An important quest in genomics since the publication of the first complete human genome in 2003 has been its functional annotation. DNA holds the instructions to the production of the components necessary for the life of cells and organisms. A complete functional catalog of genomic regions will help the understanding of the cell body and its dynamics, thus creating links between genotype and phenotypic traits. The need for annotations prompted the development of several bioinformatic methods. In the context of promoter and first exon predictors, the majority of models relies principally on structural and chemical properties of the DNA sequence. Some of them integrate information from epigenomic and transcriptomic data as secondary features. Current genomic research asserts that reference genome annotations are far from being fully annotated (human organism included).Physicians rely on reference genome annotations and functional databases to understand disorders with genetic basis, and missing annotations may lead to unresolved cases. Because of their complexity, neurodevelopmental disorders are under study to figure out all genetic regions that are involved. Besides functional validation on model organisms, the search for genotype-phenotype association is supported by statistical analysis, which is typically biased towards known functional regions.This thesis addresses the use of an in-silico integrative analysis to improve reference genome annotations and discover novel functional regions associated with neurodevelopemental disorders. The contributions outlined in this document have practical applications in clinical settings. The presented bioinformatic method is based on epigenomic and transcriptomic data, thus excluding features from DNA sequence. Such integrative approach applied on brain data allowed the discovery of two novel promoters and coding first exons in the human DLG2 gene, which were also found to be statistically associated with neurodevelopmental disorders and intellectual disability in particular. The application of the same methodology to the whole genome resulted in the discovery of other novel exons expressed in brain. Concerning the in-silico method itself, the research demanded a high number of functional and clinical datasets to properly support and validate our discoveries.This work describes a bioinformatic method for genome annotation, in the specific area of promoter and first exons. So far the method has been applied on brain data, and the extension to the whole body data would be a logical by-product. We will leverage distributed frameworks to tackle the even higher amount of data to analyse, a task that has already begun. Another interesting research direction that came up from this work is the temporal enrichment analysis of epigenomics data across different developmental stages, in which changes of epigenomic enrichment suggest time-specific and tissue-specific functional gene and gene isoforms regulation. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

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Made available in DSpace on 2014-12-17T15:36:37Z (GMT). No. of bitstreams: 1 SusanaMCCL_TESE.pdf: 1227375 bytes, checksum: 6eb36827ecd28243c12421ecff276fbd (MD5) Previous issue date: 2011-08-19 / Down syndrome (DS) is one of the most frequent causes of intellectual disability, affecting one in every 600 to 1000 live births. Studies have demonstrated that people with DS have a lower capacity for short-term memory (STM) and working memory (WM), which affects their capability to learn new words and to follow spoken instructions, specially when they involve multiple information or consecutive orders/orientations. It seems that the basis of the learning process, as it happens with language and mathematics comprehension and reasoning, relies in the STM and WM systems. Individuals with DS are increasingly included in mainstream education, and yet, very few researches have been conducted to investigate the influence of memory development and the type of enrollment (regular school and special school). This study investigated the relationship between the type of school enrollment with the performance on STM tests and also, the relationship of this performance with early stimulation (ES). The tests used in the first research were the digit span, free recall, word recognition and subtests of the Wechsler Intelligence Scale for Children Third Edition (WISC-III). Individuals enrolled in the regular schools group had higher scores on the digit span test and the subtests of the WISC-III. In the free recall and recognition tests, no differences were found. This study indicates that the type of enrollment might influence the memory development of individuals with DS and clearly points the need for future investigations. In the second research, the tests used were the digit span, free word recall and subtests of the WISC-III. The test results showed better performance by adults that received ES before six months of age. The studies showed improvement in STM both in people who attended or were attending regular school, as well as those who benefited from ES before six months of age. However, some issues still need to be better understood. What is the relation between this stimulation with the individual s education? Since ES may reflect a greater family involvement with the individual, what is the role of emotional components derived from this involvement in the cognitive improvement? These and other questions are part of the continuity of this study / A s?ndrome de Down ? uma das causas mais freq?entes da defici?ncia intelectual, afetando um a cada 600 a 1.000 beb?s nascidos vivos. Estudos demonstram que pessoas com s?ndrome de Down (SD) apresentam uma menor capacidade de mem?ria de curto prazo (MCP) e mem?ria operacional (MO), que s?o apontadas como poss?vel base dos processos de aprendizagem. Os indiv?duos com SD s?o cada vez mais inclu?dos no sistema regular de ensino, e, no entanto, poucas pesquisas foram realizadas para investigar a influ?ncia do contexto escolar no desenvolvimento da mem?ria nesses indiv?duos. Nesse sentido, esse estudo buscou investigar a rela??o da escolar regular e da escola especial com o desempenho nos testes para MCP, assim como a rela??o desse desempenho com a estimula??o precoce (EP). Duas pesquisas foram realizadas. Os testes utilizados na primeira pesquisa foram o span de d?gito, o de recorda??o livre e de reconhecimento de palavras, e subtestes da Escala Wechsler de Intelig?ncia para Crian?as terceira edi??o (WISC-III). Os indiv?duos matriculados na escola regular obtiveram maiores pontua??es no teste de span de d?gito e nos subtestes do WISC-III. Nos testes de recorda??o livre e de reconhecimento de palavras nenhuma diferen?a foi encontrada. Este estudo indicou que o contexto escolar pode influir no desenvolvimento da mem?ria dos indiv?duos com SD e aponta para a necessidade de futuras investiga??es. A segunda pesquisa investigou os efeitos da EP e os testes realizados foram o span de d?gito, a recorda??o livre de palavras e subtestes do WISC-III. Os resultados dos testes evidenciaram melhor desempenho na fase adulta das pessoas que receberam EP antes dos seis meses de idade. Os dois trabalhos demonstraram melhora na MCP tanto nas pessoas que freq?entaram ou freq?entavam a escola regular, como aquelas que se beneficiaram da EP antes dos seis meses de idade. Entretanto, algumas quest?es ainda precisam ser aprofundadas. Qual a rela??o dessa estimula??o com a escolariza??o do indiv?duo? Uma vez que estimula??o precoce pode refletir maior envolvimento familiar com o indiv?duo, qual o papel dos componentes emocionais resultantes desse envolvimento na melhora cognitiva? Essas e outras quest?es fazem parte da continuidade desse estudo

nÃo hà / A EducaÃÃo Inclusiva repercute uma mobilizaÃÃo mundial que consolida os ideais de igualdade na EducaÃÃo de qualidade para todos e revela-se um desafio da sociedade contemporÃnea. A inclusÃo de alunos com deficiÃncia na escola regular implica profundas mudanÃas na avaliaÃÃo da aprendizagem, que tradicionalmente tem se constituÃdo no exercÃcio da classificaÃÃo, seleÃÃo e exclusÃo, em oposiÃÃo ao seu papel formativo. Considerando a avaliaÃÃo do rendimento escolar pautada num processo dinÃmico, esta pesquisa objetiva investigar como à realizada a prÃtica da avaliaÃÃo da aprendizagem de alunos com deficiÃncia intelectual matriculados nas escolas regulares nos Anos Iniciais do Ensino Fundamental da rede municipal de Fortaleza-CE, na Secretaria Executiva Regional II (SER II). Especificamente, tem o propÃsito de: i) identificar o conceito dos professores sobre a avaliaÃÃo da aprendizagem de pessoas com deficiÃncia intelectual; ii) pesquisar os procedimentos avaliativos utilizados pelos professores junto aos alunos com deficiÃncia intelectual; iii) conhecer as dificuldades no tocante à avaliaÃÃo da aprendizagem dos alunos com deficiÃncia intelectual atravÃs de professores, alunos e seus familiares ou responsÃveis; iv) coletar sugestÃes do professor, e seus familiares ou responsÃveis, para a melhoria de mudanÃas educacionais e de construÃÃo de prÃticas avaliativas de carÃter sistemÃtico e reflexivo. Para esse propÃsito, foi realizada uma pesquisa de natureza qualitativa e quantitativa, na forma de um estudo de caso. Os instrumentos de coleta de dados foram a entrevista semiestruturada e o questionÃrio misto. Os dados obtidos foram categorizados segundo uma anÃlise de conteÃdo. As amostras foram constituÃdas por 16 familiares ou responsÃveis dos alunos com deficiÃncia intelectual e 7 professores das salas regulares, num total de 23 sujeitos. Os resultados revelaram que os docentes apontaram concepÃÃes limitadas e subjetivas acerca da EducaÃÃo Inclusiva, deficiÃncia intelectual e avaliaÃÃo da aprendizagem. As dificuldades assinaladas pelos sujeitos relacionam questionamentos sobre uma formaÃÃo docente contÃnua e adequada, aprimoramento fÃsico e estrutural da escola e ampliaÃÃo do envolvimento da famÃlia e da escola com a inclusÃo. Palavras-chave: AvaliaÃÃo da aprendizagem. Pessoa com deficiÃncia intelectual. EducaÃÃo Inclusiva.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2017-10-03T17:52:20Z No. of bitstreams: 2 Tese - Fabiana Gonçalves dos Reis - 2017.pdf: 5970849 bytes, checksum: e7504d09f87c5499323f6d7c66e10a0f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-10-04T12:07:46Z (GMT) No. of bitstreams: 2 Tese - Fabiana Gonçalves dos Reis - 2017.pdf: 5970849 bytes, checksum: e7504d09f87c5499323f6d7c66e10a0f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-10-04T12:07:46Z (GMT). No. of bitstreams: 2 Tese - Fabiana Gonçalves dos Reis - 2017.pdf: 5970849 bytes, checksum: e7504d09f87c5499323f6d7c66e10a0f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-08-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Neurological disorders are a group of conditions that manifest early in the development of the child, so that delayed neuropsychomotor development (ADNPM) and intellectual disability (ID) can impair cognitive, language, motor and social behavior. The etiology of ID is quite heterogeneous and prenatal, perinatal and postnatal factors are associated with an increased risk of this deficiency. However, 30 to 50% of the cases remain with the unknown etiology. In this context, the main objective of this study was to identify submicroscopic genomic alterations (<5Mb) by means of microarray chromosomal analysis (CMA) in patients with clinical indication of ADNPM and/or ID, sent by attending physicians of the state public health network of Goiás. We analyzed 149 cases of both sexes. Of the total number of patients, 47 had the diagnosis clarified using cytogenetics by G banding. Of 102 patients with an incomplete diagnosis, 72 agreed to participate in the present study and, therefore, performed the CMA. The elucidation of the diagnosis by CMA was possible in 22 patients. Among the results obtained, three rare cases were selected to compose this thesis. The first case is from a patient in whom a de novo microduplication of 0.45 Mb in the 5q35.2q35.3 region containing the NSD1 gene was identified. The effect of the dosing of this gene has been related to Sotos Syndrome and its inverted phenotype. The second case shows the molecular detection of an absent allele on the X chromosome and the presence of 28 CGG repeats in FMR1 gene in the present allele. The CMA showed that the patient had a de novo microdeletion of 4.176 Mb in the Xq27.3-q28 region that affected 34 genes, including five genes (TMEM185A, TMEM257, FMR1, IDS, and FMR2) that were directly correlated with ID phenotypes and neurological disorders. The third case is a de novo microdeletion of 1.59 Mb in the 1p32.3 region involving the DHCR24 gene, which causes a gene dosage effect influencing the activation of enzymes that cause desmosterolosis, which is a desmosterol conversion disorder in cholesterol. Thus, the results of this thesis showed the relevance of the use of the CMA technology to diagnose patients with clinical signs of ADNPM and/or ID that presented karyotype without alterations, evidencing the importance of this technology for public health. / Os distúrbios neurológicos constituem um grupo de condições que se manifestam precocemente durante o desenvolvimento da criança, de forma que o atraso do desenvolvimento neuropsicomotor (ADNPM) e a deficiência intelectual (DI) podem acarretar prejuízo às funções cognitivas, de linguagem, motricidade e comportamento social. A etiologia da DI é bastante heterogênea e fatores pré-natais, perinatais e pós-natais estão associados ao aumento do risco dessa deficiência. No entanto, 30 a 50% dos casos permanecem com a etiologia desconhecida. Neste contexto, o objetivo principal deste estudo foi identificar alterações genômicas submicroscópicas (<5Mb) por meio da análise cromossômica por microarranjos (CMA) em pacientes com indicação clínica de ADNPM e/ou DI, encaminhados por médicos assistentes da rede pública de saúde do Estado de Goiás. Foram analisados 149 casos, de ambos os sexos. Do total de pacientes, 47 tiveram o diagnóstico esclarecido utilizando-se a citogenética por bandeamento G. Dos 102 com diagnóstico não concluído, 72 concordaram em participar da presente pesquisa e, portanto, realizaram o CMA. A elucidação do diagnóstico pelo CMA foi possível em 22 pacientes. Dentre os resultados obtidos, foram selecionados três casos raros para compor esta tese. O primeiro caso é de um paciente em que foi identificada uma microduplicação de novo de 0,45 Mb na região 5q35.2q35.3, contendo o gene NSD1. O efeito da dosagem deste gene tem sido relacionado à síndrome de Sotos e ao seu fenótipo invertido. O segundo caso apresenta a detecção molecular de um alelo ausente no cromossomo X e a presença de 28 repetições CGG no gene FMR1 no alelo presente. O CMA mostrou que a paciente tem uma microdeleção de novo de 4,176 Mb na região Xq27.3-q28 que afetou 34 genes, dentre estes, cinco genes (TMEM185A, TMEM257, FMR1, IDS, and FMR2) que foram correlacionados diretamente com os fenótipos de DI e distúrbios neurológicos. O terceiro caso é de uma microdeleção de novo de 1,59 Mb na região 1p32.3 envolvendo o gene DHCR24, que acarreta um efeito de dosagem gênica influenciando na ativação de enzimas que causam a desmosterolose, que é um transtorno de conversão do desmosterol em colesterol. Assim, os resultados desta tese mostraram a relevância da utilização da tecnologia do CMA para diagnosticar pacientes com indicação clínica de ADNPM e/ou DI que apresentaram cariótipo sem alterações, evidenciando a importância desta tecnologia para a saúde pública.

Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-07-07T12:42:04Z No. of bitstreams: 1 2016 - Mariana Corr?a Pitanga de Oliveira.pdf: 61619826 bytes, checksum: 67b2715c0728e9a578c8210b92955045 (MD5) / Made available in DSpace on 2017-07-07T12:42:04Z (GMT). No. of bitstreams: 1 2016 - Mariana Corr?a Pitanga de Oliveira.pdf: 61619826 bytes, checksum: 67b2715c0728e9a578c8210b92955045 (MD5) Previous issue date: 2016-01-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / This dissertation has as its research theme the schooling of students with intellectual disabilities. According to recent researches, one of the biggest impediments has been the lack of teacher knowledge about the specifics of the teaching and learning process of these subjects. Supported by this thematic, our objective is to analyze the evaluation processes for students with intellectual disabilities and reflect on their process of elaboration and conceptual appropriation. The investigation is made up of two separate research projects, namely: (A) The reading and writing issue in the area of intellectual disability: what is the best teaching method? and (B) Schooling of students with intellectual disabilities: public policies, cognitive processes and learning evaluation, which funded this work (OBEDUC/CAPES). The study included two students with intellectual disabilities enrolled in different schools (one located in the city of Rio de Janeiro and the other in the municipality of Baixada Fluminense - RJ). We adopted qualitative research as the methodological procedure of our investigation, based on the principles of multiple case studies. We believe that research of this scale contributes towards the reflections needed to understand the singularities of the researched reality, and enable theoretical basis for intervention. Based on these assumptions, we used the participant observation, semi-structured and open interviews and the application of learning assessment tests as procedures and data collection instruments. For theoretical framework, we used the historical-cultural perspective of Vygotsky, in order to find, in his concepts, the necessary support to base our analysis on the education of the participating subjects. Under these aspects and after data analysis, the following results emerged: a) teaching mediation through interaction and clear statements of language is the main tool in the education of students, especially those with intellectual disabilities; b) evaluation mediated through collaborative activities is an instrument that permeates the Zone of Proximal Development (ZPD) of students; c) mediated teaching favours the conceptual elaboration by students with intellectual disabilities, and contributes to the development of higher mental functions; d) with the application of the tests, we verified that the mediated teacher?s intervention revealed paths for the student to appropriate a particular concept, so the evaluation itself was also a mediator of this process, showing new possibilities. At the end of this text, we present some reflections on changes in the evaluative perspective and the schooling processes of students with intellectual disabilities. In addition, this research points to paths that include learning possibilities for all / A presente disserta??o tem como tema de pesquisa a escolariza??o de alunos com defici?ncia intelectual. Para tal, segundo pesquisas recentes um dos maiores empecilhos tem sido a falta de conhecimento dos professores sobre as especificidades do processo de ensino e aprendizagem desses sujeitos. Apoiadas por essa tem?tica, tem-se como objetivo analisar os processos avaliativos dirigidos para os alunos com defici?ncia intelectual e refletir sobre o seu processo de elabora??o e apropria??o conceitual. A investiga??o est? inserida em dois projetos de pesquisa distintos, a saber: (A) A quest?o da leitura e escrita na ?rea da defici?ncia intelectual: qual a melhor forma de ensino? e (B) A escolariza??o de alunos com defici?ncia intelectual: pol?ticas p?blicas, processos cognitivos e avalia??o da aprendizagem, o qual financiou este trabalho (OBEDUC/CAPES). Participaram do estudo dois alunos com defici?ncia intelectual, matriculados em redes de ensino diferentes (uma localizada no munic?pio do Rio de Janeiro e a outra na Baixada Fluminense-RJ). Adotou-se como procedimento metodol?gico de investiga??o a pesquisa qualitativa, baseada nos princ?pios do estudo de casos m?ltiplos. Acredita-se que pesquisas dessa envergadura contribuem com reflex?es necess?rias para compreender as singularidades da realidade pesquisada, al?m de possibilitar base te?rica para a interven??o. Partindo desses pressupostos, utilizou-se como procedimento e instrumento de coleta de dados a observa??o participante, entrevistas aberta e semiestruturada e a aplica??o de provas de avalia??o da aprendizagem. Como referencial te?rico, empregou-se a perspectiva hist?rico-cultural de Vygotsky, visando encontrar, em seus conceitos, o suporte necess?rio para fundamentar as an?lises sobre a escolariza??o dos sujeitos participantes. Sob esses aspectos, ap?s a an?lise dos dados, emergiram os seguintes resultados: a) a media??o docente por meio da intera??o e da linguagem de enunciados claros ? a principal ferramenta na escolariza??o de alunos, em especial daqueles com defici?ncia intelectual; b) a avalia??o mediada por meio de atividades colaborativas ? um instrumento que perpassa a zona de desenvolvimento proximal (ZDP) dos alunos; c) o ensino mediado favorece a elabora??o conceitual por parte dos alunos com defici?ncia intelectual e contribui para o desenvolvimento das fun??es psicol?gicas superiores; d) com a aplica??o das provas verificou-se que ? medida que a interven??o mediada do professor revelava caminhos para o aluno se apropriar de um determinado conceito, a pr?pria avalia??o tamb?m foi mediadora desse processo, sinalizando novas possibilidades. Ao final deste trabalho, apresentam-se algumas reflex?es que dialogam sobre mudan?as na perspectiva avaliativa e dos processos de escolariza??o de alunos com defici?ncia intelectual. Igualmente, a pesquisa traz ind?cios de caminhos que contemplam possibilidades de aprendizagem para todos

Objetivos: Investigar anomalias dentárias, presença de fissura de lábio e/ou palato e higiene bucal em indivíduos com síndrome de Kabuki (SK) e listar as alterações sistêmicas presentes. Metodologia: Grupo 1: 46 prontuários de indivíduos com SK matriculados no HRAC/USP analisados quanto a presença de fissura de lábio e/ou palato e listadas as alterações sistêmicas presentes (cardiopatias, doenças infecciosas e imunológicas, nefropatias, comprometimento neurológicos e repercussões, aspectos genéticos). Grupo 2: formado por 15 indivíduos com SK matriculados no HRAC/USP submetidos aos exames clínicos para a investigação das alterações bucais (anomalias dentárias, presença de fissura de lábio e/ou palato e avaliação da higiene bucal índice de placa) e doenças sistêmicas existentes. Resultados: Grupo 1 43 (93,47%) indivíduos apresentaram fissura de lábio e/ou palato, 36 apresentaram fissura de palato; 17 (36,95%) indivíduos apresentaram cardiopatia congênita, 36 (76,59%) indivíduos tiveram doenças infecciosas ou imunológicas, 8 (17,39%) indivíduos apresentaram nefropatias, 40 (86,95%) indivíduos tinham deficiência intelectual e 1 (2,77%) indivíduos apresentou cariótipo com alteração. Grupo 2 todos os indivíduos com SK apresentaram fissura de lábio e/ou palato, 11 (73,33%) indivíduos apresentaram anomalias dentárias, todos os indivíduos apresentaram comprometimento da higiene bucal, 5 (33,33%) indivíduos apresentaram cardiopatias congênitas, 12 (80%) tiveram doenças infecciosas ou imunológicas, em um indivíduo foi notada nefropatia, 14 (93,33%) indivíduos demonstraram deficiência intelectual e 1 (6,66%) apresentou cariótipo alterado. Conclusões: Os indivíduos com SK apresentaram anomalias dentárias, fissura de lábio e/ou palato, higiene bucal comprometida, cardiopatias congênitas, doenças infecciosas e deficiência intelectual. / Aim: To investigate dental anomalies, presence of lip and/or cleft palate and dental hygiene in individuals with Kabuki Syndrome (KS) as well as detail their systemic alterations. Methodology: GROUP 1: 46 prontuaries of individuals with KS (patients from HRAC/USP) were analyzed concerning to the presence of lip and cleft palate and their systemic alterations were described (cardiopathies, infectious and immunological diseases, nephropathies, neurological disorders and genetical aspects). GROUP 2: 15 individuals with KS (patients from HRAC/USP) submitted to the clinical examination to investigate buccal alterations (dental anomalies, presence of lip and/or cleft palate and dental hygiene - plaque index) and systemic alterations. Results: Group 1 - 43 (93.47%) individuals showed lip and/or cleft palate, 36 showed cleft palate; 17 (36.95%) individuals showed congenic cardiopathies, 36 (36.95%) individuals showed infectious or immunological diseases, 8 (17.39%) individuals showed nephropathies, 40 (86.95%) individuals had intellectual disability and 1 (2.77%) individuals showed cariotip with alteration. Group 2 - all the individuals with KS showed lip and/or cleft palate, 11 (73.33%) individuals showed dental anomalies, all the individuals showed compromised dental hygiene, 5 (33.33%) individuals showed congenic cardiopathies, 12 (80%) showed infectious or immunological diseases, in only 1 individual nephropathy was observed, 14 (93.33%) had intellectual disabilities and 1 (6.66%) showed a cariotip with alteration. Conclusions: Individuals with KS showed dental anomalies, presence of lip and/or cleft palate, compromised buccal hygiene, congenic cardiopathies, infectious diseases and intellectual disability.

Orientador: Adriana Lia Friszman de Laplane / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T07:53:51Z (GMT). No. of bitstreams: 1 Granado_AndreaRebollo_M.pdf: 995351 bytes, checksum: b8458a11f71c23deecf157706f57ec9f (MD5) Previous issue date: 2014 / Resumo: Este estudo se propõe a conhecer a trajetória e compreender o papel da Terapia Ocupacional nas APAES do Estado de São Paulo. Estas instituições atendem pessoas com deficiência intelectual, e oferecem atendimentos em várias áreas da educação e saúde, dentre essas a Terapia Ocupacional que está presente na maioria dos planos terapêuticos e educacionais dos usuários. A pesquisa seguiu uma abordagem predominantemente qualitativa, utilizaram-se entrevistas semiestruturadas, gravadas com 06 terapeutas ocupacionais que atuaram ou atuam em APAES do estado de São Paulo. Inicialmente buscou-se resgatar alguns aspectos históricos da profissão e das instituições no Brasil. Em seguida considerando a analise do material, procurou-se destacar os aspectos relativos ao papel do profissional de terapia ocupacional nas décadas de 80, 90 e 2000 e suas bases teórico-metodológicas de atuação sendo possível refletir sobre as perspectivas atuais e futuras de participação deste profissional nas instituições. Descritores: Terapia Ocupacional. APAE, Deficiência Intelectual / Abstract: This study aims to know the history and understand the role of occupational therapy in APAES the State of São Paulo. These institutions serving people with intellectual disabilities, and offer consultations in various areas of education and health, among these occupational therapy which is present in most therapeutic and educational plans of users. The research followed a predominantly qualitative approach, we used semi-structured interviews, recorded with 06 occupational therapists who worked together in APAES the state of São Paulo. Initially we attempted to rescue some historical aspects of the profession and institutions in Brazil. After considering the analysis of the material sought to highlight those aspects of the role of occupational therapy professional in the 80, 90 and 2000 and its theoretical and methodological bases of operation being possible to reflect on the current and future prospects of participation of professional institutions. Keywords: Occupational Therapy, APAE. Intellectual Disability / Mestrado / Interdisciplinaridade e Reabilitação / Mestra em Saúde, Interdisciplinaridade e Reabilitação

Les variations du nombre de copies (CNVs) incluent les délétions et les duplications de régions chromosomiques d’une taille variant de 50 pb à plusieurs Mb. Depuis 2005, les études d’association pangénomiques (GWAS) ont permis d’associer certains larges CNVs à des maladies syndromiques associées à la déficience intellectuelle incluant les syndromes de DiGeorge, Williams, Angelman, etc. En fonction de la densité génique de la région d’intérêt et de la variabilité des phénotypes associés, l’étude de la physiopathologie des syndromes peut être extrêmement complexe. La modélisation murine offre de nombreux avantages pour l’identification des gènes candidats et la compréhension des mécanismes moléculaires associés à ces pathologies.Les travaux présentés dans ce manuscrit consistent en la caractérisation des modèles murins pour cinq maladies syndromiques associées aux CNVs : la monosomie 21 partielle ainsi que les réarrangements des régions 16p11.1 et 17q21.31. Les caractérisations anatomiques, métaboliques et comportementales des animaux nous ont permis d’évaluer un grand nombre de paramètres associés à la symptomatique humaine. Nous avons également réalisé des analyses électrophysiologiques et transcriptomiques en ciblant nos investigations sur l’hippocampe, structure cérébrale qui joue un rôle central dans les processus de mémoire et d’apprentissage. Ce projet de recherche s’inscrit dans une perspective plus large qui est l’identification des gènes candidats pour les phénotypes observés et le développement de premières stratégies thérapeutiques pouvant potentiellement aboutir à l’amélioration des capacités cognitives des patients. / Copy number variations (CNVs) include deletions and duplications of chromosomal regions ranging in size from 50bp to several Mb. Since 2005, genome-wide association studies (GWAS) have associated some large CNVs to syndromic diseases linked to intellectual disability including DiGeorge, Williams, Angelman syndroms, etc. Depending on the gene density of the region of interest and the variability of symptoms, the study of the pathophysiology of syndromes can be extremely complex. Mouse modeling show many advantages for the identification of candidate genes and the understanding of molecular mechanisms associated with these diseases.The work presented in this manuscript consists of the characterization of mouse models of five syndromic diseases associated with CNVs: partial monosomy 21 and rearrangements of 16p11.2 and 17q21.31 regions. Anatomical, metabolic and behavioral characterizations of animals allowed us to evaluate a broad number of parameters associated with human phenotypes. We also performed electrophysiological and transcriptomic analysis focusing our investigation on the hippocampus which has a major role in learning and memory processes. This project is part of a wider perspective which is the identification of candidate genes for the different phenotypes we observe in the mouse and the development of first treatment strategies which can potentially lead to the improvement of cognitive capacity of patients.

Abstract The objective of this study was to investigate intellectual disability (ID) in children, with focus on occurrence, associated biomedical and sociodemographic factors, probable psychiatric problems and temporal variations in the occurrence of ID and the associated factors in an interval of 20 years. The study population consisted of two birth cohorts of children born in northern Finland, the Northern Finland Birth Cohort 1986 (NFBC 1986, N = 9,432 live-born children) and the Northern Finland Birth Cohort 1966 (NFBC 1966, N = 12,058 live-born children). Temporal changes in ID were studied by comparing NFBC 1986 with NFBC 1966. The same definition of intellectual disability (intelligence quotient ≤70), time of follow-up (up to 11.5 years), case ascertainment methods and data sources were used. Data were collected from questionnaires, registers and records. In NFBC 1986 the incidence of ID was 12.62/1,000 by age 11.5 years and prevalence 11.23/1,000 live-born at age 11.5 years. Associated biomedical aetiology could be found in two thirds of the cases. Genetic disorders were the largest aetiological category (36.1%) associated with ID. Maternal disadvantage (unskilled worker, basic education only) had the largest impact on the incidence of ID, while among single independent factors, maternal prepregnancy obesity (body mass index ≥30) showed the highest risk for ID (OR 2.8, 95% CI 1.5, 5.3) in the offspring. According to the assessments by the teachers at school children with ID had 4.9 times more likely probable behavioural problems than their peers not having ID. In an interval of 20 years, there was no change in the incidence or in the prevalence of ID between NFBC 1986 and NFBC 1966. However, a shift occurred from more severe levels of ID towards mild ID, so that both the incidence and prevalence of mild ID increased by 50% whereas more severe ID decreased by 50%. Temporal changes appeared in the proportions of aetiological categories (NFBC 1986 vs. NFBC 1966) with a statistically significant decrease of Down syndrome and paranatally originating causes (traumas/asphyxia). The proportion of chromosomal disorders other than Down syndrome increased, as did malformations of the central nervous system. Among sociodemographic factors associated with ID, indicators of socio-economic disadvantage retained their status as having the largest impact on the incidence of ID. Over the 20 years, the mother being single, living in a remote area and mother's older age at time of delivery had lost their association with ID. Only one new maternal sociodemographic factor, prepregnancy obesity, had emerged as having an association with ID with a statistically significant difference between NFBC 1986 and NFBC 1966. In conclusion, these results indicate that although the occurrence of ID remained the same in northern Finland over a period of 20 years, temporal changes have taken place in the biomedical and sociodemographic factors contributing to the incidence and prevalence of ID. There are also factors that have retained their status as associated disadvantageous factors. Studies like this with repeatedly collected data in the same geographical area, describing the occurrence of ID, and analysing associated biomedical and sociodemographic factors, are valuable for evaluating developments in the health care and service system. They are also of value for future planning of services for individuals with ID. / Tiivistelmä Tämän tutkimuksen tavoitteena oli selvittää kehitysvammaisuuden esiintyvyyttä lapsilla, siihen liittyviä lääketieteellisiä etiologisia ja sosiodemografisia tekijöitä, mahdollisia psykiatrisia ongelmia sekä kehitysvammaisuuden esiintyvyydessä ja siihen liittyvissä tekijöissä tapahtuneita muutoksia 20 vuoden aikana. Tutkimusjoukko muodostui kahden syntymäkohortin lapsista, jotka olivat syntyneet Pohjois-Suomessa, Pohjois-Suomen syntymäkohortti 1986 (NFBC 1986, N = 9432 elävänä syntynyttä lasta) ja Pohjois-Suomen syntymäkohortti 1966 (NFBC 1966, N = 12058 elävänä syntynyttä lasta). Kehitysvammaisuudessa tapahtuneita ajallisia muutoksia tutkittiin vertaamalla Pohjois-Suomen syntymäkohortti 1986:ta Pohjois-Suomen syntymäkohortti 1966:een. Tutkimuksessa käytettiin samaa kehitysvammaisuuden määritelmää (älykkyysosamäärä ≤70, seuranta-aika 11.5 vuoteen saakka), tiedonkeruun menetelmiä ja tietolähteitä. Tiedot kerättiin kyselylomakkeista, rekistereistä ja asiakirjoista. Pohjois-Suomen syntymäkohortti 1986:ssa kehitysvammaisuuden ilmaantuvuus oli 12.62/1000 11.5 vuoden ikään mennessä ja vallitsevuus 11.23/1000 11.5 vuoden iässä. Kehitysvammaisuuteen liittyvä lääketieteellinen etiologia pystyttiin selvittämään kahdessa kolmasosassa tapauksia. Geneettiset häiriöt muodostivat suurimman etiologisen luokan (36.1%). äitiin liittyvillä epäedullisilla sosiaalisilla tekijöillä (kouluttamaton työntekijä, vain peruskoulutus) oli suurin vaikutus kehitysvammaisuuden ilmaantuvuuteen, kun taas yksittäisistä sosiodemografisista tekijöistä korkein riski (vaarasuhde 2.8, luottamusväli 1.5, 5.3) oli äidin lihavuudella (painoindeksi ≥30) raskauden alussa. Koulussa opettajien arvioiden mukaan kehitysvammaisilla lapsilla esiintyi mahdollisia käytöshäiriöitä 4.9 kertaa useammin kuin ei-kehitysvammaisilla lapsilla. 20 vuoden aikana Pohjois-Suomen syntymäkohorttien 1986 ja 1966 välillä ei ollut tapahtunut muutoksia kehitysvammaisuuden kokonaisilmaantuvuudessa eikä -vallitsevuudessa. Kuitenkin tuli esiin siirtymä vaikeammasta lievempään asteeseen siten, etta lievän kehitysvammaisuuden ilmaantuvuus ja vallitsevuus lisääntyivät noin 50%, kun taas vaikeamman väheni 50%. Lääketieteellisten etiologisten luokkien osuuksissa tuli esiin ajallisia muutoksia (Pohjois-Suomen syntymäkohortti 1986 vs. Pohjois-Suomen syntymäkohortti 1966) siten, että Downin syndrooman sekä syntymän aikaan ajoittuvan vamman ja hapenpuutteen osuudet vähenivät tilastollisesti merkitsevästi. Keskushermoston epämuodostumien sekä muiden kromosomihäiriöiden kuin Downin syndrooman osuudet kasvoivat. Kehitysvammaisuuteen liittyvistä sosiodemografisista tekijöistä sosioekonomisen huono-osaisuuden osoittimet säilyttivät asemansa suurimpana ryhmänä. 20 vuoden aikana äidin naimattomuus, asuminen syrjäseudulla sekä korkeampi ikä lapsen syntymän aikaan olivat menettäneet yhteytensä kehitysvammaisuuteen. Pohjois-Suomen syntymäkohortti 1986:n ja Pohjois-Suomen syntymäkohortti 1966:n välillä tuli esiin vain yksi uusi kehitysvammaisuuteen tilastollisesti merkitsevästi liittyvä sosiodemografinen tekijä, äidin lihavuus raskauden alussa. Yhteevetona voidaan todeta, etta vaikka kehitysvammaisuuden kokonaisesiintyvyys oli pysynyt samana Pohjois-Suomessa 20 vuoden aikana niin esiintyvyyteen liittyvät etiologiset ja sosiodemografiset tekijät olivat osittain muuttuneet. Tämänkaltaiset tutkimukset, joissa peräkkäisinä ajanjaksoina kerätään tietoja samalla maantieteellisellä alueella ja jotka kuvaavat kehitysvammaisuuden esiintyvyyttä sekä analysoivat siihen liittyviä lääketieteellisiä ja sosiodemografisia tekijoitä, ovat hyödyllisiä arvioitaessa terveydenhoidossa ja palvelujärjestelmässä tapahtunutta kehitystä. Niitä voidaan hyödyntää myös suunniteltaessa tulevaisuudessa palveluja kehitysvammaisille henkilöille.