Magister Chirurgiae Dentium - MChD / This mini-thesis assessed whether a diode laser with a wavelength of 810 ± 10nm can be utilized as an adjunct to conventional management (i.e. scaling, root planing and polishing) of chronic periodontitis during initial phase therapy. Ethical approval and study registration (Reg no: 14/9/6) was finalized prior to commencement of the study. A split mouth randomised control trial was performed on 25 participants (who presented at the Oral Medicine and Periodontology Department of the University of the Western Cape) diagnosed with active, chronic periodontitis. In order to standardise the split mouth design the quadrants 1 & 4 were assessed together as a set and quadrants 2 & 3 were assessed as a set. A set of these quadrants were randomly assigned to either the test or control quadrants after conventional management was performed in all four quadrants. The base line bacterial colony collection (Micro-IDent®-11, Hain Lifescience GmbH, Nehren, Germany) and the clinical parameters were assessed prior to the commencement of conventional management and were reassessed at the 6 week re-evaluation visit. The set of test quadrants were treated with the diode laser as an adjunct to the preceding conventional management. The control quadrant only received the conventional management. Evaluation of the results demonstrated that the diode laser produced no statistical decrease in the bacterial parameters in the periodontal pockets and resulted in a statistical increase of C. showae (Cs) and T. denticola (Td). The clinical parameters resulted in no statistical difference for any clinical parameter, with the exception of the reduction in BOP that was statistically significant (p< 0,05) with the laser as an adjunct. It is the recommendation that within the limitations of this study, that the utilization of the diode laser (810 ± 10nm) as an adjunct at the initial visit had no statistical effect in the reduction of the bacterial parameters nor resulted in an overall improvement of the clinical parameters.

Magister Commercii - MCom (Economics) / In post-apartheid South Africa, the thrust of macroeconomic framework and corresponding policies inaugurated by the first democratically elected government have been geared towards, amongst others, poverty alleviation, employment creation and economic growth. To date, South Africa still faces many challenges in the fight against poverty. These challenges are characterised by a dynamic nature, in that certain people transition in and out of poverty, whilst others remain deeply rooted in chronic poverty. Injecting resources towards addressing this complex nature of poverty is still one of the major problems faced by the South African government. In spite of the fact that there are many money-metric studies on poverty in South Africa, these studies failed to accurately depict the dynamic nature of poverty; throughout the years, many studies have only attempted to examine poverty using static analysis by comparing cross-sectional household surveys. It is for this foremost mentioned reason that these studies have produced information that is inadequate for the elimination of persistent poverty. Examining and identifying the characteristics of the different groups of poor using longitudinal data for the purpose of comparing poverty levels and trends observed over time perhaps better capture the nature of poverty in South Africa. Hence, in this study, panel data will be utilised to investigate the dynamic aspect of poverty for the evaluation of dynamics at the individual level. Using the balanced component of the panel data from the first four available waves of the National Income Dynamics Study (NIDS) conducted in 2008-2015, the empirical findings indicate that the followings individuals are significantly more likely to be chronically poor: female Africans without Matric, aged younger than 25 years at the time of the first wave in 2008 (mean age being slightly above 20 years), living in traditional areas or farms in the KwaZulu-Natal, Eastern Cape, Limpopo, Northern Cape, Mpumalanga and Free State provinces, and inactive in the labour market. Also, they came from households headed by unemployed female Africans with relatively higher mean dependency ratio (above one) and household size (about seven) with either none or only one employed member, as well as associated with a greater likelihood of the households receiving social grant income and having inferior non-income welfare.

Chronic pancreatitis (CP) is characterised by chronic, frequent, disabling abdominal pain. It often leads to exocrine and endocrine insufficiency resulting in malabsorption and diabetes mellitus respectively. The incidence of CP is 5-10 per 100,000 population worldwide and is on the rise in UK. Alcohol (70%) is the commonest aetiologic cause, idiopathic (20%) and others (10%) being second and third respectively. There are various medical and surgical treatment options available depending on clinical characteristics and the stage of disease. In spite of wide spectrum of therapeutic options, pain control still remains a challenging problem to the clinicians. Surgical treatments for chronic pancreatitis, broadly classified into resectional and drainage procedures, may offer relief of symptoms. These surgeries are associated with severe morbidity and high mortality. In addition, our comprehensive review of surgery in chronic pancreatitis demonstrated lack of criteria for baseline assessment of patients with CP; resulting in lack of standardization, variation in indication and comparability in published literature on surgical treatment of chronic pancreatitis. These factors have collectively forced the medical fraternity to look for other non or minimally invasive options. Oxidative stress and deficiency of anti-oxidants have long been implicated in pathogenesis of CP. Our review of literature on oxidative stress and antioxidants has highlighted the shortcomings and inadequacies from the previously published reports. These reports were underpowered and not all included patients had chronic pancreatitis. This in turn led us to propose a well designed randomised, double blind, placebo controlled trial of antioxidant therapy in CP. Considering the loss of time and productivity, it is necessary to undertake Qol as an outcome measure in any intervention related to CP. Our study assessed the suitability and feasibility of validated quality of life indices in patients with painful chronic pancreatitis. After correction for disease duration, the outcome of contemporary quality of life assessments showed that patients with CP taking Antox had better scores than controls. Cytokines, a group of proteins and glycoproteins that act in regulation of immunity, inflammation and haematopoiesis are implicated in oxidative stress related pathogenesis of chronic pancreatitis. They are broadly classed as pro-inflammatory and anti-inflammatory. There have been few experimental studies suggesting that antioxidants ameliorate cytokine response in chronic pancreatitis. However our study has failed to demonstrate a significant effect on cytokine levels after six months of antioxidant therapy. Similarly, on the clinical front, a randomised, double blind placebo controlled study (referred to as ANTICIPATE TRIAL) has shown no benefit of antioxidant therapy in painful chronic pancreatitis, irrespective of age, gender, aetiology or operative intervention. So we are afraid to say that until we discover any novel treatment in management of intractable painful chronic pancreatitis, surgery and interventional endoscopy might be the only viable options.

Increasingly chronic liver disease is being acknowledged as a complication of type 2 diabetes, in particular non-alcoholic fatty liver and non-alcoholic fatty liver disease. Rates of non-alcoholic fatty liver are higher in people with type 2 diabetes than in the general population, with prevalence rates believed to be between 40-70%. Given the aging Scottish population and the obesity driven diabetes epidemic, the problem of chronic liver disease is likely to increase. Despite this there has been little investigation into the natural history of nonalcoholic fatty liver disease and the risks of clinically significant chronic liver disease in community based cohorts because diagnosis has been heavily reliant on liver biopsy. The use of liver biopsy is limited in both research and clinical practice due to its associated high mortality (1/1000) and morbidity and also due to practical limitations (sampling variability, semi-quantitative scoring systems). As a result the use of non-invasive markers of liver injury (non-specific liver injury, steatosis, steatohepatitis, liver fibrosis and surrogates of advanced portal hypertension) are rising, in the diagnosis of chronic liver disease, however, their utility in both community cohorts and patients with type 2 diabetes has not been widely studied. The aims of the studies presented in the thesis, using the Edinburgh Type 2 Diabetes Study, were: (i) to describe the distributions of a range of non-invasive markers of steatohepatitis and liver fibrosis in older people with type 2 diabetes, their relationship with metabolic and liver disease risk factors, and to compare the agreement of different non-invasive markers of hepatic fibrosis; (ii) to determine the frequency (prevalence and incidence) of and risk factors for clinically significant chronic liver disease in people with type 2 diabetes; and (iii) to determine the importance of chronic liver disease as a risk factor (or risk marker) for cardiovascular mortality or morbidity in type 2 diabetes. Prior to undertaking this work I undertook a detailed systematic review of the literature relating to the use of non-invasive markers of hepatic fibrosis to inform the choice of markers used in the study. Examination of a wide range of potential markers of steatohepatitis and liver fibrosis found varied relationships with diabetes history. Most commonly, elevated markers of steatohepatitis and liver fibrosis were associated with older age and higher body fat measures. However, most of these relationships between liver markers and body fat measures lost statistical significance when limiting the population to only those with hepatic steatosis and/or non-alcoholic fatty liver disease. There were marked differences in the associations between different liver fibrosis markers and potential diabetes and metabolic risk factors, suggesting that these markers are not actually measuring the same underlying “fibrosis” condition. There was poor correlation between the five markers of liver fibrosis studied. Using the top vigintile (5%) of each marker resulted in excellent agreement on the absence of advanced liver disease but poor agreement on the presence of advanced liver disease. The prevalence of clinically significant CLD (defined as cirrhosis, HCC or gastrooesophageal varices) was 2.2% - 0.9% diagnosed prior to enrolment with an additional 1.4% identified by study investigations. Over nearly 6 years of follow-up, only 1.4% of the cohort developed incident clinically significant CLD. Higher levels of systemic inflammation, steatohepatitis and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease. Less than half of participants developing incident significant disease were identified as high risk by the study investigations. Abnormal liver enzymes were statistically significantly associated with incident cases, however the presence of hepatic steatosis was not. There were 372/1033 (36.0%) patients with prevalent CVD and 319 (30.9%) with prevalent CAD at baseline. After mean follow-up of 4.4 years there were 44/663 incident CVD events, including 27 CAD events. There were 30/82 CVD related deaths. However, risk of dying from or developing CVD was no higher in subjects with steatosis than in those without. There was also no statistically significant relationship between CVD and steatohepatitis or liver fibrosis. The only statistically significant relationship between CVD and any liver markers was with GGT (prevalent CVD, OR 1.28, p=0.007; incident CAD, OR 2.35, p=0.042), suggesting that in our study population, CLD may have little effect on the development of, or mortality from, CVD. In conclusion, the potential for using non-invasive biomarkers to diagnose clinically significant chronic liver disease in type 2 diabetes remains limited, however chronic liver disease is a significant problem in older people with type 2 diabetes and is frequently undiagnosed.

L’irruption d’une maladie chronique constitue une rupture dans la vie des individus, qui les conduit à repenser leur projet professionnel. A partir d’un dispositif collectif d’échanges sur le thème du maintien ou du retour au travail, de 35 entretiens semi-directifs de recherche et de 27 entretiens d’orientation, notre étude tend à montrer que le projet des personnes malades s'élabore soit dans la continuité de leur situation de travail antérieure, soit dans un désir de changement. Les activités des sujets, de travail ou hors travail, apparaissent comme un moyen de se dégager de la maladie et d’éprouver ce dont on est capable. Elles sont sources de projection de soi dans l’avenir et permettent, alors même que la référence à celui qu’on était auparavant n’est plus valide, d’étayer le projet sur des expériences concrètes. En cela, elles sont un déclencheur des réorganisations. Le projet est donc un moyen de restauration des capacités d’action sur soi et sur son environnement. / Whenever a chronic disease arises, it does mark a break in people’s life, which often leads them to reconsider their vocational project. Through a collective workshop about how to hang on or to return to work and the addition of 35 semi-directive research interviews and 27 counseling interviews, we aim to show that people suffering from a chronic disease build their vocational project, by either carrying on their previous professional life or trying to change it. Both work and off- work activities seem to be a way of escaping the disease and assessing their own capabilities. Through activities, people can picture themselves in the future and build a project based on real experiences, although they are not anymore the person they used to be. Thus, these activities cause reorganizations. The project becomes therefore a way of restoring the ability to act by oneself and on the environment.

Objetivo: Comparar o perfil dos pacientes com fibrose cística de dois centros de referência de Porto Alegre, Hospital São Lucas da Pontifícia Universidade Católica e Hospital da Criança Santo Antônio e correlacionar os pacientes como um grupo em relação a morbidade. Metodologia: Estudo transversal, retrospectivo, com 83 pacientes com diagnóstico de fibrose cística, idade entre um mês a dezoito anos. As variáveis analisadas pelos dois grupos foram: idade atual, idade diagnóstica, idade inicio dos sintomas, cor, número de exacerbações ao ano, internações no ano, internações na vida, idade dos pais, comprometimento pulmonar, comprometimento digestivo, íleo meconial, peso atual e ao diagnóstico, estatura atual e ao diagnóstico, colonização bacteriana em 2010, primeira colonização por Staphylococcus aureus (SA), primeira colonização por Pseudomonas aeruginosa (PSA), primeira colonização pelo Complexo Burkholderia cepacia (CBc), escore de Shwachman-Kulczycki (S-K), variáveis espirométricas, escore socioeconômico (CCEB), terapia medicamentosa, fisioterapia, distância percorrida no Teste de Caminhada dos 6 minutos (TC6M). As variáveis analisadas em conjunto foram: peso atual, estatura atual, colonização bacteriana, variáveis espirométricas, CCEB, S-K e TC6M, internações no ano de 2010 e exacerbações no ano de 2010. Resultados: As variáveis com diferença estatística entre centros foram: mais internações no ano no HCSA (p<0,001), mais internações na vida no HCSA (p<0,001), menor idade da primeira colonização por SA no HCSA (p=0,008), menor idade da mãe no HCSA (p=0,030), menor S-K no HCSA (p=0,001), menor escore sócioeconômico no HCSA (p=0,021), maior uso de dornase alfa no HCSA (p=0,003), maior uso de antibioticoterapia inalatória no HCSA (p=0,006), menor uso de solução salina hipertônica (SSH) no HCSA (p<0,001). As correlações significantes: TC6M com capacidade vital forçada e volume expiratório forçado no primeiro segundo e S-K (p=0,001, r=0,4), S-K com CCEB (p=0,02, r=0,3), CCEB com internações na vida (p=0,03, r=-0,3). Conclusão: Os centros estudados recebem uma população distinta de pacientes, tanto do ponto de vista sócioeconômico, como em relação à gravidade da doença, o que interfere na escolha da terapia medicamentosa utilizada. / Objective: To compare the profile of patients with cystic fibrosis in two reference centers in Porto Alegre, HSL-PUCRS and HCSA and to correlate the patients as a group in relation to morbidity. Methodology: Cross sectional, retrospective study, with 83 patients diagnosed with Cystic Fibrosis, aged one month to eighteen years. The variables analyzed in both groups were: current age, age of diagnosis, age onset of symptoms, color, number of exacerbations in 2010, hospitalizations in 2010 and lifetime hospitalizations, parental age, pulmonary and digestive impairment, meconium ileus, current and diagnosis weight , current and diagnosis stature, and bacterial colonization in 2010, the first SA colonization, the first PSA colonization, the first B. cepacia colonization, Shwachman-Kulczycki score (S-K), spirometric variables, socioeconomic score (CCEB), drug therapy, physiotherapy, walked distance of the Six-Minute Walk Test (6MWT). The variables analyzed together were: current weight and height, current bacterial colonization, spirometric variables, CCEB, SK and 6MWT, admissions in 2010 and exacerbations in the year 2010. Results: The variables with statistically significant differences between centers were more hospitalizations in 2010 in HCSA (p <0.001), more lifetime hospitalizations in the HCSA (p <0.001), lower age at first SA colonization in HCSA (p = 0.008), the youngest mother in the HCSA (p = 0.030), lower S-K in HCSA (p = 0.001), lower socioeconomic score in HCSA (p = 0.021), greater use of DNase in HCSA (p = 0.003), higher use of inhaled antibiotics in HCSA (p = 0.006), less use of hypertonic saline in HCSA (p <0.001). The significant correlations were: 6MWT with lung function and S-K (p = 0.001, r = 0.4), S-K with socioeconomic score (p = 0.02, r = 0.3), socioeconomic score with hospitaizations(p = 0.03, r =- 0.3). Conclusion: The study centers receive a distinct population of patients, both in terms of socioeconomic, as in the severity of the disease, which interferes with de choice of drug therapy used.

Abstract Background: Aphasia is a commonly treated language disorder; however there is discrepancy among professionals regarding classification and assessment practices (Code & Petheram, 2011; McNeil & Pratt, 2001). Current research focuses heavily on acute treatment; chronic aphasia is severely under-represented. A review of the literature revealed a wide array of standardized and non-standardized tests used to evaluate both acute and chronic aphasia cases. Overall, there appears to be variance in evaluation practices, especially among SLPs (Bland et al., 2013). Aims: The present study aims to quantify two variables that may account for this inconsistency in evaluation procedures: 1) years of clinical experience and 2) professional interest. Methods: SLPs with membership to either ASHA Special Interest Group 2 or the ABAI Speech-Pathology Interest Group were contacted to participate in a survey. They were presented with a demographic questionnaire and hypothetical vignettes detailing chronic aphasia cases. The data was collected through SurveyMonkey and exported to R for statistical analysis. Months of clinical experience were subsequently correlated to specific survey responses measuring the following variables: decision to reassess, decision of what clinical constructs to address, selection of assessments, and opinion regarding generalization of naming to functional requesting behavior. Results: Due to lack of participation, the professional interest variable was eliminated. A Spearman Rho test revealed statistical significance for 5 variables. The majority of participants supported reassessment, inclusion of functional assessments, and use of confrontational naming to target requesting. Further research is warranted on the subject, including possible development of a valid functional language assessment for chronic aphasia patients. Keywords: chronic aphasia, assessment, experience, professional interest, survey, functional behaviors

Hyperbaric Oxygen Therapy (HBOT) is an old technology which has acquired value in chronic wound care. HBOT is known to promote local and systemic healing effects by improving the oxygenation of the wound tissue. The increased tissue oxygenation hastens removal of the bacterial bioburden, which allows resolution of inflammation and facilitates matrix production, cell division, and ultimately wound closure. Staphylococcus aureus is the most frequently isolated organism from Diabetic Foot Infections (DFI). Therefore, our lab chose to use the treatment paradigm of HBOT to initially look at the single species level as to how HBOT affects S. aureus. DFI are primarily polymicrobial, so the responses of bacterial communities to this therapy were also considered. Previous research focused solely on host response to HBOT, but our pilot testing indicates that HBOT also exhibits a bacterial response. Initial testing with S. aureus indicated that HBOT can create growth defects in bacteria in vitro. In preliminary experiments, our lab discovered that bacterial culture on solid medium is greatly altered under the pressure of hyperbaric oxygen. Normal robust growth and pigmentation are seen in S. aureus cultured in ambient conditions. However, when the same strain is cultured under HBOT conditions, there is a marked decrease in pigmentation and colony size. When other species were exposed to HBOT conditions, growth on solid media was significantly diminished. Interestingly, K. pneumoniae is able to grow normally under HBOT conditions. Normal air mixtures at the increased pressure do not have any discernable effect on bacterial growth, and the limiting effects of oxygen are not seen unless used at the increased pressure. In a broth macrodilution MIC assay, various antibiotics show an increase in susceptibility after exposure to HBOT. Lastly, biofilm formation is altered under HBOT conditions, further supporting a bacterial adjustment to HBOT and an altered mode of growth. In order to better understand the effects of a high pressure high oxygen environment on the bacterial bioburden, this study investigates the effects of HBOT on bacterial species comprising a chronic wound. Primary data has suggested that HBOT increases susceptibility of antibiotics, and can alter bacterial transcription to hinder growth of many organisms. We hypothesize that Hyperbaric Oxygen Therapy affects diabetic foot infections by changing the healing process via transcriptional alteration of bacterial species in the wound. Furthermore, we hypothesize that HBOT alters the efficacy of some antibiotics as well as affecting the biofilm capacity of many bacterial species.

Late onset Alzheimer’s disease (LOAD) is the commonest form of dementia, affecting approximately 850,000 patients in the UK alone, predicted to exceed one million by 2025. The cause of LOAD is complex, but several large Genome Wide Association Studies have highlighted 21 genetic loci associated with this devastating disease and the ATP-Binding Cassette Protein, family A, member 7 (ABCA7) is one of these genetic loci. However, the exact reasons behind this association are still unknown, focusing work on identifying functional, pathogenic mutations within this locus. A total of 240 exonic variations within ABCA7 were therefore annotated in order to identify ones potentially altering the functionality of ABCA7. A total of five variants were predicted to be damaging by in silico annotation tools: rs3752233; rs59851484; rs3752237; rs114782266 and a novel mutation at genomic position 19:1056958. These were genotyped in the ARUK DNA Bank resource and three (rs59851484, rs3752239 and 19:1056958) showed tentative association with LOAD. However, lack of power in this study prevented any definitive associations from being formed. A further two variants were examined within functional cell assays. rs881768 had been predicted to affect the splicing of the ABCA7 protein and appeared to do so within minigene cellular assays. However, this did not appear to be the case when RNA from brain tissue harbouring this variation was examined. rs2020000 was examined through the dual luciferase assays, with the minor allele seeming to down regulate the reporter protein by approximately 30% (p < 0.02) in these in vitro assays. Functional variations within the ABCA7 locus do play a role in LOAD risk and improvements within functional databases and annotation programmes will assist in identifying these causative mutations, in order to put a halt to LOAD, as well as other destructive complex disorders.

Doctor of Philosophy / Department of Kinesiology / David C. Poole / The onset of skeletal muscle contractions induces rapid and robust increases in metabolic rate (V̇O₂) and blood flow (Q̇) in order to supply the energetic demands of the muscle. In young healthy populations, these variables increase proportionally to maintain oxygen flux into the myocyte for both sexes. However, while the resultant changes in V̇O₂ and Q̇ conflate to establish adequate driving pressures of oxygen (PO₂), it appears that the underlying control processes express distinct sexual dimorphism. Estrogen is crucial for cardiovascular control for young women through its relationship with nitric oxide (NO) and results in lower blood pressure and risk of cardiovascular disease for women. However, in post-menopausal women and some disease states, such as heart failure (HF), these protections are lost due to reductions in estrogen and NO bioavailability which causes women to catch and surpass men in rates of hypertension and cardiovascular disease. The purpose of this dissertation is to explore the mechanisms responsible for establishing the oxygen delivery-to-utilization matching (Q̇O₂/V̇O₂) necessary for skeletal muscle contractions in health and disease. In the first investigation (Chapter 1), we explored the effect of altered NO bioavailability on spinotrapezius muscle interstitial space PO₂ (PO₂is; determined by Q̇O₂/V̇O₂) of healthy male and female rats. We show that both sexes regulate PO₂is to similar levels at rest and during skeletal muscle contractions. However, modulating NO bioavailability exposes sex differences in this regulation with females having greater reliance on basal NO bioavailability and males having greater responsiveness to exogenous NO. In the second investigation (Chapter 2), we sought to determine whether measures of central and peripheral function in HF rats predicted exercise tolerance (as critical speed (CS)). We showed for the first time, that CS can be resolved in HF animals and that decrements in central cardiac (echocardiography) and peripheral skeletal muscle function (PO₂is) predicted CS. Building upon these findings, the third investigation (Chapter 3) aimed to determine if the sex differences in the control of PO₂is seen in healthy rats translated to greater deficits in HF for females. Furthermore, this investigation sought to determine if five days of dietary nitrate supplementation (an exogenous NO source) would raise PO₂is in HF rats, with a greater effect seen in females. We revealed that HF reduces PO₂is at rest and during skeletal muscle contractions and this negative effect is exacerbated for females. However, elevating NO bioavailability with dietary nitrate increases resting PO₂is and alters the dynamic response during contractions with females potentially being more responsive than males. The results herein reveal the importance of NO in the control of Q̇O₂/V̇O₂ in health. The onset of HF results in deleterious declines in exercise tolerance, which are mediated through reductions in central and peripheral function, due, in part, to attenuated NO bioavailability. This creates intensified Q̇O₂/V̇O₂ dysfunction in females with HF; however, this can potentially be countered with dietary supplementation of inorganic nitrate. Altogether, the present dissertation suggests that targeting NO bioavailability, particularly in female HF patients, could be a beneficial non-pharmaceutical therapeutic strategy.