Electronic Theses and Dissertations (Masters)

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An evaluation of the effects of metal complexes on lung cancer cell lines
(University of the Witwatersrand, Johannesburg, 2024) Mangena, Zanele; Harmse, Leonie
Lung cancer remains a predominant global health concern, accounting for approximately 18% of cancer-related deaths. In South Africa, it imposes a significant burden due to high rates of late-stage diagnoses, resulting in compromised survival outcomes. Despite available targeted therapies, treatment efficacy is hindered by drug resistance and severe side effects, highlighting the need for alternative agents. This study aimed to investigate a series of complexes in an in vitro setting to assess their potential as alternative agents for lung cancer therapy. This study evaluated 20 compounds, encompassing novel epidermal growth factor receptor kinase inhibitors, AD and OM copper complexes, and copper imidazo[1,2-a]pyridines in vitro. Their cytotoxicity against A549 lung cancer cells was determined by the MTT assay, and the most potent compounds were chosen for further investigation. The mode of cell death for these compounds was assessed through cell morphology, Annexin-V, caspase-3/7, mitochondrial membrane potential, and caspase-8 assays. The capacity of the active compounds to induce reactive oxygen species was measured through the CellROX™ Deep Red assay kit. Immunohistochemistry techniques were employed to analyze the expression and distribution of p21 and p53. Furthermore, changes in the expression levels of apoptosis-related proteins post-treatment with the most effective compound were assessed using the Proteome Profiler Human Apoptosis Array kit. Four copper-imidazo[1,2-a]pyridines, namely JD35, JD46, JD47, and JD88, were the most active, with IC50 values in A549 cells between 1.67 μM and 3.37 μM. These compounds induced apoptotic cell death, characterized by chromatin condensation, fragmented nuclei, Annexin-V binding, and activation of caspase-3/7. They also caused a decline in mitochondrial membrane potential, indicating activation of the intrinsic apoptotic pathway, while also inducing late caspase-8 activation. Furthermore, these compounds enhanced reactive oxygen species and upregulated nuclear p21 and p53 expression, suggesting DNA damage leading to apoptosis initiation. Analysis of apoptotic proteome array data showed that JD88 treatment significantly upregulated the wild-type tumour suppressor protein, p53 in A549 cells while significantly downregulating anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP, cIAP-2, survivin, and heat shock proteins (HSP27, HSP60, and HSP70). These findings suggest a reduced threshold for apoptosis and a potential promotion of apoptosis, possibly through p53 activation. Copper-imidazo[1,2-a]pyridines have demonstrated effectiveness in inducing apoptotic cell death in A549 cells, impacting both intrinsic and extrinsic apoptotic pathways and influencing critical proteins for cellular survival and apoptosis. This study contributes to a better comprehension of apoptotic mechanisms in A549 cells, stimulating inquiries into the activation of extrinsic apoptotic pathways especially by copper complexes. These findings support further pre-clinical evaluations of copper-imidazo[1,2-a]pyridines, including efficacy assessments in lung cancer animal models, toxicity studies, and determination of pharmacokinetic properties
The wound healing effect of exosomes derived from Lobostemon fruticosus
(University of the Witwatersrand, Johannesburg, 2024) Rajcoomar, Yashmika; Somandi, Khonzisizwe
Exosomes are increasingly being researched and recognized as a novel mode of intercellular communication which can potentially play a significant role in many cellular processes, including immune responses, signal transductions and antigen presentation. Exosomes are membrane bound nanovesicles produced by both mammalian and plant cells. Developing research is mainly focused on their ability to act as a drug delivery vehicle. Other research interests around exosomes are their therapeutic effects for many common diseases including cancer and chronic inflammation. Plant-derived exosomes have emerged as potential candidates for many clinical and therapeutic applications. The aim of this project was to isolate exosomes derived from Lobostemon fruticosus leaves and to investigate the wound healing potential from this plant species. The plant-derived exosomes were isolated by ultracentrifugation and were characterised by means of scanning electron microscopy (SEM), ZetaSizer, Energy-dispersive Xray spectroscopy and the Pierce™ BCA Protein Assay Kit. The wound healing potential was assessed by In vitro scratch assay using human keratinocytes (HaCaT). The exosomes displayed a round, spherical shape and had diameters ranging from 41 to 67 nm – falling within range of nano-sized exosomes. The exosomes had a mean particle size of 166.2 d.nm. Chemical analysis of the samples using energy dispersive spectroscopy revealed the presence of carbon, oxygen, potassium, chloride, gold, palladium and sodium. The protein quantification results revealed the exosomes were rich in proteins. The cell viability results, using various concentrations of Lobostemon fruticosus exosomes, revealed non-cytotoxicity on HaCaT cells. The In vitro scratch assay demonstrated that the exosomes enhanced the migration ability of HaCaT cells in a time dependent manner. The findings suggest and reveal that exosomes derived from Lobostemon fruticosus could accelerate the healing process and can be employed as a future drug delivery platform. Further research is required to establish the exact mechanism of action of the healing potential of this plant specie's constituents. Overall results suggest that exosomes derived from Lobostemon fruticosus are promising as a potential agent for skin regeneration
A Survey of the Delivery of Clinical Services in Independent Community Pharmacies in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Ismail, Tahir; Khan, Razeeya
Introduction The community pharmacists' role has evolved from traditional medicine dispensing to patient- centred service provision. Community pharmacy clinical service provision is an integral component of public health intervention and contributes to universal health coverage. The extent of clinical services offered in community pharmacies in South Africa has yet to be studied. Assessing the extent of clinical service provision in community pharmacies provides insight into the willingness of South African pharmacists to deliver these services. Aim This study aimed to identify the clinical services offered in independent community pharmacies in South Africa and the extent to which these services are available. In addition, the willingness to provide clinical services and the barriers to service provision were also assessed. Methodology A quantitative, cross-sectional exploratory research design was used. Responsible pharmacists of the Independent Community Pharmacy Association member pharmacies were invited to participate in an anonymous electronic REDCap© survey from September 2022 to March 2023. Data was exported to Microsoft Excel® and analysed using descriptive statistics. Results Of the 156 responses received, most were located in urban areas (70%) and based in Gauteng (34.8%). The most frequently delivered clinical services were diabetes screening (88.9%), blood pressure measurement (80.8%) and Influenza vaccination (78.9%). Clinical services were primarily delivered by a pharmacist (39.5%), with most pharmacists (94.7%) willing to implement additional clinical services. However, lack of time and remunerations for services (57.1%) were identified as barriers to implementation. Most pharmacists also expressed an interest in additional training to improve clinical skills. Conclusion This study revealed the extent of clinical service delivery in independent community pharmacies in South Africa. Although community pharmacists are willing to provide clinical services, significant barriers limit these interventions. This study also informs service providers of training programmes that need to be developed to meet the specific needs of independent community pharmacists. Further research must address how the barriers identified may be mitigated to facilitate clinical service implementation in community pharmacies
Brain concentrations and the neurochemical effects of passively administered fluoxetine in Flinders sensitive line rat offspring
(University of the Witwatersrand, Johannesburg, 2023) Steyn, Stephanus Frederik
Background: Globally, 36 % of women who have recently given birth, experience symptoms of depression and anxiety. Effective antidepressant treatments are limited, with fluoxetine being a popular treatment option. Fluoxetine is expressed in the breast milk, yet it is unclear to what extent fluoxetine, or its active metabolite, norfluoxetine, reaches the brain of the developing child and what the effects of such exposure on the related neurobiological processes would be. Due to ethical considerations and practical restrictions, clinical investigations into the neurodevelopmental effects of passively administered antidepressants (via the breast milk) are problematic. Therefore, pre-clinical investigations into this topic are not only important but clinically relevant. Aims & objectives: We aimed to quantify the concentration of passively administered, i.e., via the breast milk during nursing, fluoxetine, and its active metabolite, norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) rats (an established rodent model of depression). We further aimed to establish if said exposure would associate with changes in whole-brain serotonergic function and redox status. Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring (n = 16 per exposure group; 1:1 male: female) were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and reduced and oxidized glutathione (GSH and GSSG) concentrations were measured via liquid chromatography/mass spectrometry (LC-MS). Results: Fluoxetine, was undetectable in the brain of FSL offspring, while norfluoxetine concentrations, averaged 41.28 ± 6.47 ng/g. Neither serotonin, nor its metabolite (5-HIAA), was affected by passively administered fluoxetine in the juvenile brain. In terms of redox status, pups exposed to fluoxetine presented with a compromised antioxidant defence, as evinced by a lower GSH/GSSG ratio. Discussion and conclusion: Although fluoxetine and norfluoxetine concentrations have been measured in breast milk and infant plasma, to the best of our knowledge, it has not been quantified in the juvenile brain until now. Our results are in line with clinical findings, suggesting the infant norfluoxetine/fluoxetine ratio to be elevated, probably because of the prolonged half-life of norfluoxetine. Although only norfluoxetine was detected, this did not influence the central serotonin concentrations of offspring. However, it associated with increased oxidative stress, of which the pathophysiological significance remains to be established. Taken together, our findings confirm that passively administered fluoxetine does reach the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use during the postpartum period
Essential oil compounds in combination with conventional antibiotics for dermatology
(University of the Witwatersrand, Johannesburg, 2024) Simbu, Shivar Bram; Van Vuuren, Sandy
Skin and soft tissue infections represent a heterogeneous array of clinical entities with varying severity, causative pathogens, and rates of progression. The slow development and overuse of antimicrobial agents have perpetuated the spread and severity of antimicrobial resistance. Natural products such as essential oils and their compounds are often investigated for their pharmacological properties, with particular interest in their antimicrobial properties. This study aimed to investigate the effects of combining six essential oil compounds (α-pinene, γ-terpinene, ±linalool, eugenol, carvacrol, and cinnamaldehyde) with eight conventional antimicrobials (amoxicillin, ciprofloxacin, erythromycin, gentamicin, meropenem, tetracycline, miconazole, and nystatin) against six commonly encountered skin pathogens (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ATCC 19606, Cutibacterium acnes ATCC 11827, and Candida albicans ATCC 10231) to elucidate the interactive profiles, toxicity, and anti-inflammatory properties. The antimicrobial analysis involved determining the minimum inhibitory concentrations (MIC) of the conventional antimicrobials and essential oil compounds, singularly and in combination, using the broth microdilution assay. The sum of the fractional inhibitory concentrations (ΣFICs) was calculated to investigate the interactive profile of the combinations. Synergistic interactions were further analysed at varying ratios and depicted on isobolograms. Eight synergistic interactions were identified, with seven against Gram-positive bacteria (ΣFIC 0.07– 0.42) and one against P. aeruginosa (ΣFIC 0.32). In addition, it was demonstrated that when in combination, the selected combinations resulted in reduced toxicity (Brine-shrimp lethality assay). The combination of amoxicillin and eugenol demonstrated the lowest toxicity (LC50 = 1081 μg/mL) and the highest selectivity index (14.41) when in a (70:30) ratio with the antibiotic in the higher ratio. Based on the synergistic results from the antimicrobial analysis, a selection of essential oil compounds with conventional antimicrobials were assessed for cytotoxicity and anti- inflammatory properties. The cytotoxicity properties were determined using the MTT assay on HaCAT keratinocytes. The anti-inflammatory properties were determined using lipopolysaccharide (LPS) activated RAW 264.7 macrophages, and the reduction in nitrate (NO) production was measured. Cinnamaldehyde demonstrated the highest cytotoxicity (IC50 = 28.63 μg/mL, p < 0.05) and the greatest reduction (77.44%) in nitrite production, which was also concentration dependent. The combination of ciprofloxacin and cinnamaldehyde demonstrated the lowest cytotoxicity (88.42% ± 3.72 cell viability; combination index of 0.12) and the highest reduction in nitrite production (77.42%; ΣFa = 0.44). Further investigations on the interactive properties of ibuprofen were undertaken. The antimicrobial, cytotoxicity, and anti-inflammatory properties of ibuprofen were analysed singularly and in combination with all essential oil compounds and conventional antimicrobials against reference and clinical skin pathogens. For the MIC results, four synergistic interactions were identified between ibuprofen and conventional antimicrobials (ΣFIC 0.33 - 0.50). For the cytotoxicity (MTT assay), none of the combinations demonstrated a cytotoxic effect (cell viability of 93.6-100%) and significant reduction on nitric oxide production. Additionally, higher order combinations involving the synergistic combinations were investigated with the inclusion of the essential oil compounds. Three synergistic interactions were identified (One against C. acnes and two against A. baumannii). The triple combinations were slightly cytotoxic (cell viability of 77.59 - 90.44%; combination index of 0.95 -1.10) on the HaCAT cell line and did not reduce nitric oxide production. Based on the overall results from this study, combinations of essential oil compounds and some conventional antimicrobials demonstrate promising therapeutic approaches to attenuate antimicrobial resistance. These results demonstrated that combinations that comprise cinnamaldehyde have noteworthy antimicrobial and anti-inflammatory properties which may warrant further investigation. Combining ibuprofen with conventional antimicrobials and essential oil compounds may also offer potential advantages in managing resistant infections through direct and indirect antimicrobial mechanisms.
The development of a questionnaire to assess training and match demand in adolescent cricketers
(University of the Witwatersrand, Johannesburg, 2024) Grobler, Nico; Olivier, Benita
Background: Recording training and match demand in adolescent sports is essential in preventing overtraining and injuries while ensuring optimal performance and well-being. The study aimed to develop a valid and reliable questionnaire that would measure the training and match the demands of adolescent cricketers. Methods: In Study 1, the content validity of the training and match demand questionnaire was measured using the content validity index, while the reliability was measured using Kendall’s coefficient of concordance (Kendall’ W). In Study 2, a pilot study was performed using the questionnaire developed in Study 1. Daily training and match demand for all activities done in cricket (i.e., bowling, batting, fielding, strength and conditioning) and any other sport or activities were recorded in 17 adolescent cricketers. Acute:Chronic workload ratios (ACWR) were determined for all activities. Results: The developed questionnaire was deemed valid (I-CVI score of 0.83) and reliable (Kendall’s W score of 0.63). Over the 7-week period, some spikes in the acute training and match demand were observed. However, the overall ACWR was within the norms (0.8-1.3). Bowling reported an average ACWR of 0.91; other sports reported the highest average of 1.08, while the average for all activities combined was 0.92. Conclusion: The questionnaire measured the training and match demand of the cricketer over time and can be used as a valuable tool in future research and practice in adolescent cricket
The Effectiveness of a Multidisciplinary, Protocol-based Approach to Patients of Different Age Groups with Lower Back Pain in Bloemfontein, Gqeberha, Polokwane, and Johannesburg
(University of the Witwatersrand, Johannesburg, 2024) Bennett, Matthew Terence; Neophytou, Natalia
Introduction: Lower back pain is a chronic worldwide condition experienced by many individuals. In Africa specifically, it has been reported that the average lifetime prevalence of lower back pain is 36% within adolescence, and 62% within adults. Although exercise interventions exist there are many gaps in terms of efficacy across age groups; a lack of multidisciplinary approach; as well as, a lack of a reproducible standardised protocol. Furthermore, there is a lack of interventions focusing on pain scale improvements and ROM simultaneously. In the early 90’s, a Documentation Based Care (DBC) multidisciplinary protocol was developed in Finland which aimed to bridge this gap by reducing low back pain, Subsequently it was adapted, and implemented in South Africa, however no information exists as to whether it has been effective in the South African context in terms of improving back pain, as well as improving ROM in individuals. Objectives: To determine whether the current South African adaptation of the Finnish DBC lower back protocol is effective in reducing pain levels and improving range of motion over multiple age groups. Methods: A retrospective analysis of 1499 data sets, of individuals who participated in a standardised 6-week lower back intervention, using the adapted version of the Finnish DBC lower back programme was conducted. Data was extracted from a collated database from 5 Biokinetics practices using the adapted DBC protocol. Data included: age, pre-post intervention visual analogue scale (VAS) pain scale data and lumbar thoracic ROM including flexion, extension, lateral flexion and rotation. Descriptive statistics were used for the demographic data, student T- tests were used for pre-post ROM and pain scale data. The use of Statistical version 14.0 was used for the analysis and p value of <0.05 was deemed significant. Results: Pain: This study found that for 91.9% of individuals participating in the intervention (n=1377), there was a reduction in lower back pain measured on the VAS pain scale, while for 5.2% (n=78) there was no change in pain, and for only 2.9% there was an increase in pain (n=44). ROM: All age groups were found to have increase range of motion in all movements from pre- intervention to post-intervention. Conclusion: The South African adaptation of the DBC protocol over the last 3 years has been successful in reducing pain and increasing ROM in all age group categories pre-intervention to post-intervention
Investigating the correlation between demographic and comorbidity profiles with chemotherapeutic toxicity experiences in early-stage breast cancer patients in a private medical oncology practice in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Minns, Chantelle Pienaar; Booth, Zelna; Shaikh, Rubina; Padayachee, Neelaveni
Background: An estimated 24 million people will be diagnosed with cancer globally by 2050, with approximately 16.8 million expected to be residing in low- and middle-income countries. Breast cancer is one of the most prevalent types of cancer diagnosed in women worldwide and 23% of all diagnosed malignancies are attributed to breast cancer. The prevalence of chemotherapy-induced adverse drug reactions ranges globally between a vast 60 - 80% amongst patients, negatively impacting overall treatment outcomes. Aim of study: This study aimed to determine a potential correlation between demographic profiles and the presence of pre-existing comorbidities on the chemotherapy-related adverse effects experienced by patients with stage 0-III breast cancer at a private oncology centre in Gauteng. Furthermore, interventions applied by the oncologists to mitigate the adverse effects were investigated and reported adverse events were compared to the WHO VigiAccess Adverse Drug Reaction database. Methods: A quantitative, retrospective cohort analysis of patient charts from January 2018 to December 2019 at the private Sandton Oncology Centre was undertaken. The study sample size was 54 participants. Patient files were randomly selected. Demographic and comorbidity profiles, as well as the staging (0 – III) data were retrieved from patient medical charts, in accordance with the study inclusion criteria. Furthermore, the chemotherapeutic toxicities, experienced by patients, treated with a particular chemotherapeutic agent were reviewed. Interventions employed to alleviate toxicity were further recorded for data analysis (dose modifications, dose reductions, and premature discontinuation of oncology treatment). Descriptive statistics was analysed using pivot tables in Microsoft Excel. Inferential statistics was analysed with Stata software version 18. Ethical clearance was obtained before patient files were accessed and confidentiality of patient information was maintained throughout the study. Results: Most patients included in the study were white (57.4%), aged 50 – 59 years (29.6%), and diagnosed with stage II breast cancer (48.2%). Most of the patients had tumours which were oestrogen (66.7%) and progesterone positive (57.4%) and Human Epidermal Growth Factor Receptor 2 (HER2) negative (48.2%). The majority of patients, irrespective of ethnicity, received a combination of an anthracycline and cyclophosphamide followed by a taxane (51.8%). The most documented comorbidities were hypertension, obesity, dyslipidaemia, and diabetes. Of those patients reporting adverse effects, 77.8% reported adverse effects after the first cycle of chemotherapy. The chemotherapy-related adverse effects show similarity to the adverse effects reported on the World Health Organisation’s VigiAccess Adverse Drug Reaction database, particularly adverse effects of the digestive, integumentary, haematological and lymphatic systems. Conclusions: The number of comorbidities present increases with age. White patients with more comorbidities experienced more chemotherapy-related adverse effects. The majority of the patients for which dose reductions were implemented, experienced five or more adverse effects during their treatment. More than half of the termination of treatment cases were preceded by a dose reduction. No statistically significant correlation was found between any of the ethnic groups or age categories and the total number of adverse effects experienced. A statistically significant correlation was found between other comorbidities and the number of psychiatric adverse effects (p=0.014). Reported infections were significantly higher in patients with hypertension (p=0.043) and lymphatic system adverse effects were higher in patients with dyslipidaemia (p=0.017)
Exercise dosages for the management of generalized anxiety disorder: A scoping review
(University of the Witwatersrand, Johannesburg, 2024) Leander, Natalie; Olivier, Benita
Objective: This review was conducted to map the extent of evidence relating to the dosage of exercise for anxiolytic effect, in youth and adolescents with Generalized Anxiety Disorder (GAD). Introduction: Exercise is known for its benefit to people living with depression and anxiety in adult populations. Less is known about the differences in exercise prescriptions used for the management of anxiety subtypes in younger populations. The rationale for this topic in adolescents and youths, living with GAD was to ascertain the extent to which this cohort has been studied regarding the use of exercise in the treatment of anxiety and which dosages were used. Inclusion criteria: All studies with participants aged 10-24 years of age with a GAD diagnosis, were considered, where exercise was used as part of the management of their anxiety. No restrictions were placed on study types. A scoping review was performed using the JBI methodology. Databases searched included Pubmed, PEDro, Cochrane database of systematic reviews and Cinahl Ultimate along with grey literature databases. No time restrictions were applied, and all types of research articles were considered. The charted data was tabulated using a modified JBI data extraction instrument. The initial result of 728 results was reduced to four studies that met with inclusion criteria. The final four studies had populations in the upper range of between 18 to 24 only. No applicable data was found in the 10 to 17-year age range. The exercise types used in these four studies were treadmill running, Pilates, lower limb strengthening and dynamic cycling. Two studies incorporated a single bout of vigorous treadmill running for 30 minutes. One study did a single bout of beginner Pilates for 30 minutes and the last study used lower limb strengthening and dynamic cycling biweekly for six weeks. The literature on exercise dosage for the management of GAD in adolescents and youth is severely limited. Data on exercise for specific subtypes of anxiety in adolescents and youth seems to be limited in general as well. This is an important area for research as anxiety starts in early childhood and GAD in particular has a peak age of onset of 15 years. It seems feasible to try and approach anxiety in youth and adolescents with non-invasive therapies such as exercise but there is a definite gap in the literature regarding its use in managing GAD
Running-related injuries and risk factors among runners in Soweto township clubs, Johannesburg
(University of the Witwatersrand, Johannesburg, 2024) Masilana, Masocha Vusi; Kunene, Siyabonga
The surge in running's popularity globally has brought about an increase in running-related injuries (RRIs), particularly prevalent in sub-Saharan Africa, including South Africa's urban township of Soweto, where physical inactivity and non-communicable diseases pose significant public health challenges. This necessitates targeted research on RRIs in the region to understand the specific external and internal risk factors. The study aimed to determine the prevalence and risk factors for RRIs among recreational and professional runners in Soweto, Johannesburg. The study utilised a cross-sectional design to determine the prevalence and risk factors associated with RRIs, allowing for an efficient one-time data collection from a large sample. Runners from Soweto township was included in the study. A data collection tool in the form of a self-administered questionnaire was employed, utilising the RedCap online platform for administration. A structured analysis plan was implemented using STATA software, with an additional data processing phase in Excel to enhance the clarity and readability of results, including the customisation of charts and graphs to communicate the findings effectively. Descriptive and inferential statistics were obtained. Demographic analysis revealed a higher prevalence of female runners at the beginner level (55%, n=17), with a significant association between advancing age and injury risk. Among professional runners, the distance covered emerged as a significant risk factor, particularly for medium and long-distance runners (odds=2.07, p=0.05 and odd = 3.01, p =0.03, respectively). The frequency of training sessions demonstrated varying degrees of risk for both novice and professional runners. Additionally, terrain-specific analysis highlighted the elevated risk of injuries for beginners on varied terrain relative to professional runners. Statistical findings included significant odds ratios for female runners (odds = 0.75, p =0.05), age over 25 among beginners (odds = 1.56, p = 0.031), medium distance running among professionals (odds = 2.07, p = 0.050), and varied terrain among beginners (odds = 1.76, p = 0.006). This study provides critical insights for tailoring injury prevention and management techniques, particularly for runners of various levels. It emphasises the importance of individualised treatments by stressing nuanced damage patterns between beginners and professionals. The heightened risk on varied terrain for beginners and the unique implications of sports engagement on injury risk for professionals are noteworthy findings. These findings guide tailored prevention strategies, recognising the varied character of RRIs and addressing unique needs at various career stages, with possible policy and future research implications.

Electronic Theses and Dissertations (Masters)

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