As malformações de orelha são anomalias que ocorrem no período de desenvolvimento embrionário e podem acometer a orelha externa, média e/ou interna, podendo ser uni ou bilaterais. Na fase escolar, crianças com malformação de orelha podem ser prejudicadas pela falta de estímulos adequados ao seu potencial cognitivo, socioafetivo, linguístico e politicocultural, acarretando prejuízo considerável ao desenvolvimento da aprendizagem. Nesse contexto, esta pesquisa teve como objetivo desenvolver um programa para alunos do ensino fundamental, utilizando a teleducação interativa do Projeto Jovem Doutor, visando a promoção da saúde auditiva e a inclusão do deficiente auditivo com malformação de orelha externa e/ou média, no âmbito escolar. O estudo foi dividido em duas fases. A primeira fase foi constituída pela construção de um conteúdo educacional (roteiro), avaliação por juízes da área de Fonoaudiologia, por meio de dois questionários e adequação de acordo com as sugestões dos juízes. A segunda fase constituiu da aplicação do conteúdo para 18 alunos sem malformações craniofaciais, deficiência auditiva, visual ou intelectual, utilizando a metodologia do Projeto Jovem Doutor e foi dividida em: atividade presencial informando a dinâmica do curso e introdução do tema; etapa não presencial, com apresentação on-line do roteiro e etapa presencial, para estabelecer estratégias de repassar o conteúdo aos colegas e comunidade. Anteriormente e após a aplicação do programa de capacitação, os alunos responderam ao Questionário Situação-Problema (QSP), com o objetivo de mensurar o conhecimento teórico prévio e o adquirido ao longo do programa. Posteriormente, responderam a outros dois, denominados Questionário Opinião - (QO), com o objetivo de expressar a opinião sobre o curso à distância e a Ficha de Pesquisa Motivacional - (FMP), para verificar subjetivamente os aspectos motivacionais do programa de capacitação. Os professores também avaliaram o exercício das habilidades sociais dos alunos, por meio do Questionário de Crenças e Sentimentos do Professor (CSP). Os resultados mostram que a maioria dos juízes apresentou apreciações positivas, considerando a qualidade do roteiro como excelente (1789 respostas) e muito boa (911 respostas). Em relação ao QSP, os resultados apontaram que, comparando, estatisticamente, o antes (pré-teste) e o depois (pós-teste), os resultados apontaram que metade dos pesquisados acertou até 40% no pré-teste e metade acertou até 80% no pós-teste. Assim, os dados apresentados revelam que a aplicação do programa produziu efeito positivo em relação ao aumento dos conhecimentos dos alunos. Em resposta ao QO, a maioria dos alunos apresentou opinião positiva em relação ao curso, revelando índice de alta aprovação. A análise da FMP apontou alto índice de satisfação motivacional com o programa, por parte dos alunos, considerando-o impressionante. No questionário CSP, as professoras atribuíram alta importância para o repertório de habilidades sociais, enquanto possível fator, tanto do desenvolvimento socioemocional dos alunos, como do desempenho. Concluiu-se que a implementação do programa visando a promoção da saúde auditiva e a inclusão do deficiente auditivo com malformação de orelha externa e/ou média, no âmbito escolar, foi viável para os participantes, porém sugere-se reaplicação a outros escolares. / The ear malformations are abnormalities that occur during embryonic development and can affect the outer ear, middle and/or internal, may be unilateral or bilateral. At school age children with ear malformations may be impaired by lack of appropriate incentives to its potential cognitive, socio-emotional, linguistic, political and cultural, causing considerable damage in the development of learning. In this context, this study aimed to develop a program for elementary school students using the interactive tele-education Project Young Doctor aiming to promote hearing health and the inclusion of deaf ear malformation with external and / or middle ear in the school. The study was divided into two phases. The first phase was formed by the construction of an educational content (screenplay), evaluation by judges from the area of Audiologist, through two questionnaires and adequacy in accordance with the suggestions of the judges. The second phase consisted of applying content to 18 students without craniofacial malformations, hearing impairment, visual or intellectual, using the methodology of the project and Dr. Young was divided into: classroom activity informing the dynamics of the course and introduction to the subject; step without attending, online presentation of the script and stage presence to establish strategies to pass content to colleagues and community. Before and after the implementation of the training program the students responded to the \"Questionário Situação Problema - (QSP)\" with the objective of measuring the theoretical knowledge acquired prior and during the program. And then the other two called \"Questionário Opinião (QO)\" with the aim of expressing student opinion about the distance course and \"Ficha de Pesquisa Motivacional (FMP)\" to subjectively evaluate the motivational aspects of the training program. Teachers also evaluated whether there were changes in student behavior through the \"Crenças e Sentimentos do Professor (CSP).\" The results show that most of the judges had positive assessments, considering the quality of the script as \"excellent\" (1789 responses) and \"very good\" (911 responses). Regarding the QSP results indicate that, comparing statistically the before (pretest) and after (post-test) results showed that half of respondents agreed and 40% in the pre-test and half to hit 80% in post-test. Thus, the data presented show that the implementation of the program has produced positive effect in relation to the increased knowledge of the students. In response to QO, most students showed a positive opinion about the course, revealing high approval rate. The analysis of FMP pointed motivational high level of satisfaction with the program, by the students, considering it as \"impressive\". In the questionnaire CSP teachers assigned high importance to the repertoire of social skills as much as possible factor in socio-emotional development of students as performance. It was concluded that the implementation of the program aimed at promoting hearing health and the inclusion of deaf ear malformation with external and / or average in the school was viable for those students, but it is suggested reapplying to other schools.

<p>The present study was conducted in order to assess a role of the SH2 domain-containing adapter protein SHB in development and cell differentiation.</p><p>Embryonic stem (ES) cells overexpressing SHB and SHB with an inactive SH2 domain (R522K-SHB) were obtained. Microarray analysis in the SHB clone revealed altered expression of genes connected with neural cell function. The R522K-SHB clone exhibited altered expression of several transcription factors related to development. ES cells were differentiated by forming aggregates named embryoid bodies (EBs). The morphology of EBs was altered in the R522K-SHB clones, which showed fewer cavities. Expression of endodermal markers was decreased in the R522K-SHB EBs. </p><p>To further investigate the role of SHB in differentiation, murine ES cell lines deficient for one (SHB+/-) or both SHB alleles (SHB-/-) were generated. SHB deficient clones increased the expression of mesendodermal and endodermal markers and decreased expression of two receptors, VEGFR2 and FGFR1, connected with blood vessel differentiation. Similarly, blood vessels showed an altered morphology in SHB+/- and SHB-/- EBs after VEGF stimulation. SHB-/- ES cells also formed fewer blood colonies than control ES cells.</p><p>Finally, the role of the SHB adapter protein in vivo was analyzed by generating a SHB deficient mouse (SHB-/-). SHB-/- animals are viable, fertile, but suffer from leukopenia and anemia. SHB-/- animals demonstrate an abnormal morphology of blood vessels in the liver and kidney. Breeding of SHB+/- animals revealed an abnormal segregation of the mutant allele with an increased number of SHB+/- animals and a decreased number of SHB-/- and SHB+/+animals. Backcross analysis of SHB+/- females with SHB+/+ males displayed an increased number of SHB+/- offspring already at the blastocyst level. Simultaneously, embryos from SHB+/- mothers show an increased malformation rate in comparison to embryos from SHB+/+ mothers.</p><p>In summary, the study suggests a role of SHB in reproduction and development and in mesodermal and endodermal specification. </p>

<p>Chromosomal abnormalities are defined as changes in the chromosome structure and fall in one of two categories. The first category is numerical alterations while the second category consists of structural abnormalities. Structural chromosomal abnormalities do not always interrupt genes in order to cause disease. They can also affect gene expression by separating a gene and its promoter element from distant regulatory elements. We have used characterisation of structural chromosomal abnormalities to identify the genetic bases for several congenital disorders.</p><p>In papers I-III, we have applied molecular characterisation of chromosomal translocations in order to identify candidate genes involved in mental retardation, hypospadias and anal malformation and premature ovarian failure. In paper I, we localised the chromosome X translocation breakpoint in a t(X;15) to be in the immediate proximity of the gene <i>ZDHHC15 </i>in a patient with severe mental retardation. Subsequent experiments revealed loss of <i>ZDHHC15</i> transcription in the patient which suggests this gene to be involved in the aetiology of the patient’s phenotype. In paper II, we show that a balanced translocation between chromosomes 6 and 17 in a patient with urogential malformation disrupts 2 genes, one at each translocation breakpoint. We also identified a fusion-gene as a result of the translocation. Our hypethesis is that the translocation together with its molecular consequences is important for the phenotype in the patient. Similarly, in paper III, we have used molecular characterisation of the breakpoints in a balanced translocation between chromosomes X and 11 in order to localise candidate genes in ovarian function. Our results indicate a number of genes affected by the translocation. In paper IV, we have used array-based comparative genomic hybridisation (array-CGH) in order to investigate a cohort of autistic sib-pairs for submicroscopic chromosomal alterations. We have identified several novel duplications and one novel deletion with strong association with autism.</p>

The present study was conducted in order to assess a role of the SH2 domain-containing adapter protein SHB in development and cell differentiation. Embryonic stem (ES) cells overexpressing SHB and SHB with an inactive SH2 domain (R522K-SHB) were obtained. Microarray analysis in the SHB clone revealed altered expression of genes connected with neural cell function. The R522K-SHB clone exhibited altered expression of several transcription factors related to development. ES cells were differentiated by forming aggregates named embryoid bodies (EBs). The morphology of EBs was altered in the R522K-SHB clones, which showed fewer cavities. Expression of endodermal markers was decreased in the R522K-SHB EBs. To further investigate the role of SHB in differentiation, murine ES cell lines deficient for one (SHB+/-) or both SHB alleles (SHB-/-) were generated. SHB deficient clones increased the expression of mesendodermal and endodermal markers and decreased expression of two receptors, VEGFR2 and FGFR1, connected with blood vessel differentiation. Similarly, blood vessels showed an altered morphology in SHB+/- and SHB-/- EBs after VEGF stimulation. SHB-/- ES cells also formed fewer blood colonies than control ES cells. Finally, the role of the SHB adapter protein in vivo was analyzed by generating a SHB deficient mouse (SHB-/-). SHB-/- animals are viable, fertile, but suffer from leukopenia and anemia. SHB-/- animals demonstrate an abnormal morphology of blood vessels in the liver and kidney. Breeding of SHB+/- animals revealed an abnormal segregation of the mutant allele with an increased number of SHB+/- animals and a decreased number of SHB-/- and SHB+/+animals. Backcross analysis of SHB+/- females with SHB+/+ males displayed an increased number of SHB+/- offspring already at the blastocyst level. Simultaneously, embryos from SHB+/- mothers show an increased malformation rate in comparison to embryos from SHB+/+ mothers. In summary, the study suggests a role of SHB in reproduction and development and in mesodermal and endodermal specification.

Chromosomal abnormalities are defined as changes in the chromosome structure and fall in one of two categories. The first category is numerical alterations while the second category consists of structural abnormalities. Structural chromosomal abnormalities do not always interrupt genes in order to cause disease. They can also affect gene expression by separating a gene and its promoter element from distant regulatory elements. We have used characterisation of structural chromosomal abnormalities to identify the genetic bases for several congenital disorders. In papers I-III, we have applied molecular characterisation of chromosomal translocations in order to identify candidate genes involved in mental retardation, hypospadias and anal malformation and premature ovarian failure. In paper I, we localised the chromosome X translocation breakpoint in a t(X;15) to be in the immediate proximity of the gene ZDHHC15 in a patient with severe mental retardation. Subsequent experiments revealed loss of ZDHHC15 transcription in the patient which suggests this gene to be involved in the aetiology of the patient’s phenotype. In paper II, we show that a balanced translocation between chromosomes 6 and 17 in a patient with urogential malformation disrupts 2 genes, one at each translocation breakpoint. We also identified a fusion-gene as a result of the translocation. Our hypethesis is that the translocation together with its molecular consequences is important for the phenotype in the patient. Similarly, in paper III, we have used molecular characterisation of the breakpoints in a balanced translocation between chromosomes X and 11 in order to localise candidate genes in ovarian function. Our results indicate a number of genes affected by the translocation. In paper IV, we have used array-based comparative genomic hybridisation (array-CGH) in order to investigate a cohort of autistic sib-pairs for submicroscopic chromosomal alterations. We have identified several novel duplications and one novel deletion with strong association with autism.

Thèse d'exercice : Médecine. Médecine générale : Paris 12 : 2006. / Titre provenant de l'écran-titre. Bibliogr. f. 60-61.

Nagrinėjami sistemos sprendiniai, kai eilės išsigimimas reguliarus (p=0) ir pirmasis sistemos koeficientų dėstinio laipsnine eilute narys nepriklauso nuo kintamųjų y ir z, reiškiami laipsnine x laipsnių eilute.Nereguliaraus arba stipraus išsigimimo atveju formalūs sprendiniai laipsninėmis eilutėmis neegzistuoja.Čia sukonstruotos nagrinėjamos sistemos atskirųjų sprendinių šeimos priklauso nuo laisvai parenkamos kintamųjų y ir z funkcijos, t.y. ta funkcija priklauso nuo kintamųjų, pagal kuriuos nėra jokio išsigimimo. Paprastųjų diferencialinių lygčių teorijoje sprendiniai yra vienparametrinės kreivių šeimos.Visais atvejais sukonstruotos apskritai 4 (4 pirmos eilės dalinių išvestinių diferencialinių lygčių sistema) atskirųjų sprendinių šeimos. / Under consideration solutions of the system, when the malformation of the system’s queue is regular and first member of the system’s coefficients power queue opt out variable y and z, stands for power x power queue.Under consideration here was designed discrete’s solutions families of the system without restraint selecting variables y and z function, i.e., that function depends from variables whereby none malformation. In theory of the regular differentials equations the solutions are family’s of one-parameter curve’s.Generally, in all senses there are designed 4 (4 partial’s derived diferencials equations of the first queue’s system) families of the discrete solutions.

In this master thesis it is analyzed the system of four partial fluxions of the primary row of differential equations the row of which dwindles at the point of p+1, when p = 0. The system of partial fluxions of differential equations has been solved through the modified technique of summarized degree rows. Two cases were explored: general and when the system’s ratios initial matrix is a special structure matrix. The solutions of the system dependence on the ratios, which are near partial fluxions of the searched function, were explored. There were designed four families of the detached solutions and proved that each of them depends on one optional function of y and z variables. The structure of system of solutions at the malformation points depends not only on x degree, but also on y and z variables. There is no such type of malformation in the theory of dwindle simple differential equations, therefore this analyzed dwindle of the system of partial fluxion of differential equations is called quasi-regular malformation. Keywords: differential equation, partial derivation, quasi-regular malformation.

O presente estudo teve como objetivo investigar o processo de transição para a parentalidade no contexto de cardiopatia congênita do bebê. Participaram do estudo quatro casais, pais de crianças que nasceram com malformação cardíaca, que estavam acompanhando seus filhos durante a internação em Unidade de Tratamento Intensivo. Foi utilizado delineamento de estudo de casos coletivo e a coleta de dados foi feita através de uma entrevista individual com a mãe e com o pai sobre os primeiros momentos após o nascimento do bebê com malformação e a experiência da maternidade e da paternidade, respectivamente. Os dados foram analisados segundo os pressupostos da análise de conteúdo qualitativa. Os resultados do estudo indicaram que a notícia da malformação cardíaca do bebê interfere no processo de parentalização de maneira profunda. Destacou-se a intensa preocupação das mães com a sobrevivência dos bebês, evidenciada através de uma dedicação exclusiva a eles. Já os pais demonstram-se muito envolvidos com seus filhos, assumindo também a tarefa de proteger as mães. / The present study aimed to investigate the transition process to parenthood in the context of congenital heart disease. Four couples, whose children were born with heart malformation, took part in the study. They all stayed with their children when they were in an Intensive Care Unit. A collective-case study design was used and data were collected through an individual interview with mothers and fathers on the first moments after giving birth to a child with malformation, and the experience of motherhood and fatherhood, respectively, in the context of heart malformation. Data were analyzed through qualitative content analysis. The results indicated that the diagnosis of heart malformation interferes in the parentalization process in a very intense way. Mothers were extremely concerned about the infant's survival and very dedicated to him/her. Besides being very involved, fathers also assumed the task of protecting mothers.

Resumo: Diante do diagnóstico pré-natal da malformação, cabe à equipe de saúde individualizar cada situação e apresentar dados de fácil compreensão. Faltam estudos na literatura que apresentem a imagem fotográfica como instrumento na abordagem pré-natal de casais com filhos malformados; estes aspectos nos motivaram a descrever o papel da informação visual ou fotográfica, na consulta pré-natal a gestantes de fetos portadores de malformações aparentes. Conhecer o efeito da informação visual na assistência pré-natal de gestantes com fetos portadores de malformações. Sujeitos e Métodos Estudo descritivo com amostra de conveniência de todas as gestantes (12) atendidas no ambulatório de Medicina Fetal, Hospital das Clínicas de Botucatu - UNESP, no período de dezembro de 2005 a maio de 2007, selecionadas a partir do diagnóstico pré-natal de meningomielocele, onfalocele e gastrosquise. Apresentado um álbum de fotografias, aplicado uma entrevista/questionário no prénatal e a outra no pós-parto; sendo a entrevista/questionário estruturada para este estudo avaliando a compreensão da malformação e apego mãe e filho; já a ansiedade materna foi analisada com o Inventário de Ansiedade Traço-Estado - IDATE. Durante o pré-natal todas gestantes sabiam explicar o diagnóstico de seu bebê e os procedimentos que seriam realizados após o nascimento. Quase todas as gestantes relataram manifestações de afeto e providenciaram os preparativos para chegada de seu bebê. Na maioria das gestantes o processo de apego mãe e filho foi mantido após a descoberta da malformação; apenas duas gestantes referiram mudança no seu comportamento, mas não desfizeram todo apego e vínculo no pré-natal. No pré-natal todas as gestantes declararam ter gostado de ver o álbum de fotografia sendo que o mesmo ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Following the diagnosis of prenatal malformation, caregivers should provide individualized support, as well as easily understandable information. Few are the studies in the literature showing the use of photographic images when couples with a malformed fetus are approached before birth. Thus, the role of visual or photographic information in the prenatal counseling of women with an apparently malformed fetus was investigated. To assess the effect of visual information during the prenatal counseling of women with a malformed fetus. Subjects and Methods This descriptive study used a convenience sample consisting of all pregnant women (12) seen at the Fetal Medicine Outpatient Clinic of Botucatu Medical School Hospital- São Paulo State University/UNESP, between December 2005 and May 2007. Selection was based on a prenatal diagnosis of meningomyelocele, omphalocele and gastrochisis. A photo album was used and an interview/questionnaire was administered both preand post-partum. The interview/questionnaire was structured for this study and assessed understanding of the malformation and mother-child attachment. Maternal anxiety was evaluated by the State-Trait Anxiety Inventory - STAI. Results and Discussions During the prenatal period, all pregnant women were able to explain their babies' diagnoses and the post-partum procedures that would be performed. Nearly all subjects reported affection manifestations and prepared for their baby's arrival. In most cases, the mother-child attachment process was kept. Only two women reported behavior change to worse, though attachment and prenatal bonds were not completely broken. During the prenatal period, all women reported liking to see the photo album as it helped them to understand, provided tranquility, carried distorted images away, brought them back to reality, and helped them to prepare for delivery. After birth, the acceptance of the album was reinforced by the subjects. / Orientador: Iracema de Matos Paranhos Calderon / Coorientador: Marcos Condonni / Coorientador: Gimol Benzaquen Perosa / Banca: Maria Yolanda Makuch / Banca: Saskia Maria Wiegerinck Fekete / Mestre