3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Outcome of the antiretroviral treatment intervention in Mankweng(2016) Ledwaba, Ramatsobane JohannaThe purpose of this research was to assess outcomes of the antiretroviral treatment intervention in Mankweng. The antiretroviral treatment intervention was conceived with the aim to reduce HIV transmission through viral load suppression. Literature has shown that viral load is used as a tool to measure the performance of the intervention and studies on viral load outcomes in rural settings of Limpopo are limited. For this reason, the research was focused on viral load suppression with the aim of (1) determining the proportion of adults with viral load suppression among people taking antiretroviral treatment for 12 months, and (2) identifying factors associated with failure to achieve viral load suppression among people on antiretroviral treatment for 12 months. Binomial logistic regression model was used to identify factors associated with failure to suppress viral load. This study used the theory of change to interpret its findings as well as theories of behavioural planning and self-regulation models to understand the logic that underpins the theory of change. The findings revealed that the majority (78%) of adults achieved viral load suppression, and a quarter of the individuals failed to suppress the viral load. There was no significant difference in baseline characteristics between people who achieved viral load suppression and those who did not. In addition, males, with a low CD4 and opportunistic illnesses when in the primary disease stages were more likely to fail to suppress the viral load. Moreover, people who were initiated on a 3-pill containing treatment and do not have social support were also likely to fail to achieve viral load suppression. Although the study showed a trend of likelihood towards failure to achieve viral load suppression, the estimates were not statistically significant. Theoretical arguments from this study suggest that failure to achieve viral load was attributed to poor adherence to treatment. This is supported by the logic that underpins the theory of change, in which the assumption of adherence was possibly violated. However, the results chain framework highlighted that the implementation of the intervention was effective as it led to good outcomes and an effective intervention. Drawing all this together, the study highlights the need for intensified adherence counseling during treatment in order to improve the performance of the intervention. Author: Ramatsobane Johanna Ledwaba, Thesis Title: Outcomes of the antiretroviral treatment intervention in Mankweng, Johannesburg, March 2016Item Characterization of a novel cell death related gene, DWNN, in cervical cancer(2006-03-13) Ledwaba, Ramatsobane JohannaDWNN-deficient Chinese Hamster Ovary cells have been found to be resistant to staurosporine-induced apoptosis. The human DWNN gene is located on chromosome 16p21, with 18 exons and is 36 kb long. It is alternatively spliced at exon 16 and makes two major mRNA transcripts, 1.1 and 6.1 kb, encoding 13 kDa and 200 kDa proteins respectively. The purpose of the study was to elucidate the possible role of DWNN in cervical cancer and apoptosis, to establish tissue distribution and expression levels of DWNN at protein and mRNA levels in cervical cancer. In situ hybridization studies showed elevated levels of the three mRNA transcripts in cervical cancer as compared to the normal tissues. The transcripts were localized in the nuclei of invaded stroma, moderately differentiated islands of tumours, dysplastic epithelium and some infiltrating lymphocytes. Immunocytochemistry showed that DWNN proteins were highly expressed in the dysplastic epithelium, dysplastic endocervical glands, moderately and well differentiated islands of tumours and the invaded stroma. Image analysis indicated elevated expression levels in the islands of tumours. Apoptosis detection by TUNEL revealed high apoptotic levels in the invaded stroma and moderately differentiated islands of tumours and this significantly correlated with DWNN localization. Proliferation assay using Ki67 antibody was found to be indirectly directly proportional to DWNN expression. Antiapoptotic Bcl-2 expression levels were found to be inversely proportional to the expression levels of DWNN. The up-regulated levels of DWNN in cervical cancers in contrast to normal tissues suggest DWNN to be proapoptotic, as there were elevated levels of apoptosis in the same sites where there were high levels of DWNN expression and Bcl-2 was down-regulated in the same sites. DWNN expression significantly correlated with apoptotic levels and was indirectly proportional to ki67 in human cervical cancers. Real Time PCR also confirmed the up-regulation in levels of DWNN in cervical cancer. This study suggests that the DWNN gene may be involved in apoptosis. Further characterization of this gene could lead to its manipulation as a diagnostic marker and a potential therapeutic target for cancer treatment.