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BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e052880
Author(s):  
Tanuja Narayansamy Gengiah ◽  
Quarraisha Abdool Karim ◽  
Ishana Harkoo ◽  
Leila Mansoor ◽  
Nonhlanhla Yende Zuma ◽  
...  

IntroductionYoung African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution.Methods and analysisCAPRISA 018 is a phase I/II trial to evaluate the safety, acceptability, tolerability and pharmacokinetics (PKs) of a TAF free base subdermal silicone implant containing 110 mg of TAF with an anticipated 0.25 mg/day release rate.The phase I trial (n=60) will assess the safety of one implant inserted in six participants (Group 1), followed by dose escalation components (Groups 2 and 3) assessing the safety, tolerability and PK of one to four TAF 110 mg implants releasing between 0.25 mg and 1 mg daily in 54 healthy women at low risk for HIV infection. Data from this phase I trial will be used to determine the dosing, implant location and implant replacement interval for the phase II trial.The phase II component (Group 4) will assess extended safety, PK, tolerability and acceptability of the implant in 490 at risk women, randomised in a 1:1 ratio to the TAF implant and placebo tablet or to the placebo implant and an oral pre-exposure prophylaxis tablet. Safety will be assessed by calculating the percentage change in creatinine clearance from baseline at weeks 4, 12, 24, 36, 72, 96 and 120, compared with the percentage change in the control group.Ethics and disseminationThe South African Health Products Regulatory Authority and the University of KwaZulu-Natal’s Biomedical Research Ethics Committee have approved the trial. Results will be disseminated through open access peer reviewed publications, conference presentations, public stakeholder engagement and upload of data into the clinical trials registry.Trial registration numberPACTR201809520959443.


2021 ◽  
Author(s):  
Galya Bigman ◽  
Sally Adebamowo ◽  
King-David Terna Yaw ◽  
Monday Yilkudi ◽  
Oluwole Olaomi ◽  
...  

Abstract Purpose. Beans intake has been associated with reduced risk of breast cancer (BRCA), however; only few studies considered molecular subtypes status and none in African women. Therefore, the purpose of this study was to examine the associations between dietary intake of beans and BRCA including its subtypes in Nigerian women.Methods. Overall, 472 newly diagnosed patients with primary invasive BRCA were age-matched (±5 years) with 472 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study from 01/2014-07/2016. We collected dietary intake of beans using a food frequency questionnaire (FFQ). Beans intake was categorized into three levels of never (never in the past year), low (≤1 portion/week) and high intake (>1 portions/week). We used conditional and unconditional logistic regression models to estimate the Odds Ratio (OR) of beans intake and the risk of overall BRCA and by its molecular subtypes.Results. The mean (SD) age of cases was 44.4(10.0) and of controls was 43.5(9.5) years. In the case group, more than half (51.1%) has never consumed beans alone in the past year compared to 39.0% in the control group. In multivariable models, we found significant inverse associations between beans intake and overall BRCA risk (OR=0.57; 95%CI: 0.38-0.85), hormone receptor-positive BRCA (OR=0.45, 95%CI: 0.23-0.90) and triple-negative BRCA (OR=0.47 95%CI: 0.25-0.88). Conclusion. Dietary intake of beans of more than one portions a week is associated with reduced risk of BRCA in African women and it may play a significant role in reducing the incidence of BRCA particularly of the more aggressive triple-negative subtype, which is more prevalent in SSA.


2021 ◽  
Vol 38 (3) ◽  
pp. 448-469
Author(s):  
Damaris Parsitau ◽  
Esther Mombo ◽  
Ini Dorcas Dah ◽  
Tatiana Wairimu Gitonga

Abstract This article explores some residual entanglements of colonialism, Christianity, and Afro-western engagement in Africa by using the murder of George Floyd at the hands of police and his cries for “breath” and “mama” as a framework for examining the following. First, we argue that one way in which the repercussions of the transatlantic slave trade remain evident in Africa is the continued police brutality and dehumanization of African citizens. Secondly, with the invocation of “mama,” we consider the plight of African women and colonial/postcolonial Christianity, challenging the African church’s silence on social justice issues, and complicity in the exclusion/oppression of women. We call the church to reckon with its silence, and we offer a corrective towards constructing a theological and missiological response to our cries for breath. While this article is based on African feminist reflections, it invites global participation and indicates wider implications for social and gendered justice.


2021 ◽  
Author(s):  
Suman Mewa Kinoo ◽  
Savania Nagiah ◽  
Pragalathan Naidoo ◽  
Bhugwan Singh ◽  
Anil A. Chuturgoon

Abstract Background: Female sex, high estrogen levels, aging, obesity and dyslipidemia are some of the risk factors associated with gallstone formation. HIV infected patients on combination antiretroviral therapy (cART) are more prone to hypercholesterolemia. Bile acid synthesis is initiated by cholesterol 7-alpha hydroxylase (CYP7A1) and regulated by hepatocyte nuclear factors (HNF1α, HNF4α and LXRb).Aim/ Objective: To evaluate the expression of HNF1α, HNF4α, LXRb and miRNAs (HNF4α specific: miR-194-5p and miR-122*_1) that regulate CYP7A1 transcription in HIV-infected Black South African women on cART and presenting with gallstones relative to HIV negative patients with gallstone disease. Methods: Females (n = 96) presenting with gallstone disease were stratified based on HIV status. The gene expression of CYP7A1, HNF1α, HNF4α, LXRb, miR-194-5p and miR-122*_1 was determined using RT-qPCR. Messenger RNA and miRNA levels were reported as fold change expressed as 2-ΔΔCt (RQ min; RQ max). Fold changes >2 and <0.5 were considered significant. Results: HIV-infected females were older in age (p = 0.0267) and displayed higher low-density lipoprotein cholesterol (LDL-c) (p = 0.0419), CYP7A1 [2.078-fold (RQ min: 1.278; RQ max: 3.381)], LXRb [2.595-fold (RQ min: 2.001; RQ max: 3.000)] and HNF1α [3.428 (RQ min: 1.806; RQ max: 6.507] levels. HNF4α [0.642-fold (RQ min: 0.266; RQ max: 1.55)], miR-194-5p [0.527-fold (RQ min: 0.37; RQ max: 0.752)] and miR-122*_1 [0.595-fold (RQ min: 0.332; RQ max: 1.066)] levels were lower in HIV-infected females. Conclusions: HIV-infected women with gallstone disease displayed higher LDL-c levels and increased bile acid synthesis which was evident by the elevated expression of CYP7A1, HNF1α and LXRb. This could have been further influenced by cART and aging.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alan Trinh ◽  
Deva Chan ◽  
Douglas Brubaker

Background and Hypothesis Bacterial vaginosis, which is the imbalance of normal vaginal microbiota, contributes to preterm delivery, vaginitis, and decreased drug efficacy. Despite metronidazole efficacy in reducing BV contributing organisms, BV continues to recur in 50% of patients. Previous studies showing imidazole propionate’s role in the pathogenesis of type II diabetes suggest that similar metabolite-regulated pathways in vaginal microbiomes may be the key in pathogenesis of uterine diseases such as BV. Thus, the purpose of this study was to observe the relationship between vaginal metabolites, host or microbiome-derived, and transcriptomic responses in vaginal epithelial tissues stratified by vaginal microbiome composition (“microbiome group”). The hypothesis was that differences in vaginal microbiome composition result in differential regulation of metabolite-host pathway functional relationships. Project Methods Transcript levels and metabolite concentrations precollected from 23 East African women were processed and analyzed via R. Transcriptomic data were converted into KEGG pathway enrichment scores via ssGSEA2.0, a package within R. Enrichment scores were correlated (Spearman) with metabolite levels by microbiome group and lactobacillus dominant phenotypes, and relationships were visualized via Heatmap3 and Cytoscape. Results: The results showed varying strengths in correlation among metabolites and KEGG pathway enrichment scores after filtering for strong correlations (R > |0.5|) and significance (p< 0.05). Nonlactobacillus dominant microbiomes showed fewer strongly associated metabolite-KEGG pathway relationships compared to the lactobacillus dominant microbiome group, specifically the imidazole-related networks. Conclusion: In this study, variations in significant correlations among metabolites and KEGG pathways suggests that microbiome diversity may contribute to how metabolites regulate host pathways in vaginal epithelial cells. The reduced pathway interactions observed in imidazole compounds suggests that dysregulation may contribute to recurrence of bacterial vaginosis. This method of modelling could be used to characterize the regulation of critical pathways associated with the pathogenesis of bacterial vaginosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Smritee Dabee ◽  
Ramla F. Tanko ◽  
Bryan P. Brown ◽  
Rubina Bunjun ◽  
Christina Balle ◽  
...  

BackgroundCervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives.MethodsWe collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis.ResultsCytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota.ConclusionsBoth DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.


Author(s):  
Esther Deguenon

Con antecedentes inspiradores, desafíos, experiencias ricas y diversas, las mujeres científicas africanas han demostrado que el género no importa siempre que tengas la voluntad y la pasión. Pero ¿cuántas de estas mujeres son reconocidas en su trabajo diario? Desde la dificultad de evolucionar en un entorno dominado por los hombres hasta los desafíos de adentrarse en un campo nuevo, son muchos los desafíos que las mujeres africanas deben afrontar para encontrar su lugar en la ciencia. Las científicas africanas se enfrentan todos los días a las dificultades de ser científicas, y de ser consideradas el sexo más débil. Sería muy útil fortalecer las redes de mujeres científicas facilitando su acceso a la información y promoviendo que se apoyen entre sí y a las más jóvenes que quieran seguir una carrera científica. Las científicas africanas merecen protección en sus actividades científicas mediante textos aplicables y vinculantes. La autora leyó esta carta a los integrantes del Comité de Ética de la Investigación de Aragón y de los Comités Éticos Nacionales de Benín, Guinea Bissau, Guinea Conakry, Malí y Senegal en la apertura del 2.º International Congress on the Harmonisation of Gender Mainstreaming in West Africa, liderado por la Universidad de Zaragoza.


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