Electronic Theses and Dissertations (PhDs)
Permanent URI for this collectionhttps://hdl.handle.net/10539/37985
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Item Novel antiangiogenic peptide targeted therapeutic nanosystem for non-small-cell lung carcinoma(University of the Witwatersrand, Johannesburg, 2023) Ngema, Lindokuhle Malibongwe; Choonara, Yahya Essop; Marimuthu, Thashree; Adeyemi, AdebawoleLung cancer is the leading cause of cancer deaths globally, with nearly 1.8 million deaths and 2.2 million incidences recorded annually. Primarily, non-small-cell lung carcinoma (NSCLC) is the most commonly diagnosed type of lung cancer, which makes up approximately 85% of all reported lung cancer cases. Currently, the management of NSCLC is a global challenge, and although, various treatment protocols are available, such as surgery, radiotherapy, and chemotherapy, the survival outcomes remain poor. Combination chemotherapy is the current first-line treatment for NSCLC, however, it presents with a myriad of drawbacks, including non-specificity, high dosage, and detrimental side effects, resulting in patients intolerability to the regimen. Consequently, a new therapeutic approach is greatly needed and warrants the design of biocompatible targeted drug delivery nanosystems that can halt tumor proliferation and metastasis by targeting key molecules and deliver drugs directly to tumors, with limited side effects and toxicity to healthy cells. Tumor targeted drug delivery nanosystems such as magnetic nanoparticles (MNPs) modified with biomolecules and functionalized with homing peptides are of great interest for potential application as a potent nanomedicine in NSCLC management. Accordingly, the present study set to develop novel targeted paclitaxel (PTX) delivery nanosystems from the amenable superparamagnetic iron oxide nanoparticles (SPIONs) coated with trans-10,cis-12 conjugated linoleic acid (10E, 12Z) and functionalized with either a vascular endothelial growth factor receptor (VEGFR) binding or a matrix metalloproteinase 2 (MMP-2) binding peptide, for specific delivery of PTX to VEGFR and MMP-2 expressing NSCLC tumors. A preceding nanosystem without the peptides (CLA-coated PTX-SPIONs) was originally fabricated as proof of concept for the application of 10E, 12Z CLA as a surface coating and drug partitioning biomolecule. CLA-coated PTX-SPIONs exhibited a spherical shape, with an average particle size and zeta potential of 96.5 ± 0.6 nm and −27.3 ± 1.9 mV, respectively. The nanosystem had a drug loading efficiency of 98.5% and demonstrated a sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. Thereafter, the fabricated nanosystem was optimised for direct tumor-targeting by functionalization with HRH or CTT peptides, to give CLA-coated PTX-SPIONs@HRH and CLA-coated PTX-SPIONs@CTT. A new design methodology was established for the tandem surface functionalization of CLA-coated PTX-SPIONs with the antiangiogenic peptides, via coupling reactions. A series of robust nanotechnological techniques were employed for pertinent physicochemical characterization, in vitro evaluation of drug release, anti-proliferative activity, and quantification of VEGF-A and MMP-2 levels. Meanwhile, in vivo testing was carried out on a lung tumor xenograft mouse model. Both nanosystems exhibited a marked cellular uptake and internalization by A549 cells, and CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells (HMEC-1) from 46.9 pg/mL to 35.6 pg/mL, meanwhile CLA-coated PTX-SPIONs@CTT significantly inhibited MMP-2 secretion by almost 70% , indicating specific anti-MMP-2 activity. A 76.6% and 69.7 % tumor regression was observed in a lung tumor xenograft mouse model treated with CLA-coated PTX SPIONS@HRH and CLA-coated PTX-SPIONs@CTT, respectively, demonstrating tumor targetability and angiogenesis inhibition. Lastly, the pharmacokinetics (PK) evaluation revealed that both nanosystems prolonged the half-life of PTX and circulation time in vivo. In essence, potent antiangiogenic tumor-targeted PTX delivery nanosystems were successfully fabricated, and the obtained results suggest potential application of CLA-coated PTX SPIONs@HRH and CLA-coated PTX-SPIONs@CTT for effective management of NSCLC.Item Exercise in Ghanaian, postmenopausal women with an increased body mass index (bmi), above 25 KG/M²(University of the Witwatersrand, Johannesburg, 2023-08) Bonsu, Isaac Mensah; Myezwa, Hellen; Corlia, Brandt; Ajidahun, Adedayo TundePostmenopausal women frequently experience weight gain in addition to an increased tendency for central fat distribution. The development of metabolic syndrome and systemic inflammation caused by excess body weight (overweight and obesity), particularly in the form of visceral fat deposition in postmenopausal women, increases the risk of cardiovascular disease, diabetes, and mortality. The reported high prevalence of excess weight among Ghanaian postmenopausal women generated an inquiry into the experiences of postmenopausal women with excess weight gain. This study aimed to develop and test the effect of a culturally adapted exercise-based programme for weight loss in Ghanaian postmenopausal women. The study used a mixed-method approach with five studies to address the study's aim. A quantitative study was conducted to determine the prevalence of excess weight gain and associated socio-demographic risk factors among postmenopausal women. The results showed a high prevalence of excess weight gain of 73.2%, 91.8%, and 91.0% using body mass index (BMI), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) respectively among 378 women. Education and ethnicity were the predictors of excess weight gain (WHR) among the participants. Despite the extensive body of research on an exercise program for weight loss, these results suggest gaps in weight management. Physical activity, lifestyle, and sociocultural levels of the women were investigated quantitatively to determine contributing factors associated with the high prevalence of excess weight gain. The results showed that the majority (55.2%) of the participants had 1 to 2 days per week of moderate physical activities for 1 to 20 minutes per day during the last 7 days. This finding showed that participants are not meeting the physical activity recommendation of 150-300 minutes of moderate-intensity per week for older adults by World Health Organization (WHO) guidelines on physical activity and sedentary behaviour. Housewives and unemployed participants had a higher risk of weight gain, especially when assessed with WHR and WHtR. Most participants (59.7%) had poor eating habits and cultural beliefs regarding body size impacts their decisions regarding weight loss. A qualitative study was conducted with the study group of postmenopausal women with excess weight, twenty-four participants, and four focus group discussions (FGD), to explore their current weight management approaches or practices. From the analysis of FGD, three major themes emerged from the study namely, (i) perception of body weight, (ii) measures to reduce body weight, and (iii) support for adherence to the weight management program. Sub-theme under the perception of body weight revealed that weight gained was viewed as the presence of diseases and admired by society as a culturally accepted body image. Diet-related changes, a combination of diet modification and physical activity, and weight management supplements emerged as measures to reduce excess weight. Support for adherence to the weight program included health education, access, affordable exercise facilities, and social support. Based on literature reviews and findings from the three studies conducted as part of the project, a culturally appropriate exercise programme for weight loss was developed and validated by the Delphi study. A Delphi consists of three rounds among international (twelve) and local (twenty-one) experts with a high participation rate of 33 (80.5%) of the 41 participants was conducted. A consensus was reached on all the thirty-two (32) items related to health assessment, pre-exercise parameters, exercise dosage and physician referral after the third round. The developed culturally informed exercise-based weight loss programme was tested using a single-blind randomized controlled trial. A total of 226 postmenopausal women were randomized into exercise (113) and control (113). Anthropometrics (BMI, WHR, WHtR WC, HC and body weight) and body composition (body fat, visceral fat, muscle mass) were measured pre and post-12-week intervention. Using a repeated-measures linear mixed model, the evidence from the analysis demonstrates that except for waist-to-hip ratio (WHR), there were statistically significant reduction in body weight, BMI, WHtR, visceral fat, and total body fat in the exercise and control groups. Muscle mass increased significantly (+0.21 kg), whereas hip circumference (-2.46 cm) and waist circumference (-1.39 cm) decreased significantly compared with the control group. Within the exercise group when stratified by BMI, there were higher reductions in BMI (1.01kg/m2 vs. 0.46kg/m2), WC (2.18cm vs. 0.22cm), body weight (2.12kg vs. 1.17kg) and body fat (1.84% vs 1.6%) in obese women compared to overweight women. Weight loss programmes should be traditionally induced within the specific setting to encourage full participation and reduce the dropout rate. Implication for health professionals to prescribe physical activity in postmenopausal women’s treatment plan. In conclusion, the findings resulting from this research may improve health providers' cultural awareness and knowledge. This project is expected to help healthcare professionals improve the care given to postmenopausal women with weight excess to decrease the incidence of morbidity and mortality. It is anticipated that this initiative could direct the development of a modified culturally-sensitive weight loss programme for women in different stage in life and use with other ethnic groups.Item Development of an instrument to measure the quality of care after the withdrawal of life-sustaining treatment in the adult intensive care unit(University of the Witwatersrand, Johannesburg, 2023-09) Korsah, Emmanuel Kwame; Schmollgruber, ShelleyBackground: The majority of deaths in the intensive care unit occur after the withdrawal of life-sustaining treatment. Most patients often die within 24 hours after treatment has been withdrawn. The short time interval between treatment withdrawal and death has highlighted the urgent need to prioritize the quality of care provided for patients and their families during this period. In South Africa, the quality of care provided for patients after treatment withdrawal has been plagued with cultural differences, challenges, and ethical dilemmas. Currently, no instrument exists to measure the quality of care provided for patients at the end of life and their families after treatment is withdrawn in the adult ICU. Existing measuring instruments have been developed for western countries with no consideration for the South African context. Hence, using these measuring instruments, especially in a country where non-western cultures exist, may be inappropriate, unrealistic, and liable to fail, necessitating revision. Purpose: To develop an instrument to measure the quality of care provided for patients after the withdrawal of life-sustaining treatment and their family members in the adult intensive care unit. Methodology: An exploratory sequential mixed-methods research design was used. The study was conducted in two phases, namely: domain identification and item generation; and instrument development and validation. In Phase 1, a summary of findings from a scoping review of the literature and qualitative interviews with nurses, doctors, and family members were used to generate relevant content domains and items. Relevant items generated were synthesised and reduced to develop the first version of the measuring instrument in Phase 2. The instrument underwent further expert panel review for relevance and clarity. A content validity index and modified Kappa statistic were performed. Comments and feedback from the panel of nine experts were also used to assess the face validity of the instrument. Results: The instrument development and validation process yielded a final instrument that consisted of 64 items across 7 domains. From an initial set of 143 items, the content validity process found seven domains and 64 items. These included patient- and family-centered decision making (9 items), communication among the ICU team and with patients and families (12 items), continuity of care (3 items), emotional and practical support for patients and families (12 items), symptom management and comfort (7 items), spiritual care (5 items), and modifying the ICU environment (12 items). A study of content validity revealed that this instrument recorded an appropriate level of content validity. The overall content validity index of the instrument was high (S-CVI/Ave = 0.97) when using the average approach and moderate (S-CVI/UA = 0.77) when using the universal agreement approach. The moderate value of the S-CVI/UA can be advocated with respect to the high number of content experts that make consensus difficult. The instrument items also obtained excellent kappa values that ranged from 0.89 to 1.00. Conclusion: The researcher developed and validated the content of an instrument to measure the quality of care provided for patients and their families after the withdrawal of life-sustaining treatments in the adult ICU. This instrument will support the provision of care for patients and their families following treatment withdrawal and the training and education of healthcare providers in end-of-life care. It will also aid future research in the care of critically ill and dying patients in the ICU. Future research should conduct more assessments and pilot test the instrument.Item Development and validation of a school-based mental health education programme for in-school adolescents in Lagos, Nigeria(University of the Witwatersrand, Johannesburg, 2023-07) Olowe, Atinuke Oluwatoyosi; Tshabalala, Amme; Bruce, JudithAn increasing prevalence of mental health challenges among adolescents, with its onset identified in early/mid-adolescence, has called for global concern. Mental health disorders account for most of the leading causes of adolescent disease burden. Its impact, as measured by the financial cost and the overall risks on adolescents, families, and the community, cannot be overemphasized, especially among Low Middle-Income Countries like Nigeria. The study aimed to determine adolescents' knowledge, attitude, and mental health status and explore stakeholders' perspectives as well as documented literature on school-based mental health programmes. Then, use the information to develop and validate a school-based mental health education programme for adolescents in the school setting. A sequential, multi-method study design involving six objectives, all in three phases, was employed in this study. Phase one entailed baseline data identification involving a quantitative survey to determine the knowledge, attitude, and mental health status of in-school adolescents, qualitative exploration of stakeholders' perspectives through in-depth interviews and a scoping review to determine international literature on school-based mental health education programme. In phase two, the findings from phase one were merged to create overlapping themes. These themes identified domains from which the school-based mental health education programme was developed. In the third phase, a group of experts validated the programme's content for relevance and clarity through two rounds of Delphi. A pool of 50 items under six domains was generated for the second round of the school-based mental health education programme after the content validity was carried out. Evidence from the scoping review revealed that a theoretical framework is optional in developing a school-based mental health education programme. Also, most programmes reviewed used the universal level of intervention for comprehensive coverage. Although not all mental health programmes were part of the school curriculum, break time and after-school hours were used by some facilitators in delivering mental health education programmes. In determining the knowledge, attitude, and mental health status of in-school adolescents in Nigeria, the findings showed that only a quarter of the in-school adolescents had high knowledge of mental health. The age of in-school adolescents (p=0.005) and their class (p<0.001) were the socio-demographic information significantly associated with the attitude of in-school adolescents. Five themes and fifteen subthemes emerged from the in-depth interviews that explored stakeholders' perspectives. Overlapping themes from the scoping review, data sources from the quantitative survey, and qualitative interviews generated the domains for the designed school-based mental health education programme for adolescents. The school-based education programme was subjected to validation by a group of experts to ensure the relevance and clarity of the items in the programme. The overall scale level content validity index (S-CVI) for the second round of Delphi was 0.90. The school-based mental health education is designed based on evidence, with good content validity as regards relevance and clarity. Hence, the programme can improve adolescents' knowledge and attitude towards mental health.Item Support programme for healthcare professionals involved in adverse events in public hospitals in Gauteng(University of the Witwatersrand, Johannesburg, 2022-12) Nkosi, Elizabeth Malefu; Armstrong, Sue; Nkosi-Mafutha, NokuthulaBackground: Adverse events in the healthcare services result not only in administrative and financial costs to the healthcare institution, but also in personal costs to the patients and their families, who are often angry, disappointed, and sad. In the current litigious healthcare climate, relatives, supported by legal advisors, often seek redress as a way of managing their distress. Thus, patients are not the only victims of adverse events. The healthcare professionals that are directly involved often shoulder the blame, sometimes fairly, and sometimes unfairly, while they too need psychological support. A culture of blame in institutions can lead to healthcare professionals involved in an adverse event being marginalised, feeling personally responsible for the event and that they have failed the patient, and they are left to suffer in silence. While anecdotal evidence exists that such stress may lead to negative coping mechanisms, the researcher has not identified any research study conducted in public hospitals in Gauteng, South Africa that identifies and describes the influence that the involvement in an adverse event has on healthcare professionals. Such evidence is required to develop a support programme that could assist healthcare professionals who have been directly involved in adverse events, to minimise the concomitant stress, and to enable these professionals to continue to provide quality care after such an event. Aim: The purpose of this study was to develop, describe, and evaluate the implementation of a support programme for healthcare professionals involved in adverse events in public hospitals. Methodology: A sequential, multimethod research design was used. The study was conducted in five phases. Phase 1 consisted of a scoping review of the international literature that focused on the experiences of the nurses and doctors. The question asked in the scoping review was: What is known from existing literature about the support programmes for healthcare professionals involved in adverse events in clinical settings, and are they effective? Phase 2 involved storytelling that explored the impact of adverse events on involved healthcare professionals. Smith and Liehr’s (2005) methodology was used, that is, healthcare professionals who were directly involved in or affected by one or more adverse events in the public hospitals in Gauteng narrated their experiences. Phase 3 used semi-structured interviews with the managers to explore how best to support health professionals involved in adverse events. Phase 4 involved developing a support programme according to the Wits Trauma Model developed by Eagle, Friedman and Shumkler, from the Psychology Department of the University of the Witwatersrand, in 1993 (Eagle, 2000). Phase 5 focused on confirming and validating the programme to support healthcare professionals involved in adverse events in public hospitals. This phase was subdivided into two sections: Phase 5.1 comprised the Delphi group; and Phase 5.2 comprised the Focus group. In the first round involving the Delphi group, technical data was collected from the experts who validated the programme by means of the survey that was distributed on Research Electronic Data Capture. Concerns arising out of the first round with the Delphi group and that required attention were addressed during the Focus group discussion. Results: Hospitals were not aware of the magnitude of second victimhood and hence the delay in reviewing the structures in place to provide support to those involved. Just (fair) culture principles were not adhered to as there were no guidelines for their implementation, hence the second victims were left traumatised and in isolation following their involvement in adverse events, and they experienced blaming by management instead of being provided with much needed support. Limitations: The limitations to the study include the small sample size during the data collection phases, due to the Coronavirus disease of 2019 pandemic. Due to the restrictions that were implemented it was not possible to contact all the staff as they had been relocated to other healthcare facilities, were absent, or had resigned. Those who were snowballed were no longer at the facilities where they were originally identified, and therefore the researcher was unable to capture their experiences. Objectivity was not maintained as the documents for the Delphi group were hand-delivered, participants were able to identify the researcher, and hence the social desirability concern. The face-to-face encounters made adherence to anonymity impossible. The model components were not practical in terms of the developed programme. Round two of the Delphi group could not be scheduled, thus challenging the study model. Conclusion: The impact of adverse events on healthcare professionals remains an underestimated health concern. Experiences are magnified by unsupportive work environments, and are evident in increased hostility, blaming, fear of punishment, and reputational harm. The second victims require support to enable them to recover and learn from their involvement. The programme was developed, which included the summarised structure and the detailed process for implementation by hospital management on how to manage the adverse events in public hospitals in Gauteng.Item Development of an interprofessional education and collaborative practice curriculum for health science students at Sefako Makgatho Health Sciences University(University of the Witwatersrand, Johannesburg, 2023-09) Pitout, Susara Johanna Susanna; Barnard-Ashton, Paula; Adams, Fasloen; du Toit, Sanetta Henrietta JohannaA South African university required a contextually relevant, Interprofessional Education and Collaborative Practice (IPECP) curriculum. The study aimed to develop and validate an IPECP curriculum for health sciences students at Sefako Makgatho Health Sciences University (SMU). Planning the IPECP curriculum necessitated both a robust theoretical foundation and pragmatic problem-solving and comprised three phases. Phase I, the situational analysis included a scoping review of global peer-reviewed literature, focus groups with students and lecturers, and a university-wide needs survey. Brookfield’s lenses of critical reflection and reflexivity condensed results of the situational analysis into factors guiding curriculum planning. Phase II included a curriculum map analysis of profession-specific curricula of the eleven professions: occupational therapy, physiotherapy, speech language pathology and audiology, human nutrition and dietetics, nursing, medicine, radiography, pharmacy, dentistry, dental therapy, and oral hygiene. The curriculum mapping involved consultation with professions’ representatives in combination with information extracted from LOOOP, an electronic curriculum mapping programme. The analysis identified the gaps in addressing interprofessional collaboration core-competencies and highlighted common topics, in the professions’ specific curricula. From the curriculum foundation laid by Phase I and II, an IPECP curriculum framework and design principles were conceptualised using a Curriculum Development Research design. In Phase III, the proposed SMU-IPECP curriculum and accompanying design principles were refined during iterative stages of design, development, testing and revision. Internal and external participants validated the curriculum by rating the relevance, consistency, practicality, and feasibility of the four-year, longitudinal curriculum. A modified Delphi guided consensus on the design principles. The curriculum escalated interprofessional role development from mere exposure to immersion, striving for competent representation in research, ethics and Primary Health care. The build-up followed a trajectory from a professional individualised role in the team, to students fulfilling a dual identity of professional and an interprofessional practice-ready practitioner, who practices in an evidence-based collaborative way as a primary health care advocate, in their final year. The curriculum validation highlighted affordances and constraints for future implementation. During validation, participants agreed on the design and commended the proposed IPECP curriculum. Although the curriculum was planned for a specific university, the theoretical design principles developed through this research process could potentially be customised to fit similar university contexts.Item Design and development of a bioactive-loaded polymer-engineered neural device for potential application in reducing neurological deficits after spinal cord injuries and neuro-regeneration(University of the Witwatersrand, Johannesburg, 2017) Kumar, Pradeep; Choonara, Yahya Essop; Modi, Girish; Naidoo, Dinesh; Pillay, VinessTraumatic Spinal Cord Injuries (SCI), due to their devastating nature, present several interventional challenges (extensive inflammation, axonal tethering, scar formation, neuronal degeneration and functional loss) that need to be addressed before even a slight neuronal recovery can be achieved. Recent post-TSCI investigational approaches include support strategies capable of providing scaffold architecture to allow axonal growth and conformal repair. This research provided detailed insight towards the development and fabrication of six specialized Polymer-Engineered Neural Devices (PENDs): 1) poly(lactic-co-glycolic acid)-gliadin (PLGA-GLDN) nanofibrous mats, 2) polyacrylamidated chitosan (PAAm-g-HT) scaffold, 3) functionalized chitosan methoxypolyethylene glycol (CHT-mPEG) cryosponges, 4) polyacrylonitrile-elastin-collagen (PANi-EC) neurosponge, 5) methylcellulose-alginate-polyethylene glycol (MAP) thermogel, and 6) chitosan-luronic F127-β glycerophosphate (CHT-PF127-βGP) composite thermogel for potential restriction, repair, regeneration, restoration and reorganization post-SCI. The latest trends in biomaterials-based SCI intervention were reviewed, discussed and analyzed in detail throughout the thesis. The research also involved an in silico analytico mathematical interpretation of multi(biomed)material assemblies wherein quantification of energy surfaces and molecular attributes via atomistic, dynamic, and docking simulations was carried out. The in silico experimentation additionally confirmed the potential of curcumin as a bioactive of choice for SCI intervention. Curcumin and dexamethasone were incorporated into the compact scaffolds and the bioactive release was determined over a period extending up to 60 days. The PLGA-GLDN nanofibrous mats demonstrated the formation of a compatible blend among the component polymers at equal weight ratios (PG55) as confirmed by quantitative physicochemical characterizations. Image processing analysis (DiameterJ plug-in of ImageJ) was performed on the SEM images of nanofibers to quantify the size, porosity, and orientation of the samples. Nanofibers within the size range of 10nm and 250nm were obtained in case of compatible blend and the nano stack was used for in vivo implantation post-SCI. Polyacrylamidated chitosan (PAAm-g-CHT) was synthesized via a unique persulfate-mediated polymer slicing and complexation as determined by static lattice atomistic simulations. The graft copolymer so obtained was fabricated into an anisotropic neurodurable scaffold. The CHT/mPEG cryosponges showed unique morphological features such as fringe thread-like structures (CHT alone); hemispherical, pebble-like structures (CHT-mPEG); curved quartz crystal-like or crystal-flower-like structures (CHT-mPEG-CHO); and grouped, congealed, steep-sided canyon-like structures (CHT-mPEG COOH). A novel image processing protocol involving DiameterJ and ND plugins of ImageJ software was employed for analyses of the SEM micrographs in terms of % porosity, pore wall thickness and % xiiehaviorxii of the porous scaffolds. The PANi-EC interpenetrating polymer network neurosponges were synthesized employing free radical polymerization under acidic conditions wherein first-in-the-world spinomimetic scaffolds were obtained. The unique feature of the PANi-EC neurosponge was the formation of a fibrous neurotunnel architecture mimicking the native spinal cord. The physicochemical characterization revealed that the secondary structure of the peptide molecules (elastin and collagen) rearranged in the presence of PANi to their native extracellular matrix (ECM) form confirming the self-assembling nature of the polymer-peptide architecture. Furthermore, the PANi-EC neurosponge provided a perfect balance of matrix resilience and matrix hardness similar to the native collagen-elastin complex in vivo. Two very interesting tri-component thermogels were reported here viz. a simple blend thermogel comprising methylcellulose, sodium alginate and poly(ethylene glycol) and a complex thermogel incorporating chitosan, Pluronic F127 and β-glycerophosphate. Both the thermogels solidified at physiological temperature confirming their applicability in vivo. The outstanding feature of MAP thermogels was the formation of hydrogen bonded O-H…C=O which only formed in the tripolymeric blend while the bipolymeric blends showing no such interaction. We proposed that the MAP thermogel self-assembled into a repeating network structure represented by “PEG400-ALG-hydrophillicMChydrophobic}-{hydrophobicMC-hydrophilic}-ALG-PEG400” and the physical “compression” might have led to the formation of hydrogen bonded O-H…C=O among MC/alginate or PEG/alginate in the presence of PEG or MC, respectively. In case of the complex CHT/PF127/βGP thermogel, a unique triphasic gel-sol-gel transition xiiehavior was observed with the thermogel forming a gel-phase at lower temperatures (T<20°C), a sol-phase at intermediate temperatures (20°C35°C). The MTT proliferation studies indicated that all polymer engineered neural devices (PANi-alone matrix) were capable of efficiently supporting the growth of PC12 cells compared to the control over a period of 72 hours. The fundamental objective of this thesis was to test the applicability and capability of various biomaterial composites towards the repair and regeneration of neuronal tissue after traumatic spinal cord injury. Although drug-loaded scaffolds were also developed, only drug-free scaffolds (PLGA-Gliadin 5:5 electrospun nanofibers; PANi-Elastin-Collagen neurosponge; and Chitosan/Pluronic F127/β-glycerophosphate thermogel) were tested in vivo for the proof-of-concept. The 21-point scale BBB locomotor rating analysis demonstrated that PEND I (14), PEND II (19) and PEND III (18) provided significant motor recovery as compared to the lesion-control (5) group 28 days post-SCI and –implantation. The immunohistochemistry confirmed that reparative changes were accompanied by marked upregulation of iNOS, a notable influx of ED1-positive chronic inflammatory cells, the appearance of multinucleate cells characteristic of presumptive regenerative neuroblasts and near-complete loss of GFAP and NF-200 protein/structural integrity. Almost complete functional and neurostructural recovery was observed with post-SCI implantation of PEND II and III. In conclusion, the composite scaffolds tested in this research demonstrated immense potential in improving the neurological, neurochemical, and behavioral outcome after implantation post-SCI.Item A thermo-responsive scleral device for the management of ocular tumours(University of the Witwatersrand, Johannesburg, 2024) Abdalla, Yosra Mahjoub AhmedSeveral 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-α2bItem 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 educationItem 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, NokuthulaBackground: 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