Behind the scenes of cellular organization: Quantifying spatial phenotypes of puncta structures with statistical models including random fields.

The cellular interior is a spatially complex environment shaped by non-trivial stochastic and biophysical processes. Within this complexity, spatial organizational principles-also called spatial phenotypes-often emerge with functional implications. However, identifying and quantifying these phenotypes in the stochastic intracellular environment is challenging.

Ecology meets reproductive medicine in HIV prevention: the case for geography-informed approaches for bacterial vaginosis in Africa.

Purpose Of Review: Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated.

Natural History of High-Risk Human Papillomavirus in Kenyan and South African Women: Implications for Vaccination Campaigns and Cervical Cancer Screening Programs.

Objective: Human papillomavirus (HPV) vaccines and DNA testing roll out in resource-constrained settings. We evaluated the natural history of HPV infections in African women to contribute to normative guidance.

Methods: Women aged 16 to 35 years were enrolled from 3 sites in South Africa and Kenya and followed quarterly for 18 months.

Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

Introduction: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care.

Methods And Analysis: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part.

Defining digital coaching: a qualitative inductive approach.

The term 'digital coaching' is widely used but ill-defined. The present study therefore investigates how digital coaching is defined and how it differentiates from face-to-face coaching and other digital-technology-enabled (DT-enabled) formats, such as digital training, digital mentoring, or digital consulting. A qualitative inductive approach was chosen for more in-depth and open-minded content.

GelMap: intrinsic calibration and deformation mapping for expansion microscopy.

Expansion microscopy (ExM) is a powerful technique to overcome the diffraction limit of light microscopy by physically expanding biological specimen in three dimensions. Nonetheless, using ExM for quantitative or diagnostic applications requires robust quality control methods to precisely determine expansion factors and to map deformations due to anisotropic expansion. Here we present GelMap, a flexible workflow to introduce a fluorescent grid into pre-expanded hydrogels that scales with expansion and reports deformations.

Systems analysis reveals differential expression of endocervical genes in African women randomized to DMPA-IM, LNG implant or cu-IUD.

Although effective contraceptives are crucial for preventing unintended pregnancies, evidence suggests that their use may perturb the female genital tract (FGT). A comparative analysis of the effects of the most common contraceptives on the FGT have not been evaluated in a randomized clinical trial setting. Here, we evaluated the effect of three long-acting contraceptive methods: depot medroxyprogesterone acetate(DMPA-IM), levonorgestrel(LNG) implant, and a copper intrauterine device (Cu-IUD), on the endocervical host transcriptome in 188 women from the Evidence for Contraceptive Options and HIV Outcomes Trial (ECHO) trial.

"Words are too small": exploring artmaking as a tool to facilitate dialogues with young South African women about their sexual and reproductive health experiences.

Background: Adolescents and young women are at high risk for sexually transmitted infections (STIs) and unintended pregnancies. However, conversations about sexual and reproductive health (S&RH) are difficult and stigmatised. Visual art-based approaches have been a useful adjunct to language-dependent interviews, encouraging embodied memory recall.

Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism.

Peroxisomes and the endoplasmic reticulum (ER) are intimately linked subcellular organelles, physically connected at membrane contact sites. While collaborating in lipid metabolism, for example, of very long-chain fatty acids (VLCFAs) and plasmalogens, the ER also plays a role in peroxisome biogenesis. Recent work identified tethering complexes on the ER and peroxisome membranes that connect the organelles.

Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents.

The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15-19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex).

Cost-effectiveness analysis of different screening and diagnostic strategies for sexually transmitted infections and bacterial vaginosis in women attending primary health care facilities in Cape Town.

Background: Genital inflammation associated with sexually transmitted infections (STIs) and bacterial vaginosis (BV) is considered a key driver in the HIV epidemic. A new rapid point-of-care test (POC) that detects genital inflammation in women-Genital InFlammation Test (GIFT)-was recently developed by researchers at the University of Cape Town. The objective of this study was to establish the cost-effectiveness of this novel intervention relative to other relevant screening and diagnostic strategies for the management of STIs and BV in women seeking care in the public health sector in South Africa.

Shifting the power: scale-up of access to point-of-care and self-testing for sexually transmitted infections in low-income and middle-income settings.

Purpose Of Review: Point-of-care (POC) testing for sexually transmitted infections (STIs) can provide complementary coverage to existing HIV testing services in LMICs. This review summarizes current and emerging technologies for detecting STIs in LMICs, with an emphasis on women, discharge-causing infections (chlamydia, gonorrhoea, trichomoniasis, and syphilis), true POC, self-testing, ethics, and economic considerations related to equitable access.

Recent Findings: The WHO have recently adapted guidelines for treatment of STIs in women that advise the use of true-POC or near-POC tests to improve case finding.

Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial.

Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays.

A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome.

There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with (CT) significantly impacts the foreskin proteome composition.

Systems Analysis Reveals Contraceptive-Induced Alteration of Cervicovaginal Gene Expression in a Randomized Trial.

Hormonal contraceptives (HCs) are vital in managing the reproductive health of women. However, HC usage has been linked to perturbations in cervicovaginal immunity and increased risk of sexually transmitted infections. Here, we evaluated the impact of three HCs on the cervicovaginal environment using high-throughput transcriptomics.

Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression.

Background: Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (n = 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function.

Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial.

Background: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells.

Persistent, Asymptomatic Colonization with is Associated with Elevated Frequencies of Highly Activated Cervical Th17-Like Cells and Related Cytokines in the Reproductive Tract of South African Adolescents.

Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry).