GJB2: Frequency of the less common variants in a sample of the Portuguese population

Introduction: Sequence variants in the GJB2 gene account for up to 50% of cases of non-syndromic sensorineural hearing loss in the Caucasian population. In this study, we report the frequency of the less common variants of the GJB2 gene in a Portuguese sample and compare these frequencies with those of a group of hearing-impaired patients. Material and Methods: In order to select the less common GJB2 variants, 147 hearing-impaired patients followed in Centro Hospitalar Universitário de São João were evaluated. Afterwards, the presence of those variants was tested in 360 individuals from Generation 21. Results: The patient assessment enabled the selection of 11 GJB2 variants. Of those, 10 were investigated in Generation 21 participants, with only four being detected, in heterozygosity: p.Phe83Leu, p.Arg127His, p.Val153Ile and p.Asn206Ser, with the allelic frequencies (95% confidence interval) of 0.14% (0.01% - 0.87%), 0.28% (0.01% - 1.08%), 0.97% (0.43% - 2.04%) and 0.14% (0.01% - 0.88%), respectively. Two variants, p.Val37Ile and p.Val95Met, were more frequent in the patients’ group with statistical significance. Discussion: Our results allow for the p.Arg127His and p.Val153Ile variants to comply with polymorphism criteria and support the pathogenicity of p.Val37Ile and p.Val95Met variants. Moreover, two cases of moderate hearing loss were explained by the p.Val37Ile/p. Asn206Ser genotype, substantiating both the pathogenicity of such variants and the hypothesis that compound heterozygosity with p.Ans206Ser is associated with mild-moderate genotypes. Conclusion: Understanding the role of the variants is essential in order to provide genetic counselling to patients and their families. We explored a set of uncommon GJB2 variants that comprised 12% of the hearing-impaired patients in this study, supporting the relevance of their description.Generation XXI was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health). This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FED-ER-006862; Ref. UID/DTP/ 04750/2013), and the Calouste Gulbenkian Foundation. Ana Cristina Santos holds an FCT Investigator contract IF/ 01060/2015. (POCI-01-0145-FEDER-016837)

Sport participation legacy and the olympic games: The case of sydney 2000, london 2012, and rio 2016

© 2017 Cognizant, LLC. Sport participation as a legacy of the Olympic Games (OG) has frequently featured as a component of the "legacy package" that government bodies and organizing committees promote to the local communities to gain support for the hosting of these mega-events. However, only recently increased sport participation has been explicitly included as part of a legacy plan in OG candidature files. This article examines the changes and development of sport legacy planning and implementation from Sydney 2000, London 2012, and Rio 2016. The three case studies confirm that sport participation legacies are only achieved if host governments engage the community, develop long-term strategies, and coordinate efforts between different government portfolios and with a range of relevant stakeholders. So far, there is limited evidence available to demonstrate that relevant government bodies have attempted to strategically leverage the Games with the purpose of developing a sport participation legacy for the wider population

Cerebral Venous Thrombosis Imagiologic Features in a Pregnant Woman

A trombose venosa cerebral (TVC) é uma doença relativamente rara mas grave, potencialmente reversível com diagnóstico atempado e terapêutica médica adequada. A gravidez e o puerpério são um factor predisponente de TVC, que é responsável por 6% das causas de morte materna. As manifestações clínicas dependem da localização, extensão do trombo, bem como da rede de colaterais existente. Apresentamos o caso duma doente do sexo feminino, 33 anos, grávida de 13 semanas que recorreu ao serviço de urgência por quadro de cefaleias e cujo estudo por Ressonância Magnética revelou aspectos compatíveis com doença venosa oclusiva subtotal do seio longitudinal superior em fase aguda. A propósito deste caso discutimos as manifestações imagiológicas da trombose venosa dural na fase aguda

Prevalence of rheumatoid arthritis in South America: a systematic review and meta-analysis

Rheumatoid arthritis (RA) is among the most prevalent chronic autoimmune and inflammatory diseases worldwide. The aim of this study was to establish a pooled estimate of the RA prevalence in South America by means of a meta-analysis of the available epidemiologic studies. Systematic searches in PubMed, Lilacs, SciELO, Scopus, and Web of Science databases (updated May 2019) were done followed by a systematic grey literature search to identify original research articles and reports, published after 2000, providing data of RA prevalence in any South American country. Proportion meta-analysis of weighted pooled was performed, with between-trial heterogeneity assessed by the inconsistency relative index. Sensitivity analyses and sub-group analyses were also done. A total of 25 articles, representing 27 population-based studies were included. Pooled prevalence of RA resulted in 0.48% with 591,981 cases in a population of 114,537,812 individuals (I2=99%). Brazil and Colombia presented the lowest rates of RA prevalence 0.22%, and 0.24%, respectively. RA prevalence in indigenous population was higher 1.45%, and studies using COPCORD method reported also the highest rates 1.07%

Primary Tuberculosis of the Esophagus

Os autores reportam o caso de uma doente de 38 anos de idade com um quadro clínico de odinofagia, dor retroesternal e emagrecimento. Os exames complementares de diagnóstico revelaram a presença de uma lesão ulcerada no esófago, como forma de manifestação de tuberculose primária do esófago. A Tuberculose esofágica é uma doença pouco frequente, sendo responsável por 0,15% da mortalidade por tuberculose. A Tuberculose primária do esófago, sem envolvimento de outros órgãos, como o nosso caso clínico, é ainda mais raro. A maioria dos casos é tratada de forma eficaz com tuberculostáticos, sendo que o atraso no diagnóstico e início da terapêutica dita um mau prognóstico

Hard X-ray lags in active galactic nuclei: Testing the distant reverberation hypothesis with NGC 6814

We present an X-ray spectral and temporal analysis of the variable active galaxy NGC 6814, observed with Suzaku during November 2011. Remarkably, the X-ray spectrum shows no evidence for the soft excess commonly observed amongst other active galaxies, despite its relatively low level of obscuration, and is dominated across the whole Suzaku bandpass by the intrinsic powerlaw-like continuum. Despite this, we clearly detect the presence of a low frequency hard lag of ~1600s between the 0.5-2.0 and 2.0-5.0 keV energy bands at greater than 6-sigma significance, similar to those reported in the literature for a variety of other AGN. At these energies, any additional emission from e.g. a very weak, undetected soft excess, or from distant reflection must contribute less than 3% of the observed countrates (at 90% confidence). Given the lack of any significant continuum emission component other than the powerlaw, we can rule out models that invoke distant reprocessing for the observed lag behavior, which must instead be associated with this continuum emission. These results are fully consistent with a propagating fluctuation origin for the low frequency hard lags, and with the interpretation of the high frequency soft lags - a common feature seen in the highest quality AGN data with strong soft excesses - as reverberation from the inner accretion disk

Interaction of paraoxonase-192 polymorphism with low HDL-cholesterol in coronary artery disease risk.

A doença coronária (DC) é a principal causa de mortalidade nos países desenvolvidos. O aumento da peroxidação lipídica está associado com a progressão acelerada da arteriosclerose. A Paraoxonase (PON1) é uma enzima antioxidante, que protege contra a peroxidação lipídica e a DC. A actividade da PON1 está sob controlo genético e a sua base molecular consiste num polimorfismo do gene da PON1 que apresenta duas isoformas comuns: a forma nativa, Q (192 Gln) com elevada capacidade de protecção das LDL da peroxidação lipídica in vitro, e a isoforma mutada R (192 Arg) com baixa capacidade de protecção. Objectivo: O objectivo deste trabalho foi investigar a interacção entre o alelo R do gene da PON 1 e os níveis plasmáticos baixos de colesterol HDL, no risco do aparecimento da DC. Métodos: Participaram no estudo 818 indivíduos, 298 doentes coronários com idade média 55.0±10.3 anos, 78.9% do sexo masculino, e 520 controlos, com uma idade média de 53.3±11, 7 anos, 72, 5% do sexo masculino, tendo casos e controlos sido emparelhados por idade e sexo. Foi considerado um valor <de 40 mg/dl (0,90 mmol/L), nos homens e <de 50 mg/dl (1,11 mmol/L), nas mulheres como um nível baixo de Colesterol HDL. As comparações genotípicas, entre casos e controlos, foram efectuadas pelo teste do Chi-quadrado. A significância estatística foi aceite para valores de p <0,05. Para determinar o risco relativo de DC, em relação ao genótipo RR e aos níveis baixos de colesterol HDL, foi usada uma análise univariada e foram utilizadas as tabelas epidemiológicas 4x2 e medidas de sinergismo (modelo aditivo - SI e multiplicativo - SIM) para determinar a interacção entre o genótipo RR e os níveis baixos de colesterol HDL. Foi finalmente calculado o excesso de risco relativo (RERI) e proporção atribuída à interacção (AP). Resultados: A PON 1 192 RR está associada à DC [OR=1,61; p=0,043] para toda a população. A associação de níveis baixos de HDL com o genótipo 192 RR mostrou um aumento do risco de DC (OR=17,38; p <0,0001) comparada aos níveis normais de HDL associados ao mesmo genótipo (OR=1,39; p=0,348) e aos níveis baixos de HDL sem o genótipo RR (OR=7,79; p <0,0001). Índices de Sinergismo: SI= 2,3; SIM = 1.6; RERI=9,2; AP=0,53. Conclusão: Estes dados sugerem a existência de um efeito sinérgico entre o genótipo 192 RR da PON1 e os valores baixos de colesterol HDL, na emergência de DC, pois este genótipo aumentou o risco de DC, em especial, na população com níveis plasmáticos baixos de colesterol HDL. A proporção de DC que pode ser atribuída a esta interacção (AP) foi de 0,53 significando que 53% da DC que surgiu nestes indivíduos, foi explicada por esta interacção.INTRODUCTION: Coronary artery disease (CAD) is the main cause of mortality in developed countries. Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidant enzyme bound to high-density lipoprotein (HDL), which protects against lipid peroxidation and coronary artery disease. PON1 activity is under genetic control and its molecular basis is a polymorphism in the PON1 gene that shows two common isoforms: the wild Q form (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and the mutated R (Arg) form with lower ability. AIM: To explore the interaction of the R allele of the paraoxonase gene and low HDL-cholesterol concentrations in CAD risk. METHODS: The study population consisted of 818 individuals, 298 coronary patients, aged 55.0 +/- 10.3 years, 78.9% male, and 520 age and gender matched healthy controls, aged 53.3 +/- 11.7 years, 72.5% male. Low HDL-cholesterol was defined as < 0.90 mmol/l in men and < 1.11 mmol/l in women. Comparisons of genotypes between cases and controls were performed by a chi-square test. Statistical significance was accepted at p < 0.05. Odds ratios and 95% confidence intervals for the RR genotypes and HDL-deficient subjects were computed using univariate analysis (2 x 2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used 4 x 2 epidemiologic tables and synergy measures: the additive model (Rothman's synergy index, SI) and multiplicative model (Khoury's synergy index, SIM). The relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction (Rothman) were calculated. RESULTS: The PON1 RR192 polymorphism was associated with coronary heart disease (OR = 1.61; p = 0.043) in the whole population. HDL-deficient subjects with the RR192 genotype showed increased risk for CAD (OR = 17.38; p < 0.0001) compared to those with normal HDL and RR192 (OR = 1.39; p = 0.348) and HDL-deficient subjects not carrying the RR genotype (OR = 7.79; p < 0.0001). Synergy measures were SI = 2.3, SIM = 1.6; RERI = 9.2. CONCLUSION: These data suggest the existence of a synergistic effect of the PON1 RR192 genotype (with lower antioxidant ability) and HDL-deficient subjects in risk for development of CAD. The AP due to this interaction was 0.53, meaning that 53% of CAD was explained by this interaction.info:eu-repo/semantics/publishedVersio