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Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Background Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos. Results The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia , Prevotella , Dorea , and Coprococcus . In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus . Conclusions Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.

Background Understanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics may influence health outcomes. Typical microbiome genome-wide association studies (GWAS) marginally assess the association between individual genetic variants and individual microbial taxa. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The KRV framework evaluates the association between genetics and microbes by comparing similarity in genetic profiles, based on groups of variants at the gene level, to similarity in microbiome profiles, based on the overall microbiome composition, across all pairs of individuals. By reducing the multiple-testing burden and capturing intrinsic structure within the genetic and microbiome data, the KRV framework has the potential of improving statistical power in microbiome GWAS. Results We apply the covariate-adjusted KRV to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) in a two-stage (first gene-level, then variant-level) genome-wide association analysis for gut microbiome beta-diversity. We have identified an immunity-related gene, IL23R , reported in a previous microbiome genetic association study and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. In addition, simulation studies show that the covariate-adjusted KRV has a greater power than other microbiome GWAS methods that rely on univariate microbiome phenotypes across a range of scenarios. Conclusions Our findings highlight the value of the covariate-adjusted KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition. 3iRoYfA_uxPN1-JktGz5GL Video Abstract

Following publication of the original paper [1], an error was reported in the third paragraph in the section “ Analysis of GMB composition and its correlates” (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

Background Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. Methods We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. Results We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. Conclusions Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Genetic architecture of cardiometabolic risks in people living with HIV [RAW_REF_TEXT] Haoxiang Cheng1 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Anshuman Sewda1,2 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Carla Marquez-Luna3, [/RAW_REF_TEXT] [RAW_REF_TEXT] Sierra R. White1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Bridget M. Whitney4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Jessica Williams-Nguyen4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Robin M. Nance1,5, [/RAW_REF_TEXT] [RAW_REF_TEXT] Won Jun Lee1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Mari M. Kitahata5,6, [/RAW_REF_TEXT] [RAW_REF_TEXT] Michael S. Saag7, [/RAW_REF_TEXT] [RAW_REF_TEXT] Amanda Willig7, [/RAW_REF_TEXT] [RAW_REF_TEXT] Joseph J. Eron8, [/RAW_REF_TEXT] [RAW_REF_TEXT] W. Christopher Mathews9, [/RAW_REF_TEXT] [RAW_REF_TEXT] Peter W. Hunt10, [/RAW_REF_TEXT] [RAW_REF_TEXT] Richard D. Moore11,12, [/RAW_REF_TEXT] [RAW_REF_TEXT] Allison Webel13, [/RAW_REF_TEXT] [RAW_REF_TEXT] Kenneth H. Mayer14, [/RAW_REF_TEXT] [RAW_REF_TEXT] Joseph A. Delaney4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Paul K. Crane5, [/RAW_REF_TEXT] [RAW_REF_TEXT] Heidi M. Crane5,6, [/RAW_REF_TEXT] [RAW_REF_TEXT] Ke Hao1 na2 & [/RAW_REF_TEXT] [RAW_REF_TEXT] Inga Peter 1 na2 [/RAW_REF_TEXT] BMC Medicine volume 19, Article number: 114 (2021) Cite this article [RAW_REF_TEXT] 102 Accesses [/RAW_REF_TEXT] [RAW_REF_TEXT] Metrics details [/RAW_REF_TEXT] The Original Article was published on 28 October 2020 Correction to: BMC Med 18, 288 (2020) https://doi.org/10.1186/s12916-020-01762-z The original article [1] contained an error whereby first author, Haoxiang Cheng’s name was displayed incorrectly. Genetic architecture of cardiometabolic risks in people living with HIV [RAW_REF_TEXT] Haoxiang Cheng1 na1, Anshuman Sewda1,2 na1, Carla Marquez-Luna3, Sierra R. White1, Bridget M. Whitney4, Jessica Williams-Nguyen4, Robin M. Nance1,5, Won Jun Lee1, Mari M. Kitahata5,6, Michael S. Saag7, Amanda Willig7, Joseph J. Eron8, W. Christopher Mathews9, Peter W. Hunt10, Richard D. Moore11,12, Allison Webel13, Kenneth H. Mayer14, Joseph A. Delaney4, Paul K. Crane5, Heidi M. Crane5,6, Ke Hao1 na2 & Inga Peter 1 na2 [/RAW_REF_TEXT] BMC Medicine volume 19, Article number: 114 (2021) Cite this article [RAW_REF_TEXT] 102 Accesses Metrics details

Abstract Background Direct-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)–hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions. Methods The primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values. Results Among 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%–97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%–93.6%). Similar results were seen in multiply imputed data sets. Conclusions Our study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.

BACKGROUND:People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. METHODS:The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply–demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. RESULTS:Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). CONCLUSIONS:Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

This chapter presents an overview of the basic principles involved in designing studies or monitoring programs that seek to assess the impact of a wastewater treatment plant (WWTP) on measures of antibiotic resistant bacteria (ARB) or antibiotic resistance genes (ARG) in receiving environments. It draws on causal inference theory that was developed in the context of epidemiologic research, these principles are widely useful in observational science and share common themes that have emerged in the disciplines of ecology and environmental impact assessment. Collider stratification bias, also known as selection bias, is caused by conditioning on a common effect of either the exposure or one of its causes and the outcome or one of its causes. Designing studies that involve exposures and outcomes measured in the natural environment (e.g., rivers) have their own suite of challenges, related to the large number of variables and factors that can affect and distort the causal relationship of interest.