Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis, particularly in people with pre-disposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. To investigate the virulence of multiple isolates, a variation of the Bar-seq (barcode sequencing) method was employed. A conserved chromosomal site was identified for subsequent insertion of a barcode identifier, unique for each strain. Barcode insertion did not affect growth in vitro or in a rabbit model of endocarditis. Pooling of these strains and inoculation into rabbits demonstrated that all strains were capable of causing disease; however, virulence varied widely among strains. Genomic comparisons of the more virulent strains versus less virulent strains failed to conclusively identify any single gene responsible for virulence. Given this result, we continued our examination of the manganese transport system SsaACB, which is present in every strain of S. sanguinis examined. Although its contribution to virulence has not been confirmed in any strain other than SK36, it has been shown to be required for virulence in multiple species of streptococci, making it a candidate for emerging targeted therapies. In S. sanguinis strain SK36, previous studies have confirmed that loss of the manganese transport protein SsaB is tantamount to loss of virulence. Moreover, ssaB-deficient mutants are deficient for serum growth—a phenotype we have previously found to be associated with virulence. Our in vitro studies of manganese transporter-deficient strain SK36 supported this, but also revealed the emergence of suppressor mutants. In each suppressor mutant that was isolated, mutations were identified that mapped to a common gene, SSA_0696. Deletion of SSA_0696 resulted in restored in vitro growth in the ssaACB-deficient background, unearthing a novel mechanism for bacterial growth under manganese limitation. Fortunately, the suppressor mutant phenotype was not maintained in vivo; however, the combined results of these experiments suggest the efficacy of future therapeutics may require consideration of virulence at the species level and the incorporation of multiple targets.

Bisphenol A (BPA), a widely used chemical in plastic, has drawn wide attention due to its presence in many consumer products and the environment. The purpose of this study was to examine the association between urinary BPA and the reporting of cardiovascular diseases (CVD), and then to examine the effect of C-reactive protein (CRP) as a moderating variable. The data used in this research were extracted from the National Health and Nutrition Examination Survey collected in 2009-2010. Guided by the advanced epidemiological triangle, analysis involved 2 stepwise binary logistic regressions. The first step suggested that the controls were significant in predicting CVD (Ï?2 (5) = 83.72, p < .001, R2 = .15). The Nagelkerke R2 coefficient of determination indicated that the controls explained approximately 15% of the variance in instances of CVD. The second step of the binary logistic regression included the controls and BPA level in the model together. The regression analysis suggested that the Nagelkerke coefficient of determination (Ï?2 (6) = 83.76, p < .001, R2 = .15) did not increase from the 15% explained by the controls, and BPA level was found to be a nonsignificant predictor of CVD (p = .853). Due to lack of association between BPA and CVD, the analysis was shifted to examine the association between urinary BPA and serum CRP. The association between urinary BPA and serum CRP was also statistically nonsignificant (Spearman correlation coefficient, rs= .06, p = .015). The results may have positive social change by contributing to the body of knowledge on BPA and by increasing scientific scrutiny for substances used in people's daily lives.

Tumor-like proliferative vascular lesions manifest in several diseases such as peripheral arterial disease (PAD) and atherosclerosis (AS) after arterial injury. The cause of the vascular cell dysfunction in PAD patients is not known. Our recent novel discovery shows that inhibitor of differentiation 3 (ID3) is highly expressed in intimal lesions of clinical vascular disease samples. The central hypothesis of our study is: estrogenic chemical induced dysregulation of ID3 target genes is involved in the development of vascular disease. NHANES data analysis demonstrated higher geometric levels of all 6 PCB congeners in both PAD diagnosed participants and participants at risk of AS when compared to the rest of the population. Adjusted models showed association between higher exposure of PCBs, phthalates, BPA, and increased risk of PAD. Furthermore PCB153 was shown to have the highest geometric mean amongst all PCB congeners in both participants diagnosed with PAD and at risk of AS. Gene expression of ID3 & ID3 candidate targets in blood & tissue studies identified ID3 & ID3 candidate target genes as a driver of vascular disease. Overlapping ID3 & ID3 candidate target genes included: ABCB6, ACP1, BYSL, CAD, CDH15, DCBLD2, DHRS3, DNMT1, ID3, MCM4, and NDUFA7. The ID3 target genes involved in the: focal adhesion pathway were ACTN1, COL1A2, COL3A1, COL6A1, CTNNB1, IBSP, ID3, ITGA8, and MYL2; ECM-receptor interaction were COL1A2, COL3A1, COL6A1, IBSP, ID3, and ITGA8; oxidative phosphorylation pathway ATP5D, ATP5H, ATP6V0B, ATP6V0D1, ATP6V1B2, COX5A, COX7C, COX8A, CYC1, ID3, NDUFA1, NDUFA7, NDUFS4, NDUFV1, NDUFV2; and cell cycle pathway ANAPC10, ATM, CDKN2B, E2F5, MCM3, and MCM4. In summary our results showed an association between exposure to PCBs, phthalates, BPA, and increased risk of PAD and AS, and possible molecular mechanisms of interaction of ID3 target genes and estrogenic chemicals involved in PAD and AS.

Doenças cardiovasculares são a principal causa de morte no Brasil. Em contraste a esse cenário, o treinamento físico aeróbio (TFA) figura como importante ferramenta de combate a esse quadro, atuando, dentre diversos mecanismos, na expressão de microRNAs (miRNA) e na hipertrofia cardíaca (HC). Nesse sentido, seria o TFA capaz de reduzir expressão do miR-34c-3p em cardiopatologias, gerando melhora aos danos causados? Na tentativa de elucidar essa lacuna, ratos Wistar machos (2 meses) passaram por oclusão da coronária gerando infarto do miocárdio (IMS; IMT) ou indução de diabetes tipo I por STZ (DS;DT: 45mg/kg). Após a verificação do dano, estes foram submetidos a TFA (10 sem), e os ventrículos esquerdos (VE) foram dissecados a posteriori. Ao analisar a expressão gênica por RT-PCR, o TFA diminuiu (39%; p<0,02) a expressão do miRNA-34c-3p no VE de IMT vs. IMS. Em consonância, houve diminuição (27%; p<0,04) do miRNA em DT vs. DS. Investigando o potencial terapêutico dessa inibição, ao proceder análise in vitro em cultura primária de cardiomiócitos tratados com inibidor do miRNA (amiR-34c-3p), houve diminuição de sua expressão em 71% (50nM; p<0,01) vs. grupo controle (C), enquanto houve aumento de 41000% (50nM; p<0,01) entre o superexpressor (mmiR) e C. Analisando os marcadores de HC patológica entre amiR e C, verificou-se redução na a-actina esquelética (6,1%;p<0,02), aumento no ANF (84,4%; p<0,05) e redução na b-MHC (66%; p<0,007), demonstrando HC fisiológica em cardiomiócitos tratados com amiR. Buscando alvos do miR-34c-3p responsáveis por essas alterações, analisou-se o eIF4E, último fator iniciador de tradução ativado por via não canônica da PI3K-AKTmTOR. Sua direta ativação pode representar importante avanço na busca por terapias que induzam a HC fisiológica. O amiR aumentou o eIF4E (64%; p<0,003), com validação por diminuição da atividade da luciferase (48%; p<0,02) através de ensaio com vetor 3\'UTR do gene e miR-34c-3p. Outro alvo predito analisado, o KLF11, tem homologia com gene da insulina e pode estar relacionado com melhora metabólica do VE. O tratamento com amiR aumentou (192%; p<0,006) a expressão gênica do KLF11, validado com redução de 55% na atividade da luciferase, e aumento da captação de glicose (13%; p<0,04). Com os dados expostos, o TFA foi eficiente em inibir a expressão do miR-34c-3p em VE de animais cardiopatas que, atuando em seus alvos agora validados, foi capaz de promover HC fisiológica e melhora metabólica em cardiomiócitos. Considerando os efeitos cardioprotetores da inibição desse miRNA, vislumbra-se o potencial terapêutico dessa inibição em paciente na perspectiva de atenuação de prejuízos causados por cardiopatias / Cardiovascular diseases are the leading cause of death in Brazil. In contrast to this scenario, aerobic exercise training (AET) is an important tool to combat this condition, acting, among several mechanisms, on the expression of microRNAs (miRNA) and cardiac hypertrophy (CH). In this sense, would AET be able to reduce expression of miR-34c-3p in cardiac pathologies, generating improvement to the damages caused by them? In an attempt to elucidate this knowledge gap, male Wistar rats (2 months) underwent coronary occlusion, causing myocardial infarction (IMS; IMT) or induction of type I diabetes by STZ (DS: DT: 45mg kg). After proof that cardiac damage was caused, they were submitted to AET (10 wk), and left ventricles (LV) were dissected post mortem. Analyzing gene expression by RT-PCR, AET decreased (39%; p <0.02) miRNA-34c-3p expression in the LV of IMT vs. IMS. In agreement, there was a decrease (27%; p <0.04) of the miRNA in DT vs. DS. Investigating the therapeutic potential of this inhibition, through in vitro analysis in primary culture of neonatal rat cardiomyocytes treated with miRNA inhibitor (amiR-34c-3p), expression of miRNA- 34c-3p was decreased in 71% (50nM; p <0.01) vs. (C), whereas there was an increase of 41000% (50nM; p <0.01) between the superexpressor (mmiR) and C. Analyzing the pathologic HC markers between amiR and C, there was a reduction in skeletal a-actin (P <0.05), an increase in ANF (84.4%, p <0.05) and reduction in b-MHC (66%; p <0.007), demonstrating physiological HC in cardiomyocytes treated with amiR. Searching for miRNA-34c-3p targets responsible for these changes, eIF4E, the last non-canonically activated translation initiator of PI3K-AKT-mTOR, was analyzed. Its direct activation may represent an important advance in the search for therapies that induce physiological CH. The amiR increased eIF4E expression (64%, p <0.003), with validation for decreased luciferase activity (48%; p <0.02) by assaying 3\'UTR vector of the gene and miR-34c-3p. Another predicted target analyzed, KLF11, has homology with insulin gene and may be related to LV metabolic improvement. The treatment with amiR increased KLF 11 gene expression (192%; p <0.006), with a 55% reduction in luciferase activity and an increase in glucose uptake (13%; p <0.04). With the data presented, AET was efficient in inhibiting the expression of miRNA-34c-3p in LV of cardiopathic animals that, acting on their now validated targets, was able to promote physiological CH and metabolic improvement in cardiomyocytes. Considering the cardioprotective effects of inhibition of this miRNA, we can speculate a therapeutic potential of the inhibition of miR-34c-3p in patients in prospect of mitigating the damage caused by cardiopathies

Introdução: O aumento da prevalência de obesidade entre populações cada vez mais jovens tem sido observado em várias partes do mundo e representa uma condição associada à presença de fatores de risco centrais para o desenvolvimento de doenças cardiovasculares. Estudos epidemiológicos em adolescentes têm demonstrado uma relação inversa entre a frequência de refeições e o peso corporal e adiposidade abdominal. Recentemente, esse efeito também tem sido observado em relação às concentrações de lipídios séricos, porém os dados ainda são inconsistentes. Objetivo: analisar a associação da frequência de refeições com o estado nutricional e marcadores cardiometabólicos de adolescentes de escolas públicas do município de João Pessoa, Paraíba. Metodologia: Trata-se de um estudo transversal, desenvolvido a partir dos dados da linha de base do Estudo LONCAAFS, com amostra representativa de adolescentes de ambos os sexos, estudantes do sexto ano de escolas públicas do município de João Pessoa, PB, totalizando 1.438 indivíduos. O consumo alimentar foi avaliado por meio do Recordatório de 24h. Medidas antropométricas (peso, altura, circunferência da cintura) foram realizadas para classificação do estado nutricional através do IMC, da razão cintura/estatura e do índice de conicidade. Para avaliar o perfil lipídico, foi realizada coleta de sangue em uma subamostra (n=808) e dosado a concentração sérica de colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade e triglicerídeos plasmáticos. Os adolescentes foram estratificados em dois grupos, de acordo com a mediana de consumo energético (2040,5kcal). Para avaliar a associação da frequência de refeições com o estado nutricional e perfil lipídico, foram utilizados modelos de regressão logística. O nível de significância foi estabelecido em p <0,05. Resultados: A porcentagem de excesso de peso na população de estudo foi de 32%. Dentre os adolescentes que realizaram a coleta de sangue, cerca de 77% apresentaram dislipidemia. Na análise estratificada, o maior número de refeições associou-se inversamente com a obesidade abdominal no grupo com consumo energético abaixo da mediana. Nos indivíduos com consumo energético acima da mediana, houve tendência à quanto maior o número de refeições, menor a chance de HDL-c baixo (p=0,03). Não houve associação significativa entre número de refeições e as demais variáveis de risco cardiometabólico. Conclusão: A frequência de refeições mostrou-se significativamente associada à obesidade abdominal em indivíduos com consumo energético abaixo da mediana de ingestão da população e ao HDL-c nos indivíduos com consumo energético acima da mediana. / Introduction: The increasing prevalence of obesity among younger and younger populations has been observed in several parts of the world and is a condition associated with the presence of central risk factors for the development of cardiovascular diseases. Epidemiological studies in adolescents have shown an inverse relationship between meal frequency and body weight and abdominal adiposity. Recently, this effect has also been observed in relation to serum lipid concentrations, but the data are still inconsistent. Objective: to analyze the association of meal frequency with nutritional status and cardiometabolic markers of adolescents from public schools in the city of João Pessoa, Paraíba. Methodology: This is a cross-sectional study, based on data from the LONCAAFS study, with a representative sample of adolescents of both sexes, sixth-year students from public schools in the city of João Pessoa, PB, totaling 1,438 individuals. Food consumption was assessed through the 24-hour Reminder. Anthropometric measurements (weight, height, waist circumference) were performed to classify the nutritional status through BMI, waist / height ratio and conicity index. To evaluate the lipid profile, blood was collected in a subsample (n = 808) and serum levels of total cholesterol, high density lipoprotein, low density lipoprotein and plasma triglycerides were measured. Adolescents were stratified into two groups, according to the median energy consumption (2040.5kcal). To evaluate the association of meal frequency with nutritional status and lipid profile, logistic regression models were used. The level of significance was set at p <0.05. Results: The percentage of overweight in the study population was 32%. Among adolescents who performed blood collection, approximately 77% had dyslipidemia. In the stratified analysis, the highest number of meals was inversely associated with abdominal obesity in the group with energy consumption below the median. In individuals with energy consumption above the median, there was a tendency to the higher the number of meals, the lower the chance of low HDL-c (p = 0.03). There was no significant association between number of meals and the other variables of cardiometabolic risk. Conclusion: Meal frequency was significantly associated with abdominal obesity in subjects with energy consumption below the median ingestion of the population and with HDL-c in subjects with energy consumption above the median.

<p>Aim: The aim of this study was to investigate the prevalence and determinants of obesity amongst NAMDEB employees working at Pocket Beaches diamond mine.</p>

Objective: We aimed at investigating the association of age-dependent IGF-I SDS with diabetes, dyslipidemia, hypertension, and heart diseases, in a large patient sample. Background: IGF-I has been suggested to be associated with several diseases and a prognostic marker for the development of cardiovascular diseases and risk factors. The findings, though, have been inconsistent possibly due to the methodological factors. Methods: We studied 6773 consecutive primary care patients, aged 18+ years, in a cross-sectional, epidemiological study in primary care, Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment study. All patients underwent a standardized clinical diagnostic and laboratory assessment. IGF-I levels were measured with an automated chemiluminescence assay system. We calculated the odds ratios (OR) for diseases in quintiles of IGF-I, and additionally analyzed the association of age-dependent IGF-I SDS with these conditions. Results: After multiple adjustments for confounders, we found increased ORs for coronary artery disease in patients with high IGF-I. Women, but not men, with low IGF-I also showed increased ORs for coronary artery disease. Dyslipidemia was positively associated with IGF-I. Type 2 diabetes showed a curvilinear association with IGF-I SDS. Conclusions: The findings suggest the existence of multiple and complex interactions between IGF-I and several health conditions. The complex nature of disease- and subgroup-specific associations along with the methodological factors can be held responsible for divergent findings in previous studies.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. / Bibliography: leaves 67-70.

Bisphenol A (BPA), a widely used chemical in plastic, has drawn wide attention due to its presence in many consumer products and the environment. The purpose of this study was to examine the association between urinary BPA and the reporting of cardiovascular diseases (CVD), and then to examine the effect of C-reactive protein (CRP) as a moderating variable. The data used in this research were extracted from the National Health and Nutrition Examination Survey collected in 2009-2010. Guided by the advanced epidemiological triangle, analysis involved 2 stepwise binary logistic regressions. The first step suggested that the controls were significant in predicting CVD (Ï?2 (5) = 83.72, p < .001, R2 = .15). The Nagelkerke R2 coefficient of determination indicated that the controls explained approximately 15% of the variance in instances of CVD. The second step of the binary logistic regression included the controls and BPA level in the model together. The regression analysis suggested that the Nagelkerke coefficient of determination (Ï?2 (6) = 83.76, p < .001, R2 = .15) did not increase from the 15% explained by the controls, and BPA level was found to be a nonsignificant predictor of CVD (p = .853). Due to lack of association between BPA and CVD, the analysis was shifted to examine the association between urinary BPA and serum CRP. The association between urinary BPA and serum CRP was also statistically nonsignificant (Spearman correlation coefficient, rs= .06, p = .015). The results may have positive social change by contributing to the body of knowledge on BPA and by increasing scientific scrutiny for substances used in people's daily lives.

Tyrimo tikslas – nustatyti reabilitacijos ligoninėje po širdies ir kraujagyslių ligų gydomų pacientų subjektyvios sveikatos sąsajas su gyvenimo prasme ir socialiniu palaikymu sociodemografinių veiksnių kontekste. Eiga. Tyrime dalyvavo 172 tiriamieji (vyrai: n=91 (52,9 %), moterys: n=81 (47,1 %), amžiaus intervalas: 40 – 88 metai (vidurkis 67,9, st.n. 10,954)), LSMUL KK filialo Viršužiglio reabilitacijos ligoninės pacientų, besigydančių šioje ligoninėje po širdies ar kraujagyslių ligų. Tyrimo rezultatai parodė, kad subjektyvi sveikata statistiškai reikšmingai susijusi su psichologiniais veiksniais: gyvenimo prasmingumo turėjimu (p(0,000) < 0,05), sociodemografiniais veiksniais: socialiniu palaikymu (p(0,038) < 0,05), darbiniu statusu (p(0,011) < 0,05). Subjektyvios sveikatos ryšys su kitais veiksniais (gyvenimo prasmės ieškojimu, lytimi, amžiumi, gyvenama vieta, šeimynine padėtimi, išsilavinimu, turimų vaikų skaičiumi, ligos pobūdžiu) statistikai nereikšmingas (p > 0,05). Nustatyta, kad geresnę subjektyvią sveikatą gali lemti tai, jog tiriamasis yra dirbantis, mažiau ieško gyvenimo prasmės ir daugiau jos jau turi (p < 0,05). / The aim of the study was to establish rehabilitation hospital cardiovascular recovery patients subjective health links to the meaning of life and social support in the context of socio-demographic factors. The subjects of the study were 172 rehabilitation hospital cardiovascular recovery patients (men: n=91 (52,9 %), women: n=81 (47,1 %), age: 40 – 88 years (mean 67,9, st.d. 10,954)). Study was carried out in Hospital of Lithuanian University of Health Sciences Kaunas Clinics Virsuziglis Hospital of Rehabilitation. The results of the study showed that the subjective health significantly associated with psychological factors: the meaning of life presence (p (0,000) < 0,05), and sociodemographic factors: social support (p (0,038) < 0,05), working status (p (0,011 ) < 0,05). Subjective health link with other factors (meaning of life searching, gender, age, place of residence, marital status, education, number of children, the nature of the disease) is statistical insignificant (p > 0,05). It was found that better subjective health may lead to the fact that the patients are working, less searching the meaning of life and the more they already have (p < 0,05).