Dyslipidaemia is a commonly encountered clinical condition and is a major risk factor for cardiovascular diseases. Although there are many factors associated with dyslipidaemia, a strong genetic component is evident. Apolipoprotein E (APOE), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transfer protein (CETP) are key regulators of plasma cholesterol levels. Thus, genetic variation in the genes coding for these proteins contributes to dyslipidaemia. In this study, a cohort of black South African Type 2 Diabetes Mellitus (T2DM) patients was characterized for mutations in genes coding for APOE, PCSK9, and CETP, and the possible effects of these variants on their lipid profiles was evaluated. Participants (n=417) were recruited from the Chris Hani Baragwaneth Hospital Diabetes Clinic, Johannesburg from whom blood samples were obtained for DNA extraction. The cohort was further stratified into two groups; individuals on statin treatment (Sim+, n=291), and the second that was not on treatment (Sim-, n=87). Lipid profiles were determined by enzymatic methods. DNA was genotyped for APOE, PCSK9, and CETP variants using PCRRFLP and Sanger sequencing. Analysis of the effects of the genetic variants was carried out in two ways. Firstly, for all the participants combined, and then by separating those on statin treatment from those without (Sim+ vs. Sim-). Genotype and allele frequencies were calculated followed by genotype-phenotype correlations with lipid profiles. Univariate analysis showed a significant association between the APOE4 isoform and lower HDL-c levels in the combined cohort (p=0.034). The effects were more pronounced in the Sim- group (p=0.004) but were absent in the Sim+ group. Contrary to above, APOE2 was significantly associated with lower total cholesterol (TC) (p< 0.001) and lower LDL-c (p< 0.001) when compared to APOE3 in the combined cohort. Upon analysing treatment groups, the correlations were observed in the Sim+ group (p=0.027 and p=0.003, respectively), while there were no observed correlations in the Sim- group. The CETP rs34065661C/G and G/G genotypes were significantly associated with increased HDL-c levels (p=0.017; when applying a dominant genetic model) in the combined cohort, as well as in the Sim+ group (p=0.026). Multivariate analysis, using a generalized linear model, confirmed associations between APOE rs429358C and lower HDL-c (OR=0.881, p=1.64e04), and APOE rs7412T and decreased LDL-c (OR=0.759, p=0.012). No significant associations were observed for PCSK9 polymorphisms. We report significant associations between APOE and CETP genetic variations and altered lipid levels in this black South African T2DM population. These genetic variants could be biomarkers for dyslipidaemia among Africans. However, it is imperative that the APOE, PCSK9, and CETP genes are fully characterized for additional polymorphisms in order to come up with a better genetic profile that explains the variance in lipid levels observed in the black South African population. The impact of these genetic variants could be relevant to other black African populations as well.

Bibliography: p. 400-445. / The aim of this thesis was to investigate the relationship between chronic exercise activity, aging, the neuromuscular system and the symptom of fatigue in a series of studies. The hypothesis of the thesis was that in contrast to the accepted dogma that exercise is beneficial to an individual, increasing longevity and improving quality of life, excessive or chronic exercise activity may accelerate the aging process, lead to neuromuscular damage, and cause the development of pathological symptoms or levels of fatigue.

The Optional Protocol to the International Covenant on Economic, Social and Cultural Rights (the 'Optional Protocol' or the 'OP-ICESCR') has recently been adopted by the General Assembly of the United Nations. This document establishes a new complaints procedure for economic, social and cultural rights ('ESCR') within the United Nations human rights system. Hence, those rights ' as it is already the case for civil and political rights (CPR) ' will become quasi-justiciable at international level. Once the Optional Protocol will enter into force, individuals and groups victims of violations of any right contained in the International Covenant on Economic, Social and Cultural Rights (the 'Covenant' or the 'ICESCR') will have the possibility to submit communications to the United Nations Committee on Economic, Social and Cultural Rights (the 'Committee' or the 'CESCR'), as long as the state concerned is party to the OP-ICESCR.

Includes bibliographical references.

Includes abstract. / Includes bibliographical references. / A patriarchal reading of the Qur'ānic verse 4:34 implies the subordination of wives to their husband within their families. The fundamental duty of the husband to support his wife materially has led to the entrenched notion of male protection of women. In exchange for such protection, the wife has the reciprocal duty of obedience to her husband, which may lead to the restriction of her right to work, amongst other rights. In contemporary societies where women are increasingly participating in the maintenance of the family, different interpretations of the verse are now becoming more influential than the patriarchal view. Allowing women access to equal opportunities on the labour market and to receive equal remuneration will not only contribute to the overall improvement of society but could also lead to the effective implementation of gender equality as required by international legal standards and religious doctrines.

Includes abstract. / Includes bibliographical references. / Host genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns.

Includes bibliographical references (p. 141-166).

Bibliography: leaves 161-191. / Cancer of the colon and rectum is the third-most common cause of death due to neoplasia in Western countries. Colorectal cancer (CRC) can broadly be divided into the hereditary, non-hereditary and sporadic forms. Hereditary cancers account for approximately 10% of the CRCs. Familial cancers can be divided into thos types in which polyps are a dominant feature (e.g. familal adenomatous polyposis-FAP) and the non-polypotic forms (e.g. hereditary nonpolyposis colorectal cancers-HNPCC).

Includes bibliographical references.

As of 2017, 1.8 – 2.1 million children vertically infected with HIV were living in sub-Saharan Africa, of whom an estimated 320, 000 were in South Africa. Since implementation of the prevention of mother to child transmission (PMTCT) strategy, the infection rate has reduced substantially. More recently, the World Health Organisation's (WHO) recommendation of early antiretroviral therapy (ART) initiation for children with perinatal HIV infection has considerably decreased the immediate effects of perinatal HIV infection, including mortality and morbidity. Despite this, not much is known about the long-term outcome of continued ART on early-treated, perinatally HIV-infected children. Early HIV invasion of the developing brain is associated with neurodevelopmental delays and neurocognitive deficits including encephalopathy, slower processing speed, language impairment, lack of concentration and attentiveness, and psychomotor slowing. Alterations in the neurodevelopmental trajectories of brain morphology, including cortical thickness and folding (gyrification) and sub-cortical volumes may be related to the observed neurocognitive deficits during a critical period of brain development spanning from mid-childhood into early adolescence (age 5 -13 years). The effects may be studied using structural magnetic resonance imaging (MRI) and automated segmentation software. FreeSurfer (https://surfer.nmr.mgh.harvard.edu/) is a valuable tool for investigating brain morphology but was not originally designed for segmenting pediatric brains. In this study we therefore first validate the latest FreeSurfer version 6.0.0 against manual segmentation for the study of pediatric HIV. We then assessed the long-term effects of perinatal HIV infection, early ART initiation as well as clinically designed ART interruption, HIV-related encephalopathy, disease severity at ART initiation and immune health measures on the developmental trajectories of cortical thickness and folding (gyrification) over the period from 5-9 years. Study participants were 141 children (75 HIV+, 66 uninfected controls; 72 male) from the Cape Town arm of the children with HIV early antiretroviral therapy (CHER) clinical trial. HIV+ children were randomized at age 6 -12 weeks to receive either immediate limited ART for 40 or 96 weeks, to be restarted when clinical and/or immunological criteria were met, or to start ART only when they developed HIV symptoms or CD4 percentage dropped below 20% (25% in the first year) as per guidelines at the time. Uninfected controls comprised children born to HIV+ mothers (HIV-exposed uninfected (HEU)) or uninfected mothers (HIV-unexposed (HU)) and were recruited from an interlinking vaccine trial. MRI scans were performed at time points around their 5th, 7th and 9th birthdays, in accordance with protocols approved by the human research ethics committees of the Universities of Stellenbosch and Cape Town and voluntary informed consent was received from either participants or their guardians. Both automated and manual methods were used to segment brain regions from high-resolution structural MRI scans. In addition, FreeSurfer was used to examine cross-sectional differences in cortical thickness and gyrification over the cortical surface at age 5. Linear mixed-effects models were used in conjunction with FreeSurfer's longitudinal processing stream to calculate and compare the annual rate of change in cortical thickness and gyrification between ages 5 and 9 in HIV+ children and controls. Results showed that automated FreeSurfer segmentation tended to overestimate volumes of all structures relative to manual segmentation, except the left caudate nucleus. Consistency and agreement between methods were highest for the putamen (Consistency: right ICC=0.89, left ICC=0.90; agreement: right ICC=0.84, left ICC=0.83) and lowest for the corpus callosum (consistency ICC=0.64, agreement ICC=0.26). There were no subcortical volume differences between HIV+ children and controls, except the globus pallidus which was smaller in HIV+ children using both manual and automated segmentation. Subsequent cross-sectional FreeSurfer analyses showed widespread regional increases in cortical thickness and decreases in gyrification at age 5 years, related to the effects of perinatal HIV-infection and early ART initiation. Clinically designed interruption led to thicker cortex in the left rostral middle frontal and right insula regions and, lower left precuneus and right superior frontal, as well as higher lateral occipital gyrification compared to HIV- controls. There were significant regional differences due to HIV severity based on CDC classification and viral burden at enrolment both in cortical thickness and gyrification compared to controls. Cortical thickness was not associated with immune health parameters, while gyrification was negatively associated with immune health measures. However, the linear rate of change of cortical thickness and gyrification from age 5 to 9 in the HIV+ children was not different from that of uninfected controls, nor was it different between controls and children on interrupted or continuous ART. Children with HIV-related encephalopathy showed a decrease in gyrification with age during this period, in contrast to controls who showed stable gyrification except in frontal regions where gyrification increased with age. Children with perinatal HIV infection display alterations in cortical development due to ART interruption and disease severity at age 5 years, despite starting ART early in life. Our results suggest that cortical gyrification is more sensitive than cortical thickness to effects of perinatal HIV infection. ART interruption and disease severity at ART initiation affect cortical morphometry development at age 5 years in a perinatally infected, early-treated pediatric cohort. However, on continued ART the cortical developmental trajectory is no different from that of uninfected controls. Any structural defects resulting from ART interruption appear to normalise by age 9, except in children with HIV-related encephalopathy, who show an altered trajectory of gyrification development.