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    Epidemiology, Functioning and Reintegration into the Community of Patients with Spinal Cord Injuries in Kenya
    (University of the Witwatersrand, Johannesburg, 2025) Muli, George Mutuku
    Background Spinal cord injury (SCI) occurs when damage to the spinal cord affects its structure and function, leading to neurological impairments in motor, sensory, and autonomic functions, depending on the severity and location of the injury. Globally, the primary objectives of SCI care remain consistent, highlighting the need for epidemiological data to guide medical and governmental organizations in allocating resources effectively. Functional outcomes are influenced by factors such as injury severity, rehabilitation quality, staff-to-patient ratio, and community support. Successful reintegration into the community is essential for individuals with SCI to regain competence and achieve life satisfaction. This study aimed to examine the epidemiology, functional outcomes, and community reintegration of SCI patients in Kenya. Methodology The study was conducted in three counties in Kenya: Machakos, Nairobi, and Mombasa. A mixed- methods design was employed in three phases. Phase I: Focused on the epidemiology of SCI through a retrospective cross-sectional design that involved reviewing medical records from a four-year period. The sample size included 159 participants from Nairobi, 61 from Machakos, and 70 from Mombasa. Phase II: Utilized an explanatory sequential mixed-methods design. The quantitative component involved a prospective longitudinal study using the SCIM III tool for activity-level functional outcomes and the CHART tool for participation-level functional outcomes. The qualitative component employed a grounded theory design to explore factors affecting reintegration, using CHIEF and LSQ outcome measures. Quantitative data were analyzed using SPSS version 15, while qualitative data were processed with ATLAS Ti software. Phase III: Focused on developing guidelines to improve community reintegration using the Delphi procedure study design. In round one, demographic data were analyzed through frequency distribution and percentages, while qualitative data underwent thematic content analysis. In round two, a Likert scale was used to rate participants' statements in terms of importance, and SPSS was used to analyze measures of central tendency and variations. In round three, participants re-rated statements from round two using a Likert scale, and SPSS was employed again to assess the level of agreement among participants. Results The results reveals that spinal cord injuries (SCI) primarily affect young, working-age males with limited education, with motor traffic accidents and falls being the leading causes. Incomplete injuries were more common in road accidents, while falls resulted in more severe injuries. Preventive measures, such as road safety campaigns and workplace safety programs, are crucial in reducing SCI cases. The study also highlights the high prevalence of neuropathic pain among male patients, emphasizing the need for specialized pain management. Functional outcome assessments showed significant recovery, especially in individuals with incomplete injuries, though challenges in respiration and sphincter management persist, necessitating long-term, multidisciplinary rehabilitation. Social participation 14 improved notably, with functional ability and injury severity being strong predictors of recovery, alongside psychosocial factors like social support and depression. Environmental and societal barriers, particularly affecting younger, lower-income, and less-educated individuals, remain significant obstacles to healthcare access and community reintegration. Racial disparities were evident, with Black participants facing greater accessibility and social acceptance challenges. The Delphi study further identified key factors for successful reintegration, such as removing physical barriers, strengthening community support, and improving access to assistive technology and healthcare policies. Major barriers included stigma, financial struggles, inadequate infrastructure, and insufficient specialist training. The study underscores the need for a holistic, multidisciplinary approach that integrates physical, social, and economic interventions to foster independence, social participation, and long-term well-being for individuals with SCI. Conclusion The study provided comprehensive insights into the epidemiology of SCI in Kenya, revealing that most cases occurred among males aged 26–35 years with primary education. This study highlights the significant challenges faced by individuals with spinal cord injuries (SCI), particularly young, working- age males with limited education. Motor traffic accidents and falls were the leading causes, with incomplete injuries more common in road accidents and severe injuries resulting from falls. While functional outcomes showed significant improvements, persistent challenges in respiration, sphincter management, and neuropathic pain emphasize the need for long-term, multidisciplinary rehabilitation. Social and environmental barriers, especially for lower-income and less-educated individuals, further hinder recovery and reintegration. Racial disparities in accessibility and social acceptance were also evident. The Delphi study identified key factors for successful reintegration, including removing physical barriers, strengthening community support, and improving healthcare policies. Addressing systemic gaps such as stigma, financial struggles, and inadequate specialist training is crucial. Ultimately, a holistic, multidisciplinary approach is essential to enhance independence, social participation, and long-term well-being for individuals with SCI.
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    The home environment and play: The co-creation of an intervention aimed at increasing participation in infant play in a low- income community in Johannesburg, South Africa.
    (University of the Witwatersrand, Johannesburg, 2025) Bennin, Fiona; Prioreschi , Alessandra
    Background: Infants require their caregivers to provide opportunities to engage in playful activities that promote early development and encourage further positive health outcomes later in life. Mothers require a certain level of health literacy to access, appraise and understand information to have the capability to make decisions that encourage optimal health for their child. However, some mothers living in low-income settings do not have access to information or adequate support for encouraging play and development. Mobile Health applications have the potential to provide cost effective, scalable interventions and improve health outcomes in low-resources settings, such as South Africa, when effectively implemented. The aim of this thesis was to develop and implement an intervention aimed at improving maternal health literacy around infant play and development and to determine whether this intervention was acceptable, feasible, and effective. Methods: A Community Advisory Group co-created and tested an intervention prototype aimed at increasing maternal health literacy around play and development, through focus group discussions and testing the activities at home. The intervention was then implemented as part of the PLAY study, a Randomised Controlled Trial, conducted from September 2022 to June 2024 (N=133). From 6-12 months postpartum, intervention group participants (n=68) received interactive App-based content promoting health literacy and encouraging infant active play and development. The control group (n=65) received the normal standard of care. The primary outcome was the Health Literacy Questionnaire scores, while secondary outcomes included maternal beliefs about infant physical activity, home affordances for motor development, and infant physical/sedentary behaviors. A combined “opportunities for active play” score was derived from the secondary measures. Data were analysed in STATA, using an intention to treat approach. Descriptive data were reported using N (%) for categorical data and means (Standard Deviation) for continuous data. Wilcoxon rank tests determined the effect of the treatment. Feasibility and acceptability of the intervention were measured and explored at the end of the study (12 months) through participant Focus Group Discussions and semi- structured questionnaire. Results: Community Advisory Group participants suggested that the intervention content be delivered every 1-2 weeks, through a data-free app. Overall, the prototype activities tested at home were deemed 19 acceptable. At intervention baseline, the 67 intervention and 65 control participants averaged 29 years old; most were single (64%) and had completed secondary education (64%). No significant differences were observed at 12 months between groups in maternal Health Literacy Questionnaire (t=-1.05 p=0.3), maternal beliefs (t=0.71; p=0.48), infant physical activity (t-0.15; p=0.88) or sedentary time (-0.89; p=0.38), and opportunities for play (p=0.36). However, the change in Maternal Beliefs score from 6 to 12 months was significant (p=0.00), with the intervention group’s scores increasing on average, 35.44 points compared to an average of 25.7 points in the control group. Participants in the intervention group showed a significant decrease of 1.53 units in the AHEMDS score, compared to the control group, at 12 months When looking at the change in opportunities for play from 6 to 12 months, there was a significant (p=0.001) difference between the intervention and control group, with 27 participants (40%) in the intervention group increasing between 1 and 3 points (compared to 8% in the control group) and 43 participants (42%) of the control group decreasing between 1 and 4 score units (compared to 31% in the intervention group). The health literacy intervention content was found to be highly acceptable based on the questionnaire and Focus Group Discussions. Over 80% of participants attended the 12 month exit appointment. Most of the participants (70%) could access the intervention content over the 12 months of the PLAY Study and of those, 59% looked at content more than once a week and 10% every day. Less than a quarter only looked at the content sporadically. Access was impacted by technical difficulties attributed to using inconsistent external service providers. Other factors which negatively impacted implementation included low intervention dosage, questionnaire burden and resource constraints. Conclusion: While the intervention was found to be highly acceptable to participants, it did not have a significant effect on Health Literacy Questionnaire scores. While adherence numbers were positive, there were numerous implementation challenges which researchers need to consider carefully when planning a complex intervention in a similar low resource context.
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    Investigating the molecular and neurobehavioral effects of monoamine antidepressants and ketamine in a rodent model of ACTH-induced HPA axis dysfunction
    (University of the Witwatersrand, Johannesburg, 2025) Sallie, Farhanah Nabilah
    Major depressive disorder (MDD) is a debilitating mental illness and is among the leading causes of disability worldwide, severely impacting patients' quality of life. The pathophysiology of MDD is multifactorial. Several theories have been proposed, including neuroinflammation, monoamine and neurotrophic dysregulation, hippocampal atrophy, and excitatory/inhibitory imbalances. Of these theories, hypothalamic-pituitary-adrenal (HPA) axis dysregulation is suggested as a frequently pathophysiological mechanism of MDD. HPA axis dysregulation is attributed to chronic stressors, both physiological and emotional, which disrupt glucocorticoid signalling and impair negative feedback mechanisms. Studying the pathophysiology of MDD in humans is limited by confounding factors and access to post-mortem tissues. Therefore, in rodents, administration of exogenous adrenocorticotropic hormone (ACTH) has been used to induce HPA axis dysregulation and produce depressive-like responses. However, there is a lack of comprehensive neurobehavioral and mechanistic evidence to support the validity of this model. In addition, the investigation of the molecular effects of different classes of antidepressants is important to understand the clinical translation of this model. In Chapter 2, I developed and validated the ACTH model using a battery of neurobehavioural tests. Previous studies demonstrated the inefficacy of tricyclic antidepressants (TCAs) in this model suggesting that ACTH-induced HPA axis dysregulation may be associated with treatment resistant depression (TRD), therefore, I also investigated the effect of impramine, a TCA, in this chapter. Male and female Sprague-Dawley rats were randomly assigned to the control or ACTH groups that received saline or ACTH, respectively, for two weeks. Thereafter, rats in the ACTH group were subdivided to receive ACTH plus saline or ACTH plus imipramine for a further four weeks. Neurobehavioral changes were assessed using the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT). The brain regional mRNA expression of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), neuroplasticity molecules implicated in depression pathology, was determined using real-time polymerase chain reaction (RT-PCR). ACTH administration resulted in a depressive-like phenotype, significantly increasing immobility in the FST, decreasing interaction with the centre of the OFT, and increasing sucrose consumption in male, but not female rats. ACTH administration significantly increased the expression of BDNF, a neurotrophin important for synaptic plasticity, in the hippocampus and CREB, a transcription factor that regulates neuronal development, in all brain regions in males, but not in female rats. Co-treatment with imipramine did not ameliorate these ACTH-induced neurobehavioral or molecular changes. This chapter showed that ACTH administration resulted in a sex-specific onset of depressive-like symptoms and changes in brain regional expression of neuroplasticity markers, suggesting sex-specific mechanisms in a model of ACTH-induced HPA axis dysregulation. Furthermore, molecular analyses indicate that chronic ACTH alters BDNF and CREB signalling, suggesting that dysregulated neurotrophic signalling is associated iv with HPA axis dysregulation. Although these agents primarily act to regulate neurotransmitters, their effects on neurotrophic signalling, particularly in the ACTH model, remain poorly understood. Following the development and neurobehavioural evaluation of the ACTH model, in Chapter 3, I further validated the model by comparing the neuroplasticity effects of imipramine, a TCA, to citalopram, a selective serotonin reuptake inhibitor (SSRI) and first-line therapy for MDD. The ACTH model was repeated with experimental animals being treated with either citalopram or imipramine for four weeks, respectively. I determined the brain regional mRNA expression of intracellular markers of neurotrophic signalling, including BDNF, CREB, tropomyosin receptor kinase B (TrkB), protein kinase B (Akt), mechanistic target of rapamycin (mTOR), and eukaryotic elongation factor 2 (eEF2) using RT- PCR. In addition, the brain distribution of citalopram and imipramine was determined using atmospheric pressure matrix-assisted laser desorption/ionisation mass spectrometry imaging (AP- MALDI-MSI). ACTH administration increased hippocampal BDNF mRNA expression, coupled with decreased mRNA expression of intermediate neurogenesis signalling factors, TrkB, Akt, mTOR, and eEF2. Citalopram showed a greater capacity to ameliorate ACTH-induced neurotrophic dysregulation compared to imipramine, particularly by enhancing BDNF-TrkB-mTOR signalling, independent of brain drug distribution. These findings highlight the distinct pharmacodynamic effects of different classes of antidepressants in targeting dysregulated neurotrophic signalling. Despite the widespread use of monoamine-based antidepressants, approximately one-third of individuals diagnosed with MDD have TRD, where patients do not respond to two or more classes of conventional antidepressants. Ketamine has emerged as a novel, rapid-acting therapeutic agent for the management of TRD. Unlike monoamine antidepressants that require months to reach their full therapeutic effect, ketamine provides antidepressant relief following a single dose. However, the respective effects of acute and chronic ketamine treatment on neurobehavior, as well as on neurotrophic and monoamine neurotransmitter signalling in an ACTH model of depressive-like symptoms, remain unclear. In Chapter 4, I investigated the behavioural, molecular, and neurochemical effects of acute and chronic ketamine treatment in ACTH-treated rats. In the acute group, following two weeks of ACTH administration, rats received a single dose of ketamine. In the chronic group, after two weeks of ACTH administration, rats received a ketamine injection once a week for four weeks. Neurobehavioural changes were assessed using the FST, OFT, and SPT. Following termination, brain regional mRNA expression of BDNF, TrkB, Akt, mTOR, eEF2, and CREB was measured using RT-PCR. Brain regional protein expression of phosphorylated-CREB (p-CREB) and corticosterone were assessed using an enzyme-linked immunosorbent assay (ELISA). In addition, serotonin, dopamine, and norepinephrine neurotransmitter abundance were determined at various bregma levels using MALDI-MSI. ACTH administration increased behavioural despair in the FST and altered corticosterone and p-CREB protein v expression, mainly in the prefrontal cortex. However, by week six, neurobehaviour and gene and protein expression remained largely unchanged, suggesting a state of homeostatic adaptation. At week six, ACTH-treated rats showed changes in serotonin and norepinephrine levels in the hippocampus and midbrain. Acute ketamine treatment effectively reversed ACTH-induced behavioural despair in the FST and modulated the region-specific expression of monoamines (serotonin) and increased CREB mRNA expression. With chronic ketamine treatment, besides increased striatal mTOR mRNA expression, there were limited effects on the expression of neuroplasticity markers. Our findings indicate that when administered acutely, ketamine modulates neurotrophic pathways and monoaminergic neurotransmission, which impacts behavioural outcomes. In contrast, the minimal behavioural and molecular effects of repeated ketamine treatment suggest that prolonged exposure attenuates ketamine’s neuroplastic and antidepressant actions in this model. These findings highlight the differential mechanism of action of ketamine following acute and chronic dosing, in a model of HPA axis dysregulation. In conclusion, the findings from this thesis contribute to our understanding of the molecular mechanisms underlying the neurobehavioural effects of chronic exogenous ACTH administration in rodents as well as the model-specific effects of imipramine, citalopram, and ketamine. I provide evidence that chronic ACTH exposure induces depressive-like behaviours as assessed using the FST, OFT, and SPT. These effects were sex-dependent, with male rats exhibiting both behavioural changes and elevated hippocampal BDNF and CREB mRNA expression, while females were largely unaffected. I further demonstrate that citalopram was more effective than imipramine at ameliorating ACTH- induced disruptions in the mRNA expression of neurogenesis-related signalling factors across brain regions. I also show that acute ketamine treatment has more pronounced effects on ACTH-induced neurobehaviour and molecular changes, than chronic ketamine. Overall, this thesis provides evidence that chronic ACTH administration models HPA-dysregulation induced depressive-like symptoms, resulting in disturbances in neurotrophic and monoaminergic signalling. Moreover, neurogenesis- enhancing agents such as SSRIs and acute ketamine may offer greater therapeutic efficacy than classic antidepressants in depressive disorders where HPA axis dysfunction is a core aetiological feature
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    Determining Synchrony of Mother-Infant Non-Verbal And Movement Behaviours Using First-Person Observation and Accelerometer Data
    (University of the Witwatersrand, Johannesburg, 2025) Maduna, Dumsile Nontokozo
    Mother-infant synchrony—the dynamic, coordinated exchange of behaviours and movements between caregivers and their infants—is fundamental for promoting healthy emotional, cognitive, and socio-emotional child development. Despite extensive global research, current evidence remains predominantly derived from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies, raising questions about its generalizability to low-resource and culturally diverse contexts such as South Africa. This thesis aimed to address this critical gap by exploring synchrony using innovative multimodal methodologies, specifically first-person observational approaches via head-mounted cameras (headcams) and wrist-worn accelerometer, within a socioeconomically constrained urban South African setting (Soweto). Three interconnected studies were conducted among mother-infant dyads at critical developmental periods (4 and 8 months postpartum) to assess patterns, determinants, and developmental trajectories of non-verbal behavioural and movement synchrony. Study one employed headcam footage to provide intimate, ecologically valid insights into everyday caregiver-infant interactions, highlighting delays in the emergence and stability of synchronised behaviours compared to high-income contexts. Study two utilised accelerometer data to objectively capture mother-infant movement patterns, revealing detailed temporal synchrony particularly during caregiving routines and demonstrating a developmental shift from mother-led to infant-led coordination. The final study, a longitudinal analysis combining both methodologies, identified maternal employment as a consistent predictor of reduced synchrony, underscoring how structural constraints significantly influence relational caregiving capacities. iv | P a g e Collectively, these findings affirm that synchrony is a dynamic, developmentally evolving process substantially influenced by caregiving context and availability. The integration of first- person observational and accelerometry methods provided robust, objective data, overcoming biases associated with traditional observational techniques. This methodological innovation represents a significant advancement in synchrony research, particularly for low- and middle- income countries. Furthermore, findings hold practical implications for developing culturally sensitive, synchrony-focused early childhood interventions and policy frameworks designed to mitigate developmental risks associated with socioeconomic adversity. Future research recommendations include extending longitudinal assessments, explicitly incorporating maternal mental health and psychosocial variables, broadening the scope to include multi-caregiver roles, and employing qualitative methodologies to enrich contextual understanding. This thesis thus lays critical groundwork for enhancing early developmental outcomes through evidence-based, culturally responsive synchrony interventions tailored to the South African caregiving landscape.
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    A Terminal Condition in Linear Bond‑pricing Under Symmetry Invariance
    (Springer Nature, 2023) Maphanga, Rivoningo; Jamal, Sameerah
    In this paper, we examine a general bond-pricing model with respect to its solutions that satisfy a given terminal condition. Firstly, we obtain reversible transformations that change the model to a classical and well known partial differential equation, the one dimensional heat equation. We further show that the terminal condition is transformed into a nonsmooth initial condition. The important result that emerges is that the Lie symmetries are adopted to solve the equation subject to its unique configuration of initial conditions.