Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Non-inferiority trials with time-to-event data: clarifying the impact of censoring.

In non-inferiority (NI) trials with time-to-event data, different types and patterns of censoring may occur, but their impact on trial results is not entirely clear. We investigated the influence of informative and non-informative censoring by conducting extensive simulation studies under the assumption that the NI margin is defined as a maximum acceptable hazard ratio and scenarios typically observed in recent NI trials. We found that while non-informative censoring tends to only affect the power, informative censoring can impact the treatment effect estimates, type I error rate, and power. The magnitude of these effects depends on the between-group differences in the failure and informative censoring risks, as well as the correlation between censoring and failure times, among other factors. The adverse impact of informative censoring was generally decreased with larger NI margins.

Association of Gut Microbiota With Objective Sleep Measures in Women With and Without Human Immunodeficiency Virus Infection: The IDOze Study.

BACKGROUND: Poor sleep health is an underrecognized health challenge, especially for people with human immunodeficiency virus (HIV). Gut microbiota related to sleep are underinvestigated. METHODS: The IDOze microbiota substudy included 190 women (114 with HIV and 76 without HIV). Wrist actigraphy measured total sleep duration, sleep efficiency, number of wake bouts, wake after sleep onset, fragmentation index, and sleep timing. 16S rRNA gene sequencing identified gut microbial genera. Analysis of compositions of microbiomes with bias correction was used to investigate cross-sectional associations between gut microbiota and sleep. Abundances of sleep-related gut microbial genera were compared between women with and without HIV. RESULTS: Enrichment of 7 short-chain fatty acid-producing genera (eg, Butyricimonas, Roseburia, and Blautia) was associated with lower fragmentation index. Enrichment of 9 genera (eg, Dorea) was associated with lower sleep efficiency and/or more wake after sleep onset. Enrichment of proinflammatory Acidaminococcus was associated with late sleep midpoint and offset time. These associations were largely consistent regardless of HIV status. The abundance of Butyricimonas was lower among women with HIV compared to those without HIV. CONCLUSIONS: Seventeen genera were identified to be associated with sleep continuity or timing. Butyricimonas, a potentially beneficial genus associated with sleep continuity, was less abundant among women with HIV.

Human Immunodeficiency Virus and Cardiac End-Organ Damage in Women: Findings From an Echocardiographic Study Across the United States.

BACKGROUND: People with human immunodeficiency virus (HIV) have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators. METHODS: We performed echocardiography in the Women's Interagency HIV Study to investigate associations of HIV and HIV-specific factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV). RESULTS: Of 1654 participants (age 51 ± 9 years), 70% had HIV. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared with women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted relative risk = 1.69; 95% confidence interval = 1.00 to 2.86; P = .051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4+ count among WWH that approached or reached significance for isolated LVDD, LAE, and LVH. WWH with CD4+ count <200 cells/mm3 had significantly higher prevalence of LAE, LVH, and high TRV than WWOH. There were no consistent associations for viral suppression or antiretroviral drug exposure. CONCLUSIONS: This study suggests that WWH have a higher risk of LVSD compared with sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4+ count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population.

Single-junction organic solar cells with over 19% efficiency enabled by a refined double-fibril network morphology.

In organic photovoltaics, morphological control of donor and acceptor domains on the nanoscale is the key for enabling efficient exciton diffusion and dissociation, carrier transport and suppression of recombination losses. To realize this, here, we demonstrated a double-fibril network based on a ternary donor-acceptor morphology with multi-length scales constructed by combining ancillary conjugated polymer crystallizers and a non-fullerene acceptor filament assembly. Using this approach, we achieved an average power conversion efficiency of 19.3% (certified 19.2%). The success lies in the good match between the photoelectric parameters and the morphological characteristic lengths, which utilizes the excitons and free charges efficiently. This strategy leads to an enhanced exciton diffusion length and a reduced recombination rate, hence minimizing photon-to-electron losses in the ternary devices as compared to their binary counterparts. The double-fibril network morphology strategy minimizes losses and maximizes the power output, offering the possibility of 20% power conversion efficiencies in single-junction organic photovoltaics.

Similar Efficacy Observed for First-Line Immunotherapy in Racial/Ethnic Minority Patients With Metastatic NSCLC.

BACKGROUND: Limited data exist on the impact of immunotherapy use in ethnic minority patients with non-small cell lung cancer (NSCLC), because they have been underrepresented in immunotherapy trials. This study aims to evaluate race/ethnicity and other demographic, socioeconomic, and clinical factors of patients with metastatic NSCLC treated with first-line immunotherapy. METHODS: A retrospective cohort study of 5,920 patients diagnosed with lung cancer treated at Montefiore Einstein Cancer Center from January 1, 2013, to June 1, 2022, was used to identify patients with metastatic NSCLC without EGFR, ALK, or ROS1 alterations who underwent first-line immunotherapy (n=248). The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of immunotherapy. RESULTS: Among the 248 patients, median follow-up time was 12.0 months, median age at start of treatment was 66 years, and 39.1% were non-Hispanic Black, 30.2% were Hispanic, and 30.7% were non-Hispanic White. OS (P=.39), PFS (P=.29), and TTD (P=.98) were similar among racial/ethnic groups. Patients with an ECOG performance status (PS) of <2 at the start of immunotherapy had longer OS compared with those with ECOG PS of ≥2 (P<.0001). PD-L1 expression (<50% vs ≥50%; P=.03) and body mass index (BMI) (P=.01) were also found to be associated with PFS, and ECOG PS (P<.0001) and BMI (P=.02) were associated with TTD. In a multivariate analysis of OS and PFS, ECOG PS was the only variable found to be significant. CONCLUSIONS: Our study observed similar benefits of immunotherapy in patients with metastatic NSCLC in different racial and ethnic groups. Furthermore, ECOG PS was associated with OS, and PD-L1 expression and BMI were associated with PFS and TTD. These findings help identify potential factors associated with outcomes and care while patients are undergoing immunotherapy.

Characterizing longitudinal change in accelerometry-based moderate-to-vigorous physical activity in the Hispanic Community Health Study/Study of Latinos and the Framingham Heart Study.

BACKGROUND: Physical activity promotes health and is particularly important during middle and older age for decreasing morbidity and mortality. We assessed the correlates of changes over time in moderate-to-vigorous physical activity (MVPA) in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL: mean [SD] age 49.2 y [11.5]) and compared them to a cohort of primarily White adults from the Framingham Heart Study (FHS: mean [SD] 46.9 y [9.2]). METHODS: Between 2008 and 2019, we assessed accelerometry-based MVPA at two time points with an average follow-up of: 7.6 y, SD 1.3 for HCHS/SOL, and 7.8 y, SD 0.7 for FHS. We used multinomial logistic regression to relate socio-demographic and health behaviors with changes in compliance with 2018 US recommendations for MVPA from time 1 to time 2 (remained active or inactive; became active or inactive) across the two cohorts. RESULTS: In HCHS/SOL mean MVPA was 22.6 (SD, 23.8) minutes at time 1 and dropped to 16.7 (19.0) minutes at time 2. In FHS Mean MVPA was 21.7 min (SD, 17.7) at time 1 and dropped to 21.3 min (SD, 19.2) at time 2. Across both cohorts, odds of meeting MVPA guidelines over time were about 6% lower in individuals who had lower quality diets vs. higher, about half in older vs. younger adults, about three times lower in women vs. men, and 9% lower in individuals who had a higher vs. lower BMI at baseline. Cohorts differed in how age, gender, income, education, depressive symptoms, marital status and perception of general health and pain associated with changes in physical activity. High income older Hispanics/Latino adults were more likely to become inactive at the follow-up visit as were HCHS/SOL women who were retired and FHS participants who had lower levels of education and income. Higher depressive symptomology was associated with becoming active only in HCHS/SOL women. Being male and married was associated with becoming inactive in both cohorts. Higher perception of general health and lower perception of pain were associated with remaining active only in FHS adults. CONCLUSIONS: These findings highlight potentially high-risk groups for targeted MVPA intervention.

Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice.

Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of healthspan and related biochemical markers (n = 10-19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of healthspan in the context of a metabolic stressor with aging.

The IDOze Study: The Link Between Sleep Disruption and Tryptophan-Kynurenine Pathway Activation in Women With Human Immunodeficiency Virus.

BACKGROUND: Poor sleep is associated with human immunodeficiency virus (HIV), particularly among women with HIV (WWH), although mechanisms are unclear. We explored cross-sectional associations between sleep disruption and tryptophan-kynurenine (T/K) pathway activation, measured by the kynurenine-to-tryptophan ratio (K:T). METHODS: HIV-uninfected women (HIV-) and WWH aged 35-70 years and on stable antiretroviral therapy were included. Sleep metrics were measured using wrist actigraphy. Plasma T/K pathway metabolites were measured using liquid chromatography-tandem mass spectrometry. Multivariate linear regression models examined relationships between K:T and actigraphy-based sleep metrics by HIV status. RESULTS: WWH (n = 153) and HIV- women (n = 151) were demographically similar. Among WWH, median CD4 was 751 cells/µL; 92% had undetectable HIV RNA. Compared to HIV- women, WWH had higher K:T (P < .001) and kynurenine (P = .01) levels but similar tryptophan levels (P = .25). Higher K:T was associated with more wake bouts (P = .001), more time awake after sleep onset (P = .01), and lower sleep efficiency (P = .03) in WWH only. CONCLUSIONS: HIV infection was associated with T/K pathway activation; this activation was associated with poorer sleep efficiency and more fragmented sleep. While longitudinal studies are needed to elucidate the directionality of these associations, these findings may help identify treatments to reduce sleep disruption in WWH by targeting residual inflammation and T/K pathway activation.

Menopause Is Associated With Immune Activation in Women With HIV.

BACKGROUND: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. METHODS: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years. RESULTS: Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (ß = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods. CONCLUSIONS: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.

Racial disparity in distant recurrence-free survival in patients with localized breast cancer: A pooled analysis of National Surgical Adjuvant Breast and Bowel Project trials.

BACKGROUND: Black race is associated with worse outcome in patients with breast cancer. The distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in National Cancer Institute-sponsored clinical trial was evaluated. METHODS: Pooled data were analyzed from 8 National Surgical Adjuvant Breast and Bowel Project (NSABP) trials including 9702 women with localized breast cancer treated with adjuvant chemotherapy (AC, n = 7485) or neoadjuvant chemotherapy (NAC, n = 2217), who self-reported as Black (n = 1070) or White (n = 8632) race. The association between race and DRFS was analyzed using log-rank tests and multivariate Cox regression. RESULTS: After adjustment for covariates including age, tumor size, nodal status, body mass index and taxane use, and treatment (AC vs NAC), Black race was associated with an inferior DRFS in estrogen receptor-positive (ER+; hazard ratio [HR], 1.24; 95% CI, 1.05-1.46; P = .01), but not in ER- disease (HR, 0.97; 95% CI, 0.83-1.14; P = .73), and significant interaction between race and ER status was observed (P = .03). There was no racial disparity in DRFS among patients with pathologic complete response (pCR) (log-rank P = .8). For patients without pCR, Black race was associated with worse DRFS in ER+ (HR, 1.67; 95% CI, 1.14-2.45; P = .01), but not in ER- disease (HR, 0.91; 95% CI, 0.65-1.28; P = .59). CONCLUSIONS: Black race was associated with significantly inferior DRFS in ER+ localized breast cancer treated with AC or NAC, but not in ER- disease. In the NAC group, racial disparity was also observed in patients with residual ER+ breast cancer at surgery, but not in those who had pCR. LAY SUMMARY: Black women with breast cancer have worse outcomes compared with White women. We investigated if this held true in the context of clinical trials that provide controlled treatment setting. Black women with cancer expressing estrogen receptors (ERs) had worse outcome than White women. If breast cancers did not express ERs, there was no racial disparity in outcome. We also observed racial disparity in women who received chemotherapy before their cancer was removed, but only if they had cancer expressing ERs and residual disease on completion of treatment. If the cancer disappeared with presurgical chemotherapy, there was no racial disparity.

Jointly modeling of sleep variables that are objectively measured by wrist actigraphy.

Recently developed actigraphy devices have made it possible for continuous and objective monitoring of sleep over multiple nights. Sleep variables captured by wrist actigraphy devices include sleep onset, sleep end, total sleep time, wake time after sleep onset, number of awakenings, etc. Currently available statistical methods to analyze such actigraphy data have limitations. First, averages over multiple nights are used to summarize sleep activities, ignoring variability over multiple nights from the same subject. Second, sleep variables are often analyzed independently. However, sleep variables tend to be correlated with each other. For example, how long a subject sleeps at night can be correlated with how long and how frequent he/she wakes up during that night. It is important to understand these inter-relationships. We therefore propose a joint mixed effect model on total sleep time, number of awakenings, and wake time. We develop an estimating procedure based upon a sequence of generalized linear mixed effects models, which can be implemented using existing software. The use of these models not only avoids computational intensity and instability that may occur by directly applying a numerical algorithm on a complicated joint likelihood function, but also provides additional insights on sleep activities. We demonstrated in simulation studies that the proposed estimating procedure performed well in estimating both fixed and random effects' parameters. We applied the proposed model to data from the Women's Interagency HIV Sleep Study to examine the association of employment status and age with overall sleep quality assessed by several actigraphy measured sleep variables.

Association of sleep duration and insomnia with metabolic syndrome and its components in the Women's Health Initiative.

BACKGROUND: Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women's Health Initiative (WHI). METHODS: The study included postmenopausal women (ages 50-79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated. RESULTS: In cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12-2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01-1.40 and OR = 1.23; 95%CI 1.05-1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99-1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03-1.34 and OR = 1.17; 95%CI 1.02-1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01-1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08-2.03). CONCLUSIONS: Among postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.

Predictors of incident diabetes in two populations: framingham heart study and hispanic community health study / study of latinos.

BACKGROUND: Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly. METHODS: Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry. Among individuals without diabetes, Cox proportional hazards regression models (both age- and sex-adjusted, and then multivariable-adjusted for all candidate predictors) identified predictors of incident diabetes over a decade of follow-up, defined using clinical history or laboratory assessments. RESULTS: Four independent predictors were shared between FHS and HCHS/SOL. In each cohort, the multivariable-adjusted hazard of diabetes increased by approximately 50% for every ten-year increment of age and every five-unit increment of body mass index (BMI), and was 50-70% higher among hypertensive than among non-hypertensive individuals (all P < 0.01). Compared with full-time employment status, the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for part-time employment was 0.61 (0.37,1.00) in FHS and 0.62 (0.41,0.95) in HCHS/SOL. Moderate-to-vigorous physical activity (MVPA) was an additional predictor in common observed in age- and sex-adjusted models, which did not persist after adjustment for other covariates (compared with MVPA ≤ 5 min/day, HR for MVPA level ≥ 30 min/day was 0.48 [0.31,0.74] in FHS and 0.74 [0.56,0.97] in HCHS/SOL). Additional predictors found in sex- and age-adjusted analyses among the FHS participants included male gender and lower education, but these predictors were not found to be independent of others in multivariable adjusted models, nor were they associated with diabetes risk among HCHS/SOL adults. CONCLUSIONS: The same four independent predictors - age, body mass index, hypertension and employment status - were associated with diabetes risk across two disparate US populations. While the reason for elevated diabetes risk in full-time workers is unclear, the findings suggest that diabetes may be part of the work-related burden of disease. Our findings also support prior evidence that differences by gender and socioeconomic position in diabetes risk are not universally present across populations.

Diet quality comparisons in Hispanic/Latino siblings: Results from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

The objective of this study was to determine how well Hispanic/Latino siblings' diet quality correlate with each other and whether social and environmental factors explained potential differences. Hispanic/Latino 8-16-year-olds from the cross-sectional Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth) with at least one sibling enrolled in the study were examined (n = 740). Diet quality was assessed with the Healthy Eating Index 2010 (HEI-2010), calculated from two 24-h recalls. Mixed effects models were used with HEI-2010 score as the outcome, and correlations in siblings' diet quality were assessed with intraclass correlation coefficients (ICCs). All models were examined stratified by age and sex. Diet-related social and environmental measures were added as fixed effects in a secondary analysis. Mean (standard deviation) overall HEI-2010 score was 53.8 (13.0). The ICC for siblings' HEI-2010 score was 0.31 (95% CI: 0.25, 0.38). Siblings who were born <3 vs. ≥3 years apart had stronger correlations in overall diet quality (0.47 [95% CI: 0.37, 0.58] vs. 0.21 [95% CI: 0.13, 0.30]), but no differences were observed in overall HEI-2010 score according to sex. Greater peer support for fruit and vegetable intake (ß = 1.42 [95% CI: 0.62, 2.21]) and greater away-from-home food consumption (ß = -1.24 [95% CI: -2.15, -0.32]) were associated with differences in siblings' diet quality. Overall diet quality scores of Hispanic/Latino siblings in this study were slightly correlated, with stronger correlations among siblings closer in age. Differences in peer support and foods consumed outside the home may explain differences in siblings' diet quality. Future research should investigate additional determinants of differences in siblings' diets.

Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses.

Previous studies have shown that dexamethasone (Dex) reduces the levels of anti-nuclear (ANA) and anti-dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+ CXCR5+ ICOS+ , CD4+ CXCR5+ PD-1+ or CD4+ BCL-6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL-21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+ CXCR5+ ICOS+ , CD4+ CXCR5+ PD-1+ or CD4+ BCL-6+ ) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl-6 and c-Maf mRNA expression of CD4+ T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl-6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE.

Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

BACKGROUND: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). METHODS: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. RESULTS: Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing" had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing" (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. CONCLUSIONS: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

Altered Gut Microbiota and Host Metabolite Profiles in Women With Human Immunodeficiency Virus.

BACKGROUND: Alterations in gut microbiota (GMB) and host metabolites have been noted in individuals with HIV. However, it remains unclear whether alterations in GMB and related functional groups contribute to disrupted host metabolite profiles in these individuals. METHODS: This study included 185 women (128 with longstanding HIV infection, 88% under antiretroviral therapy; and 57 women without HIV from the same geographic location with comparable characteristics). Stool samples were analyzed by 16S rRNA V4 region sequencing, and GMB function was inferred by PICRUSt. Plasma metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry, and 133 metabolites (amino acids, biogenic amines, acylcarnitines, and lipids) were analyzed. RESULTS: Four predominant bacterial genera were identified as associated with HIV infection, with higher abundances of Ruminococcus and Oscillospira and lower abundances of Bifidobacterium and Collinsella in women with HIV than in those without. Women with HIV showed a distinct plasma metabolite profile, which featured elevated glycerophospholipid levels compared with those without HIV. Functional analyses also indicated that GMB lipid metabolism was enriched in women with HIV. Ruminococcus and Oscillospira were among the top bacterial genera contributing to the GMB glycerophospholipid metabolism pathway and showed positive correlations with host plasma glycerophospholipid levels. One bacterial functional capacity in the acetate and propionate biosynthesis pathway was identified to be mainly contributed by Bifidobacterium; this functional capacity was lower in women with HIV than in women without HIV. CONCLUSIONS: Our integrative analyses identified altered GMB with related functional capacities that might be associated with disrupted plasma metabolite profiles in women with HIV.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study.

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[-]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[-] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[-] women correlated with lower PRs (ρ = -0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV- + b*PHIV- 2 ; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[-] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[-] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.