BACKGROUND AND AIMS: Obesity is associated with vascular endothelial dysfunction, which predisposes obese persons to cardiovascular disease. Fat loss in obese persons can lead to metabolic improvements that promote improved cardiovascular health and decrease risk of stroke or myocardial infarction. The objective of this study was to assess the potential of weight loss achieved by bariatric surgery to improve endothelial function. METHODS: Patients scheduled to undergo bariatric surgery were prospectively followed. Biochemical analyses and vascular function testing were performed preoperatively and again at 1, 3, 6, and 12 months postoperatively. FMD and NMD were measured to assess macrovascular endothelial function and ∆ hyperemic flow was measured to assess microvascular endothelial function. RESULTS: Patients (n = 375) ages 41.76 ± 12.35 years, with baseline BMI of 45.64 ± 8.36, experienced a weight reduction of 82.07 ± 33.98 lbs the year following surgery. FMD % increased by 1.28 ± 5.49, NMD % by 4.26 ± 6.23, and ∆ hyperemic flow % by 262.1 ± 519.97. All vascular function variables demonstrated a significant increase over time (p < 0.05) with ∆ hyperemic flow % experiencing the most significant change (p < 0.0001). No difference was found in improvement in vascular function between high (>13 µIU/ml) and low (≤13 µIU/ml) baseline plasma insulin groups (p values all > 0.05). CONCLUSIONS: Bariatric surgery was associated with an improvement in macrovascular and microvascular endothelial function. Further analyses is needed to determine which clinical parameters are optimal predictors of improvements in vascular endothelial function after bariatric surgery.

The foot-and-mouth disease (FMD) virus poses a considerable threat both to farmers and to the wider economy should there be a future incursion into the UK. The most recent large-scale FMD epidemic in the UK was in 2001. Mathematical models were developed and used during this epidemic to aid decision-making about how to most effectively control and eliminate it. While the epidemic was eventually brought to a halt, it resulted in a huge loss of livestock and is estimated to have cost the UK economy around ¿6 billion. The mathematical models predicted the overall spatial spread of FMD well, but had low predictive ability for identifying precisely which farm premises became infected over the course of the epidemic. This will in part have been due to the stochastic nature of the models. However, the transmission probability between two farm premises was represented as the Euclidean distance between their point locations, which is a crude representation of FMD transmission. Additionally, the premises' point location data contain inaccuracies, sometimes identifying the farmer's residential address rather than the farm itself which may be a long way away. Local FMD transmission occurs via contaminated fomites carried by people or vehicles between premises, or by infected particles being blown by wind between proximal fields. Given that these transmission mechanisms are thought to be related to having close field boundaries, it is possible that some of the inaccuracy in model predictions is also due to imprecisely representing such transmission. In this thesis I use fine-scale geographical data of farm premises' field locations to study the contiguity of premises (where contiguous premises (CPs) are defined as having field boundaries < 15m apart). I demonstrate that the distance between two premises' point locations does not accurately represent when they are CPs. Using an area of southern Scotland containing 4767 livestock premises, I compare the predictions of model simulations using two different model formulations. The first is one of the original models based on the 2001 outbreak, and the second is a new model in which transmission probability is related to whether or not premises were contiguous. The comparison suggests that the premises that became infected during the course of the simulations were more predictable using the new model. While it cannot be concluded that this will translate into more accurate predictions until this can be validated during a future outbreak, it does suggest that the new model is more predictable in its route through the landscape, and therefore that it may better reflect local transmission routes than the original model. Networks based on contiguity of premises were constructed for the same area of southern Scotland, and showed that 90.6% (n=4318) of the premises in the area were indirectly connected to one another as part of the Giant Component (GC). The network metric of 'betweenness' was used to identify premises acting as bridges between otherwise disconnected sub-populations of premises. It was found that removing 100 premises with highest betweenness served to fragment the GC. Model simulations indicated that, even with some longer-range transmission possible, removing these premises from the network resulted in a large decrease in mean number of infected premises and outbreak duration. In real terms, premises removal from the network would mean ensuring these premises did not become infected by enhanced biosecurity and/or vaccination depending on policy. In this thesis I also considered the role of biosecurity practices in shaping FMD spread. A sample of 200 Scottish farmers were interviewed on their biosecurity practices, and their biosecurity risk quantified using a biosecurity 'risk score' developed during the 2007 FMD outbreak in Surrey. Using Moran's I and network assortativity measures it was found that there did not appear to be any clustering of biosecurity risk scores on premises. Statistical analysis found no association between biosecurity risk and the mathematical model's premises' susceptibility term (which describes the increase in a premises' susceptibility with increasing numbers of livestock). This suggests that the model's susceptibility term is not indirectly capturing a general pattern in biosecurity on different sized farm premises. Thus, this body of work shows that incorporating a more realistic representation of premises location into mathematical models, in terms of area (i.e. as fields) rather than a point, alters predictions of spatial spread. It also demonstrates that targeted control at a relatively small number of farms could effectively fragment the farming landscape, and has the potential to considerably reduce the size of an FMD outbreak. It also demonstrates that variations in premises' FMD biosecurity risks are unlikely to be indirectly affecting the spatial or demographic components of the model. This increase in understanding of how geographic, social and demographic factors relate to FMD spread through the landscape may enable more effective control of an outbreak, should there be an incursion in the UK in future.

A proposed Foot and Mouth Disease (FMD) free zone, in the eastern region of Thailand, was evaluated by FMD experts with the World Organisation for Animal Health (OIE) during 2012-2013. The zone, however, did not qualify for an FMD-free zone with vaccination because it did not comply with the requirements in the OIE Terrestrial Code. Then, the Department of Livestock Development (DLD) within the government of Thailand revised laws and regulations related to the FMD control program in order to be in compliance with the OIE's requirements. The revised FMD control program has been implemented since 2015. These revisions and implementations, however, have not been evaluated. The main objectives of this study were to determine whether the revised regulations (since 2015) currently being implemented are fully in compliance with the OIE's requirements, and to verify whether the implementation of the current FMD control program is sufficient to control FMD effectively. First, this study developed an evaluation framework and assessment tools for use in the evaluation of the FMD control policies and their implementation in the eastern region of Thailand. The assessment tools include assessment matrices, three sets of questionnaires, and interview questions. When applied, the assessment matrices identify shortcomings of policy design, policy implementation, veterinary capacity, and stakeholder engagement. Questionnaires and interview questions collect information that examines the consistency of elements of the FMD control program against criteria in the assessment matrix. Then, the design of current FMD control policies was assessed by interviews of DLD officers at national level who formulate policies related to FMD control program and by reviews of DLD existing written policies and documents. This study found that the design of current FMD control system is appropriate and meets the OIE's requirements. Next, the implementation of the current FMD control program in the eastern region of Thailand was assessed. The assessment was conducted by (i) questionnaire surveys with DLD officers at local level, private veterinarians, and farmers, (ii) interviews with DLD officers at national and regional level and private veterinarians, and (iii) field observations. The assessment found that the current implementation of the FMD control program in the eastern region of Thailand needs further improvement in order to meet the OIE's requirements. This study also proposes recommendations to the DLD in improving the FMD control system in the eastern region of Thailand including surveillance system, reporting system, vaccine strategy, animal movement control system, and response plans. For example, there should be an increase of stakeholders' awareness of disease reporting requirements. Evidence of adequate vaccination coverage and population immunity should be available and accessible. Allocation of staff at local level should be reconsidered for more appropriate service deliveries. Communications between DLD and stakeholders regarding the FMD control program need to be strengthened for more effective message delivery. Lastly, this study strongly recommends that there should be strong commitments and supported by the higher level of the Thai's government. / Doctor of Philosophy / Foot and Mouth Disease is a highly contagious and the most economically important infectious viral disease of livestock. The disease exists in Thailand and interrupts livestock trade through the loss of access to international markets. The Department of Livestock Development (DLD) within the government of Thailand has proposed to make the eastern region of Thailand an officially recognized FMD-free zone with vaccination in order to advance market access and trade facilitation. In order to be an official FMD-free zone, the proposed FMD-free zone (eastern region of Thailand) needs to be evaluated by experts within the World Organization for Animal Health (OIE) and must meet all requirements of the OIE standard for this certification. Since 2015, there has not been an evaluation to determine the effectiveness and appropriateness of the current FMD control program in the eastern region of Thailand. This study aims to evaluate the design and implementation of the current FMD control program in the eastern region of Thailand. This study, first, developed an evaluation framework and assessment tools for use in the evaluation of the FMD control policies and their implementation in the eastern region of Thailand. Then, the design of the current FMD control policies and their implementation were evaluated. The assessment found that the design of the current FMD control system is appropriate and meets the OIE's requirements. However, the current implementation of the FMD control program needs further improvement. This study also proposes recommendations to the DLD in order to enhance and improve the FMD control system in the eastern region of Thailand to be recognized as an FMD-free zone by the OIE.

The Nicoya Peninsula of Costa Rica is unusually close to the Middle America Trench (MAT), such that interface locking along the megathrust is observable under land. Here, rapid convergence between the downgoing Cocos and the over-riding Caribbean plates at ~85mm/yr allows for observable high strain rates, frequent large earthquakes and ongoing micro-seismicity. By taking advantage of this ideal location, a network of 20 on-land broadband seismometers was established in cooperation between UC Santa Cruz, Georgia Tech, and OVSICORI, with most stations operating since 2008. To evaluate what seismicity tells us about the ongoing state of coupling along the interface, we must consistently evaluate the location and magnitude of ongoing micro- seismicity. Because of large levels of anthropogenic, biologic, and coastal noise, automatic detection of earthquakes remains problematic in this region. Thus, we resorted to detailed manual investigation of earthquake phases. So far, we have detected nearly 7,000 earthquakes below or near Nicoya between February and August 2009. From these events we evaluate the fine-scale frequency-magnitude distribution (FMD) along the subduction megathrust. The results from this b-value mapping‟ are compared with an earlier study of the seismicity 9 years prior. In addition, we evaluate them relative to the latest geodetically derived locking. Preliminary comparisons of spatial and temporal variations of the b-values will be reported here. Because ongoing manual detection of earthquakes is extremely laborious and some events might be easily neglected, we are implementing a match-filter detection algorithm to search for new events from the continuous seismic data. This new approach has been previously successful in identifying aftershocks of the 2004 Parkfield earthquake. To do so, we use the waveforms of 858 analyst-detected events as templates to search for similarly repeating events during the same periods that have been manually detected. Preliminary results on the effectiveness of this technique are reported. The overall goal of this research is to evaluate the evolution of stress along the megathrust that may indicate the location and magnitude of potentially large future earthquakes. To do so, I make the comparison between the FMD and the interface locking. Only positive correlations are observed in the Nicoya region. The result is different from the one derived from the seismic data set that was recorded 9 years before our data. Therefore, to substantiate the causes for the different relationships between the b-value and the coupling degree, we need additional data with more reliable magnitudes.

In this dissertation, several essays in the field of bio-security are presented. The estimation of the probability of an FMD outbreak by type and location of premises is important for decision making. In Essay I, we estimate and predict the probability/risk of an FMD outbreak spreading to the various premises in the study area. We first used a Poisson regression model with adjustment dispersion associated with random simulation results from the AusSpead model to estimate the parameters of the model. Our estimation and prediction show that large cattle loss could be concentrated in three counties-Deaf Smith, Parmer, and Castro. These results are based on approximately 70% of the feedlots with over 10,000 cattle located in the three counties previously mentioned. In Essay II, our objective is to determine the best mitigation strategies in minimizing animal loss based on AusSpead simulation model. We tested 15 mitigation strategies by using multiple comparison. The results show that the best mitigation strategies for all four scenarios are regular surveillance, slaughter of the infected animals, and early detection. We then used the Mixed Integer Programming to estimate costs of disposing of animal carcasses and transportation. Results show that the unit disposal cost will vary with carcass scale and the unit transportation cost also varies with the distribution of the infected premises and disposal locations. FMD seems to have varying impacts on equity markets. In Essay III, we studied returns at three different levels of the stock market. We determined results in a structural break, and then estimated the impact of the announcement of confirmed cases of FMD disease on the volatility of stock market returns by using a GARCH-Mean model. Our results show that the structure break occurs on the day with the largest number of confirmed cases for meat product firms rather than the day of the first confirmed case. We found that the conditional volatilities over the FMD period are higher than those over the sample period. The announcement of confirmed cases had the largest marginal impact on meat products. Investors may always consider maintaining a portfolio consisting of index funds or hedge funds.

Contexto: A suplementação de ácido fólico (AF) melhora a função endotelial de indivíduos infectados pelo HIV em uso contínuo de terapia antirretroviral (TARV). A literatura não demonstra com clareza esse benefício em indivíduos coinfectados HIV-HCV. Introdução: Indivíduos infectados pelo HIV ou em coinfecção pelo HIV-HCV apresentam um conjunto de fatores de risco que podem levar a disfunção endotelial. Estudos demonstram que a administração de AF possui efeitos benéficos sobre a função endotelial de diferentes populações com risco cardiovascular, inclusive em HIV monoinfectados. Objetivo: Determinar o efeito da suplementação de AF por quatro semanas sobre a dilatação mediada (FMD) pelo fluxo da artéria braquial em indivíduos infectados pelo HIV ou HIV-HCV em uso contínuo de TARV. Delineamento: Ensaio clínico randomizado (ECR), controlado por placebo. Local: Ambulatório de doenças infecciosas do Hospital Universitário de Santa Maria. População: Foram avaliados 69 indivíduos com idade entre 18-50 anos, de ambos os sexos, infectados pelo HIV com ou sem coinfecção pelo HCV, em TARV e com carga viral indetectável há mais de seis meses. Excluíram-se participantes com diabetes mellitus, infarto agudo do miocárdio, revascularização miocárdica, ou acidente vascular encefálico prévios, com creatinina >1,5 mg/dL, diagnóstico clínico, ecográfico, endoscópico ou laboratorial de cirrose hepática, em uso de estatinas, fibratos, terapia de reposição hormonal, sulfonamidas, suplementos vitamínicos, ou AF nos últimos 30 dias. Adicionalmente foram excluídas mulheres grávidas, e participantes de outro ECR. Intervenção: Indivíduos alocados para o grupo intervenção receberam AF, 5 mg, via oral, em dose única diária, pela manhã, durante quatro semanas. Os participantes alocados para grupo placebo receberam orientação para seguir a mesma posologia, sendo os comprimidos indistinguíveis em cor, aroma, sabor, forma e tamanho. Desfechos: Utilizaram-se as variações nos níveis de homocisteína, vitamina B12 e na FMD, aferida por Doppler, na artéria braquial, obtidos na randomização e ao final do seguimento. Resultados: Realizou-se o rastreamento de 239 participantes, sendo 72 elegíveis, 69 randomizados e 68 acompanhados, entre outubro de 2012 e julho de 2013. Em indivíduos infectados pelo HIV houve aumento significativo nos níveis de AF (12,8 ng/ml) no grupo intervenção em comparação ao placebo (P<0,001), acompanhada de variação negativa de homocisteína (-1,9 umol/l) no grupo intervenção e aumento mínimo no grupo placebo (P<0,001). Não houve variação significativa na FMD (P=0,9). Entre indivíduos coinfectados por HIV-HCV, a variação nos níveis de AF foi decorrente da elevação no grupo intervenção (12,6 ng/ml) e redução no grupo placebo (-0,7 ng/ml) (P<0,001). Os níveis de homocisteína aumentaram no grupo placebo (4,6 umol/l) e diminuíram no grupo intervenção (-1,0 umol/l) (P<0,0003). Em relação ao FMD, houve tendência à redução percentual no grupo intervenção e aumento no grupo placebo (P=0,007). As variações de vitamina B12 não foram significativas, independente do status de infecção para HCV. Conclusão: Esse estudo demonstrou que a suplementação de AF por um curto período de tempo, esteve associada com redução de homocisteína sérica, mas não modificou a FMD da artéria braquial, aferida por Doppler, em indivíduos adultos infectados pelo HIV ou HIV-HCV em uso de TARV. / Context: The supplementation of folic acid (FA) improves endothelial function in HIV-infected individuals in continuous use of highly active antiretroviral therapy (HAART). The literature does not clearly show this benefit in coinfected HIV-HCV. Introduction: Individuals infected with HIV or HIV-HCV coinfected presents a set of risk factors that can lead to endothelial dysfunction. Studies show that FA management has beneficial effects on endothelial function in different populations with cardiovascular risk, including HIV monoinfected. Objective: To determine the effect of FA supplementation for four weeks on the mediated dilation (FMD) by brachial artery flow in patients infected with HIV or HIV-HCV continuous HAART. Design: Randomized clinical trial (RCT), placebo-controlled study. Location: Division of Infectious Diseases, University Hospital of Santa Maria. Population: A total of 69 subjects aged 18-50 years, of both sex, HIV or HIV-HCV infected, on HAART, with undetectable viral load for more than six months. Patients presenting with diabetes mellitus, acute myocardial infarction, coronary revascularization, or stroke prior, with creatinine >1,5 mg/dL, clinical diagnosis, ultrasound, endoscopic or laboratory evidence of liver cirrhosis, on statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days. In addition pregnant women were excluded, and participants in a RCT. Intervention: Subjects allocated to the intervention group received FA, 5 mg orally once daily in the morning for four weeks. Participants allocated to placebo group were instructed to follow the same dosage, being indistinguishable tablets in color, aroma, taste, shape and size. Outcomes: changes were used in the levels of homocysteine, vitamin B12 and FMD, measured by Doppler, in the brachial artery obtained at randomization and at the end of follow-up. Results: We carried out the screening of 239 participants, 72 eligible, 69 randomized and 68 accompanied, between October 2012 and July 2013. In HIV-infected patients there was a significant increase in the levels of FA (12.8 ng/ml) in the intervention group compared to placebo (P <0.001), accompanied by negative variation of homocysteine (1.9 umol/L) in the group intervention and minimal increase in the placebo group (P <0.001). There was no significant change in FMD (P = 0.9). Between individuals coinfected with HIV-HCV, the variation in FA levels was due to the increase in the intervention group (12.6 ng/ml) and reduction in the placebo group (-0.7 ng / ml) (P <0.001). Homocysteine levels increased in the placebo group (4.6 umol/L) and decreased in the intervention group (-1.0 umol/L) (P <0.0003). Regarding the FMD, there was a tendency to percentage reduction in the intervention group and increased in the placebo group (P = 0.007). Variations of B12 were not significant, independent of HCV infection status. Conclusion: This study showed that AF supplementation for a short term, was associated with reduced serum homocysteine, but did not change the FMD of the brachial artery, measured by Doppler in adults infected with HIV or HIV-HCV in HAART.

Contexto: A suplementação de ácido fólico (AF) melhora a função endotelial de indivíduos infectados pelo HIV em uso contínuo de terapia antirretroviral (TARV). A literatura não demonstra com clareza esse benefício em indivíduos coinfectados HIV-HCV. Introdução: Indivíduos infectados pelo HIV ou em coinfecção pelo HIV-HCV apresentam um conjunto de fatores de risco que podem levar a disfunção endotelial. Estudos demonstram que a administração de AF possui efeitos benéficos sobre a função endotelial de diferentes populações com risco cardiovascular, inclusive em HIV monoinfectados. Objetivo: Determinar o efeito da suplementação de AF por quatro semanas sobre a dilatação mediada (FMD) pelo fluxo da artéria braquial em indivíduos infectados pelo HIV ou HIV-HCV em uso contínuo de TARV. Delineamento: Ensaio clínico randomizado (ECR), controlado por placebo. Local: Ambulatório de doenças infecciosas do Hospital Universitário de Santa Maria. População: Foram avaliados 69 indivíduos com idade entre 18-50 anos, de ambos os sexos, infectados pelo HIV com ou sem coinfecção pelo HCV, em TARV e com carga viral indetectável há mais de seis meses. Excluíram-se participantes com diabetes mellitus, infarto agudo do miocárdio, revascularização miocárdica, ou acidente vascular encefálico prévios, com creatinina >1,5 mg/dL, diagnóstico clínico, ecográfico, endoscópico ou laboratorial de cirrose hepática, em uso de estatinas, fibratos, terapia de reposição hormonal, sulfonamidas, suplementos vitamínicos, ou AF nos últimos 30 dias. Adicionalmente foram excluídas mulheres grávidas, e participantes de outro ECR. Intervenção: Indivíduos alocados para o grupo intervenção receberam AF, 5 mg, via oral, em dose única diária, pela manhã, durante quatro semanas. Os participantes alocados para grupo placebo receberam orientação para seguir a mesma posologia, sendo os comprimidos indistinguíveis em cor, aroma, sabor, forma e tamanho. Desfechos: Utilizaram-se as variações nos níveis de homocisteína, vitamina B12 e na FMD, aferida por Doppler, na artéria braquial, obtidos na randomização e ao final do seguimento. Resultados: Realizou-se o rastreamento de 239 participantes, sendo 72 elegíveis, 69 randomizados e 68 acompanhados, entre outubro de 2012 e julho de 2013. Em indivíduos infectados pelo HIV houve aumento significativo nos níveis de AF (12,8 ng/ml) no grupo intervenção em comparação ao placebo (P<0,001), acompanhada de variação negativa de homocisteína (-1,9 umol/l) no grupo intervenção e aumento mínimo no grupo placebo (P<0,001). Não houve variação significativa na FMD (P=0,9). Entre indivíduos coinfectados por HIV-HCV, a variação nos níveis de AF foi decorrente da elevação no grupo intervenção (12,6 ng/ml) e redução no grupo placebo (-0,7 ng/ml) (P<0,001). Os níveis de homocisteína aumentaram no grupo placebo (4,6 umol/l) e diminuíram no grupo intervenção (-1,0 umol/l) (P<0,0003). Em relação ao FMD, houve tendência à redução percentual no grupo intervenção e aumento no grupo placebo (P=0,007). As variações de vitamina B12 não foram significativas, independente do status de infecção para HCV. Conclusão: Esse estudo demonstrou que a suplementação de AF por um curto período de tempo, esteve associada com redução de homocisteína sérica, mas não modificou a FMD da artéria braquial, aferida por Doppler, em indivíduos adultos infectados pelo HIV ou HIV-HCV em uso de TARV. / Context: The supplementation of folic acid (FA) improves endothelial function in HIV-infected individuals in continuous use of highly active antiretroviral therapy (HAART). The literature does not clearly show this benefit in coinfected HIV-HCV. Introduction: Individuals infected with HIV or HIV-HCV coinfected presents a set of risk factors that can lead to endothelial dysfunction. Studies show that FA management has beneficial effects on endothelial function in different populations with cardiovascular risk, including HIV monoinfected. Objective: To determine the effect of FA supplementation for four weeks on the mediated dilation (FMD) by brachial artery flow in patients infected with HIV or HIV-HCV continuous HAART. Design: Randomized clinical trial (RCT), placebo-controlled study. Location: Division of Infectious Diseases, University Hospital of Santa Maria. Population: A total of 69 subjects aged 18-50 years, of both sex, HIV or HIV-HCV infected, on HAART, with undetectable viral load for more than six months. Patients presenting with diabetes mellitus, acute myocardial infarction, coronary revascularization, or stroke prior, with creatinine >1,5 mg/dL, clinical diagnosis, ultrasound, endoscopic or laboratory evidence of liver cirrhosis, on statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days. In addition pregnant women were excluded, and participants in a RCT. Intervention: Subjects allocated to the intervention group received FA, 5 mg orally once daily in the morning for four weeks. Participants allocated to placebo group were instructed to follow the same dosage, being indistinguishable tablets in color, aroma, taste, shape and size. Outcomes: changes were used in the levels of homocysteine, vitamin B12 and FMD, measured by Doppler, in the brachial artery obtained at randomization and at the end of follow-up. Results: We carried out the screening of 239 participants, 72 eligible, 69 randomized and 68 accompanied, between October 2012 and July 2013. In HIV-infected patients there was a significant increase in the levels of FA (12.8 ng/ml) in the intervention group compared to placebo (P <0.001), accompanied by negative variation of homocysteine (1.9 umol/L) in the group intervention and minimal increase in the placebo group (P <0.001). There was no significant change in FMD (P = 0.9). Between individuals coinfected with HIV-HCV, the variation in FA levels was due to the increase in the intervention group (12.6 ng/ml) and reduction in the placebo group (-0.7 ng / ml) (P <0.001). Homocysteine levels increased in the placebo group (4.6 umol/L) and decreased in the intervention group (-1.0 umol/L) (P <0.0003). Regarding the FMD, there was a tendency to percentage reduction in the intervention group and increased in the placebo group (P = 0.007). Variations of B12 were not significant, independent of HCV infection status. Conclusion: This study showed that AF supplementation for a short term, was associated with reduced serum homocysteine, but did not change the FMD of the brachial artery, measured by Doppler in adults infected with HIV or HIV-HCV in HAART.

Contexto: A suplementação de ácido fólico (AF) melhora a função endotelial de indivíduos infectados pelo HIV em uso contínuo de terapia antirretroviral (TARV). A literatura não demonstra com clareza esse benefício em indivíduos coinfectados HIV-HCV. Introdução: Indivíduos infectados pelo HIV ou em coinfecção pelo HIV-HCV apresentam um conjunto de fatores de risco que podem levar a disfunção endotelial. Estudos demonstram que a administração de AF possui efeitos benéficos sobre a função endotelial de diferentes populações com risco cardiovascular, inclusive em HIV monoinfectados. Objetivo: Determinar o efeito da suplementação de AF por quatro semanas sobre a dilatação mediada (FMD) pelo fluxo da artéria braquial em indivíduos infectados pelo HIV ou HIV-HCV em uso contínuo de TARV. Delineamento: Ensaio clínico randomizado (ECR), controlado por placebo. Local: Ambulatório de doenças infecciosas do Hospital Universitário de Santa Maria. População: Foram avaliados 69 indivíduos com idade entre 18-50 anos, de ambos os sexos, infectados pelo HIV com ou sem coinfecção pelo HCV, em TARV e com carga viral indetectável há mais de seis meses. Excluíram-se participantes com diabetes mellitus, infarto agudo do miocárdio, revascularização miocárdica, ou acidente vascular encefálico prévios, com creatinina >1,5 mg/dL, diagnóstico clínico, ecográfico, endoscópico ou laboratorial de cirrose hepática, em uso de estatinas, fibratos, terapia de reposição hormonal, sulfonamidas, suplementos vitamínicos, ou AF nos últimos 30 dias. Adicionalmente foram excluídas mulheres grávidas, e participantes de outro ECR. Intervenção: Indivíduos alocados para o grupo intervenção receberam AF, 5 mg, via oral, em dose única diária, pela manhã, durante quatro semanas. Os participantes alocados para grupo placebo receberam orientação para seguir a mesma posologia, sendo os comprimidos indistinguíveis em cor, aroma, sabor, forma e tamanho. Desfechos: Utilizaram-se as variações nos níveis de homocisteína, vitamina B12 e na FMD, aferida por Doppler, na artéria braquial, obtidos na randomização e ao final do seguimento. Resultados: Realizou-se o rastreamento de 239 participantes, sendo 72 elegíveis, 69 randomizados e 68 acompanhados, entre outubro de 2012 e julho de 2013. Em indivíduos infectados pelo HIV houve aumento significativo nos níveis de AF (12,8 ng/ml) no grupo intervenção em comparação ao placebo (P<0,001), acompanhada de variação negativa de homocisteína (-1,9 umol/l) no grupo intervenção e aumento mínimo no grupo placebo (P<0,001). Não houve variação significativa na FMD (P=0,9). Entre indivíduos coinfectados por HIV-HCV, a variação nos níveis de AF foi decorrente da elevação no grupo intervenção (12,6 ng/ml) e redução no grupo placebo (-0,7 ng/ml) (P<0,001). Os níveis de homocisteína aumentaram no grupo placebo (4,6 umol/l) e diminuíram no grupo intervenção (-1,0 umol/l) (P<0,0003). Em relação ao FMD, houve tendência à redução percentual no grupo intervenção e aumento no grupo placebo (P=0,007). As variações de vitamina B12 não foram significativas, independente do status de infecção para HCV. Conclusão: Esse estudo demonstrou que a suplementação de AF por um curto período de tempo, esteve associada com redução de homocisteína sérica, mas não modificou a FMD da artéria braquial, aferida por Doppler, em indivíduos adultos infectados pelo HIV ou HIV-HCV em uso de TARV. / Context: The supplementation of folic acid (FA) improves endothelial function in HIV-infected individuals in continuous use of highly active antiretroviral therapy (HAART). The literature does not clearly show this benefit in coinfected HIV-HCV. Introduction: Individuals infected with HIV or HIV-HCV coinfected presents a set of risk factors that can lead to endothelial dysfunction. Studies show that FA management has beneficial effects on endothelial function in different populations with cardiovascular risk, including HIV monoinfected. Objective: To determine the effect of FA supplementation for four weeks on the mediated dilation (FMD) by brachial artery flow in patients infected with HIV or HIV-HCV continuous HAART. Design: Randomized clinical trial (RCT), placebo-controlled study. Location: Division of Infectious Diseases, University Hospital of Santa Maria. Population: A total of 69 subjects aged 18-50 years, of both sex, HIV or HIV-HCV infected, on HAART, with undetectable viral load for more than six months. Patients presenting with diabetes mellitus, acute myocardial infarction, coronary revascularization, or stroke prior, with creatinine >1,5 mg/dL, clinical diagnosis, ultrasound, endoscopic or laboratory evidence of liver cirrhosis, on statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days. In addition pregnant women were excluded, and participants in a RCT. Intervention: Subjects allocated to the intervention group received FA, 5 mg orally once daily in the morning for four weeks. Participants allocated to placebo group were instructed to follow the same dosage, being indistinguishable tablets in color, aroma, taste, shape and size. Outcomes: changes were used in the levels of homocysteine, vitamin B12 and FMD, measured by Doppler, in the brachial artery obtained at randomization and at the end of follow-up. Results: We carried out the screening of 239 participants, 72 eligible, 69 randomized and 68 accompanied, between October 2012 and July 2013. In HIV-infected patients there was a significant increase in the levels of FA (12.8 ng/ml) in the intervention group compared to placebo (P <0.001), accompanied by negative variation of homocysteine (1.9 umol/L) in the group intervention and minimal increase in the placebo group (P <0.001). There was no significant change in FMD (P = 0.9). Between individuals coinfected with HIV-HCV, the variation in FA levels was due to the increase in the intervention group (12.6 ng/ml) and reduction in the placebo group (-0.7 ng / ml) (P <0.001). Homocysteine levels increased in the placebo group (4.6 umol/L) and decreased in the intervention group (-1.0 umol/L) (P <0.0003). Regarding the FMD, there was a tendency to percentage reduction in the intervention group and increased in the placebo group (P = 0.007). Variations of B12 were not significant, independent of HCV infection status. Conclusion: This study showed that AF supplementation for a short term, was associated with reduced serum homocysteine, but did not change the FMD of the brachial artery, measured by Doppler in adults infected with HIV or HIV-HCV in HAART.

Foot-and-mouth disease (FMD) is an economically devastating picornaviral disease affecting over 40 species of cloven-hoofed animals. The virus occurs as seven immunologically distinct serotypes which are characterized by high levels of intra- and intertypic variation. The three South African Territories (SAT) serotypes 1-3 are endemic to sub-Saharan Africa, a region where the epidemiology of the disease is particularly complex due to the presence of six of the seven serotypes, the role of wildlife in virus maintenance and the apparently higher levels of variation in the endemic serotypes. These factors make it imperative to establish methods suited to elucidating the regional epidemiology. One of the integral parts of this process is the genetic characterization of regionally representative viruses in order to assess the variation in the field and to clarify the role of wildlife. Nucleotide sequence data and methods suited to studying the SAT-types are however limited. A first priority was therefore to establish a PCR-based nucleotide sequencing technique targeting the highly immunogenic and phylogenetically informative 1D genome region encoding the VP1 protein. The screening of multiple serotypes and subtypes prevalent on the African continent confirmed that this method was robust and well-suited to molecular epidemiological studies in the southern Africa region. The method was first applied in the characterization of FMD virus recovered from the reproductive tract of free-living African buffalo in the Kruger National Park. Nucleotide sequencing assisted in authentication of the results and indicated that carrier status was likely, but it was not possible to unequivocally demonstrate persistent infection of FMDV. In a separate study, the role of impala antelope (Aepyceros melampus) in the epidemiology of the disease in South Africa was assessed. Genetic characterization of impala and African buffalo (Syncerus caffer) viruses collected over an eleven year period confirmed that inter-species transmission occurred on several occasions and that virus can persist in impala populations for more than 12 months. Inter-species transmission and investigation of the possible mechanisms facilitating virus transmission from persistently infected buffalo focussed on the Kruger National Park in South Africa. In order to ensure regional relevance the study was broadened to incorporate buffalo populations throughout southern Africa. Viruses of the three SAT-types recovered from diverse African buffalo populations were therefore characterized. The results reveal that independently evolving viral lineages occur in distinct geographical regions for each of the SAT-types examined and that the levels of intratypic variation are in the order of 52 - 55 % on nucleotide level across the genome region characterized. Given the strict locality-specific grouping of buffalo viruses the likely usefulness of this database for tracing the origin and course of contemporary and historical SAT-type outbreaks was investigated. Molecular epidemiological studies conclusively show that buffalo are indeed the ultimate source of infection for susceptible cloven-hoofed animals occurring in close proximity, that interspecies transmission occurs between cattle and antelope and that trans-boundary transmission of virus remains a threat to disease security in southern African countries. / Thesis (PhD (Microbiology))--University of Pretoria, 2007. / Microbiology and Plant Pathology / unrestricted

Foot-and-mouth disease virus (FMDV) is a highly infectious virus affecting cloven-hoofed animals. The most prominent of its clinical signs is the development of vesicular lesions on the feet and in or around the mouth, which are a consequence of extensive FMDV-induced epithelial cell death. Currently, there is no certain biological knowledge on why extensive epithelial cell death occurs in some FMDV-infected tissues, but not in others. Using the epithelial tissues of tongue and dorsal soft palate as examples of a tissue where lesions occur and one that does not visibly exhibit FMDV-induced cell death, this work aims to identify the potential drivers of epithelial cell death and survival. A partial differential equation (PDE) model informed by experimental data on epithelial structure, is used to test epithelium thickness and cell layer structure as potential determinants. A second PDE model investigates FMDV-interferon (IFN) dynamics and their impact on the levels of cell death and survival, while an experimental study is undertaken to provide data for model validation. The work carried out casts light on the important role of a variety of factors including FMDV replication, IFN production and release, and IFN antiviral action.