Electronic Theses and Dissertations (Masters)

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A documentation of the morphology of the lungs of the Sprague Dawley rat after chronic heat exposure
(University of the Witwatersrand, Johannesburg, 2023) Peya, Yolanda; Reddy, Deran
Climate change is a natural phenomenon that is exacerbated by mul4ple human ac4vi4es in the environment. These ac4vi4es lead to a rise in global temperatures. This increases the occurrence of heatwaves which pose a major threat to ecosystems, biodiversity, and the conserva4on of species on Earth. This study, aimed to document the effects of chronic heat exposure on the lungs of the Sprague Dawley rat using histological and immunofluorescence techniques. Twenty-four (24) rats were assigned to three groups; each exposed to different temperatures; (i) group A (n = 8) exposed to 25 °C (ii) group B (n = 8) exposed to 33 °C and (iii) group C (n = 8) exposed to 34 °C. This was done for a period of 4 weeks and the rats were euthanised therea`er. Methods employed included Intratracheal instillation, and histological and immunofluorescence techniques. This study found that rats in group A (25 °C) displayed no structural adapta4ons in comparison to groups B and C. Enlarged blood vessels with thick smooth muscle and prominent elas4c fibres, bronchus-associated lymphoid 4ssue (BALT), and increased collagen deposi4on were observed in group B (33 °C). These indicate the ac4va4on of immune responses and adapta4on to new environmental temperatures. In group C (34 °C), the lung morphology was severely damaged. There was an increased loss of epithelial integrity, oedema, pulmonary alveolar proteinosis (PAP), and a severe decrease in the lung- to-surface area ra4o. The significant changes caused by the 1 °C temperature difference between groups B (33 °C) and C (34 °C) illustrate the detrimental effects of chronic heat stress. It is evident that increasing environmental temperatures due to climate change is harmful to life and immediate interven4ons are necessary to combat rising temperatures
Characterizing Luminal A breast cancer heterogeneity and in vitro response to hormone therapy
(University of the Witwatersrand, Johannesburg, 2024) Gallant, Simone
Breast cancer is the most prevalent form of cancer diagnosed amongst women worldwide, responsible for a mortality rate of 6.9% and responsible for 684,996 deaths. Breast cancer is the most heterogeneous disease characterised by variations in genomic, epigenomic transcriptomic and proteomic profiles. The limited research on intratumoural heterogeneity in breast cancer and hormone therapy is the motivation for our study to further aid in understanding stemness markers influencing luminal A breast cancer and the effects hormone therapy has on biomarkers associated with breast cancer. In our study, we optimised modified essential 8 media to culture sorted cell populations in optimal conditions without differentiation ensuring stemness markers are maintained. Magnetic cell sorting was used to separate cells based on stemness markers CD133 and CD44. To verify these sorted markers flow cytometry was performed. The evaluation of the effects hormone therapy had on biomarkers was performed via immunocytochemistry and analysed using cell profiler. Our study revealed significant differences between subpopulations in MCF7 and T47D cell lines. It emphasizes the importance of CD44 and CD133’s role in tumour progression and its possible influence in hormone therapy. Our findings show that in populations with both stemness markers present in T47D cell line there is a reduction in progesterone receptor expression when treated with Tamoxifen. We also noticed the difference between population and hormone therapy impact on these changes. Thus, stemness markers are vital in tumour progression and the interaction of biomarkers and hormone therapy. However future research in the biological process and pathway activation is needed to further understand the intricacies of CD44 and CD133 mechanism of action as well as its association to biomarkers common pathways
Effects of binge alcohol consumption on the development of the femur of adolescent Sprague Dawley rats
(University of the Witwatersrand, Johannesburg, 2024) Mngoma, Ndabenzinhle Ronald; Bhika, Akaashni
Excessive alcohol consumption adversely affects bone metabolism, thus resulting in reduced bone length, density, and strength. While excessive alcohol consumption is an established risk factor for osteoporotic fractures, there remains a dearth of information in literature regarding bone effects of binge alcohol consumption in adolescents. Therefore, our study aimed to examine the effects of binge alcohol consumption in an acute and chronic binge model, on the development and growth of the adolescent femur. Forty-eight Sprague Dawley rats (24 male and 24 female) aged 7 weeks were randomly allocated to one of the 4 treatment groups (n= 12/group) receiving binge alcohol (3g/kg of 20% alcohol) or caloric equivalent of maltose dextrin (pair-fed control), via oral gavage. The treatment groups were; A1, receiving alcohol on 3 alternating days for one week, C1, receiving the caloric equivalent of maltose dextrin in the same manner as A1 (acute), A4 and C4 received treatments in the same manner as A1 and C1 for four consecutive weeks (chronic). Trabecular morphometry in both the proximal and distal epiphysis, and cortical dimensions were assessed by using three-dimensional Micro- Focus X-ray Computed Tomography (3D-μCT) and Volume Graphics Studio® software. The morphology of the epiphyseal growth plate was examined by Haematoxylin and Eosin staining, whereas Ki-67 immunostaining was employed to quantify the proliferation of chondrocytes in the proliferative zone of the growth plate. A three-point bending test was employed to examine the effects of alcohol on bone strength. Results showed that binge alcohol consumption causes thinner trabeculae that are more widely spaced and with a smaller bone to volume ratio (BV/TV). However, the tensile strength was similar in the alcohol exposed rats and paired fed groups in male rats, whereas it appeared improved in female rats exposed to alcohol. A binge model also affected the number of chondrocytes in the proliferative zone negatively. All the adverse changes observed in the osseous tissue in the current study were shown in the male rats. Our study found alcohol to have no adverse effects on female rats, which could be due to hormonal differences.”
Impact of Cannabidiol and Tamoxifen treatment on cell death and cell survival in breast cancer in vitro
(University of the Witwatersrand, Johannesburg, 2024) Mahasha, Mahlatse Fortunate; Augustine, Tanya
The main non-psychotropic component of Cannabis sativa, Cannabidiol (CBD), alleviates breast cancer treatment-associated side effects but its effects with standard therapy remain unclear. In breast cancer, CBD has been shown to exhibit anti-cancer properties by inducing apoptosis and pro-death autophagy. This study aimed to investigate the effects of combined CBD and Tamoxifen treatment on metabolism, cell death, and cell survival mechanisms in luminal-A breast cancer cell lines MCF7 and T47D. The CBD concentration relative to IC50 was established by testing a range of CBD concentrations: 5 μM, 7 μM, and 10 μM, at 24 h, 48 h, and 72 h using the neutral red cell viability assay. The scratch assay was used to determine the effects of the concentrations on migratory capacity. Two models of treatment were used, single-dose treatment (model 1) and daily-replacement treatment (model 2), and appropriate controls were included. Treatment with 2 μM Tamoxifen and 5 μM CBD for 48 h was determined to be the optimal treatment condition. The MTT assay was performed, and the absorbance ratio indicative of cell proliferation was calculated. The ability of the cells to metabolize the drug components was examined through an assessment of CYP450 reductase (CPR) enzyme activity. The mRNA and protein expression levels of three autophagic markers; BECN1, LC3B, and p62, were investigated using qPCR and immunocytochemistry, respectively. Friedman’s Anova (p<0.05) and Kruskal Wallis (p<0.05) post hoc tests were used to statistically analyse the data. Combined CBD and Tamoxifen treatment showed the greatest decrease in the proliferation of MCF7 cells and T47D cells compared with all other treatments across both treatment models, with the daily- replacement treatment model (model 2) showing more efficacy thus suggesting that combined treatment may inhibit cell proliferation. CYP450 enzyme reductase activity was higher in T47D cells compared with MCF7 cells in both treatment models suggesting increased metabolic activity and susceptibility to combined treatment. However, in the daily replacement model, MCF7 cell CPR activity could not be ascertained, suggesting either prodrug availability or reduced CPR activity. Further analysis is required in this regard. For immunolocalization, optimization was conducted in late 2021 and all three antibodies showed clear and expected immunolocalization but when the experiments were repeated early 2022, immunofluorescence was reduced (P62 and BECN1), with LC3B not detectable. P62 and BECN1 were expressed in both MCF7 and T47D cells across both treatment models although BECN1 expression was not sufficient to be quantified and assessed statistically. LC3B protein levels could not be accurately quantified irrespective of the treatment model used. Low amounts of target mRNA in MCF7 cells resulted in undetermined Cq values of LC3B, P62 and BECN1 genes across both treatment models. In T47D cells, Cq values of target genes were determined across both treatment models and the fold change in gene expression indicated that combined CBD and Tamoxifen treatment effectively upregulates target genes albeit not significantly (LC3B, P62 and BECN1) with the single-dose treatment model (model 1) compared with the daily replacement model. Both the immunofluorescence and qPCR experiments would be required to be repeated to ensure conclusive results. The findings of this study nevertheless indicate that combined CBD and Tamoxifen treatment may inhibit tumour growth, but tumour cells may be able to evade cell death pathways resulting in tumour cell survival
Assessment of disability resulting from degenerative joint disease in a southern African skeletal population
(University of the Witwatersrand, Johannesburg, 2023) Gavin, Jessica Robyn Brinkworth; Carrasco, Lorena Nunez; Meyer, Anja; Keyes, Craig
Age-related skeletal changes, like degenerative joint disease (DJD), are often used to estimate age in forensic settings, yet these changes also reflect the living experience of individuals as they progress through life. This study set out to assess the impact of DJD in a sample of southern African deceased individuals and the subsequent effects on these individuals’ Activities of Daily Living (ADLs). A novel scoring system was created, translating DJD frequency and severity into how the individual was potentially physically disabled. A sample of 150 southern African individuals between the ages of 35 and 90 years were assessed for signs of DJD in each of the major joints, both for the peripheral (TMJ, shoulder, elbow, wrist, finger, hip, knee, ankle and toe joints) and axial (cervical, thoracic and lumbar vertebral joints) regions. The severity of DJD was then translated into various ADLs (transferring, eating, talking, object manipulation, walking and posture changes: head rotation; twisting and bending) that may have been affected. Socio-economic Status (SES) was included as this would have a significant impact on the types of DJD and subsequent ADL impairment seen, as well as how these individuals may have been impacted within their respective contexts. Results for DJD severity and frequencies indicated that the shoulder most often presented with the most severe DJD score with 42.67% of the pooled sample presenting with a score of 3. It was also interesting to note that most of the upper peripheral joints were affected, with the entire sample presenting with some form of DJD in the elbow, specifically. For the axial skeleton, severity scores were much more variable across different vertebral regions, with the highest severity percentage per region was seen in the thoracic vertebra (5%). In general, females presented with higher severity scores for DJD across all joints, with the TMJ (47%) and toe (22%) joints being statistically higher in females. When controlling for population affinity and sex the same trend was observed in the white sample, specifically the white females (TMJ = 22%). Black males; however, presented with higher severity frequency of DJD in the axial skeleton, specifically the lumbar vertebrae (32%). The white cohort showed very little correlation with age in relation to the TMJ, whereas this was true for the elbow and ankle in the southern African black individuals. This study indicated moderate impacts in transferring (53%), walking (51%), and eating (41%) activities for all individuals. Females presented with significantly higher ADLs for all activities except posture changes whereas problems with eating and talking were more often seen in southern African white individuals. Differences between different socio-economic status groups were also noticed with the lower SES group showing increased levels of impairment across most of the ADLs which may relate to activity differences when age is controlled for. The focus of this research was to provide deeper information into impairment and disability caused by DJD. To conduct research on individuals were their lives and stories were limited and underexplored. This research highlights the need to continue studies on skeletal remains of individuals impaired by DJD, with focus on trends on joint and activity limitations within past and present contexts
The effects of ibogaine on myelination in Sprague Dawley rats
(University of the Witwatersrand, Johannesburg, 2024) Govender, Demi Natisha
Introduction: The growing opioid epidemic is a worldwide issue which is prevalent in South Africa with the use of opioid cocktails such as nyaope. A possible solution to this problem is the use of psychedelic assisted psychotherapy. Ibogaine is a psychedelic that has been shown to curb addiction cravings and have neuroplastic effects in the brain. Ibogaine is extracted from the root bark of a West African plant and has shown to have neuroplastic effects in the brain. We investigated whether these antiaddictive properties are due to remyelination of the brain’s white matter. Methods: This study uses qPCR and western blotting to determine how myelin specific proteins and genes such as CNPase (CNP), Myelin Basic Protein (MBP) and Proteolipid Protein (PLP) are affected by morphine (opioids) and ibogaine. The experimental rat groups included a saline, morphine and ibogaine only controls, a combination morphine and ibogaine and a second combination morphine and ibogaine which included a 3 day withdrawal after ibogaine injection. Results: CNP protein was increased in the second morphine ibogaine group (p<0,0001) and the CNP mRNA fold expression was increased in the first morphine ibogaine group compared to the second morphine ibogaine group (p=0,0343). The 18,5 kDa isoform of MBP had increased expression in the ibogaine control (p=0,0384) and second morphine ibogaine group (p=0,0037). PLP shows increased protein expression in the second morphine ibogaine group when compared to the first group (p=0,0464). There is decreased PLP mRNA expression in the ibogaine control group when compared to morphine control (p=0,0033), first morphine ibogaine (p<0,0001) and second morphine ibogaine groups (p=0.003) Conclusion: Ibogaine may cause remyelination following demyelination by morphine. A consistent trend in the data shows that the myelin proteins were increased after the 3 days after administration of ibogaine following chronic morphine administration compared to 1 day after administration of ibogaine. This suggests that remyelination takes between 24-72 hours before it begins to produce new myelin around the axons due to ibogaine. These results also shows that CNP and MBP increase in expression earlier than PLP and are good markers for early remyelination. This is consistent with increase in CNP mRNA expression for CNP seen in the first morphine ibogaine but not the second group revealing an immediate effect on mRNA but a delay in protein expression
The role of human papilloma virus (HPV) in oropharyngeal squamous cell carcinoma: a clinicopathologic and molecular analysis
(2024) Disenyane, Dineo
Context: Human papillomavirus (HPV) is an established aetiology in a subset of oropharyngeal squamous cell carcinoma (OPSCC). However, literature on the association between HPV and OPSCC in the African context is lacking. Objective: To determine the association of HPV in OPSCC and to correlate it with the clinicopathologic and molecular analysis. Design: A total of 60 OPSCCs were evaluated with HPV in-situ hybridisation (HPV ISH) and immunohistochemistry (IHC) for p16, p53 and Ki67. This was correlated with the site of occurrence of the tumours, the patients' smoking and alcohol usage and microscopic features of tumours (NKSCC;n=30 and KSCC;n=30). Results: HPV DNA was found in 24/60 (40%) cases. HPV16, was positive in 18/60 (30%) cases and HPV6 in 8/60 (13.3%) tumours. Two of the 60 (3.3%) cases were positive for both HPV16 and HPV6. HPV positive (+ve) tumours occurred more in males (n=22; 73%) than females (n=7; 23%); median age: 62.5 years. The primary tumour sites were the tonsil (n=7; 11.6%) and posterior tongue (n=6; 10%). Of the NKSCCs, 11 (36.7%) were HPV16+ve and 8 (26.7%) HPV6+ve. Seven (23.3%) KSCC were HPV16+ve and none (0%) HPV6+ve. Of the 24 HPV+ve tumours, 13 (54.1%) were p16+ve and 14 (58.3%) were p53+ve. Three (12.5%) tumours exhibited the molecular phenotype: p16+ve in > 70% of tumour cells, a low (25%) proliferation index. Conclusion: HPV positive OPSCC is seen more in older male patients. The distinct molecular phenotype, (p16 positive, low p53, high KI67) highlights tumours that are of true viral aetiology. In this study, the low p16 IHC stain sensitivity towards HPV ISH positive tumours infers that p16 is less reliable when used alone as a surrogate marker for HPV associated OPSCC. Therefore, in OPSCC with a high suspicion for HPV and which display a basaloid and non-keratinising morphology, a negative p16 IHC stain should be followed by other molecular techniques such as HPV ISH.
The epidemiology of paediatric burn injuries in 6 Johannesburg, South Africa
(2024) Banga, Agatha Tafadzwa
Background Children remain the most common victim of burns in Sub-Saharan Africa. We investigated the epidemiology of burn injuries of the paediatric patients admitted to the Paediatric Burns Unit (PBU) at the Chris Hani Baragwanath Academic Hospital (CHBAH). Objectives To describe the epidemiology of paediatric burn injury among those admitted to CHBAH. Methods This was a hospital based cross-sectional study, with data collected at the time of admission via an accompanying caregiver questionnaire and via clinical examination of the patient by the admitting doctor. Results A total of 509 patients were admitted to the unit over a 12-month period, with 482 patients included for baseline analysis. 50% of admitted patients were between 15 and 47 months with a median age of 25 months. 205 58% of participants were male. 53% of all admissions had burns above 10% total body surface area and were considered severe burns. The predominant mechanism of injury was scalding (84%), with most overall in the winter season (32%). The most common site of burn was upper limb (75%). 63% of all admissions received 208 first aid. Among those who received first aid,an appropriate first aid method was provided in 74% of the cases. 226 out of 482 participants (47%) provided sociodemographic information. Access to basic amenities such as electricity was high, with most admissions coming from households with access to electricity (91%) and using electricity for cooking (83%). Basic level education was shown by 90% of caregivers holding at least a high school leaving certificate. Migrant caregivers made 19% of the caregivers, which was four times the proportion of foreign nationals counted in the national census. Over three quarters of admissions (79%) were 214 referrals from other centres. Severe burns were associated with thermal mechanism of injury (p<0.01), multiple burn sites (p <0.01), and receiving first aid prior to admission (p=0.01). No sociodemographic factors were associated with increased burn severity. Conclusion Children under two years of age and minority groups are at greatest risk for burn injury and should therefore be targeted for burn injury prevention. Education on appropriate first aid is essential to educate the community. Future research should investigate caregivers of children with burn injury
A comparison of malignant histopathological diagnoses on uterine curettings and hysterectomy specimens
(2024) Ismail, Abdullah
Background. Endometrial carcinoma (EC) is a common gynaecological malignancy in postmenopausal females. Diagnosis is made on endometrial biopsy, where histological subtype and tumour grade are used to predict disease progression and to plan surgical management. Objectives. We aimed to determine the accuracy of preoperative biopsies compared to the final diagnosis on hysterectomy specimens in our department. Methods. This was a retrospective, cross sectional study in which 126 biopsies and corresponding hysterectomy specimens, over a 3-year period, were reviewed. Patient demographics and histological features were recorded and statistically analysed. Results. The most prevalent tumours were endometrioid endometrial carcinoma (EEC) (48.5%), serous carcinomas (25.4%) and carcinosarcomas (16.7%). The majority (66.7%) of tumours were high-grade tumours on biopsy and hysterectomy specimens (58.7%). EECs had a poor sensitivity level (65.12%) compared to other subtypes but had a high specificity rate 90%. There was moderate agreement between biopsy and excision specimen diagnoses. High-grade tumours had a high sensitivity (94.29%) level. Conclusions. Our study showed moderate agreement between histopathological diagnoses on biopsy, and excision specimens. EEC was the most prevalent tumour subtype. There was a high sensitivity (94.29%) level for biopsies of high-grade tumours, concordant with other studies. The sensitivity of low-grade EECs (42-46%) was lower than international studies, likely due to the comparatively low prevalence of EECs in our population. Accurate preoperative tumour subtyping and grading are needed to guide surgical management. It is envisaged that use of a combined histological and molecular tumour classification will better guide patient treatment and allow for reproducible results.
Evaluation of histomorphometric changes in the small intestinal epithelium and paneth cells of male Sprague Dawley rats exposed to alcohol and/or combination anti-retroviral drug (Atripla) therapy (cART)
(2024) Maseko, Zekhethelo Leticia
Significant number of individuals who have HIV/AIDS are also chronic alcohol consumers (Pandrea et al., 2010). Alcohol intake has been found to disrupts ARV drug bioconversion and innate immunity of the gut (Bishehsari et al., 2017), but the exact effects of the combined use of alcohol and/or cARV on small intestinal epithelium and Paneth cells remains unclear. Paneth cells are the main regulator of innate immunity of the gut (Salzman et al., 2010). This study evaluated the histomorphologic appearances of Paneth cells and crypt-villous morphology in small intestine of rats exposed to alcohol and/or combination anti-retroviral drug therapy (cART). The study utilized an experimental study design of 32 adult male Sprague-Dawley rats which were divided into 4 groups and treated with normal saline, alcohol, cART or a combination of alcohol and cART. The animals were sacrificed after 90 days. Segments of small intestine were collected and studied to evaluate the morphometric changes of crypts and villi dimensions in the jejunum and ileum, determine the location of the Paneth cells along the axis of the intestinal crypts of the jejunum and ileum. Furthermore, to examine the histomorphological appearance of Paneth cells including their morphology and amounts of secretory granules, in the jejunum and ileum and examine the histomorphological appearance of stem cells in the crypts of the jejunum and ileum using H&E,special stains and immunohistochemistry. Histomorphometric measurements were done using ImageJ software. Analysis of data was done using STATA SE 15 statistical software. Morphometry and morphological analysis showed significant (p < 0.05) reduction in villous height, villous width, crypt’s depth, intestinal stem cells, increased villous stripping, increased crypt’s width, increased muscular wall thickness, increased number of Paneth cells and staining intensity of Paneth cell granules in alcohol + cART treated group. The increase in number of villi was in all experimental groups and highest following treatment with cART alone or in combination with alcohol. The shortest villi, shallowest crypts and the least number of crypts were seen in ileum of animals that had cART alone. The alcohol alone group had the least number of villi but showed increased collagen content. Paneth cells were noted in the proliferation zone of intestines of animals that had combined treatment (alcohol +cART). Concomitant use of alcohol and cART led to thickening of small intestinal wall, shortening and/or stripping the villi, reduction of crypt depth, appearance of Paneth cells in proliferation zone and a decrease in intestinal stem cells. The structural changes in the small intestine and Paneth cells may adversely affect the regulation of gut innate immunity. These findings are clinically invaluable in the management of HIV patients considering the critical significance of innate immunity amongst HIV patients.
Testing the use of three-dimensional surface rendering and mesh-to-mesh comparisons as a method of pair-matching commingled human skeletal remains
(2024) Pillay, Kamini
When dealing with mass graves, natural disasters, or mass fatalities, forensic anthropology faces a complex scenario that necessitates specific methods for sorting, matching, and identification. The main aim of dealing with commingled human remains is to sort the remains to identify the minimum number of individuals (MNI). Traditional sorting methods, such as visual-pair-matching, articulation, process of elimination, and taphonomy, are welldocumented but subjective and rely heavily on the experience and knowledge of the forensic anthropologist. The study aimed to evaluate the effectiveness three-dimensional surface renderings of bone and the subsequent comparison of mesh-to-mesh values as a more objective and repeatable method for pair-matching commingled human remains. The Structure-from-Motion (SfM) technique was used to create and render 171 three-dimensional mesh model samples using Agisoft Metashape. These models were used to test the effectiveness of a new digital pairmatching method, the mesh-to-mesh value comparison (MVC) method against a South African populated sample. To generate the mesh-to-mesh values, different softwares were used: Viewbox 4.1, which is proprietary and uses a Trimmed Iterative Closest Point (ICP) algorithm to run the program, and Meshlab 2022.12, an open-source software that does not require a license and uses a general ICP algorithm to run the program. Each software was programmed to generate a root mean square value, which was used as the mesh-to-mesh value required for comparison. Analysis was performed using two techniques: LCV (Lowest Common Value) mesh-to-mesh comparison using Microsoft Excel and ROC curve analysis performed using MedCalc. The LCV mesh-to-mesh comparison requires the user to filter, sort, and eliminate values based on observation using specific commands on Microsoft Excel until the lowest agreed upon value is found across left-right and right-left. The ROC curve analysis on MedCalc follows the principle stated by Delong et al. (1988), which works with a scoring system. The closer the threshold value is to the top-left corner of the graph, the higher the accuracy of the test being performed. For the complete cadaveric humeri and femora analysis, both elements performed moderately well with the LCV mesh-to-mesh comparison method, while the ROC curve analysis produced considerably higher results, comparatively. For the complete cadaveric bones, the femur performed better with both softwares when compared to the humerus. Mesh-to-mesh values iv obtained through Meshlab and analysed with the ROC curve method generated significantly higher results and were more adept at correctly identifying and distinguishing differences between matches and non-matches. Differences in mesh-to-mesh values between sexes and different population groups were observed. In the simulated fragmented remains, the distal mesh fragment performed the best with 100% sensitivity for Viewbox, and the shaft performed the best using Meshlab with sensitivity results greater than 79%. For the fragmented remains, the distal mesh fragment and the shaft mesh fragments generated significantly high results when using the values obtained through Viewbox and statistically analysed with the ROC curve method. The mesh-to-mesh value comparison method was applied to a real-world forensic commingled assemblage with high fragmentation and taphonomically altered bones. The Structure-fromMotion technique was effective in capturing distinct details on bones, aiding in 3D modelling. However, the method failed to identify true positive matches in the humeri bone sample, as there were no individuals matched with visual pair matching in the original case. In conclusion, the mesh-to-mesh value comparison method has the potential to improve the accuracy and objectivity of forensic anthropology in handling commingled human remains. By utilizing advanced technologies like SfM, ROC curve analysis, and real-world forensic commingled assemblages, this method can be applied to enhance the accuracy and reliability of forensic anthropological research.
An assessment of developmental anomalies in the thoraco-lumbosacral region of South Africans
(2024) Nchabeleng, Elsie Koketso
Developmental anomalies, typically caused by epigenetic interactions, are very common in the human vertebral column. Many studies have been conducted to assess their prevalence in different populations. Several studies have shown differences in the prevalence and expression of vertebral anomalies among populations and between the sexes. These differences may be related to different geographical areas and the environmental conditions posed by these, socioeconomic status, diets, lifestyles and/or gender roles, to name a few. Therefore, this study aimed at assessing the prevalence and pattern of six developmental anomalies in the thoracolumbosacral regions and their possible associations with vertebral pathologies in South Africans. The study comprised skeletal remains of 902 individuals. The remains were procured from the Raymond A. Dart Collection of Modern Human Skeletons, the Pretoria Bone Collection and the Kirsten Bone Collection. The sample included South African Blacks (SAB) (n=325), South African Coloureds (SAC) (n=286) and South African Whites (SAW) (n=291). The most common vertebral developmental anomaly observed in this study was sacralisation (5.7%), followed by spina bifida occulta (4.5%), spondylolysis (4.5%), L6 (3.1%), and T13 (2.2%). The lowest prevalence was seen for lumbarisation at 1.9%. Overall, developmental anomalies were most prevalent in the SAB sample compared to the SAC or SAW. These anomalies were generally more prevalent in males of the total sample and within the three populations groups of the study. The high prevalence of most developmental anomalies in the SAB sample may be mostly related to the low socio-economic status associated with Black South Africans under the apartheid era. The presence of multiple anomalies was more prevalent in Blacks (44.4%). Blacks also had a higher prevalence for multiple anomalies accompanied by some form of spinal pathology (50%). Whites, on the other hand, had a higher prevalence of a single developmental anomaly accompanied by some form of spinal pathology (50%). In general, males were more prone to developing multiple anomalies accompanied by some form of spinal pathology. There was substantial variation observed with regards to the presentation of the six developmental anomalies in and between the samples under study. Therefore, inter- and intrapopulation differences, as well as sex differences, should be considered when dealing with the above developmental anomalies in biological anthropological and clinical setting
Evaluation of the neuroprotective effects of simvastatin against alcohol-induced damage to the sciatic nerve and the somatosensory barrels in adolescent C57BL/6J mice
(2024) Efuntayo, Alice Adetokunbo
Alcohol is a commonly used and abused drug among adolescents which has an adverse effect on the body’s overall health, especially on the developing brain. It causes neurodevelopmental, neurobehavioral, neurocognitive, and social problems because alcohol exerts its neurodegenerative effects by up-regulating oxidative stress which is responsible for neuronal death. The rising prevalence of alcohol-related diseases and disabilities and the cost to the government necessitates investigation into interventions that could protect the neurons against the damaging effects of alcohol. One drug with antioxidant properties is Simvastatin, a U.S. Food and Drug Administration (FDA) approved drug for lowering blood cholesterol levels. The neuroprotective effects of Simvastatin against alcohol neurotoxicity were evaluated on the sciatic nerves and the somatosensory barrel cortices of adolescent mice. 40 four–week old C57BL/6J male and female mice were administered 20% alcohol (i.p.), 5 or 10 mg/kg Simvastatin orally followed by 20% alcohol (i.p.) or the controls (i.e. 5 mg/kg Simvastatin only or non-treated) consecutively for 28 days. The axonal density, myelin thickness and g-ratio of the sciatic nerves were assessed as well as the sizes of the Posteromedial barrel subfield (PMBSF) barrels. The results confirmed alcohol neurotoxicity on the axonal density and myelination in both sexes. At the same time, Simvastatin was effective against the onset of alcohol nerve damage. For the somatosensory barrels, alcohol did not significantly reduce the mean areas of (I) the PMBSF barrels, (II) the enclosure, or (III) the septal portion in both sexes. However, the barrel-to-barrel comparison revealed alcohol toxicity on specific barrels in specific rows and arcs of the PMBSF barrels. Both concentrations of Simvastatin were also effective against alcohol–induced damage on those specific barrels. These may explain the reasons for the sensory-motor delays that are often seen in alcoholics due to possible delays in the relaying of sensory input and the processing and interpreting of information from the somatosensory cortex. Simvastatin seems to have the ability to protect against the damaging effect of alcohol on the peripheral nerves and the somatosensory cortex and this may be beneficial in reducing the prevalence of alcohol-related diseases or disabilities, especially in adolescents that are prone to abusing alcohol.
A morphometric analysis of the growth of the immature and sub-adult human palate
(2021) Onwochei-Bolum, Nkemakonam Vincent
Postnatal nutrition in humans is associated with advancement in the mode of feeding from the neonatal and infancy period of growth to adulthood. During the neonatal and infancy periods, the palate functions in suckling, tongue manipulation and swallowing, while in adulthood and with dental eruption, the palate participates in both mastication and in the production of sound. It is anticipated that the transition in the role of the palate due to alterations in its function over time will cause morphological changes. Thus, the aim of this study was to analyse alterations in the shape and dimensions of the human palate from birth through the stages of dental eruption to the complete emergence of the permanent dentition in the sub-adult stages of life. Crania from 72 South African individuals were sourced from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand. The sample was divided into three age groups to correspond with the age ranges of the eruption of the deciduous dentition (birth to 5 years of age), mixed dentition (6 to 12 years of age) and the permanent dentition (13 to 20 years of age) respectively. A series of 14 osteological landmarks were digitized across the oral surface of the palate using an Immersion MicroScribe G2 unit. Landmark data were converted to linear distances and the length, width and elevation of the palate were assessed in relation to the state of the dentition. Analysis included both quantitative (linear measurements) and qualitative (wireframes) methods. The length and width of the palate in the permanent dentition group was significantly larger when compared to the mixed and deciduous dentition groups. While elevation of the palatal dome in the permanent dentition group was significantly greater than that of the palate in the mixed dentition group, no further significant differences were observed. Thus, changes in the morphology of the palate appear to be progressive with dental eruption and development across the different states of the dentition. By establishing the nature of the changes in the functional environment of the palate during development and growth, abnormalities in the postnatal development of the palate could be diagnosed.
The association between skeletal lesions and tuberculosis in a South African sample
(2021) Masiu, Rethabile
Tuberculosis is an infectious disease. Skeletal TB is the extra-pulmonary manifestation of Mycobacterium tuberculosis infection and occurs in about 1-5% of all TB cases. The aim of this study was to assess the sensitivity and specificity of skeletal lesions to accurately diagnose TB in a pre-antibiotic South African skeletal sample. For this purpose, 23 skeletal lesions were assessed on 436 skeletons from the Raymond A. Dart Skeletal Collection. These skeletons were divided into three groups: individuals where TB was recorded as cause of death (n=177), individuals where other pulmonary diseases were recorded as cause of death (n=109) and individuals where a variety of diseases, excluding TB and other pulmonary diseases, were recorded as causes of death (n=150). Chi-squared and Fisher’s Exact tests were used to assess differences between groups. The skeletal lesions’ respective sensitivities and specificities were also calculated and compared to a similar study by Dangvard Pedersen et al. (2019a). Lesions on the ventral surface of thoracic and lumbar vertebral bodies were observed significantly more in TB cases than in controls. This lesion type was also found to be the most valuable indicator with a high sensitivity and 55% probability of a true TB diagnosis if observed. An association between skeletal lesions and TB could only be found for rib and vertebral lesions. Distinct differences between this study and the study by Dangvard Pedersen et al. (2019a) indicated that TB-related changes were likely to be observed in a South African skeletal sample even when individuals were not documented to have died of the disease.
The effect of all-trans retinoic acid on the migration of avian neural crest cells in vitro an in vivo
(University of the Witwatersrand, Johannesburg, 2007-02-15T11:43:45Z) Tshabalala, Vincent Abie Thabiso
Retinoic acid, the active metabolite of Vitamin A is known to play a major role in embryonic growth and differentiation during development. It has been shown that either excess or deficiency of retinoic acid during embryogenesis can be teratogenic. In order to study the teratogenic effects of retinoic acid, the aim of the present study was therefore to investigate the effect of all-trans retinoic acid on the migration and fate of neural crest cells in vitro and in vivo. In addition, the study investigated the effect of retinoic acid on the cytoskeletal elements of neural crest cells and on Rac and Rho, two members of the Rho family of GTPases. The neural tubes containing neural crest cells of quail embryos were removed at cranial levels and cultured on fibronectin as a substrate. The neural tubes were cultured in either Dulbecco’s minimal essential medium (DMEM) or in DMEM+Dimethylsulphoxide (DMSO) as controls. In order to test the effect of retinoic acid, the neural tubes were cultured in 10⁻⁵M all-trans retinoic acid (RA) which was reconstituted in DMSO. The distance of migration of the cultured quail neural crest cells was measured and compared between the controls and the experimentals. To study the effect of RA on the cell actin cytoskeleton in vitro, cultured neural crest cells were stained with rhodamine phalloidin. In addition, following 24 hours of culture, the quail neural crest cells were brought into suspension and micro-injected into 36 hour-old chick hosts. While the migration of neural crest cells was extensive in the control cultures in vitro, migration was inhibited in the retinoic acid-treated neural crest cells. In addition, retinoic-acid treated neural crest cells showed pigmentation and neuronal processes earlier than did the control neural crest cells. Retinoic acid-treated neural crest cells showed a disarray of the cytoskeletal elements as they were devoid of stress fibres and focal adhesions. In addition, retinoic acid appears to decrease the expression of Rac and Rho of cultured quail neural crest cells. Following micro-injection of cultured control and RA-treated quail neural crest into the cranial region of chick hosts, the control cells populated the beak area, whereas the retinoic acid-treated quail neural crest cells migrated to the retina of the eye, a region they normally do not populate. These results suggest that retinoic acid disturbs the migration of neural crest cells. It appears to do this by affecting the cytoskeletal elements of neural crest cells and the genes that are involved in forming these elements.

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