Stroke is the second most common cause of death worldwide and the leading cause of long-term neurological disability. In the UK, stroke accounts for approximately 6% of total National Health Service and Social Services expenditure. The burden of stroke is predicted to increase because of the ageing population. Whilst effective primary prevention is important, about 30% of strokes occur in individuals with a previous transient ischaemic attack (TIA) or minor stroke. Recent prospective studies have shown a high early risk of recurrent stroke in the days after TIA or minor stroke. The prompt use of preventative strategies has been shown to be highly effective in reducing this early risk of recurrence and there is now a consensus in favour of rapid access services and urgent secondary prevention after TIA. However, there are several areas where clinical practice still needs to be improved, including delays in seeking medical attention, the reliability of clinical diagnosis of TIA in the acute phase, prediction of stroke recurrence risk and the control of risk factors, particularly blood pressure (BP), in longer-term secondary prevention. My thesis will focus on these clinically important areas. I have used data from a population-based study; the Oxford Vascular Study (OXVASC). OXVASC is a prospective, population-based incidence study of vascular disease in all territories in Oxfordshire, UK, which started in 2002 and is ongoing. The study population comprises approximately 91 000 individuals registered with nine general practices and uses multiple overlapping methods of “hot” and “cold” pursuit to identify all patients with acute vascular events. The research described in this thesis has several clinically useful findings which address areas for improvement during the patient journey after TIA and minor ischaemic stroke. First, I have highlighted that despite public education campaigns, about 70% of patients still fail to correctly recognise TIA or minor stroke symptoms and about 30% delay seeking medical attention for over 24 hours. Second, I have shown that recurrent TIA within 7-days is not associated with a greater stroke risk than after a single TIA, other than in the capsular warning syndrome. Third, in patients with definite posterior circulation TIA or stroke, preceding transient isolated “brainstem” symptoms occur in 26%, which has implications for the current diagnostic criteria for TIA. Fourth, I have shown that the Face Arm and Speech Test does not reliably identify patients at high early risk of recurrent stroke after TIA and minor stroke and has limited potential to improve access to care. Fifth, I have shown that outpatient management of clinic-referred minor stroke is feasible and may be as safe as inpatient care. Sixth, that stroke recurrence risk after minor stroke is delayed compared with TIA, and is high during the subacute phase despite current best medical treatment. Seventh, I have assessed Bluetooth- based home BP monitoring after TIA or minor stroke as a way of achieving better BP control and shown that this method is feasible, irrespective of age, and patient satisfaction is high. Finally, I have studied the late outcomes after TIA and stroke in OXVASC in comparison with a similar cohort from the 1980’s. I have shown that the age and sex specific later risk of recurrent stroke after TIA and stroke in Oxfordshire has fallen. However, the risk of fatal recurrent stroke remains high in contrast with the risk of fatal cardiac events which is low.

This research focuses on vulnerable children in Swaziland, the country with the highest level of adult HIV prevalence in the world, where nearly 25 percent of children will be orphaned by 2010. It investigates the experiences of relatively poor urban children growing up in the epidemic and the coping strategies the children and their adult carers adopt. Through the lens of both children and adult carers, it explores the ways sexual knowledge is gained and used by older children in the context of HIV/AIDS as well as the experience of coping with widespread bereavement. In this way, it adds to the literature on childhoods in the 'South' and the increasing recognition of the heterogeneity of children's lived experiences. Rather than being seen as passive, the agency of both vulnerable children and their adult carers emerges as they seek to improve their livelihoods. The way this agency connects with government, NGO and community structures is revealed by showing the opportunities for and constraints on gaining access to education and health-care. The interwoven roles of government, international donors, NGOs and civil society is explored by assessing the relative merits of supporting vulnerable children by either welfare assistance to poor families or new forms of 'community' care structures or institutionalised residential care. The critical importance of relationships and power relations between key actors in different organisations and the effect this has on implementation of interventions for children is discussed as well as the relevance of these findings to vulnerable children in other settings.

TITLE: Knowledge and attitudes towards HIV / AIDS among adolescents in the selected region AUTHOR: Bc. Magdalena Sajdlová DEPARTMENT: Department of education and social education, department of health education SUPERVISOR: Peadr. Eva Marádová, Csc. ABSTRACT: The thesis is divided into the two parts. The first part describes basic information about HIV and AIDS - the essence of the disease, transmission of disease, method of spreading the principles of diagnosis, therapy options. I describe the basic principles of prevention for a wide strata of the population and the basic principles of teaching, education and prevention in the elementary school. The second part is called research investigation. It describes the basic structure of the work. The research part contains the way of teaching of HIV and AIDS in three selected elementary schools and one selected secondary school in eighth classes. Information was obtained using a questionnaire, where I find the knowledge and attitudes of pupil sin individual schools and an interview with a teacher who has taught this subject. The results of the schools compare with each other. Based on the results of the evaluation recommendations processing (content, form) for individual schools. KEYWORDS: HIV / AIDS, disease characteristics, disease prevention

Philosophiae Doctor - PhD / Background: Non-communicable diseases (NCDs) continue to rise in South Africa, accounting for 43% of total deaths in 2012. Smoking and a diet high in salt are among the major modifiable risk factors for NCDs that can be addressed through cost-effective policy interventions in the form of regulation or legislation and active multisectoral engagement. Population-based prevalence and mortality data are necessary for monitoring and evaluation such interventions. South Africa has developed a National Strategic Plan for NCDs but there is limited evaluation of NCD policies. Furthermore, there is a need to explore the availability of population-based data and the role that it can play to monitor interventions. Aim: The overall aim of the thesis is to assess the implementation of policies for reducing risk factors for chronic NCDs in South Africa, and to explore the role of population-based data in supporting environmental and policy approaches to prevent NCDs. The thesis will also examine whether there are differences in urban and rural settings in the implementation of tobacco control and salt reduction regulation as well as the barriers to implement the National Strategic Plan for prevention of NCDs. Methods: Multiple methods of data collection were used. A desk review of policies to address NCDs in South Africa was undertaken and semi-structured interviews with the NCD policymakers and managers in two provinces (the Eastern Cape and Western Cape) were undertaken, to explore challenges and successes of implementation of the NSP. The Cross-sectional baseline questionnaire and quantified food frequency data from the PURE study were used to determine the prevalence of smoking and the intakes of sodium and potassium in a selected urban and a rural community. Data collected using a validated community audit tool was used to assess the physical environment related to tobacco as well as questionnaire data from face-to-face interviews about perceptions about tobacco use in the urban and rural communities. Trends in mortality from tobacco related and high salt consumption related conditions together with prevalence data from national health surveys were reviewed to assess the health impact.

A dissertation submitted to the Faculty of Science under the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master in Science. Johannesburg, June 2017. / In South Africa, the anti-HIV-1 activity of various indigenous plants has not been studied extensively. Most of the phytochemical screening work has focused on anti-cancer activity with less attention given to infectious diseases. A large proportion of South Africans (70-80%) still rely on traditional medicines for treatment of various ailments. And, therefore, there is a need to evaluate and validate the effectiveness of the traditional medicines. The aim of this study was to identify, screen, phytochemically characterize and isolate bioactive compounds from a South African herbal extract that exhibit the best anti-HIV-1 activity. Three extracts were prepared: an ethanol extract, a dereplicated ethanol extract and an aqueous extract from a herbal concoction comprised of a mixture of six plants. These herbal concoctions were investigated for anti-HIV-1 subtype C activity. Phytochemical profiling of the ethanol- and dereplicated ethanol- extracts from the herbal concoctions showed the presence of intermediate polar compounds (flavonoids, alkaloids, sugars and terpenes) for both extracts, while the aqueous extract contained predominantly highly polar compounds. Anti-HIV-1 screening of the three extracts showed that the ethanol and dereplicated ethanol herbal- extracts had the best anti-reverse transcriptase activity. The ethanol extract had mean IC50 values of 56.53, 53.96 and 55.39 μg/ml against MJ4, Du179 and CM9 HIV-1 subtypes C isolates, respectively. The dereplicated ethanol extract had mean IC50 values of 51.87, 47.56 and 52.81 μg/ml against MJ4, Du179 and CM9 HIV-1 isolates, respectively. The aqueous extract was inactive against HIV-1 activity. Moreover, both the ethanol- and dereplicated ethanol- extracts showed activity against HIV neutralization. The ethanol- and dereplicated ethanol- extracts had mean IC50 values of 36.33 and 32.06 μg/ml, respectively. Furthermore, they also potently neutralized Vesicular stomatitis virus (VSV) yielding mean IC50 values of 24.91 and 20.82 μg/ml for ethanol- and dereplicated ethanol- extracts, respectively. All extracts were inactive against Murine leukemia virus (MLV). The isolation and phytochemical characterization of the bioactive compound(s) was done by utilizing various chromatographic and spectroscopic methods. Four homoisoflavanoids were isolated and tested for anti-HIV-1 subtype C activity. Three compounds (1, 3a and 3b) were inactive while compound 2 was found to be bioactive against HIV-1 reverse transcriptase (RT) and yielded mean IC50 values of 7.23 ± 1.88, 12.83 ± 0.41 & 12.81 ± 0.10 μg/ml for MJ4, CM9 and Du179 HIV-1 subtype C isolates, respectively. Compound 2 had a mean CC50 value of 23.08 ± 0.1981 μg/ml against HEK293T cells. Overall, the data suggested that ethanol- and dereplicated ethanol- herbal extracts possess direct and indirect anti-HIV-1 activity. They possess a cocktail of phytochemicals that can inhibit HIV-1 RT, HIV-1 entry. Furthermore, these extracts possess phytochemicals that can lower the activation of inflammatory responses during an infection and, hence, reduction in the number new cells infected during the course of HIV-1 infection. Moreover, they possess phytochemicals that have antioxidant activity which, in relation to HIV infection, results in a boosted immune system response in order to ward off the virus. / MT 2017

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. Johannesburg, 2016 / According to UNAIDS, there are ~36.9 million people infected with HIV-1 in the world. Of those, 25.8 million live in sub-Saharan Africa and 6.8 million in South Africa. HIV-1 subtype C accounts for over 95% of HIV infections in South Africa. HIV-1 retrovirus acquires mutations rapidly because of the viral reverse transcriptase. Naturally occurring polymorphisms distinguishing wild type C-SA PR from other proteases make it less susceptible to inhibitors. E35D↑G↑S is a C-SA PR variant with a double insertion in the flap region of the protease. The insertions and background mutations may decrease susceptibility to inhibitors as well as alter kinetic parameters due to increased flap flexibility. This study intended to characterise the effect of the mutations and insertions in E35D↑G↑S on structural, kinetic activity and drug susceptibility. Chemically-synthesised E35D↑G↑S autocatalyses rapidly, impeding further characterisation. There was no detectable overexpression of the E35D↑G↑S protease in Escherichia coli BL21 (DE3)pLysS and Rosetta 2® cells. If the protease is catalytically enhanced, attributed cytotoxicity may prevent overexpression of the protein. Increased autocatalytic activity could also prevent crystallisation. Inactive E35D↑G↑S D25A did not overexpress either, indicating that codon harmonisation with the expression host ought to be performed. C-SA PR was shown to be a predominantly beta-sheeted protein using circular dichroism spectroscopy. The KM of the fluorogenic substrate resembling the capsid/ p2 cleavage site for C-SA PR was 22.02 ±4.09 μM. The specific activity, catalytic turnover and catalytic efficiency of the wild-type C-SA PR protease were found to be 35.68 ±1.06 μmole.min-1.mg-1, 12.79 ±0.38 s-1 and 1.17 ±0.055 s-1.μM-1, respectively. The thermodynamics of binding of atazanavir, ritonavir and darunavir to C-SA PR were determined using isothermal titration calorimetry. The binding of atazanavir and ritonavir to C-SA PR is entropically driven and enthalpically opposed. However, the binding of darunavir to C-SA PR was found to be both entropically and enthalpically favourable. The dissociation constants of the inhibitors in the absence of substrate (Kd) are in the pico-molar range and increased by approximately one order of magnitude when saturating concentrations of substrate were introduced. Atazanavir, ritonavir and darunavir have dissociation constants (Kd) of 160.56 ±54.59 pM, 113.34 ±46.47 pM and 10.24 ±6.02 pM, respectively. Darunavir binds significantly tighter. Keywords: C-SA PR, E35D↑G↑S, insertion mutations, protease, autocatalysis, ITC.

Introdução: O câncer é uma doença que acomete grande parte da população mundial, sendo o segundo maior responsável pelas mortes no Brasil. A maior parte do cânceres é passível de prevenção e outra grande parte tem altos índices de cura se diagnosticados precocemente. Por isso, o papel dos profissionais de saúde é de fundamental importância para programas eficazes de rastreamento e prevenção do câncer. Objetivos: Avaliar o conhecimento e as práticas de médicos que trabalham em equipes da APS (Estratégia Saúde da Família e Unidades Básicas de Saúde Tradicionais) relacionadas à prevenção do câncer. Material e métodos: Foram realizadas entrevistas com os profissionais da atenção primária: Médicos de Família e Comunidade, Clínicos Gerais e Ginecologistas e Obstetras, vinculados a Unidades de Saúde da Família e Unidades Básicas de Saúde do município de Ribeirão Preto. Os As entrevistas foram realizadas utilizando-se um questionário semi-estruturado, subdividido em 5 partes: dados profissionais, rastreamento do câncer de mama e colo de útero, rastreamento do câncer de cólon e reto, rastreamento do câncer de pulmão e rastreamento de outros tipos de câncer. Resultados: Apesar de afirmarem conhecer as diretrizes de rastreamento de câncer dos principais órgãos nacionais de combate à doença, a análise das práticas referidas pelos entrevistados estava muito aquém daquilo preconizado por essas instituições. Conclusões: Há que se investir em estratégias de conscientização dos profissionais de saúde como um todo (e não apenas os médicos) para o correto aconselhamento de medidas de promoção de saúde relacionada ao câncer, bem como dos exames de rastreamento para o diagnóstico precoce dessas doenças. / Introduction: Cancer is a disease that affects a big part of the world\'s population, and is the second most prevalent cause of death in Brazil. The majority of cancers are preventable and another large part has high rates of cure if diagnosed in early stages. Therefore, the role of health professionals is fundamental for effective cancer prevention and screening programs. Objectives: Evaluate the practices and knowledge of physicians that work in primary health centers (Family Health Strategy Centers and traditional Health Posts) related to cancer prevention. Methodology: Interviews were made with the primary care professionals: family health practitioners, general practitioners and gynecologists and obstetricians, who work at primary health centers in Ribeirão Preto´s local health system. The Interviews were made using a semi-structured questionnaire, divided into 5 parts: professional data, cervical and breast cancer screening, colon and rectal cancer screening, lung cancer screening and screening of other types of cancer. Results: In spite of respondents declare to know the main cancer screening guidelines from the major national institutions for fighting the disease, the analysis of the referred practices of the interviewed participants were too far from what is recommend by those institutions. Conclusion: There is a need to invest in awareness strategies as a whole (and not just the the physicians) for the correct health promotion counseling related to cancer, as well as in the screening tests for early diagnosis of these diseases.

As doenças cardiovasculares são uma realidade no país, apresentando um impacto significativo na morbi-mortalidade dos indivíduos e no gasto público relacionado aos tratamentos e aposentadorias precoces. Os altos índices de morte por doença cardiovascular podem ser explicados pela grande incidência de fatores de risco associados a baixos níveis de intervenção sobre esses fatores. O presente trabalho tem como objetivos: caracterizar os indivíduos segurados por planos de saúde privados com relação às variáveis sociodemográficas, antropométrica, comportamental e clínicas; identificar o risco cardiovascular obtido por meio do Escore de Risco de Framingham (ERF) e comparar o ERF entre os indivíduos com relação às referidas variáveis.Trata-se de um estudo transversal comparativo/correlacional, de abordagem quantitativa. A pesquisa foi realizada em uma empresa privada prestadora de serviços de gerenciamento de doentes crônicos para operadoras de planos privados de saúde, em diversos estados do Brasil. Os critérios de inclusão na amostra foram ter pessoas de ambos os sexos; com idade entre 30 e 74 anos e com prontuários eletrônicos completos para a realização do estudo. Foram estudados 2967 associados, sendo 1339 homens e 1628 mulheres. A amostra foi composta em sua maioria por mulheres (54,9%), por pessoas com 60 anos ou mais (57,4%), com sobrepeso ou obesas (79,5%), com colesterol total e HDL-c dentro da normalidade (61,5% e 59%, respectivamente), normotensos (PAS < 130 = 55,2%; PAD < 85 = 83,1%), não diabéticos (57,9%), não tabagistas (91,4%) e aposentados e donas do lar (60,1%). A escolaridade mostrou predomínio de indivíduos analfabetos ou com nível de escolaridade até o ensino fundamental (39,1%). As patologias mostraram predomínio de indivíduos portadores da HAS (35,8%) e de HAS acompanhada por DM (20,9%). Com relação à estratificação do risco cardiovascular, a maior parte da amostra estava classificada na faixa de médio e alto, ou seja, risco superior a 10% de desenvolver doença arterial coronariana em 10 anos - (55,6%). A análise de regressão logística mostrou que possuem maior risco de apresentar ERF médio/alto os indivíduos do sexo masculino, mais velhos, obesos, com baixa escolaridade, fumantes, com CT >= 200 mg/dl, com baixos níveis de HDL-c, com PAS >= 130 mmHg, com PAD > 90 mmHg e diabéticos (p< 0,05). A análise de regressão multinomial mostrou que possuem maior risco de apresentar ERF médio e alto os indivíduos do sexo masculino, acima do peso, com baixa escolaridade, fumantes, CT >= 200 mg/dl, HDL < 60 mg/dl, PAS >= 130 mmHg, PAD >= 85 mmHg e diabéticos (p< 0,05). O uso da curva ROC mostrou que o ERF pode identificar indivíduos de baixo risco, médio/alto risco, médio risco e alto risco com acurácia considerada ótima (com valores da área sob a curva variando de 0,82 a 0,94). Esses resultados fornecem subsídios na determinação de prioridades de intervenção na pratica clinica com relação aos fatores de risco / The cardiovascular diseases are reality in Brazil, presenting a significant impact in morbi-mortality of the population and in the public expenses related to treatments and precocious retirements. The high averages of death for cardiovascular illness can be explained by the great incidence of risk factors associated to low levels of intervention on these factors. The present research has as objective: to characterize people insured for private health plans related to sociodemographics, anthropometrics, behavioral and clinical variables; to identify the cardiovascular risk by the Framingham Heart Score (FHS) and to compare the FHS among the participants and based on the related variables. This is a transversal, comparative/correlational, quantitative study. The research was realized in a private company that manages people who has chronic diseases for private health plans operators, in diverse states of Brazil. The criteria of inclusion in the sample was: to include people of both the gender; aged between 30 and 74 years and having complete electronic medical register for the accomplishment of the study. 2967 associates had been studied, 1339 men and 1628 women. The sample was composed in its majority by women (54,9%), 60 years old or more (57,4%), overweight or obeses (79,5%), normal results of serum cholesterol and HDL-c (61.5% and 59%, respectively), normal blood presure (systolic blood pressure - SBP < 130 = 55,2%; diastolic blood pressure - DBP < 85 = 83.1%), non diabetic (57,9%), non smoking (91,4%) and pensioners and housewives (60,1%). The scholarity level showed predominance of illiterate individuals or with low scholarity level (39,1%). The patologies showed predominance of associates who have hypertension (35,8%) and hypertension and diabetes (20,9%). About the stratification of the cardiovascular risk, most of the sample was classified in the band of medium/high risk, and/or risk higher than 10% to develop coronary arterial disease in 10 years (55,6%). The analysis of logistic regression showed that have greater risk to present FHS medium/high: male sex associates, older, obeses, with low scholarity levels, smokers, serum cholesterol >= 200 mg/dl, low levels of HDL-c, SBP >= 130 mmHg, DBP > 90 mmHg and diabetic (p < 0,05). The analysis of multinomial regression showed that have greater risk to present average and high FHS: male sex associates, overweight, low scholarity levels, smokers, serum cholesterol >= 200 mg/dl, HDL-c < 60 mg/dl, SBP >= 130 mmHg, DBP >= 85 mmHg and diabetic (p < 0,05). The ROC curve showed FHS can identify individuals of low risk, medium/high risk, medium risk and high risk with accuracy considered excellent (values of the area under the curve varying from 0,82 to 0,94). These results supply subsidies to determine priorities of intervention on risk factors in clinical practice

Background: Hypertension is the biggest contributor to the global burden of disease, and has a big impact on low-to middle-income countries. Nurses are important actors in disease prevention and health promotion which is typically used to prevent hypertension. Vietnam is a middle-income country with elaborate hypertension problems. Aim: The aim of this study is to explore nurses´ experiences of working with hypertension (HT) prevention in Vietnam.  Method: This is a qualitative study using semi-structured interviews and content analysis. Result: Challenges, methods and perceptions from the experiences of working as a nurse with HT prevention were identified. Lack of equipment, methods and funds, and to help the patient change bad habits were the main challenges. Conclusion: Nurses in Vietnam experience many challenges in their work to prevent HT. The challenges include lack of education, resources and difficulties to help people change behaviour. Few opportunities were perceived by the nurses. Further research is needed to explore the situation of nurses working with HT prevention, and what needs to be done on different levels to facilitate their work.

Thesis (MTech (Environmental Health and Occupational Studies))--Cape Peninsula University of Technology, 2016 / Currently, the world faces many challenges such as a food shortages, fossil fuel depletion, floods, earthquakes, recession, wars, and climate change. It also faces diseases such as Human Immune Deficiency Virus /Acquired Immune Deficiency Syndrome /Sexually Transmitted Infections and Tuberculosis (HIV/AIDS /STI and TB). This study focused on HIV/AIDS/STI and TB, and the impact of changes in sexual behaviours of student peer educators as a result of peer education programmes offered by the HIV/AIDS Unit at the Cape Peninsula University of Technology (CPUT). Although young people today have a better understanding of risky sexual behaviours, HIV remains a health problem among the youth in South Africa. HIV/AIDS is a disease that affects all sectors of the population- rich and poor, young and adult, educated and uneducated. Tertiary institutions are places where many young female and male students live independently, unsupervised by their parents or guardians, in either private accommodation or student residences. Under these circumstances it may be expected that some students will explore and experience intimacy in their relationships. Hence, universities could play a vital role in shaping students’ attitudes and behaviours towards relationships, safer practices, and respect for others. Given the current absence of a cure or vaccine for HIV/AIDS, peer education should appear as an important tool in HIV prevention strategy. It draws on several well-known behavioural theories and many researchers view peer education as an effective behavioural change strategy. A formal structured Peer Education Programme was initiated and implemented at the HIV/AIDS Unit at Cape Peninsula University of Technology (CPUT) since 2004. This initiative was in line with one of the twelve strategic objectives of the HIV/AIDS Unit at the CPUT. This study therefore, aimed to assess the reflexive effect that the Peer Education Programme had on student peer educators who volunteer their services at the HIV/AIDS Unit at CPUT. It further attempted to assess the effect of the Peer Education Programme on changes in sexual behaviours that could occur amongst student peer educators. The purpose of this programme was to explore peer educators who were based in the HIV/AIDS Unit applying their acquired knowledge and skills; so that they may become role models for their peers by practising what they taught, and not taught what they proposed to practice. The study furthermore, forms on how effective the Peer Education Programme of CPUT’s HIV/AIDS Unit is in changing sexual behaviours of the student peer educators.