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While machine learning (ML) has shown great promise in medical diagnostics, a major challenge is that ML models do not always perform equally well among ethnic groups. This is alarming for women's health, as there are already existing health disparities that vary by ethnicity. Bacterial Vaginosis (BV) is a common vaginal syndrome among women of reproductive age and has clear diagnostic differences among ethnic groups. Here, we investigate the ability of four ML algorithms to diagnose BV. We determine the fairness in the prediction of asymptomatic BV using 16S rRNA sequencing data from Asian, Black, Hispanic, and white women. General purpose ML model performances vary based on ethnicity. When evaluating the metric of false positive or false negative rate, we find that models perform least effectively for Hispanic and Asian women. Models generally have the highest performance for white women and the lowest for Asian women. These findings demonstrate a need for improved methodologies to increase model fairness for predicting BV. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease (RHD) is the major cause of cardiovascular morbidity and mortality in children and young adults in low- and middle-income countries. Acute rheumatic fever (ARF) is characterised by multiorgan infl ammatory symptoms initiated through cross reaction of immune responses (IRs) to group A streptococcus (GAS) proteins to host proteins. Recurrence of these IRs targeting the heart valves may lead to permanent damage, a sequela which is termed RHD. Preliminary studies suggested genetic associations in RF reactions, but that other host factors are also involved, leaving the determinants of RHD progression incompletely understood. Previous clinical and recent epidemiological studies support differential clinical phenotypes, with varying history from different settings. This review summarises the protein-centric biomolecular changes in RHD and highlights outstanding molecular gaps where urgent focus is required to improve our understanding RHD pathophysiology. Numerous studies have confi rmed alterations in the expression of structural and immune response proteins, but the modifi cations giving rise to neo-epitopes and their involvement in RHD have not been established. As RHD is associated with poor living conditions, identifi cation of other factors driving infl ammation to enhance RHD progression is necessary to advance our knowledge and improve patient management. Furthermore, biomarkers for early identifi cation, disease stratifi cation, and alternative therapeutic strategies are necessary to improve treatment and prevention strategies in order to reduce the burden of RHD. Relevance: Despite the explosion of scientifi c innovation over the last few decades, fundamental scientifi c studies to understand the pathophysiological mechanisms of RHD remain in their infancy and the determinants of RHD progression thus remain uncertain. Moreover, inconsistency in natural history and phenotypic presentations are seen between Africans and other cohorts in which preliminary studies were conducted, implying that differences in genetic complexity and environmental factors may be responsible for the differential disease progression rates. [ABSTRACT FROM AUTHOR]

Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART-naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire, 4-6 months after ART initiation. 86 % of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin-positive patients were twice as likely to have detectable viral loads (RR 2.32 95 % CI 1.26-4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis-based assay makes it a prime candidate for implementation in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa. Methods: Adult HIV-negative (n = 36), treatment naïve (n = 51), efavirenz (EFV)-treated (n = 91), nevirapine (NVP)-treated (n = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (n=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured. Results: PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure. Conclusions: Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors. [ABSTRACT FROM AUTHOR]

Major advances in highly active antiretroviral therapies (HAART) have extended the lives of people living with HIV, but there still remains an increased risk of death by cardiovascular diseases (CVD). HIV proteins have been shown to contribute to cardiovascular dysfunction with effects on the different cell types that comprise the arterial wall. In particular, HIV-1 transactivating factor (Tat) has been shown to bind to endothelial cells inducing a range of responses that contribute to vascular dysfunction. It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development. When exposed to low or oscillatory shear stress, such as that found at branches and bifurcations, endothelial cells contribute to proteolytic vascular remodeling by upregulating cathepsins, potent elastases and collagenases that contribute to altered biomechanics and plaque formation. Mechanisms to understand the influence of Tat on shear stress mediated vascular remodeling have not been fully elucidated. Using an in vivo HIV-Tg mouse model and an in vitro cone and plate shear stress bioreactor to actuate physiologically relevant pro-atherogenic or atheroprotective shear stress on human aortic endothelial cells, we have shown synergism between HIV proteins and pro-atherogenic shear stress to increase endothelial cell expression of the powerful protease cathepsin K, and may implicate this protease in accelerated CVD in people living with HIV. [ABSTRACT FROM AUTHOR]

HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease (CVD), including a higher risk of myocardial infarction and prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness (c-IMT), increased arterial stiffness, and impaired flow-mediated dilation. Both HAART and HIV-infection are independent risk factors for atherosclerosis and myocardial infarction. Studies implicate the HIV proteins tat, gp120, vpu, and nef in early on-set atherosclerosis. The objective of this study was to quantify the role of expression of HIV-1 proteins on the vascular function, biomechanics, and geometry of common carotid arteries and aortas. This study employed NL4-3Δ gag/pol transgenic mice (HIV-Tg), which contain the genetic sequence for the HIV-1 proteins env, tat, nef, rev, vif, vpr, and vpu but lacks the gag and pol genes and reports that HIV-Tg mice have impaired aortic endothelial function, increased c-IMT, and increased arterial stiffness. Further, HIV-Tg arteries show decreased elastin content, increased cathepsin K and cathepsin S activity, and increased mechanical residual stress. Thus, mice that express HIV proteins exhibit pre-clinical markers of atherosclerosis and these markers correlate with changes in markers of vascular remodeling. These findings are consistent with the hypothesis that HIV-proteins, independent of HAART treatment or HIV infection, could play a role in of the development of CVD. [ABSTRACT FROM AUTHOR]