HIV seroconversion among female sex workers: retrospective cohort study from a large-scale HIV prevention and sexual and reproductive health program in Tanzania.

Introduction: In 2016, UNAIDS set ambitious targets to reduce global HIV infections by 75% by 2020 and 90% by 2030, based on the 2.1 million new infections reported in 2010. However, by 2022, new HIV infections had only decreased by 38%, from 2.1 million in 2010 to 1.3 million in 2022, raising concerns about reaching the 2030 goal. Female sex workers (FSWs) in sub-Saharan Africa face a disproportionately high risk of HIV acquisition, contributing 5%-20% of all new infections in several countries in the region. This analysis investigates HIV seroconversion and associated factors among FSWs, offering insights into critical interventions for preventing HIV transmission in this population and advancing the goal of ending the HIV pandemic by 2030. Methods: We conducted a retrospective cohort study involving 17,977 FSWs who initially tested HIV negative upon enrollment in the Sauti project between October 2016 and September 2018. HIV incidence rates were calculated by dividing the number of new HIV cases by observed person-time within the cohort. Cox regression analysis identified factors associated with seroconversion. Results: The study revealed an HIV incidence rate of 8.6 per 100 person-years among FSWs [95% confidence interval (CI): 8.1-9.1]. Factors independently associated with HIV seroconversion included age 35 years or older [adjusted hazard ratio (aHR): 2.53; 95% CI: 2.03-3.14], unprotected sex (aHR: 1.27; 95% CI: 1.13-1.42), STI symptoms (aHR: 1.99; 95% CI: 1.67-2.38), and alcohol consumption before sex (aHR: 1.20; 95% CI: 1.07-1.34). Conclusion: Targeted interventions are vital in curbing HIV transmission among FSWs, with a focus on expanding access to primary HIV prevention services, particularly for older FSWs who face heightened risk. Tailored sexual health education programs are imperative to encourage consistent condom use and enable informed decision-making. Accessible and timely STI screening and treatment services are crucial to mitigate HIV transmission risk. Collaborative partnerships between healthcare providers, community organizations, and government agencies are essential in implementing these interventions among FSWs.

Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V.

Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV-C2) by characterizing its membrane binding the specific lipid-protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2-25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1-3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid-protein interactions. Despite existing crystal structures representing presumed "open" and "closed" states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both "open" and "closed" states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1-3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures.

Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET.

PURPOSE: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. METHODS: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. RESULTS: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). CONCLUSION: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

Controlling the first wave of the COVID-19 pandemic in Malawi: results from a panel study

Many African countries have experienced a first wave of the COVID-19 pandemic between June and August of 2020. According to case counts reported daily by epidemiological surveillance systems, infection rates remained low in most countries. This defied early models of the potential impact of COVID-19 on the continent, that projected large outbreaks and massive strain on health systems. Theories proposed to explain the apparently limited spread of the novel coronavirus in most African countries have emphasized 1) early actions by health authorities (e.g., border closures) and 2) biological or environmental determinants of the transmissibility of SARS-CoV-2 (e.g., warm weather, cross-immunity). In this paper, we explored additional factors that might contribute to the low recorded burden of COVID-19 in Malawi, a low-income country in Southeastern Africa. To do so, we used 4 rounds of panel data collected among a sample of adults during the first 6 months of the pandemic in the country. Our analyses of survey data on SARS-CoV-2 testing and COVID-related symptoms indicate that the size of the outbreak that occurred in June-August 2020 might be larger than recorded by surveillance systems that rely on RT-PCR testing. Our data also document the widespread adoption of physical distancing and mask use in response to the outbreak, whereas most measured patterns of social contacts remained stable during the course of the panel study. These findings will help better project, and respond to, future waves of the pandemic in Malawi and similar settings.