Impact of metformin on feeding, behavior, and metabolism in Drosophila melanogaster.

Metformin is a first-line drug used in the treatment of type II diabetes mellitus and is the 4th-most prescribed drug in the United States. It functions in lowering blood glucose levels and increasing insulin sensitivity. Despite its wide scale use, the degree to which it affects aspects of behavior and metabolism unrelated to diabetes is not fully understood. Recent studies have attempted to fill this gap, particularly in the context of metformin’s impact on lifespan. We decided to extend this research by focusing on measurable behaviors as well as traits related to metabolism and physiology. Using the fruit fly Drosophila melanogaster as a model organism, we investigated metformin’s impacts on food consumption, body weight, starvation resistance, and sleep. We observed preliminary evidence of increased feeding in Drosophila when given a metformin-supplemented diet. The same diet had an effect on body weight while making the flies less vulnerable to starvation stress. Metformin did not appear to have a significant impact on sleep patterns, except at low concentrations. These data show that metformin does cause multiple levels of side effects in the whole organism level. Given that the molecular pathways of metformin action are conserved between Drosophila and humans, similar effects on food consumption and weight may be found in human subjects treated with metformin. Future study should include an analysis of the molecular, genetic, and neuronal mechanisms of the above physiological and metabolic changes

Us adolescent Rest-Activity Patterns: insights From Functional Principal Component analysis (Nhanes 2011-2014)

BACKGROUND: Suboptimal rest-activity patterns in adolescence are associated with worse health outcomes in adulthood. Understanding sociodemographic factors associated with rest-activity rhythms may help identify subgroups who may benefit from interventions. This study aimed to investigate the association of rest-activity rhythm with demographic and socioeconomic characteristics in adolescents. METHODS: Using cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) 2011-2014 adolescents (N = 1814), this study derived rest-activity profiles from 7-day 24-hour accelerometer data using functional principal component analysis. Multiple linear regression was used to assess the association between participant characteristics and rest-activity profiles. Weekday and weekend specific analyses were performed in addition to the overall analysis. RESULTS: Four rest-activity rhythm profiles were identified, which explained a total of 82.7% of variance in the study sample, including (1) High amplitude profile; (2) Early activity window profile; (3) Early activity peak profile; and (4) Prolonged activity/reduced rest window profile. The rest-activity profiles were associated with subgroups of age, sex, race/ethnicity, and household income. On average, older age was associated with a lower value for the high amplitude and early activity window profiles, but a higher value for the early activity peak and prolonged activity/reduced rest window profiles. Compared to boys, girls had a higher value for the prolonged activity/reduced rest window profiles. When compared to Non-Hispanic White adolescents, Asian showed a lower value for the high amplitude profile, Mexican American group showed a higher value for the early activity window profile, and the Non-Hispanic Black group showed a higher value for the prolonged activity/reduced rest window profiles. Adolescents reported the lowest household income had the lowest average value for the early activity window profile. CONCLUSIONS: This study characterized main rest-activity profiles among the US adolescents, and demonstrated that demographic and socioeconomic status factors may shape rest-activity behaviors in this population

Sensitivity and specificity of a commercial urinary ethyl glucuronide (ETG) test in heavy drinkers.

Introduction:To advance the use of alcohol metabolites as biomarkers in the context of alcohol research, the present study tested the sensitivity and specificity of a commercially available urinary ethyl glucuronide (uEtG) test (DrugConfirm Advanced 80hr EtG) in a clinical research context. Methods:A community sample of heavy drinkers (N = 68) completed the 30-day Timeline Follow-Back (TLFB) interview and provided a urine sample for uEtG analysis. Analyses of sensitivity and specificity of the uEtG assay were conducted using the following outcomes: (a) past day drinking, (b) past day binge drinking (defined as ≥4 drinks for women and ≥5 drinks for men), (c) past 3-day drinking, and (d) past 3-day binge drinking. Results:The majority of participants reported past-3-day drinking (80.9%) and a sizeable minority reported past day drinking (33.8%). While uEtG-based detection of past day drinking and binge drinking was acceptable (sensitivity = 73.91%, and 83.33%; specificity = 80.00% and 66.13%, respectively), detection of any drinking and binge drinking in the past 3 days was poor (sensitivity and specificity of 43.64% and 84.62%, and 39.39% and 62.86%, respectively). Conclusions:This study contributes to the mixed findings on the validity of EtG tests, which suggest that commercial uEtG tests with conservative detection thresholds are not a reliable alcohol biomarker without corroborating self-report data. Lower detection thresholds are recommended when using uEtG as an alcohol biomarker. Efforts to reach acceptable levels of sensitivity and specificity with commercial assays hold potential to advance the measurement of alcohol intake, overcoming the pitfalls of self-report data

2022 Indiana Family Medicine Residencies Exit Survey Report

In order to plan effective healthcare workforce development initiatives, it is important to understand the reasons why Indiana family medicine residents choose to practice in specific locations. Thus, having a better understanding of the factors that influence how residents choose a practice location will help improve efforts to recruit and retain family medicine physicians in areas of need within the state. The 2022 Indiana Family Medicine Residencies Exit Survey© determines what these physicians plan to do after graduation; and, for those planning to primarily provide clinical care, to determine where they plan to practice. In addition, the survey also obtained overall feedback on the residents’ training and their program’s curricula, as well as ideas and suggestions for improvement.Indiana Medical Education Boar

Luminal hypertonicity and acidity modulate colorectal afferents and induce persistent visceral hypersensitivity

Carbohydrate malabsorption such as in lactose intolerance or enteric infection causes symptoms that include abdominal pain. Because this digestive disorder increases intracolonic osmolarity and acidity by accumulation of undigested carbohydrates and fermented products, we tested whether these two factors (hypertonicity and acidity) would modulate colorectal afferents in association with colorectal nociception and hypersensitivity. In mouse colorectum-pelvic nerve preparations in vitro, afferent activities were monitored after application of acidic hypertonic saline (AHS; pH 6.0, 800 mosM). In other experiments, AHS was instilled intracolonically to mice and behavioral responses to colorectal distension (CRD) measured. Application of AHS in vitro excited 80% of serosal and 42% of mechanically-insensitive colorectal afferents (MIAs), sensitizing a proportion of MIAs to become mechanically sensitive and reversibly inhibiting stretch-sensitive afferents. Acute intracolonic AHS significantly increased expression of the neuronal activation marker pERK in colon sensory neurons and augmented noxious CRD-induced behavioral responses. After three consecutive daily intracolonic AHS treatments, mice were hypersensitive to CRD 4-15 days after the first treatment. In complementary single fiber recordings in vitro, the proportion of serosal class afferents increased at day 4; the proportion of MIAs decreased, and muscular class stretch-sensitive afferents were sensitized at days 11-15 in mice receiving AHS. These results indicate that luminal hypertonicity and acidity, two outcomes of carbohydrate malabsorption, can induce colorectal hypersensitivity to distension by altering the excitability and relative proportions of colorectal afferents, suggesting the potential involvement of these factors in the development of abdominal pain.Fil: La, Jun Ho. University of Pittsburgh; Estados UnidosFil: Feng, Bin. University of Pittsburgh; Estados UnidosFil: Schwartz, Erica S.. University of Pittsburgh; Estados UnidosFil: Brumovsky, Pablo Rodolfo. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gebhart, G. F.. University of Pittsburgh; Estados Unido

Adherence to guidelines and the Screening Tool of Older Persons' potentially inappropriate Prescriptions criteria for colchicine dosing for gout treatment in beneficiaries of the Nova Scotia Seniors' Pharmacare Program Clinical Therapeutics

Purpose: Colchicine is commonly used in the management of gout; however, older persons have higher risks of toxicity. Accordingly, the Screening Tool of Older Person’s potentially inappropriate Prescriptions (STOPP) criteria for colchicine consider 43 months of treatment as potentially inappropriate in older persons. Recent evidence also suggests lower dosing of colchicine is as effective and results in fewer toxicities than high-dose colchicine. The objectives of this study were to determine the dose, duration, and prescribers of colchicine and to evaluate adherence to the STOPP criteria and international guidelines for colchicine in older persons. Methods: A retrospective, observational study was conducted from April 1, 2006 to March 31, 2011 to evaluate colchicine use. Nova Scotia Seniors’ Pharmacare Program beneficiaries who met inclusion criteria for an incident case of gout and who filled at least 1prescription for colchicine during the study period were included. Colchicine dose and duration were reported descriptively. Multivariate logistic regression was used to identify predictors of the study population in making a claim for colchicine 490 and 4180 days. Findings: A total of 518 persons were dispensed 1327 courses of colchicine during the study period. The mean daily dose of colchicine ranged from 1.39 to 1.50 mg. Colchicine doses 41.2 mg were prescribed in approximately one-third of the study population. Colchicine was prescribed for 490 days in 14.2% of treatment courses and for 4180 days in 8.1% of treatment courses. Female sex was the only predictor of treatment duration 490 days. Implications: This study is the first to report on colchicine dose and duration using STOPP criteria in a specific cohort of older persons with incident gout. Strategies to improve colchicine prescribing in older persons are needed

An International Multi-center Study on Self-assessed and Family Quality of Life in Children with Atopic Dermatitis

Atopic dermatitis (AD) is a common childhood chronic inflammatory skin condition that greatly affects the quality of life (QoL) of affected children and their families. The aim of our study was to assess QoL and family QoL of children with AD from 4 different countries and then compare the data, evaluating the effects of AD severity and age of children. Data on the Children’s Dermatology Life Quality Index (CDLQI) and the Dermatitis Family Impact (DFI) questionnaires and the SCORAD index of 167 AD children 5-16 years old from Ukraine, Czech Republic, Singapore, and Italy was used for the study. SCORAD correlated with the CDLQI in all 4 countries and with DFI in all countries except Singapore. Only in Czech children did the CDLQI correlate with their age. No significant correlations between age and DFI results were found. AD symptoms and expenditures related to AD were highly scored in all countries. Impact of AD on friendship and relations between family members were among the lower scored items, and family problems did not increase proportionately with duration of AD in any of the four countries. Self-assessed health-related QoL of children with AD in our study correlated better in most cases with disease severity than family QoL results. Parents of school children with AD were generally less stressed, tired, and exhausted than parents of preschool children. These data together with results showing that duration of AD in children does not affect relations between parents and other family members is optimistic news for families with children with AD who did not recover until adolescence.</p

2021 Indiana Family Medicine Residencies Exit Survey Report

In order to plan effective healthcare workforce development initiatives, it is important to understand the reasons why Indiana family medicine residents choose to practice in specific locations. Thus, having a better understanding of the factors that influence how residents choose a practice location will help improve efforts to recruit and retain family medicine physicians in areas of need within the state. The 2021 Indiana Family Medicine Residencies Exit Survey© determines what these physicians plan to do after graduation; and, for those planning to primarily provide clinical care, to determine where they plan to practice. In addition, the survey also obtained overall feedback on the residents’ training and their program’s curricula, as well as ideas and suggestions for improvement.Indiana Medical Education Boar

2021 Graduate Medical Education Exit Survey Report

In order to plan effective healthcare workforce development initiatives, it is important to understand the reasons why the Indiana University School of Medicine (IUSM) residency and fellowship graduates’ choose to practice in specific locations. This study documented the proportion of residency and fellowship graduates that were planning to practice in areas of need in Indiana. The 2021 IUSM Graduate Medical Education Exit Survey© identified factors affecting graduates’ choice of practice location and gathered feedback on their self-rated level of competency training to serve the rural and underserved populations; assessment of their training program and the six Accreditation Council for Graduate Medical Education (ACGME) competency areas.IUSM Office of Graduate Medical Educatio

Intrathecal Morphine and Post-Operative Pain Relief in Robotic Surgeries : A Systematic Review and Meta-Analysis

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