Browsing by Subject "human biology"

Now showing 1 - 14 of 14
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    An analysis of the partial feasibility of a novel cardiac exercise rehabilitation programme for patients suffering from cardiovascular disease
    (2022) Ross, Tayla Jane; Kroff, Jacolene; Atterbury, E
    Introduction: Substantial research has shown that the inclusion of exercise in cardiac rehabilitation has a favourable effect on many outcome variables, and that exercise should be considered a vital and central component for cardiovascular disease (CVD) rehabilitation. South Africans are facing a growing epidemic of CVD, which has major implications for healthcare services and has placed increasing strain on the already grabbling South African healthcare system. Cost-effective primary and secondary prevention and management strategies are needed to slow down the growing CVD epidemic and relieve strain on health-care systems. The need exists for more evidence to demonstrate that cardiac exercise rehabilitation programmes (CRPs) can significantly reduce readmissions, mortality, comorbidities, and improve quality of life. Aims: The aims of this study were to determine the partial feasibility of a novel CRP in a South African public hospital setting by evaluating the following: 1) The recruitment potential and sample population characteristics of those considered eligible to partake in the exercise component of a novel CRP; and 2) The testretest reliability of the tools utilized for the safe monitoring of the exercise intensity during the prospective CRP. Methods: The recruitment potential and sample population characteristics of the target population were determined via retrospective analysis of a hospital admission patient database spreading over three months. The database was searched for demographic data including age, sex, height, weight, waist circumference and BMI, the admission diagnosis, patient co-morbidities and medications. The test-retest reliability of the monitoring tools was conducted on apparently healthy participants who underwent a series of monitoring measures before and after a 6-min motion test on two separate occasions. The test-retest reliability of each monitoring tool was determined using intraclass correlation coefficients (ICCs), effect size calculation and Bland-Altman plots. Results: One hundred and nine patients (52.2%) were considered ineligible for a CRP, whereas 100 individuals (47.8%) were considered eligible. Significant differences were identified between the eligible and ineligible populations were for four comorbidities and two medications. Twenty-two outcome measures were assessed for reliability, five of which were classified as having “poor” reliability, nine as “moderate”, three as “good” and five as “excellent' according to ICCs. Eighteen measures revealed excellent test-retest reliability, and the remaining 8 measures (Baseline Systolic Blood Pressure; Baseline Diastolic Blood Pressure; Baseline Oxygen Saturation; Immediately Post-Exercise Oxygen Saturation; Immediately Post-Exercise RPE; 5-Minutes Post-Exercise Systolic Blood Pressure; 5-Minutes Post-Exercise Oxygen Saturation; and 5-Minutes Post-Exercise RPE) had showed small effect sizes between 0.2-0.5, which was considered acceptable. Conclusion: The results from the analysis of the recruitment potential from a public hospital setting reveal that approximately 33 patients (100 patients/3 months) will be eligible per CRP intake, and the recruitment potential of eligible patients currently exceeds the prospective resource and staff capacity of the CRP. Further investigation is required to address and resolve the shortcoming in resources to offer the CRP to all eligible participants. The results from the test-retest reliability of the monitoring tools used within the CRP revealed that most of the equipment and measures achieved sound reliability, except for the blood pressure monitors, pulse oximeters and RPE scale. Alternative devices for monitoring blood pressure, oxygen saturation and RPE are recommended.
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    Assessment of subnational level birth registration data in South Africa
    (2021) Madamombe, Tawanda; Moultrie, Thomas
    Birth registration data forms part of vital statistics. It is the right of the child to be registered immediately after birth and to acquire an identity and a nationality as stipulated by the Convention on the Rights of the Child (UNICEF 1989). The assessment of birth registration is important to help authorities in the processes of planning and decision making. This study investigates birth registration data at a district level with the aim to establish the data's usefulness in determining reliable completeness of births and estimating total fertility rate (TFR). The study further analyses the spatial relationships between respective districts to each other based on levels of birth completeness and total fertility rate. The Geographical Information Systems (GIS) technique of the Global Moran's Index spatial autocorrelation is used to examine the spatial distribution of completeness and TFR. The Indirect method of relational Gompertz model is used to calculate robust estimates of actual births that occurred in the twelve-month period before 2011 Census and 2016 Community Survey, respectively. Then, the Hauer and Schmertmann (2020) method of determining fertility was used to validate results from the Gompertz model. The study establishes that there was an improvement in the promptness of birth registration between 2011 and 2016, highlighted by an 82% completeness in 2011 that increased to 85% in 2016 for births that were registered within the same year of occurrence. This is evidence that mothers are registering births at younger ages than before. The TFR decreased from 2.55 in 2011 to 2.28 in 2016. Apart from that, the study illustrated that districts with higher completeness levels tend to be in major urban agglomerations. However, no spatial relationship could be established meaning that the neighbouring districts do not follow any pattern when compared to each other. It was also noted that districts with low fertility are clustered near major cities. Although there are issues with data at lower levels of disaggregation such as districts, it has been shown that the use of robust methods produces results that help to give meaningful insights of birth registration data.
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    Investigation of the mechanisms underlying the effects of hyperglycaemia on cardiac structural and electrical remodelling
    (2022) Aboalgasm, Hamida; Gwanyanya, Asfree; Ballo, Robea
    Background: Diabetes mellitus with uncontrolled hyperglycaemia is a major cause of cardiovascular complications and mortality. The developing foetal heart in-utero is particularly susceptible to hyperglycaemia through pathological remodelling, which results in life-long structural abnormalities such as cardiomyopathy and electrical defects like arrhythmias. However, the underlying mechanisms and potential therapeutic drug targets remain unclear. In this study, a cardiac developmental cellular model was used to study hyperglycaemia-induced remodelling. Methods: Mouse embryonic stem cells (mESCs) were differentiated into pulsatile, cardiac-like cells via embryoid body (EB) formation and cultured under baseline- or high glucose conditions. A Ca2+ -sensitive fluorescent dye Fluo-4 was used to measure calcium transients and a voltage-sensitive dye di-4-ANEPPS was used to record action potentials. Cellular biomarkers were detected using immunocytochemistry, confocal microscopy, and Western blotting as well as terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and 5-ethynyl-2-deoxyuridine (EdU) assay. Results: Undifferentiated mESCs were positive for pluripotent transcription factors Nanog and Oct3/4, whereas the cardiac differentiated mESCs were positive for cardiac proteins troponin T, α-actinin 2, connexin 43, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA 2) and α- and β-myosin heavy chain. Hyperglycaemia decreased the number of beating EBs, their beating rate, and their amplitude of contraction. It also decreased the calcium transient amplitude and the contractile response to ryanodine receptor stimulation by caffeine but did not alter the SERCA 2 expression. The amplitude and duration of action potentials in beating EBs were not altered by hyperglycaemia. However, structural changes included a decrease in EB size and expression of myofilament proteins, α-actinin and α- and β-myosin heavy chain and a disruption of the striated organization of the myofilaments. Hyperglycaemia increased the proportion of TUNEL-positive cells and the expression of the pro-apoptotic marker cytochrome c and decreased the anti-apoptotic protein Bcell lymphoma 2 but did not alter the mitochondrial staining with Mitotracker. It also increased the oxidative stress marker nitrotyrosine but did not alter the extent of EdU nuclear staining nor the expression of the receptor of advanced glycation end-product. The antioxidant n-acetyl cysteine decreased the fraction of hyperglycaemia-induced TUNEL-positive cells and improved the α-actinin striated pattern. Conclusion: Hyperglycaemia suppressed the cardiac differentiation and contractile activity of mESCs as well as disrupted the cardiac myofilament organisation and expression. These effects of hyperglycaemia were likely mediated by mitochondrial-dependent apoptosis triggered by oxidative stress as well as by the abnormalities in calcium signalling. These results have potential clinical implications in foetal diabetic cardiac disease and add novel insights into the mechanistic factors that represent new therapeutic drug targets in the developing foetal heart.
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    Preliminary investigations for studying the effects of low carbohydrate high fat diets on gluconeogenesis in type 2 diabetes patients
    (2020) Webster, Christopher; Smith, James; Noakes Timothy
    Type 2 diabetes (T2D) is currently one of the major health challenges across the globe. Lifestyle changes are a key component of T2D management and there is growing interest in low carbohydrate high fat (LCHF) diets as a potential dietary strategy to improve glycaemic control, reduce T2D medication requirements, and improve body weight and lipid profiles. However, carbohydrate restriction is controversial. Results from observational studies generally do not support the food choices associated with carbohydrate restriction while results from short-term randomised controlled trials (RCTs) are more likely to show significant benefits of LCHF diets. Additionally, both study designs have limitations and opinion on LCHF diets is polarised due to ambiguities in how to interpret the available data. Chapter 1 of this thesis reviews the impact of prospective cohort studies, randomised controlled trials, and dietary policies on current opinions towards LCHF diets for the management of T2D. Uncertainty over the safety of LCHF diets remains a concern and additional observational studies and short-term RCTs of the same quality as existing research are unlikely to add any further clarity. For this reason, research focused on understanding the underlying mechanisms of carbohydrate restricted diets may be an alternative approach to alleviate or validate some of the concerns being expressed about LCHF diets. One such mechanism is the dysregulation of glucose production via gluconeogenesis, which is a key pathology of T2D but which has been incompletely studied. Indeed, the effects of LCHF eating on gluconeogenesis in T2D patients has not yet been studied, nor has gluconeogenesis been investigated in the context of T2D remission. This is an area of interest for future research and the aim of this thesis was to conduct preliminary studies to prepare the groundwork for such studies. There is large heterogeneity in the low carbohydrate diets that have been prescribed in controlled trials and the composition and characteristics of the LCHF diets that patients are finding effective in the real world is unknown. Study 1 (Chapter 2 of this thesis) aimed to better understand the LCHF diet by investigating the diet, diabetes status, and personal experiences of T2D patients who had self-selected and followed an LCHF diet of their own accord. This study was a multi-method investigation which consisted of quantitative assessments of diet and diabetes status, as well as in-depth interviews which were analysed using qualitative methods. Results from this study will be used to inform design and protocol decisions in future controlled trial studies. Study 2 (Chapter 3 of this thesis) piloted the use of stable isotope tracers for the quantification of endogenous glucose production and gluconeogenesis in the early postabsorptive state (5 hours after a meal). For methodological reasons, prior investigations have usually measured gluconeogenesis after an overnight fast and therefore, little is known about the effects of dietary composition on gluconeogenesis within the early post-absorptive state. Study 2 quantifies gluconeogenesis 5 hours after a meal and the validity of the data is discussed. Finally, Chapter 4 outlines future perspectives for research based on findings from Chapter 2 and Chapter 3.
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    Pulsatile Flow in Computational Modelling of Thrombosis in Cerebral Aneurysms
    (2019) Hume, Struan; Ngoepe, Malebogo; Ho, Wei Hua
    Ngoepe and Ventikos have developed one of a growing number of computational models of thrombosis of cerebral aneurysms designed with consideration towards clinical use and research. Their model, amongst many others, utilizes computationally inexpensive steady flow conditions. However, pulsatile flow better characterizes blood flow in-vivo. Steady flow is an acceptable approximation of pulsatile flow from a fluid dynamics perspective, but there is no prior evidence suggesting whether it is an acceptable approximation when considering clot formation within a flowing environment. To this end a pulsatile flow model has been created in ANSYS® Fluent, and a function from Ngoepe and Ventikos’s computational model that simulates the release of thrombin, a chemical responsible for clotting activation, has been implemented. The output of this simulation is compared to the output of an otherwise identical simulation utilizing Particle-Image-Velocimetry (PIV) validated steady flow conditions, to determine whether clotting outcome of Ngoepe and Ventikos’s model, amongst others, differs with pulsatile flow This experiment revealed that the concentration of thrombin required for clotting activation is generated in nearly half the time when utilizing pulsatile flow over steady flow. Pulsatile flow creates unsteady flow patterns within the aneurysm, which create an environment where less thrombin is carried out of the aneurysm and into the regular bloodstream. This indicates that steady flow approximations for realistic clotting in computational models of thrombosis of cerebral aneurysms without strong consideration for the effects of pulsatile flow are inaccurate.
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    Socio-ecological risk factors, explanatory models and treatment-seeking behaviours associated with Mseleni joint disease: a biocultural mixed methods study
    (2022) Dinkele, Elizabeth Sarah; Gibbon, Victoria E; Ballo, Robea
    Mseleni Joint Disease (MJD) is a crippling osteoarthropathy of unknown aetiology endemic to southern African Bantu-language speakers in a remote region of Northern KwaZulu-Natal, South Africa. Effective management of MJD has been hindered by limited insight into risk factors, explanatory models or treatment-seeking behaviours in those affected. Until MJD is better understood, disability, unemployment and dependence on social assistance grants and family income for subsistence will remain a reality for those affected. A mixed methods study was conducted with the aims of examining risk factors, explanatory models and treatment-seeking behaviours associated with MJD. The distribution, differential diagnosis and treatment of MJD were statistically analysed using medical records (n=723), MJD-patient surveys (n=37) and a meta-analysis. Socio-economic and cultural risk factors were assessed from surveys (n=99) and census publications. Interviews with MJD patients (n=6), nurses (n=7) and doctors (n=9) were qualitatively analysed for themes pertaining to perceptions, experiences and treatment-seeking for MJD. A point prevalence of 9% was estimated. Women were nearly twice as likely to have MJD than men (OR= 1.89; p=0.03) and the likelihood of MJD increased almost three-fold in those older than 50 years (OR= 2.83; p<0.01). Age was a confounder of the association between gender and MJD, as the sample was skewed in the representation of elderly women. MJD was only detected in patients older than 35 years, indicative of a later onset age than previously reported. The prevalence of MJD in settlements along tar and concrete roads, with access to public transport but limited piped water was suggestive of environmental risk factors or differential access to hospital-based care. Explanatory models of MJD were supernatural (witchcraft or ancestral displeasure); natural (nutritional deficiencies, 'genetics' and/or environmental); and/or social (gender-based practices and lifestyle). MJD patients described supernatural and natural aetiologies, and conceptualised disability as an inevitable reality. Consequently, patients reported taking few measures to prevent joint immobility, focussing instead on immediate symptomatic relief. Psychosocial and systemic barriers to treatment were suggestive of a disconnect between traditional African healing and Western biomedicine. This work demonstrates the value of the biocultural approach in identifying spatial, ecological, social and cultural processes that shape population patterns of health and disease.
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    St John's Wort photomedicine for Melonoma
    (2013) Kleemann, Britta; Davids, Lester Merlin
    The use of photomedicine in ancient civilizations dates back 4000 years ago but it wasn't until the beginning of the 20th century that photodynamic therapy was discovered by man. The “trinity” of photodynamic therapy (PDT) comprises a photosensitizer, light and molecular oxygen. Following cellular uptake of the photosensitizer, its activation by light produces reactive oxygen species in the presence of oxygen. The resulting cytotoxic oxidative stress elicits cancer cell death by various mechanisms including apoptosis, necrosis and autophagy. Hypericin, an extract from St John's Wort, is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. However, limited reports on the efficacy of this photomedicine for the treatment of melanoma have been published. South Africa has the second highest incidence of malignant melanoma skin cancer in the world; a highly aggressive tumor due to its metastasizing potential and resistance to conventional cancer therapies. The aim of this study was to investigate the response mechanisms of melanoma cells to hypericinPDT in an in vitro tissue culture model. This investigation was three-fold. Firstly, the susceptibility of melanoma cells to the treatment was determined using cell viability assays. We found a dose of 3 µM light-activated hypericin was effective in reducing cell viability to 50 % or less than the control, for all melanoma cells employed in this study. We therefore used this killing-dose for further experiments. Next, hypericin uptake and its specific association with intracellular organelles was characterized using organelle-specific fluorescent-fusion proteins and dyes, in conjunction with the red fluorescent nature of hypericin and visualization by live confocal fluorescent microscopy. The intracellular localization of a photosensitizer directly influences its cytotoxic action and is thus crucial for effective cell death induction. Hypericin was taken up by all melanoma cells and co-localized with lysosomes and variably with melanosomes, the pigment producing organelles. No co-localization with the cell membrane, mitochondria, endoplasmic reticulum or nucleus was found. Investigating intracellular hypericin after treatment revealed a time-dependent decrease in all melanoma cells. Finally, melanoma cell death mechanisms were elucidated in response to the killing-dose of lightactivated hypericin. Ultrastructural examination of the cells with transmission electron microscopy 2 revealed extensive cytoplasmic vacuolisation, at 4 hours after treatment. In pigmented melanoma cells, the treatment furthermore induced the formation of glycogen aggregations. Fluorescent activated cell sorting analyses revealed a time-dependent increase in phosphatidylserine exposure, indicating apoptosis, in conjunction with a loss of cell membrane integrity, indicating necrosis, in all melanoma cells. An initial early necrotic population was found which decreased with time after treatment, whereas the late apoptotic/necrotic population increased. Minimal early apoptotic populations were found in all cell lines. In addition, melanoma cells showed a decrease in cellular size accompanied by an increase in granularity/pigmentation after treatment. Western blot analyses of proteins involved in specific cell death cascades furthermore verified the induction of apoptosis in melanoma cells by hypericin-PDT. The extrinsic apoptotic cascade was initiated in unpigmented A375 melanoma cells at 24 hours after treatment, mediated by activation of the suicidal proteases caspase 8 and caspase 3. Intrinsic apoptosis was found in pigmented UCT Mel-1 cells at 4 and 7 hours, mediated by activation of caspase 3 and cleavage of poly(ADP-ribose)polymerase 1 (PARP1). Induction of apoptosis by cleavage of PARP1 was furthermore evident in 501mel cells at 7 hours after treatment; however this cleavage was not mediated by caspase 3. Apoptosis inducing factor was found in its vital form in all melanoma cells, indicating that caspase-independent apoptosis or regulated necrosis by parthanatos were not induced by hypericin-PDT. In summary, this study demonstrated the effectiveness of hypericin-PDT in killing both unpigmented and pigmented melanoma cells by the induction of apoptosis. Further investigations into the exact mechanisms of the cell death response, including the observed loss of cell membrane integrity and the involvement of lysosomes and melanosomes are interesting avenues to explore in future studies. Translation of hypericin-PDT into a three-dimensional skin model with melanoma invasion is of particular interest, to further simulate the natural environment of this aggressive cancer and thereby enable the identification of enhanced treatment options.
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    The effect of calcium intake on body weight in pregnant women from South Africa, Zimbabwe and Argentina participating in the Calcium and Pre-eclampsia trial
    (2019) Cormick, Gabriela; Harbron, Janetta; Belizán, José M; Betrán, Ana Pilar
    Introduction: The prevalence of overweight and obesity is increasing worldwide. It has been estimated that every kilogram of weight gain during adulthood represents a 3% to 6% risk increased of cardiovascular disease. There are some studies showing an inverse relationship between calcium intake and body weight. Overweight and obese women are advised to lose weight before conception, however the evidence on how to achieve this is scarce. No studies have investigated the effect of calcium supplementation on weight management before conception or during pregnancy. Aims and objectives: The overarching purpose of this project was to provide information and enrich the body of evidence of the effect of calcium intake on body weight. The first aim was to evaluate the effect of calcium intake on body weight of fertile or pregnant women; secondly to investigate the pre-pregnancy weight status, weight gain during pregnancy and adequacy of dietary intake of pregnant women participating in the Calcium and Pre-eclampsia (CAP) trial. The third aim was to perform a systematic review of studies evaluating the effect of calcium intake on body weight. I was part of the core research team throughout the CAP trial duration and also lead the nutritional component. The trial sample size included 540 pregnant women recruited between 2012 and 2017 in South Africa, Zimbabwe and Argentina. Women were randomized pre-pregnancy to receive 500 mg of elemental calcium or placebo until 20 weeks´ gestation, whereafter they received 1500 mg. Weight was measured pre-pregnancy and at 8, 20 and 32 weeks’ gestation. Diet was assessed at 20 weeks´ gestation. Ethical approval was obtained from appropriate national and institutional ethical review bodies as applicable for each study site. Results: There was a high proportion of women who started their pregnancy overweight or obese (73.7% in South Africa and 60.2% in Zimbabwe). Most women had an inadequate intake of micronutrients at 20 weeks pregnancy. For the most basic micronutrients like iron, calcium, folate and zinc, the percentage of women with intakes below requirements was above 90%. Although there was no effect of calcium supplementation on body weight in the sample of the CAP trial, the calcium group had a no statistically significant smaller increase in body weight during pregnancy especially in those who were obese at the start of the trial. The systematic review shows a small but statistical effect of calcium supplementation in body weight (Mean Difference (MD) -0.33 kg, 95% CI -0.57 to -0.09); (p=0.007); 819 participants; 15 studies) and in BMI (MD -0.17, 95% CI -0.21 to -0.13); p < 0.00001; 695 participants; 10 studies). Conclusion: We found a high prevalence of obesity found together with the micronutrient inadequacy which show a very poor nutritional status of women who have the possibility of getting pregnant again. This needs to be addressed so that maternal and perinatal outcomes are improved. There is a need to implement nutritional counselling preconceptionally to these women before they fall pregnant. The results of this thesis show a no statistically significant smaller increase in body weight in women supplemented with calcium, opening a promising area of research for weight management including the study of the mechanisms involved. Before making clinical recommendations further studies are needed with higher sample size to have the power to detect clinically significant effects.
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    The evaluation of social media to increase engagement rate, reach and health education: the case for WoW!
    (2023) Lekota, Feroza; Lambert, Estelle
    Introduction: In 2021, South Africans had a 51.9 percent chance of dying from an NCD. The Western Cape on Wellness (WoW!) program advocates for wellness, through partnership, innovation and policy, including health in communities, worksites and schools. Increasing knowledge and awareness regarding health behaviors and NCD risk factors is an important pathway in preventing and mitigating the problem at hand through a combination of structural and social policy change. Social media provides an unprecedented opportunity and innovative way to provide a solution to the problem. The internet has increasingly become a popular source of health information by connecting individuals with health content, experts, and support. Aim & Objective: To use a social media campaign with expert knowledge to change healthy lifestyle actions and increase health knowledge and engagement in a para-social western cape on wellness social media group. Methods: A mixed methods quantitative and qualitative analysis was undertaken to assess key messages, which were publicly available on the WoW! Facebook group. 60 lifestyle messages were posted on the WoW! Facebook group 5 times a week from Monday through to Friday. Each message was disseminated by a moderator and followed a theme for the day. Three icons were used to measure levels of participant engagement likes, shares, comments. Associated comments were extracted and coded using a codebook based on items from the supportive accountability model and peer social support analysis. The identified search material was reviewed allowing removal of any personally identifying or geographical material in order that that the comments were rendered anonymous. One –way ANOVA was performed to determine whether level of likes, shares and comments differed between posts. One-way ANOVA was performed to determine whether level of engagement differed between post types, with Tukey–Kramer test used to determine post hoc differences. An independent samples t-test was conducted to determine whether total engagement differed between moderator initiated posts and Facebook user-initiated posts. Results: The most common form of engagement was "likes," and engagement was higher for moderator initiated rather than participant-initiated posts. Overall traffic to the page increased over the 3 month period from 1083 WoW! Facebook users to 1300. Likes were the most common and easiest form of engagement (M=7.6, SD 9.8) with comments being the lowest (m=0.81, SD 2.3). The most engaged with and resonative messages were the #transformationthursday posts. Empirically physical activity behaviour and change in eating patterns did increase over time. The 7 main themes that were identified constituted 53.3% (112/210) of all comments in the pre and during campaign analyses. The most prevalent theme was social cohesion and connectedness at 29% (33/112). The least common theme was developing professional communication and organisational support at 4.5% (5/112). Overall, there were more comments before the campaign (n=63), than during (n=49). In terms of Geographical proximity most of the comments and posts came from participants in the Metro (58.3%) and rural districts Paarl (48.3%) and George (40%). A proximal or virtual tie to a place adds connection and thus value to the information. Conclusion: The favourable results of the WoW! Facebook campaign shows promise for future social media-driven health campaigns to educate and prevent lifestyle related chronic conditions. Social media content for knowledge sharing should be created through a well-intentioned process with the support of moderators to facilitate the conversation and drive engagement.
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    The impact of maternal HIV infection on uninfected neonate brain structure
    (2022) Ibrahim, Abdulmumin; Holmes, Martha; Meintjes, Ernesta; Warton, Fleur
    Successful prevention of mother-to-child HIV transmission (PMTCT) programs have reduced the risk of infant HIV infection in South Africa from 8% in 2008 to an estimated 1.4% in 2015, resulting in an increasing population of HIV-exposed uninfected (HEU) children. However, the long-term effects of HIV and antiretroviral therapy (ART) exposure on the developing brain is not well understood. While HEU children perform better than their counterparts living with HIV, they continue to demonstrate greater neurodevelopmental delay than HIV-unexposed uninfected (HUU) children. As a result, neuroimaging studies have looked at the developing brain in this population, however there is little consensus about typical exposure related effects. In addition, it is unclear whether previously reported exposure-related results are directly related to in utero exposure to HIV, or indirectly via family and/or environmental factors. Research focused on newborns allows one to eliminate possible contributions from other factors, clarifying the influence of ART and HIV exposure on the developing brain. This dissertation employs neuroimaging and neurocognitive data in a well-characterized infant cohort to better understand the influence of maternal HIV infection on the uninfected brain. HEU infants were exposed to ART in utero between 3 and 9 months, allowing for the study of potential ART exposure effects of as well as HIV exposure. This dissertation will identify HIV and ART exposure effects on brain structure. In addition, the relationship between neonate brain structural outcomes and cognitive abilities at 9-12 months will be determined to identify potential functional consequences of early structural abnormalities. Chapter two presents an analysis of manually traced subcortical volumes in 120 unexposed uninfected (HUU) and exposed uninfected (HEU) neonates. HEU neonates demonstrated significantly reduced mean caudate volumes bilaterally and left mean putamen volumes relative to HUU neonates. Further analysis revealed the observed differences in basal nuclei volumes were related to duration of ART in utero. Infants exposed to ART throughout pregnancy had similar caudate and putamen volumes compared to their HU counterparts. While infants exposed to ART post conception (from 3 - 8 months in utero) had significantly smaller mean caudate volumes bilaterally, and a trending smaller left putamen volume compared to HUU infants. Chapter three examines the potential functional consequences of HIV/ART volumetric reductions. We modelled manually traced neonatal subcortical volumes with neuropsychological outcomes at 9 - 12 months. Among HUU infants, bilateral pallidum volumes predicted neuropsychological measures across all domains. All volumes, with the exception of bilateral thalamus and vermis, predicted the general quotient score in HUU infants. In contrast, among the HEU infants, volumes did not relate to neuropsychological outcomes with the exception of the caudate, putamen and vermis predicting locomotion scores in the preconception group. While no HIV exposure differences were present in neuropsychological domains, HEU infants recruit alternative subcortical structures compared to typically developing unexposed infants. Chapter four presents a DTI-tractographic analysis of white matter connections between subcortical structures manually traced. HEU demonstrate white matter alterations in two tracts - higher FA between right putamen and left thalamus and higher MD between caudate and thalamus on the right hemisphere. The WM alterations observed in HEU appear to be from roles of both HIV and ART exposure. In contrast to ART dependent subcortical grey matter reductions, the observed white matter alterations are independent of maternal treatment initiation. In addition, we also find associations between unaltered white matter connections and both maternal immune health and ART duration during pregnancy. These results suggest white matter is influenced to varying degrees by HIV and ART exposure, as well as maternal health in pregnancy. Chapter five looks at the possible functional consequences of the reported alterations in white matter integrity. We modelled white matter connections between manually traced neonatal subcortical volumes with neuropsychological outcomes at 9 - 12 months. Similar to chapter 3, within HUU infants, we observed a number of white matter connections predictive of neuropsychological outcomes across all domains. And almost no white matter tracts predicted neuropsychological measures in HEU infants. These results again point to HEU infants recruiting different pathways to perform basic tasks. In conclusion, the results documented in this thesis points to the influence of HIV exposure, ART duration and maternal immune health on fetal brain development. However, these factors impact grey and white matter differently. ART initiated pre-conception was protective of caudate volumes but did not protect two white matter connections, the WM tract between right thalamus and right caudate, and WM that between left thalamus and right putamen. Within HUU neonates, basal ganglia and cerebellar volumes and white matter connections predicted neuropsychological outcomes in late infancy. However, HEU infants did not demonstrate the same associations suggesting they utilize alternate pathways from their HUU peers. While there were no exposure related differences across neuropsychological domains, the long-term functional consequences of altered structural recruitment is unknown. Finally, this thesis adds to the body of literature that early ART in pregnancy is neuroprotective, and that HIV exposure related structural alterations are evident as early as 2 - 4 weeks after birth.
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    The inflammatory potential of the diet of 1-9-year-old children living in two urbanized and economically active provinces in South Africa
    (2021) Malczyk, Sonia; Senekal, Marjanne; Eksteen, Gabriel
    The challenge of preventing and treating noncommunicable diseases (NCDs) has become a global issue of paramount importance. Climbing obesity rates among children could become a major contributor to the burden of NCDs. While there are numerous factors that contribute to the development of obesity and NCDs, an abundance of research suggests that “sustained inflammation is the common denominator of all chronic disease” (Noland, 2017). Low-grade inflammation is characterized by raised concentrations of inflammatory biomarkers without any overt symptoms (Bonaccio et al., 2017). To date, many studies have demonstrated that unhealthy eating patterns contribute to the development and/or maintenance of low-grade inflammation with particular eating patterns having been categorized as either pro-inflammatory or anti-inflammatory; however, information on the inflammatory potential of the diet of children is sparse, specifically in South Africa. To assess the overall inflammatory potential of an individual's diet, researchers first attempted to provide a tool to classify the inflammatory potential of diets in 2009, with the development of the Dietary Inflammatory Index (DII) tool (Cavicchia et al., 2009). This tool has since been revised and adapted. Key values used in the calculation of the DII include the inflammatory score for each of the 45 parameters in the tool, the mean±SD intake of the population (adults in this case) of each parameter and the mean±SD intake of the actual study sample (Shivappa et al., 2014); however, there is no version of the DII that is suitable for use in children in the South African setting. The aims of this research are: 1) to adapt the DII for application in South African children (the South African Child Dietary Inflammatory Index: the SACDII) (sub-study 1) 2) to apply the SACDII in the investigation of the inflammatory potential of the diet of 1–9-year-old children in two urbanized and economically active provinces in South Africa and the association thereof with sociodemographic, anthropometric, and dietary diversity variables (sub-study 2) SUB-STUDY 1: Adaptation of the DII for use in South African Children Aim: To adapt the DII for application in South Africa by generating a mean±SD intake value for the food parameters on the adult DII (Shivappa et al., 2014) for South African children. Objectives: To identify quantified dietary surveys that involved 1 – 10-year-old South African children published over the last three decades; to obtain the raw data sets (food codes and grams consumed for each food parameter) of identified surveys from the principal investigators (PIs); to generate a nutrient/food data base that includes values for the majority of the 45 food parameters included in the DII (Shivappa et al., 2014); and to combine all raw data obtained and reanalyse the combined data to derive the mean±SD intake of each food parameter using the generated data base.
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    (The necessity of) reflexive labour practices at triggerfish animation studios: an ethnography
    (2021) Irvine, Laura Anne; Mohamed, Kharnita
    This ethnographic dissertation argues for reflexive labour practices at Triggerfish Animation Studios in Cape Town, South Africa. Affect is used both as an analytical lens to examine the various social labour processes at Triggerfish, as well as a vitalising medium in reflexivity, which is a form of affect itself. Research was conducted over two months at Triggerfish during January and February 2018, where participant observation was practiced to collect data, along with focus groups and visual diaries collated from participants. The analysis centres on engaging the affective dimension of labour, as well as the ways that affect animates the different relationships that the studio embodies. Employees and management engage with each other through the affective notion of ‘care', and this sustains relationships within a neoliberal labour environment. This sets the context of an affective workplace whose care-economy is carefully balanced and regulated through ‘caring about' and ‘caring for', which has the potential to hide power dynamics, as well as gendered labour expectations. Triggerfish's claims of difference, as well as making a difference, allows them to sell the idea of ‘Africa' through identity claimed as well as identity distanced from. Recognising Triggerfish as a white, historically settler colonial company with an elitist history in a still-segregated society is important, even as the company is also located geographically in the Global South. There is thus the need for reflexivity within the geopolitical relationships involved in creating and selling media. Self-awareness is folded in on itself as an affective medium for understanding the ways that individuals conceptualise service work provided for the Global North, as well as service work provided by the Global North for Triggerfish. This uncovers and allows multiple, sometimes oxymoronic definitions and lived experiences to coexist. I argue that reflexivity at Triggerfish should be encouraged just as it is in Social Anthropology as a discipline. It allows for a multi-dimensional studio that is aware of its history and context, and can therefore make better-informed business decisions and produce better content.
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    Variations in arterial supply via the external and internal carotid arteries to the bony orbit and eyeball in full-term fetuses, infants, children, adolescents, and adults – a South African perspective
    (2022) Mpolokeng, Kentse Sana; Louw, Graham J; van der Merwe, Elizabeth
    The anatomy of the orbital region is of great importance for many highly specialised clinical disciplines such as ophthalmology, maxillofacial surgery, and neurosurgery. The main source of arterial blood supply to the orbital region is by the ophthalmic artery, a branch of the internal carotid artery, and to a lesser extent by the anastomotic patterns which are formed through the external carotid artery. A range of arterial variations which may be developmental in origin, or which may develop due to pathologies later in life, may affect the ophthalmic artery in terms of its origin, course, and branching. If clinicians are not aware of the variations occurring in this region, the eye of the patient may be at risk of injury during invasive procedures, which may lead to partial or complete visual loss. Up until the present time, there have been only a few cadaveric studies that revealed some of the variant patterns and the overall frequencies of the recorded anastomotic patterns for the orbital blood supply. Whilst the anatomical variations are known, the frequencies of variations in the population are not. Furthermore, no published data exists regarding the variations in the orbital blood supply in a South African population. Therefore, the aim of this study was to investigate the orbital vascular supply within the South Africans of different age groups, to document and describe any variations in anastomotic patterns and record their frequencies. The current study was conducted through dissections of bodies in the Department of Human Biology, University of Cape Town, and patients' angiograms from Groote Schuur Hospital. The angiograms included data obtained from other hospitals within the Cape Town area and were reviewed retrospectively. The dissection sample included six full term fetuses and 63 adults, and the angiograms accounted for 870 individuals. The ophthalmic artery was studied from the point of origin from the internal carotid artery and its course in relation to the optic nerve, and both sides were compared to note any similarities or differences. Statistical analyses were performed to record the frequencies of the patterns of variations and to note whether there were any associations between sex, age, sidedness, and these variations. The results revealed statistically significant associations between age and sex for the patterns of variation. Several variations were noted in the current study. Among the novel findings were those in the origin of the ophthalmic artery from the internal carotid artery, whereby a lateral and inferior origin were recorded in both samples (dissected bodies and angiograms). In addition, it was noted that the ophthalmic artery may take origin from the A2 segment of the anterior cerebral artery, which is also a novel finding. This study, therefore, adds significantly to the current body of knowledge regarding the patterns of arterial supply to the ophthalmic region in a South African sample.
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    Whole genome sequencing approach to identifying genetic risk factors underlying anterior cruciate ligament injuries in a twin family study
    (2022) Feldmann, Daneil; September, Alison V; Collins, Malcolm; Chimusa, Emile
    Background: Predisposition to ACL rupture is multifactorial, resulting from a complex interplay of intrinsic and extrinsic risk factors. Variation in the genome is now considered a key intrinsic risk factor, but the majority of currently implicated loci have been identified through case-control genetic association studies, which are limited by a candidate gene approach and insufficient statistical power. The primary aim of this thesis was to use a whole genome sequencing (WGS) approach within the context of a twin family study to identify novel or previously implicated genetic loci contributing to ACL rupture predisposition (Chapter 2). Additionally, this research aimed to explore prioritised genetic polymorphisms previously associated with ACL rupture and functioning in key biological pathways implicated through the WGS analyses, independently and as a collective, with ACL rupture predisposition in a large combined ACL rupture dataset (Chapter 3 and 4). Methods: The complete genomes of all family members in two unrelated families, each with affected twins were sequenced. Variants with potential loss of function effect were prioritised, and explored for probable biological function in the ACL rupture risk pathway. Furthermore, identity by descent analysis (IBD) was performed to identify potential disease causing mutations, on chromosomal regions shared between family members, and across families. Enriched biological pathway analyses were further explored to prioritise potential candidate genes. Two biological networks were prioritised which highlighted the angiogenesis and proteoglycan family of proteins. Specific polymorphisms within previously investigated candidate genes were further explored in case-control genetic association studies conducted in a large collective data set, including participants from three independent (Sweden, Poland and Australia) cohorts, combined with previously published South African and Polish data. The anterior cruciate ligament (ACL) rupture group included individuals diagnosed with a clinical diagnosis of an ACL rupture based on physical examination, and confirmed by either magnetic resonance imaging or arthroscopy. Only ACL ruptures resulting from a non-contact mechanism of injury were included. The control group comprised individuals of similar age to cases with no prior history of ACL injury or other ligament and tendon injuries, and participating in regular sporting activity, which was similar to cases. Participant samples were genotyped for single nucleotide polymorphisms in the VEGFA (rs699947 C/A rs1570360 G/A, rs2010963 G/C) and KDR (rs2071559 A/G, rs1870377 T/A) genes (Sweden CON: 116 ACL: 95; Poland CON: 149 ACL: 127 and Australia CON: 83 ACL: 342). Additionally, in the ACAN (rs2351491 C/T, rs1042631 T/C, rs1516797 T/G), DCN (rs516115 T/C) and BGN (rs1126499 C/T, rs1042103 G/A) genes (Sweden and Poland). Haplotype analyses were explored (VEGFA, KDR, ACAN and BGN) using the individual genotype data. In addition, inferred allele interactions were presented for VEGFA-KDR, ACAN-BGN ACAN-DCN, BGN-DCN, and VEGFA-DCN as a proxy for gene-gene interactions within the discrete angiogenesis and proteoglycan gene families, and between genes as a proxy for pathway interactions. For association studies, frequencies were calculated for the genotype, allele, inferred haplotypes and allele interactions, and the distributions compared between the control and ACL rupture participants. The statistical programs in R were used for all the analyses, and a p value < 0.05 was accepted to be significant. Results: The WGS analyses highlighted six candidate genetic loci in three genes (COL12A1, CATSPER2, and KCNJ12) with predicted loss of function effects in all affected and unaffected family members within the two studied families. Of the three genes, polymorphisms within COL12A1 were previously associated with ACL rupture predisposition, while CATSPER2 and KCNJ12 are two novel genetic loci with no known previous association with predisposition to ACL rupture. The IBD analyses identified several regions shared in each independent family, of which a segment including a long intergenic non-protein coding RNA (lincRNA) LINC01250 gene in the telomeric region of chromosome 2p25.3 was shared between affected twins in both families, and an affected brother. Furthermore, several functional partners were highlighted. Genetic association analyses of the prioritised polymorphisms in a combined cohort identified an independent association of the VEGFA rs2010963 CC genotype and C allele with increased risk (genotype p = 0.0001, FDR p = 0.001, OR 2.16, 95% CI: 1.47-3.19; allele p = 0.0006, FDR p = 0.003, OR 1.29, 95% CI: 1.11-1.49). Furthermore, the association of the VEGFA A-A-G and A-G-G inferred haplotypes (rs699947 A/C-rs1570360 G/Ars2010963 G/C) with reduced risk (p = 0.010, haplo.score: -2.58, OR: 0.85, 95% CI: 0.69-1.05; A-G-G: p = 0.036, haplo.score: -2.09, OR: 0.81, 95% CI: 0.64-1.02) of ACL rupture. Moreover, a reduced interval (rs1570360 G/A-rs2010963 G/C) revealed an association of the VEGFA -GG and -A-G inferred haplotypes with reduced risk (-G-G: p = 0.031, haplo.score: -2.15, OR: 1.00 and -A-G: p = 0.024, haplo.score: -2.25, OR: 0.98, 95% CI: 0.82-1.18) and the -G-C inferred haplotype with increased risk p = 0.012, haplo.score: 2.50, OR: 1.18, 95% CI: 0.99- 1.40). The KDR genotype and haplotype analyses illustrated that it is highly unlikely that the investigated KDR polymorphisms are associated with modulating ACL rupture risk. Inferred allele interactions noted a significant association of the VEGFA (rs699947 A/C, rs2010963 G/C) - KDR (rs2071559 A/G, rs1870377 T/A) A-G-A-A (p = 0.005, OR: 0.51, 95% CI: 0.30- 0.87) and A-G-G-A (p = 0.018, OR: 0.93, 95% CI: 0.54-1.60) combinations with reduced ACL rupture risk. Further, a significant association of the VEGFA (rs699947 C/A, rs1570360 G/A, rs20109630 G/C) - DCN (rs516115 T/C) A-G-G-T (p = 0.010, OR: 0.53, 95% CI: 0.30-0.91), A-A-G-C (p = 0.010, OR: 0.42, 95% CI: 0.21-0.81) and A-A-G-T (p = 0.046, OR: 0.77, CI: 0.49-1.2) allele combinations with reduced risk was noted for male participants in the collective cohort. No independent or haplotype associations with ACL rupture risk were noted for any of the investigated proteoglycan polymorphisms, in the collective cohort. Conclusion: Collectively, this work has expanded current knowledge on the genetic regions contributing to ACL rupture predisposition, and further highlights the polygenic nature of multifactorial phenotypes. Employing whole genome sequencing in a twin family context, together with a pathway based approach, novel and previously implicated genetic loci were identified towards the aims of the thesis. The catalogue of candidate in silico mutations and modifier genes that clustered in pathophysiological pathways important in ACL rupture, and with implications for therapeutic intervention were identified, and need to be interrogated. Of particular interest are the novel CATSPER2, KCNJ12 and LINC01250 genetic loci. Furthermore, additional evidence to support the implication of the VEGFA gene in modulating ACL rupture risk is provided, and highlighted is the potential collaboration of members within the angiogenesis and proteoglycan gene family in modulating risk. The studies in Chapter 3 and 4 suggest genetic association studies in single populations are less informative, and instead larger collective cohorts with increased statistical power should be employed. Further to that, rather than investigating single polymorphisms, larger regions of the genome should be explored to determine the potential interacting components contributing to musculoskeletal injury risk. Going forward, characterisation of the functional biological effect of implicated loci may assist in unravelling the underlying mechanisms altering tissue homeostasis, and subsequently an individual's capacity for healing and adaptive response.