Antidiabetic effectiveness of Phyllanthus niruri bioactive compounds via targeting DPP-IV.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

Compliance of Adolescent Friendly Health Clinics with National and International Standards: Quantitative findings from the i-Saathiya study.

OBJECTIVE: Indian adolescents experience several health challenges requiring acceptable, equitable, appropriate and effective healthcare services. Our objective was to assess the compliance of Adolescent Friendly Health Clinics (AFHCs) in two of India's largest states, using both national benchmarks (under Rashtriya Kishor Swasthya Karyakram-RKSK) and global standards (by WHO). DESIGN: Cross-sectional study comprising structured observations and interactions (November 2021 to June 2022). SETTING: Fourteen AFHCs across all levels of health system were included from two districts of Maharashtra (n=8) and Madhya Pradesh (n=6). These AFHCs were observed using checklist, and few items of checklist were verified by interactions with AFHC's health workers (medical officers/auxillary nurse midwives/counsellors) handlings adolescents. The developed checklist included 57 items based on adapted global standards and 25 items using national benchmarks. RESULT: High compliance of AFHCs with RKSK's benchmarks was attributed to various items including the accessibility through local transport (n=14, 100%), clean surroundings (n=11, 78.5%), presence of signage (n=10, 71.4%), convenient operating days and time (n=11, 78.5%), and secure storage of records (n=13, 92.9%). Concurrently, items that showed low compliance encompassed, the availability of Information, Education and communication (IEC) resources, which were deficient in 57.1% of AFHCs (n=8). Similarly, designated areas for clinical services (n=10, 71.4%) and commodity disbursement (n=9, 64.3%) lacked in more than half of the recruited AFHCs. Additionally, lack of guidelines for referrals (n=13, 92.9%), as well as standard operating procedures to ensure equity, non-judgemental attitude, competence, confidentiality and referral as per WHO standards. CONCLUSION: Evidence spotlights the strengths and gaps in AFHCs, aligning with, government's priorities on adolescent health. Addressing the identified gaps is crucial to creating healthcare facilities that are adolescent-friendly, easily accessible and effectively navigate adolescent health challenges. This concerted effort would contribute to their development and transformation, playing a pivotal role in India's progress.

Delirium among people aging with and without HIV: Role of alcohol and Neurocognitively active medications.

BACKGROUND: People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs. METHODS: Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, race/ethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The case/control date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Medication exposure was measured from 45 to 3 days prior to index date; medications were classified as anticholinergic NCAM, non-anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses. RESULTS: PWH experienced a higher incidence of delirium (5.6, [95% CI 5.3-5.9/1000 PY]) than PWoH (5.0, [95% CI 4.8-5.1/1000 PY]). In multivariable analysis, anticholinergic and non-anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose-response associations with delirium. CONCLUSIONS: Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH.

CD4+ cell count and outcomes among HIV-infected compared with uninfected medical ICU survivors in a national cohort.

BACKGROUND: People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count. SETTING: We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015. METHODS: Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors. RESULTS: In adjusted models, CD4+ categories <350 cells/µl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200-349 hazard ratio [HR] = 1.35 [1.12-1.63]; CD4+ <50 HR = 2.14 [1.72-2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points. CONCLUSION: PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors.

The Association Between Hospital End-of-Life Care Quality and the Care Received Among Patients With Heart Failure.

CONTEXT: Improving end-of-life care (EOLC) quality among heart failure patients is imperative. Data are limited as to the hospital processes of care that facilitate this goal. OBJECTIVES: To determine associations between hospital-level EOLC quality ratings and the EOLC delivered to heart failure patients. METHODS: Retrospective analysis of the Veterans Health Administration (VA) and the Bereaved Family Survey data of heart failure patients from 2013 to 2015 who died in 107 VA hospitals. We calculated hospital-level observed-to-expected casemix-adjusted ratios of family reported excellent EOLC, dividing hospitals into quintiles. Using logistic regression, we examined associations between quintiles and palliative care consultation, receipt of chaplain and bereavement services, inpatient hospice, and intensive care unit death. RESULTS: Of 6256 patients, mean age was 77.4 (SD = 11.1), 98.3% were male, 75.7% were white, and 18.2% were black. Median hospital scores of "excellent" EOLC ranged from 41.3% (interquartile range 37.0%-44.8%) in the lowest quintile to 76.4% (interquartile range 72.9%-80.3%) in the highest quintile. Patients who died in hospitals in the highest quintile, relative to the lowest, were slightly although not significantly more likely to receive a palliative care consultation (adjusted proportions 57.6% vs. 51.2%; P = 0.32) but were more likely to receive chaplaincy (92.6% vs. 81.2%), bereavement (86.0% vs. 72.2%), and hospice (59.7% vs. 35.9%) and were less likely to die in the intensive care unit (15.9% vs. 31.0%; P < 0.05 for all). CONCLUSION: Patients with heart failure who die in VA hospitals with higher overall EOLC quality receive more supportive EOLC. Research is needed that integrates care processes and develops scalable best practices in EOLC across health care systems.

Correction to: Excess Weight Gain After Cure of Hepatitis C Infection with Direct-Acting Antivirals.

JGIM published the article matched with the editorial in this issue in the July 2020 issue. Our apologies to the authors of the paper and the editorial.

Excess Weight Gain After Cure of Hepatitis C Infection with Direct-Acting Antivirals.

BACKGROUND: Cure from chronic hepatitis C virus (HCV) infection is readily achievable with direct-acting antivirals (DAA), but little is known about optimal management after treatment. Weight gained after DAA treatment may mitigate benefits or increase risk for liver disease progression. As the single largest sample of HCV-infected individuals receiving DAA treatment in the United States, the Veterans Affairs (VA) Birth Cohort is an ideal setting to assess weight gain after DAA treatment. METHODS: We performed a prospective study of patients dispensed DAA therapy from January 2014 to June 2015. Weight change was calculated as the difference in weight from sustained virologic response (SVR) determination to 2 years later. Demographic, weight, height, prescription, laboratory, and diagnosis code data were used for covariate definitions. We used multiple logistic regression to assess the association between candidate predictors and excess weight gain (≥ 10 lbs) after 2 years. RESULTS: Among 11,469 patients, 78.0% of patients were already overweight or obese at treatment initiation. Overall, SVR was achieved in 97.0% of patients. After 2 years, 52.6% of patients gained weight and 19.8% gained excess weight. In those with SVR, weight gain was as high as 38.2 lbs, with the top 10% gaining ≥ 16.5 lbs. Only 1% of those with obesity at treatment initiation normalized their weight class after 2 years. Significant predictors of post-SVR weight gain were SVR achievement, lower age, high FIB-4 score, cirrhosis, and weight class at treatment initiation. CONCLUSION: Weight gain is common after DAA treatment, even among those who are overweight or obese prior to treatment. Major predictors include age, baseline weight, alcohol, cirrhosis, and SVR. Everyone receiving DAAs should be counseled against weight gain with a particular emphasis among those at higher risk.

Polypharmacy Increases Risk of Dyspnea Among Adults With Serious, Life-Limiting Diseases.

BACKGROUND: Polypharmacy is associated with dyspnea in cross-sectional studies, but associations have not been determined in longitudinal analyses. Statins are commonly prescribed but their contribution to dyspnea is unknown. We determined whether polypharmacy was associated with dyspnea trajectory over time in adults with advanced illness enrolled in a statin discontinuation trial, overall, and in models stratified by statin discontinuation. METHODS: Using data from a parallel-group unblinded pragmatic clinical trial (patients on statins ≥3 months with life expectancy of 1 month to 1 year, enrolled in the parent study between June 3, 2011, and May 2, 2013, n = 308/381 [81%]), we restricted analyses to patients with available baseline medication count and ≥1 dyspnea score. Polypharmacy was assessed by self-reported chronic medication count. Dyspnea trajectory group, our primary outcome, was determined over 24 weeks using the Edmonton Symptom Assessment System. RESULTS: The mean age of the patients was 73.8 years (standard deviation [SD]: ±11.0) and the mean medication count was 11.6 (SD: ±5.0). We identified 3 dyspnea trajectory groups: none (n = 108), mild (n = 130), and moderate-severe (n = 70). Statins were discontinued in 51.8%, 48.5%, and 42.9% of patients, respectively. In multivariable models adjusting for age, sex, diagnosis, and statin discontinuation, each additional medication was associated with 8% (odds ratio [OR] = 1.08 [1.01-1.14]) and 16% (OR = 1.16 [1.08-1.25]) increased risk for mild and moderate-severe dyspnea, respectively. In stratified models, polypharmacy was associated with dyspnea in the statin continuation group only (mild OR = 1.12 [1.01-1.24], moderate-severe OR = 1.24 [1.11-1.39]) versus statin discontinuation (mild OR = 1.03 [0.95-1.12], and moderate-severe OR = 1.09 [0.98-1.22]). CONCLUSION: Polypharmacy was strongly associated with dyspnea. Prospective interventions to decrease polypharmacy may impact dyspnea symptoms, especially for statins.

Self-Reported Cognitive Function and Mental Health Diagnoses among Former Professional American-Style Football Players.

Clinical practice strongly relies on patients' self-report. Former professional American-style football players are hesitant to seek help for mental health problems, but may be more willing to report cognitive symptoms. We sought to assess the association between cognitive symptoms and diagnosed mental health problems and quality of life among a cohort of former professional players. In a cross-sectional design, we assessed self-reported cognitive function using items from the Quality of Life in Neurological Disorders (Neuro-QOL) Item Bank. We then compared mental health diagnoses and quality of life, assessed by items from the Patient-Reported Outcome Measurement Information System (PROMIS®), between former professional players reporting daily problems in cognitive function and former players not reporting daily cognitive problems. Of the 3758 former professional players included in the analysis, 40.0% reported daily problems due to cognitive dysfunction. Former players who reported daily cognitive problems were more likely to also report depression (18.0% vs. 3.3%, odds ratio [OR] = 6.42, 95% confidence interval [CI] [4.90-8.40]) and anxiety (19.1% vs. 4.3%, OR = 5.29, 95% CI [4.14-6.75]) than those without daily cognitive problems. Further, former players reporting daily cognitive problems were more likely to report memory loss and attention deficit(/hyperactivity) disorder and poorer general mental health, lower quality of life, less satisfaction with social activities and relationships, and more emotional problems. These findings highlight the potential of an assessment of cognitive symptoms for identifying former players with mental health, social, and emotional problems.

Increased CMV IgG Antibody Titer is Associated with Non-AIDS Events among Virologically Suppressed HIV-Positive Persons.

BACKGROUND: Among HIV-positive individuals, increased levels of inflammation and immune activation persist even in the setting of effective antiretroviral therapy (ART) and are associated with greater rates of non-AIDS events. The etiology of this persistent inflammation is incompletely understood. METHODS: Using a well-characterized cohort of 322 HIV-infected individuals on suppressive ART, we conducted a case-control study. Cytomegalovirus (CMV) immunoglobulin G (IgG) levels, plasma biomarkers, and T-cell phenotypes were measured/characterized from samples collected 1 year after ART initiation. Conditional logistic regression for matched case-control studies analyzed the associations of year 1 CMV-specific IgG level with the subsequent occurrence of any non-AIDS event. Correlations between continuous CMV IgG antibody levels and soluble and cellular markers were assessed. RESULTS: We found that higher levels of CMV IgG were associated with increased risk of non-AIDS events (OR = 1.58 per IQR [95% CI: 1.12, 2.24], P = 0.01) and with elevated soluble and cellular markers of inflammation. CONCLUSIONS: The magnitude of the host immune response to CMV may play a role in the persistent inflammation and resultant morbid events observed in the HIV-positive population.

Regional and Rural-Urban Differences in the Use of Direct-acting Antiviral Agents for Hepatitis C Virus: The Veteran Birth Cohort.

BACKGROUND: Veterans with hepatitis C virus (HCV) infection may face geographic obstacles to obtaining treatment. OBJECTIVE: We studied the influence of region and rural versus urban residence on receipt of direct-acting antiretroviral (DAA) medications for HCV. SUBJECTS: Veterans receiving care within Veterans Affairs Healthcare System born between 1945 and 1965. RESEARCH DESIGN: This is a observational study using national electronic health record data. MEASURES: Receipt of DAAs was defined as ≥1 filled prescription from January 1, 2014 to December 31, 2016. Region (South, Northeast, Midwest, and West) and residence (urban, rural-micropolitan, small rural towns, and isolated rural towns) variables were created using residential zone improvement plan codes and rural-urban commuting area (RUCA) codes. Multivariable models were adjusted for age, race, sex, severity of liver disease, comorbidities, and prior treatment experience. RESULTS: Among 166,353 eligible patients 64,854 received, DAAs. Variation by rural-urban residence depended on region. In unadjusted analyses, receipt varied by rural-urban designations within Midwest, and West regions (P<0.05) but did not vary within the South (P=0.12). Southern rural small town had the lowest incidence of DAA receipt (40.1%), whereas the incidence was 52.9% in Midwestern isolated rural towns. In adjusted logistic analyses, compared with southern urban residents (the largest single group), southern rural small town residents had the lowest odds ratio, 0.85 (95% confidence interval, 0.75-0.93), and Midwestern residents from isolated and small rural towns had the highest odds (odds ratio, both 1.27) to receive treatment. CONCLUSIONS: Substantial geographic variation exists in receipt of curative HCV treatment. Efforts are needed to provide more equitable access to DAAs.

Relation of Anterior Cruciate Ligament Tears to Potential Chronic Cardiovascular diseases.

We have enrolled a cohort of former National Football League players (n = 3,506) who played since 1960 to assess potential long term health consequences associated with participating in the sport. Each participant has completed a self-administered questionnaire including reporting of physician-diagnosed health conditions. One of the early assessments was to evaluate whether anterior cruciate ligament (ACL) tears were associated with later life co-morbidities, including cardiovascular effects. We used Cox proportional hazards to estimate hazard ratios (HR) for joint replacement surgeries, myocardial infarction, sleep apnea, arthritis, dementia, and stroke by history of ACL tear during their professional career. For additional outcomes without date of occurrence reported we used logistic regression to estimate odds ratios adjusted for potential confounding variables in all models. After adjusting for covariates, former National Football League players who tore their ACL had approximately a twofold increase in muscular skeletal co-morbidities, including knee joint replacement and arthritis, compared with those without ACL tears. In addition, those with a history of ACL tears also had more than a 50% increased risk of myocardial infarction (HR 1.52; 95% confidence interval 0.97 to 2.38) and a slight increase in sleep apnea (HR 1.15; 95% confidence interval 0.96 to 1.38). ACL tears sustained by athletes may increase the risk of co-morbidities beyond the musculoskeletal system. As there are more than 100,000 ACL reconstructions annually in the United States, our findings could have widespread public health importance if these findings generalize to a population beyond professional football players. In conclusion, enhanced screening for other risk factors for these conditions in patients who have torn their ACL might identify those who could most benefit from prevention strategies.

Weight Gain and Health Affliction Among Former National Football League Players.

BACKGROUND: Professional American-style football players are among the largest athletes across contemporary sporting disciplines. Weight gain during football participation is common, but the health implications of this early-life weight gain remain incompletely understood. We sought to define weight trajectories of former professional American-style football athletes and to establish their relationship with 5 common health afflictions (cardiovascular disease, cardiometabolic disease, neurocognitive impairment, sleep apnea, and chronic pain). METHODS: A health survey was distributed to former National Football League (NFL) players. Former players reported body weight at 4 time points (high school, college, professional, and time of survey response) as well as maximal retirement weight. Logistic regression was used to assess associations between weight gain during football participation and health affliction. RESULTS: In this cohort of former NFL players (n = 3,506, age 53 ± 14 years), mean weight increase from high school to time of survey response was 40 ± 36 pounds, with the majority of weight gain occurring during periods of football participation (high-school-to-college and college-to-professional). The prevalence of health afflictions ranged from 9% (cardiovascular disease) to 28% (chronic pain). Weight gain during football participation was independently associated with risk of multiple later-life health afflictions in models adjusted for football exposure, lifestyle variables, and post-career weight gain. CONCLUSIONS: Early-life weight gain among American-style football athletes is common and is associated with risk of adverse health profiles during later-life. These findings establish football-associated weight gain as a key predictor of post-career health and raise important questions about the central role of targeted weight gain in this population.

Antidiabetic phytoconstituents and their mode of action on metabolic pathways.

Diabetes Mellitus, characterized by persistent hyperglycaemia, is a heterogeneous group of disorders of multiple aetiologies. It affects the human body at multiple organ levels thus making it difficult to follow a particular line of the treatment protocol and requires a multimodal approach. The increasing medical burden on patients with diabetes-related complications results in an enormous economic burden, which could severely impair global economic growth in the near future. This shows that today's healthcare system has conventionally been poorly equipped towards confronting the mounting impact of diabetes on a global scale and demands an urgent need for newer and better options. The overall challenge of this field of diabetes treatment is to identify the individualized factors that can lead to improved glycaemic control. Plants are traditionally used worldwide as remedies for diabetes healing. They synthesize a diverse array of biologically active compounds having antidiabetic properties. This review is an endeavour to document the present armamentarium of antidiabetic herbal drug discovery and developments, highlighting mechanism-based antidiabetic properties of over 300 different phytoconstituents of various chemical categories from about 100 different plants modulating different metabolic pathways such as glycolysis, Krebs cycle, gluconeogenesis, glycogen synthesis and degradation, cholesterol synthesis, carbohydrate metabolism as well as peroxisome proliferator activated receptor activation, dipeptidyl peptidase inhibition and free radical scavenging action. The aim is to provide a rich reservoir of pharmacologically established antidiabetic phytoconstituents with specific references to the novel, cost-effective interventions, which might be of relevance to other low-income and middle-income countries of the world.

Phytochemicals As Uropathognic Escherichia Coli FimH Antagonist: In Vitro And In Silico Approach.

BACKGROUND: Urinary tract infection (UTI) is caused by uropathogenic Escherichia coli (UPEC). The UPEC initiate pathogenesis by expressing type 1 pili, which attach to membrane receptors on the uroepithelial cells. Inhibition of attachment can provide a valuable target for prophylaxis in symptom-free milieu. METHODS: The antibacterial efficacy of alcoholic, hydroalcoholic and aqueous extracts of four plants namely Achyranthes aspera, Andrographis paniculata, Artemissia vulgaris and Glycyrrhiza glabra was evaluated against seven isolated bacterial strains and procured E. coli (UTI89/UPEC) strain. Screening of isolated strains was based on morphological characteristics and biofilm forming ability followed by physiological and biochemical analysis. RESULTS: The hydroalcoholic extracts of G. glabra at 50 µg/ml showed an impending antioxidant (DPPH) effect of 95.65% compared to ascorbic acid. The MIC values of all the plant extracts against selected bacterial strains ranged between 125 to 1000 µg/ml. In silico molecular docking performed to make out the antiadhesive role of 115 documented phytochemicals from selected plants identified quercetin-3-glucoside, ethyl caffeate, liquiritoside, liquiritin and isoliquiritigenin as potential phytochemicals. Molecular dynamics simulation performed by PTRAJ module of Amber11 package to monitor the stability of hydrogen bond showed that quercetin-3-glucoside and ethyl caffeate are potential phytochemicals as antiadhesive forming H-bonds with the FimH protein ligand. CONCLUSIONS: Aforesaid phytochemicals demonstrate effective antibacterial activity through the anti-adhesion mechanism.

Impact of aging on neurocognitive performance in previously antiretroviral-naive HIV-infected individuals on their first suppressive regimen.

BACKGROUND: Despite treatment with virologically suppressive antiretroviral therapy (ART), neurocognitive impairment may persist or develop de novo in aging HIV-infected individuals. We evaluated advancing age as a predictor of neurocognitive impairment in a large cohort of previously ART-naive individuals on long-term ART. DESIGN: The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials was a prospective cohort study of HIV-infected individuals originally enrolled in randomized ART trials. This analysis examined neurocognitive outcomes at least 2 years after ART initiation. METHODS: All participants underwent annual neurocognitive testing consisting of Trail making A and B, the wechsler adult intelligence scale-revised Digit Symbol and Hopkins Verbal Learning Tests. Uni and multivariable repeated measures regression models evaluated factors associated with neurocognitive performance. Predictors at parent study entry (ART naive) included entry demographics, smoking, injection drug use, hepatitis B surface antigen, hepatitis C virus serostatus, history of stroke, ART regimen type, pre-ART nadir CD4 cell count, and plasma viral load and as well as time-updated plasma viral load and CD4 cell count. RESULTS: The cohort comprised 3313 individuals with median pre-ART age of 38 years, 20% women; 36% Black, non-Hispanic; 22% Hispanic. Virologic suppression was maintained at 91% of follow-up visits. Neurocognitive performance improved with years of ART. After adjusting for the expected effects of age using norms from HIV-negative individuals, the odds of neurocognitive impairment at follow-up visits among the HIV infected increased by nearly 20% for each decade of advancing age. CONCLUSION: Despite continued virologic suppression and neurocognitive improvement in the cohort as a whole, older individuals were more likely to have neurocognitive impairment than younger individuals.

In vivo and in silico investigation of antidiabetic activity of fruit of withania coagulans Dunal.

This study evaluates the antidiabetic activities of methanolic extract of Withania coagulans Dunal (Ashutosh booti) fruit (WCFE) in poloxamer-407 induced type 2 diabetic Wistar rats. The electrochemical behaviour of WCFE with anodic peak of 1.19± 0.01V was found similar to standards used indicating that extract is antioxidant in nature. Unlike diabetic control rats, the WCFE treated diabetic rats presented significant amelioration of glycaemia, insulinamia and lipid dysmetabolism, remarkable reduction of oxidative markers and improved cecal and pancreatic characteristics. HYBRID and FRED docking were performed for 25 documented WCFE botanicals for putative action mechanism concerning three diabetic therapeutic proteins namely PTP-1B, PPAR-γ and DPP-IV fully support the in vivo findings. Botanicals like nicandrenone10 and Acnistin F have shown considerable interaction potential with aforesaid proteins. Results provide pharmacological evidence of WCFE as antihyperglyceamic mediated by interaction of various botanicals with various targets operating in diabetes mellitus.

Regional variation in HIV clinical trials participation in the United States.

OBJECTIVES: To ensure generalizability of clinical research results, it is important to enroll a heterogeneous population that is representative of the target clinical population. Earlier studies have found regional variation in participation in human immunodeficiency virus (HIV) clinical trials, with the lowest rates seen in the southern United States. Rates of new HIV diagnoses are highest in the South, highlighting the need for in-depth understanding of disparities in clinical trial participation. We evaluated whether regional variation in study participation remains, and describe factors that facilitate or prevent HIV clinical trial participation by region. METHODS: A one-time, anonymous, bilingual, self-administered survey was conducted among HIV-infected adults receiving HIV care at all 47 domestic AIDS Clinical Trials Group clinical research sites, with a goal of completing 50 surveys per site. χ(2) tests were used to evaluate differences in knowledge of and participation in HIV clinical trials by region, including Northeast, Midwest, South, and West regions. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for the effect of region on knowledge of and participation in HIV clinical trials. RESULTS: Of 2263 completed surveys, 2125 were included in this analysis. The proportion of respondents in the South who reported knowledge of studies (66%) was significantly lower than in the Northeast (76%), Midwest (77%), and West (73%) (P = 0.001). Respondents in the South also were the least likely group to report ever having tried to or having participated in a research study (51%) compared with respondents in the Northeast (60%), Midwest (57%), and West (69%; P < 0.001). After adjusting for age, sex, education, race/ethnicity, tobacco use, and alcohol use, the odds ratio for knowledge of and participation in clinical trials for the Northeast (1.36; 95% CI 1.07-1.72) and West (1.85; 95% CI 1.39-2.45) remained significant compared with the South. African American respondents in the South were the most likely population group to report not understanding research studies (15%) as a reason for not participating, compared with the Northeast (9%), Midwest (8%), and West (6%; P < 0.001). CONCLUSIONS: Significant regional variations in knowledge of and participation in HIV clinical trials exist. Our results suggest that increasing awareness and understanding of research studies, particularly among African Americans in the South, may facilitate HIV clinical trial participation that is more representative of the HIV-infected population across the United States.

Changes in metabolic syndrome status after initiation of antiretroviral therapy.

BACKGROUND: Data on changes in metabolic syndrome (MetS) status in HIV-infected adults on antiretroviral therapy (ART) are limited. METHODS: MetS was assessed at ART initiation and every 48 weeks on ART in ART-naive HIV-infected individuals from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) cohort. MetS, defined using the Adult Treatment Panel III criteria, required at least 3 of the following: elevated fasting glucose, hypertension, elevated waist circumference, elevated triglycerides, low high-density lipoprotein (HDL) cholesterol. Prevalence of MetS and the individual criteria were compared between ART initiation and during follow-up using McNemar test. RESULTS: At ART initiation, 450 (20%) ALLRT participants had MetS. After 96 weeks of ART, 37% of the 411 with MetS at ART initiation and with available data at this time point did not meet the MetS criteria. Among these participants, there was a dramatic decline in the proportion with low HDL (95% versus 26%, P < 0.0001). Among the 63% who continued to meet MetS criteria at week 96, the proportion with ≥4 criteria was higher at week 96 compared to at the time of ART initiation (48% versus 40%, P = 0.03); at week 96, the proportion with high triglycerides was greater (87% versus 69%, P < 0.0001) as was the proportion with high glucose (59% versus 42%, P < 0.0001). CONCLUSIONS: One in 5 ART-naive subjects met criteria for MetS at ART initiation. Although more than half of these individuals continued to have MetS after 96 weeks of ART, 37% with MetS at ART initiation no longer met criteria for MetS; this decrease was driven largely by increases in HDL cholesterol.