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Recent Submissions

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    The Role of Atherosclerosis in HIV-Related Stroke in South Africa
    (University of the Witwatersrand, Johannesburg, 2025) Sadiq, Mohammad Eitzaz
    Stroke in people living with HIV (PLWH) is an incompletely understood entity. The purpose of this cross-sectional research was to study a population of PLWH who have suffered a stroke in a low-and-middle-income country at the epicentre of the world’s HIV epidemic. Of particular interest was exploring the role of atherosclerosis, which appears to be the primary mechanism mediating HIV-related stroke in data from high-income countries. This study was conducted at a quaternary-level hospital in Johannesburg, South Africa, between August 2014 and November 2017. Patients with new-onset stroke were recruited and assessed using investigations including CT angiography and echocardiography. Validated non- invasive biomarkers of subclinical atherosclerosis, namely carotid intima-media thickness and aortic pulse wave velocity, were used to assess the role of atherosclerosis in patients with strokes of different aetiologies. A total of 346 patients were recruited, of which 87 (25.1%) were PLWH. Of these, 33 (37.9%) were newly diagnosed with HIV on presentation with stroke. In the PLWH with ischaemic stroke (n=85, mean age 43.4±12.5 years), vasculopathy was the most common stroke aetiology (28/85, 32.9%), of which only four were due to atherosclerosis (4.7%). There was no evidence of subclinical atherosclerosis in the other 24 PLWH with vasculopathy nor in those with undetermined stroke aetiology. HIV status had no impact on carotid intima-media thickness in multivariate regression models. Vasculopathy was due to varicella-zoster virus in 8/28 PLWH with vasculopathy (21.4%). This was despite excluding patients with abnormal basic cerebrospinal fluid examination and the unavailability of optimal varicella-zoster diagnostics, suggesting the likely under-diagnosis of this potentially treatable stroke risk factor. Routine testing for varicella-zoster in the cerebrospinal fluid of all PLWH with stroke is thus recommended. In the first 6 months of starting antiretroviral therapy, 32.1% of patients had a stroke, translating to a 3.5 times greater stroke risk in this period compared to beyond 6 months (p=0.0002). This was despite excluding all patients with opportunistic infections, suggesting a novel role of the Immune Reconstitution Inflammatory Syndrome as a stroke risk factor in the absence of such infections. This was also shown to be independent of atherosclerosis. xi Cardioembolism accounted for 20% of strokes, compared to 4-9% in previous regional literature. This likely indicates the under-diagnosis of such conventional stroke aetiologies due to resource limitations. Cardiomyopathy was the predominant aetiology of cardioembolic stroke (76.4%), emphasising the need for a cost-effective and accessible biomarker in a region with limited access to echocardiography. In conclusion, our findings of a low atherosclerotic burden, covert varicella-zoster-related strokes, and the role of immune reconstitution in the absence of opportunistic infections are examples of an alternative view to that in the current literature from high-income countries. This may be more applicable to the management of the vast majority of PLWH globally, who mostly reside in low-and-middle-income countri
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    The Potential Prophylactic Effect of Moringa oleifera Lam. Leaf Extracts Against Fructose-Induced Metabolic Dysfunction in Early-Weaned Female Rats
    (University of the Witwatersrand, Johannesburg, 2025) Mosana, Mmahiine Christina
    Early weaning has become increasingly common worldwide due to urbanisation, socioeconomic demands, and health reasons. It is estimated that 88% of infants are early-weaned (less than 6 months old) globally. Consequently, early-weaned infants, especially when weaned onto high fructose diets, are at risk of developing disorders like metabolic dysfunction associated with fatty liver disease and kidney disease early in childhood. These metabolic disorders then progress into adulthood, affecting their lifespan and functionality, and are a financial burden to the healthcare system. This study investigated the long-term potential prophylactic effects of Moringa oleifera leaf extracts when administered for the first two weeks post-weaning, in female Sprague-Dawley rats early-weaned onto high fructose diets. The rats were weaned early (18 days old), and fed either standard rat feed, a fructose-rich diet, a normal diet with Moringa extracts, or a combination of high fructose with Moringa extracts for 18 days. The normal control group was weaned at 21 days old. Post weaning, the rats were fed a high-fructose diet or a normal diet for 111 days. The rats were terminated on postnatal day 112. Early weaning with fructose-induced elevated serum concentrations of leptin, low-density lipoproteins (LDL), triglyceride, total cholesterol, and alanine transaminase (p<0.05, ANOVA). It also resulted in increased hepatic micro- and macrosteatosis, hypertrophy, inflammation, area fraction of the collagen, peroxisome proliferator-activated receptor alpha (PPARα), and sterol regulatory element-binding protein 1c (SREBP-1c) gene expression (p<0.05). Early weaning with fructose decreased serum concentrations of insulin, adiponectin, high-density lipoprotein (HDL), and hepatic carnitine palmitoyltransferase I (CPT-1) gene expression (p<0.05). However, early weaning treatment with Moringa for only two weeks, demonstrated a broad scope of protection against the fructose-induced metabolic dysfunction, specifically hepatic steatosis, and modulated gene expression related to lipogenesis and fatty acid oxidation by decreasing hepatic SREBP-1c, Acetyl-CoA Carboxylase 1 (ACC-1), and fatty acid synthase (FAS) gene expression and increasing CPT-1 and PPARα gene expression (p<0.05), with dose- dependent effects observed. Early weaning alone did not significantly affect kidney mass, relative mass, serum renal function markers (kidney injury molecule-1 (KIM-1), creatinine, or blood urea nitrogen (BUN) levels, but led to increased serum neutrophil gelatinase-associated lipocalin (NGAL) serum concentrations) and kidney glomerular/Bowman’s capsule area (BCA) (p<0.0001). Fructose caused significant v functional (↑KIM-1, BUN, NGAL; ↓creatinine) and structural kidney damage (enlarged and deformed glomeruli), which Moringa reversed. Dose differences were minimal but indicated slightly better biochemical function with higher doses, but greater histopathological protection with lower doses. In conclusion, early weaning combined with high fructose consumption resulted in significant metabolic dysfunction, hepatic steatosis, and renal damage in female Sprague-Dawley rats. The short-term supplementation of Moringa oleifera leaf extract immediately after early weaning offered long term sustained, multi-organ protection. Given its low cost, accessibility, and translational potential, Moringa represents a promising early-life nutritional strategy to protect against long-term metabolic, hepatic, and renal dysfuncti
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    Epigenetic associations with sex hormone levels and cardiometabolic disease risk factors in pre- and post-menopausal women from West Africa
    (University of the Witwatersrand, Johannesburg, 2025) Naidoo, Merusha
    Menopause is the permanent decline in ovarian function in women, signifying the discontinuation of reproductive potential. Changes in hormone levels due to the menopausal transition have been found to promote the progression to cardiometabolic diseases. Possible epigenetic mechanisms behind changes in hormone levels during the menopausal transition require further research, especially among underrepresented African populations. This cross-sectional cohort study aims to examine epigenetic mechanisms, specifically DNA methylation, to assess its role in differences in sex hormone levels and the prevalence of cardiometabolic disease in pre-and post-menopausal women from Nanoro, Burkina Faso, in West Africa. Genomic DNA derived from blood samples of 99 pre- and 98 post-menopausal participants from the ‘Africa Wits-INDEPTH Partnership for Genomic Research’ (AWI-Gen) was bisulfite modified in preparation for sequencing and methylation calling. Target-specific PCR products amplified with custom-designed methylation primers for androgen receptor (AR), follicle-stimulating hormone receptor (FSHR), inhibin B (INHBB), sex hormone binding globulin (SHBG) and oestrogen receptor β (ESR2) were purified, tagged with indexes, and pooled before next-generation sequencing. Methylation levels across five CpG islands and 86 CpG sites with high-depth sequencing coverage of ~50 000x were determined bioinformatically with the Illumina DRAGEN Methylation Pipeline through BaseSpace. Differences in demographic, behavioural, epigenetic, hormonal, cardiometabolic, anthropometric, and socioeconomic data between pre- and post- menopausal groups were assessed with the Student’s T-test and Mann-Whitney U- test. Bivariate correlation analyses were conducted with Spearman’s Rank Correlation analyses to inform multiple regression analyses of 19 dependent variables. Levels of diastolic blood pressure, estimated glomerular filtration rate (eGFR), LDL-c, visceral fat, oestrogen, FSH, and bioavailable testosterone differed between pre- and post- menopausal women. SHBG, oestrogen, bioavailable testosterone, DHEA-S, and FSH were significantly correlated with several cardiometabolic risk factors, anthropometric variables, and hormone levels. Gene methylation did not differ between menopause stages, and no association of gene methylation with CMD risk factors or hormone levels were noted suggesting that DNA methylation of sex hormone regulatory genes is unlikely to be a mechanism that modulates gene expression during the menopause transition in this cohort.
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    Fuel Saving Performance of Low Rolling Resistance Tyres on Heavy Goods Vehicles
    (University of the Witwatersrand, Johannesburg, 2025-08) Matiane, Arnold Ripfumelo; Atkins, Michael D.
    Understanding the real-world fuel-saving potential of low-rolling-resistance (LRR) tyres in heavy goods vehicles (HGVs) is vital for improving operational efficiency and reducing fuel costs in South Africa’s logistics sector. This study evaluated two identical Scania R460 HGVs, each paired with 2020 Afrit 25 Cube Side Tipper Links trailers, one fitted with LRR tyres and one with conventional tyres. High-frequency data from the CAN bus was collected over three months across 45,000 km, yielding over 2,200 valid observations analysed using the SRF Miner methodology to isolate stable driving segments based on longitudinal acceleration, accelerator pedal position, RPM, vehicle speed, gear, and throttle position. LRR tyres demonstrated a statistically significant fuel-saving benefit of 2.72 L/h (7.3%) across all terrain types under both segment-based (78 to 81 km/h) and route-based (79.5 to 80.5 km/h) analyses. Regression analysis confirmed that the benefit was independent of road gradient since slope coefficients were nearly identical for both tyre types (e.g., 536.6 L/h/rad vs. 527.3 L/h/rad uphill). Fuel savings were consistent across terrains, with reductions of 1.87 L/h (5.3%) on uphill, 1.87 L/h (5.4%) on flat, and 1.87 L/h (7.1%) on downhill segments. Slight variations in fuel savings across terrains under the route-based analysis can be attributed to differences in regression model fit, gravitational effects reducing engine load on downhill segments, and smaller sample sizes causing minor statistical fluctuations. Economically, LRR tyres save R154,143 per truck annually at R20.16/litre, totalling R7.7 million for a 50-truck fleet in South African HGV operations. These findings highlight the operational and economic value of LRR tyres in enhancing fuel efficiency under real-world conditions.
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    Film cooling jet lift-off under a streamwise pressure gradient at different blowing ratios
    (University of the Witwatersrand, Johannesburg, 2025) Gomez-Olive Fernandez, Marc; Atkins, Michael; Kim, Tongbeum; Schekman, Sjouke
    This study introduces the concept of a critical blowing ratio, defining the point at which a film cooling jet detaches from an endwall under a streamwise pressure gradient. Four pressure gradients, extracted over a turbine blade were tested: favourable (FPG), mild favourable (MFPG), zero (ZPG), and mild adverse (MAPG) with acceleration parameters of K = 2.61×10-6, K = 1.53×10-6, K = 0.00×10-6, and K = (-)0.31×10-6. Engine representative conditions were employed with a ReD~14000, hole diameter of 20.0 mm at an injection angle of 30°. The blowing ratio (M) ranged from 0.5 to 2.0 in increments of 0.1. Velocity measurements and visualisation techniques extracted using Particle Image Velocimetry (PIV), Planar Laser Visualisation (PLV), and end-wall oil-dye mixture techniques showed that the coolant jet, at a particular blowing ratio, was either attached, semi-detached or fully detached regardless of the pressure gradient imposed. The critical blowing ratio, in a FPG, was ~1.8 times greater than in a MAPG, indicating better attachment of the coolant jets in FPGs.