Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility.

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3 + CD4 + CCR5 + cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm 2 BV-vs 106.9 cells/mm 2 BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39 + conventional CD4 + T cells (Tconv) (median frequency 15% BV-vs 30% BV+, p adj =0.0331) and tissue-resident CD69 + CD103 + Tconv (median frequency 24% BV-vs 38% BV+, p adj =0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

Kinless Older Adults With Dementia: Qualitative Analysis of Data From the Adult Changes in Thought Study.

OBJECTIVES: To examine the circumstances and needs of older adults who were "kinless," defined as having no living spouse or children, when they developed dementia. METHODS: We conducted a secondary analysis of information from the Adult Changes in Thought study. Among 848 participants diagnosed with dementia between 1994 and 2016, we identified 64 who had no living spouse or child at dementia onset. We then conducted a qualitative analysis of administrative documents pertaining to these participants: handwritten comments recorded after each study visit, and medical history documents containing clinical chart notes from participants' medical records. RESULTS: In this community-dwelling cohort of older adults diagnosed with dementia, 8.4% were kinless at dementia onset. Participants in this sample had an average age of 87 years old, half lived alone, and one third lived with unrelated persons. Through inductive content analysis, we identified 4 themes that describe their circumstances and needs: (1) life trajectories, (2) caregiving resources, (3) care needs and gaps, and (4) turning points in caregiving arrangements. DISCUSSION: Our qualitative analysis reveals that the life trajectories that led members of the analytic cohort to be kinless at dementia onset were quite varied. This research highlights the importance of nonfamily caregivers and participants' own roles as caregivers. Our findings suggest that clinicians and health systems may need to work with other parties to directly provide dementia caregiving support rather than rely on family, and address factors such as neighborhood affordability that particularly affect older adults who have limited family support.

CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions.

We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

Estimating the size of populations at high risk for HIV using respondent-driven sampling data.

The study of hard-to-reach populations presents significant challenges. Typically, a sampling frame is not available, and population members are difficult to identify or recruit from broader sampling frames. This is especially true of populations at high risk for HIV/AIDS. Respondent-driven sampling (RDS) is often used in such settings with the primary goal of estimating the prevalence of infection. In such populations, the number of people at risk for infection and the number of people infected are of fundamental importance. This article presents a case-study of the estimation of the size of the hard-to-reach population based on data collected through RDS. We study two populations of female sex workers and men-who-have-sex-with-men in El Salvador. The approach is Bayesian and we consider different forms of prior information, including using the UNAIDS population size guidelines for this region. We show that the method is able to quantify the amount of information on population size available in RDS samples. As separate validation, we compare our results to those estimated by extrapolating from a capture-recapture study of El Salvadorian cities. The results of our case-study are largely comparable to those of the capture-recapture study when they differ from the UNAIDS guidelines. Our method is widely applicable to data from RDS studies and we provide a software package to facilitate this.

Estimating hidden population size using Respondent-Driven Sampling data.

Respondent-Driven Sampling (RDS) is n approach to sampling design and inference in hard-to-reach human populations. It is often used in situations where the target population is rare and/or stigmatized in the larger population, so that it is prohibitively expensive to contact them through the available frames. Common examples include injecting drug users, men who have sex with men, and female sex workers. Most analysis of RDS data has focused on estimating aggregate characteristics, such as disease prevalence. However, RDS is often conducted in settings where the population size is unknown and of great independent interest. This paper presents an approach to estimating the size of a target population based on data collected through RDS. The proposed approach uses a successive sampling approximation to RDS to leverage information in the ordered sequence of observed personal network sizes. The inference uses the Bayesian framework, allowing for the incorporation of prior knowledge. A flexible class of priors for the population size is used that aids elicitation. An extensive simulation study provides insight into the performance of the method for estimating population size under a broad range of conditions. A further study shows the approach also improves estimation of aggregate characteristics. Finally, the method demonstrates sensible results when used to estimate the size of known networked populations from the National Longitudinal Study of Adolescent Health, and when used to estimate the size of a hard-to-reach population at high risk for HIV.

Evaluation of an intervention to increase human immunodeficiency virus testing among youth in Manzini, Swaziland: a randomized control trial.

There is an urgent need for effective HIV prevention programs for adolescents in Swaziland, given the high prevalence of HIV and lack of HIV-related knowledge and skills among Swazi youth. This study set out to determine whether an HIV education intervention designed in the United States, and adapted for Swaziland, would be effective in changing participants' HIV-related knowledge, attitudes, and protective behaviors including HIV testing. We also explored whether the components of Self-Efficacy Theory are associated with these behaviors. Data were obtained from 135 students who participated in a school-based program. The study found significant differences between the intervention and control groups regarding HIV knowledge, self-efficacy for abstinence, condom use, and getting HIV test results, outcome expectations for knowing one's own HIV status, and the protective behavior of getting an HIV test. This is evidence that school-based HIV education programs can successfully increase HIV testing among in-school youth in Swaziland.

Impact of school district sugar-sweetened beverage policies on student beverage exposure and consumption in middle schools.

PURPOSE: To determine the associations between 1) exposure to sugar-sweetened beverages (SSB) in middle schools and student consumption of SSB during the school day; and 2) school district policies about SSB and exposure to SSB in schools. METHODS: The strength of school district SSB policies was scored on three SSB policy indicators. Student SSB consumption at school was assessed by a self-administered Beverage and Snack Questionnaire. Exposure to SSB at school was defined as the number of vending slots and SSB venues as determined on-site at each school. Multivariate analysis considered the multilevel nature of the data. RESULTS: Data from 9151 students in 64 middle schools in 28 districts were used in the analysis. With schools as the unit of analysis, the proportion of students who consumed any SSB at school ranged from 19.2% to 79.8%. SSB exposure was a significant predictor of SSB consumption (beta=.157, p < .001). SSB consumption was not significantly associated with the size of the school, the racial or ethnic composition of the school's students, or the proportion of students eligible for free and reduced price meals. District SSB policy scores ranged from 0 to 6 with a mean score of 3.25 (+/-2.15). District SSB policy was a significant predictor of SSB exposure (beta=-9.50, p < .0002). CONCLUSIONS: School district SSB policies and exposure to SSB in middle schools are associated with student SSB consumption. Interventions to improve policies and their implementation may offer opportunities to improve the diets of adolescents.

An interactive computer tutorial to teach pain assessment.

Under-treated pain is a significant problem. Health care institutions are under increasing pressure from patients and accreditation bodies to improve staff training in pain management. Pain assessment, a necessary pre-cursor to good pain management, is a complex multi-step process requiring sophisticated understanding and superior communication skills. This article describes the development and usability testing of an interactive, Internet-deliverable, multimedia tutorial to teach best practice pain assessment. The software platform allowed non-programmers to create multimedia tutorials and included the capability to simulate role-plays. The tutorial was designed to actively engage and respond to the learner and to include skills practice. Twenty-five nurses took the tutorial and rated it positively on a usability questionnaire in terms of ease-of-use and learning method.