Faculty of Health Sciences (ETDs)

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Start date: 2021Subject: search.filters.subject.UCTD

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    Identification of (Novel) Immune Targets with Potential Roles in the Progression of Pancreatic Ductal Adenocarcinoma (PDAC)
    (University of the Witwatersrand, Johannesburg, 2024) Nsingwane, Zanele; Nweke, Ekene
    Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a growing incidence and mortality despite novel therapeutic strategies. Its aggressiveness and difficulty to treat suggest the need for a better understanding of associated molecular mechanisms which could be targeted for treatment. The complement signalling pathway may play diverse roles in PDAC by eliciting an immune response, inducing inflammatory responses, and may elevate pathways linked to chemoresistance. However, their role in the progression of PDAC is not fully understood. This study aimed to identify potential immune response-related targets in a group of patients. Methods: In this study, 30 tissue samples (tumours and corresponding normal tissues) were obtained from 15 PDAC patients, 34 plasma samples were obtained from 25 PDAC patients, 6 patients with chronic pancreatitis, and 3 healthy control participants. Targeted pathway-specific PCR analysis was conducted to determine the gene expression profiles of immune-response-related genes. The circulating levels of complement proteins C3 and C5 were further investigated. Pharmacological inhibition of the complement pathway in MIA PaCa-2 pancreatic cancer cell lines was performed and the effect on cells was assessed by cell proliferation, cell migration, and cell cycle assays. Finally, SWATH-mass spectrometry was performed to identify potential molecular mechanisms during inhibition. Results: The results identified C3 to be overly expressed in early PDAC compared to later stages in plasma (p=0.047). Pharmacological inhibition of the complement pathway led to increased cell growth (p<0.0001), proliferation (p=0.001) and migration (p=0.002) in vitro. Proteomic analysis implicated several proteins such as the mitochondrial and histone proteins, that could play a role in inducing this phenotype. Conclusion: Both Complement C3 and C5 are elevated in PDAC samples compared to healthy ones. Furthermore, the inhibition of the complement pathway was shown in vitro to result in a more aggressive phenotype by stimulating cellular growth, proliferation, and migration, indicating the involvement of complement C3 and C5 in tumour progression. This study helps to further delineate the role of the complement pathway in PDAC progression.
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    A thermo-responsive scleral device for the management of ocular tumours
    (University of the Witwatersrand, Johannesburg, 2024) Abdalla, Yosra Mahjoub Ahmed
    Several ocular diseases that lead to blindness could benefit from effective treatment delivery to the site of action. Efficacy, however, remains restricted due to the multiple static and dynamic barriers present in the eye, despite substantial study into administration procedures and delivery vehicle. Ocular tumours are a broad group of diseases that range from benign to malignant and that occur in different anatomical regions within the eye. Ocular surface tumours are tumours of the conjunctiva of the eye and are therefore readily accessible for drug delivery. The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy that meets individual patient needs, considering their anatomical location. Foremost is the need to develop strategies with high benefit to risk ratios. This is closely followed by the need to develop therapies that improve patient compliance while limiting the need for frequent hospital visits. Thirdly, the high cost of immune-therapeutic agents currently used for the management such as interferon demands sustained release strategies that deliver the same efficacy from much lower doses. Interferon alpha has been used to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This novel study employed a pH responsive/protective nanoparticle embedded into a thermo-responsive hydrogel for site-specific IFN-α2b delivery in the treatment of ocular tumours. Loading the IFN-α2b in a hydrogel isolates the drug from the releasing medium; the inclusion of core-shell nanoparticles increases the loading capacity of the drug and provided pH-responsiveness to the acidic tumour microenvironment, protecting the entrapped drug. As a result, the concentration gradient is reduced and the release pathway extended, furthermore, shielding the IFN-α2b against rapid clearance, and degradation at lower pH of the tumour microenvironment. Nano-embedded thermo-responsive hydrogel were prepared and their physiochemical properties, thermo-responsive behaviour, pH-responsiveness, in vitro and in vivo release and toxicity were evaluated. Fourier transform infrared (FTIR), 1H–nuclear magnetic resonance (1H-NMR), and X-ray powder diffraction (XRPD) analysis confirmed the synthesis of the copolymer. The rheological analysis revealed a sol-gel transition temperature in the range of 26-45°C which was concentration–dependent. A concentration of 20% w/v was selected based on suitability for in vivo application. The surface morphology of the hydrogel was evaluated using scanning electron microscopy (SEM) and porositometric analyser, the SEM images revealed the presence of a mesh-like structure on the surface of the hydrogel. The presence of the pores was further confirm by porositometric analysis. The presence of pores is critical for the diffusion of liquid within the hydrogel, which allows the NP to diffuse out of the hydrogel and release the loaded drug. The formed nanoparticles had particle sizes ranging from 137.1 to 230.6 nm (PDI 0.27–0.137) and zeta potentials ranging from -23.9 to -3.36 mV, demonstrating a pH-responsive controlled release in an acidic medium simulating the tumour environment, with an entrapment efficiency of 89%. The in vitro release studies demonstrated a two-phase release pattern of IFN-α2b and stability of the released IFN-α2b from IFN-α2b nano-embedded PECE hydrogel (IFNPH) for the duration of the study; thus, the IFNPH exhibits pH-protective and temperature-responsive properties. In vitro biocompatibility findings on the human retinal pigment epithelial cell line highlighted that the IFNPH is safe within the tested range of 5000 to 0.625 μg/mL and does not pose any adverse cytotoxic effects. The in vivo studies were performed by administering a single subconjunctival injection of the IFNPH to New Zealand albino rabbits. The pharmacokinetic data revealed that the Cmax of 129.7 pg/mL was reached after 24 hrs (Tmax) in the vitreous humour. The IFNPH delivered biological active IFN-α2b in a sustained manner, compared to eye drops and subconjunctival injection of IFN-α2b solution, thus limiting dosing frequency and enhancing patient compliance. This investigation highlights that the IFNPH is a potential suitable candidate for ocular delivery of IFN-α2b
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    An in-silico analysis of the glycosylation inhibitors Brefeldin A and Tunicamycin C in colorectal cancer; characterization of novel targets
    (University of the Witwatersrand, Johannesburg, 2024) Naidoo, Vivash
    Colorectal cancer (CRC), a prevalent malignancy in South Africa, is significantly influenced by posttranslational modifications such as glycosylation. This study investigates the complex interactions between genes, signalling pathways, and cellular processes involved in CRC progression and glycosylation. The glycosylation inhibitors, Tunicamycin and Brefeldin A, are known to hinder colon cancer cell proliferation, migration, and invasion, making them potential therapeutic agents. We used Swiss Target Prediction Software to identify target proteins for both compounds and revealed that Protein Kinase C Alpha (PRKCA), Peroxisome Proliferator- Activated Receptor Gamma (PPARG), and Mitogen-Activated Protein Kinase 1 (MAP2K1) are specific for Brefeldin A, and TK1 and PRKCA for Tunicamycin, respectively. These proteins were selected based on their potential role in the glycosylation process and their role in CRC-related pathways. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis disclosed significantly enriched pathways, including Epstein-Barr virus infection, cellular senescence, and cancer pathways. The 3D-crystallographic structures of PrKC1 (PDB ID 6ar4), TK1 (PDB ID 1w4r), PrCK1 (PDB ID: 6ar4) and MAPK (PDB ID: 3eqc) were retrieved from RCSB Protein Data Bank. The compounds BSP and EGCG were downloaded from PubChem. All non-relevant co-crystallized molecules, including ions, crystallographic water, and others, were removed. Missing residues in the proteins were filled in using the MODELLER algorithm on the UCSF Chimera Graphic User Interface. Molecular docking of Tunicamycin C and Brefeldin A was performed with UCSF Chimera, and the docked conformations were visualised in Maestro and Chimera. The complexes with the top docking scores were selected and prepared for molecular dynamics simulation studies to offer structural and dynamic perspectives on the inhibitory potential of the compounds against the target proteins. The Origin Lab software tool was used to post- analyze the docking conformations. Molecular Dynamics simulation was conducted using Graphics Processing Units version of the Particle Mesh Ewald Molecular Dynamics engine in the AMBER18 suite. Our investigation into the dynamic events leading to the proximal binding of Tunicamycin at the pockets of TK1 and PrKC1 suggested that the binding of Tunicamycin induced a conformational perturbation of the 3D structures of these proteins, resulting in a structural deviation that inhibited their activity. Tunicamycin's time-based dynamics indicated a stable pattern, leading to optimal interaction and maximal stabilization in the hydrophobic pockets of TK1 and PrKC1. Binding energy calculations showed a high-affinity interaction of Tunicamycin with these proteins. Similarly, the structural investigation revealed that the binding of Brefeldin A to Mitogen- Activated Protein Kinase (MAPK) and Protein Kinase C (PrKC1) inhibited their activity. A detailed analysis of active site residues revealed crucial residues that contributed to the binding stabilization of Brefeldin A. It was noted that the Brefeldin A/MAPK complex produced a binding energy of -22.18±4.50Kcal/mol while the Brefeldin A/PrCK1 complex produced a binding energy of -23.90±5.36Kcal/mol. These findings provide crucial insights into designing novel inhibitors of TK1 and PrKC1, potentially blocking glycosylation progression in cancer treatment. This study underscores the potential for exploiting glycosylation inhibition as a therapeutic strategy against CRC, opening avenues to mitigate cancer progression
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    Salient beliefs, preferences and intention to use HIV pre- exposure prophylaxis among pregnant and breastfeeding women in Zambia
    (University of the Witwatersrand, Johannesburg, 2024) Hamoonga, Twaambo Euphemia
    Pregnant and breastfeeding women living in sub-Saharan Africa are at substantial risk for HIV infection, and maternal seroconversion may affect the quality of life for the mother, and is a risk for vertical transmission of HIV. Despite the adoption of PrEP into national guidelines for HIV prevention, its uptake in antenatal and postnatal settings in Zambia remains low. We used an exploratory sequential mixed methods design to explore facilitators and barriers to uptake of PrEP among pregnant and breastfeeding women (18 years or older) not living with HIV in Zambia. We purposively recruited 24 women for the qualitative component and conveniently selected 389 women for the quantitative component of the study at Chipata Level 1 Hospital in Lusaka. For qualitative data, Nvivo was used for data management and data was analysed using thematic analysis. Quantitative data was analysed using chi-square test, pearson correlation coefficient (r) and logistic regression analysis using Stata v.16. Findings from our qualitative study showed that women had positive attitudes and favourable intentions to use PrEP. Most women felt that people who are important to them, especially their male partners, would not support PrEP use during pregnancy and breastfeeding. The anticipated disapproval from partners made women believe that PrEP use would not entirely be under their control, with some reporting that they would not use PrEP if their partners disapproved. Women also cited rude health care provider attitude as a potential barrier to uptake. Some women preferred receiving PrEP from a health facility for fear of stigma in the community while others preferred community-based delivery as an avenue for creating PrEP awareness. This paper was published in Frontiers in Reproductive Health In our second paper, we determined intention to use PrEP during pregnancy and breastfeeding and also identified salient beliefs associated with it. Participants had positive attitude and favourable intention to use PrEP during pregnancy and breastfeeding (mean = 6.65, SD = 0.71 and mean = 6.01, SD = 1.36), respectively. They felt that people who are important to them would approve of their use of PrEP (mean = 6.09, SD = 1.51) and also believed that they would be able to use PrEP if they desired (mean = 6.52, SD = 1.09). All salient beliefs positively and significantly predicted intention to use PrEP during pregnancy and breastfeeding: attitude (β = 0.24, p<0.01); subjective norms (β = 0.55, p<0.01); and perceived behavioural control (β = 0.22, p < 0.01). This paper was published in Global Public Health. The third paper discusses findings from a discrete choice experiment (DCE) on preferences for PrEP service delivery among pregnant and breastfeeding women. In this study, waiting time, travel time, health care provider attitude and amount of PrEP supply at each refill were important considerations likely to influence PrEP use during pregnancy and breastfeeding (all p<0.01). Women expressed strong preference for 3-month’s supply of PrEP compared to other attribute levels (β= 1.69, p<0.01). They were willing to wait for 5 hours at the facility, walk for more than an hour to a facility dispensing PrEP, encounter a health care provider with a negative attitude as long as they received PrEP enough for 3 months. This paper is under review in Frontiers in Reproductive Health. The overall contribution of this PhD research to the body of knowledge on HIV prevention strategies is the ability to identify beliefs about PrEP and how each salient belief influences intention to use PrEP during pregnancy and breastfeeding. It is also one of the first to estimate the benefit (value or satisfaction) that women derive from different attributes of PrEP service delivery for pregnant and breastfeeding populations interested in using PrEP. This information could provide guidance on specific beliefs and service delivery attributes of PrEP that women prefer the most and therefore need to be prioritized if PrEP uptake is to improve in antenatal and postnatal settings
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    Adolescent health in rural South Africa: building an evidence-base to inform a health promotion intervention supporting healthier lifestyles
    (University of the Witwatersrand, Johannesburg, 2024) Seabi, Tshegofatso Martha; Kahn, Kathleen; Wagner, Ryan G
    Background Low- and middle-income countries (LMICs), including South Africa, face the persisting double burden of malnutrition, with undernutrition and overnutrition coexisting within the population. This issue is particularly pronounced among rural adolescents, who experience limited access to healthcare services, inadequate infrastructure, poverty, and a scarcity of nutritious foods. Addressing this double burden of malnutrition is essential for improving the health outcomes of rural adolescents and breaking the intergenerational cycle of malnutrition. Community health worker-led interventions have shown promise in promoting healthier lifestyles in this population, making it crucial to understand the feasibility and acceptability of such interventions. Aim This thesis aims to provide context-specific information on the changing distribution of Body Mass Index (BMI) and views on obesity among rural South African adolescents to inform the development of a targeted behaviour change intervention. Furthermore, it seeks to determine the feasibility, acceptability, and overall experience of implementing a complex intervention aimed at promoting healthier lifestyles in this population. Methods Using a mixed methods approach focusing on adolescents 12-20 years of age living in rural South Africa. This work is nested within the MRC/Wits rural public health and health transitions research unit (Agincourt) Health and Demographic Surveillance System, which is where the sample was drawn and provided explanatory variables such as SES. This work includes data from two studies with comparable measures, conducted in 2007 (n= 1309) and in 2018 (n=518), this study analysed comprehensive data on the prevalence and trends of BMI, including both undernutrition and overweight/obesity, among rural adolescents in 2007 and 2018. This was done through weight and height measures. Growth z-scores were used to determine stunting, underweight and overweight and overweight/obesity was generated using the 2007 WHO growth standards for adolescents aged up to 17 years and adult cut-offs of BMI of <=18.5 for underweight and =>30 kg/m2 for overweight and obese respectively for adolescents 18 to 20 years. Qualitative data was collected in the form of focus group discussions and in-depth interviews. Pre-intervention, three focus group discussions were held with male (n = 16) and female adolescents (n = 15) focusing on obesity to capture views, attitudes and perceptions surrounding obesity. Post-interventions, six focus group discussions were held with male and female adolescents. In-depth interviews were conducted with adolescents (n=20), parents (n=5) and CHWs (n=3), focusing on the feasibility and acceptability of the health promotion intervention. All qualitative data were analysed using inductive thematic analysis. Results This study found that there is a persistent double burden of malnutrition amongst rural adolescents. The pattern of underweight and overweight/obesity remains similar between 2007 and 2018, with an increase in overweight and obesity, and a decrease in underweight observed across different age and gender groups throughout this period. The prevalence of stunting and underweight, particularly in males in both 2007 and 2018 was substantial although lower in the later year. Adolescents expressed conflicting views of obesity, highlighting their knowledge of the cause and long-term consequences of obesity. In regard to the intervention, participants expressed support for the CHWs and the community-based intervention guided by them. The findings demonstrated the feasibility of providing the intervention to adolescents in a rural context, with modifications needed to ensure participant uptake, such as changes to the time and location. Responses from participants show how the intervention, which included dietary and quantity modifications, was acceptable to adolescents. The gathered information in this study serves as a foundation for developing a health promotion intervention tailored to the specific needs and circumstances of rural adolescents, considering both undernutrition and overweight and obesity. Conclusion This research provides valuable context-specific insights into the burden of malnutrition and perceptions of obesity among rural South African adolescents, considering the complexities of the double burden of malnutrition. The findings contribute to the development of tailored health promotion interventions that address both undernutrition and overweight/obesity in this population. Understanding the feasibility and acceptability of such interventions is vital for successful implementation and sustainability in rural communities.
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    Association of genetic variants with breast cancer intrinsic subtypes and splice variants of the fibroblast growth factor receptor 2 in a South African population
    (University of the Witwatersrand, Johannesburg, 2023) Dix-Peek, Thérèse; Duarte, Raquel; Augustine, Tanya
    African populations are more genetically diverse than other groups, but there is a paucity of information about breast carcinomas. South Africa uses immunohistochemistry (IHC) rather than multiparameter genomic assays, such as PAM50, to classify tumors. Genome-wide association studies have shown variants in fibroblast growth factor receptor 2 (FGFR2) are associated with breast cancer, but this has not been examined in black, African women. This thesis investigated intrinsic subtypes; the effects of four FGFR2 single nucleotide polymorphisms (SNPs), and FGFR2 mRNA expression and splice variants associated with breast cancer subtypes. In a cohort of 378 breast cancer patients, we investigated the concordance between tumor samples classified by IHC and PAM50. The SNPs rs2981582, rs35054928, rs2981578 and rs11200014 were examined in 1001 patients with, and 1005 participants without, cancer. The FGFR2 mRNA expression and IIIb and IIIc isoforms were examined using cBioPortal, TCGA Splice Seq and TSVdb databases. Statistical analyses were performed using STATA v14.2. This study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (clearance certificate no M161116). IHC classified patients as estrogen receptor-positive (77.45%), progesterone receptor-positive (70.56%), and epidermal growth factor receptor 2 (HER2)-positive (32.28%). These results, together with ki67, were used as surrogates for intrinsic subtyping, and showed 7% IHC-A-clinical, 73% IHC-B-clinical, 5% IHC-HER2-clinical and 15% triple negative (TNBC). PAM50 gave 19% luminal-A, 32% luminal-B, 24% HER2-enriched and 25% basal-like. Concordance was highest between basal-like and TNBC and lowest between luminal-A and IHC-A. There was no association with the SNPS, rs2981582, rs35054928, rs2981578 and rs11200014, and breast cancer in the black, South African population. However, rs2981578 was associated with invasive lobular carcinoma (ILC) and HER2-positive breast cancer was associated with rs11200014. ILC and ER-positive cancers were associated with higher FGFR2, while TNBC or HER2-positive breast cancers were associated with lower FGFR2. The IIIb isoform was prevalent in ER- positive breast cancer and IIIc prevalent in HER2-positive breast cancer. Genetic information from the black South African population can improve understanding of breast cancer in our population. We suggest that the cutoff for Ki67 be changed to 20-25% to better reflect the luminal subtype classifications. Lobular carcinoma is associated with rs2981578, and HER2-postive carcinoma is associated with rs11200014. Increased levels of FGFR2 mRNA and IIIb isoforms are associated with ER-positive breast cancer, while lower levels of FGFR2 and higher IIIc isoforms are associated with HER2 and TNBC
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    Development of an Anopheles arabiensis sex separation strain and optimisation of mosquito handling, packaging and transport conditions for the South African Mosquito Sterile Insect Technique programme
    (University of the Witwatersrand, Johannesburg, 2023) Mashatola, Thabo; Munhenga, Givemore; Koekemoer, Lizette
    South Africa is taking significant strides towards eliminating malaria transmission within its borders. However, existing vector control strategies that focus on indoor mosquito management face challenges with Anopheles arabiensis, the primary malaria vector. To bolster these efforts, the sterile insect technique (SIT) is being considered as an additional vector control strategy. SIT involves mass-rearing and sterilising specific pest insects, which are then released to mate with wild insects, effectively reducing the pest population. The South African SIT project faces a crucial challenge of efficiently separating female mosquitoes from the production line. This is because female mosquitoes are capable of transmitting the malaria parasite, making their elimination vital. Current methods like manual separation and resistance-based sorting have operational limitations and require further optimisation for field trials. To address this challenge, this thesis conducted optimisation and acclimatisation experiments on adult Anopheles arabiensis females, aiming to transition them to an artificial membrane feeding technique. Comparative assessments demonstrated that artificial blood-feeding methods utilising a Hemotek® membrane feeding system and hog casing could effectively replace conventional methods without significant detriment to reproductive fitness. Subsequently, the study explored the use of ivermectin, a toxicant, to spike blood during artificial feeding to target and eliminate females. An optimal concentration of ivermectin (7.5 ppm) was identified, showing potential for segregating females from males during laboratory rearing. However, complete female elimination within the desired timeframe was not achieved, indicating that this method serves as a secondary phase for female elimination. The study also investigated the use of genetic sexing strains (GSSs) to selectively eliminate females. Although efforts to induce temperature-sensitive lethal mutations temperature sensitive lethality mutations and random morphological variations were unsuccessful, further cross mating studies and insights from previous studies on thermosensitive strains from Cameroon informed future research aimed at developing GSSs tailored to the South African genetic background Another challenge addressed was the optimal temperature and compaction conditions for chilling and immobilising sterile males during handling and transport. This is crucial for maintaining the quality of sterile males. Optimal knockdown temperature ranges (4°C – 8°C for 20 minutes) and packaging conditions (1000 sterile, marked adult males per 27000 cm³ Bugdorm-1® cage) were identified for laboratory handling and transport, facilitating recent small-scale pilot trials with successful packaging and transportation of sterile males to field sites. These advancements signify significant strides in South Africa's malaria elimination endeavours, while also playing a pivotal role in shaping the development of efficient operational protocols for SIT. Furthermore, as the country remains steadfast in its commitment to eliminating malaria, these innovative approaches offer a promising trajectory forward and establish a robust framework for orchestrating the SIT operational phase.
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    A Framework for Integrating Simulation into the Bachelor of Nursing Science Programme in Eswatini
    (University of the Witwatersrand, Johannesburg, 2024) Shongwe, Sithembile Siphiwe; Armstrong, Susan J.
    Background: Simulation-based education is a required pedagogical method for preparing undergraduate students to become nurses. Its ultimate goal is to develop practice-ready professionals rather than introduce the latest technology into training. In Eswatini, simulation is used; however, no framework guides nursing education institutions on how to integrate simulation into their educational programmes to enhance clinical teaching and learning effectively. Purpose: The aim of this study was to develop a framework for integrating simulation into the Bachelor of Nursing Science programme in Eswatini. Research methods: A mixed methods approach utilising multilevel designs guided the inquiry process. Inferences drawn from the various strands of the mixed methods data were integrated to address the study problem. Phase one was a scoping review conducted to explore best practices of simulation-based education in the educational preparation of undergraduate nursing students locally (sub-Saharan Africa) and internationally. A Joanna Briggs Institute methodological approach guided the research process. Sixty articles were included in this scoping review. Phase two was a survey study conducted to assess the state of simulation use in the educational preparation of Bachelor of Nursing Science Students in Eswatini through auditing four (4) simulation laboratories (Study A) and a survey with (n=46) nurse educators, a census (total) sampling technique was used to select the study participants. Phase three used an iterative process together with simulation experts (n=2) to develop the framework and to identify activities to consider when integrating simulation in Eswatini. These were sourced from tabulated lessons learned or inferences drawn based on the findings of phases 1 and 2. The NLN Jeffries simulation theory guided the development of the framework. In phase four, Eswatini nurse educator experts (n=16) evaluated the framework’s utility in a Delphi study completed in two rounds. Findings: In phase one, best practices principal to simulation-based education emerged. The study findings were inductively developed, resulting in four core codes, namely: (i) lecturer preparation, (ii) student elements, (iii) designing simulations and (iv) innovations in simulation. Ninety-five per cent (95%) of the literature was from international settings compared to 5% from the African context. Phase two: Eswatini nursing education institutions were somewhat ready for simulation; this status was attributed to the lack of trained educators in simulation principles, a lack of financial and resource planning and limited infrastructure and equipment for supporting simulation-based education. Phase three: a framework with the following five domains was developed to guide the process of integrating simulation into the Nursing Education programme in Eswatini: Training or preparation of educators; Integration of simulation into the nursing/midwifery programme; Simulation equipment; Simulation infrastructure; and Student/simulation participants. Phase four: Eswatini nurse educators found the framework relevant and suggested feasible strategies for the Eswatini nursing education context. The strategies included sensitising management to increase simulation-based education support and sourcing funding for procuring equipment and infrastructure development. Conclusion: The framework for integrating simulation into the Bachelor of Nursing Science Programme was designed to allow a step-by-step implementation approach due to existing contextual challenges. The challenges include a lack of trained educators/lecturers on simulation-based education principles, an absence of simulation champions, insufficient equipment, infrastructure inadequacies, fiscal constraints and dwindling management support. The framework can potentially guide the successful integration of effective simulation into Eswatini nursing education institutions. Recommendations: There is a need for the current nurse educators to be trained in the simulation teaching and learning strategy to ensure the effective use of simulation-based education. Nursing education institutions must develop financial plans for funding the required simulation resources (educators’ training, equipment and infrastructure) to ensure the sustainability of simulation-based education
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    Attrition in the dental therapy profession: an exploration of the contributing factors
    (University of the Witwatersrand, Johannesburg, 2024) Sodo, Pumla Pamella; Jewett, Sara
    Background: A new type of oral health profession called dental therapy was introduced to address the growing need for affordable and accessible oral healthcare services, especially among marginalised communities. Extensive global research has demonstrated that dental therapists provide cost-effective and high-quality services, effectively addressing the issue of limited access to basic oral health services. The introduction of dental therapy into the South African healthcare system took place in 1977, however, disparities in accessing basic oral healthcare persist, particularly among some population groups where the highest prevalence of oral diseases has been reported. Despite being established over four decades ago, the number of registered dental therapists remains low, and there have been reports of attrition within this professional group. This PhD aimed to explore the factors contributing to attrition in the dental therapy profession. The first objective was to determine South African dental therapists' attrition rate and demographic profile over 42 years (1977-2019). The second objective explored factors contributing to attrition, while the third objective explored the applicability of the Hertzberg Two-Factor Theory in the context of dental therapy attrition in South Africa. Methods: This was a concurrent mixed methods study, involving registered graduate dental therapists, former dental therapists, and key stakeholders. The conceptual framework that guided the study was derived from Hertzberg's Two-Factor Theory. Data sources included the HPCSA registry and primary data collected using a quantitative survey investigating job satisfaction and intention to leave among registered graduate dental therapists and qualitative in-depth interviews with former dental therapists and key stakeholders to gain insights into their perspectives on attrition in the dental therapy profession. The attrition rate was determined by using the formula (Attrition Rate = Number of dental therapists who left the profession divided by the total number of dental therapists registered during the period of interest, multiplied by 100). Quantitative data was analysed in STATA version 15 using descriptive and inferential statistics, and qualitative data was analysed using thematic analysis. Findings: A total of 1232 dental therapists were registered with HPCSA over 42 years, with only 714 registered in 2019, two-thirds of whom were Africans. The attrition rate over the 42 years was 40%, while it reduced to 9% during the 10 years from 2010 to 2019. Of the 200 registered dental therapists who took part in the survey, 74.5% being Africans, approximately 51.5% expressed their intention to leave the profession and a notable 69.5% reported job dissatisfaction. In logistic regression analysis, job satisfaction correlated positively with several factors, including qualification from UKZN (AOR= 2.28, CI: 1.06-4.91), post-graduation job availability (AOR=3.87, CI: 1.73-8.69), awareness of postgraduate opportunities (AOR=2.28, CI: 1.05-4.96), and feeling valued (AOR= 6.91, CI: 1.45-26.36). Conversely, job satisfaction was negatively associated with becoming aware of the scope of work only after enrolment (AOR= 0.31, CI: 0.21-0.81). Job satisfaction was inversely correlated with the intention to leave; satisfied individuals had significantly lower odds of intending to leave (AOR= 0.25, CI: 0.11-0.57). In-depth interviews with 14 former dental therapists identified diverse reasons for enrolling in dental therapy and a shared enthusiasm for the dental therapy profession. Most reasons they cited for attrition, such as inadequate remuneration, job scarcity, poor working conditions, lack of career advancement opportunities, and policy implementation gaps aligned with Herzberg's Two-Factor Theory. One novel factor contributing to attrition not covered by the theory was a lack of professional identity. The 12 key stakeholders who were interviewed echoed similar factors contributing to the attrition of dental therapists. To address limitations in moving from a description of factors to recommendations on how to address system-level challenges, I adapted a framework that is a combination of Herzberg's Two-Factor Theory and the Human Resources for Health System Development framework. This new framework addresses multifaceted issues affecting dental therapists, covering production, deployment, and retention. Conclusion: This study sheds light on challenges within South Africa's dental therapy profession, highlighting their profound implications for both the profession and the broader healthcare system. Despite comparable attrition rates to other mid-level health professionals, there were alarmingly high job dissatisfaction levels and intentions to leave the profession, demanding immediate attention and intervention. Identifying key factors contributing to attrition and the novel insight into the lack of professional identity collectively highlight the multifaceted nature of the issue. To address these challenges, embracing a comprehensive human resource retention framework is imperative. This study emphasizes the urgent need for proactive measures to ensure the sustainability and contentment of dental therapists, ultimately benefiting the healthcare system and the communities it serves. Addressing these factors will lead to increased retention rates and improved access to basic oral health services nationwide
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    Developing strategies for alleviating caregiver burden among informal caregivers of persons with severe mental disorders in Bushbuckridge, Mpumalanga province
    (University of the Witwatersrand, Johannesburg, 2025) Silaule, Olindah Mkhonto; Adams, Fasloen; Nkosi, Nokuthula
    Background: Globally, implementation of deinstitutionalisation led to a shift from institutional to community care of persons with severe mental disorders. This move calls for informal caregivers including families, relatives, friends, or neighbours to become key role players in the care and management of persons with severe mental disorders. The role of informal caregiving results in stress that consequently leads to caregiver burden. In South Africa, limited evidence exists on the extent of the burden experienced by the informal caregivers of persons with severe mental disorders and strategies for supporting these informal caregivers in their role are lacking. This study aimed to explore the burden of care to inform the development of strategies for alleviating burden among informal caregivers of persons with severe mental disorders in Bushbuckridge, Mpumalanga province. Methods: This study used a three-phased mixed methods approach with a multiphase design to facilitate a comprehensive investigation of caregiver burden among informal caregivers and to develop the multilevel strategies for alleviating the burden. Sequential and concurrent methods were combined to collect quantitative and qualitative data across five studies that were conducted to address the study objectives. Results: The established extent of burden revealed that most informal caregivers (44.7%) reported moderate-to-severe levels of objective burden, and 35.9% reported moderate-to-moderate levels of subjective burdens. Objective burden levels were significantly associated with age, gender and residence (p = 0.025, p = 0.034, and p = 0.038, respectively), while subjective burden was significantly associated with daily caregiving (p = 0.012). The exploration of lived experiences revealed that most informal caregivers experienced burden with subsequent impact on their emotional, mental, and physical health. The subsequent burdens were attributed to dealing with the chronic nature of severe mental disorders, role and financial strain, and stigmatisation from family and community. To deal with their caregiving demands informal caregivers expressed reliance on their internal resources, including resilience and resourcefulness. Expressed support needs included access to mental health services, and empowerment and social support from family, government, and religious and community organisations. The findings identified the need for conducting health screenings among the informal caregivers, as well as the need for strategies to support informal caregivers to complement their internal coping resources. The findings of the scoping review revealed that most studies were conducted in Asian countries. Psychoeducation and support group interventions were identified as predominant strategies for alleviating caregiver burden. The service provider’s perspectives revealed that the current state of formal and informal community mental health services is inadequate to meet the needs of the informal caregivers. Conclusion: The study’s findings informed the development of strategies for alleviating caregiver burden among informal caregivers in a low-resourced setting. The complexity of caregiver burden requires multilevel strategies, namely caregiver-driven, health worker-driven, community-based, intersectoral, policy, and legislature strategies across the individual, interpersonal, organisational, community, and policy levels. Caregiver empowerment, family and peer support, development of caregiver-orientated institution and community-based services, task sharing, and task shifting were identified as overriding strategies relevant for alleviating informal caregiver burden in a low- resourced setting