O Ferro (Fe) atua em vários processos metabólicos, principalmente do neurodesenvolvimento, cujo conteúdo corporal é ainda de difícil determinação, podendo sofrer influência de fatores como a prematuridade e o Crescimento Intrauterino Restrito (CIUR). Este estudo objetivou descrever a evolução hematológica e do conteúdo de Fe em Recém-Nascidos (RN) de Termo (T) e Pré-Termo Tardios (PT T), com e sem CIUR, em aleitamento materno exclusivo, durante os primeiros dois meses de vida, analisando a influência da prematuridade, presença de CIUR e evolução nutricional. Incluiu-se 95 RN: Grupo 1A, 25 RN PT T sem CIUR; Grupo 1B, 24 RN PT T com CIUR; Grupo 2A, 21 RN T sem CIUR e Grupo 2B, 25 RN T com CIUR. A presença de CIUR foi determinada pelo peso nascimento <P5 para a curva de Alexander. Determinou-se ao nascimento, com um e dois meses de idade: medidas antropométricas (peso, comprimento e perímetro cefálico) e Índice de Massa Corporal (IMC), Hemoglobina (Hb), Hematócrito (Ht), Reticulócitos (Ret), Volume Corpuscular Médio (VCM), Hemoglobina Corpuscular Média (HCM), Variação da Distribuição das Células Vermelhas (RDW), Capacidade de Ligação do Fe (CLFe), Saturação de Transferrina (SatTf), Fe sérico e Ferritina. As análises estatísticas basearam-se: Teste não paramétrico de Kolmogorov-Smirnov para testar normalidade. ANOVA One-Way ou Kruskall-Wallis para a análise das variáveis contínuas; Teste Exato de Fischer ou Qui-quadrado para comparação de proporções; Coeficiente de Pearson para análise de correlações. Odds Ratio e respectivos 95% Intervalos de Confiança para avaliação do risco de anemia. Significância de 5%. As medidas antropométricas e IMC evoluíram com aumento ao longo do tempo (p<0,001). Os valores hematológicos reduziramse ao longo do tempo (p<0,001). A Hb foi maior nos grupos com CIUR ao nascimento e no T sem CIUR com dois meses (p<0,001). A variação relativa da Hb entre dois meses e nascimento foi maior no PT T com CIUR e menor no T sem CIUR (p<0,001). As reservas de Fe modificaram-se em todos os grupos. A CLFe foi maior no T sem CIUR ao nascimento (p<0,001) e com um mês vida (p=0,008). O Fe foi maior no T sem CIUR ao nascimento (p<0,001) e menor no PT T com CIUR que os grupos RN T com um mês de vida (p=0,007). A ferritina não apresentou diferenças entre os grupos. A Resumo _____________________________________________________________________________________________ xxxii SatTf foi maior no T sem CIUR ao nascimento (p<0,001) e a variação relativa da SatTf superior no PT T com CIUR (p=0,001). A Hb correlacionouse com o peso em todos os grupos (p<0,001) e a Ferritina nos PT T sem CIUR (r=-0,3250; p=0,0068) e com CIUR (r=-0,3280; p=0,0063). A anemia foi mais frequente nos grupos com CIUR (90,5% PT T com CIUR e 90% T com CIUR), sendo maior entre os RN de T com CIUR em relação aos sem CIUR (OR=16,500; p=0,0013) e nos PT T com CIUR em relação aos T sem CIUR (OR=17,417; p=0,0005). Provavelmente, as diferentes evoluções das reservas de Fe e a maior redução da hemoglobina no PT T com CIUR deveram-se à influência da prematuridade e do CIUR sobre seu crescimento. O CIUR parece ser o fator mais importante no desenvolvimento de anemia em RN em aleitamento materno exclusivo, pois somente os grupos com CIUR apresentaram risco de anemia aos dois meses de idade / Iron (Fe) acts in several metabolic processes, especially neurodevelopmental ones, which body content is still the difficult access and could be influenced by factors, such as, prematurity and Intrauterine Growth Restriction (IUGR). This study aimed at describing the hematological evolution and iron body content in Term (T) and Late Pre-Term (LPT) Newborns (NB), with and without IUGR, exclusive breastfeeding, during the first two months of life, and analyzing the prematurity influence, UGR presence and nutritional evolution. 95 NB were included: Group 1A, 25 LPTNB without IUGR, Group 1B, 24 LPTNB with IUGR, Group 2A, 21 TNB without IUGR and Group 2B, 25 TNB with IUGR. The presence of IUGR was determined by birth weight <P5 of Alexander Curve. At birth, one and two months of age were determined: anthropometric measures (weight, length, cephalic circumference) and Body Mass Index (BMI), Hemoglobin (Hb), Hematocrit (Ht), Reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, red blood cells distribution width, serum Fe, ferritin, Iron Binding Capacity (IBC) and Transferrin Saturation (TfSat). Statistical analysis was based on: Kolmogorov-Smirnov Test was used to verify normality. ANOVA One-Way or Kruskal-Wallis Test for continuous variables analysis, Fisher\'s Exact Test or Chi-Square Test for Comparison of proportions, Pearson Coefficient for correlations analysis, Odds Ratio and 95% Confidence Intervals for evaluation of anemia risk, Multiple Regression Stepwise Backward and Binary Logistic Regression for risk factors of Hb and anemia analysis at two months. Significance was set at 5%. The anthropometric measures and BMI increased along the time (p<0.001) and the hematological values decreased (p<0.001). The Hb was higher in groups with IUGR at birth and in T without IUGR at 2 months (p<0.001). The relative variation between 2 months and birth was higher in LPT with IUGR and lower in T without IUGR (p<0.001). The iron stores were modified in all the groups along the time. The IBC was higher in T without IUGR at birth (p<0,001) and 1 month of life (p=0.008). The serum iron was higher in T without IUGR at birth (p<0.001) and lower in LPT with IUGR than in the T NB groups at 1 month at life (p=0.007). Ferritin levels did not differ among the groups. The TfSat levels were higher in T without IUGR at birth (p<0.001) and the relative variation of TfSat was higher in LPT with IUGR (p=0.001). The Hb correlated with weight in all the groups (p<0.001) and the Ferritin in LPT without IUGR (r=-0.3250; p=0.0068) and with IUGR (r=-0.3280; p=0.0063). The anemia was more frequent in IUGR groups (90.5% in LPT with IUGR and 90% in T with IUGR). The anemia risk was hugher in T with IUGR than in without IUGR (OR=12.37, p=0.0022) and in LPT with IUGR in relation to T without IUGR (OR=13.06, p=0.0019). The different evolutions of the iron stores and the higher reduction of Hb in LPT with IUGR could be an effect of prematurity and IUGR influence on their growth. The IUGR must be the most important anemia development factor in exclusive breastfeeding NB, because only groups with IUGR showed risk for anemia at two months of age

Submitted by CARLA MARIA GOULART DE MORAES (carlagm) on 2015-05-08T19:30:30Z No. of bitstreams: 1 CassianoRicardoHaagLinguisticaAplicada.pdf: 994930 bytes, checksum: 72ebaccc09263b8d0686b5d392e30087 (MD5) / Made available in DSpace on 2015-05-08T19:30:30Z (GMT). No. of bitstreams: 1 CassianoRicardoHaagLinguisticaAplicada.pdf: 994930 bytes, checksum: 72ebaccc09263b8d0686b5d392e30087 (MD5) Previous issue date: 2011-03-23 / Nenhuma / A deficiência mental é, como qualquer outro conceito da ciência, um trabalho social, histórico e discursivo. Esse conceito tem se transformado, portanto, e pesquisadores têm buscado respostas para como enfrentar essa condição de forma que as pessoas envolvidas tenham, cada vez mais, melhor qualidade de vida. Por mais que o conceito se transforme, todavia, nunca deixou de estar baseado na ideia de limitação intelectual, e , nesta pesquisa, se acredita que esse é um ponto nevrálgico do problema. A pesquisa tem caráter empírico e investiga as manifestações de linguagem de um indivíduo com esse diagnóstico, durante uma atividade lúdica, problematizando a hipótese de limitação, restrição ou deficiência para explicar o desenvolvimento. O corpus se constitui de gravações em vídeo realizadas em uma escola da rede municipal de uma cidade do Vale do Paranhana-RS. Para a análise dos resultados, dialoga-se com a visão de desenvolvimento e de aprendizagem propostas por Vygotsky (1989; 2001) relacionadas aos conceitos de auto-organização e de caos (JOHNSON, 2003). A partir do quadro epistemológico do interacionismo sociodiscursivo (BRONCKART, 1999; 2006b), no campo da linguagem, é explorada uma noção de construção de sentidos, composta por quatro atividades complementares e inseparáveis, a saber, a referência, a co-construção da memória, a produção de hipóteses e a antecipação de situações. Essas quatro atividades são estudadas do ponto de vista linguístico e parecem ser suficientes para problematizar a ideia de limitação de inteligência. Os resultados permitem verificar uma instabilidade cognitiva que é não somente manifestada na atividade de linguagem, como também por ela produzida de forma coletiva. / Mental retardation is, like any other concept in science, a social historical and discursive work. This concept, thus, has been changing, and researchers have sought answers to how to deal with this condition so that the people involved can have better quality of life. As much as the concept changes, however, it has never ceased to be based on the idea of intellectual limitations, and in this research, we believe that this is a crucial aspect of the problem. The research is empirical and investigates the language manifestations of an individual with this diagnosis during a play activity, discussing the hypothesis of limitation, restriction or disability to explain the development. The corpus is constituted of video recordings made at a public school in a city of Vale do Paranhana-RS. For the analysis of results, we dialogue with the view of development and learning proposed by Vygotsky (1989, 2001) related to the concepts of self-organization and chaos (Johnson, 2003). From the epistemological framework of Sociodiscursive interactionism (BRONCKART, 1999, 2006b) in the of language area, we explore a notion of meaning construction, comprised of four inseparable and complementary activities, namely, reference, co-construction of memory, production of hypotheses and anticipation of situations. These four activities are studied from the linguistic point of view and they seem to be sufficient to discuss the idea of intelligence limitation. The results allowed the verification of a cognitive instability which is manifested not only in language activity but also produced collectively by it.

Estudamos 32 crianças com HC devido à agenesia ou ectopia tireoideana para mutações no PAX8 e 30 crianças com hipoplasia da tireóide para mutações no rTSH. Todos os exons de ambos os genes foram amplificados a partir do DNA genômico, seguido por seqüenciamento direto. Encontramos, em dois pacientes com ectopia, duas alterações no gene PAX8, uma no promotor, e outra no exon um. Os outros indivíduos estudados apresentaram as seqüências codificáveis dos genes PAX8 e rTSH normais. Em relação ao caráter funcional e ensaios de luciferase verificamos que no promotor a resposta transcricional diminuiu significativamente na presença de TSH, por um mecanismo dependente de cAMP / We studied 32 children with hypothyrodism (CH) from thyroid agenesis or ectopia for PAX8 mutations, and 30 children with thyroid hypoplasia for rTSH mutations. All exons of both genes were amplified from the genomic DNA, then sequenced directly. We found two alterations in the PAX8 gene in two patients, one in the promoter and the other in exon one. The other children had normal sequences in both PAX8 and rTSH genes. In relation to functional character and luciferase assays, we verified that transcriptional response was significantly reduced in the presence of TSH by a cAMP dependant mechanism

Orientadores: Ricardo Barini, Lourenço Sbragia Neto / Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-27T12:29:22Z (GMT). No. of bitstreams: 1 Bueno_MarciaPereira_D.pdf: 2898828 bytes, checksum: 2c6dcaa4a20ec185bea4b47114c30a0e (MD5) Previous issue date: 2010 / Resumo: A restrição do crescimento intrauterino (RCIU) limita o desenvolvimento fetal adequado aumentando a morbidade e mortalidades perinatais. Os mecanismos fetais adaptativos na RCIU podem desencadear alterações endócrinas e metabólicas que explicariam a ocorrência de doenças na idade adulta. O objetivo do estudo foi avaliar na RCIU experimental pela ligadura da artéria uterina se existem alterações na morfometria e histologia do fígado, intesti no e rins e se existem diferenças na expressão dos receptores de insulina, IR-(3, IRS-1, IRS-2, IGF-IR(3 no grupo de fetos submetidos à RCIU. O presente experimento foi submetido ao Comitê de Ética e Experimentação Animal da Universidade Estadual de Campinas (CEEA-UNICAMP) e aprovado como projeto de pesquisa N° 1644-1. Para realização do estudo utilizamos fetos de ratas Sprague Dawley divididos em 3 grupos. Grupo I (RCIU) - 40 fetos submetidos à ligadura da artéria uterina unilateral com 18,5 dias de gestação, Grupo II (Controle-RCIU) - 40 fetos do corno oposto ao da ligadura da artéria uterina e Grupo III (Controle Externo) - 40 fetos sem procedimento cirúrgico ou alimentar. Os resultados mostraram no modelo experimental de RCIU uma diminuição do peso corporal (PC), hepático (PH) e intestinal (PI) (p<0,01) no grupo RCIU, as relações entre PH/PC, PI/PC, PR/PC foram mantidas, fetos RC IU tem diminuição das camadas submucosas e mucosas intestinais (p<0,05); diminuição da camada cortical renal e do número de glomérulos, com aumento do volume glomerular (p<0,05). Na RCIU encontramos menor expressão hepática do IR-(3, IRS-1 e IRS-2, menor expressão do IRS-2 no intestino e rins e maior expressão do IGF-IR(3 em todos os tecidos. O modelo experimental estudado causou uma RCIU simétrica com alterações morfométricas e do metabolismo da glicose que poderiam justificar no futuro um maior risco de doenças metabólicas / Abstract: Intrauterine growth restriction (IUGR) limits appropriate fetal development increasing morbidity and perinatal mortality. Adaptive mechanisms in fetal IUGR may leave to endocrine and metabolic alterations that could explain the occurrence of diseases in adulthood. The aim of this study was to evaluate whether experimental IUGR by uterine artery ligation causes changes in morphology and histology of the liver, intestines and kidneys. We also evaluated if there were differences in the expression of insulin receptors, IR-(3, IRS-1, IRS-2, IGF-IR(3 of fetuses subjected to IUGR. This experiment was submitted to the Ethics and Animal Experimentation of the Campinas State University (UNICAMP CEEA) and was approved as a research project No. 1644-1. The study used fetuses Sprague-Dawley rats divided into 3 groups. Group I (IUGR) - 40 fetuses who underwent uterine artery ligation sided with 18.5 days of pregnancy Group II (Control-IUGR) - 40 fetuses of the horn opposite to the uterine artery ligation, and Group III (External Control) - 40 fetuses without surgery or food The results showed the experimental model of IUGR, a reduction in body weight (BW), liver (PH) and intestine (PI) (p <0.01) in IUGR, the relationship between PH/PC, PI/PC, PR/PC have been retai ned, IUGR fetuses have reduced layers of the intestinal mucosa and submucosa (p<0,05), decreased renal cortical layer and the glomerular number and increased volume rate (p<0,05). In IUGR found lower hepatic expression of IR-(3, IRS-1 and IRS-2, reduced expression of IRS-2 in the intestine and kidney and increased expression of IGF-IR(3 in all tissues. The experimental model studied caused a symmetrical IUGR with histological changes and glucose metabolism that could justify a greater risk of metabolic diseasesin the future / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

O Ferro (Fe) atua em vários processos metabólicos, principalmente do neurodesenvolvimento, cujo conteúdo corporal é ainda de difícil determinação, podendo sofrer influência de fatores como a prematuridade e o Crescimento Intrauterino Restrito (CIUR). Este estudo objetivou descrever a evolução hematológica e do conteúdo de Fe em Recém-Nascidos (RN) de Termo (T) e Pré-Termo Tardios (PT T), com e sem CIUR, em aleitamento materno exclusivo, durante os primeiros dois meses de vida, analisando a influência da prematuridade, presença de CIUR e evolução nutricional. Incluiu-se 95 RN: Grupo 1A, 25 RN PT T sem CIUR; Grupo 1B, 24 RN PT T com CIUR; Grupo 2A, 21 RN T sem CIUR e Grupo 2B, 25 RN T com CIUR. A presença de CIUR foi determinada pelo peso nascimento <P5 para a curva de Alexander. Determinou-se ao nascimento, com um e dois meses de idade: medidas antropométricas (peso, comprimento e perímetro cefálico) e Índice de Massa Corporal (IMC), Hemoglobina (Hb), Hematócrito (Ht), Reticulócitos (Ret), Volume Corpuscular Médio (VCM), Hemoglobina Corpuscular Média (HCM), Variação da Distribuição das Células Vermelhas (RDW), Capacidade de Ligação do Fe (CLFe), Saturação de Transferrina (SatTf), Fe sérico e Ferritina. As análises estatísticas basearam-se: Teste não paramétrico de Kolmogorov-Smirnov para testar normalidade. ANOVA One-Way ou Kruskall-Wallis para a análise das variáveis contínuas; Teste Exato de Fischer ou Qui-quadrado para comparação de proporções; Coeficiente de Pearson para análise de correlações. Odds Ratio e respectivos 95% Intervalos de Confiança para avaliação do risco de anemia. Significância de 5%. As medidas antropométricas e IMC evoluíram com aumento ao longo do tempo (p<0,001). Os valores hematológicos reduziramse ao longo do tempo (p<0,001). A Hb foi maior nos grupos com CIUR ao nascimento e no T sem CIUR com dois meses (p<0,001). A variação relativa da Hb entre dois meses e nascimento foi maior no PT T com CIUR e menor no T sem CIUR (p<0,001). As reservas de Fe modificaram-se em todos os grupos. A CLFe foi maior no T sem CIUR ao nascimento (p<0,001) e com um mês vida (p=0,008). O Fe foi maior no T sem CIUR ao nascimento (p<0,001) e menor no PT T com CIUR que os grupos RN T com um mês de vida (p=0,007). A ferritina não apresentou diferenças entre os grupos. A Resumo _____________________________________________________________________________________________ xxxii SatTf foi maior no T sem CIUR ao nascimento (p<0,001) e a variação relativa da SatTf superior no PT T com CIUR (p=0,001). A Hb correlacionouse com o peso em todos os grupos (p<0,001) e a Ferritina nos PT T sem CIUR (r=-0,3250; p=0,0068) e com CIUR (r=-0,3280; p=0,0063). A anemia foi mais frequente nos grupos com CIUR (90,5% PT T com CIUR e 90% T com CIUR), sendo maior entre os RN de T com CIUR em relação aos sem CIUR (OR=16,500; p=0,0013) e nos PT T com CIUR em relação aos T sem CIUR (OR=17,417; p=0,0005). Provavelmente, as diferentes evoluções das reservas de Fe e a maior redução da hemoglobina no PT T com CIUR deveram-se à influência da prematuridade e do CIUR sobre seu crescimento. O CIUR parece ser o fator mais importante no desenvolvimento de anemia em RN em aleitamento materno exclusivo, pois somente os grupos com CIUR apresentaram risco de anemia aos dois meses de idade / Iron (Fe) acts in several metabolic processes, especially neurodevelopmental ones, which body content is still the difficult access and could be influenced by factors, such as, prematurity and Intrauterine Growth Restriction (IUGR). This study aimed at describing the hematological evolution and iron body content in Term (T) and Late Pre-Term (LPT) Newborns (NB), with and without IUGR, exclusive breastfeeding, during the first two months of life, and analyzing the prematurity influence, UGR presence and nutritional evolution. 95 NB were included: Group 1A, 25 LPTNB without IUGR, Group 1B, 24 LPTNB with IUGR, Group 2A, 21 TNB without IUGR and Group 2B, 25 TNB with IUGR. The presence of IUGR was determined by birth weight <P5 of Alexander Curve. At birth, one and two months of age were determined: anthropometric measures (weight, length, cephalic circumference) and Body Mass Index (BMI), Hemoglobin (Hb), Hematocrit (Ht), Reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, red blood cells distribution width, serum Fe, ferritin, Iron Binding Capacity (IBC) and Transferrin Saturation (TfSat). Statistical analysis was based on: Kolmogorov-Smirnov Test was used to verify normality. ANOVA One-Way or Kruskal-Wallis Test for continuous variables analysis, Fisher\'s Exact Test or Chi-Square Test for Comparison of proportions, Pearson Coefficient for correlations analysis, Odds Ratio and 95% Confidence Intervals for evaluation of anemia risk, Multiple Regression Stepwise Backward and Binary Logistic Regression for risk factors of Hb and anemia analysis at two months. Significance was set at 5%. The anthropometric measures and BMI increased along the time (p<0.001) and the hematological values decreased (p<0.001). The Hb was higher in groups with IUGR at birth and in T without IUGR at 2 months (p<0.001). The relative variation between 2 months and birth was higher in LPT with IUGR and lower in T without IUGR (p<0.001). The iron stores were modified in all the groups along the time. The IBC was higher in T without IUGR at birth (p<0,001) and 1 month of life (p=0.008). The serum iron was higher in T without IUGR at birth (p<0.001) and lower in LPT with IUGR than in the T NB groups at 1 month at life (p=0.007). Ferritin levels did not differ among the groups. The TfSat levels were higher in T without IUGR at birth (p<0.001) and the relative variation of TfSat was higher in LPT with IUGR (p=0.001). The Hb correlated with weight in all the groups (p<0.001) and the Ferritin in LPT without IUGR (r=-0.3250; p=0.0068) and with IUGR (r=-0.3280; p=0.0063). The anemia was more frequent in IUGR groups (90.5% in LPT with IUGR and 90% in T with IUGR). The anemia risk was hugher in T with IUGR than in without IUGR (OR=12.37, p=0.0022) and in LPT with IUGR in relation to T without IUGR (OR=13.06, p=0.0019). The different evolutions of the iron stores and the higher reduction of Hb in LPT with IUGR could be an effect of prematurity and IUGR influence on their growth. The IUGR must be the most important anemia development factor in exclusive breastfeeding NB, because only groups with IUGR showed risk for anemia at two months of age

Neste trabalho utilizamos diferentes abordagens para o estudo de genes associados com desenvolvimento e funcionamento do SNC assim como com doenças neurológicas: 1) uma das abordagens consistiu na identificação do alelo associado a uma forma de retardo mental sindrômico com herança recessiva ligada ao cromossomo X, síndrome de Snyder-Robinson, em uma família Brasileira. Utilizando as estratégias de estudo de ligação genética e análise de genes candidatos, identificamos a segunda mutação patogênica no gene SMS (que codifica a enzima espermina sintase) associada à síndrome de Snyder-Robinson. A identificação dessa mutação contribuiu para: delinear e expandir o espectro clínico da síndrome, evidenciar domínios importantes para o funcionamento da proteína espermina sintase, comprovar a importância dessa proteína nos processos cognitivos, e também possibilitar um aconselhamento genético preciso para membros da família; 2) outra abordagem consistiu em analisar (triar mutação) o gene codificador da proteína colibistina (ARHGEF9), a qual está envolvida em sinaptogênese inibitória, em pacientes Brasileiros portadores de hiperecplexia (6 pacientes) e em pacientes portadores de retardo mental associado com epilepsia (22 pacientes). Não identificamos nenhuma alteração patogênica no gene ARHGEF nos 28 pacientes estudados; contudo, o número de pacientes analisados foi muito pequeno. Julgamos que a análise de um número maior de pacientes com essas doenças neurológicas pode vir a revelar novas mutações deletérias em ARHGEF9; 3) a última abordagem consistiu no estudo funcional da proteína colibistina. Com o objetivo de identificar outras proteínas que interagem com a colibistina humana utilizamos o sistema de duplo-híbrido em leveduras e experimentos de co-imunoprecipitação in vitro e in vivo. Identificamos a proteína eIF3-p40 interagindo com a proteína colibistina e também com a proteína gefirina (a qual, por sua vez, também interage com colibistina e está envolvida com funcionamento de sinapses inibitórias). A proteína eIF3-p40 é uma das subunidades do complexo do fator 3 de iniciação de tradução protéica em eucariotos (eIF3). Essas interações ligam as proteínas colibistina e a gefirina à maquinaria de tradução protéica, revelando uma provável nova função dessas proteínas no controle da tradução em sítios pós-sinápticos inibitórios. / In this work we have used different approaches to the study of genes associated with CNS development and function as well as with neurological diseases: 1) one study involved the identification of the allele associated with an X-linked recessive sindromic form of mental retardation, Snyder-Robinson syndrome, in a Brazilian family. Using genetic linkage analysis and candidate gene strategy, we identified the second pathogenic mutation in the SMS gene (that encodes the spermine synthase enzyme) associated with the Snyder-Robinson syndrome. The identification of this mutation contributed to: the delineation and expansion of the clinical spectrum of the syndrome, highlight important domains for spermine synthase protein functioning, demonstrate the importance of this protein in cognitive processes, and also a precise genetic counseling for family members; 2) a second study involved the mutation screening of ARHGEF9, gene encoding the collybistin protein, which is involved in inhibitory synaptogenesis, in Brazilian patients with hyperekplexia (6 patients) and in patients with mental retardation associated with epilepsy (22 patients). We did not identify any pathogenic alteration in the ARHGEF9, gene in the 28 studied patients, but the number of patients analysed was very small. However, the possibility remains that additional mutations in ARHGEF9, may contribute to other cases of hyperekplexia and mental retardation associated with epilepsy; 3) the last study involved the functional analysis of collybistin protein. In order to identify other proteins that interact with human collybistin, we used the yeast two-hybrid system and in vitro e in vivo co-immunoprecipitation experiments. We identified the eIF3-p40 protein as collybistin and gephyrin (another protein involved in the function of inhibitory synapses that also interacts with collybistin) binding partner. The eIF3-p40 protein is one of the subunits of the eukaryotic initiation factor 3 complex (eIF3). These interactions link the collybistin and gephyrin proteins to the protein translation machinery, revealing a putative new role of these proteins in the translation control at inhibitory postsynaptic sites.

Because many individuals with developmental disabilities prefer to be as independent as possible, strategies need to be developed to teach them functional skills. Video prompting is a fairly new technology, in which a person learns to engage in a complex behavior by viewing steps of a task analysis on video. The steps are broken down so that the task is more manageable for the individual. The present study evaluated how many steps needed to be presented in the video model for the learner to acquire a functional skill. Three individuals between the ages of 17 and 29 and diagnosed with mental retardation were selected as participants. The target behaviors were to complete a 10 component laundry skill in a group home setting. Starting with viewing the entire task on video, the task was broken down into halves, then thirds, and so on until the individual performed all steps to criterion. A multiple baseline design was used to show the results of the video prompting procedure. The results showed that one individual learned the task with 5 steps in each video segment, another learned the task with the video broken into 4, 3, and 3 segments, and the final participant did not learn from video. For this participant, a least to most prompting procedure was effective.

Building upon the genuine interest regarding consensus about the learning-process, the pur-pose of this study is to examine special teachers´ and teacher-assistants´ vision regarding their teaching in a Swedish upper secondary school for pupils with learning disabilities, focusing on their own priorities within their profession. Based on my own experiences as a teacher-assistant and a special teacher in the Swedish compulsory school and upper secondary school for pupils with learning disabilities,The ambition is to be able to draw conclusions from the study's focus groups and how the pro-fessionals discuss different concepts that form the basis of the present study. My hope is that this study will provide knowledge about these central concepts which are “foundation, collabora-tion, curriculum, consensus, development, learning, independence, relationships, teaching, knowledge, adaptations and care”.In order to get the special teachers´ and teacher assistants´ views on the teaching and what the focus is in the teaching, the focus groups were divided into two groups, one with special teach-ers and one with teacher assistants. The reason for this was to allow the participants to speak freely and discuss based on their own view of their professions in interaction with others in the same situationFrom the data gathered in this study, one can conclude that special teachers and teacher assis-tants work in a sociocultural perspective where interactions between the different parties are seen as the most important aspect within their teaching. The results also show that the school in question has a good integration between the professions. However, the term consensus has proven difficult to interpret in connection to dealing with the students and may be used as a topic for future studies.

Inorganic contaminants, while transported through the bentonite layer, are chemically adsorbed onto the particle surfaces and exhibit a delay in solute breakthrough in hydraulic barriers. Transport of inorganic leachate contaminants through bentonite occurs by advection, diffusion or a combination of these two mechanisms. During the process of chemical solute transport through low permeability bentonite, the amount of cation exchange on the clay particle surface is directly related to the cation exchange capacity (CEC) of montmorillonite and other mineral constituents. The process of diffusion and advection of various inorganic leachate contaminants through bentonite is thoroughly investigated in this study. Diffusion characteristics are of specific interest as they have a prominent effect on the long term properties of bentonite compared to advection. This is mostly true if the hydraulic conductivity of the material is less than 10-8 cm/s and if the thickness of the barrier is small. Chemical reactions in the form of cationic exchange on the clay particle surfaces has been incorporated in the analysis of the diffusion process. Adsorption-desorption (sorption) reactions of chemical compounds that influence the concentrations of inorganic leachates during transport in bentonite clay have been modeled using the Fick's fundamental diffusion theory. Partition coefficients of the solutes in pore space, which affect the retardation factor of various individual ions of chemical solutions, have been investigated during transient diffusion and advection processes. Several objectives have been accomplished during this research study. An evaluation has been carried out of the hydraulic conductivity of bentonite with respect to single species salts and various combinations of electrolyte solutions. Diffusion properties of inorganic leachates through bentonite have been characterized in terms of apparent and effective diffusion coefficients. Time-dependent behavior of the diffusive ions has been analyzed in order to determine the total retention capacity of bentonite before electrical conductivity breakthrough and steady-state chemical stability are reached. An analytical solution of the attenuation of various inorganic ions concentrations through bentonite has been developed. Finally, recommendations were made for landfill liners exposed to highly concentrated inorganic leachates.

Retard de croissance intra-utérin (RCIU) et prééclampsie (PE) sont des complications majeures de la grossesse humaine et sont le plus souvent due à une insuffisance de vascularisation utéro-placentaire. Notre objectif était d'évaluer l’angiographie Doppler énergie tridimensionnelle (PDA) comme nouvel outil de dépistage de la PE et du RCIU et d’étude de la fonction placentaire et du RCIU sur modèles animaux. La corrélation entre les indices Doppler 3D et l'écoulement de sang réel au sein de l'unité utéro-placentaires a d'abord été évaluée sur modèle de brebis gravide, ainsi que l'impact des réglages de la machine. Un degré de corrélation plus élevé a été observé pour VI et VFI (r = 0,86 et 0,82 respectivement, p <0,0001) que pour FI (r = 0,64, p <0,0001).L'intérêt de la technique a été ensuite démontré dans un modèle de RCIU chez le lapin (femelles traitées par du L-NAME).Troisièmement, la valeur prédictive du PDA comme test de dépistage du RCIU et de la PE a été démontrée par la réalisation d'une étude prospective multicentrique chez 70 femmes enceintes à bas risque (AUC 0,95, 100% VAN avec une spécificité de 85% pour un seuil de 36.784 FI placentaire). / Intra-uterine growth retardation (IUGR) and preeclampsia (PE) are major complications of human pregnancy & are most often due to an insufficient utero-placental vascularization. Our aim was to evaluate the three-dimensional power Doppler angiography (PDA) as a new tool for the screening IUGR & PE & for the study placental function and IUGR in animal models. The correlation between 3D Doppler indices and the real blood flow within the utero-placental unit was first evaluated in the pregnant sheep model, as well as the impact of machine settings. A higher correlation degree was observed for VI and VFI (r = 0.86 and 0.82 respectively p<0.0001) than for FI (r = 0.64; p<0.0001).The interest of the technique was secondly demonstrated in a rabbit IUGR model (females treated with L-NAME).Thirdly, the predictive value of PDA as a screening test for IUGR & PE was demonstrated by conducting a prospective multicentric study in 70 low risk pregnant women (AUC 0.95, 100% NPV with a specificity of 85% for a 36.784 placental FI threshold).