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Pharmacogenetic analysis of admc polymorphisms affecting the efficacy of TB treatment in tuberculosis patients from Tanzania and Uganda, and pharmalogical evaluation of potent medicinal plant extracts used in the treatment of tuberculosis
PhD (Microbiology)Department of Biochemistry and MicrobiologyBackground: Despite the availability of antibiotics which can cure tuberculosis (TB), it remains the leading cause of death from a single infectious disease worldwide. Recent research has shown that the way anti-tuberculous drugs are processed by the body (pharmacokinetics) and their effects on the disease (pharmacodynamics) play a crucial role in determining the success of treatment. To find new treatments which are less harmful than current regimens, medicinal plants are being explored for their potential to produce compounds with anti-TB properties. Therefore, it was hypothesised that the effectiveness of anti-TB drugs may also depend on an individual's ADME polymorphisms.
Aim: This study was aimed at evaluating the pharmacogenetics of Tanzanian and Ugandan tuberculosis patients, and pharmacological effects of medicinal plants [S. brachypetala (MMV004), R. caffra (MMV003), S. molle (MMV005), Z. mucronata (MMV002) and S. petersiana (MMV001)], used for the treatment of symptoms related to tuberculosis infection.
Methodology: Saliva samples were collected from the study participants at treatment initiatiion using Genotek tissue collection kit. DNA Genotek extraction procedure was used to extact DNA from the samples and used in evaluation of custom-designed ADME targets for polymorphisms using real-time polymerase chain reaction on 96 well plates. The pharmacogenetic analysis included target genes responsible for the ADME of isoniazid, rifampin, pyrazinamide, and levofloxacin/moxifloxacin, which are currently the most widely used anti-TB drugs, including medicinal plants. For the pharmacological evaluation of the medicinal plants, plant materials were dried and ground it into fine powder and extracted with solvents of varying polarity. The phytochemical profile of each plant species was assessed using Thin Layer Chromatography (TLC) plates developed in three solvent systems - benzene/ethanol/ammonium hydroxide (BEA), chloroform/ethyl acetate/formic acid (CEF), and ethyl acetate/methanol/water (EMW) - and sprayed with vanillin sulphuric acid. Quantitative analysis of phytochemical constituents using a series of biochemical tests was conducted to determine the presence of alkaloids, cardiac glycosides, terpenoids, and tannin compounds in all plant species. Antioxidant activity was evaluated qualitatively and quantitatively using 2, 2-diphenyl-1-picrylhydrazyl (DPPH)
and Ferric ion reducing power (FRAP) assays, respectively. The presence of antimycobacterial phytochemical constituents was determined using broth microdilution procedures against Mycobacterium smegmatis, Mycobacterium aurum, and Mycobacterium tuberculosis strains. To identify the phytochemical compounds responsible for the antimycobacterial activity against M. tuberculosis, ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was used on R. caffra and S. molle extracts. The cytotoxicity of plant extracts was evaluated on C3A and Vero monkey kidney cell lines and the anti-inflammatory activity of the compounds against RAW 264.7 macrophages. Finally, the anticancer activity of the plant extracts was evaluated against triple-negative breast cancer MDA-MB 231 cell line and determined the type of cell death using flow cytometry.
Outcomes: Through successful DNA extraction, genotyping of ADME genes was made possible. Both adult and pediatric patients from Tanzania were found to have a highly expressed slow acetylator NAT2 variant, while homogenous CC variant SLCO1B1 c.521T/C was absent in Tanzanian adults and Ugandan patients. These genotypes are highly associated with hepatotoxicity. Chromatograms showed that all plant species separated at three solvent systems had both fluorescing and vanillin reactive compounds. Biochemical tests revealed the presence of alkaloids, cardiac glycosides, terpenoids, and tannins compounds in all plant species. Antioxidant activity was observed to increase in a concentration-dependent manner, and extracts at the 0.02 mg/ml concentration showed scavenging activity lower than 50% compared to ascorbic acid. All plant extracts displayed the presence of ferric reducing antioxidant, and R. caffra absorbance was directly proportional to that of ascorbic acid. Antimycobacterial activity against M. tuberculosis was observed only in R. caffra and S. molle dichloromethane extracts, with minimum inhibitory concentration (MIC) values of 0.25 and 0.125 mg/ml. UPLCMS phytochemical profiling showed that R. caffra dichloromethane extracts had abundant alkaloids compounds, while S. molle extracts had terpenoids compounds. Cytotoxicity was higher on the C3A cell line than on the Vero cells, and toxicity was observed in a concentration-dependent manner. A high production of nitric oxide was observed with a slight change in the percentage of viable cells, suggesting potential anti-inflammatory activity of the plant species. S. molle extracts' potential anti-inflammatory activity was discovered to be due to its toxicity on the cells, as it had less than 70% viable cells at all concentrations.
Antiproliferative activity on cancer cells showed that S. petersiana (D5) had percentages of early (41.97%) and late apoptosis (38.26%) which were above Cisplatin (16.15% and 30.55%).
Conclusion: By understanding the ADME profile of individual TB patients or regions with a predisposition to the disease (such as East Africa) would allow personalized interventions in drug choice, dosage, and duration. This knowledge can also help inform new drug development and clinical trial planning. Additionally, the ADME profile can provide insight into the potential toxicity of phytochemical compounds and antituberculosis-phytochemical interactions. The observed antioxidant, anti-inflammatory, and anticancer activities may lead to the development of new antibiotics. This was the first study to evaluate S. molle extracts which showed antimycobacterial activity against Mycobacterium bacteria. Further evaluation of biological activities in in-vivo models is needed to facilitate communication between scientists and traditional healers.NR
The impact of talent acquisition on municipal servive delivery - the case of Ethekwini Metropolitan Municipality
MAdminDepartment of Public and Development AdministrationThe public sector institutions in South Africa face numerous difficulties in providing public services. Both public and private sector institutions must now provide their clients with services of the highest calibre in this day and age of public administration. When a customer's demands are not met or the expected level of service is not met, this may give rise to complaints about the delivery of public services, which can occasionally lead to communities engaging in boycotts, riots, and protests. This may have an adverse effect on employee motivation and lower workplace morale. To ensure that the good service standard is constantly met in public sector organizations and to support the success of municipal service delivery, talent acquisition is consequently of the utmost importance.
In order to effectively impact the rendering of public services, this study intends to evaluate how talent acquisition can be employed in employee motivation. This study implemented a mixed-methods research methodology to acquire data and analyse the role that talent acquisition plays in employee motivation—and ultimately in the success and efficacy of municipal service delivery. The research project also examines how recruiting practices are impacted by the human resource management process, which can assist in the provision of effective, efficient, and reasonably priced services, notably in the eThekwini Metropolitan Municipality. The study also made use of the pragmatism paradigm and an exploratory research design. All these tools were used to guarantee the correctness and dependability of the collected data. In the eThekwini Municipality, improving the process and approach for talent acquisition is the study's main goal. Additionally, it was useful in providing suggestions for upcoming practices, procedures, and personnel acquisition rules. The eThekwini Municipality, together with other local government institutions as well as the provincial and national spheres of government, must undertake this study in order to support the adoption of tried-and-true talent acquisition procedures. According to the survey, there are a lot of gaps because of dissatisfied workers. These employees either believed that the procedures did not support their professional development inside the organization or were impacted by local policies. The research also advocated for the Municipality to support programs for employee growth and development to enhance the provision of municipal services. The study also suggested changing a few municipal rules to better support staff members both professionally and personally. By raising worker morale, this improves service delivery.NR
Influence of digital marketing on the growth of Small and Medium enterprises: A Case of Tshwane Metropolitan Municipality, South Africa.
M. Com (Business Management)Department of Business ManagementDigital marketing refers to marketing conducted on digital channels such as email, social media, websites, and mobile applications. It has become an important strategy for businesses to connect with consumers and expand their markets. The goal of this study was to explore the influence of digital marketing on the growth of small and medium enterprises (SMEs) in Tshwane Metropolitan Municipality, South Africa. The study employed a qualitative research design utilizing interviews and the theory of consumer engagement to explore relationships between SMEs and customers online. Digital marketing channels including email, social media, search engine optimization and online advertising were examined in relation to SME growth measured by sales and market share. Fourteen participants from seven SMEs were interviewed, including CEOs, marketing managers and mid-level employees. Data was analysed using qualitative content analysis software. Initial familiarization identified key themes which were coded and analyzed to produce the findings. Trustworthiness was ensured through measures like triangulation, member checks and an audit trail. Ethical protocols of informed consent, anonymity and approvals were followed. The study's findings provide insight for SMEs, policymakers, and scholars. Digital marketing was found to improve brand awareness, customer engagement and sales leads. Tools like social media, blogs, and influencer marketing enhanced connectivity while search engine optimization boosted organic traffic. However, fast-changing digital trends, limited skills and resources posed challenges for some SMEs. Therefore, digital marketing positively influences SME growth in Tshwane by boosting exposure and interactions at lower costs than traditional methods. However, ongoing skills development and flexible strategies are required to capitalize on opportunities while navigating an environment of rapid technological change and scarce resources.NR
Nonlinear and Asymmetric Exchange Rate Pass-Through to Consumer Prices in South Africa
M.Com (Economics)Department of EconomicsAfter the breakdown of the Bretton Woods fixed exchange rate system, some economies, including South Africa, abandoned fixed exchange rate regimes in favour of floating exchange rate systems. When a country adopts a floating exchange rate and an open trade policy, it loses the ability to shield its economy from external economic shocks. One possible channel for the transmission of these shocks is the exchange rate. The extent to which exchange rate fluctuations are transmitted to import prices and subsequently, to final consumer prices is referred to as exchange rate pass-through. Recent literature suggests that exchange rate pass-through is asymmetric and nonlinear, particularly in emerging nations. Despite the relevance or prominence of these issues, there seems to be a dearth of studies analyzing nonlinear and asymmetric exchange rate pass-through (ERPT) to consumer prices in South Africa. The current study, therefore, aims to deepen the literature on this topic by examining the asymmetric and nonlinear exchange rate pass-through on consumer prices in South Africa using the nonlinear autoregressive distributed lag approach and quarterly data spanning from January 2015 to July 2023. The outcome of this study is that there is a nonlinear and asymmetric exchange rate pass-through in South Africa. The nonlinear autoregressive distributive lag (NARDL) model results reveal the nonexistence of a significant nonlinear asymmetric long-run correlation between exchange rate and consumer inflation. This is portrayed by the Wald test results, which suggest the absence of a nonlinear asymmetric correlation between inflation and exchange rate. This is supported by a significant p-value (0.0000), less than 0.05. The policy suggestion is that the South African monetary authorities should not duly worry about exchange rate depreciations as they don’t have a significant impact on consumer pricesNR
Deviant Healing Practices within Contemporary Religious Movements in Ṱhohoyanḓou, Limpopo: Towards a Post-Colonial African Practical Theology Perspective
Ph.D. (Theology)Department of Human SciencesThe legacy of imperialism on Indigenous belief systems has imprinted an arguable influence on the identity and traditions of religiosity in the histories of Africa. The phenomenon of religion entails socio-political and cultural realities, some of which may overlap, correspond, or compete with different fields of study, which ultimately bears an impact on the conventional understanding of religious meaning, practice, and function. The introduction of Eurocentric orientations into African spirituality did not only encounter Indigenous religious systems but resulted in the development of religious pluralism. As such the researcher felt obliged to explore the Christian religious setting from an African perspective. The study unpacked the universality of the religion and focused on the underlying philosophy of African religious experiences and expression. The latter was engaged from two complimentary investigative angles: i) the researcher defined and explained deviant healing practices within contemporary religious movements in Ṱhohoyanḓou from a Practical Theology perspective and thereby probed consequent incidents of spiritual abuse; ii), in addition the researcher also appraised the implications and challenges of melding Indigenous religious beliefs and practices, and those of Western origination. This sought to unearth the depth of missionary influence or lack thereof; that contributed to deviant healing practices amongst identities within the Vhavenḓa spiritual landscape and heritage. The study is qualitative in nature and encompasses an ethnographic research methodology. This comprised of literature review, an empirical survey of deviant practices and an assessment of Western and African religious inclinations in modern day society. Hopefully, the research poses a benefit to faith communities, religious and government leaders and consequently, equips individuals who can provide positive influence. Ultimately, the study served to present religious insights from a Practical Theology perspective and equally expound on the interpretations of pastoral care within contemporary religious belief systems.NR
Challenges faced by children living in child-headed households in the Capricorn District, Limpopo Province, South Africa
MPHDepartment of Public HealthChild-headed households are homes where parents or guardians are absent and where children support and take care of each other. Commonly, the eldest child becomes the head of the household. This study determined challenges experienced by children in child-headed households in the Capricorn District of the Limpopo Province of South Africa. The study followed a qualitative approach with an exploratory phenomenological design. The population of the study comprised of children living in child-headed households, particularly orphans residing in Mphogodiba Municipality in the Capricorn District of the Limpopo Province, South Africa. A non-probability purposive sampling was used to select participants. Data saturation was reached by the fifteenth participants. The collected data was transcribed and translated from Sepedi into English language and thematic analysis was used to analyze the data. The study findings revealed that there are various challenges faced by children living in child headed households such as, socioeconomic, financial, and psychological challenges. The study recommends that learners from child-headed households must continue to receive grants even after the age of 15 as they still need care and support. They should also receive counselling from school-based support team.NR
Influence of firing temperature on ceramic properties of kaolinitic clays from Duthuni, Limpopo Province (South Africa)
MESMEGDepartment of Earth SciencesThis study investigated the ceramic suitability of two representative kaolin samples from Duthuni area, subjected to four firing temperatures (800 oC, 900 oC, 1000 oC and 1100 oC).The objectives were to ascertain the effects of the raw clay physical, mineralogical, chemical characteristics on its ceramic potential, elucidate on the thermal evolution and associated mineral phase transformations, and to technologically characterize the raw clays. Physical properties were identified by particle size distribution, consistency limits and clay activity. Mineralogical and chemical properties were investigated by XRD, FTIR and XRF. Firing characteristics were measured by weight loss (WL), bulk density (BD), linear shrinkage (LS), water absorption (WA) and flexural strength (FS).
The characteristic mineral assemblage comprised; quartz + kaolinite ± mica + microcline + goethite + hematite + anatase + ilmenite. Quartz occurred as major constituent in both samples, while kaolinite, Goethite and Anatase are present as minor constituents. Visual appraisal of the clay workability chart indicated that D1 and D2 plot within the high shrinkage field, with D1 displaying comparatively higher potential for shrinkage than D2. The potential for high shrinkage suggests possible detrimental effects during clay body formulation (extrusion and molding) as well as firing phases of the ceramic manufacturing process.
Interpretations drawn from the Holtz and Kovacs diagram are consistent with the mineral phases identified by XRD. Kaolinite was the main clay mineral in both samples, occurring as minor constituent. The loam to silty texture of D2 and and D1 respectively are consistent with the predominance of quart phases revealed by the XRD and Si – O functional groups observed in the IR.
The studied materials are siliceous (SiO2: 38.5–45.5 wt%), aluminous (Al2O3: 23.9–16.7 wt%) and ferruginous (Fe2O3: 23.5–21.3 wt%), with the SiO2/A Al2O3 ratios ranging from 1.61 to 2.71. The geochemistry of the clay samples also shows relatively high amounts of TiO2 (2.91 – 2.71 wt% respectively for D1 and D2). Low kaolinite content and high iron oxide contents equally suggests kaolin impurity and colouring effect on the fired clays. Furthermore, appraisal of the ceramic suitability of D1 and D2 based on their geochemistry indicates suitability for red bodies (D2) and a close outlier for red bodies and porous tiles
The DSC curve portrayed three endothermic peaks; 85 oC to 90 oC, 295 oC to 300 oC and 530 oC to 535 oC corresponding to elimination of adsorbed water, goethite dehyroxylation and formation of metakaolinite respectively. A weak exothermic was observed at 945 oC and 955 oC suggesting recrystallization of metakaolinite to spinel or mullite. Small mass loses where observed between 20 oC to 120 oC (2% - 7.2%), 250 oC to 320 oC (1.3% - 3.8%) and 400 oC to 600 oC (5.2% - 6.2%). The relatively low kaolinite dehydroxylation temperature (535 oC) coupled with the generally asymmetric shape of the endothermic peaks suggests a poorly ordered and crystalline structure.
The highest percentage of weight loss (WL) was recorded at 1100 oC in D1(12.41%) and at 900 oC in D2 (16.96%). The bulk density (Bd) increased with firing temperature in both samples. The LS in D1 ranged from 10.2 % to 18.59% from 800 oC to 1100 oC. A corresponding increase in LS was also observed in D2 (8.06 % to 11.8%).The FS of D1 increased steadily up to 1000 oC and then experienced a slight decline at 1100 oC. The FS values for D1 ranged from 0.86 to 1.25 MPa, with acceptable strength attained at 1000 oC and 1100 oC. The FS of D2 showed a similar increasing trend and slight decline at 1100 oC. The WA for D1 showed a decrease with firing temperature, ranging from 24.48 % at 800 oC to 9.01% at 1100 oC. A similar trend was observed for D2 (19.39 % to 10.88 %) from 800 oC to 1100 oC respectively. D2 satisfies the conditions for massive bricks, ceramic blocks and roof tiles. The studied clays show moderate potentials for exploitation based on their inherent characteristics (without modification). This, however, limits the exploitation to predominantly face bricks. Beneficiation is thus recommended to increase value and range of structural ceramic applications.National Research Foundation (NRF
Effective and efficient governance as a catalyst for service delivery in developmental local government with specific reference to the City of Johannesburg Metropolitan Municipality
PhD (Public Management)Oliver Tambo Institute for Governance and Policy StudiesThe purpose of the study was to investigate the effect of governance on service delivery in developmental local government, with specific reference to the City of Johannesburg Metropolitan Municipality. The reciprocity between governance and service delivery was demonstrated by evaluating the extent to which municipalities adhere to good ethical values in executing the mandate of developmental local government. In the process, the principles and values of governance were identified and analysed as well as, the causes of community protests, vandalizing of infrastructure and boycotts, with the intention of providing a robust governance framework to improve service delivery in local government in South Africa. Furthermore, governance systems and leadership, personnel skills were assessed in relation to their contribution to developmental local government. Corporate governance theory which describes governance pillars that influence effective functioning of an institution was used as the conceptual framework. The rationale behind the choice of the foregoing theory is its ability to create a professional and effectively governed institution which can, for example, provide quality service delivery. Corporate governance pillars and principles enable an institution to move from a dysfunctional state to effective operations. Both qualitative and quantitative methods (mixed-method) were used, however, the study was more qualitative and only used quantitative segments in data interpretation and analysis. Primary and secondary sources of data were used in this probe, interviews and questionnaires were utilized as instruments for data collection and pragmatism was the philosophical base for this quest. The findings of the investigation established that developmental local government governance’s inadequacies and flaws detract the provision of quality service delivery. As a result, the researcher proposes an implementation of a robust hierarchical corporate governance framework, which focuses on providing employees with relevant skills, retraining of personnel to attune to corporate governance principles in the developmental local government context. This pathway would ameliorate any negative governance practices in developmental local governments in South Africa by positioning them into catalytic roles towards service delivery. Such practices, if local government departments adhere to, would result in the realization of their mandate.NR
Constraints and opportunities of using information and communications technology to support teachinh and learning of Physical Sciences in Sekhukhune East District
M.Ed. (Curriculum Studies)Department of Educational StudiesIncorporating technology into teaching and learning allows teachers and learners to
enhance their collaboration and performance within the educational setting. ICT
limitations can act as a barrier for educators in utilising technology in the classroom and
hinder their ability to incorporate additional resources using ICT. Challenges to the
implementation of ICT in teaching Physical Sciences prevent teachers and learners from
the benefits of online learning and access to learning materials in classrooms. In the
modern era, the integration of ICT in the classroom is crucial, as it allows learners to
develop skills in navigating, analysing and understanding information through online
platforms and collaborative interactions with their peers. The study explored the
constraints and opportunities of using technology to support the teaching and learning of
Physical Science in Sekhukhune East District Limpopo Province. This qualitative
research used observations and semi-structured interviews where the respondents,
comprising principals, teachers and learners from sampled secondary schools in
Sekhukhune East District participated. Identifying challenges related to using ICT in high
school settings can help teachers address barriers in the classroom and ultimately
become more proficient in integrating technology into their teaching practices. Utilising a
qualitative research approach alongside an interpretative paradigm enabled the study to explore the profound, subjective meanings of participants experiences.
This improved
the understanding of the limitations of teaching Physical Sciences with the help of ICT
resources. Purposive sampling methods were used to choose participants in order to
align with the characteristics of a quantitative research approach. Data were further
examined and interpreted using the theoretical framework of Actor Network Theory to
better understand it.National Research Foundation (NRF
Youth perceptions on the use of indigenous Africa languages broadcasting health awareness messages in commercial radio stations: A case study of Capricorn FM
M.A. (Linguistics)Department of English, Media Studies and LinguisticsLanguage is not only seen as a medium of expression for thoughts and feelings but also as a system in which every item of communication derives its value from the total context in which it functions. Without language, the homo sapiens would find it difficult, if not impossible, to exist, as no one may find it easy to communicate with another person. This study aims to examine the youth’s perceptions of the use of indigenous African languages by Capricorn FM as a commercial radio station to broadcast health awareness messages to listeners. Furthermore, the case study research design and qualitative research method were applied to answer the research questions and objectives. A purposive sampling technique was used to select 20 Capricorn FM youth listeners aged between 18 and 35 years based in the Vhembe District of Limpopo Province. Data was collected using semi-structured interviews and analysed through the qualitative thematic analysis technique to develop themes and sub-themes. The respondents' results showed the youth's insights on the use of indigenous African languages by Capricorn FM as a commercial broadcaster in broadcasting health awareness messages in the Vhembe District, Limpopo Province. This study revealed that majority of youth at a rural university actively listen to Capricorn FM. Most youth indicated that using indigenous African languages helps the listeners better understand the message that is being conveyed. Capricorn FM broadcasts predominately in English, according to their licence registration with ICASA, which occupies 70% of the overall broadcast language.NR