ABSTRACT
OBJECTIVE: Focal cortical dysplasias (FCDs) are an important cause of drug-resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II. METHODS: We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study. RESULTS: hsa-let-7f (p = 0.039), hsa-miR-31 (p = 0.0078), and hsa-miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2-target, is upregulated (p < 0.001). In vitro experiments showed that hsa-miR-34a downregulates NEUROG2 by binding to its 5'-untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway. INTERPRETATION: Our findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa-miR-34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623-635.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Epilepsy/metabolism , Focal Dermal Hypoplasia/metabolism , Malformations of Cortical Development/metabolism , Nerve Tissue Proteins/metabolism , Adolescent , Adult , Child , Child, Preschool , Drug Resistant Epilepsy/genetics , Epilepsy/drug therapy , Epilepsy/genetics , Female , Focal Dermal Hypoplasia/genetics , Humans , Infant , Male , Neurons/metabolism , TOR Serine-Threonine Kinases/metabolism , Transcription Factors/genetics , Young Adult , rho GTP-Binding Proteins/metabolismABSTRACT
Abstract Objective: To verify the psychometric properties of the Cerebral Palsy: Quality of Life Questionnaire Children – child report (CPQol-Child) questionnaire, after it was translated and culturally adapted into Brazilian Portuguese. Methods: After the translation and cultural adaptation of the tool into Brazilian Portuguese, the questionnaire was answered by 65 children with cerebral palsy, aged 9–12 years. The intraclass correlation coefficient and Cronbach's alpha were used to assess the reliability and internal consistency of the tool and its validity was analyzed through the association between CPQol-Child: self-report tool and Kidscreen-10 using Pearson's correlation coefficient. Results: Internal consistency ranged from 0.6579 to 0.8861, the intraobserver reliability from 0.405 to 0.894, and the interobserver from 0.537 to 0.937. There was a weak correlation between the participation domain and physical health of CPQol-Child: self-report tool and Kidscreen-10. Conclusion: The analysis suggests that the tool has psychometric acceptability for the Brazilian population.
Resumo Objetivo: Verificar as propriedades psicométricas da versão traduzida e adaptada culturalmente para o português do Brasil do instrumento Cerebral Palsy Quality of Life Questionnaire for Children – Child report. Métodos: Após a tradução e a adaptação cultural do instrumento para o português, o questionário foi respondido por 65 crianças com paralisia cerebral, entre nove e 12 anos. Os coeficientes de correlação intraclasse e alfa de Cronbach foram usados para avaliar a confiabilidade e consistência interna do instrumento e a validade do instrumento foi analisada pela relação entre CPQol-Child: self-report toole a Kidscreen-10 por meio do coeficiente de correlação de Pearson. Resultados: A consistência interna variou de 0,6579 a 0,8861, a confiabilidade intraobservador de 0,405 a 0,894 e a interobservador de 0,537 a 0,937. Verificou-se uma fraca correlação entre o domínio participação e saúde física da CPQol-Child e Kidscreen-10. Conclusão: A análise feita sugere que o instrumento usado tem aceitabilidade psicométrica para a população brasileira.
Subject(s)
Humans , Male , Female , Child , Quality of Life , Cerebral Palsy/psychology , Surveys and Questionnaires , Psychometrics , Translations , Severity of Illness Index , Brazil , Observer Variation , Reproducibility of Results , Cultural CharacteristicsABSTRACT
OBJECTIVE: To verify the psychometric properties of the Cerebral Palsy: Quality of Life Questionnaire Children - child report (CPQol-Child) questionnaire, after it was translated and culturally adapted into Brazilian Portuguese. METHODS: After the translation and cultural adaptation of the tool into Brazilian Portuguese, the questionnaire was answered by 65 children with cerebral palsy, aged 9-12 years. The intraclass correlation coefficient and Cronbach's alpha were used to assess the reliability and internal consistency of the tool and its validity was analyzed through the association between CPQol-Child: self-report tool and Kidscreen-10 using Pearson's correlation coefficient. RESULTS: Internal consistency ranged from 0.6579 to 0.8861, the intraobserver reliability from 0.405 to 0.894, and the interobserver from 0.537 to 0.937. There was a weak correlation between the participation domain and physical health of CPQol-Child: self-report tool and Kidscreen-10. CONCLUSION: The analysis suggests that the tool has psychometric acceptability for the Brazilian population.
Subject(s)
Cerebral Palsy/psychology , Quality of Life , Surveys and Questionnaires , Brazil , Child , Cultural Characteristics , Female , Humans , Male , Observer Variation , Psychometrics , Reproducibility of Results , Severity of Illness Index , TranslationsABSTRACT
Casos de hantavirose foram notificados em diferentes regioes do Estado de Sao Paulo (SP), Brasil, durante o primeiro semestre de 1998. Dois casos fatais de sindrome pulmonar ocorreram em maio de 1998 na Cidade de Guariba, localizada na Regiao Nordeste de SP. Ambos os pacientes trabalhavam no mesmo local, estocando milho em um paiol infestado de roedores. Este pacientes, apos 2 ou 3 dias de doenca febril aguda inespecifica, desenvolveram uma grave pneumonia intersticial, que espalhou-se difusamente por ambos os pulmoes causando insuficiencia respiratoria e obito. A autopsia, ambos os casos apresentavam edema pulmonar intersticial com infiltrado de celulas mononucleares (imunoblastos) sugestivo de etiologia viral...