Diffuse Large B Cell Lymphoma is one of the most common Non-Hodgkin’s Lymphomas. It is prevalent in older age patients but as of late there has been a rise in the younger population in South Africa due to the rise of HIV. DLBCL is quite an aggressive cancer but can be treated, however the relapse rate is high. There are prognostic indicators which can be seen as factors which can be indicative of a poor outcome for patients. Micro-RNA(miRNA) are small non-coding RNA which can remain stable to be tested. There are several miRNAs which may be linked to prognosis, including miRNA-21 whose upregulated expression has been associated with bad prognosis. However, this is not specific to DLBCL and some studies done have indicated that there may be other miRNAs which are better suited to be biomarkers for DLBCL. Studies have pointed to the direction of miRNA127 as a more reliable microRNA in its association with prognosis in breast, cervical and gastric cancer as well as DLBCL. Objective: The primary aim of this study was to determine the association between miRNA127 and prognostic markers including immunohistochemical stains, survival status and the IPI factor to determine its significance as a prognostic indicator. An additional aim was to determine the correlation between HIV status and expression level of miRNA-127. Design: A total of 42 DLBCL cases were collected from the archive of Division of Anatomical Pathology, University of Cape Town/NHLS Groote Schuur. The H&E slides were assessed before RNA was extracted from FFPE tissue and converted to cDNA. Real time quantitative RT-qPCR was used to assess the expression of the microRNA. Normal tissue as well as reactive lymph node tissue were used as controls. The expression patterns were also correlated to the clinical information to determine if there was any relationship. Results: Out of the 42 cases used, 10 cases were silenced, and 31 cases had high miRNA-127 expression. The expression levels were correlated with the IPI factors and the other clinicopathologic features however no significant conclusion were determined. Conclusion: We found high expression of miRNA-127 cases in the majority of the DLBCL cases. There was no correlation between HIV status and the expression of miRNA-127, nor between the expression and any of the clinicopathological feature. For future studies it is advised that more equally distribution of samples (both HIV status and gender) are obtained, this will allow for a better comparative study.

Includes bibliographical references (leaves 56-69).

Includes abstract. / Includes bibliographical references. / The developing central nervous system is especially vulnerable and research has implicated early life stress (ELS) as a potentiating factor to cell death in a rat model of Parkinson’s disease (PD). PD is a movement disorder resulting from the selective degeneration of dopamine neurons in the substantia nigra pars compacta (SNc). Dopamine neurons have been shown to exhibit mitochondrial dysfunction, oxidative stress and misfolded protein aggregation in patients with PD. Since ELS has been shown to negatively affect the nigrostriatal pathway and mitochondrial function, developmental stress may create a vulnerable microenvironment which results in a greater rate of cell death during the development of PD. Many proteins play a role in establishing a positive microenvironment that is neuroprotective, and may be good candidates for the mechanism by which ELS potentiates neurodegeneration in the PD rat model. This study aimed to investigate whether the finding that ELS increases neuronal susceptibility to 6-hydroxydopamine(6-OHDA)-induced degeneration of dopamine neurons occurs through dysregulation of the oxidative stress-related heat shock protein (HSP)25, or plasticity-related proteins, chondroitin sulphate proteoglycans (CSPGs) or Nogo-A.

Includes abstract. / Includes bibliographical references (leaves 140-144). / Automated microscopy for the detection of tuberculosis (TB) in sputum smears seeks to address the strain on technicians in busy TB laboratories and to achieve faster diagnosis in countries with a heavy TB burden. As a step in the development of an automated microscope, the project described here was concerned with microscope auto-positioning; this primarily involves generating a point of reference on a slide, which can be used to automatically bring desired fields on the slide to the field-of-view of the microscope for re-examination. The study was carried out using a conventional microscope and Ziehl- Neelsen (ZN) stained sputum smear slides. All images were captured at 40x magnification. A digital replication, the virtual slide map, of an actual slide was constructed by combining the manually acquired images of the different fields of the slide. The geometric hashing scheme was found to be suitable for auto-stitching a large number of images (over 300 images) to form a virtual slide map. An object recognition algorithm, which was also based on the geometric hashing technique, was used to localise a query image (the current field-of-view) on the virtual slide map. This localised field-of-view then served as the point of reference. The true positive (correct localisation of a query image on the virtual slide map) rate achieved by the algorithm was above 88% even for noisy query images captured at slide orientations up to 26°. The image registration error, computed as the average mean square error, was less than 14 pixel2 (corresponding to 1.02 μm2 and 0.001% error in an image measuring 1030 x 1300 pixels) corresponding to a root mean square registration error of 3.7 pixels. Superior image registration accuracy was obtained at the expense of time using the scale invariant feature transform (SIFT), with a image registration error of 1 pixel2 (0.07 μm2). The object recognition algorithm is inherently robust to changes in slide orientation and placement, which are likely to occur in practice as it is impossible to place the slide in exactly the same position on the microscope at different times. Moreover, the algorithm showed high tolerance to illumination changes and robustness to noise.

Secondary leach concentrate (SLC) is an important bleed stream for minor elements from Anglo Platinum's Base Metal Refinery (BMR) which produces copper nickel and cobalt sulphate. It contains mainly sulphur, iron jarosites, unleached base metals and platinum group metals (PGMs), which makes the treatment of SLC necessary. The SLC is currently toll-refined at Umicore's Hoboken smelter and refinery to recover revenue from entrapped valuable metals. This method of treatment results in excessively high costs due to high transport and toll refining expenses as well as penalties. Thus, an in-house method of treatment by Anglo Platinum itself would prove beneficial in that it would eliminate these excessive costs and also provide a method of treatment in the event of residues exporting becoming banned or strongly penalised in future. Therefore, a method for treating SLC in-house is investigated. The first stage of the proposed treatment method involves a pyrometallurgical process where the removal of amphoterics by oxidative fuming, followed by reduction to recover base metals from the slag takes place. The PGMs are reported mainly to the metal alloy phase along with the base metals during this process. The project discussed in this report deals with the treatment of this furnace alloy which is referred to as Cu alloy. The Cu alloy is used to produce anodes to be applied to an electrorefining application for the recovery of Cu as a Cu cathode and PGMs in the form of anode slimes. Spent electrolyte from the BMR copper electrowinning section adjusted to specific pH and Cu concentration is used as electrolyte to which dissolvable metals (such as Ni and Fe) are recovered. The purpose of the process is to recover PGMs to anode slimes with a composition suitable to be blended with the final concentrate that is sent to the Precious Metals Refinery (PMR). The performance of this process on the Cu alloy provided is investigated and the anode slimes produced are characterised in order to propose further methods of purification before blending with PMR feed. The typical energy consumption, cathodic current efficiency, anodic copper dissolution rate and deportment of elements (especially PGMs) are determined. The effects of various operating parameters on the performance are also investigated in order to propose operating conditions. The operating parameters that are investigated are current density, Cu and H2SO4 concentrations in electrolyte and the use of an additive. A preliminary process design based on knowledge and experience gained during the literature review and test work is given. -PAGE 3 OF 181 The major technical factors in electrorefining are the cathode purity, the production rate and the specific energy consumption. These factors are influenced primarily by anode quality, electrolyte conditions and cathode current density. Design considerations and typical design parameters for other industrial Cu electrorefining applications are studied as well as possible further treatment of anode slimes for the concentration of PGMs. A total of eleven experiments were performed with a variety combinations of Cu concentration (30, 40 and 50 g/l), H2SO4 concentration (110, 130, 160 and 190 g/l) and current density (100, 125, 150, 250, 300 A/m2). In each experiment only one parameter was changed while all others were kept constant at the base-case setting of 40 g/l Cu, 160 g/l H2SO4, and 125 A/m2. The testwork showed that electrolytic refining of the Cu alloy, produced by a two stage pyrometallurgical treatment of current SLC, produces a highly concentrated PGM residue at an overall SLC mass reduction of 99.3%, with excellent PGM recovery to the anode slimes material. The different operating parameters that were tested successfully, all showed very good repeatability and greater than 99% PGM recovery from the Cu alloy, which would result in an overall recovery of 98% from SLC. Very little or none of the base metals that were supplied by the anode or the electrolyte feed reported to the anode slimes. The typical operating conditions (cell potential, current efficiency, anodic Cu dissolution and element deportment) that were observed correlated well with literature and the theoretically calculated values. The characteristics of the anode slimes produced stayed relatively similar throughout the different operating parameters and strong confidence can be placed in the production thereof and the recovery of the PGMs. The characteristics of the spent electrolyte and the Cu cathodes were also found to be suitable for integration in the BMR circuit. The anode slimes composition was 20 to 30% PGMs, 20 to 30% base metals, 15 to 20% Ag, As, Te, Se, Pb and 2 to 5% Al, Si, Sb, Bi, Zn and Sn. The blending of these slimes with typical PMR feed will result in a new PMR feed where the Pt grade of the feed to PMR is reduced by 4 to 5.5%, the Cu grade increased by 2 to 4% and the Ni content reduced by +-4%. Other concerns are the increase of As, Te, and Pb by between 0.5 and 1%. -PAGE 4 OF 181 The PGM-rich (<60%) phase in the anode slimes is a mostly amorphous matrix phase containing mostly palladium and other PGMs, arsenic and tellurium [Pd73As6Te21] with small amounts of Cu. Anode slimes produced from electrorefining can either be subjected to an additional process step to remove Ag, Pb and base metals before it is blended with the final concentrate (FICO) as feed for PMR, or it can be sent to the metallics section in PMR which includes a roast and a leach stage. The treatment of the anode slimes depends on the nature of the slimes. A preliminary process design was performed with proposed design parameters of electrolyte concentrations of 40 g/l Cu and 160 g/l H2SO4 at 65 deg C and a current density of 200 A/m2. The process consists out of seven cells in series with 55 anode cathode pairs in parallel per cell. The process has a maximum capacity of 127 t/m of anode material which allows 56 days of downtime per year if the current SLC produced (6600 t/a) is treated. The maximum capacity for Cu production is 1349 t/a and anode slimes 50.3 t/m. The power consumption per kg of anode dissolved will be 0.175 kWh/kg.

Bibliography: leaves 139-155. / This study was conducted in order to evaluate the effectiveness of a "self-help" ergonomics-training program, which was instituted in order to reduce the risk of musculoskeletal disorders and eyestrain in video display terminal (VDT) operators.

Includes bibliographical references. / Current literature supports the need to make the prevention and management of chronic diseases an international health priority. In South Africa, our Health Minister has committed the government to tackling the burden of chronic diseases alongside communicable diseases. The Western Cape has developed an excellent policy and framework to guide and improve the prevention and management of chronic diseases at a primary care level, however limited literature exists around the alignment of the policy with current practice and around any challenges to its implementation. Should the policy be well implemented, it has the potential to make a significant difference to the health of the population served. For this reason, the overall purpose of this study is to improve the care and management of patients with chronic diseases within primary health care facilities. The aim of this study is to assess the alignment of current primary care practices with the PGWC Adult Chronic Disease Management policy (which includes an audit tool), using one primary health care facility in the Cape Town metropolis as a case study.

Includes bibliographical references. / The consumption of wine dates back to the Stone Age, but its potential health benefits only really began to make an impact after the French Paradox was postulated by Renaud and de Lorgeril in the 1990s. Their observations indicated that moderate consumption of red wine may have health benefits. Research since then has shown that wine, in particular red wine, is a source of a large number of different polyphenolic compounds that have antioxidant activity. The finding that the consumption of red wine might have a beneficial health effect was very appealing, resulting in a large number of epidemiological and experimental studies. To date, controversy still surrounds wine and its health effects. Several pertinent questions are still to be answered: What in vitro methods can be used to determine the antioxidant effects of wine? What are some of the in vivo effects of wine? Can wine be used directly as an antioxidant in cooking of the food that would ordinarily be exposed to conditions that may induce peroxidation of lipids? What effects does wine have at the cellular level?

Includes bibliographical references. / Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure which leads to right ventricular hypertrophy and failure. The mechanism involved in the pathophysiology of the disease remains unclear but it is suggested that oxidative stress may trigger cardiovascular dysfunction associated with the disease. To date, there is no efficient therapy against PH and novel therapies are urgently needed. Melatonin is a powerful antioxidant that can confer benefit against ischemia-reperfusion injury and hypertension. We therefore hypothesised that melatonin may confer cardiovascular benefits against PH. Methods: Oxidative stress (plasma lipid peroxidation, antioxidant capacity and antioxidant enzyme activity) was assessed in healthy (n=10), in patients with PH (n=10), in Long Evans rats (n&#8805;6) or in a rat model of PH induced 28 days after the injection of monocrotaline (MCT, 80mg/kg, subcutaneous) (n&#8805;6). Melatonin (75ng/L, nutritional concentration), 4mg/kg or 6mg/kg (therapeutic dose) was given daily in the drinking water of rats, with the treatment started 5 days before the injection of MCT, on the day of the injection or 14 days after the injection of MCT. The development of PH was measured by assessing right ventricular hypertrophy, cardiac fibrosis, oxidative stress and cardiac function (via echocardiography and the isolated heart Langendorff perfusion model). Results: Plasma oxidative stress was increased in both patients and rats with PH compared with their respective controls. A chronic treatment with melatonin (75ng/L, 4mg/kg or 6mg/kg) starting on the day of the injection with MCT in rats with PH reduced right ventricular hypertrophy, cardiac dysfunction and plasma oxidative stress compared with control rats. Furthermore, the beneficial effect of melatonin (6mg/kg) could be observed when given as a preventive (5 days prior to the injection of MCT) or as a curative therapy (14 days after the injection of MCT). Conclusions: Our data demonstrate that chronic treatment of melatonin confers cardioprotection in a rat model of PH. As melatonin is inexpensive, safe (no reported side effects) and already available over the counter in many countries, we propose that melatonin should be considered as a novel preventive/curative therapy to limit cardiac dysfunction in patients with PH.

Introduction A common complication of Human Immunodeficiency Virus (HIV) and anti-retroviral therapy (ART) is distal sensory polyneuropathy (DSP). Older age and previous TB are risk factors for DSP among HIVinfected Africans before and shortly after ART initiation. Little is known about autonomic dysfunction in Africans on long-term ART and the impact of DSP and autonomic impairment on their quality of life. Our aim was to describe the frequency, characteristics and functional consequences of DSP and autonomic dysfunction in a healthy HIV-infected community-based cohort after at least 5 years of ART. Methods HIV-infected South Africans on the government-sponsored ART program for at least 5 years were included in this cross-sectional analysis. Each consenting participant underwent a focussed neurological assessment using the Brief Peripheral Neuropathy Screen (BPNS) and a reduced version of the Total Neuropathy Score (rTNS). DSP was defined as the presence of at least 2 neuropathic signs in a distal and symmetrical distribution, and symptomatic DSP (SDSP) when accompanied by neuropathic symptoms. Heart rate variability and orthostatic hypotension were measured as described by the Ewing classic battery, and the Survey of Autonomic Symptoms (SAS) questionnaire assessed the presence and severity of autonomic symptoms. We used a modified version of the Lower Extremity Functional Scale (LEFS) to assess lower limb physical ability. Results The 67 participants had a median age of 41 years (interquartile range (IQR) 36-46) and 61 (91 %) were women. The median duration of ART was 7 years (IQR 6-10). DSP criteria were met in 54 (80.6%) and 24 (44.4%) had symptomatic DSP. Comparing participants with DSP to those without DSP, there was no difference in sex (P=0.39), age (P=0.79), current CD4 (P=0.69), viral suppression (P=0.34), ART duration (P=0.22) or previous tuberculosis (TB) (P=0.72) in those with DSP. Similar outcomes were obtained for SDSP. Abnormal autonomic tests were present in 60%. Those with SDSP had more severe autonomic symptoms than those with asymptomatic DSP (P=0.0008). We found that those with DSP and SDSP had significantly lower LEFS percentage scores than those without (P=0.039 and P=0.013 respectively). 5 Conclusion DSP remains a common complication of HIV in the modern era of ART and can lead to significant functional impairment. Autonomic dysfunction is prevalent in SDSP.