School of Therapeutic Sciences (ETDs)

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Start date: 2020Subject: search.filters.subject.UCTD

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    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.
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    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, Neelaveni
    Background: 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.
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    A thermo-responsive scleral device for the management of ocular tumours
    (University of the Witwatersrand, Johannesburg, 2024) Abdalla, Yosra Mahjoub Ahmed
    Several ocular diseases that lead to blindness could benefit from effective treatment delivery to the site of action. Efficacy, however, remains restricted due to the multiple static and dynamic barriers present in the eye, despite substantial study into administration procedures and delivery vehicle. Ocular tumours are a broad group of diseases that range from benign to malignant and that occur in different anatomical regions within the eye. Ocular surface tumours are tumours of the conjunctiva of the eye and are therefore readily accessible for drug delivery. The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy that meets individual patient needs, considering their anatomical location. Foremost is the need to develop strategies with high benefit to risk ratios. This is closely followed by the need to develop therapies that improve patient compliance while limiting the need for frequent hospital visits. Thirdly, the high cost of immune-therapeutic agents currently used for the management such as interferon demands sustained release strategies that deliver the same efficacy from much lower doses. Interferon alpha has been used to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This novel study employed a pH responsive/protective nanoparticle embedded into a thermo-responsive hydrogel for site-specific IFN-α2b delivery in the treatment of ocular tumours. Loading the IFN-α2b in a hydrogel isolates the drug from the releasing medium; the inclusion of core-shell nanoparticles increases the loading capacity of the drug and provided pH-responsiveness to the acidic tumour microenvironment, protecting the entrapped drug. As a result, the concentration gradient is reduced and the release pathway extended, furthermore, shielding the IFN-α2b against rapid clearance, and degradation at lower pH of the tumour microenvironment. Nano-embedded thermo-responsive hydrogel were prepared and their physiochemical properties, thermo-responsive behaviour, pH-responsiveness, in vitro and in vivo release and toxicity were evaluated. Fourier transform infrared (FTIR), 1H–nuclear magnetic resonance (1H-NMR), and X-ray powder diffraction (XRPD) analysis confirmed the synthesis of the copolymer. The rheological analysis revealed a sol-gel transition temperature in the range of 26-45°C which was concentration–dependent. A concentration of 20% w/v was selected based on suitability for in vivo application. The surface morphology of the hydrogel was evaluated using scanning electron microscopy (SEM) and porositometric analyser, the SEM images revealed the presence of a mesh-like structure on the surface of the hydrogel. The presence of the pores was further confirm by porositometric analysis. The presence of pores is critical for the diffusion of liquid within the hydrogel, which allows the NP to diffuse out of the hydrogel and release the loaded drug. The formed nanoparticles had particle sizes ranging from 137.1 to 230.6 nm (PDI 0.27–0.137) and zeta potentials ranging from -23.9 to -3.36 mV, demonstrating a pH-responsive controlled release in an acidic medium simulating the tumour environment, with an entrapment efficiency of 89%. The in vitro release studies demonstrated a two-phase release pattern of IFN-α2b and stability of the released IFN-α2b from IFN-α2b nano-embedded PECE hydrogel (IFNPH) for the duration of the study; thus, the IFNPH exhibits pH-protective and temperature-responsive properties. In vitro biocompatibility findings on the human retinal pigment epithelial cell line highlighted that the IFNPH is safe within the tested range of 5000 to 0.625 μg/mL and does not pose any adverse cytotoxic effects. The in vivo studies were performed by administering a single subconjunctival injection of the IFNPH to New Zealand albino rabbits. The pharmacokinetic data revealed that the Cmax of 129.7 pg/mL was reached after 24 hrs (Tmax) in the vitreous humour. The IFNPH delivered biological active IFN-α2b in a sustained manner, compared to eye drops and subconjunctival injection of IFN-α2b solution, thus limiting dosing frequency and enhancing patient compliance. This investigation highlights that the IFNPH is a potential suitable candidate for ocular delivery of IFN-α2b
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    A Framework for Integrating Simulation into the Bachelor of Nursing Science Programme in Eswatini
    (University of the Witwatersrand, Johannesburg, 2024) Shongwe, Sithembile Siphiwe; Armstrong, Susan J.
    Background: Simulation-based education is a required pedagogical method for preparing undergraduate students to become nurses. Its ultimate goal is to develop practice-ready professionals rather than introduce the latest technology into training. In Eswatini, simulation is used; however, no framework guides nursing education institutions on how to integrate simulation into their educational programmes to enhance clinical teaching and learning effectively. Purpose: The aim of this study was to develop a framework for integrating simulation into the Bachelor of Nursing Science programme in Eswatini. Research methods: A mixed methods approach utilising multilevel designs guided the inquiry process. Inferences drawn from the various strands of the mixed methods data were integrated to address the study problem. Phase one was a scoping review conducted to explore best practices of simulation-based education in the educational preparation of undergraduate nursing students locally (sub-Saharan Africa) and internationally. A Joanna Briggs Institute methodological approach guided the research process. Sixty articles were included in this scoping review. Phase two was a survey study conducted to assess the state of simulation use in the educational preparation of Bachelor of Nursing Science Students in Eswatini through auditing four (4) simulation laboratories (Study A) and a survey with (n=46) nurse educators, a census (total) sampling technique was used to select the study participants. Phase three used an iterative process together with simulation experts (n=2) to develop the framework and to identify activities to consider when integrating simulation in Eswatini. These were sourced from tabulated lessons learned or inferences drawn based on the findings of phases 1 and 2. The NLN Jeffries simulation theory guided the development of the framework. In phase four, Eswatini nurse educator experts (n=16) evaluated the framework’s utility in a Delphi study completed in two rounds. Findings: In phase one, best practices principal to simulation-based education emerged. The study findings were inductively developed, resulting in four core codes, namely: (i) lecturer preparation, (ii) student elements, (iii) designing simulations and (iv) innovations in simulation. Ninety-five per cent (95%) of the literature was from international settings compared to 5% from the African context. Phase two: Eswatini nursing education institutions were somewhat ready for simulation; this status was attributed to the lack of trained educators in simulation principles, a lack of financial and resource planning and limited infrastructure and equipment for supporting simulation-based education. Phase three: a framework with the following five domains was developed to guide the process of integrating simulation into the Nursing Education programme in Eswatini: Training or preparation of educators; Integration of simulation into the nursing/midwifery programme; Simulation equipment; Simulation infrastructure; and Student/simulation participants. Phase four: Eswatini nurse educators found the framework relevant and suggested feasible strategies for the Eswatini nursing education context. The strategies included sensitising management to increase simulation-based education support and sourcing funding for procuring equipment and infrastructure development. Conclusion: The framework for integrating simulation into the Bachelor of Nursing Science Programme was designed to allow a step-by-step implementation approach due to existing contextual challenges. The challenges include a lack of trained educators/lecturers on simulation-based education principles, an absence of simulation champions, insufficient equipment, infrastructure inadequacies, fiscal constraints and dwindling management support. The framework can potentially guide the successful integration of effective simulation into Eswatini nursing education institutions. Recommendations: There is a need for the current nurse educators to be trained in the simulation teaching and learning strategy to ensure the effective use of simulation-based education. Nursing education institutions must develop financial plans for funding the required simulation resources (educators’ training, equipment and infrastructure) to ensure the sustainability of simulation-based education
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    Developing strategies for alleviating caregiver burden among informal caregivers of persons with severe mental disorders in Bushbuckridge, Mpumalanga province
    (University of the Witwatersrand, Johannesburg, 2025) Silaule, Olindah Mkhonto; Adams, Fasloen; Nkosi, Nokuthula
    Background: Globally, implementation of deinstitutionalisation led to a shift from institutional to community care of persons with severe mental disorders. This move calls for informal caregivers including families, relatives, friends, or neighbours to become key role players in the care and management of persons with severe mental disorders. The role of informal caregiving results in stress that consequently leads to caregiver burden. In South Africa, limited evidence exists on the extent of the burden experienced by the informal caregivers of persons with severe mental disorders and strategies for supporting these informal caregivers in their role are lacking. This study aimed to explore the burden of care to inform the development of strategies for alleviating burden among informal caregivers of persons with severe mental disorders in Bushbuckridge, Mpumalanga province. Methods: This study used a three-phased mixed methods approach with a multiphase design to facilitate a comprehensive investigation of caregiver burden among informal caregivers and to develop the multilevel strategies for alleviating the burden. Sequential and concurrent methods were combined to collect quantitative and qualitative data across five studies that were conducted to address the study objectives. Results: The established extent of burden revealed that most informal caregivers (44.7%) reported moderate-to-severe levels of objective burden, and 35.9% reported moderate-to-moderate levels of subjective burdens. Objective burden levels were significantly associated with age, gender and residence (p = 0.025, p = 0.034, and p = 0.038, respectively), while subjective burden was significantly associated with daily caregiving (p = 0.012). The exploration of lived experiences revealed that most informal caregivers experienced burden with subsequent impact on their emotional, mental, and physical health. The subsequent burdens were attributed to dealing with the chronic nature of severe mental disorders, role and financial strain, and stigmatisation from family and community. To deal with their caregiving demands informal caregivers expressed reliance on their internal resources, including resilience and resourcefulness. Expressed support needs included access to mental health services, and empowerment and social support from family, government, and religious and community organisations. The findings identified the need for conducting health screenings among the informal caregivers, as well as the need for strategies to support informal caregivers to complement their internal coping resources. The findings of the scoping review revealed that most studies were conducted in Asian countries. Psychoeducation and support group interventions were identified as predominant strategies for alleviating caregiver burden. The service provider’s perspectives revealed that the current state of formal and informal community mental health services is inadequate to meet the needs of the informal caregivers. Conclusion: The study’s findings informed the development of strategies for alleviating caregiver burden among informal caregivers in a low-resourced setting. The complexity of caregiver burden requires multilevel strategies, namely caregiver-driven, health worker-driven, community-based, intersectoral, policy, and legislature strategies across the individual, interpersonal, organisational, community, and policy levels. Caregiver empowerment, family and peer support, development of caregiver-orientated institution and community-based services, task sharing, and task shifting were identified as overriding strategies relevant for alleviating informal caregiver burden in a low- resourced setting
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    Sedentary behaviour in a sample of south african office-based workers
    (University of the Witwatersrand, Johannesburg, 2024) Phaswana, Merling; Gradidge, Philippe
    Background Sedentary behaviour is associated with cardiometabolic diseases amongst office- bound workers, primarily through extended sitting and engaging in low-energy- demanding activities during work hours. Similar to developed countries, South African workplaces are experiencing an increasing prevalence of obesity and related cardiovascular diseases, with sedentary behaviour and physical inactivity being the main contributors. However, there is limited data on the effectiveness of sedentary behaviour strategies in improving South African office-based workers' cardiometabolic risk markers. Objectives This study aims to assess the effectiveness of the height-adjustable sit-to-stand work on cardiovascular parameters in a cohort of office-based workers and to explore the perceptions of these workers about the feasibility and suitability of this intervention to reduce occupational sitting time. Methods A mixed-methods study design was used on office workers from the University of the Witwatersrand and a credit bureau company in South Africa. The qualitative papers used in-depth semi-structured interviews to explore office-based workers' perceptions and experiences using sit-to-stand workstations. The interview audio was recorded audio using Microsoft Teams (version 11, Microsoft Way, United States) and Phillips (DVT4010 Voice Tracer, Vienna, Austria). All transcripts were checked against the recordings to verify accuracy and credibility, and grammatical editing was adopted where necessary. For quantitative measures, participants were randomised into an intervention or control group to collect measures at baseline and 12 weeks in a cohort of South African desk-based workers. These biomarkers include anthropometry, sedentary behaviour and physical activity, sleep duration, blood pressure, glucose, glycated haemoglobin (HbA1c) and lipid profile. The cross- sectional paper quantified sedentary behaviour, overall physical activity, and the association with select cardiometabolic risk factors. The randomised control trial evaluated the short-term effects of height-adjustable sit-to-stand workstations on cardiometabolic risk markers. Descriptive and inferential statistics were used to describe and compare baseline and follow-up changes in the intervention. Results The height-adjustable sit-to-stand workstation was deemed feasible and well-accepted by our participants. Participants expressed that it motivated them to stand up and work and effectively alleviated discomfort associated with prolonged sitting. Most (68.0%) of the study participants were women, with a mean age of 40.2 ± 9.3 years. Our participants spend an average of 8 to 10 hours in sedentary behaviour. Both systolic (β: -0.234, p = 0.037 mmHg) and diastolic blood pressure (β: -0.250, p <0.001 mmHg) were inversely associated with accelerometery-measured light physical activity. However, there was no relationship between accelerometery- measured sedentary behaviour and cardiometabolic risk factors after analysis. The 12-week randomised control trial showed small improvements with blood pressure - 0.26 (d =1.10 mmHg) and Light physical activity -0.26 (d=3.57 min/day). We observed trivial effects, with most of our cardiometabolic outcomes including body mass index (BMI) -0.11 (d=1.07 kg.m2). Most participants withdrew early from workplace intervention due to the design and functionality of the height-adjustable sit-to-stand workstation. Conclusions This study adds to the limited evidence on environmental workstation modifications for reducing sedentary behaviour. Our findings show that South African office workers spend a substantial amount of time sitting during work hours and support the need for public health workplace interventions to mitigate the potential health risks associated with such sedentary behaviour. This study confirms that short-term height-adjustable sit-stand interventions effectively reduce workplace sitting time and promise to improve cardiometabolic health outcomes, suggesting that clinically significant effects might be noticed in long-term interventions. Therefore, future studies should consider individual preferences, workstation design, functionality, education, and motivation to ensure successful implementation, utilization, and compliance with sit-to-stand workstations
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    Contextually responsive support and development strategies for generalist occupational therapists delivering hand-injury care in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Stormbroek, Kirsty van
    Hand injuries are common in South Africa and safe and effective hand therapy is critical to appropriate care. By necessity, this care is delivered by non-specialist occupational therapists working in challenging settings, despite hand therapy commonly being considered a specialist area of practice. Safe and competent management of hand injuries by therapists is crucial for achieving a return to full participation in daily life. It is therefore necessary to describe what the support and development needs of these non-specialist occupational therapists are, and how these needs can be met effectively and sustainably. This project aimed to describe how the support and development needs of generalist occupational therapists delivering hand-injury care within the South African public health sector can be met in a contextually responsive manner. A multi-method approach was chosen, with a separate study design employed for each of the three studies. The policy context is an essential aspect of contextually responsive intervention; therefore the first study aimed to develop policy-based principles for hand rehabilitation services delivered by occupational therapists in South Africa. A descriptive qualitative approach was employed, and framework analysis, as a content analysis method, was undertaken. Local and international policies (n=29) were included in the analysis, and eighteen principles were generated that articulate the goal of rehabilitation (principle 1), prescribe the nature of rehabilitation (principles 2-6), and outline the enablers of rehabilitation (principles 8-18). These generic principles are applied to the practice of hand-injury care in South Africa. Contextually responsive intervention responds to the needs and experiences of service providers. Study two (which consisted of Study 2A and Study 2B) used a qualitative instrumental case-study design to describe generalist occupational therapists’ experience of delivering hand –injury care in order to identify their support and development needs and to describe how these can be met in a contextually responsive manner. Study 2A undertook this aim with a group of novice occupational therapists (n=9) completing a compulsory year of state service directly after graduation and made use of an online community of practice for data collection. Study 2B used site visits and in-depth interviews to collect data from fully registered occupational therapists (n=6) working in diverse public health settings in South Africa. Reflexive thematic analysis was used to generate rich themes, which informed recommendations for the support and development of therapists extrapolated from both studies. Study 3 sought to combine the evidence produced by Studies 1 and 2 with the diverse perspectives of service users, other service providers, local and international scholars, educators and professional bodies. The aim of the study was to identify capacity strengthening strategies for generalist occupational therapists responsible for delivering hand-injury care in the South African Public Sector. A hybrid consensus development conference was used to facilitate the presentation of relevant evidence. A stakeholder panel (n=14) followed a nominal group guided by a skilled facilitator. The panel generated and ranked ideas, which were developed into ten prioritized areas for action. Extensive ideas within each of these ten areas were recorded. These areas formed the foundation of the guidelines developed by the project. A pragmatist approach to evidence synthesis was used in the final stage of the project to systematically generate guidelines for the support and development of generalist occupational therapists delivering hand-injury care in South Africa. Eleven guidelines were developed, with the first guideline addressing the need to align hand-injury care services with professional values (1), including the mandate to improve participation and inclusion. Five guidelines address generalist occupational therapists’ direct need for support and supervision (2), resources (3), core competencies for hand-injury (4), the creation of a learning stratosphere to support this (5), as well as the imperative to nurture resilience (6). The final five guidelines address factors that are indirectly essential to therapists capacity to deliver hand-injury care: the need to strategize and operationalize (7), strengthen health systems (8), build stronger communities (9), strengthen human resourcing (10), and strengthen the medical and surgical management of hand injuries and conditions (11). Finally, key implications for practice, learning and development, leadership and management, policy, and research are proposed
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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
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    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
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    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