School of Therapeutic Sciences (ETDs)
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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 Design and engineering of a bio-responsive, nano-enabled vitreous substitute for the treatment of retinal diseases(University of the Witwatersrand, Johannesburg, 2023-07) Naik, Kruti; Du Toit, Lisa C.; Choonara, Yahya E.The vitreous humour is a soft gel between the lens and the retina in the eye. It protects the surrounding ocular tissues functioning as a shock absorber and a vessel for oxygen and metabolite transport. Vitreous liquefaction leads to vitreous detachment resulting in ocular tissue damage such as retinal detachment and vitreous haemorrhage. Current treatment includes total vitreous replacement via pars plana vitrectomy utilising silicone oil. Cataracts, inflammation, and retinal toxicity as a result of silicone oil treatment have led to the need for a more effective long-term vitreous substitute. It is essential to treat vitreoretinal diseases concurrently with vitreous substitution. This study aimed to investigate and design the proposed concept of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. An initial study in the selection of polymers for the hydrogel identified a blend of natural and synthetic polymers. Hyaluronic acid with a blend of two poloxamers of differing molecular weights were identified and optimisation allowed for their selection prior to nanoparticle loading and characterisation. Poly(ᴅ,ւ-lactide-co-lycolide) acid nanoparticles encapsulating triamcinolone acetonide were synthesised with a spherical morphology and mean diameter of 153 nm allowing nanoparticle penetration into the retinal layers from the vitreous. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 minutes for the unloaded and nanoparticle-loaded hydrogels respectively. The hydrogels displayed in situ formation properties and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel indicated that a sustained drug release was visible over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 hours for the unloaded hydrogel and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study with a New Zealand White rabbit model displayed minimal toxicity with localised drug release behaviour. In conclusion, the unloaded and nanoparticle-loaded hydrogels developed in this research demonstrate their potential as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.Item Incidences associated with enalapril-induced angioedem in a public regional hospital, Limpopo Province (South Africa)(University of the Witwatersrand, Johannesburg, 2023-10) Muremela, Blessing; Bangalee, Varsha; Padayachee, NeelaveniBackground: The study explored enalapril-induced angioedema reactions at Tshilidzini Regional Hospital (South Africa), from January 2017 to December 2019. The aim was to identify and describe incidences of enalapril- induced angioedema in a public regional hospital, over a three-year period. Materials and Methods A retrospective record review was undertaken at Tshilidzini Hospital. Data were collected from medical files of patients who had experienced enalapril-induced angioedema, between January 2017 to December 2019. Cases were retrieved using the pharmacovigilance ADR database records. Demographic information, medical history, clinical presentations, therapeutic management and outcomes were collected and consolidated on a data collection tool. A Microsoft Excel spreadsheet was used to record the information which was then interpreted utilizing the Statistical Package for Social Sciences (SPSS) version 29. Ethical clearance was acquired from the University of the Witwatersrand Human Research Ethics Committee (Medical). Results: Forty cases (37.3%) of enalapril-induced angioedema were included out of a total of hundred and seven cases reviewed from the Pharmacovigilance ADR database records. The results indicated that demographic details - gender, age and race - affected the incidence of enalapril-induced angioedema. Out of the forty cases, most were female (95%) and between the ages of 50-59 (25%) and 70-79 (25%). Majority of the participants presented with swollen lips (34%) and tongue (24%) as clinical presentations of enalapril- induced angioedema. All participants were counselled and they discontinued enalapril after the incident. Hospitalization occurred in 15% of the participants and death occurred in 5% of the participants. Conclusion: Amongst the cases reviewed, swelling of the lips and tongue was reported to be the most common clinical presentation of enalapril-induced angioedema. The study findings suggest a need for awareness among all healthcare professionals, so that they could identify and treat enalapril-induced angioedema as well as report all incidences. ACE-induced angioedema may be occurring more regularly but may not be known due to misdiagnosis and underreporting by healthcare professionals. This shows that healthcare professionals must constantly be conscious about the significance of reporting enalapril-induced angioedema to improve patients’ safety and treatment outcomes. More reporting of incidences and further research is required for healthcare professionals to become knowledgeable about this life-threatening condition.Item Experience of bowel, bladder and sexual problems and the effectiveness of a health program on quality of life and mental health in people with spinal cord injury in Manguzi(University of the Witwatersrand, Johannesburg, 2023) Tomes, Lauren Meagan; Sonti PilusaBackground: The quality of life of people with spinal cord injury is significantly affected by secondary health conditions such as bowel, bladder, and sexual problems. Literature on the experiences of bowel, bladder, and sexual problems is limited and studies on health interventions in people with SCI are also scarce in South Africa. Aim: To explore the experience of bowel, bladder and sexual problems and the effectiveness of a health program on the quality of life and mental health, as well as to determine the effectiveness of a health program on the quality of life (QoL) and mental health of people with SCI in Manguzi, KwaZulu Natal. Method: This study was a mixed study. An explorative qualitative study design using semi structured interviews was employed. The interviews were transcribed verbatim, and content analysis was conducted to identify the themes and categories. A Quasi-Experimental quantitative design was used. A face-to-face health program on the prevention and management of bowel, bladder, and sexual problems in SCI was conducted for the participants with SCI. WHOQoL Bref and SF-12 questionnaires were administered before and six weeks post-intervention respectively. Paired t-test was used to identify changes in QOL and mental health pre and post intervention. Significance was set at p-value ≤ 0.05. Results: The themes that emerged from the experience of bladder and bowel problems were “no control” and “frustration”. The categories related to the experiences were: types of bladder and bowel problems, managing bladder and bowel problems and the effects on well-being: The main theme for the experience of sexual health problems was “Dissatisfaction”. The categories were: types of sexual health problems, factors influencing sexual activity, the impact of sexual problems, and the management of sexual health problems. The long-term care needs for bowel and bladder problems included access to proper toilets, nappies, medication (Dulcolax), ease of bowel movement, and health information on diet and how to manage their bowel and bladder problems better. The long-term care needs for sexual health problems included the need for medication (sexual enhancement pills) and information on how to manage sexual health problems. There were no statistically significant changes in the pre-test and post-test scores of both the quality of life and mental health.