This work aimed to describe and characterize the GnG-PK/PD-AD study and the population of subjects diagnosed with depression and treated with fluoxetine, paroxetine, and venlafaxine recruited in the ...scope of this project, particularly in terms of antidepressant pharmacokinetics and clinical outcomes and relevant genetic and nongenetic individual factors. 182 subjects diagnosed with depression and treated with these drugs were clinically and therapeutically characterized and submitted to the quantification of drug/metabolite plasma concentrations and genotyping of ABCB1, CYP2C9, CYP2C19, and CYP2D6 genes. Clinical outcomes, including remission and antidepressant adverse effects, were assessed by means of the Hamilton Depression Rating Scale and Antidepressant Side-Effect Checklist, respectively. Most subjects were women (81.9%), suffered from chronic depression (73.6%) and displayed a high prevalence of comorbidities (76.9%), polytherapy (88.5%), and genetic polymorphisms/non-wild-type genotype-predicted phenotypes at the level of CYP2C9, CYP2C19, CYP2D6, and ABCB1 genes (39-78.6%). Noteworthy, most of them were under risk of presenting P-gp, CYP2C9, CYP2C19, and CYP2D6 inhibited due to drug-induced phenoconversion (64.3-98.4%) and 80.8% were at risk of occurrence of at least one antidepressant-drug interaction. Around 40% presented drug plasma concentrations outside of the recommended therapeutic range, 66.5% did not achieve remission of the depressive symptoms and 67.6% presented at least one relevant antidepressant adverse effect. Pharmacokinetics and clinical outcomes with fluoxetine, paroxetine, and venlafaxine were found to be suboptimal and highly variable between subjects. Several genetic and nongenetic factors were identified as potential sources of interindividual variability in the antidepressant outcomes, which deserve to be further investigated.
Public Health Significance
The present work provides a real-world clinical characterization of subjects with depression under treatment with fluoxetine, paroxetine or venlafaxine, recruited in the scope of the GnG-PK/PD-AD study, focusing more specifically the impact of relevant genetic and nongenetic individual factors on the pharmacokinetics and clinical outcomes reached with these antidepressant drugs. This contributes to improve the clinical characterization and understanding of the state of art of the treatment of depression with these three antidepressant drugs and to support further studies focused on the identification of potential therapeutic biomarkers.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The autosomal dominant spinocerebellar ataxias (SCAs) are a clinical and genetically heterogeneous group of debilitating, neurodegenerative diseases, related to fourteen different loci - SCAs 1, 2, ...4, 5, 6, 7, 8, 10, 11,12,13 and 14, Machado-Joseph disease (MJD/SCA 3), and DRPLA.
(1) To verify the frequency of SCA1, SCA2, MJD, DRPLA, SCA6, SCA7 and SCA8 in a series of new SCA patients from South Brazil and (2) to compare their molecular and clinical characteristics with other patients previously described.
Sixty-six cases were included in the present study: 52 were familial and 14 sporadic. Molecular analysis of the trinucleotide repeat loci were performed according to methods in the literature.
92% of families with autosomal dominant inheritance segregated the MJD1 mutation,2% of families segregated the SCA7 mutation and 6% remained undiagnosed. Among 14 isolated cases, one showed the SCA8 mutation. Clinical and molecular findings were similar to those already described in the literature, but revealed (1) one SCA7 patient with eyelid retraction, a sign usually related to MJD; and (2) one sporadic case of SCA8.
The proportion of MJD cases was very high, probably reflecting an Azorean founder effect. The estimated frequency of affected individuals with MJD, in our region, was 1.8 / 100,000, and of SCAs other than MJD, 0.2/100,000.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introdução: A gestação de alto risco ocorre quando a gestante apresenta alguma doença ou condição sociobiológica que possa prejudicar a evolução da gravidez. Objetivos: Objetivou-se traçar o perfil ...das gestantes de alto risco atendidas em uma cidade de Minas Gerais. Métodos: Foi realizado um estudo descritivo, observacional, de caráter transversal, com abordagem quantitativa, realizado na Unidade de Obstetrícia da Policlínica Municipal de Divinópolis-MG, no período de março de 2013 a fevereiro de 2014. Os dados foram obtidos por meio de um questionário aplicado na consulta puerperal e complementados com a investigação do prontuário e do cartão da gestante. Resultados: Das 218 gestantes acompanhadas no serviço, apenas 52 retornaram à consulta puerperal. A maioria das gestantes eram multigestas (65,5%) e não referiram aborto prévio (73,1%); somente 30,8% foram admitidas precocemente e os diagnósticos mais frequentes foram Diabetes Mellitus Gestacional (23,1%), pré-eclâmpsia (21,2%) e disfunção tireoidiana (13,5%). A maior parte teve o parto a termo (82,7%) e cesariana (59,6%). Destaca-se que 88,5% e 96,2% das mulheres não foram submetidas ao exame de colpocitologia oncótica e das mamas, respectivamente. Conclusões: Deve-se alertar para a necessidade de aprimoramento da atenção à saúde da gestante, com a realização dos exames preventivos rotineiramente, indicação mais precisa da cesariana e educação das gestantes com relação à importância da consulta puerperal.
O objetivo deste estudo foi compreender como a temática das relações étnico raciais tem sido estudada na educação física escolar. Para isso, realizou-se uma revisão integrativa de teses e ...dissertações nas bases de dados da CAPES e da BDTD. A amostra totalizou 25 estudos que puderam ser organizados em três grandes grupos: formação; identificação/investigação e intervenção/proposição que apontaram para um crescimento no interesse em pesquisar à temática. Por fim, pudemos concluir que, mesmo havendo interesse por parte dos pesquisadores em, há uma necessidade da oferta de formações para que se consiga a ampliação das discussões no sentido da busca de estratégias mais concretas de inserções dessa temática nas aulas de educação física escolar.
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