good basis for good medical practice and therefore for good medical ethics. This paper argues that the four prima facie principles-beneficence, non-maleficence, respect for autonomy and justice-afford a good and widely acceptable basis for 'doing good medical ethics'. It confronts objections that the approach is simplistic, incompatible with a virtue-based approach to medicine, that it requires respect for autonomy always to have priority when the principles clash at the expense of clinical obligations to benefit patients and global justice. It agrees that the approach does not provide universalisable methods either for resolving such moral dilemmas arising from conflict between the principles or their derivatives, or universalisable methods for resolving disagreements about the scope of these principles-long acknowledged lacunae but arguably to be found, in practice, with all other approaches to medical ethics. The value of the approach, when properly understood, is to provide a universalisable though prima facie set of moral commitments which all doctors can accept, a basic moral language and a basic moral analytic framework. These can underpin an intercultural 'moral mission statement' for the goals and practice of medicine.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_009

[Re]considering Respect for Persons in a Globalizing World. Contemporary clinical ethics was founded on principlism, and the four principles: respect for autonomy, nonmaleficence, beneficence and justice, remain dominant in medical ethics discourse and practice. These principles are held to be expansive enough to provide the basis for the ethical practice of medicine across cultures. Although principlism remains subject to critique and revision, the four-principle model continues to be taught and applied across the world. As the practice of medicine globalizes, it remains critical to examine the extent to which both the four-principle framework, and individual principles among the four, suffice patients and practitioners in different social and cultural contexts. Using the four-principle model we analyze two accounts of surrogate decision making - one from the developed and one from the developing world - in which the clinician undertakes medical decision-making with apparently little input from the patient and/or family. The purpose of this analysis is to highlight challenges in assessing ethical behaviour according to the principlist model. We next describe cultural expectations and mores that inform both patient and clinician behaviors in these scenarios in order to argue that the principle of respect for persons informed by culture-specific ideas of personhood may offer an improved ethical construct for analyzing and guiding medical practice in a globalized and plural world.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_010

[Re]considering Respect for Persons in a Globalizing World. Contemporary clinical ethics was founded on principlism, and the four principles: respect for autonomy, nonmaleficence, beneficence and justice, remain dominant in medical ethics discourse and practice. These principles are held to be expansive enough to provide the basis for the ethical practice of medicine across cultures. Although principlism remains subject to critique and revision, the four-principle model continues to be taught and applied across the world. As the practice of medicine globalizes, it remains critical to examine the extent to which both the four-principle framework, and individual principles among the four, suffice patients and practitioners in different social and cultural contexts. Using the four-principle model we analyze two accounts of surrogate decision making - one from the developed and one from the developing world - in which the clinician undertakes medical decision-making with apparently little input from the patient and/or family. The purpose of this analysis is to highlight challenges in assessing ethical behaviour according to the principlist model. We next describe cultural expectations and mores that inform both patient and clinician behaviors in these scenarios in order to argue that the principle of respect for persons informed by culture-specific ideas of personhood may offer an improved ethical construct for analyzing and guiding medical practice in a globalized and plural world.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_011

[Re]considering Respect for Persons in a Globalizing World. Contemporary clinical ethics was founded on principlism, and the four principles: respect for autonomy, nonmaleficence, beneficence and justice, remain dominant in medical ethics discourse and practice. These principles are held to be expansive enough to provide the basis for the ethical practice of medicine across cultures. Although principlism remains subject to critique and revision, the four-principle model continues to be taught and applied across the world. As the practice of medicine globalizes, it remains critical to examine the extent to which both the four-principle framework, and individual principles among the four, suffice patients and practitioners in different social and cultural contexts. Using the four-principle model we analyze two accounts of surrogate decision making - one from the developed and one from the developing world - in which the clinician undertakes medical decision-making with apparently little input from the patient and/or family. The purpose of this analysis is to highlight challenges in assessing ethical behaviour according to the principlist model. We next describe cultural expectations and mores that inform both patient and clinician behaviors in these scenarios in order to argue that the principle of respect for persons informed by culture-specific ideas of personhood may offer an improved ethical construct for analyzing and guiding medical practice in a globalized and plural world.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_012

Islam and the four principles of medical ethics. The principles underpinning Islam's ethical framework applied to routine clinical scenarios remain insufficiently understood by many clinicians, thereby unfortunately permitting the delivery of culturally insensitive healthcare.This paper summarises the foundations of the Islamic ethical theory, elucidating the principles and methodology employed by the Muslim jurist in deriving rulings in the field of medical ethics. The four-principles approach, as espoused by Beauchamp and Childress, is also interpreted through the prism of Islamic ethical theory. Each of the four principles (beneficence, nonmaleficence,justice and autonomy) is investigated in turn, looking in particular at the extent to which each is rooted in the Islamic paradigm. This will provide an important insight into Islamic medical ethics, enabling the clinician to have a better informed discussion with the Muslim patient. It will also allow for a higher degree of concordance in consultations and consequently optimise culturally sensitive healthcare delivery.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_013

Islam and the four principles of medical ethics. The principles underpinning Islam's ethical framework applied to routine clinical scenarios remain insufficiently understood by many clinicians, thereby unfortunately permitting the delivery of culturally insensitive healthcare.This paper summarises the foundations of the Islamic ethical theory, elucidating the principles and methodology employed by the Muslim jurist in deriving rulings in the field of medical ethics. The four-principles approach, as espoused by Beauchamp and Childress, is also interpreted through the prism of Islamic ethical theory. Each of the four principles (beneficence, nonmaleficence,justice and autonomy) is investigated in turn, looking in particular at the extent to which each is rooted in the Islamic paradigm. This will provide an important insight into Islamic medical ethics, enabling the clinician to have a better informed discussion with the Muslim patient. It will also allow for a higher degree of concordance in consultations and consequently optimise culturally sensitive healthcare delivery.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_014

Islam and the four principles of medical ethics. The principles underpinning Islam's ethical framework applied to routine clinical scenarios remain insufficiently understood by many clinicians, thereby unfortunately permitting the delivery of culturally insensitive healthcare.This paper summarises the foundations of the Islamic ethical theory, elucidating the principles and methodology employed by the Muslim jurist in deriving rulings in the field of medical ethics. The four-principles approach, as espoused by Beauchamp and Childress, is also interpreted through the prism of Islamic ethical theory. Each of the four principles (beneficence, nonmaleficence,justice and autonomy) is investigated in turn, looking in particular at the extent to which each is rooted in the Islamic paradigm. This will provide an important insight into Islamic medical ethics, enabling the clinician to have a better informed discussion with the Muslim patient. It will also allow for a higher degree of concordance in consultations and consequently optimise culturally sensitive healthcare delivery.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_015

When four principles are too many: a commentary. This commentary briefly argues that the four prima facie principles of beneficence, non-maleficence, respect for autonomy and justice enable a clinician (and anybody else) to make ethical sense of the author's proposed reliance on professional guidance and rules, on law, on professional integrity and on best interests, and to subject them all to ethical analysis and criticism based on widely acceptable basic prima facie moral obligations; and also to confront new situations in the light of those acceptable principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_016

When four principles are too many: a commentary. This commentary briefly argues that the four prima facie principles of beneficence, non-maleficence, respect for autonomy and justice enable a clinician (and anybody else) to make ethical sense of the author's proposed reliance on professional guidance and rules, on law, on professional integrity and on best interests, and to subject them all to ethical analysis and criticism based on widely acceptable basic prima facie moral obligations; and also to confront new situations in the light of those acceptable principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_017

When four principles are too many: a commentary. This commentary briefly argues that the four prima facie principles of beneficence, non-maleficence, respect for autonomy and justice enable a clinician (and anybody else) to make ethical sense of the author's proposed reliance on professional guidance and rules, on law, on professional integrity and on best interests, and to subject them all to ethical analysis and criticism based on widely acceptable basic prima facie moral obligations; and also to confront new situations in the light of those acceptable principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_018

When four principles are too many: a commentary. This commentary briefly argues that the four prima facie principles of beneficence, non-maleficence, respect for autonomy and justice enable a clinician (and anybody else) to make ethical sense of the author's proposed reliance on professional guidance and rules, on law, on professional integrity and on best interests, and to subject them all to ethical analysis and criticism based on widely acceptable basic prima facie moral obligations; and also to confront new situations in the light of those acceptable principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_019

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_020

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_021

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_022

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_023

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_024

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_025

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_026

Determining the common morality's norms in the sixth edition of Principles of Biomedical Ethics. Tom Beauchamp and James Childress have always maintained that their four principles approach (otherwise known as principlism) is a globally applicable framework for biomedical ethics. This claim is grounded in their belief that the principles of respect for autonomy, non-maleficence, beneficence and justice form part of a 'common morality', or collection of very general norms to which everyone who is committed to morality subscribes. The difficulty, however, has always been how to demonstrate, at least in the absence of a full-blooded analysis of the concept of morality, whether the four principles are foundational, and so globally applicable, in this way. In the recently published sixth edition of Principles of Biomedical Ethics, an imaginative and non-question-begging empirical method of determining the common morality's norms is suggested. In this paper, I outline this method, before arguing that it is difficult to see how it might be thought to achieve its purpose.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_027

Determining the common morality's norms in the sixth edition of Principles of Biomedical Ethics. Tom Beauchamp and James Childress have always maintained that their four principles approach (otherwise known as principlism) is a globally applicable framework for biomedical ethics. This claim is grounded in their belief that the principles of respect for autonomy, non-maleficence, beneficence and justice form part of a 'common morality', or collection of very general norms to which everyone who is committed to morality subscribes. The difficulty, however, has always been how to demonstrate, at least in the absence of a full-blooded analysis of the concept of morality, whether the four principles are foundational, and so globally applicable, in this way. In the recently published sixth edition of Principles of Biomedical Ethics, an imaginative and non-question-begging empirical method of determining the common morality's norms is suggested. In this paper, I outline this method, before arguing that it is difficult to see how it might be thought to achieve its purpose.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_028

Determining the common morality's norms in the sixth edition of Principles of Biomedical Ethics. Tom Beauchamp and James Childress have always maintained that their four principles approach (otherwise known as principlism) is a globally applicable framework for biomedical ethics. This claim is grounded in their belief that the principles of respect for autonomy, non-maleficence, beneficence and justice form part of a 'common morality', or collection of very general norms to which everyone who is committed to morality subscribes. The difficulty, however, has always been how to demonstrate, at least in the absence of a full-blooded analysis of the concept of morality, whether the four principles are foundational, and so globally applicable, in this way. In the recently published sixth edition of Principles of Biomedical Ethics, an imaginative and non-question-begging empirical method of determining the common morality's norms is suggested. In this paper, I outline this method, before arguing that it is difficult to see how it might be thought to achieve its purpose.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_029

Determining the common morality's norms in the sixth edition of Principles of Biomedical Ethics. Tom Beauchamp and James Childress have always maintained that their four principles approach (otherwise known as principlism) is a globally applicable framework for biomedical ethics. This claim is grounded in their belief that the principles of respect for autonomy, non-maleficence, beneficence and justice form part of a 'common morality', or collection of very general norms to which everyone who is committed to morality subscribes. The difficulty, however, has always been how to demonstrate, at least in the absence of a full-blooded analysis of the concept of morality, whether the four principles are foundational, and so globally applicable, in this way. In the recently published sixth edition of Principles of Biomedical Ethics, an imaginative and non-question-begging empirical method of determining the common morality's norms is suggested. In this paper, I outline this method, before arguing that it is difficult to see how it might be thought to achieve its purpose.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_030

Medical ethics for children: applying the four principles to paediatrics. I will argue that there are difficulties with the application of the four principles approach to incompetent children. The most important principle - respect for autonomy - is not directly applicable to incompetent children and the most appropriate modification of the principle for them is not clear. The principle of beneficence - that one should act in the child's interests - is complicated by difficulties in assessing what a child's interests are and to which standard of interests those choosing for children should be held. A further problem with the four principles approach is that parental authority does not follow clearly from the four principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_031

Medical ethics for children: applying the four principles to paediatrics. I will argue that there are difficulties with the application of the four principles approach to incompetent children. The most important principle - respect for autonomy - is not directly applicable to incompetent children and the most appropriate modification of the principle for them is not clear. The principle of beneficence - that one should act in the child's interests - is complicated by difficulties in assessing what a child's interests are and to which standard of interests those choosing for children should be held. A further problem with the four principles approach is that parental authority does not follow clearly from the four principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_032

Ethical dilemmas in forensic psychiatry: two illustrative cases. One approach to the analysis of ethical dilemmas in medical practice uses the "four principles plus scope" approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_033

Ethical dilemmas in forensic psychiatry: two illustrative cases. One approach to the analysis of ethical dilemmas in medical practice uses the "four principles plus scope" approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_034

Ethical dilemmas in forensic psychiatry: two illustrative cases. One approach to the analysis of ethical dilemmas in medical practice uses the "four principles plus scope" approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_035

Ethical dilemmas in forensic psychiatry: two illustrative cases. One approach to the analysis of ethical dilemmas in medical practice uses the "four principles plus scope" approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_036

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_037

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_038

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_039

The four principles: can they be measured and do they predict ethical decision making? BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. METHODS: The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. RESULTS: Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. CONCLUSIONS: People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_040

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_041

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_042

Medical ethics: four principles, two decisions, two roles and no reasons. The 'four principle' view of medical ethics has a strong international pedigree. Despite wide acceptance, there is controversy about the meaning and use of the principles in clinical practice as a checklist for moral behaviour. Recent attempts by medical regulatory authorities to use the four principles to judge medical practitioner behaviour have not met with success in clarifying how these principles can be incorporated into a legal framework. This may reflect the philosophical debate about the relationship between law and morals. In this paper, legal decisions from two cases in which general practitioners have been charged with professional shortcomings are discussed. Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. The four principles are relevant to medical practitioner behaviour, but if applied as justifications for disciplinary decisions without explanation, perverse results may ensue. Solutions are suggested to minimise ambiguities in the application of the four principles: adjudicators should acknowledge the difference between professional and common morality and the statutory requirement to give decisions with reasons.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_043

Preparedness: medical ethics versus public health ethics. Medical ethics generally applies to individual interactions between physicians and patients. Conversely, public health ethics typically applies to interactions between an agency or institution and a community or population. Four main principles underlie medical ethics: autonomy, nonmaleficence, beneficence, and justice. By contrast, public health ethical principles address issues such as interdependence, community trust, fundamentality, and justice. In large part because of the significant community-level effects of public health issues, medical ethics are suboptimal for assessing community-level public health interventions or plans-especially in the area of emergency preparedness. To be effective, as well as ethical, public health preparedness efforts must address all of the core principles of public health ethics.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_044

Preparedness: medical ethics versus public health ethics. Medical ethics generally applies to individual interactions between physicians and patients. Conversely, public health ethics typically applies to interactions between an agency or institution and a community or population. Four main principles underlie medical ethics: autonomy, nonmaleficence, beneficence, and justice. By contrast, public health ethical principles address issues such as interdependence, community trust, fundamentality, and justice. In large part because of the significant community-level effects of public health issues, medical ethics are suboptimal for assessing community-level public health interventions or plans-especially in the area of emergency preparedness. To be effective, as well as ethical, public health preparedness efforts must address all of the core principles of public health ethics.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_045

Preparedness: medical ethics versus public health ethics. Medical ethics generally applies to individual interactions between physicians and patients. Conversely, public health ethics typically applies to interactions between an agency or institution and a community or population. Four main principles underlie medical ethics: autonomy, nonmaleficence, beneficence, and justice. By contrast, public health ethical principles address issues such as interdependence, community trust, fundamentality, and justice. In large part because of the significant community-level effects of public health issues, medical ethics are suboptimal for assessing community-level public health interventions or plans-especially in the area of emergency preparedness. To be effective, as well as ethical, public health preparedness efforts must address all of the core principles of public health ethics.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_046

The medical ethics of paid egg sharing in the UK. Paid egg sharing occurs when infertile patients receive infertility treatment free or at reduced cost in exchange for sharing some of their eggs with patients who require donated eggs. This approach to treatment is discussed in the context of the four principles of medical ethics, namely respect for autonomy, justice, beneficence and non-maleficence. The implications of these ethical considerations for responsible practice and regulation are considered.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_047

The medical ethics of paid egg sharing in the UK. Paid egg sharing occurs when infertile patients receive infertility treatment free or at reduced cost in exchange for sharing some of their eggs with patients who require donated eggs. This approach to treatment is discussed in the context of the four principles of medical ethics, namely respect for autonomy, justice, beneficence and non-maleficence. The implications of these ethical considerations for responsible practice and regulation are considered.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_048

The medical ethics of paid egg sharing in the UK. Paid egg sharing occurs when infertile patients receive infertility treatment free or at reduced cost in exchange for sharing some of their eggs with patients who require donated eggs. This approach to treatment is discussed in the context of the four principles of medical ethics, namely respect for autonomy, justice, beneficence and non-maleficence. The implications of these ethical considerations for responsible practice and regulation are considered.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_049

The medical ethics of paid egg sharing in the UK. Paid egg sharing occurs when infertile patients receive infertility treatment free or at reduced cost in exchange for sharing some of their eggs with patients who require donated eggs. This approach to treatment is discussed in the context of the four principles of medical ethics, namely respect for autonomy, justice, beneficence and non-maleficence. The implications of these ethical considerations for responsible practice and regulation are considered.

List four principles of medical ethics.

5a6f7e6ab750ff4455000052_050

Heerfordt's Syndrome Presenting with Recurrent Facial Nerve Palsy: Case report and 10-year literature review. Heerfordt's syndrome is defined as a combination of facial palsy, parotid swelling, uveitis and fever in sarcoidosis cases. Heerfordt's syndrome as a cause of facial palsy is very rare. We report a case of alternating facial nerve palsy in a 52-year-old female initially treated for Bell's palsy. The patient was referred to the All India Institute of Medical Sciences, Bhubaneswar, India, in January 2013 for clinical evaluation. She was found to have a parotid swelling and anterior intermediate uveitis. A pathoradiological evaluation suggested sarcoidosis and a final diagnosis of Heerfordt's syndrome was made. Steroid treatment was initiated which led to an improvement in the facial palsy and uveitis as well as the disappearance of the parotid swelling with a corresponding decrease in angiotensin-converting enzyme levels. An English literature review was carried out to analyse the varied presentation of this syndrome. The analysis focused on presenting symptoms, biochemical markers and radiological findings of Heerfordt's syndrome cases.

List symptoms of Heerfordt syndrome.

5a70d12899e2c3af26000001_001

Heerfordt's Syndrome Presenting with Recurrent Facial Nerve Palsy: Case report and 10-year literature review. Heerfordt's syndrome is defined as a combination of facial palsy, parotid swelling, uveitis and fever in sarcoidosis cases. Heerfordt's syndrome as a cause of facial palsy is very rare. We report a case of alternating facial nerve palsy in a 52-year-old female initially treated for Bell's palsy. The patient was referred to the All India Institute of Medical Sciences, Bhubaneswar, India, in January 2013 for clinical evaluation. She was found to have a parotid swelling and anterior intermediate uveitis. A pathoradiological evaluation suggested sarcoidosis and a final diagnosis of Heerfordt's syndrome was made. Steroid treatment was initiated which led to an improvement in the facial palsy and uveitis as well as the disappearance of the parotid swelling with a corresponding decrease in angiotensin-converting enzyme levels. An English literature review was carried out to analyse the varied presentation of this syndrome. The analysis focused on presenting symptoms, biochemical markers and radiological findings of Heerfordt's syndrome cases.

List symptoms of Heerfordt syndrome.

5a70d12899e2c3af26000001_002

The Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis. Sarcoidosis is a granulomatous disease of unclear etiology, which commonly presents with cough, dyspnea, chest pain, fever, weight loss, arthralgias, and erythema nodosum. Heerfordt-Waldenström syndrome, a rare presentation of sarcoidosis, is characterized by the presence of parotid gland enlargement, facial palsy, anterior uveitis, and fever. Here we present a case of a 59-year-old nonsmoking African American woman who presented with 3 days of progressively worsening left facial droop, difficulty swallowing, and blurred vision. Over the prior 4 months, she had had a productive cough, fevers, night sweats, and an unintentional 30-pound weight loss. Physical examination revealed a left facial droop involving the forehead, cheek, and chin with an inability to close the left eyelid. Her serum angiotensin-converting enzyme level was twice the upper limit of normal. Prominent hilar markings were identified on chest x-ray, but no focal opacity was seen. Fine-needle aspiration of a preauricular lymph node revealed noncaseating granulomas consistent with granulomatous lymphangitis. The patient was given a diagnosis of Heerfordt-Waldenström syndrome, or uveoparotid fever. Treatment with a high-dose steroid improved her parotid gland enlargement, facial palsy, and anterior uveitis.

List symptoms of Heerfordt syndrome.

5a70d12899e2c3af26000001_003

The Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis. Sarcoidosis is a granulomatous disease of unclear etiology, which commonly presents with cough, dyspnea, chest pain, fever, weight loss, arthralgias, and erythema nodosum. Heerfordt-Waldenström syndrome, a rare presentation of sarcoidosis, is characterized by the presence of parotid gland enlargement, facial palsy, anterior uveitis, and fever. Here we present a case of a 59-year-old nonsmoking African American woman who presented with 3 days of progressively worsening left facial droop, difficulty swallowing, and blurred vision. Over the prior 4 months, she had had a productive cough, fevers, night sweats, and an unintentional 30-pound weight loss. Physical examination revealed a left facial droop involving the forehead, cheek, and chin with an inability to close the left eyelid. Her serum angiotensin-converting enzyme level was twice the upper limit of normal. Prominent hilar markings were identified on chest x-ray, but no focal opacity was seen. Fine-needle aspiration of a preauricular lymph node revealed noncaseating granulomas consistent with granulomatous lymphangitis. The patient was given a diagnosis of Heerfordt-Waldenström syndrome, or uveoparotid fever. Treatment with a high-dose steroid improved her parotid gland enlargement, facial palsy, and anterior uveitis.

List symptoms of Heerfordt syndrome.

5a70d12899e2c3af26000001_004