Faculty of Health Sciences (ETDs)
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Item Design and development of a bioactive-loaded polymer-engineered neural device for potential application in reducing neurological deficits after spinal cord injuries and neuro-regeneration(University of the Witwatersrand, Johannesburg, 2017) Kumar, Pradeep; Choonara, Yahya Essop; Modi, Girish; Naidoo, Dinesh; Pillay, VinessTraumatic Spinal Cord Injuries (SCI), due to their devastating nature, present several interventional challenges (extensive inflammation, axonal tethering, scar formation, neuronal degeneration and functional loss) that need to be addressed before even a slight neuronal recovery can be achieved. Recent post-TSCI investigational approaches include support strategies capable of providing scaffold architecture to allow axonal growth and conformal repair. This research provided detailed insight towards the development and fabrication of six specialized Polymer-Engineered Neural Devices (PENDs): 1) poly(lactic-co-glycolic acid)-gliadin (PLGA-GLDN) nanofibrous mats, 2) polyacrylamidated chitosan (PAAm-g-HT) scaffold, 3) functionalized chitosan methoxypolyethylene glycol (CHT-mPEG) cryosponges, 4) polyacrylonitrile-elastin-collagen (PANi-EC) neurosponge, 5) methylcellulose-alginate-polyethylene glycol (MAP) thermogel, and 6) chitosan-luronic F127-β glycerophosphate (CHT-PF127-βGP) composite thermogel for potential restriction, repair, regeneration, restoration and reorganization post-SCI. The latest trends in biomaterials-based SCI intervention were reviewed, discussed and analyzed in detail throughout the thesis. The research also involved an in silico analytico mathematical interpretation of multi(biomed)material assemblies wherein quantification of energy surfaces and molecular attributes via atomistic, dynamic, and docking simulations was carried out. The in silico experimentation additionally confirmed the potential of curcumin as a bioactive of choice for SCI intervention. Curcumin and dexamethasone were incorporated into the compact scaffolds and the bioactive release was determined over a period extending up to 60 days. The PLGA-GLDN nanofibrous mats demonstrated the formation of a compatible blend among the component polymers at equal weight ratios (PG55) as confirmed by quantitative physicochemical characterizations. Image processing analysis (DiameterJ plug-in of ImageJ) was performed on the SEM images of nanofibers to quantify the size, porosity, and orientation of the samples. Nanofibers within the size range of 10nm and 250nm were obtained in case of compatible blend and the nano stack was used for in vivo implantation post-SCI. Polyacrylamidated chitosan (PAAm-g-CHT) was synthesized via a unique persulfate-mediated polymer slicing and complexation as determined by static lattice atomistic simulations. The graft copolymer so obtained was fabricated into an anisotropic neurodurable scaffold. The CHT/mPEG cryosponges showed unique morphological features such as fringe thread-like structures (CHT alone); hemispherical, pebble-like structures (CHT-mPEG); curved quartz crystal-like or crystal-flower-like structures (CHT-mPEG-CHO); and grouped, congealed, steep-sided canyon-like structures (CHT-mPEG COOH). A novel image processing protocol involving DiameterJ and ND plugins of ImageJ software was employed for analyses of the SEM micrographs in terms of % porosity, pore wall thickness and % xiiehaviorxii of the porous scaffolds. The PANi-EC interpenetrating polymer network neurosponges were synthesized employing free radical polymerization under acidic conditions wherein first-in-the-world spinomimetic scaffolds were obtained. The unique feature of the PANi-EC neurosponge was the formation of a fibrous neurotunnel architecture mimicking the native spinal cord. The physicochemical characterization revealed that the secondary structure of the peptide molecules (elastin and collagen) rearranged in the presence of PANi to their native extracellular matrix (ECM) form confirming the self-assembling nature of the polymer-peptide architecture. Furthermore, the PANi-EC neurosponge provided a perfect balance of matrix resilience and matrix hardness similar to the native collagen-elastin complex in vivo. Two very interesting tri-component thermogels were reported here viz. a simple blend thermogel comprising methylcellulose, sodium alginate and poly(ethylene glycol) and a complex thermogel incorporating chitosan, Pluronic F127 and β-glycerophosphate. Both the thermogels solidified at physiological temperature confirming their applicability in vivo. The outstanding feature of MAP thermogels was the formation of hydrogen bonded O-H…C=O which only formed in the tripolymeric blend while the bipolymeric blends showing no such interaction. We proposed that the MAP thermogel self-assembled into a repeating network structure represented by “PEG400-ALG-hydrophillicMChydrophobic}-{hydrophobicMC-hydrophilic}-ALG-PEG400” and the physical “compression” might have led to the formation of hydrogen bonded O-H…C=O among MC/alginate or PEG/alginate in the presence of PEG or MC, respectively. In case of the complex CHT/PF127/βGP thermogel, a unique triphasic gel-sol-gel transition xiiehavior was observed with the thermogel forming a gel-phase at lower temperatures (T<20°C), a sol-phase at intermediate temperatures (20°C35°C). The MTT proliferation studies indicated that all polymer engineered neural devices (PANi-alone matrix) were capable of efficiently supporting the growth of PC12 cells compared to the control over a period of 72 hours. The fundamental objective of this thesis was to test the applicability and capability of various biomaterial composites towards the repair and regeneration of neuronal tissue after traumatic spinal cord injury. Although drug-loaded scaffolds were also developed, only drug-free scaffolds (PLGA-Gliadin 5:5 electrospun nanofibers; PANi-Elastin-Collagen neurosponge; and Chitosan/Pluronic F127/β-glycerophosphate thermogel) were tested in vivo for the proof-of-concept. The 21-point scale BBB locomotor rating analysis demonstrated that PEND I (14), PEND II (19) and PEND III (18) provided significant motor recovery as compared to the lesion-control (5) group 28 days post-SCI and –implantation. The immunohistochemistry confirmed that reparative changes were accompanied by marked upregulation of iNOS, a notable influx of ED1-positive chronic inflammatory cells, the appearance of multinucleate cells characteristic of presumptive regenerative neuroblasts and near-complete loss of GFAP and NF-200 protein/structural integrity. Almost complete functional and neurostructural recovery was observed with post-SCI implantation of PEND II and III. In conclusion, the composite scaffolds tested in this research demonstrated immense potential in improving the neurological, neurochemical, and behavioral outcome after implantation post-SCI.Item Surgical aortopulmonary shunts - a thirty-seven year experience in a South African tertiary institution(University of the Witwatersrand, Johannesburg, 2019-11) Dladla-Mukansi, Nontobeko Charity; Cilliers, Antoinette; Mammen, Vijay; Vanderdonk, KathyIntroduction: The surgical aortopulmonary shunt is a valuable palliative procedure in the management of congenital heart diseases. There is a paucity of data regarding aortopulmonary shunts in the developing world, including South Africa. Objectives: The primary objective was to describe the demographic, clinical and echocardiographic characteristics of children between ages 0 and 14 years that underwent surgical aortopulmonary shunts. The secondary objectives were to describe trends in aortopulmonary shunt designs, outcomes in terms of morbidity and mortality, progression to definitive surgery and to assess patency of shunts. Material and Methods: A retrospective clinical audit of patient files who underwent an aortopulmonary shunt between 01 January 1980 to 30 December 2016 was undertaken at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg. The study period was divided into 3 stages and for descriptive purposes as follows: 1980-1991 refers to period 1, 1992-2003 refers to period 2 and 2004-2016 refers to period 3. Results: A total of 177 aortopulmonary shunts were done over the 37-year study period. Of these 177 patients, 165 (93.2%) patient files were available. Fifty-six percent of the patients included in the study were male. The majority of patients were from the Gauteng Province (76.8%). The four most common diagnoses across the entire study period were tricuspid atresia (26.0%), pulmonary atresia with VSD (23.7%), tetralogy of Fallot (23.2%) and complex cardiac lesions (16.9%), with no particular trend in the proportion of these diagnoses presenting across this study period. There was no statistical difference between period 1 and 2 (p-value a=0,328) and between period 1 and 3 (p-value b=0,548). The total number of all surgeries done over the entire study period was 2145, of which 8.3% were aortopulmonary shunts. Period 1 had the highest percentage [35 (10.9%)] of aortopulmonary shunts compared to the total number of surgeries performed. There was a decline in the number of aortopulmonary shunts performed over the study periods 1-3. With no statistical difference across periods as shown in table 1 with p-value a and b. Of the different types of aortopulmonary shunts, most patients [157 (88.7%)] had a modified Blalock-Taussig shunt (BTS). The remainder of the shunts included 3 (1.7%) classic BTS, 12 (6.8%) central shunts and 5 (2.8%) unknown BTS. The percentage of modified BTS done increased from 80% in period 1 to 87.3% in period 2 and to 95.2% in period 3. Period 1 had the most complications (28.6%) compared to 11.4% in period 2 and 19.1% in period 3. Sepsis as a complication following surgery increased over the study period from 2.9% in period 1 to 3.8% and 7.9% in periods 2 and 3 respectively. Early mortality was 17.1%, 26.6% and 25.4% from periods 1-3 respectively. Late mortality declined from 17.0% in period 1 to 11.4% and 0% in periods 2 and 3 respectively. Only 37 (20.9%) patients were documented to have further surgery after the initial aortopulmonary shunt. Across all three study periods, no blocked shunts were documented. Conclusions: This study describes the characteristics and outcomes of aortopulmonary shunts over a 37-year period in a tertiary care resource limited low to middle income country setting. The commonest cardiac lesions for which aortopulmonary shunts are performed are tricuspid atresia, pulmonary atresia with VSD, tetralogy of Fallot and other complex cyanotic cardiac lesions. The frequency of aortopulmonary shunts compared to total surgeries has corrective surgery for these cardiac lesions. The modified BTS is the most frequently performed aortopulmonary shunt used for palliative surgery in our setting, which is a similar trend in developed countries. The morbidity and mortality in this study is higher than developed countries, with sepsis being the most common complication. Attention to infection control practises need to be emphasized peri- and post-operatively in our hospitals.Item Liver cancer epidemiology and risk factors in South Africa(2019) Mak, Daniel Wei-HongPrimary liver cancer (LC) in South Africa (SA) is a public health concern; it is currently the seventh leading cause of death among SA men and women after colon cancer according to GLOBOCAN 2018. Despite this, publications of this disease remains scarce, if not absent. Accordingly, trend analysis for LC incidence (from 1993-2012) and mortality (from 1999-2015) rates demonstrated an overall decrease in SA, and these trends varied between different sex-, age- and population-subgroups. Specifically, rates markedly increased in the middle-aged black African women in the recent years. LC risk was highest in black African men in their early 30s, and survival from this malignancy provided a dismal outlook as most patients were only diagnosed during autopsy rather than during hospital and/or clinic consultations. Barring this, these findings demonstrate the utility of mortality data in supplementing the cancer registries for cancer that progress quickly. Liver cancer has several types, each originate from various type of cells that becomes cancerous. Hepatocellular carcinoma (HCC) accounts for the majority of liver cancers and originates from hepatocellular cells. The study of 150 HCC patients and 438 non-HCC cancer controls showed that risk factors that were significantly associated with HCC include: rural birthplace, male sex and living in an urban area for <14 years, Hepatitis B virus (HBV) DNA levels (>2000-≥200,000 IU/ml) and antibodies against hepatitis C virus (anti-HCV) positivity. Interestingly, human immunodeficiency virus (HIV) infection alone did not confer any risk in developing HCC, nor did it synergistically interact with HBV infection. Comparably, lifestyle-related risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were not associated with HCC risk. Phylogenetic analyses of the HBV isolates from the HCC patients and non-HCC controls demonstrated that HBV subgenotypes included A1 (90.7%), A2 (2.3%) and A3 (7%). Core promoter mutations (T1753V, A1762T and G1764A), preS deletions, ps2F22L, and preS2 start codon mutations were associated with HCC development, and the combination of which may potentially assist in the development of more targeted screening in high-risk groups. In view of these findings, this work provides much needed analysis of LC trends in SA and provides a critical assessment of current control strategies, or gaps, in the prevention of and interventions for LC in SA. Moreover, this work pays particular attention to the consolidation of what is an overview of LC in SA by reporting various aspects: incidence, mortality, demographics, viral and non-viral risk factors and a combination of HBV mutations as biomarkers.Item 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 VallentineThis 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).Item The relationship between awareness of violence against women prevention campaigns and gender attitudes and talking about violence among women in Gauteng(2016-10-12) Mataba, Rumbidzayi B.Introduction: Gender based violence (GBV) is a public health problem with as many as 35% of women having been subjected to either physical and or sexual violence globally. Gender attitudes and silence around gender based violence, are factors that exacerbate GBV. Global and local awareness campaigns are means for preventing violence against women. Campaigns have the potential to challenge women and men’s underlying gender beliefs and attitudes that contribute to unequal power relations between women and men. The overall objective of this study was to examine the association between awareness campaigns and gender attitudes or talking about domestic violence among women in Gauteng, South Africa. Materials and Methods: This study is a secondary analysis of data from a cross-sectional study conducted in Gauteng, South Africa from April to July 2010. The study aimed to describe the prevalence and patterns of experiences of GBV, HIV risk, gender attitude and awareness of GBV prevention campaigns in Gauteng. The main exposure variable in this study is having heard about 16 Days of Activism for No Violence Against Women and Children campaign and the 365 Days National Action Plan to End Gender Based Violence. The two primary outcomes are gender attitudes and discussing about domestic violence. Gender attitudes were measured using three scales: the Gender Equitable Women’s Scale, the Ideas about Gender Relations Scale and the Ideas about Rape Scale. Univariate analysis was conducted to describe the socio-demographic characteristics, awareness of campaigns, gender attitudes and talking about domestic violence among the participants. Multivariate analysis was conducted to examine the associations between awareness of campaigns and the outcomes while adjusting for age, education, employment, nationality, race and relationship status. Results: The results show that only a minority of the participants had heard of the 16 Days of Activism for No Violence Against Women and Children campaign (32.6%) and the 365 Days National Action Plan to End Gender Based Violence (9.2%) campaigns. Most of the participants had progressive gender attitudes; GEWS (71.7%), IGRS (82.1%) and the IRS (88.1%) while less than half (48.7%) had spoken about domestic violence to someone else. Women who were exposed to the 16 Days of Activism for No Violence Against Women and Children campaign were twice as likely to have progressive gender attitudes measured by the Gender Equitable Women’s Scale (aOR 2.2, 95% CI 1.2-3.8) compared to those who had not been exposed. Education, relationship status and nationality were found to be significantly associated with gender attitudes on the same scale. No association was found between awareness of 16 Days of Activism for No Violence Against Women and Children campaign and gender attitudes measured through the Ideas about Gender Relations Scale and the Ideas about Rape Scale. Awareness of 16 Days of Activism for No Violence Against Women and Children campaign was also associated with talking about domestic violence (aOR 1.9, 95% CI 1.2 - 3.0). Age and education were also significantly associated with talking about domestic violence. Gender attitudes were also significantly associated with talking about domestic violence (aOR 1.2 95% CI 1.1 – 3.6). No association was found between exposure to the 365 Days National Action Plan to End Gender Based Violence and gender attitudes or talking about domestic violence. Conclusions: From this study, the majority of the women interviewed had progressive gender attitudes. However, the majority of the women had never spoken about domestic violence to someone else. Women exposed to GBV campaigns had more progressive gender attitudes and spoke about domestic violence more than those who were not exposed. These findings are evidence to the need for wider coverage and different messaging approaches in the implementation of GBV campaigns in South Africa. Wider coverage of campaigns is only possible with more funding for national, provincial and local GBV programmes. Key messages in GBV campaigns need to include a priority focus on addressing the underlying social and cultural norms that contribute to the imbalances of power due to gender difference.Item Unmasking serial murder: a comparison of a South African murder series with characteristics from the Federal Bureau of Investigation Serial Murder Database(2015) Holland, ShakeeraThe term ‘serial killer’ brings to mind notorious criminals whose crimes are so heinous as to test the limits of the most vivid imagination and make us question their humanity. What is the reality of serial murder? In 2005, the Federal Bureau of Investigation (FBI) hosted a symposium on serial murder, which brought together international experts in the field of serial murder with the aim of clarifying and understanding this multifarious crime. On the 12th of March 2008, Gcinumzi Richman Makhwenkwe, ‘The Moffat Park Serial Murderer’ was convicted of 5 counts of murder, 3 counts of rape and 3 counts of robbery with aggravating circumstances. The Department of Forensic Medicine and Pathology of the University of the Witwatersrand, based at the Johannesburg Forensic Pathology Service (FPS) Medicolegal Mortuary Facility performed the medicolegal investigations of death in all the victims. This research report explores the characteristics of serial murder and serial murderers as documented in the literature; documents the features and characteristics of the Moffat Park murder series; compares the features of this South African murder series to those from the findings of the FBI serial murder symposium; explores the role of the forensic medical practitioner in the investigation of the Moffat Park series and serves to educate and inform forensic medical practitioners of the features of serial murder as awareness may potentially lead to earlier identification of a murder series. This could ultimately lead to earlier implementation of specialist investigative methods, earlier apprehension of the serial murderer and most importantly fewer victims.Item The effect of temperature on the vector competence of culex univittatus theobald (diptera : culicidae) for West Nile and Sindbis viruses(2015-02-13) Cornel, Anthony John; Swanepoel, R.; Jupp, P.G.Item The demographic profile, substance use, competence to stand trial and criminal responsibility among “ Observation Patients” admitted for forensic psychiatric evaluation at Sterkfontein Hospital, Gauteng, South Africa.(2011-10-19) Pillay, AnbenA review of the literature indicates that young males, who are unemployed with low levels of education, predominate in populations of pre-trial criminal offenders suspected of having a psychiatric illness, also known as “Observation Patients” according to the Criminal Procedures Act of 1977 in South Africa. Other contributory factors include a history of mental illness and non-compliance on psychiatric medication, a previous forensic history, co-morbid substance abuse and being intoxicated at the time of the offence. Dual diagnosis is considered a key contributor to criminal behaviour in this group of patients. The review of the literature also shows a significant proportion of co-morbid intellectual disability among offenders found to be psychiatrically ill at the time of the criminal event. A previous study conducted 20 years earlier, in 1986 at the Sterkfontein Forensic Psychiatric Unit by Vorster (1986) showed that the typical profile was a single, unemployed, poorly educated male in his twenties, usually with a history of psychiatric treatment. This typical profile confirmed the evidence in the literatures at the time of the study.Item Levels and factors associated with homicide-related deaths in a rural South African population(2011-03-25) Otieno, George OmondiBackground: World Health Organization (WHO) estimates that more than 1.6 million people die every year because of violence and out of these deaths, homicide accounts for almost one third. Ninety percent (90%) of homicide are thought to occur in low and middle income countries. South Africa has one of the most disturbing rates of homicide in the world. These high homicide rates besides resulting in reduced life expectancy also have serious health, social and economic consequences. Aim: The study aimed at quantifying the burden as well as and identifying factors associated with homicide deaths in rural KwaZulu-Natal in South Africa during the period of 2000 to 2008. Objectives: To estimate a 9 year period (2000-2008) homicide incidence rates as well as identify factors associated with homicide-related deaths. Further, the analysis described spatial distribution of homicide-related deaths in a rural South African population. Design: Analytical longitudinal study. Methods: Using data drawn from the Verbal Autopsies (VAs) conducted on all deaths recorded during annual demographic and health surveillance over a 9-year period (2000-2008), Kaplan-Meier (K-M) survival estimates of incidence rates were used to estimate the cumulative probability of death until the end of the period. Estimates were reported by sex and residency. Weibull regression methods were used to investigate factor associated with homicide deaths. Kulldorff spatial scan statistics was used to describe homicide clustering. Results: With 536 homicide-related deaths, and 814, 715 total Person Years of contribution, the study found an overall incidence rate of 66 (95% CI= (60, 72) per 100, 000 Person Years of v Observation (PYOs) for the period studied. Death due to firearm was reported the leading cause of mortality (65%). Most deaths occurred over the weekends (43%), followed by Friday (16.2%).The highest homicide incidence rates were recorded in 2001 (90; 95% CI= (71, 111) per 100,000 person years at risk and 2004 (86; 95% CI= (68, 108) per 100,000 person years at risk. Males had a rate that was about six times more than females 115 (95% CI=105,127) per 100,000 PYOs. Age-specific homicide rate were highest among males aged 25-29 years (209.90 per 100,000 PYOs) and females aged 50-54 years (78 per 100,000 PYOs). Resident, age, sex, education, socioeconomic status, and employment independently predicted homicide risk. The study identified two geographical clusters with significantly elevated homicide risk. Conclusion: A significant six fold difference in homicide rate existed between males and females. Sex differential increases with age, with males aged 15-54 years the most likely to be killed, and females aged 55 years and above having the highest homicide rate. Increase in wealth status and level of education increases one‘s risk of homicide. Employment per se was protective from homicide risk. Firearm was the leading cause of mortality. Most deaths occur over the weekend. Two geographical areas with elevated homicide risk were observed. These findings underscore the need to have timely information and strategies for effective violence prevention program to subgroups and areas at risk.Item Understanding intimate femicide in South Africa(2010-09-22) Mathews, ShanaazWhen a woman is killed she is most likely to be murdered by an intimate partner. This form of homicide known as intimate femicide is conceptualised to be the most extreme consequence of intimate partner violence. Not much is known about such killings in South Africa or in other developing settings. This thesis studied intimate femicide using two complimentary studies from two methodological perspectives. The first study was quantitative with the aim of describing the incidence and pattern of intimate femicide in South Africa. The second study used qualitative methods and explored the social construction of the early formation of violent masculinities. Five papers written from these two studies are presented in this thesis. Study one was a retrospective national mortuary-based study and collected data on all female homicides, 14 years and older, who died in 1999 from a stratified, multi-stage sample of 25 mortuaries. Data was collected from the mortuary file, autopsy report, and a police interview. The second study used a cluster of qualitative in-depth interviews with 20 incarcerated men in prison who have been convicted for the murder of an intimate partner, as well as interviews with family and friends of both the perpetrator and the victim. Overall it was found that 50.3% of women murdered in South Africa are killed by an intimate partner, with an intimate femicide rate of 8.8/100 000 and an intimate-femicide suicide rate of 1.7/100 000 females 14 years and older. Blunt force injuries were shown to be associated with intimate killings, while gun ownership was associated with intimate femicide-suicides. vi elevated Blood Alcohol Concentration (BAC) combined with unemployed status was also found to be associated with intimate killings. The qualitative study showed that traumatic childhood experiences such as violent and neglectful parenting practises particularly by mothers made these men feel unloved, inferior and powerless with this found to be a pathway to violent models of masculinity used as a means to attain power and respect. This study shows that such traumatic experiences can lead to a suppression of emotions. It is argued that cognitive dissonance act as a protective mechanism which allows these men to perpetrate acts of violence without consideration of its impact. These findings suggests that intimate femicide is a complex phenomenon with a “web” of associated and mediating factors which all contribute to it excessive levels in South Africa. It shows that intimate femicide is an extension of intimate partner violence and as such has to take into account the unequal gender relations in society. Building gender equity and shifting patterns of femininity and masculinity is a key strategy in reducing this form of violence.