I have conducted sequence analysis of a zebrafish cDNA that encodes the protein DNA (5-cytosine) methyltransferase. I show that during development transcription of this zebrafish DNA methyltransferase gene is most high at blastula where it is ubiquitously expressed. At 24 hours of development, highest expression is observed in the brain, neural tube, eyes, and differentiating somites. To further assess the role of DNA methylation during development, I treated zebrafish embryos with 5-aza-cytidine (5-azaC), a nucleotide analog known to induce cellular differentiation and DNA hypomethylation in mammalian cell cultures. Treatments with 5-azaC during blastula and early gastrula caused a perturbation of the body axis resulting in loss of tail, and loss or abnormal development of the somites. Histological sections and in situ hybridization revealed whole or partial loss of a differentiated notochord and mid-line muscle in treated embryos. There was loss of expression of no tail in the notochord and eng in muscle-pioneer cells at 24 hours. When examined during gastrulation, 5-azaC treated embryos has a shortened and thickened axial mesoderm. DNA analysis on 5-azaC-treated embryos indicated an overall decrease in DNA methylation when compared to untreated controls. Embryos treated with 6-aza-cytidine, a cytidine analog not known to affect DNA methylation, showed neither abnormal development nor hypomethylation. Our findings suggest that normal DNA methylation is required for proper differentiation of dorsal mesoderm and pattern development of the dorsal-ventral body axis.

The neural crest (NC) is a vertebrate specific early embryonic stem-cell population that forms an array of derivatives in the developing embryo. These cells are induced from the developing ectoderm at the boundary of the neural plate and non-neural ectoderm (termed the neural plate border). After initial induction the NC migrate along predefined routes within the developing embryo and upon reaching their destination begin to differentiate into this myriad of derivatives. These derivatives include neurons, glia, cartilage, bone, connective tissue and pigmented melanocytes, among others. Through genetic studies a variety of genes important in these various stages of NC development have been identified. Together, these genes comprise the emerging NC gene-regulatory-network (NC-GRN). Although a variety of genetic components have been identified exactly how they interact with one another during NC development is not fully understood. One key family of genes important in the NC-GRN is the transcription factor activator protein 2 (TFAP2). Initial studies had identified an important role for TFAP2 in initial NC induction, as elimination of two family members (TFAP2A and TFAP2C) resulted in a complete absence of NC and all subsequent derivatives. Although TFAP2 was critical for NC development it was not clear exactly how TFAP2 fit into the NC-GRN and whether additional roles of TFAP2 existed within this network. Here in, we have addressed these questions by identifying a key transcriptional target of TFAP2, SOX10, during NC development. In addition, we have examined how TFAP2 is regulated by Wnt-signaling during NC development. Finally, we have identified an additional role for TFAP2 family members in regulating an additional step of NC development mainly the differentiation of NC-derived melanocytes and identified several targets that may mediate this effect. Together these findings provide a more clear understanding of TFAP2's role in the NC-GRN during development. Given disruption of this network contributes to disease of the NC these findings should provide insight into the etiology as well as provide potential therapeutic intervention for these diseases. In addition, understanding differences in the vertebrate NC-GRN to non-vertebrate GRN's should provide insight into the emergence of this important cell type during evolution.

Lumbosacral transitional vertebrae (LSTV) are defined as congenital anatomical variations, observed unilaterally or bilaterally, in which the transverse process of the last lumbar vertebra exhibits signs of dysplasia evident as increased craniocaudal height, with varying degrees of articulation or fusion to the ‘first' sacral vertebra. Such variations give rise to vertebral morphology that may display lumbar or sacral characteristics at the terminal lumbar spine, together with subsequent enumeration variation. The purpose of this study was to establish baseline data on the prevalence rates of LSTV and to describe the morphological characteristics (Type, subtype, frequency of side and spinal enumeration) of LSTV in the South African population. This study was subdivided into two main sections, namely Part 1: medical imaging appraisal and Part 2: osteological morphology appraisal. In Part 1, both retrospective and prospective cohort randomised sampling methods of data collection of medical images were used. The appraisal of the medical images included radiographs, magnetic resonance imagers and computerised tomography scans. Prevalence rates, utilising the Castellvi et al. (1984) classification, were established via radiographs only. Additionally, lumbar spine enumeration, namely lumbarisation and sacralisation, was made through the appraisal of lumbar radiographs. Images were obtained from medical radiology practices located at Groote Schuur Hospital in Cape Town, Western Cape Province and Charlotte Maxeke Johannesburg Academic Hospital in Johannesburg, Gauteng Province. The total imaging cohort included 3096 individuals of which 308 individuals (10%) were found to contain LSTV. Prevalence rates were further evaluated by subdivision of the three largest ancestries in South Africa. Ancestries were classified as African (n=1032), Mixed (n=1032) and European (n=1032). The prevalence of LSTV in the three ancestral groups was 10.5%, 9.3% and 9.9% respectively and the sex distribution was greater in females (52.1%) then in males (47.9%). The morphological assessment found the prevalence of LSTV by Type was Type II (67.9%) followed by Types III (27.6%) and IV (4.5%). The most frequent subtype by prevalence was Type IIA (41.9%) followed by Type IIB (26%), Type IIIB (21.8%), and Type IV (5.8%). Additionally, the frequency of side was bilateral (47.7%), left (26.6%), right (21.1%), and other (4.5%). Comparison of ancestry and spinal enumeration analyses established statistical significance for individuals of African-ancestry (67.0%) and Mixed-ancestry (72.9%) both of which demonstrated a greater affinity of prevalence for sacralisation (p=0.008), with a small effect size (V=0.178) over the European-ancestry subgroup (52.4%). Furthermore, a statistical significance with a medium effect size (V=0.256) was found in males (p=0.010) when comparing ancestry and spinal enumeration between sexes. In Part 2, a systematic search of the total cadaveric skeletal collection housed at the University of Witwatersrand (the Dart Collection of skeletons) yielded 1797 human skeletal specimens of between 21 and 65 years of age at time of death. One-hundred and fourteen skeletal remains were identified as containing LSTV. Damage and loss of vertebral elements resulted in a subset of 91 LSTV for study. A sex balanced control group cohort of 30 males and 30 females was selected at random from the Dart Collection for comparative analyses. A number of osteometric measurements were evaluated comparing the LSTV and control group cohorts. Numerous osteometric comparisons were statistically significant highlighting the many changes in lumbar and sacral morphology associated with LSTV. There are several original findings to emerge. Thisis the first study to establish the prevalence of LSTV in a large sample from the South African population, subdivided into the three largest ancestral groups. Novel findings associated with LSTV include iliolumbar articulation, bipartition of the sacral foramen, intra-articular vacuum phenomenon of accessory articulations of LSTV, enlargement of the contralateral TVP associated with Types III and IV LSTV, lumbar ossified bridging syndrome and a novel complex named by the researcher as the transverso-sacro-iliac articulation. Furthermore, the researcher has proposed three modifications to the Castellvi et al. (1984) classification, namely (1) that there should be a sub-classification of the Type IV LSTV into right and left nomenclature, (2) the inclusion of a new subtype of Type II LSTV morphology, a unilateral right or left iliolumbar articulation associated with contralateral Type IIA morphology, and (3) a modified morphological classification of LSTV based on the presence of an extended sacroiliac articulation either directly or via the transverso-sacro-iliac articulation. The latter effectively increases the size of the sacroiliac joint and is thought to increase spinopelvic stability. The transverso-sacroiliac articulation was demonstrated for all clinically significant LSTV Types (II-IV), both unilateral (right or left) and bilateral. Finally, this is the first study to incorporate an in situ and an ex situ study in the same population by examining spinal morphology of LSTV using medical images and skeletal remains for descriptive analyses.

The purpose of this study was to explore the perceived value of supplementing the traditional cadaver dissection course at the University of Cape Town's Faculty of Health Sciences (UCT FHS) with alternatives in order to aid students in their learning of anatomy. The study aimed to collect information which could be used to provide insight into facilitating a deeper educational experience for students and teachers alike in the future with the aim of better retention of knowledge over time. The intention of the study was to obtain results which could potentially provide insight into the feasibility of adopting a contemporary view on anatomy education at UCT FHS and thus inform the anatomy course in the future by acquiring feedback directly from the students and staff of the university. Data was collected by way of a 22 question survey delivered to second to sixth year MBChB students as well as the staff and postgraduate students at UCT FHS. The survey was entirely voluntary. A total of 190 complete responses were collected. The results of the study indicate that both staff and students feel that the cadaver dissection course is an irreplaceable part of the curriculum, and if the faculty chose to use any technological alternatives to teach anatomy, that they should supplement and not replace traditional dissection. Furthermore, the study showed that the staff and students are comfortable with technology in general, and are open to the use of various technologies such as online material, virtual software, media sites, applications and the like in order to bolster their learning. These results may provide insight into the viability of adopting a contemporary view on anatomy education at UCT FHS and may thus inform changes to the anatomy curriculum in the future.

In his thesis, Correlation between invasive abdominopelvic and lower limb procedures and the detailed anatomical description of the lumbar plexus in a South African population, the promovendus conducted an in-depth examination of the anatomy of the lumbar plexus. The origin, as well as the course and termination of the five terminal branches were investigated. The first aspect of the study was to observe the root values and describe the origin and abdominopelvic course of its main branches. Thereafter, distances of the nerves to clinically relevant bony landmarks were measured. Lastly, the results were correlated to current guidelines of clinical procedures performed on the pelvis and lower limb. In conclusion, the promovendus was able to support many of the techniques currently performed through detailed, quantitative anatomical descriptions and, where prudent, was able to provide recommendations to assist medical practitioners with pre-operative planning in a clinical setting. / Thesis (PhD)--University of Pretoria, 2019. / Anatomy / PhD / Unrestricted

Human and faunal skeletal remains were found scattered around the base of a talus cone at the bottom of a 30 metre sinkhole at Khoraxa-ams northwest of the Central Namib Desert. Subsequent dating of the site indicated that the remains had been deposited in the cavern in the order of a thousand years ago. The aim of this study was to examine skeletal remains recovered from the site and draw possible conclusions as to who they were and the circumstances surrounding their deposition in the cave. A forensic analytical approach was utilized to uncover the evidence, allowing us to manage the site as a 'crime scene.' This approach included determining the MNI, constructing a demographic profile and analysing post-mortem preservation as well as posing questions vital to forensic investigations including ante-mortem features that could lead to the ethnic identification of unknown individuals and the peri-mortem circumstances surrounding the deposition of the remains. Sixteen individuals, based on cranial bone representation were identified in the sample, consisting of only adult individuals with the exception of one sub-adult, and a male to female ratio of roughly 1:1. The people of Khoraxa-ams were of Negroid ancestry, consumed a mixed diet of gathered and agricultural foods, were in fairly good health at the time of their death, showed signs of involvement in low-impact labour and practiced dental modification. Their most likely identity, based on these biological markers, lifestyle observations and cultural practices, is a group similar or ancestral to the modern Herero of Namibia. The exact nature and circumstance surrounding the cause of death is unknown. Based on the extent of skeletal injuries, it is likely that they received peri-mortem blunt force trauma and post-mortem trauma after death by being dropped into the 30 metre cave. It is speculated, given the demographic profile of women and children presenting with more severe blunt force trauma, the lack of defence wounds and the fact the individuals were dead before being dropped in the cave, that the site at Khoraxa-ams represents an execution location, though no secure evidence exists to support this theory. The forensic approach to this study has enabled the identification of otherwise unknown archaeological remains, and has also provided insight into a period of Namibian history where relatively little is known.

Summary The anatomical description of the erector spinae -, paravertebral - and epidural block for post-operative pain management in paediatric care S Govender Supervisor: Prof AN van Schoor Co-supervisor: Prof AT Bosenberg Department of Anatomy: Clinical Anatomy, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa The fundamental indicative constituent for any successful clinical procedure is patient satisfaction, which is directly related to post-operative analgesia. In paediatric care, due to the nature of the patient – and depending on the age group – it is often difficult, or even impossible, to fully understand the extent of pain perceived, leading to insufficient pain management. A variety of regional anaesthetic techniques have been thoroughly investigated for the ease of administration, as well as enhanced patient satisfaction. Coupled with image modalities, these blocks can be safe and efficient. However, these investigations mainly apply to an adult population. Paediatric procedures may be inaccurately extrapolated from an adult population, when the anatomical discrepancies that exist between population groups are not taken into consideration. Until recently, the gold standard for paediatric truncal procedures relied solely on paravertebral and epidural blocks. With the discovery of the novel interfascial erector spinae plane block, however, this is no longer the case. This block is hypothesised to target the ventral and dorsal rami of spinal nerves, as local anaesthetic is deposited into the erector spinae fascial plane space. The therapeutic effect of the block is attributed to the cranio-caudal spread of anaesthetic over multiple vertebral levels within the tissue plane. This ‘happily accidental’ block serves as a “paravertebral block by proxy” and is an alternative approach, targeting similar nerves as in the paravertebral and epidural blocks. However, the anatomy of the erector spinae plane block is not fully understood. This study aimed to investigate the anatomical differences of these three blocks for the management of post-operative pain in paediatric care, based on observations and measurements from a fresh paediatric cadaver sample, as well as ultrasound and computed tomography scans. Apart from the easily identifiable bony landmarks, together with the distant application of the erector spinae plane block, the block offers a higher safety profile with various clinical advantages such as improved pre- and post-operative pain management, as well as reduced opioid requirement. In conclusion, it is vital to acknowledge the anatomical differences that exist in a paediatric population for the safe and successful administration of any regional technique to improve the management of pain in a vulnerable population. Keywords: Erector spinae plane block, paravertebral block, epidural block, interfascial block, paediatric, regional anaesthesia, pain management / Thesis (PhD (Anatomy))--University of Pretoria, 2020. / National Research Foundation (NRF) / Anatomy / PhD (Anatomy) / Unrestricted

Knowledge of the normal arterial diameter at a given anatomical point is the first step towards quantifying the severity of cardiovascular diseases. According to several studies, parameters such as age, weight, height, Body Mass Index and sex, can explain morphometric variations in arterial anatomy. There is no specific differentiation point between normal age-related arterial changes and pathological changes. Therefore, it remains challenging to distinguish between physiological and pathological processes as structural changes in arteries are bound to occur with the advancement of age. There is no point at which an artery can be said to have stopped growing or developing and started to degenerate or becoming diseased. Hence the knowledge of changes in arterial anatomy with age is vital for understanding arterial pathology. Arterial dimensions studied by other researchers were measured on cadaveric material or diagnostic imaging methodologies such as magnetic resonance imaging, computed tomography and ultrasound. The comparability and compatibility of cadaveric and image diagnostic methodology measurements has often been fiercely debated; repeatedly raising the question on the validity of cadaveric research. The primary purpose of this study was thus to compare the measurements taken on cadaveric material with measurements taken with computed tomography and ultrasound. The aim was to establish whether there is a statistically significant difference between arterial measurements taken via these different approaches. In addition, the study also aimed to examine the effects of various demographic parameters on the arterial diameters of a South African population. Digital arterial measurements were taken on computed tomography images at selected arterial sites and the age and sex of each individual were noted. These computed tomography images, representative of a living South African population, were retrospectively selected from the database of diagnostic images at the Department of Radiology, Steve Biko Academic Hospital. The arterial diameter at the identified arterial sites was measured with the assistance of computer software. Digital measurements of arteries on ultrasound images were also measured at the selected arterial sites and the age, sex, weight, height and Body Mass Index of each individual were noted or calculated. Ultrasound images were taken on volunteers in the Department of Anatomy, University of Pretoria. Demographic information, including age, sex, weight and height, was gathered via a paper-based questionnaire. Body Mass Index was calculated. Newly available cadaveric data was added to the cadaveric database compiled during two pilot studies that took place in the Department of Anatomy at the University of Pretoria. The collected data allowed for the comparison of diameters measured with the different methodologies. The South African sample was divided into comparable age and sex groups that also allowed for the determination of correlations between the changes in arterial diameters and the changes in the demographic parameters. Analyses of these correlations answered questions such as whether arterial diameter increase or decrease with an increase in age, height or weight. This study found that age is a vital demographic parameter when assessing change in arterial dimensions. Age was also found to influence muscular and elastic arteries differently. Even though some sexual dimorphism was noted, sex had a significantly smaller effect on arterial dimensions compared to age. Weight, height and BMI correlated weakly with a change in arterial dimension. Comparisons between the different populations indicated that cadaver measurements compared well to CT measurements as well as ultrasound measurements, but that CT measurements and ultrasound measurements were significantly different. Arterial pathology is a major contributor to cardiovascular disease and mortality. Data on normal arterial dimensions for a South African population is scarce, but essential when evaluating whether a dilatation or stenosis are pathological. Studies on the arterial morphology on a cadaver sample are thus comparable to living populations and support the premise that there is an age-related increase in the dilatation of the arterial lumen. The arterial diameter is a useful indicator of the vascular ageing process. This study provided us with valuable information regarding the validity and comparability of several arterial measuring methodologies as well as vital information regarding arterial changes in a South African population. / Thesis (PhD (Anatomy))--University of Pretoria, 2020. / National Research Foundation / Anatomy / PhD (Anatomy) / Unrestricted

No description available.

A research report submitted to the Faculty of Science, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Science (Physiotherapy) Johannesburg, 2017. / Background: Research has proven that conditions such as developmental coordination disorder (DCD) and attention deficit hyperactivity disorder (ADHD) are becoming more prevalent in children of school going age and that children presenting with these conditions have intrinsic barriers to learning. ADHD has been found in 3-5% of children. A 2001 census in South Africa showed 12% of the population had intellectual disabilities and 7% communication problems. A 2011 South African census show 3, 2% of the South African population aged five and above has mild concentration/remembering difficulties. When a child has poor performance, this can cause low self-esteem, poor social functioning, risk of obesity and vascular disease. The comorbidity between DCD and ADHD has been considered at a rate of 50%. Aim: The aim of this study was to determine whether children with intrinsic barriers to learning have specific motor development deficits. Method: There were 27 participants assessed using the Movement Assessment Battery for Children second version (M-ABC 2). The children were recruited from a private remedial school in Honeydew, South Africa and were identified as having intrinsic barriers to learning. The assessment looked at Aiming and Catching, Balance and Manual Dexterity. Each participant was assessed once. These results were analysed by looking at the prominent deficit and correlation to demographics or conditions. An ANOVA analysis was done to compare the different between conditions to Aiming and Catching, Balance and Manual Dexterity. Results: There were 10 females and 17 male children enrolled in the study. The mean age was seven years three months and fourteen days. The standard deviation of age was ±140.6 days. The most common diagnosis was ADHD (48%) followed by speech problems (33%). The Manual Dexterity mean score was 7.82 (± 2.22), the Aiming and Catching mean score was 9.78 (± 3.28) and the Balance mean score was 7.59 (± 2.91). The total mean score for the M-ABC was 7.63 (± 2.84). Manual dexterity and Balance scores were both significantly lower than the Aiming and Catching scores (p=0.02 and p=0.01, respectively). The results indicated no significant difference between the Manual Dexterity and Balance scores (p= 0.55). The ANOVA analysis showed that children with speech problems scored slightly higher in Manual Dexterity than children with anxiety problems and processing problems but this difference was not significant (p=0.52). Children with ADHD and speech problems appeared to score slightly higher in Aiming and Catching than children with anxiety problems and processing problems but this was not significantly different (p=0.15). Children with processing problems scored significantly higher (p=0.03) in Balance than children with the other conditions. Conclusion: Children who have intrinsic barriers to learning have been recognised to have motor deficits that fall into the diagnosis of DCD. It is important to assess these children to optimise their intervention program; not just from a cognitive aspect but from a motor aspect as well. The results of this study found that Manual Dexterity and Balance are motor components that were the most affected. Addressing these aspects may help improve the activity levels and participation of these children. / LG2019