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Continuous flow synthesis of lenalidomide key intermediate
Full text linkContinuous flow synthesis has emerged as an innovative technology and is progressively becoming popular in the pharmaceutical industry. The flow technology offers accelerated, safer automized chemical reactions in high throughput and purity. The motive of this research was to exploit the continuous flow systems, to develop an effective synthetic method for the synthesis of 3-(4-nitro-1-oxoisoindolin-2-yl) piperidine-2,6-dione, a key intermediate towards the synthesis of lenalidomide, an anti-cancer drug. Additionally, to explore the effect of flow parameters (residence time, temperature, mole equivalent and type of solvent) on the conversion and selectivity of the reactions. Herein, we detail a comprehensive background on multiple myeloma cancer (MM), introduce lenalidomide (anti-cancer drug) and its analogues, and outline the issue of drug supply chains in Africa. Additionally, a brief introduction on the game-changer continuous flow technology, detailing its benefits and different reactors based on their properties and functions. A four-step synthetic route was established in batch and translated to continuous flow system. The optimized continuous flow route towards the synthesis of the 3-(4-nitro-1-oxoisoindolin-2-yl) piperidine-2,6-dione, a key intermediate afforded 96 % yield and 98 % HPLC purity at 100 ºC in 4 minutes residence time using THF solvent in an OMNIFIT column reactor.Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 202
Anti-diabetic effects of green synthesized cerium oxide nanoparticles (CeO2-NPs) using oleanolic acid in liver and skeletal muscle cell lines
Full text linkDiabetes mellitus, a global chronic disease, has, during the past decades, continued to rise. In recent years, even though the increment rate has slowed down, it remains a highly important priority for public health. Nanotechnology could greatly enhance the quality of life of individuals diagnosed with diabetes through its applications in management and treatment, including innovative blood sugar monitoring, targeted controlled insulin release, regenerative medicine, and enhanced wound healing. Recent developments in diabetes treatment using nanotechnology have attracted increasing interest due to their potential to improve patient outcomes. Accordingly, the current research aimed to investigate the anti-hyperglycaemic potential of green-manufactured CeO2 nanoparticles using oleanolic acid derived from Syzygium aromaticum methanolic cloves extract. Material and methods: In this study, CeO2 NPs were synthesized using pure oleanolic acid (Oleanolic Acid capped cerium oxide nanoparticles, OA-CeO2 NPs) and methanol clove extracts (Syzygium aromaticum methanolic crude cloves extract capped Cerium oxide nanoparticles, CCE-CeO2 NPs), and the physicochemical features were evaluated by spectrometry, electron microscopy and dynamic light scattering. The effects of CeO2 NPs on cell viability were determined using an MTT assay. The hypoglycaemic potential of CeO2 NPs was investigated using the glucose colourimetric assay on the human liver cancer cell line (HepG2) and mouse myoblast cell line (C2C12). The cells were treated for 0, 24, 48 and 72 hours with different concentrations of CeO2 NPs (1, 25, 50 and 100μg/mL), oleanolic acid (160μg/mL) and cloves crude extracts (160μg/ml) where metformin (160μg/mL) acted as a positive control. Results and Discussion: The average size range of synthesized CeO2 NPs diameter was 173±56 nm, with polydispersity index values of 0.28 and 0.20. The zeta potential of CeO2 NPs varied between - 22.7 mV to -36.8 mV. The CeO2 NPs showed no cytotoxic effects on both the cell lines as the results revealed no significant statistical variations between the treated cells and untreated cells following the MTT assay. Our data demonstrated a pronounced anti-hyperglycaemic effect, with glucose levels significantly decreasing from 21.60 ± 0.10 mmol/L to 5.0 ± 0.84 mmol/L in liver cells treated with OA-CeO2 NPs at the lowest dose (1 μg/mL). Conversely, the highest dose (100 μg/mL) of the CCE-CeO2 NPs significantly decreased glucose concentrations from 21.60 ± 0.10 to 4.90 ± 0.74 mmol/L in the HepG2 cell line. In the mouse myoblast cell line (C2C12), glucose concentrations declined to normal physiological levels of 4.5 -5 mmol/L following treatment at doses of 50 and 100 μg/mL of the OA-CeO2 NPs and at 25 μg/mL dose of the CCE-CeO2 NPs which reveals improved glucose utilization by the cells, as a result of the improved drug bioavailability, permeability, and solubility. The glycogen assay showed that C2C12 and HepG2 cells had an increase in glycogen concentration after administration of CeO2 NPs within the period of 72 hours compared to the negative control which correlate with the increase of glucose uptake by the cells. The green synthesized CeO2 NPs using oleanolic acid lowers glucose concentration in both muscle and liver cell lines without toxic effects on the cells. Furthermore, the CeO2 NPs restored the depleted glycogen following glucose utilization by the cells. These findings may lead to the development of CeO2 NPs synthesized using oleanolic acid for the management of diabetes mellitus with improved pharmaceutical qualities.Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 202
Effects of oxytocin treatment and calcium inhibition on hydrogen peroxide-induced oxidative changes in c8-b4 microglial cells
Full text linkOxidative stress is implicated in the aetiology of several diseases as it leads to the destruction of cellular structures. In the central nervous system (CNS), oxidative stress results in neurodegeneration and the development of diseases such as Alzheimer’s disease and Parkinson’s disease. Microglia play a crucial role in maintaining brain homeostasis. Of importance is the intracellular calcium regulatory activities that reinforce both microglia phenotype and functions, which are implicated in several neurodevelopmental disorders. Despite extensive literature about the neuroprotective role of oxytocin, its impact on microglial activity has not been studied and it remains unclear whether the underpinned molecular mechanism of action is calcium-dependent or not. Thus, this study aimed to study the effects of inhibited calcium channel and oxytocin treatment on microglial response to hydrogen peroxide (H2O2)- oxidative stress. Initially, the C8-B4 microglial cells were evaluated as valid constructs for the calcium inhibition and oxidative stress models. For the calcium inhibition model, the calcium channels were inhibited by treating the cells with 12.5 μM and 25 μM nickel chloride (NiCl2) for 24 and 48 hours. The intracellular calcium levels were measured using a calcium detection assay and the viability of the cells was determined using 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. For the oxidative stress model, the cells were treated with H2O2 for 1-4 hours to induce oxidative stress. The viability of the cells was measured, and markers of oxidative stress (malondialdehyde (MDA), glutathione (GSH), interleukin (IL) -6) were quantified. Once the treatments were validated, the cells were treated with 12.5 μM NiCl2 and 1000 nM oxytocin for 24 hours, followed by 0.5 mM H2O2 for 1 hour. The cell viability was measured, and markers of oxidative stress were quantified (IL-6, MDA, superoxide dismutase (SOD)). The study found that NiCl2 inhibited calcium channels in C8-B4 cells, thereby disrupting calcium homeostasis. There was a decrease in the levels of intracellular calcium levels and cell viability following treatment with NICl2. H2O2 induced oxidative stress and inflammation in the cells. This was demonstrated by increase in SOD and MDA activity, as well as a decrease in the levels of GSH. Inflammation was confirmed xii by an increase in the levels of IL-6. Disrupted calcium signalling exacerbates oxidative stress and diminishes the therapeutic efficacy of oxytocin against such stress. Conversely, when calcium signalling remains intact, oxytocin demonstrates a notable therapeutic effect against oxidative stress. In conclusion, the study adds to the existing literature and leads to an improved understanding of the importance of calcium homeostasis and the functions of microglial cells in the brain. The research findings also shed light on the potential use of oxytocin in the treatment of neurodegenerative disorders as well as other neurological disorders linked to oxidative stress.Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 202
An information architecture for a first-year programming module on the Moodle learning management system : a Nelson Mandela University case study
Full text linkStudents enrolled in first‐year programming modules at higher education institutions often have difficulty in mastering the modules (Van Heerden & Goosen, 2019; Figueiredo & García- Peñalvo, 2024). According to Cao, Seow, Lim, Keoh, Dale, Honeychurch, Tasler & Bremner (2023) despite the implementation of various pedagogical approaches, including blended learning to enhance student performance, many students continue to face difficulties with programming modules. The use of online learning platforms, such as Learning Management Systems (LMSs), to facilitate teaching of, for example, programming modules, necessitates the structuring of course content in such a way that students can easily find and digest the learning material. Furthermore, the learning materials used must accommodate the students' various learning styles to effectively support their learning experiences. This research aimed to determine the effectiveness of using an Information Architecture (IA) explicitly designed for structuring different types of content in online courses, with the goal of supporting students’ diverse learning styles. This research focused on a first-year programming module of the Nelson Mandela University (NMU) Department of Computing Sciences and used Modular Object-Oriented Dynamic Learning Environment (Moodle) as the LMS. This study included a group of first-year programming students, a learning experience (LX)designer (LT-Collab staff member), and the first-year programming lecturer from theNMU Department of Computing Sciences as participants. This study adopted Design Science Research (DSR) as the research methodology and applied the DSR process model to this research. DSR seeks to develop knowledge about how artefacts can and should typically be arranged or built by humans to accomplish desired goals (Hevner et al., 2008). Through the DSR process model, this study used a literature review, a questionnaire, interviews, and Focus Group Discussions (FGDs) to identify the most suitable methods of structuring learning content in LMSs to create an IA that allows the lecturer of a first-year programming module to present learning materials that cater to different learning styles. The results showed that the students preferred to learn programming using learning materials such as videos, exercises, voice-over slides, and lecture notes that enable them to practically engage with the material. To accommodate for different learning styles, the LX designer highlighted the significance of using a universal design while developing online courses. This study made both practical and theoretical research contributions. For the practical component, IA was developed to structure the learning materials of a first-year programming module in the Department of Computing Sciences at NMU in the Moodle LMS. The theoretical contribution was the proposed guidelines for developing an IA for a first-year programming module, specifically for providing learning materials that encourage student engagement and to support students’ diverse learning styles in LMSs.Thesis (MSc) -- Faculty of Science, School of Computer Science, Mathematics, Physics and Statistics, 202
Professional nurses’ knowledge regarding diabetes screening of patients diagnosed with tuberculosis who have delayed smear conversion in primary health care facilities in Nelson Mandela Bay Health District
Full text linkTuberculosis (TB) is a significant public health burden in South Africa (SA) and a leading cause of death (Ndamase et al., 2020). The prevalence of TB disease is found to be higher in patients with Diabetes Mellitus (DM) compared to patients without DM, and a higher DM prevalence was also found to be present amongst people with TB disease (Goletti et al., 2023). Therefore, all professional nurses need to know how to screen patients diagnosed with TB who have delayed smear conversion for DM. This study aimed to identify the knowledge of professional nurses' regarding DM screening of patients diagnosed with TB who have delayed smear conversion in Primary Healthcare facilities ( PHC) facilities in Nelson Mandela Bay Health District (NMBHD) to enable making recommendations to optimise the knowledge of the professional nurses treating patients with TB and, ultimately, improve patient care. The researcher explored and described the knowledge of the professional nurses in the PHC facilities regarding DM screening of patients diagnosed with TB who have delayed smear conversion. The study applied a quantitative, descriptive design. The target population was all professional nurses in the PHC facilities in NMBHD. A census sampling method was utilised and included all 257 professional nurses working in PHC facilities in NMBHD with a total number of n=14 PHC facilities in Sub-district B and n=17 PHC facilities in Sub-district C. Data collection was done after ethical permission was obtained from all the applicable stakeholders. A fieldworker was employed, and the questionnaire was an English, self-administered, close-ended and open-ended question. Data was analysed using IBM Statistical Package for Social Sciences (IBM SPSS) version 27 (IBM Corp. Released 2022. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp) and STATA version 18 (StataCorp. 2023. Stata Statistical Software: Release 18. College Station, TX: StataCorp LLC). The researcher and fieldworker applied all ethical considerations adopted from the Belmont Report (1979) throughout the study. Most of the respondents had adequate knowledge about the assessment of knowledge about TB in items that scored the highest, more than (>80%) were as follows: questions about the causes of TB (97.65%), diagnostic tests (94.71%), duration of TB treatment (94.12%), and sputum monitoring (87.06%) and the least (<80%) on the question on the diagnostic test used to monitor treatment response (70.59%). However, the study found that the respondents had insufficient knowledge about the impact of DM on TB, with a knowledge score of (<80%). The highest score was (74.12%) on the question about the significance of TB and DM in the same patient and the lowest (50.59%) on the question about the risk of a high glucose level on the diagnosis of TB. A statistically significant association was found between years of employment and, knowledge of what is considered a high glucose level when screening for DM (p-value=0.003), and knowledge about the diagnostic test used to monitor treatment response (p-value=0.000). To improve the knowledge of professional nurses regarding DM screening of patients diagnosed with TB in PHC facilities in NMBHD, the researcher made recommendations to the PHC facilities and NMBHD for interventions such as training programs, the development of standardised guidelines and policies, and increased access to up-to-date resources and information.Thesis (MCur) -- Faculty of Health Sciences, School of Clinical Care & Medicinal Sciences, 202
A food list for persons diagnosed with TB and/or HIV
Full text linkTuberculosis and HIV are among the leading causes of death in South Africa. These conditions are also associated with poor nutritional status and food insecurity and exacerbated by rising food prices. The researcher’s personal experiences in counselling patients with these diagnoses, highlighted the significant challenges these patients face, following nutritional education due to financial constraints. Despite understanding the importance of dietary diversity, poverty often limits their ability to implement recommended nutritional changes. To address this issue, a practical and affordable food list, designed to empower individuals to make informed choices within their financial means, was developed. Therefore, the aim of the study was to determine the dietary preferences as well as the dietary diversity among patients diagnosed with tuberculosis and/or HIV with the view to compile and assess the usefulness and relevance of a practical, feasible, and scientifically justifiable food list. A quantitative approach with a descriptive cross-sectional study design, and a small qualitative component, was used. The study setting was three rural towns in the Eastern Cape namely Somerset East, Cookhouse, and Pearston. Data was collected by means of a data collection instrument, consisting of a biographical information questionnaire, a food preference questionnaire and collecting the diet history of participants with a 24-hour recall and a food frequency questionnaire. The food list was developed and tested with a questionnaire. Data was captured using a Microsoft Office 2016 Excel Spreadsheet and was analysed with Stata Version 18. The significance level was set at p=<0.05 and was determined by the Pearson Chi-Square Test and Fisher’s Exact Test. Results and recommendations: Poverty was a major concern as 62.50% of study participants lived below the food poverty line, facing difficulties in affording nutritious food. A large proportion (42.11% to 62.02%) had a low dietary diversity score. This study is one of the first to explore the potential of a food list as a tool to improve dietary diversity among rural populations, and while it did not significantly impact dietary diversity in this study, the majority of participants (85.47%) found the food list valuable for informed food choices and expressed intent to continue using it. To enhance effectiveness, more extensive training and repeated exposure are recommended. Longitudinal studies and studies into the combined use of the food list with behaviour change models could be done to further investigate the effect of the food list on various populations. This research contributes to the field of nutrition by providing a practical tool for improving the dietary diversity of vulnerable populations at community level, particularly those with tuberculosis and/or HIV.Thesis (MSc) -- Faculty of Health Sciences, School of Behavioural & Lifestyle Sciences, 202
Factors contributing to stunting among children under five years of age in the farm areas of Sarah Baartman Health District: Eastern Cape
Full text linkStunting, defined as a height-for-age Z (HAZ) score below -2 according to WHO growth charts, indicates impaired growth and development. In South Africa, the national stunting prevalence was 29%, with the Eastern Cape at 33% during 2021-2023. In the Kouga Sub-District, stunting trends are monitored at primary healthcare facilities, early childhood development centers, and hospitals. This comparative, quantitative, cross-sectional study involved 198 randomly sampled children under five years and their parents/caregivers from farm areas served by mobile clinics across three Local Municipalities (LMs). Data collection, conducted from April 5 to September 6, 2024, utilised structured questionnaires and the WHO Anthroplus tool version 1.0.4 for nutritional status assessment. Data was processed using STATA, with reliability and associations tested via Cronbach’s alpha, Pearson’s chi-squared test, Fisher’s exact test, and logistic regression. The study included 198 participants: 93 from Koukamma, 33 from Kouga, and 72 from Sundays River Valley. The stunting prevalence in the Kouga Sub-District was 38%, with 31% of participants having moderate and 7% severe stunting. Underweight prevalence was 7%, severe underweight 1%, overweight 9%, and obese 2%. Stunting was highest in Sundays River Valley, while Kouga had the highest prevalence of underweight, severely underweight, overweight, and obese cases. Significant factors included the number of children born to the same mother, birth order, the mother's age, timing of antenatal care, birth length, breastfeeding practices, and vitamin A and deworming. The findings highlight the multifactorial nature of stunting, emphasising the need for comprehensive interventions. Significant associations identified through bivariate analysis included the number of children born to the same mother (p = 0.002), birth order (p = 0.006), the mother's age (p = 0.007), timing of the first antenatal care booking (p = 0.020), birth length (p = 0.038), breastfeeding duration (p = 0.045), and vitamin A and deworming (p = 0.047). These factors underline the importance of maternal and child health services in preventing stunting. Addressing stunting requires multifaceted strategies, including but not limited to health interventions and broader sectoral approaches involving farmers, and relevant local partners, for capacity building, self-help projects, as well as rehabilitation from alcohol and substance abuse. Health-specific programs such as micronutrient supplementation for girls of reproductive age are crucial. Capacity building should include awareness campaigns and engagements to correct misconceptions and beliefs during the first and second thousand days of a child’s life. Strategies should focus on improving maternal nutrition, ensuring timely antenatal care, promoting optimal breastfeeding practices, and providing adequate vitamin A supplementation and deworming. This study did not explore the relationship between heredity and stunting nor consider pesticide exposure, although existing literature suggests significant associations. Future research should investigate these factors to provide a more comprehensive understanding of stunting determinants. The study underscored the critical need for targeted interventions to address the high prevalence of stunting in the Sarah Baartman Health District. By focusing on the identified contributing factors, it is possible to improve child growth and development outcomes, thereby enhancing overall community health and economic well- being.Thesis (MSc) -- Faculty of Health Sciences, School of Behavioural & Lifestyle Sciences, 202
Bicultural young African adults reuniting with their absent fathers during adolescence: experiences and coping strategies used when negotiating and integrating their bicultural identity
Full text linkBeing bicultural refers to the integration of two distinct cultures, often involving the constant juggling of diverse cultural norms, languages, and identities, frequently complicated by asymmetrical power relations. In the context of African youth, biculturalism can present challenges, particularly when shaped by the absence of fathers and divergent cultural expectations. This study therefore explored the experiences of African youths in negotiating and integrating their bicultural identity within their families and communities after reuniting with their absent fathers during adolescence. Using a qualitative, exploratory-descriptive design rooted in phenomenology, the research aimed to develop an understanding of how participants experienced and coped with their dual cultural identities. Participants were recruited through purposive and snowball sampling, and semi-structured telephonic interviews were conducted until the point of data saturation. Thematic analysis was applied to identify key themes. The findings revealed that participants encountered significant challenges in reintegrating with their paternal families, including cultural exclusion, language barriers, and limited emotional support. Despite these difficulties, they employed various coping strategies such as learning about both cultural backgrounds, practicing self-construction, integrating, or separating cultures, and relying on religious or traditional practices. Biculturalism offered benefits like exposure to diverse cultural perspectives and bilingualism but also posed challenges of misidentification and unclear social expectations. Family support, particularly socio-emotional support, was highlighted as critical in navigating these complexities. The study contributes valuable insights into the lived experiences of bicultural African youths, emphasizing the need for effective family communication and emotional support to foster successful cultural integration. The findings shows that successful integration of bicultural identity can be promoted through cultural understanding, addressing language 8 barriers, and fostering bicultural identity development through programs such as language immersion, cultural education, community initiatives, and mentorship. By supporting bicultural youth with emotional and social support, enhanced communication with their families, and through opportunities for cultural integration, families and communities can create more inclusive environments that enable bicultural youth to thrive in both their personal and professional lives.Thesis (MSW) -- Faculty of Health Sciences, School of Behavioural & Lifestyle Sciences, 202
A psychobiographical study of Charles Manson: an Eriksonian view
Full text linkCharles Miles Manson was a cult leader whose life became of interest to the world after his followers committed several murders on his demand. The instabilities and inconsistencies that Manson experienced in childhood supported progressive delinquent behaviour, that eventually led to several convictions. After release from incarceration, Manson gathered a cult following known as the “Manson family”, and ultimately ordered members to murder several people. The personality that orchestrated these events continues to intrigue members of the public. This study aims to explore Manson’s life experiences in order to gain an understanding of his personality development. This is accomplished by applying Erikson’s Theory of Psychosocial Development to his life experiences. This is a qualitative, psychobiographical study, and Manson was selected using non- probability purposive sampling. Multiple sources of evidence were used to collect data on Manson’s life. Miles Huberman and Saldana’s (2014) three step process of data analysis was utilised to analyse the data, and they include data reduction, data display and conclusion drawing and verification. The study found that Manson unsuccessfully completed each stage of development, with no evidence for the formation of the ego strengths associated with the stages. Evidence points to him having either developed a maladaptive or malignant tendency within many of the stages.Thesis (MA) -- Faculty of Health Sciences, School of Behavioural & Lifestyle Sciences, 202
Exploring psychological trauma treatment and clinical assessment: a systematic review
Full text linkPsychological trauma seems to be an integral part of any given society. Most experiences of psychological trauma occur even before an individual reaches adulthood. Research has shown that dysfunction results from exposure to psychological trauma at any given point across the lifespan. Literature suggests in the last years that there has been an increasing need for mental health practitioners to gain a better understanding of psychological trauma. In particular, the assessment thereof and effective treatment strategies when working with individuals experiencing trauma. Because of the potentially long-lasting negative impact of psychological trauma on physical and mental health, ways to address clients’ history of psychological trauma are drawing the attention of mental health care policy makers and providers across the country. The main aim of this study was to summarize available literature regarding psychological trauma as it manifests globally. The researcher systematically reviewed the available literature regarding psychological trauma, highlighting the importance process of clinically assessing, and explored common treatment strategies utilised in psychological trauma treatment. A qualitative systematic review was conducted, including a comprehensive representation of published documents and research on the topic of this study. A thematic analysis was conducted, and the following themes emerged: Psychological trauma and the context thereof; Reactions, symptoms or common mental health disorders within psychological trauma; Highlighting the importance of clinically assessing psychological trauma and lastly Counselling and treatment implications when working with psychological trauma treatment.Thesis (MA) -- Faculty of Health Sciences, School of Behavioural & Lifestyle Sciences, 202