The purpose of this study is to survey self-reported health symptoms and knowledge of Sickle Cell Trait in young adults with an African heritage. The aim is to expand a comprehensive assessment system to measure factors associated with carrying the Sickle Cell Trait. Historically being a Sickle Cell Trait carrier was thought to be asymptomatic. However, current research has suggested this may not be true. While young adults may have greater knowledge of Sickle Cell Disease, little is known about their awareness of Sickle Cell Trait. Furthermore, no research on these topics have been conducted in young adults with African heritage (Latino/Hispanic, Caribbean, Multi-Racial, etc.). Measures of Sickle Cell Trait Carrier Awareness, Sickle Cell Trait Knowledge, and Physical Health Symptoms are presented from 54 young adults with African Heritage. The Hispanic and Multi-Racial participants reported lower awareness of their Sickle Cell Trait Carrier status compared to the African American participants. Hispanic and Multi-Racial participants reported lower Sickle Cell Trait Knowledge compared to the African American participants. All subjects demonstrated lower levels of Sickle Cell Trait Knowledge than would be expected given the potential health consequences.

Sickle cell trait (SCT), sickle cell disease’s carrier status, is a common genetic variant found in many people of African, South Asian, Middle Eastern and Mediterranean descent. While overall considered a benign carrier status, it has been associated with an increased risk of several diseases, including exertional rhabdomyolysis (ER), and chronic kidney disease. While epidemiological evidence links SCT with ER, the actual pathophysiological mechanism less understood. Additionally, while there is an increased prevalence of atrial fibrillation (AF) documented in people with sickle cell disease, studies in individuals with SCT are lacking. The objectives of this thesis are twofold: The first chapter is a literature review of studies to examine the physiological mechanisms linking SCT and exertional rhabdomyolysis. The second chapter is original research into the associations of SCT with AF. The first chapter reviews studies that identify aggravating factors that may promote ER. It then reviews observed pathophysiological changes in people with SCT that may increase the risk of ER. It summarizes studies that assess mitigating factors that decrease the risk of ER. It then presents a postulated pathway of mechanisms that associate SCT with ER. The second chapter uses data from African-American participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study to assess the association of SCT with prevalent AF (by electrocardiogram or medical history) using logistic regression models adjusting for age, sex, income, education, history of stroke, myocardial infarction, diabetes, hypertension, and chronic kidney disease. In 10,409 participants with baseline ECG data and genotyping, 778 (7.5%) had SCT and 811 (7.8%) had prevalent AF. After adjusting for age, sex, education and income, SCT was associated with AF, OR 1.32 (95% CI 1.03-1.70). SCT remained associated with prevalent AF after adjusting for potential factors on the causal pathway such as hypertension and chronic kidney disease suggesting alternate mechanisms for the increased risk. SCT was associated with a higher prevalence of AF and a non-significantly higher incident AF over a 9.2 year period independent of AF risk factors.

Thesis (M.S.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Genetics. Includes bibliographical references.

Thesis (Ph.D)--University of Tennessee Health Science Center, 2008. / Title from title page screen (viewed on January 6, 2009). Research advisor: Ann K. Cashion, Ph.D. Document formatted into pages (x, 102 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 81-88).

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-26T18:59:48Z No. of bitstreams: 1 EMANUELLE DAL PONTE.pdf: 853027 bytes, checksum: 3383ad493f7b637d87265a5e9064c8f0 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-26T19:00:18Z (GMT) No. of bitstreams: 1 EMANUELLE DAL PONTE.pdf: 853027 bytes, checksum: 3383ad493f7b637d87265a5e9064c8f0 (MD5) / Made available in DSpace on 2018-09-26T19:00:18Z (GMT). No. of bitstreams: 1 EMANUELLE DAL PONTE.pdf: 853027 bytes, checksum: 3383ad493f7b637d87265a5e9064c8f0 (MD5) Previous issue date: 2017-07-03 / O traço falciforme (HbAS) é o heterozigoto da anemia falciforme, portador do gene S assintomático e considerado, ainda, clinicamente normal. Estudos epidemiológicos mostram sua alta prevalência na população brasileira sendo que, em determinadas cidades do Rio Grande do Sul, estima-se uma frequência de 1:75 habitantes. Novos estudos têm apontado que o portador do traço falciforme, por apresentar aproximadamente 40% de HbS, tem envolvimento com estresse oxidativo, o qual pode atuar na progressão da doença. A Superóxido Dismutase (SOD) é uma enzima antioxidante que pode ter sua atividade diminuída em algumas patologias. O polimorfismo mais comum da MnSOD é o Ala16Val, que é resultado de uma mutação que substitui o códon original GCT (alanina) para GTT (valina). O alelo valina (V) dificulta o transporte e a entrada da enzima para dentro da mitocôndria diminuindo, assim, a capacidade antioxidante do indivíduo e favorecendo as vias de estresse oxidativo. O objetivo deste trabalho foi analisar a presença do polimorfismo Ala16Val MnSOD em portadores do traço falciforme e associá-lo com biomarcadores de estresse oxidativo. Os participantes do estudo foram recrutados junto ao Banco de Sangue do Hospital da Santa Casa de Caridade de Uruguaiana. Ao total obteve-se 102 indivíduos, sendo 50 do grupo controle e 52 do grupo traço falciforme (HbAS). Após a assinatura do termo de consentimento livre e esclarecido, foi realizada a coleta de sangue venoso. Dois tubos contendo EDTA foram coletados para as análises hematológicas, genômicas e de estresse oxidativo. Os resultados encontrados apontam que os portadores do traço falciforme apresentam as atividades da catalase, superóxido dismutase e glutationa peroxidase significativamente diminuídas (p<0,001) em relação ao grupo controle. O mesmo também foi observado com os níveis de compostos antioxidantes como a glutationa, vitamina C e status antioxidante total (p<0,001). Entretanto, os portadores do traço falciforme apresentam aumento estatisticamente significativo (p<0,001) no dano oxidativo a biomoléculas como carbonilação de proteínas, lipídeos e o DNA. A análise do polimorfismo Ala16Val MnSOD mostrou 100% do genótipo AV no grupo controle e 21% do genótipo AA e 79% do genótipo AV no grupo HbAS. O presente estudo não conseguiu, todavia, associar o polimorfismo com os biomarcadores de estresse oxidativo. Sugere-se, dessa forma, que o portador do traço falciforme possui aumento do estresse oxidativo e o polimorfismo Ala16Val MnSOD parece não estar associado aos parâmetros analisados. Entretanto, por esse estudo ser o primeiro a ser relatado, espera-se que em uma população maior de HbAS seja possível ampliar o conhecimento acerca dessa alteração genética. / Sickle cell trait (SCT) is the heterozygote of sickle cell anemia (HbAS), which carries the asymptomatic S gene and is considered clinically normal. Epidemiological studies show its high prevalence in the overall Brazilian population, and in certain cities such as Rio Grande do Sul, where a frequency of 1:75 is estimated. Recent studies have pointed out that the SCT because it represents approximately 40% of hemoglobin S (HbS), is involved with oxidative stress, which can act in the progression of the disease. Superoxide dismutase (SOD) is an antioxidant enzyme that may have decreased activity in some pathologies. The most common MnSOD polymorphism is Ala16Val, which is the result of a mutation that replaces the original GCT (alanine) codon for GTT (valine). The valine allele (V) hinders the transport and entry of the enzyme into the mitochondria, thereby both reducing the antioxidant capacity of the individual and favoring oxidative stress pathways. The aim of this study is to analyze the presence of the Ala16Val MnSOD polymorphism in patients with SCT and to associate it with biomarkers of oxidative stress. The study participants were recruited from the Blood Bank of the Santa Casa de Caridade Hospital of Uruguaiana. A total of 102 individuals were enrolled, 50 in the control group and 52 in the SCT group. After obtaining written informed consent, venous blood was collected. For each one, two tubes containing EDTA were collected for hematological, genomic, and oxidative stress analyses. The results showed that sickle cell carriers exhibit significantly decreased (p < 0.001) catalase, superoxide dismutase, and glutathione peroxidase activities compared with the control group. The same was also observed for the levels of antioxidant compounds such as glutathione, vitamin C, and total antioxidant status (p < 0.001). However, patients with SCT presented a statistically significant increase (p < 0.001) in oxidative damage to biomolecules such as protein carbonylation, lipid peroxidation, and DNA. Analysis of the Ala16Val MnSOD polymorphism showed 100% of the AV genotype in the control group, and 21% of the AA genotype and 79% of the AV genotype in the HbAS group. Although the current study could not associate the polymorphism with oxidative stress biomarkers, it suggested the SCT increased oxidative stress, and the Ala16Val MnSOD polymorphism was not associated with the parameters analyzed. However, because this study is the first to report these findings regarding the Ala16Val MnSOD polymorphism, it is expected that in a larger HbAS population, it will be possible to gain a better understanding of this genetic alteration.

O metabolismo de nutrientes abriga um alto potencial para o desenvolvimento de novos alvos quimioterápicos para o tratamento do parasita da malária Plasmodium falciparum. A partir de ensaios de crescimento do parasita dentro de eritrócitos geneticamente diferentes, concentrando-se na via catabólica da hemoglobina plasmodial usando parasitas transgênicos, a natureza protetora das variantes da hemoglobina foi investigada. Sendo que Falcipain 2 (FP2) prolifera três vezes mais elevada no sangue de células falciformes do que o Mock, a célula de controle. Adicionalmente, estudos de inibidores indicam que FP2 é uma proteína essencial para o parasita. Em cooperação com o DESY em Hamburgo, Alemanha a estrutura cristalina da amino peptidase P foi resolvida difratando até 1,7 Å. / The metabolism of nutrients harbors a high potential for the development of new chemotherapeutic targets for the treatment of the malaria parasite Plasmodium falciparum. From parasite growth assays within genetically different erythrocytes, concentrating on the catabolic pathway of plasmodial hemoglobin using transgenic parasites, the protective nature of hemoglobin variants was investigated. Since Falcipain 2 (FP2) proliferates three times higher in sickle cell blood than the Mock, the control cell. In addition, inhibitor studies indicate that FP2 is an essential protein for the parasite. In cooperation with DESY in Hamburg, Germany the crystalline structure of the amino peptidase P was resolved diffracting up to 1.7 Å.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-04-27T18:56:24Z No. of bitstreams: 1 Dona Jeanne Alladagbin Traço Falciforme....pdf: 838221 bytes, checksum: 204db68a171afff48af9789675612a48 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-04-27T18:56:34Z (GMT) No. of bitstreams: 1 Dona Jeanne Alladagbin Traço Falciforme....pdf: 838221 bytes, checksum: 204db68a171afff48af9789675612a48 (MD5) / Made available in DSpace on 2016-04-27T18:56:34Z (GMT). No. of bitstreams: 1 Dona Jeanne Alladagbin Traço Falciforme....pdf: 838221 bytes, checksum: 204db68a171afff48af9789675612a48 (MD5) Previous issue date: 2016 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / INTRODUÇÃO: A doença renal crônica (DRC) é uma doença grave que atinge cerca de 10% da população mundial. Devido à perda irreversível da função dos rins, os pacientes precisam do tratamento dialítico e desde 2010, no Brasil, a taxa de pacientes em diálise cresce de 3% cada ano. Cerca 93% do tratamento está financiado pelo SUS o que corresponde a 10% do orçamento do Ministério da Saúde. As principais causas de DRC no Brasil e no mundo são diabetes mellitus (DM) e hipertensão arterial sistêmica (HAS), seguido de glomerulopatias. As alterações podem ser complicadas por condições de hipóxia tecidual, as quais podem ser intensificadas pela doença falciforme. Os indivíduos com traço falciforme podem apresentar esse quadro clínico em condições extremas como um esforço físico intenso e prolongado. OBJETIVO: O objetivo deste estudo foi investigar a associação entre o traço falciforme e a progressão de DRC em Salvador-BA. MATERIAL E MÉTODOS: Foi desenvolvido um estudo de corte transversal, no qual no período de maio de 2014 até novembro de 2015; foram incluídos 306 indivíduos portadores de DRC em programa de hemodiálise nos hospitais e clínicas de referência tais como, Instituto de Nefrologia e Diálise (INED), Hospital Ana Nery (HAN) e Hospital Geral Roberto Santos (HGRS) há no máximo três anos. cinco mililitros (mL) de sangue total foram coletados em cada paciente para a caracterização do perfil de hemoglobinas variantes pela técnica de cromatografia líquida de alta eficiência (HPLC). Como grupo controle, foram utilizados os resultados dos testes de triagem neonatal do APAE realizados em recém-nascidos em Salvador de 2012-2014. RESULTADOS: A frequência de HbAS foi significamente maior nos pacientes em hemodiálise (10,2%) em comparação ao grupo controle (5,05%) OR: 2,04 IC 95% (1,35–2,99). Quando comparamos os pacientes com DRC com e sem traço falciforme, não houve diferença em relação à distribuição do sexo (homens 57,6% vs 50%, respectivamente, p = 0,43). A média de idade não foi diferente entre os dois grupos (52 ± 1 anos vs 56 ± 2, p = 0,21). CONCLUSÕES: A frequência do traço falciforme é maior em pacientes portadores de DRC em programa de hemodiálise em comparação à população geral. Estudos que avaliam o impacto e fisiopatologia da doença renal em indivíduos portadores de traço falciforme podem fornecer informações importantes para desenvolvimento de estratégias de prevenção da progressão para estágio final da doença renal. / INTRODUCTION: Chronic Kidney Disease (CKD) is a serious disease that affects about 10% of world population. It is due to irreversible loss of kidney function, so necessitating the patient’s need of dialysis treatment and since 2010, in Brazil, the rate of patients on dialysis is growing by 3% each year. About 93% of the treatment is funded by SUS which corresponds to 10% of the Health Ministry´s budget. The main causes of CKD in Brazil and in the world are diabetes mellitus and arterial hypertension, followed by glomerulopathies. The alterations can be complicated by conditions of tissue hypoxia, which can be intensified by the sickle cell disease. Individuals with sickle cell trait, although asymptomatic may present these clinical features in extreme conditions such as intense and prolonged physical activities. AIM: The aim of this study was to investigate the association between sickle cell trait and progression of CKD in patients on hemodialysis (HD) in Salvador, Bahia. MATERIAL AND METHODS: A cross-sectional cohort study was conducted from May 2014 to November 2015. The subjects consisted of 394 of both sexes with chronic renal failure on hemodialysis sessions for up to three years and treated in hospitals and clinics of reference such as the Institute of Nephrology and Dialysis (INED), Ana Nery’s Hospital (HAN) and Roberto Santos General Hospital (HGRS). 5mls of whole blood was collected from each patient to characterize the hemoglobin variants profile by High Performance Liquid Chromatography (HPLC). As a control group, the results of neonatal screening tests of APAE performed on newborns in Salvador 2012-2014 were used. RESULTS: The frequency of HbAS was significantly higher in hemodialysis patients (10.2%) compared to the control group (5.05%) OR: 2.04 95% CI (1.35 to 2.99). When comparing patients with CKD with and without sickle cell trait, there was no difference in relation to the distribution of sex (men 57.6% vs 50%, respectively, p = 0.43). The mean age was not different between the two groups (52 ± 1 years vs 56 ± 2, p = 0.21). CONCLUSIONS: The frequency of the sickle cell trait is higher in patients with CKD on hemodialysis compared to the general population. Studies assessing the impact and pathophysiology of renal disease in patients with sickle cell trait can provide important information for developing strategies to prevent the progression of CKD to end-stage renal disease.

Sickle cell disease (SCD) is a severe genetic disease, affecting over 100,000 in the United States and millions worldwide. Individuals suffer from stroke, acute chest syndrome, and cardiovascular complications. Much of these associated morbidities are primarily mediated by blockages of the microvasculature, events termed vaso-occlusive crises (VOCs). Despite its prevalence and severity, the pathophysiological mechanisms behind VOCs are not well understood, and novel experimental tools and methods are needed to further this understanding. Microfluidics and computational fluid dynamics (CFD) are rapidly growing fields within biomedical research that allow for inexpensive simulation of the in vivo microenvironment prior to animal or clinical trials. This study includes the development of a CFD model capable of simulating diseased and healthy blood flow within a series of microfluidic channels. Results will be utilized to further improve the development of microfluidic systems.

Sickle cell disease (SCD) is a genetic disorder that affects millions of people worldwide. According to the Centers for Disease Control and Prevention, over 100,000 Americans have SCD, and more than 2 million Americans have a sickle cell trait (SCT). People with SCD are more likely than others to suffer premature mortality. Genetic screening is an important step in improving quality of life and increasing longevity for those with SCD. Early detection may lead to effective management of the disease and reduction of complicating factors. The purpose of this quasi-experimental study was to determine whether health education about SCD would impact college students' knowledge, attitudes, perceived risk, and intention to seek genetic screening and counseling in relation to the disease. The theoretical foundation for this study was the health belief model (HBM). This study involved 80 college students selected from a North Texas college. These students completed pre and post versions of an SCD questionnaire. Independent samples t tests were used to determine if there were significant differences in pre- and posttest scores of participants in both groups, and a MANOVA was used to determine differences among the scores of participants in the experimental group when grouped by age, gender, race, religiosity, and socioeconomic status. The results of this study showed that SCD health education improved the knowledge of and attitudes towards participants. Future research could explore barriers to seeking SCD screening and genetic counseling. Results of this study may further social change by encouraging the development of college-based health education efforts to increase awareness about SCD.

Sickle cell disease (SCD) is a genetic disorder that affects millions of people worldwide. According to the Centers for Disease Control and Prevention, over 100,000 Americans have SCD, and more than 2 million Americans have a sickle cell trait (SCT). People with SCD are more likely than others to suffer premature mortality. Genetic screening is an important step in improving quality of life and increasing longevity for those with SCD. Early detection may lead to effective management of the disease and reduction of complicating factors. The purpose of this quasi-experimental study was to determine whether health education about SCD would impact college students' knowledge, attitudes, perceived risk, and intention to seek genetic screening and counseling in relation to the disease. The theoretical foundation for this study was the health belief model (HBM). This study involved 80 college students selected from a North Texas college. These students completed pre and post versions of an SCD questionnaire. Independent samples t tests were used to determine if there were significant differences in pre- and posttest scores of participants in both groups, and a MANOVA was used to determine differences among the scores of participants in the experimental group when grouped by age, gender, race, religiosity, and socioeconomic status. The results of this study showed that SCD health education improved the knowledge of and attitudes towards participants. Future research could explore barriers to seeking SCD screening and genetic counseling. Results of this study may further social change by encouraging the development of college-based health education efforts to increase awareness about SCD.