Diabetic Nephropathy-Associated Impaired Aortic Function Is Not Mediated by Mean Arterial Pressure and Its Determinants.

The study aimed to assess the potential impacts of mean arterial pressure (MAP) and its determinants (cardiac output and systemic vascular resistance) on diabetic nephropathy (DNP)-associated impaired aortic function. This multi-ethnic study included 115 chronic kidney disease (CKD) patients (67 non-dialysis and 48 dialysis). Six aortic function measures were evaluated by SpygmoCor.

Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients Monocyte/lymphocyte bioenergetic signatures post-TB treatment.

The impact of human pulmonary tuberculosis (TB) on the bioenergetic metabolism of circulating immune cells remains elusive, as does the resolution of these effects with TB treatment. In this study, the rates of oxidative phosphorylation (OXPHOS) and glycolysis in circulating lymphocytes and monocytes of patients with drug-susceptible TB at diagnosis, 2 months, and 6 months during treatment, and 12 months after diagnosis were investigated using extracellular flux analysis. At diagnosis, the bioenergetic parameters of both blood lymphocytes and monocytes of TB patients were severely impaired in comparison to non-TB and non-HIV-infected controls.

Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection.

Introduction: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.

Patulin alters alpha-adrenergic receptor signalling and induces epigenetic modifications in the kidneys of C57BL/6 mice.

Patulin (PAT) is a food-borne mycotoxin produced by Penicillium and Byssochlamys species. It is widely known for its mutagenic, carcinogenic, and genotoxic effects and has been associated with kidney injury; however, the mechanism of toxicity remains unclear. To address this gap, we conducted a study to explore the changes in α-adrenergic receptor signalling pathways and epigenetic modifications induced by PAT in the kidneys of C57BL/6 mice during acute (1 day) and prolonged (10 days) exposure.

Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation.

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion.

Key programmatic and policy considerations for introducing multipurpose prevention (MPT) methods: reflections from healthcare providers and key stakeholders in South Africa.

Introduction: Multipurpose prevention technologies (MPTs) simultaneously prevent HIV, other sexually transmitted infections, and/or unintended pregnancy. Key gatekeepers, [healthcare providers (HCPs) and key stakeholders] require proactive engagement before product implementation. This manuscript identifies HCP demand creation strategies, key stakeholder considerations for the adoption of MPTs in South Africa.

Factors influencing the uptake of a mono-PrEP implant for the prevention of HIV: Males' perspectives from three South African provinces.

Introduction: Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method; however, males over 15 years face challenges with its effective use. Long-acting prevention products could address barriers to effective PrEP use. This study aimed to estimate the potential uptake of a mono-PrEP implant and the factors influencing uptake among males in South Africa.

Preferences, educational messaging, and demand creation channels for multipurpose-prevention technologies (MPTs) among women in South Africa.

Background: South African women, including female sex workers (FSWs), are disproportionately affected by HIV, experience a high unmet need for contraception and high rates of sexually transmitted infections (STIs). Products that address the interlinked risk between HIV, unplanned pregnancy, and other STIs are needed. There are several multipurpose-prevention technologies (MPTs) in development, aimed at preventing both HIV and pregnancy.

Antiretrovirals Promote Insulin Resistance in HepG2 Liver Cells through miRNA Regulation and Transcriptional Activation of the NLRP3 Inflammasome.

Metabolic syndrome (MetS) is a non-communicable disease characterized by a cluster of metabolic irregularities. Alarmingly, the prevalence of MetS in people living with Human Immunodeficiency Virus (HIV) and antiretroviral (ARV) usage is increasing rapidly. Insulin resistance is a common characteristic of MetS that leads to the development of Type 2 diabetes mellitus (T2DM).

Planning for decentralized, simplified prEP: Learnings from potential end users in Ga-Rankuwa, gauteng, South Africa.

Background: In South Africa, youth experience challenges with oral Pre-Exposure Prophylaxis (PrEP) access and uptake. Taking services out of healthcare settings has the potential to increase reach and overcome these challenges. This paper presents young and older people's preferences for decentralized, simplified PrEP service delivery and new long-acting HIV prevention methods, in Ga-Rankuwa, South Africa.

Synthesis of 2,4,5-Trisubstituted Oxazoles from Copper-Mediated Benzylic sp C-H Aerobic Oxidative Annulation of Ketones and Amines via a Cascade Reaction.

The functionalization of sp carbons is deemed challenging in synthetic organic chemistry yet has tremendous potential in producing potent organic compounds. A facile synthesis of 2,4,5-trisubstituted oxazoles through an oxidative, copper-catalyzed, and solvent-free annulation is described. Various arylated oxazoles were efficaciously synthesized at a mild temperature from readily available substrates under a molecular oxygen atmosphere.

HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway.

Background: HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections.

Methods: We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features.

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection.

SARS-CoV-2 Omicron (B.1.1.

Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis.

Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of (Mtb) among persons on anti-TB treatment (ATT) are unknown.

Omicron infection enhances Delta antibody immunity in vaccinated persons.

The extent to which Omicron infection, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.

Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment.

SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape.

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections.

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

Omicron variant (B.1.1.

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity.

Unlabelled: Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant.

HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave.

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants.

Increased Neutrophil Count and Decreased Neutrophil CD15 Expression Correlate With TB Disease Severity and Treatment Response Irrespective of HIV Co-infection.

Tuberculosis remains a leading cause of death globally despite curative treatment, partly due to the difficulty of identifying patients who will not respond to therapy. Simple host biomarkers that correlate with response to drug treatment would facilitate improvement in outcomes and the evaluation of novel therapies. In a prospective longitudinal cohort study, we evaluated neutrophil count and phenotype at baseline, as well as during TB treatment in 79 patients [50 (63%) HIV-positive] with microbiologically confirmed drug susceptible TB undergoing standard treatment.

Dysregulation of circulating sTie2 and sHER2 in HIV-infected women with preeclampsia.

Objective: This study assesses whether circulating sTie2 and sHER2 are altered in HIV-negative and HIV-positive pregnant normotensive and preeclamptic women.

Methods: Serum samples were obtained from 80 pregnant women, stratified into four groups, namely, HIV-negative normotensives (20); HIV-positive normotensives (20); HIV-negative preeclamptics (20); and HIV-positive preeclamptics (20). The concentration of sTie2 and sHER2 was analyzed by Bio-Plex multiplex immunoassay and generated from a standard curve.

Process Evaluation of a Pilot Intervention for Psychosocial Rehabilitation for Service Users with Schizophrenia in North West Province, South Africa.

This study investigated a non-specialist delivered programme for psychosocial rehabilitation for service users with schizophrenia in a low-resource South African setting. Forty-four service users with schizophrenia living in the community, receiving ongoing medication through primary care, participated in a structured support group. Quantitative measures (WHODAS 12 item, Brief Psychiatric Rating Scale and Internalized Stigma of Mental Illness Inventory) were assessed at baseline and 12 months.

Drug-resistant tuberculosis among HIV-infected patients starting antiretroviral therapy in Durban, South Africa.

Objective: To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa.

Design: Cross-sectional cohort study.

Methods: Consecutive HIV-infected adults (≥ 18y/o) initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB.