South African Cohort Research Articles

Intimate Partner Violence Among Adolescent Mothers Living With and Without HIV: A Pre- and During–COVID-19 South African Cohort Analysis

PurposeAdolescent mothers face heightened economic and social vulnerabilities, which can place them at increased risk of intimate partner violence (IPV), prepandemic, and during COVID-19. However, few studies examine this population, and even less disaggregate findings by HIV status. MethodsWe analyzed data from 834 South African adolescent mothers, 35% living with HIV (LHIV), who reported on physical, psychological, and sexual IPV exposure at two interviews: 2018-2019 (prepandemic) and 2021-2022 (during COVID-19). We estimated lifetime prevalence of IPV, disaggregating by HIV status. We used inverse weighted probability multivariate mixed-effects logistic regression to examine changes in IPV between the two periods and if changes in IPV differed by HIV status. ResultsA quarter of adolescent mothers had experienced any IPV during COVID-19, quadruple prepandemic levels (24.7% vs. 6.0%). The increase was driven by surges in physical (+15.7%) and psychological (+11.2%) IPV. In both periods, psychosocial and physical IPV were the most prevalent forms and the most common combination among those who had experienced multiple forms of IPV. Exposure to any IPV was significantly more prevalent among those LHIV compared to those without HIV, prepandemic (9.5% vs. 4.1%, p = .026) and during COVID-19 (31.8% vs. 20.6%, p < .001). Adjusted models revealed an 18.2% significant increase in the average predicted probability of reporting IPV during COVID-19 compared to prepandemic, with no differential effect by HIV status. DiscussionAdolescent mothers experienced a significantly higher burden of IPV during COVID-19 than prepandemic, with those LHIV experiencing the highest level. Initiatives to reduce IPV need to reach adolescent mothers, particularly those living with HIV.

Unique Gene Expression Profiles within South Africa Are Associated with Varied Chemotherapeutic Responses in Conventional Osteosarcoma.

We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2-∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR -0.27; CI -0.504 to -0.032; p = 0.036]; osteoblastic subtype [OR -0.36; CI -0.652 to -0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR -2.5; CI -3.616 to -1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR -1.04; CI -1.592 to -0.487; p = 0.035]; chondroblastic subtype [OR -0.83; CI -1.106 to -0.520; p = 0.012]; and osteoblastic subtype [OR -1.28; CI -1.664 to -0.901; p = 0.007]. In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent.

A GWAS of ACE Inhibitor-Induced Angioedema in a South African Population.

Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is a life-threatening adverse event and, globally, the commonest cause of emergency presentations with angioedema. Several large genome-wide association studies (GWAS) have found genomic associations with AE-ACEI. However, despite African Americans having a 5-fold increased risk of AE-ACEI, there are no published GWAS from Africa. The aim of this study was to conduct a case-control GWAS of AE-ACEI in a South African population and perform a meta-analysis with an African American and European American population. The GWAS included 202 South African adults with a history of AE-ACEI and 513 controls without angioedema following angiotensin-converting enzyme inhibitor (ACEI) treatment for at least 2 years. A meta-analysis was conducted with GWAS summary statistics from an African American and European American cohort (from Vanderbilt/Marshfield with 174 cases and 489 controls). No SNPs attained genome-wide significance. However, 26 SNPs in the post-imputation standard GWAS of the South African cohort and 37 SNPs in the meta-analysis were associated to AE-ACEI with suggestive threshold(p-value<5.0×10-06). Some of these SNPs were found to be located close to the genes PRKCQ and RIMS1, previously linked with drug-induced angioedema, and also close to the CSMD1 gene linked to ACEI cough, providing replication at the gene level, but with novel lead SNPs. Our results highlight the importance of African populations to detect novel variants in replication studies. Further increased sampling across the continent and matched functional work are needed to confirm the importance of genetic variation in understanding the biology of AE-ACEI.

Tumour-associated macrophages in diffuse large B-cell lymphoma: the prognostic and therapeutic impact in a South African centre with high HIV seroprevalence.

Diffuse large B-cell lymphoma (DLBCL) is a common malignancy among people living with HIV. Macrophage enrichment of the tumour microenvironment (TME) is a prognostic factor in DLBCL among immunocompetent people, with some studies reporting that macrophage enrichment predicts a superior response to rituximab therapy. The macrophage phenotype is also important, with reportedly poorer outcomes with enrichment of anti-inflammatory (M2) macrophages. To date, the relationship between the type/number of tumour macrophages and outcomes in HIV-associated DLBCL (HIV-DLBCL) has been poorly explored. In this study, we assessed tumour macrophage numbers in a South African cohort of patients with DLBCL and a high HIV-seropositivity rate. Immunohistochemistry for CD68 and CD163 was performed on the diagnostic biopsies of 79 patients with DLBCL. Relevant information was documented from the clinical records, including disease stage, international-prognostic index score, HIV-related parameters, C-reactive protein, ferritin levels and immune cell numbers (monocytes, lymphocytes and neutrophils). Survival analysis was performed using Kaplan-Meier survival estimates, and the correlation between tumour macrophage numbers and a variety of immunological parameters was assessed using Spearman's rho. Of the 79 patients included, 87.2% were living with HIV, and rituximab therapy was used in 46.9%. Tumour macrophage numbers were not related to HIV status, but low pro-inflammatory (M1) macrophage numbers (CD68 + CD163 -) were significantly associated with poorer outcomes (HR 2.02, p = 0.03). M2 macrophage (CD68 + CD163 +) enrichment was not predictive of survival but was associated with improved response to rituximab therapy (HR 0.19; p = 0.002). Macrophage numbers were marginally correlated with ferritin levels, which showed modest performance as a peripheral blood biomarker of the TME macrophage status (AUC 0.6 at a level of 374µg/L), and high ferritin levels were associated with a superior response to rituximab-therapy (HR 0.28, p = 0.034). Pro-inflammatory macrophages are important in tumour control in HIV-DLBCL, while M2 macrophage enrichment improves the response to rituximab therapy. Ferritin shows promise as a biomarker for identifying patients more likely to benefit from rituximab therapy.

Health status and disability in persons with spinal cord injuries in South Africa and Kenya

Background: There is a lack of understanding regarding the nature of disabilities and functioning limitations associated with spinal cord injuries (SCI) in developing economies given limited healthcare resources.Aim: Our purpose was to assess and compare SCI-related disability among individuals with SCI in South Africa and Kenya to inform rehabilitation service planning.Settings: Two hundred individuals from South Africa and 90 from Kenya with SCI took part in this cross-sectional survey study, examining the comprehensive functioning of individuals with long-term SCI.Methods: This study utilised the International SCI (InSCI) Community Survey questionnaire. Subsections of the questionnaire were used to investigate the differences in the period-prevalence of secondary medical conditions, activity limitations and participation restrictions in persons with SCI.Results: In both countries, sexual dysfunction (55% – 57%), pain (48% – 49%), spasticity (41% – 42%) and bladder dysfunction (27% – 60%) emerged as the predominant secondary medical complications, with sexual dysfunction and pain showing overlap. There was no notable superiority in terms of treatment rates for secondary medical conditions between countries; however, exceptions were found. Both countries experienced similar overlaps in prevalent activity limitations and participation restrictions, including standing unsupported, using the toilet, bladder and bowel impairments, using public transport and reaching destinations. However, the Kenyan cohort showed significantly higher prevalence rates compared to the South African cohort for challenges related to carrying out daily routines, getting to destinations and using public transportation, while maintaining intimate relationships was more prevalent in South Africa.Conclusion: This study provides insight into the similarities and differences in both the nature and prevalence of disability in two developing economies. It appears that universal functioning patterns after SCI exist in the two countries, and a further need emerged to examine these functioning problems on other major life areas.Contribution: While some functioning problems could be addressed through healthcare and rehabilitation alone, others will require improved coordination and a whole-of-government approach, namely issues related to participation, community integration and inclusion.

Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort.

Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years. In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA. Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction. Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.

O51 EXPLORING GENETIC BASIS OF RESISTANT HYPERTENSION IN EUROPEAN AND AFRICAN POPULATIONS

Background: Approximately 15% of hypertensive (HTN) patients experience resistant hypertension (RHTN) despite the use of ≥ 3 antihypertensive agents (diuretic and blockers of calcium channels and the renin-angiotensin system) at maximum tolerated doses. Intriguingly, genetic variation and alterations in gene content may contribute to RHTN developing. Aim: To comprehend the genetic determinants of RHTN across diverse ethnicities, this study has compared the gene content and presence of single nucleotide variants (SNVs) in RHTN versus controlled-HTN and normotensive participants within European (EU) and South African (SA) populations. Methods: Blood-isolated DNA was collected from 6 participants from EU and 15 from SA. Patients were categorized into 3 groups: RHTN (SA; n=5 and EU; n=6), controlled-HTN (n=5), and normotensive (n=5). DNA was used for Whole Exome Sequencing (WES) analysis. Library preparation and exome capture were done using the MGIEasy Universal DNA library prep and exome capture v5 probe set. Mapping was done using GATK, and the variant calling and annotation were performed using with the SIFT tool and R software. Results: PCA analysis and minimum spanning network showed significant genetic diversity between EU and SA populations. WES identified 16 common genes, with 207 and 220 genes associated to RHTN in EU and SA, respectively. These genes were involved in cardiac electrical conduction (K+/Ca++ channels) and lipid storage (HDL deficiency). In addition, SNV within pharmacogenes in SA (CYP2D6, CYP3A5, APOE) and EU (ADD1) cohorts alongside genes linked to disease susceptibility (RyR1 and PPP1CA) were also identified. RyR1 and PPP1CA are both implicated in HTN development through their roles in calcium signaling and vascular smooth muscle cell function. Noteworthy, two SNVs, rs121918006 and rs61732908, within RyR1 were previously linked to HTN. Conclusions: The large genetic differences observed between EU and SA subjects highlight the diverse genetic landscape surrounding RHTN. Notably, specific genes and their related SNV that associated to cardiac calcium channels and lipid storage could show potential targets for personalized therapeutic intervention. Scientific Session 15: Exploring Novel Therapeutic Approaches to Kidney Disease

Hepatitis B prevalence and risk factors among adults living with HIV in South Africa: a clinic-based cohort study

BackgroundPeople living with HIV (PLHIV) may have concurrent Hepatitis B Virus (HBV) infection, and certain antiretroviral therapies are recommended for HBV-HIV co-infected individuals. Routine screening for Hepatitis B virus may influence management of antiretroviral therapy for PLHIV, but risk factors for co-infection have not been well defined. The objective of this study was to identify risk factors for HBV infection among PLHIV in South Africa.MethodsWe conducted a cross-sectional analysis of a prospective, clinic-based cohort study of adults seeking HIV testing from 2013–2017 in Umlazi township, South Africa. Patients newly diagnosed with HIV were enrolled and subsequently tested for Hepatitis B surface antigen positive (HBsAg +). We used a Poisson linear regression model to assess which factors, pertaining to sociodemographic status, medical history, clinical symptoms, mental health were associated with HBV.ResultsAmong 3,105 PLHIV participants in South Africa, 6% were positive for HBV. Males had a higher HBV prevalence (10.4%) than females (5.2%). Within the HBV-positive group, the mean age was 33.2 years, with 38.3% females and 43.9% having completed high school or higher. About 39.9% reported alcohol use, 24.7% had a smoking history, and 8.3% reported substance use in the past year. Older participants born before 1995, when routine infant HBV vaccination was introduced, were more likely to have HBV. In multivariable analyses, smoking history increased HBV risk in females (aPR = 2.58; 95% CI 1.47–2.52), while alcohol use decreased HBV risk in males (aPR = 0.36; 95% CI 0.19–0.70).ConclusionsIn a South African cohort, roughly one in 16 PLHIV had HBV co-infection, and this rate was higher in males. The most prominent risk factors for HBV infection in PLHIV were alcohol use, higher income, and smoking history, which may help inform targeted treatment and prevention strategies. Creating HBV-specific screening and prevention strategies for PLHIV may be useful for reducing HBV infections.

The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis

Tuberculous meningitis (TBM)—the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture—an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified—1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol—which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Associations between prenatal exposure to phenols and child neurodevelopment at two years of age in a South African birth cohort

Associations between prenatal exposure to phenols and child neurodevelopment at two years of age in a South African birth cohort

The Joint Effects of Prenatal Pesticide Exposure and Psychosocial Stressors on Child Psychopathology in a South African Birth Cohort

The Joint Effects of Prenatal Pesticide Exposure and Psychosocial Stressors on Child Psychopathology in a South African Birth Cohort

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Internal migration and depressive symptoms: Exploring selection and outcomes in a South African cohort

IntroductionInvestigations of migration effects on mental health conditions, including depression are sparse in low- and middle-income countries (LMIC), yet mental health may play a role in a decision to migrate, and migration in turn can impact on mental health outcomes. MethodsThis paper uses two waves of data from the Migrant Health Follow-Up Study, a young adult cohort of 2967 internal migrants and residents of the Agincourt study site in rural northeast South Africa to explore the relationship between internal migration and depressive symptoms, as measured on the Center for Epidemiological Studies Depression (CES-D) scale. We employ logistic regression analysis to investigate selectivity of migrants in relation to depressive symptoms, and we fit generalized linear models to analyse depressive symptoms (CES-D scores) as a function of migration status and sociodemographic and health characteristics, accounting for temporal sequence. ResultsAlthough we observe systematically low reporting of depressive symptoms, average CES-D scores are lower among migrants (comprising approximately 53% of the cohort) compared to Agincourt residents at both survey timepoints. We do not find evidence of a selection effect in relation to mental health among those newly migrating between Wave 2 and 3 (n = 1393). In analyses of the CES-D score outcome, the significant influence of migration status on depressive symptoms is reduced with the inclusion of controls in the models. Consistent employment and higher levels of education are associated with lower CES-D scores, while diagnosis of a chronic condition is associated with higher scores. ConclusionThe relationship between migration and depressive symptoms is influenced by factors preceding a migration and destination-place characteristics and experiences. Further examination of the role of migration at different stages of the process, along with continuing attention to psychosocial measurement considerations for LMIC subpopulations, can improve our understanding of these complex interrelationships and contribute to evidence.

Exposure to Violence and Mental Health Outcomes Among Pre-schoolers in a South African Birth Cohort.

Little is known about the relationship between violence exposure and mental health in preschoolers living in low- and middle-income countries (LMICs).Multiple regression analyses investigated associations between violence exposure and mental health in the Drakenstein Child Health Study (N = 978), a South African birth cohort. Lifetime violence exposure was assessed at age 4.5 years using the parent-report Child Exposure to Community Violence Checklist (CECV). Mental health was assessed at age 5 years using the Child Behaviour Checklist (CBCL 1.5-5).Eighty-three percent of the children were exposed to some form of violence. Internalising and externalising behaviours were positively associated with overall violence exposure (β per one unit change in the overall score = 0.55 [0.16, 0.94] and β = 0.53 [0.23, 0.84], respectively), domestic victimisation (β per one unit change in the subscore = 1.28 [0.28, 2.27]; β = 1.14 [0.37, 1.90]) and witnessing community violence (β = 0.77 [0.15, 1.39]; β = 0.68 [0.19, 1.18]). There was a positive association between polyvictimisation and externalising (β = 1.02 [0.30, 1.73]) but not internalising (β = 0.87 [-0.06, 1.80]) behaviour problems. Evidence for an association of witnessing domestic violence with internalising (β = 0.63 [-0.97, 2.24]) or externalising (β = 1.23 [-0.04, 2.50]) behaviours was less robust. There was no association between community victimisation and internalising or externalising behaviours (β = 0.72 [-1.52, 2.97; β = 0.68 [ -1.06, 2.41]).Observations highlight the risk for mental health problems among preschoolers living in high-violence contexts and emphasize the need for early interventions.

Impact of Variable Sampling on Estimates of HIV-1 Reservoir Formation Dates.

Timing of human immunodeficiency virus-1 (HIV-1) reservoir formation is important for informing HIV cure efforts. It is unclear how much of the variability seen in dating reservoir formation is due to sampling and gene-specific differences. We used a Bayesian extension of root to tip regression (bayroot) to reestimate formation date distributions in participants from Swedish and South African cohorts, and assessed the impact of variable timing, frequency, and depth of sampling on these estimates. Significant shifts in formation date distributions were only observed with use of faster-evolving genes, while timing, frequency, and depth of sampling had minor or no significant effect on estimates.

An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort

BackgroundTo determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC.MethodsFifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV.Resultsp16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%.ConclusionFindings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.

Polymorphism of Genes Encoding Inflammatory Interleukins and the Risk of Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis.

Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case-control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case-control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02-1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54-1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70-1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84-1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible.

Morphometric Integration of Brain Networks in Young Children Exposed to Maternal Depression in a South African Birth Cohort

Morphometric Integration of Brain Networks in Young Children Exposed to Maternal Depression in a South African Birth Cohort

Next generation sequencing: A possible answer to sudden unexplained deaths in a young South African cohort?

Next generation sequencing: A possible answer to sudden unexplained deaths in a young South African cohort?

Trends in body mass index in the pre-dolutegravir period in South Africa.

Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Longitudinal analysis of the Ndlovu Cohort Study including 36-48 months' follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.