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The magnetic resonance imaging (MRI) visible perivascular space (PVS) reportedly clears amyloid-β and metabolic waste during sleep. Previous studies reported an association between sleep and the PVS in small vessel disease, traumatic brain injury, and Alzheimer's disease. However, this relationship in a healthy cohort is still unclear. Here, we used the Human Connectome Project Aging dataset to analyze the relationship between sleep and the PVS in cognitively healthy adults across the aging continuum. We measured sleep parameters using the self-reported Pittsburgh Sleep Quality Index questionnaire. We found that older adults who had better sleep quality and sleep efficiency presented with a larger PVS volume fraction in the basal ganglia (BG). However, sleep measures were not associated with PVS volume fraction in the centrum semiovale (CSO). In addition, we found that body mass index (BMI) influenced the BG-PVS across middle-aged and older participants. In the entire cognitively healthy cohort, the effect of sleep quality on PVS volume fraction was mediated by BMI. However, BMI did not influence this effect in the older cohort. Furthermore, there are significant differences in PVS volume fraction across racial/ethnic cohorts. In summary, the effect of sleep on the PVS volume alteration was different in the middle-aged adults and older adults.

Background and objectivesSleep and physical activity have gained traction as modifiable risk factors for Alzheimer's disease. Sleep duration is linked to amyloid-β clearance while physical activity is associated with brain volume maintenance. We investigate how sleep duration and physical activity are associated with cognition by testing if the associations between sleep duration or physical activity to cognition are explained by amyloid-β burden and brain volume, respectively. Additionally, we explore the mediating role of tau deposition in sleep duration-cognition and physical activity-cognition relationships.MethodsThis cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a randomized clinical trial. In trial screening, cognitively unimpaired participants (age 65-85 years) underwent amyloid PET and brain MRI; APOE genotype and lifestyle questionnaire data were obtained. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Self-reported nightly sleep duration and weekly physical activity were the primary predictors. Regional Aβ and tau pathologies and volumes were the proposed variables influencing relationships between sleep duration or physical activity and cognition.ResultsAβ data were obtained from 4322 participants (1208 with MRI, 59% female, 29% amyloid positive). Sleep duration was associated with a Aβ composite score (β = -0.005, CI: (-0.01, -0.001)) and Aβ burden in the anterior cingulate (ACC) (β = -0.012, CI: (-0.017, -0.006)) and medial orbitofrontal cortices (MOC) (β = -0.009, CI: (-0.014, -0.005)). Composite (β = -1.54, 95% CI:(-1.93, -1.15)), ACC (β = -1.22, CI:(-1.54, -0.90)) and MOC (β = -1.44, CI:(-1.86, -1.02)) Aβ deposition was associated with PACC. Sleep duration-PACC association was explained by Aβ burden in path analyses. Physical activity was associated with hippocampal (β = 10.57, CI: (1.06, 20.08)), parahippocampal (β = 9.3, CI: (1.69, 16.91)), entorhinal (β = 14.68, CI: (1.75, 27.61), and fusiform gyral (β = 38.38, CI: (5.57, 71.18)) volumes, which were positively associated with PACC (p

IntroductionWe evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle.MethodsParticipants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans.ResultsTsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia.DiscussionThe prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

IntroductionIt is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal women. Pooled analyses in postmenopausal women report higher androgen and estrogen levels in current heavy cigarette smokers compared to nonsmokers. However, evidence among premenopausal women has been inconsistent.Aims and methodsWe conducted a systematic review and meta-analysis to estimate differences in standardized mean hormone levels among current premenopausal smokers compared to nonsmokers. We reviewed and collated publications with sex hormone levels by smoking status among healthy, premenopausal women who were nonusers of exogenous hormones, including oral contraceptives, using PubMed through December 2019. A random effects meta-analysis was conducted to combine the standardized mean differences (SMD) and 95% confidence intervals (CIs) for estradiol, progesterone, testosterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and sex hormone-binding globulin by smoking status. Findings were summarized by menstrual cycle phase and overall.ResultsNineteen published peer-reviewed articles were included. Significantly increased testosterone levels among smokers compared to nonsmokers were identified from cross-sectional studies with varied menstrual phase timing (SMD 0.14; 95% CI 0.0005, 0.29) and significantly increased dehydroepiandrosterone-sulfate levels were found over all phases (SMD 0.12; 95% CI 0.01, 0.22). However, substantial heterogeneity existed in these studies.ConclusionsThis meta-analysis suggests that smoking may increase blood androgen levels in healthy premenopausal women which may increase breast cancer risk; however, the differences were modest. Larger and covariate-adjusted studies with standardized collection over the menstrual cycle are needed to better understand this relationship and to reduce heterogeneity.ImplicationsExisting research has described associations between high prediagnostic estradiol and androgen levels with breast cancer risk among premenopausal women and has established active smoking as a breast cancer risk factor. However, the smoking and circulating sex hormone associations among premenopausal women remain inadequately studied. In this meta-analysis, we identified an association between smoking and higher mean testosterone and dehydroepiandrosterone-sulfate levels with consideration of menstrual phase, providing additional information on smoking's potential pathway to premenopausal breast cancer.

PurposeTo evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed

The published article contained an error in the western blot image in Figure 4A. The C5 and C5[alpha] strips were duplicate images of the same blot. Due to lack of [...]

Objective: To describe extracurricular activity participation and explore its relationship with college students' health. Participants: 159 college students majoring in dental hygiene or occupational therapy. Methods: Data were collected prospectively at baseline, one- and two-year follow-ups. Self-reported participation in extracurricular activities over the past six months was grouped into eight categories: Fitness, Sports, Creative arts, Leisure, Social, Work, Caregiving, and Animal care. Physical and mental health were measured using SF-36, a valid tool measuring general health. Results: Participation in fitness, sports, creative arts, and work significantly decreased at one-year and two-year follow-ups (p < 0.01). Work/volunteer activity participation was associated with poorer physical health ([beta] = -1.4, 95% CI: (-2.2, -0.5), p < 0.01), but a change from nonparticipation to some participation in work/volunteer activity was associated with better mental health ([beta] = 2.6, 95% CI (0.3, 4.9), p = 0.04). Conclusions: Educators should consider the potential impact of maintaining extracurricular activities on college students' health when designing academic courses.

The original article [1] contained significant errors in Fig 1A which necessitated correction; the figure has since been updated to the corrected version.

BackgroundCryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.ResultsAmong 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.ConclusionsIn conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

BackgroundAdverse childhood experiences (ACEs) are potentially traumatic events occurring before age 18, such as maltreatment or exposure to violence. ACE screening is increasingly recommended to prevent and address physical and mental health conditions associated with ACEs. To promote ACE screening uptake, the state of California issued the "ACEs Aware" policy that provides Medicaid reimbursement for ACE screening annually for child primary care visits. However, policy directives alone often do not translate into effective screening efforts and greater access to care. Few rigorous studies have developed and tested implementation strategies for ACE pediatric screening policies. This study will fill this gap by testing a multifaceted implementation strategy in partnership with a Federally Qualified Health Center (FQHC) system serving low-income families in Southern California to support the ACE Aware policy.MethodsWe will use Implementation Mapping, with study process and consideration of determinants and mechanisms guided by the EPIS framework, to co-create and refine an implementation strategy. The proposed strategy is comprised of online training videos, a customized algorithm and use of technology to improve workflow efficiency, implementation training to internal FQHC personnel, clinic support and coaching, and written implementation protocols. A hybrid type 2, stepped-wedge cluster randomized trial design with five primary care clinics will test whether a multifaceted implementation strategy improves (a) fidelity to the ACE screening protocol, (b) reach defined as the proportion of eligible children screened for ACEs, and (c) the impact of the ACE policy on child-level mental health referrals and symptom outcomes. The study will use mixed methods with data to include electronic health records, surveys, and interviews with clinic personnel and caregivers.DiscussionThis study is designed to increase the capacity of FQHCs' inner context to successfully implement an outer context-initiated ACE policy designed to benefit pediatric patients. It capitalizes on a rare opportunity to use a co-creation approach to develop, adapt, refine, and pilot test an implementation strategy to maximize the impact of a new state-wide policy intended to improve ACE assessment and subsequent care to improve child health, particularly those from underserved communities.Trial registrationTrial # NCT04916587  registered at ClinicalTrials.gov on June 4, 2021.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate β^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. β^T was compared to the corresponding regression coefficient estimate β^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis β T = β R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

Abstract: Previous studies have found that tobacco exposure is associated with an increased risk of premenopausal breast cancer (BC) overall and some studies suggest that risk is only increased for Luminal A BC. Few studies have described the association between tobacco exposure and BC risk with characterization of the human epidermal growth factor receptor 2 (HER2) subtype. This analysis explored associations between smoking over the life course and BC risk overall and by BC subtype among a socioeconomically diverse population of young non-Hispanic (NH) Black and White women. Data were examined from a population-based case-control study in women under 50 years of age, the Young Women’s Health History Study. In total, 1,812 women with invasive BC (1,130 NH White, 682 NH Black) and an area-based sample of 1,381 (716 NH White, 665 NH Black) control women, frequency matched to cases by five-year age group, study site and self-reported race were identified from the Los Angeles County and Metropolitan Detroit SEER registry areas. Lifetime smoking histories were collected from in-person interviews. Sample-weighted logistic regression analysis was conducted to estimate the association between lifetime cigarette smoking status (never versus ever smoker) and BC risk adjusted for known BC risk factors and study site. Multinomial logistic regression analysis was conducted for analyses by BC subtype. Heterogeneity in the odds ratio (OR) estimates by BC subtype and cross-product interaction terms of smoking status by race and by household percent poverty (HHP) were evaluated by the Wald test. In adjusted models, BC risk overall was not significantly associated with ever smoking at least 1 cigarette a day for 6 months or more (OR 1.18; 95% confidence interval (CI) 0.97- 1.43). By BC subtype, ever smokers displayed a statistically significant 30% increase in Luminal A BC risk compared to never smokers (OR 1.30; 95% CI 1.03-1.64) and a 90% increased risk of HER2-type BC (OR 1.90; 95% CI 1.17-3.08). Smoking was not associated with risk of Luminal B or Triple Negative BC. Associations between ever smoking and BC risk significantly differed by BC subtype (Pheterogeneity=0.02). Statistical interactions by race or by HHP were not observed. However, we noted that in stratified models the association between smoking and risk for HER2-type BC was higher among NH White compared to NH Black women and among women with HHP ≥150% compared to HHP

BackgroundBlunt pancreatic injury is frequently managed nonoperatively in children. Nutritional support practices - either enteral or parenteral - are heterogeneous and lack evidence-based guidelines. We hypothesized that use of parenteral nutrition (PN) in children with nonoperatively managed blunt pancreatic injury would 1) be associated with longer hospital stay and more frequent complications, and 2) differ in frequency by trauma center type.MethodsWe conducted a retrospective cohort study using the National Trauma Data Bank (2007-2016). Children (≤18 years) with blunt pancreatic injury were included. Patients were excluded for duodenal injury, mortality

Abstract: The etiology of breast cancer (BC) among young women is not well understood. Recent studies have suggested that tobacco exposure is associated with an increased risk of BC but few studies have evaluated risk among women under age 50 or racial and socioeconomic disparities in risk. We hypothesized that racial and socioeconomic differences in age at smoking initiation and lifetime cigarette smoking contribute to disparities in BC risk among young women. Data were examined from a population-based case-control study in women under 50 years of age, the Young Women’s Health History Study. In total, 1,812 women with invasive BC (1,130 Non-Hispanic (NH) White, 682 NH Black) and an area-based sample of 1,381 control women (716 NH White, 665 NH Black), frequency matched to cases by five-year age group, study site and race were identified and interviewed from the Los Angeles County and Metropolitan Detroit SEER registry areas. Lifetime smoking history (including age at initiation, duration, and frequency) were collected from structured in-person interviews. Survey-weighted multivariable logistic regression was used to evaluate the association between lifetime cigarette smoking and BC risk adjusted for matching and known BC risk factors. Additionally, cross-product interaction terms of smoking exposure by race and by socioeconomic position (SEP; based on household percent poverty) were evaluated by Wald’s test. Among controls, 36.5% reported ever smoking at least 1 cigarette a day for at least 6 months in their lifetime with White women compared to Black women (38.3% vs. 32.3%) and women of lower SEP (

IntroductionAllopregnanolone is an endogenous neurosteroid with the potential to be a novel regenerative therapeutic for Alzheimer's disease (AD). Foundations of mechanistic understanding and well-established preclinical safety efficacy make it a viable candidate.MethodsA randomized, double-blinded, placebo-controlled, single and multiple ascending dose trial was conducted. Intravenous allopregnanolone or placebo was administered once-per-week for 12 weeks with a 1-month follow-up. Participants with early AD (mild cognitive impairment due to AD or mild AD), a Mini-Mental State Examination score of 20-26 inclusive, and age ≥55 years were randomized (6:2 to three allopregnanolone dosing cohorts or one placebo cohort). Primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetic (PK) parameters and maximally tolerated dose (MTD). Exploratory endpoints included cognitive and imaging biomarkers.ResultsA total of 24 participants completed the trial. Allopregnanolone was safe and well tolerated in all study participants. No differences were observed between treatment arms in the occurrence and severity of adverse events (AE). Most common AE were mild to moderate in severity and included rash (n = 4 [22%]) and fatigue (n = 3 [17%]). A single non-serious AE, dizziness, was attributable to treatment. There was one serious AE not related to treatment. Pharmacokinetics indicated a predictable linear dose-response in plasma concentration of allopregnanolone after intravenous administration over 30 minutes. The maximum plasma concentrations for the 2 mg, 4 mg, 6 mg, and 10 mg dosages were 14.53 ng/mL (+/-7.31), 42.05 ng/mL (+/-14.55), 60.07 ng/mL (+/-12.8), and 137.48 ng/mL (+/-38.69), respectively. The MTD was established based on evidence of allopregnanolone-induced mild sedation at the highest doses; a sex difference in the threshold for sedation was observed (males 10 mg; females 14 mg). No adverse outcomes on cognition or magnetic resonance imaging-based imaging outcomes were evident.ConclusionsAllopregnanolone was well tolerated and safe across all doses in persons with early AD. Safety, MTD, and PK profiles support advancement of allopregnanolone as a regenerative therapeutic for AD to a phase 2 efficacy trial.Trial registrationClinicalTrials.gov-NCT02221622.

BackgroundTrauma prediction scores such as Revised Trauma Score (RTS) and Trauma and Injury Severity Score (TRISS)) are used to predict mortality, but do not include comorbidities. We analyzed the American Society of Anesthesiologists physical status (ASA PS) for predicting mortality in trauma patients undergoing surgery.MethodsThis multicenter, retrospective study compared the mortality predictive ability of ASA PS, RTS, Injury Severity Score (ISS), and TRISS using a complete case analysis with mixed effects logistic regression. Associations with mortality and AROC were calculated for each measure alone and tested for differences using chi-square.ResultsOf 3,042 patients, 230 (8%) died. The AROC for mortality for TRISS was 0.938 (95%CI 0.921, 0.954), RTS 0.845 (95%CI 0.815, 0.875), and ASA PS 0.886 (95%CI 0.864, 0.908). ASA PS + TRISS did not improve mortality predictive ability (p = 0.18).ConclusionsASA PS was a good predictor of mortality in trauma patients, although combined with TRISS it did not improve predictive ability.

ObjectivesA fracture risk assessment tool (FRAX) using clinical risk factors (CRFs) alone underestimates fracture risk in HIV-infected men. Our objective was to determine whether accuracy of FRAX would be improved by considering HIV as a cause of secondary osteoporosis, and further improved with addition of dual-energy X-ray absorptiometry parameters in HIV-infected women.DesignSubgroup analysis of Women's Interagency HIV Study.MethodsWe included 1148 women (900 HIV-infected and 248 uninfected) over age 40 with data to approximate FRAX CRFs and 10-year observational data for incident fragility fractures; 181 (20%) HIV-infected women had dual-energy X-ray absorptiometry data. Accuracy of FRAX was evaluated by the observed/estimated ratios of fracture in four models: CRFs alone; CRFs with HIV included as a cause of secondary osteoporosis; CRFs and femoral neck bone mineral density (FN BMD); and CRFs, FN BMD and trabecular bone score.ResultsFRAX using CRFs were less accurate in HIV-infected than uninfected women for major osteoporotic (observed/estimated ratio: 5.05 vs. 3.26, P

ObjectiveHIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV.DesignRetrospective cohort study.MethodsA total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status.ResultsMedian (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 μm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 μm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction).ConclusionIn our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

PURPOSE:Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors. METHODS:Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period. RESULTS:EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection.

BackgroundMonocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.MethodsWe examined 778 women (74% HIV+) in the Women's Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years.ResultsMarker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque.ConclusionssCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.