Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug induced arrhythmia and sudden unexplained deaths

Abstract Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic variation. Our objective was to study the genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying suspected drug-induced arrhythmias and sudden unexplained deaths in 32 patients. The genetic component in the pharmacodynamic pathway was studied by analyzing 96 genes associated with higher risk of SCD through massive parallel sequencing. Pharmacokinetic mediated genetic susceptibility was investigated by studying the genes encoding cytochrome P450 enzymes using medium-throughput genotyping. Pharmacodynamic analysis showed three probably pathogenic variants and 45 variants of uncertain significance in 28 patients, several of them previously described in relation to mild or late onset cardiomyopathies. These results suggest that genetic variants in cardiomyopathy genes, in addition to those related with channelopathies, could be relevant to drug-induced cardiotoxicity and contribute to the arrhythmogenic phenotype. Pharmacokinetic analysis showed three patients that could have an altered metabolism of the drugs they received involving CYP2C19 and/or CYP2D6, probably contributing to the arrhythmogenic phenotype. The study of genetic variants in both pharmacodynamic and pharmacokinetic pathways may be a useful strategy to understand the multifactorial mechanism of drug-induced events in both clinical practice and forensic field. However, it is necessary to comprehensively study and evaluate the contribution of the genetic susceptibility to drug-induced cardiotoxicity. (AU)

The systems approach in developmental psychology: fundamental concepts and principles / Visão Sistêmica na Psicologia do Desenvolvimento: Conceitos e Princípios Fundamentais

Developmental Psychology seems to have come to an unifying theoretical framework which may make feasible to overcome the fragmentation so frequently referred to within the discipline. This is indicated by the widespread support being given to the systems approach, enriched by dialectic and contextual postulates. In this article, we briefly review the antecedents of this approach and explore its core concepts, indicating their roots and the precise way in which they are applied to developmental analyses today. We also examine the implications of the systems approach for developmental investigation, and its challenges.

A Psicologia do Desenvolvimento parece ter chegado a uma estrutura teórica de trabalho que pode tornar possível vencer a barreira da fragmentação, frequentemente referida na disciplina. Isto pode ser verificado pelo vasto suporte dado a visão dos sistemas, enriquecido pelos postulados contextuais e dialéticos. Neste artigo, nós brevemente revisamos os antecedentes dessa abordagem e exploramos seus conceitos básicos (centrais), indicando suas origens e caminhos precisos nos quais eles são aplicados na análise do desenvolvimento nos dias de hoje. Nós também examinamos as implicações da visão sistêmica para investigação do desenvolvimento e seus desafios.

Cognitive style and learning strategies as factors which affect academic achievement of brazilian university students / Estilo cognitivo e estratégias de aprendizagem em estudantes universitários brasileiros: repercussões no rendimento acadêmico

In the present study, the influence of the cognitive style called field dependence-independence on academic achievement of Brazilian university students was explored as well as the mediating effect of learning strategies on that influence. Learning strategies of 313 first-year university students (189 women and 124 men; M age = 20.86, SD = 3.86) from different fields, with upper, medium and lower scores on field dependence-independence were assessed on a self-report questionnaire and their overall academic marks in the first year were registered. Results of a regression analysis showed that cognitive style and learning strategies significantly contributed to academic achievement. A path analysis revealed that planning strategies mediated the influence of cognitive style on achievement.

No presente estudo, a influência do estilo cognitivo dependência-independência de campo no rendimento acadêmico de estudantes universitários brasileiros foi explorada, bem como o efeito mediador das estratégias de aprendizagem nesta influência. As estratégias de aprendizagem de 313 estudantes universitários de primeiro curso (189 mulheres e 124 homens, idade M=20,86, DP= 3,86) a partir de diferentes domínios, com pontuações elevadas, intermediárias e baixas em dependência-independência de campo, foram avaliadas em um auto questionário e as suas médias globais de rendimento acadêmico no primeiro ano foram registradas. Resultados de uma análise de regressão mostraram que o estilo cognitivo e as estratégias de aprendizagem contribuem significativamente para o sucesso acadêmico. Uma path analysis revelou que as estratégias de planejamento mediam a influência do estilo cognitivo na sua realização.

Processos atencionais e dependência-independência de campo: estudo com crianças e adolescentes portugueses / Attention processes and field dependence-independence: a Study with portuguese children and adolescents

Este artigo relaciona o estilo cognitivo "dependência-independência de campo" com o desempenho em tarefas envolvendo vários processos e recursos de atenção. Com uma amostra de 98 crianças e 95 adolescentes portugueses, foram aplicadas quatro tarefas de atenção: capacidade de armazenamento (Dígitos em ordem direta); memória de trabalho verbal (Dígitos em ordem inversa); capacidade para dirigir, mudar e manter a atenção (Código); e capacidade de atenção sustentada (Teste de Atenção e Rastreio Visual, VSAT). Recorreu-se, ainda, à aplicação de uma prova de fator g, tendo em vista o controle da inteligência. Os resultados revelam diferenças entre dependentes e independentes de campo, especialmente relevantes no grupo de crianças na prova de VSAT. Esses resultados abrem novas linhas de investigação para explicar a pior execução acadêmica dos indivíduos dependentes de campo.

The present study relates the "field dependence-independence" cognitive style to the performance on tasks involving several attention processes and resources. With a 98 Portuguese children and 95 Portuguese adolescents sample, four attention tasks were applied: storage capacity (Digits Forward Test); verbal working memory (Digits Backward Test); capacity to focus, shift, and maintain attention (Digit Symbol Test); and capacity for sustained attention (Visual Search and Attention Test, VSAT). It was also applied a factor g test for intelligence control. Results showed differences on attention processes between field-dependence and field-independence cognitive styles. These differences are more evident in the children subgroup on VSAT. These results open new research topics to explain lowest academic performance of field-dependent children.