42 research outputs found

    Sleep and Inflammation During Adolescents\u27 Transition to Young Adulthood

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    Purpose This study investigated the extent to which multiple sleep dimensions are associated with inflammation during adolescents\u27 transition to young adulthood, a developmental period when sleep difficulties and systemic inflammation levels are on the rise. Additionally, the moderating roles of socioeconomic status (SES) and ethnicity were explored. Methods A total of 350 Asian American, Latino, and European American youth participated at two-year intervals in wave 1 ( n = 316, M age = 16.40), wave 2 ( n = 248 including 34 new participants to refresh the sample, M age = 18.31), and wave 3 ( n = 180, M age = 20.29). Sleep duration (weekday and weekend) and variability in duration (nightly and weekday/weekend) were obtained from eight nights of wrist actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index. Levels of C-reactive protein (CRP), a biomarker of systemic inflammation, were assayed from dried blood spots obtained from finger pricks. Results Multilevel models demonstrated that greater weekday/weekend sleep variability and worse sleep quality were associated with higher CRP; shorter weekend duration was associated with higher CRP only at younger ages. Shorter weekday duration was associated with higher CRP only among high-SES youth, whereas greater nightly variability was associated with higher CRP only among European American youth. Conclusions Aspects of poor sleep may contribute to the rise of CRP during adolescents\u27 transition to young adulthood, especially in earlier years. In addition, some sleep-CRP associations may vary as a function of youth\u27s SES and ethnicity

    Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

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    Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study

    Urinary Eicosanoid Metabolites in HIV-Infected Women with Central Obesity Switching to Raltegravir: An Analysis from the Women, Integrase, and Fat Accumulation Trial

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    Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m2 completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus −0.02; P=0.06). Baseline PGI-M was lower in the RAL arm (P=0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho=0.45; P=0.04) and TxB2 (rho=0.44; P=0.005) changes, with a trend seen for PGE-M (rho=0.41; P=0.07). In an adjusted model, age ≥ 50 years (N=8) was associated with increased PGE-M (P=0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Evaluating efforts to diversify the biomedical workforce: the role and function of the Coordination and Evaluation Center of the Diversity Program Consortium

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    Abstract Background The National Institutes of Health (NIH)-funded Diversity Program Consortium (DPC) includes a Coordination and Evaluation Center (CEC) to conduct a longitudinal evaluation of the two signature, national NIH initiatives - the Building Infrastructure Leading to Diversity (BUILD) and the National Research Mentoring Network (NRMN) programs - designed to promote diversity in the NIH-funded biomedical, behavioral, clinical, and social sciences research workforce. Evaluation is central to understanding the impact of the consortium activities. This article reviews the role and function of the CEC and the collaborative processes and achievements critical to establishing empirical evidence regarding the efficacy of federally-funded, quasi-experimental interventions across multiple sites. The integrated DPC evaluation is particularly significant because it is a collaboratively developed Consortium Wide Evaluation Plan and the first hypothesis-driven, large-scale systemic national longitudinal evaluation of training programs in the history of NIH/National Institute of General Medical Sciences. Key highlights To guide the longitudinal evaluation, the CEC-led literature review defined key indicators at critical training and career transition points – or Hallmarks of Success. The multidimensional, comprehensive evaluation of the impact of the DPC framed by these Hallmarks is described. This evaluation uses both established and newly developed common measures across sites, and rigorous quasi-experimental designs within novel multi-methods (qualitative and quantitative). The CEC also promotes shared learning among Consortium partners through working groups and provides technical assistance to support high-quality process and outcome evaluation internally of each program. Finally, the CEC is responsible for developing high-impact dissemination channels for best practices to inform peer institutions, NIH, and other key national and international stakeholders. Implications A strong longitudinal evaluation across programs allows the summative assessment of outcomes, an understanding of factors common to interventions that do and do not lead to success, and elucidates the processes developed for data collection and management. This will provide a framework for the assessment of other training programs and have national implications in transforming biomedical research training
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