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Background and Purpose: Women engaged in sex work (WESW) are disproportionately affected by HIV. In Uganda, HIV prevalence among WESW is estimated at 37%, accounting for 18% of all new infections in the country. WESW experience poverty, gender-based violence, and other issues that reduce their power and limit their ability to negotiate condom use. Female-controlled strategies, including pre-exposure prophylaxis (PrEP), may afford women more transmission protection, but barriers to access and use persist. This study examined baseline PrEP acceptability and initiation among WESW recently enrolled in a randomized clinical trial in Uganda to test the impact of a combination HIV risk reduction and economic empowerment intervention on sexual risk outcomes (clinicaltrials.gov, NCT03583541). Methods: A total of 542 WESW from 19 high HIV-prevalent geographical areas were enrolled in the Kyaterekera study between June 2019 and March 2020. Women were eligible for the study if they: 1) were age 18 or over; 2) reported engagement in transactional sex (a sex act in exchange for pay) in the past 30 days; and 3) reported engagement in one or more episodes of unprotected sex in the past 30 days. Women completed a baseline assessment, were tested for HIV and other sexually transmitted infections (STIs) at enrollment, and were connected with antiretroviral therapy (ART), STI treatment, or PrEP, based on need and interest. Descriptive statistics examined baseline data on PrEP acceptability and initiation. Independent variables (i.e. years in sex work, recent sexual coercion, perceived HIV and sex work stigmas, harmful alcohol use, barriers to medical care, and social support) were derived from the empirical literature and women’s self-report. Bivariate analysis was performed to test associations between main effects of these variables. Using binomial logistic regression, predictive models were evaluated for two distinct outcomes—PrEP acceptability and PrEP initiation/uptake. Findings: At baseline, 59% of women (n=322) tested HIV negative. Among WESW testing negative, 11% (n=36) were already PrEP enrolled. Most women reported willingness to use PrEP (n=317; 91%). Only slightly over half of WESW not already on PrEP agreed to initiate PrEP (n=158; 55%). Logistic regression models demonstrate that acceptability of or willingness to use PrEP was significantly associated with fewer years engaged in sex work (r= .147, n=273, P

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling.

Approximately 450 million people, many of whom live in poverty and are from low and middle-income countries (LMICs), experience serious mental health challenges. Children in sub-Saharan Africa comprise half of the total regional population, yet existing mental health services are severely under-equipped to meet their needs and evidence-based practices (EBPs) are scarce. In Uganda, one in five children present mental health challenges, including disruptive behavior disorders. Guided by the Practical, Robust Implementation and Sustainability (PRISM) framework, this paper describes the strategies by which we have engaged community and government partners to invest in a collaborative, longitudinal study in Uganda aimed at improving youth behavioral health outcomes by testing a collaboratively adapted EBP. We emphasize that implementation scientists should be prepared and willing to invest time and effort engaging key stakeholders and sustain relationships through a full range of collaborative activities; ensure that their science meets a felt need among the stakeholders; and translate their research findings rapidly into accessible and actionable policy recommendations. Finally, we highlight that collaboration with global communities and governments plays a critical role in the adaptation, uptake, scalability, and sustainability of EBPs, and that the process of engagement and collaboration can be guided by conceptual frameworks.

Background: Globally, 1.8 million children