School of Anatomical Sciences (ETDs)

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Mathematical representation and analysis of articular surfaces: application to the functional anatomy and palaeo-anthropology of the ankle joint
(University of the Witwatersrand, Johannesburg, 1990) Webb, Christie Peter; Tobias, Phillip Vallentine
This thesis is a study of quantifiable variation in the geometric shape of the superior articular surface of the talus of higher primates, with special reference to fossil tali of Plio-Pleistocene hominids. (Abbreviation abstract).
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.
Maternal and child oral health status: investigation of the effect of parity and socio-behavioural factors
(2020) Obhioneh, Oziegbe Elizabeth
Background: Reproduction in women is associated with physiologic, metabolic and nutritional changes due to adjustments during pregnancy, breastfeeding and childrearing. These changes are thought to be potentially cumulative when parity is high and may have negative effects on the general health of women. It is likely that maternal oral health is affected as well, as ‘a tooth for every child’ is a common adage in many cultures. Even so, there is limited information on the relationship between parity and maternal oral health status. The available evidence is largely from European populations. Most research investigated tooth loss in women of fairly low parities and failed to consider caries and periodontal disease or the behaviours that are likely confounders affecting oral health status. Furthermore, there are no studies on the beliefs of high parity mothers regarding parity and tooth loss. Aim: The aim of this study was to determine the relationship between parity level and oral health status in a high parity population. Age, nutritional status, socio-economic status and oral health practices (frequency of consumption of refined sugar and tooth brushing, use of fluoridated toothpaste and number of dental visits) were considered when investigating tooth loss, dental caries and periodontitis levels in Nigerian Hausa mothers. Early childhood caries was evaluated for mother-child dyads. Women participated in focus group discussions to elicit qualitative data used to contextualise the study for the Hausa cultural environment. Materials and methods: This was a cross-sectional study with a mixed methods design. A total of 635 married Hausa women of all parity levels aged 13-80 years and 346 accompanying children aged less than 72 months were recruited. Women with 5 or more children were considered high parity while those with less than 5 children were regarded as low parity. Information on the socio-demographic status and oral health behaviour/practices of the women was obtained using a structured interviewer-administered questionnaire. A separate questionnaire was used to obtain information from the mother on the child’s socio-demographic profile and oral health behavior/practices. The weight and height of the participants were measured to calculate their BMI status (kg/m2). The oral hygiene status of the mothers and their children was assessed using the Simplified Oral Hygiene Index (OHI-S) of Greene and Vermillion. All teeth present in the mouth excluding the third molars were recorded, and all missing teeth were recorded regardless of the reason for tooth loss. Women’s caries status was determined using the Decayed Missing Filled Tooth (DMFT) index. Periodontal status was assessed with a lightweight periodontal probe using the Community Periodontal Index (CPI). Caries in the children was also assessed using the dmft index. Women’s beliefs on causes of tooth loss and any link between parity and tooth loss were explored through a qualitative analysis using a grounded theory approach through focus-group discussions with 33 women of differing parities. Data were analyzed using SPSS (version 16) software for Windows. Analyses included frequencies, cross-tabulations and regressions. Statistical significance was inferred at p<0.05. Associations between categorical variables were determined using chi-square tests while those between continuous variables were tested with Student’s t-tests and ANOVA. The mean DMFT scores and tooth loss with standard deviation were computed for the different age cohorts, parity levels, parity groups (high and low) and nutritional statuses. Comparisons between parity groups were done using Student’s t-tests, while comparisons between age cohorts and nutritional statuses were tested using ANOVA. In addition, the mean number of sextants with CPI scores of 0-3 and 4 was determined for the different age groups, parity levels and nutritional status. Comparisons across age groups, parity levels and nutritional status were done using ANOVA. Linear regression was performed to predict the factors that best contribute to caries, periodontal disease and tooth loss in the women with caries, periodontal disease and tooth loss modeled as dependent variables (each in separate analyses) and socio-demographic variables, oral health behaviour/practices, reproductive parameters and nutritional status as independent variables. Information obtained through focus group discussions on causes of tooth loss, parity and tooth loss were analyzed thematically using ATLAS-ti. Associations between caries experience in mother-child dyads were tested using Fisher’s exact tests. Binary logistic regression was done to predict factors that best contribute to early childhood caries (ECC) in the children. Results: Women in the earlier reproductive stages (18-37 years) characterize the study population (65.1%) with 55.7% of them of low parity. The mean parity (4.33±3.04) was slightly below what is regarded as high parity. There was limited variability in the SES and BMI of the participants. Both measures were associated with age, as older women were typically of middle SES and higher BMI. SES and BMI were not associated with caries experience, periodontal disease or tooth loss Hausa women generally had low prevalences of caries, serious periodontal disease and tooth loss, despite their poor oral hygiene and limited use of dental care facilities. A traditional diet that is low in refined sugars, along with good enamel quality, may contribute to this oral health profile. While tooth loss in the Hausa women was generally low, older and higher parity women experienced significantly more tooth loss. In addition, increased duration of reproduction was significantly related to fewer remaining teeth. The contributory weights of age, duration of reproduction and parity to tooth loss were 13.6%, 1.2% and 1.0%, respectively. Caries experience in the women was also low, yet higher parity women were found to experience significantly more caries. Women’s age contributed 8.5%, while parity accounted for 0.8% of their caries experience. The prevalence of some level of periodontal disease in the participants was very high. The majority had calculus deposits (code 2), although those with periodontal pockets (codes 3 and 4) were few. Age, level of education and frequency of tooth cleaning were significantly associated with periodontal disease. Notably, parity was not significantly associated with periodontal disease. The caries frequency (ECC) in the children was very low. Binary logistic regression analysis revealed that only the age of the child was significantly associated with ECC. The mother’s caries experience was not related to ECC in the child. The focus group participants did not associate parity per se with tooth loss, although they believed that payar baka (vomiting during childbirth) resulted in loss of teeth. The women perceived other causes of tooth loss to be dirty mouth, tooth worm, ageing and sugar cravings. Conclusion: The cumulative effects of high parity, as observed in older women, were associated with maternal oral health status (caries and tooth loss) in a fairly homogenous sample of Hausa women with low variation in oral hygiene status, diet, oral health practices, SES and BMI. Thus, reproductive history is an important determinant of oral health conditions in Hausa women.
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.
Post-mortem interval estimation and insect succession patterns in the tropical climate of nigeria
(2022) Etoniru, Izuchukwu Stanley
Post-mortem interval (PMI) estimation is the first step in the identification of badly decomposed remains. Apart from identifying the victim, obtaining the PMI is an important aspect in investigation into the cause and manner of death, and helps to narrow down the number of suspects. The ongoing armed conflict in Nigeria which has lingered over a decade has left a large burden of human remains. These remains are mostly left in the fields where the attacks occurred for fear of further attacks, especially in cases of terrorism. They are, therefore, badly decomposed at the time they are recovered, and identification becomes more difficult in a country that has very few forensic scientists. Law enforcement agencies usually resort to mass burials without identification. The aim of this study was to assess decomposition rates in southern Nigeria and to derive formulae for PMI estimation using the quantitative variables Accumulated Degree Days (ADD) and total body score (TBS), and to obtain the arthropod succession pattern during decomposition using a pig model. To achieve this aim, a longitudinal examination of quantitative variables, TBS and ADD, was conducted over a period of 14 months. This period included both the dry and wet seasons. Scatter plots between TBS and PMI, and TBS and ADD were used to show decomposition patterns. Arthropod succession patterns were also observed during the study for each carcass. Decomposition was found to progress rapidly, and desiccation was a frequent occurrence during decomposition. There were marked differences in decomposition patterns between the seasons, with the wet season exhibiting a more rapid decomposition. Linear regression formulae for ADD and PMI, and 95% confidence interval charts for TBS for ADD were derived. The arthropods arrived very early on the pig cadavers. There was more arthropod abundance and species richness in the wet season than in the dry season. There were also some arthropods that were observed only in the wet season. A combination of these formulae and insect activity will lead to a more precise PMI estimation in Nigeria and regions with similar climate. The data on insect succession developed from this study will serve as a reference for forensic researchers
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
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.
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.
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 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.
Characterising skeletopathy in an animal model of Type 2 diabetes
(2024) Dlamini, Gcwalisile Frances
Type two diabetes (T2D) is a chronic, progressive heterogonous syndrome with a genetic and environmental origin. It is now recognized as an epidemic with a high morbidity and mortality rate. The endocrinology of type 2 diabetes (T2D) and its predisposing factors have been studied extensively, while diabetic skeletopathy has received negligible research. Previous studies report that fractures in T2D vary with specific sub regions in bones, therefore prompting our study to focus mainly on the femoral head and neck as well as the humerus head. Femoral neck fractures are the commonest, followed by the proximal femur, distal radius and proximal humerus. Susceptibility to fracture is a sequelae of poor bone remodeling. Poor bone remodeling is established at molecular and cellular levels. It depends on the activity of osteoblasts, osteocytes and osteoclasts, which are under the influence of TGF-β1, a pro-osteogenic cytokine, together with BMP3, an anti-osteogenic cytokine.T2D induced bone marrow adipocity and the accumulation of AGEs in cortical bone have also been implicated in increasing susceptibility to fracture. It is still unclear how T2D affects molecular and cellular elements that culminate in weaker bones observed in diabetic patients. In addition, it is debatable if T2D affects the skeleton at disease onset or later in the disease. Therefore, this study aimed to characterize T2D induced skeletopathy and related it to age, in the Zucker Diabetic Sprague Dawley (ZDSD) rat, using the femur and humerus. This study initially confirmed the diabetic state by monitoring animal weights, fasting blood glucose levels, and fasting oral glucose tolerance tests (OGTTs) every fortnight. Then triglyceride levels and quantified serum levels of osteoregulatory hormones such as insulin and osteocalcin were monitored. To assess oxidative stress, Malondialdehyde (MDA) serum levels were also determined by ELISA. Once diabetes was successfully induced, rats were grouped according to strain and age at termination. Termination age was at 20 weeks and 28 weeks . The Sprague Dawley (SD) rats were v the controls, while the Zucker Diabetic Sprague Dawley rats (ZDSD) were the experimental groups. These were designated as SD20WK (n=8) and ZDSD20WK (n=7) respectively. Another batch was designated as SD28WK (n=8), and ZDSD (n=15) that were terminated at 28 weeks of age. The latter were further divided into moderate diabetes (ZDSD28WK-MOD) (n=9) and severe diabetes (ZDSD28WK-SVD) groups (n=6). Bilateral humeri and femora were harvested then fixed in 10% buffered formalin. Right proximal femora and humeri were scanned using a 3D-μCT scanner (Nikon XTH 225L) to analyse trabecular morphometric parameters, cortical bone area and medullary canal area. Biomechanical strength was analyzed by three point bending tests using a universal tensile tester. Left proximal femora and humeri were processed for histology. Some sections were stained with Haematoxylin and Eosin (H&E) to assess normal histologic morphology and adipocyte quantification. Remnant sections were immunolabelled using the anti-TRAP and anti-ALP antibodies for osteocyte and osteoblast quantification respectively, to assess osteolysis and osteogenesis. Immunolocalization of AGEs, TGF-β1 and BMP3 was also conducted to investigate their role in diabetic skeletopathy. We found that diabetes affected osteoblastogenesis as measured by ALP positive cells and bone marrow adipocytes. TRAP positive osteocytes numbers were increased in the presence of T2D, suggesting an increased osteolysis. There was reduced TGFB1 expression with increased BMP3 expression. The number of AGEs immuno-positive cells as well as its extracellular expression was increased. Our finding suggest that osteoblast and osteocyte numbers are regulated by TGFβ1 and BMP3 in both bones, under the influence of AGEs. Our findings from osteometry, 3-point bending tests and Micro CT support that diabetes weakens bone. The diabetic effect results in lighter, shorter hollow bones that perform poorly under loading, as well as exhibit unfavourable trabeculae microarchitecture. Our findings confirm that T2D causes increased fragility in the proximal femur and humerus as well the mid-diaphysis. These perturbations occur early and late in the disease, and they are also exacerbated by the presence of hyperglycemia. vi We conclude that the ZDSD rat can be used as a translational model for diabetic skeletop
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.
Evaluation of antioxidant properties and neuroprotective effects of methanolic leaf extract of combretum molle in D-galactose-induced aging model of Sprague Dawley rats
(2024) Fasemore, Thandi Mamorapelo Dorothy
Several physical and biochemical changes in the body occur because of the biological process of aging. As part of natural aging, the brain encounters morphological and functional changes that affect dendritic trees and synapses, neurotransmission, circulation, and metabolism. The brain's high metabolism, elevated levels of lipids, and inadequate antioxidant defences make it susceptible to oxidative stress. A reducing sugar called D-galactose (D-gal) causes a significant build-up of reactive oxygen species (ROS). Combretum molle (C.molle) is a plant rich in compounds that scavenge free radicals and is frequently used to cure a variety of human illnesses in African traditional medicine. This study investigated the potential impact of C.molle on rat brain aging brought on by D-galactose. Fifty adult male Sprague Dawley rats were treated for 90 days and were composed of 5 groups (n=10) as follows: I) Control group received saline and distilled water, II) C.molle only group received intragastric gavage of C.molle (500 mg/kg), III) D-gal only group received a subcutaneous injection of D-galactose (150 mg/kg), IV) CMD 90 group received D-galactose and C.molle simultaneously for 90 days, V) CMD 45 group received D-galactose for the first 45 days and C. molle for the remaining 45 days. The animals underwent behavioral evaluation post-treatment for a further period of 7 days twice a day. The rat’s cognitive function was evaluated through Novel object recognition and object location tests. The C.molle ’s neuroprotection was evaluated through levels of acetylcholinesterase (AchE), Acetylcholine (Ach), Brain Derived Neurotropic Factor (BDNF), and Tumor Necrosis Factor (TNF) alpha including the effects on adult neurogenesis through Ki-67 and doublecortin (DCX) immunohistochemistry. The oxidative stress level was measured through the evaluation of lipid peroxidation marker malondialdehyde (MDA), glutathione peroxidase (GSH-Px), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity. The C.molle significantly attenuated the effects of D-galactose-induced changes in the hippocampus and cortex, ranging from cognitive capacity, and oxidative stress by increasing GSH, BDNF, Ach, GSH-Px, CAT, and SOD activity. Additionally, C. molle caused a decrease in the levels of MDA, TNF alpha, and AchE activity, and ameliorated reduced cell proliferation and neuroblast differentiation brought about by D-galactose.
In vitro and in silico characterization of the anticholinesterase activity of select terpenoids against anopheles vectors
(2024) Rants’o, Thankhoe Abram
Malaria is a life-threatening plasmodial disease that is transmitted by female Anopheles mosquitoes. Major African malaria vectors include Anopheles arabiensis, An. funestus, An. gambiae and An. coluzzii. Malaria vector control programs have shown effectiveness in reducing the Anopheles populations. The main insecticide classes used in these interventions include pyrethroids, organochlorines, organophosphates, carbamates, and neonicotinoids. Nevertheless, the development of Anopheles resistance to these insecticide classes has greatly reduced the effectiveness of these interventions. A common resistance mechanism is through rapid detoxification of insecticides by overexpressed P450 monooxygenases. Although acetylcholinesterase (AChE) is a valid target in Anopheles vector, current anticholinesterase insecticides suffer from resistance and low selectivity between insect and mammal AChE targets. This indicates the urgent need to discover novel AChE inhibitors with higher affinity to Anopheles AChE compared to the mammal target, and less prone to resistance caused by the overexpressed monooxygenases. Identification of novel AChE inhibitors from natural sources and their potential to kill Anopheles during all its different life stages, presents a cost-effective approach. This PhD study aimed to identify such novel AChE inhibitors from essential oil sources and assess them for consistent activity against Anopheles species with hyperactive P450 monooxygenases. In this study, molecular differences between Anopheles and human AChEs were identified showing the opportunity to develop selective Anopheles AChE inhibitors. A novel approach was used to integrate the in silico and in vitro assays in assessing the Anopheles AChE inhibitory potential of select terpenoids and coupled these to the in vivo assays against different life stages of Anopheles. The terpenoids, farnesol, (-)-α-bisabolol, cisnerolidol, trans-nerolidol, and methyleugenol were identified as potent Anopheles AChE inhibitors and larvicidal agents with moderate adulticidal effects. Farnesol and (-)-α-bisabolol also displayed pupicidal activity, while methyleugenol inhibited the hatching of Anopheles eggs. Generally, farnesol and (-)-α-bisabolol were highly active across the Anopheles species, except in the strain with P450-based metabolic resistance. In contrast, the efficacy of cisnerolidol, trans-nerolidol, and methyleugenol was not affected by this resistance mechanism. This research suggests that cis-nerolidol, trans-nerolidol, and methyleugenol are potential candidates for further development as anticholinesterase bioinsecticides.
Effect of boophone disticha on the behaviour and hippocampal neuroanatomy in a BALB/c mouse model
(2024) Xhakaza, Nkosiphendule Khuthazelani
Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, light dark box, open field forced swimming, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five-day repeated forced swim stress (5dRFSS) and 28 days chronic restraint stress. Male Balb/c mice were subjected to the 5dRFSS and 28 days chronic restraint protocols to induce depressivelike behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test, increased time in dark box in the light dark box test, reduced frequency of rearing and increased time on the sides of the open field in the open field test), and treated with distilled water, fluoxetine and BD. Three weeks Boophone disticha treatment (10mg/kg/p.o) significantly attenuated both the 5dRFSS and chronic restraint-induced behavioural abnormalities and the elevated brain tissue corticosterone levels observed in stressed mice. Additionally, 5dRFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. In the chronic restraint stressed mice, similar effects of BD treatment were observed after 21 days of treatment, however, the levels of corticosterone were not different in control and stressed animals, probably due to habituation to stress. In both 5dRFSS and chronic restraint stress, the antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. It is important to note that in chronic restraint stress mice, it appeared that animals seemed to have habituated to stressful conditions, demonstrated in part by brain tissue levels of corticosterone that were not elevated in stressed animals treated with distilled water. However, BDNF levels remained significantly low in stressed animals treated with distilled water, suggesting that the effect of chronic stress in this parameter were not reversed when animals habituated. In conclusion, our study shows that BD exerted antidepressant-like effects in both 5dRFSS and chronic restraint stress mice, mediated in part by normalizing brain corticosterone and BDNF levels. Due to some degree of habituation in chronic stress model, caution should be exercised when evaluation effects of treatment in different parameters to evaluate antistress effects of tested agents, particularly levels of corticosterone. Furthermore, the persistent low levels of BDNF suggest that habituation of animals to chronic stress is due to normalising levels of corticosterone but not BDNF. The above occurrence could suggest that recovery from chronic stress without antidepressant treatment could alleviate other behavioural symptoms but not cognitive impairment which is influenced in part by BDNF levels.

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