Understanding the specificity of homeobox genes has been hampered by the lack of verified direct transcriptional targets. The Dlx family of homeobox genes is expressed in the ganglionic eminences of the developing forebrain. Dlx1/Dlx2 double knockout (DKO) mice die at birth. Phenotypic analyses demonstrate abnormal development of the basal telencephalon, including defects in neuronal differentiation in the basal ganglia, reduced expression of GABA in the basal telencephalon, and loss of migration of GABAergic inhibitory interneurons to the neocortex. The mechanisms underlying DLX protein regulation of differentiation and migration of GABAergic interneurons are poorly defined. We have successfully applied chromatin immunoprecipitation to identify potential direct transcriptional targets of DLX homeoproteins from embryonic tissues in vivo. Reporter gene assays demonstrated the transcriptional significance of the binding of DLX proteins to different downstream regulatory elements, which were confirmed in vitro by electrophoretic mobility shift assay and site-directed mutagenesis. The functional significance of DLX mediated transcriptional regulation of these targets was further elaborated through several series of loss-of-function assays including gene expression in Dlx1/2 knockout embryonic forebrain tissues, as well as siRNA or Lentiviral mediated shRNA knockdown experiments with primary forebrain cultures. Quantitative analysis of the regulatory effect of Dlx genes on various forebrain markers of differentiation and migration was performed using in situ hybridization, high-performance liquid chromatography coupled with cell counting. Neuronal migration was assessed by forebrain explants and diI labelling of migratory cells from ganglionic eminence to neocortex. We have demonstrated that DLX1 and DLX2 can transcriptionally activate (Gad1, Gad2) or repress (Nrp2) different downstream targets. In the Dlx1/2 DKO, reduction of GABA expression and failure of GABAergic interneurons to migrate to the neocortex is partly due to loss or aberrant expression of these DLX downstream targets. In the triple Dlx1/2; Nrp2KO, partial restoration of tangential migration of GABAergic interneurons from basal ganglia to the neocortex was successfully established signifying the importance of DLX regulation of Semaphorin-Neuropilin signalling during forebrain development.

It is suggested that the lack of progress made towards understanding and preventing, or even in many cases even alleviating, psychological suffering has been due, in large part, to the way in which such suffering is conceptualised – as ‘disorder’, ‘illness’ or ‘disease’ which is located, and is thus potentially locatable, within the individual. This conceptualisation of psychological suffering is referred to in this thesis as the ‘Dysfunctional Mind Account’ (DMA). The DMA, it is argued, underlies all accepted models/theories of psychological suffering and is the dominant way of conceptualising such suffering for both professionals and lay-people in Western cultures. It is further argued that the main reason the DMA is unable to assist in understanding and alleviating psychological suffering is because it is underpinned by assumptions about human beings and their suffering which are inherently flawed. The account presented in this thesis places at its centre an analysis of persons and their experience that attempts to overthrow these assumptions. The resulting reconceptualisation presents a view of psychological suffering as emergent from our continual personal and embodied enmeshment within our social world, rather than as arising primarily out of the various processes occurring ‘within’ us (whether that be our neurochemistry or our ‘mental mechanisms’ or an ‘interaction’ between them). It is essentially suggested that psychological suffering emerges from the same source as all other aspects of our personal being; from the constant coactions between the various aspects of our being in the world – personal, organismic and molecular – with the environment within which we are enmeshed. This means that the feelings/thoughts/behaviours conceptualised as ‘mental disorder’ are as much part of our personal being as any other aspect of us; they are not ‘other’, they are not ‘disease’, ‘illness’ or ‘dysfunction’. Such feelings/thoughts/ behaviours, it is argued, almost always, perhaps inevitably, represent a very adaptive response, at every level of our being, to environmental contingencies. Thus, when understood in its full context, the suffering conceptualised as ‘mental disorder’ can be seen as the very understandable responses of the embodied person to what is happening to them, rather than ‘un-understandable’ dysfunctions, aberrations and pathological processes of the ‘mind’ (or brain).

The RNA-binding protein Quaking (QKI) plays a fundamental role in post-transcriptional gene regulation during mammalian nervous system development. QKI is well known for advancing oligodendroglia differentiation and myelination, however, its functions in astrocytes and embryonic central nervous system (CNS) development remain poorly understood. Uncovering the complete spectrum of QKI molecular and functional repertoire is of additional importance in light of growing evidence linking QKI dysfunction with human disease, including schizophrenia and glioma. This thesis summarizes my contribution to fill this gap of knowledge.         In a first attempt to identify the QKI-mediated molecular pathways in astroglia, we studied the effects of QKI depletion on global gene expression in the human astrocytoma cell line. This work revealed a previously unknown role of QKI in regulating immune-related pathways. In particular, we identified several putative mRNA targets of QKI involved in interferon signaling, with possible implications in innate cellular antiviral defense, as well as tumor suppression. We next extended these investigations to human primary astrocytes, in order to more accurately model normal brain astrocytes. One of the most interesting outcomes of this analysis was that QKI regulates expression of transcripts encoding the Glial Fibrillary Acidic Protein, an intermediate filament protein that mediates diverse biological functions of astrocytes and is implicated in numerous CNS pathologies. We also characterized QKI splice variant composition and subcellular expression of encoded protein isoforms in human astrocytes. Finally, we explored the potential use of zebrafish as a model system to study neurodevelopmental functions of QKI in vivo. Two zebrafish orthologs, qkib and qki2, were identified and found to be widely expressed in the CNS neural progenitor cell domains. Furthermore, we showed that a knockdown of qkib perturbs the development of both neuronal and glial populations, and propose neural progenitor dysfunction as the primary cause of the observed phenotypes.        To conclude, the work presented in this thesis provides the first insight into understanding the functional significance of the human QKI in astroglia, and introduces zebrafish as a novel tool with which to further investigate the importance of this gene in neural development.

Understanding the specificity of homeobox genes has been hampered by the lack of verified direct transcriptional targets. The Dlx family of homeobox genes is expressed in the ganglionic eminences of the developing forebrain. Dlx1/Dlx2 double knockout (DKO) mice die at birth. Phenotypic analyses demonstrate abnormal development of the basal telencephalon, including defects in neuronal differentiation in the basal ganglia, reduced expression of GABA in the basal telencephalon, and loss of migration of GABAergic inhibitory interneurons to the neocortex. The mechanisms underlying DLX protein regulation of differentiation and migration of GABAergic interneurons are poorly defined. We have successfully applied chromatin immunoprecipitation to identify potential direct transcriptional targets of DLX homeoproteins from embryonic tissues in vivo. Reporter gene assays demonstrated the transcriptional significance of the binding of DLX proteins to different downstream regulatory elements, which were confirmed in vitro by electrophoretic mobility shift assay and site-directed mutagenesis. The functional significance of DLX mediated transcriptional regulation of these targets was further elaborated through several series of loss-of-function assays including gene expression in Dlx1/2 knockout embryonic forebrain tissues, as well as siRNA or Lentiviral mediated shRNA knockdown experiments with primary forebrain cultures. Quantitative analysis of the regulatory effect of Dlx genes on various forebrain markers of differentiation and migration was performed using in situ hybridization, high-performance liquid chromatography coupled with cell counting. Neuronal migration was assessed by forebrain explants and diI labelling of migratory cells from ganglionic eminence to neocortex. We have demonstrated that DLX1 and DLX2 can transcriptionally activate (Gad1, Gad2) or repress (Nrp2) different downstream targets. In the Dlx1/2 DKO, reduction of GABA expression and failure of GABAergic interneurons to migrate to the neocortex is partly due to loss or aberrant expression of these DLX downstream targets. In the triple Dlx1/2; Nrp2KO, partial restoration of tangential migration of GABAergic interneurons from basal ganglia to the neocortex was successfully established signifying the importance of DLX regulation of Semaphorin-Neuropilin signalling during forebrain development.

It is suggested that the lack of progress made towards understanding and preventing, or even in many cases even alleviating, psychological suffering has been due, in large part, to the way in which such suffering is conceptualised – as ‘disorder’, ‘illness’ or ‘disease’ which is located, and is thus potentially locatable, within the individual. This conceptualisation of psychological suffering is referred to in this thesis as the ‘Dysfunctional Mind Account’ (DMA). The DMA, it is argued, underlies all accepted models/theories of psychological suffering and is the dominant way of conceptualising such suffering for both professionals and lay-people in Western cultures. It is further argued that the main reason the DMA is unable to assist in understanding and alleviating psychological suffering is because it is underpinned by assumptions about human beings and their suffering which are inherently flawed. The account presented in this thesis places at its centre an analysis of persons and their experience that attempts to overthrow these assumptions. The resulting reconceptualisation presents a view of psychological suffering as emergent from our continual personal and embodied enmeshment within our social world, rather than as arising primarily out of the various processes occurring ‘within’ us (whether that be our neurochemistry or our ‘mental mechanisms’ or an ‘interaction’ between them). It is essentially suggested that psychological suffering emerges from the same source as all other aspects of our personal being; from the constant coactions between the various aspects of our being in the world – personal, organismic and molecular – with the environment within which we are enmeshed. This means that the feelings/thoughts/behaviours conceptualised as ‘mental disorder’ are as much part of our personal being as any other aspect of us; they are not ‘other’, they are not ‘disease’, ‘illness’ or ‘dysfunction’. Such feelings/thoughts/ behaviours, it is argued, almost always, perhaps inevitably, represent a very adaptive response, at every level of our being, to environmental contingencies. Thus, when understood in its full context, the suffering conceptualised as ‘mental disorder’ can be seen as the very understandable responses of the embodied person to what is happening to them, rather than ‘un-understandable’ dysfunctions, aberrations and pathological processes of the ‘mind’ (or brain).

Submitted by GABRIELA MELLONI ZUCULO null (gabriela.zuculo@gmail.com) on 2016-05-11T20:23:14Z No. of bitstreams: 1 DISSERTAÇÃO DEFESA GABRIELA ZUCULO PRONTO.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-13T16:28:45Z (GMT) No. of bitstreams: 1 zuculo_gm_me_mar.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) / Made available in DSpace on 2016-05-13T16:28:45Z (GMT). No. of bitstreams: 1 zuculo_gm_me_mar.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) Previous issue date: 2016-04-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As características comuns ao quadro do Transtorno do Espectro do Autismo (TEA) destacadas pelo DSM-5 são: déficit de comunicação, dificuldade em fazer amizades ou se relacionar, dependência de rotina, resistência a mudanças e obsessão por itens inapropriados. Tais comportamentos podem ser observados desde a infância, porém com variações em cada indivíduo, o que levou o TEA a ser considerado um “continuum” que varia de menos comprometido (leve) a muito comprometido (grave). Dentre a complexa sintomatologia do TEA nos diferentes graus destaca-se a alta prevalência de distúrbios de sono, com influência negativa nas alterações comportamentais, instabilidade de humor, déficits nas funções neurocognitivas, incluindo memória, atenção, criatividade verbal, flexibilidade cognitiva e raciocínio abstrato. Como possível causa dos distúrbios de sono nessa população, está o déficit na produção de melatonina, hormônio que tem dentre suas funções a modulação da qualidade do sono. Com o intuito de fornecer dados para futuros tratamentos visando à melhora da qualidade de vida de indivíduos com TEA, esse estudo teve como objetivo investigar parâmetros de ritmo sono-vigília, aspectos comportamentais e de fluência verbal, antes e após o uso de melatonina exógena em indivíduos com TEA leve. Indivíduos com TEA leve de ambos os gêneros, de 7 a 18 anos, foram avaliados por meio da Escala de sono para crianças (EDSC), actigrafia, Child Behavior Checklist (CBCL) e Teste de fluência verbal fonêmica antes e após o uso oral de melatonina (3mg). A análise estatística descritiva foi feita a partir da média e erro padrão da média ou do percentual nos diferentes parâmetros e a análise estatística inferencial foi feita a partir do teste Anova com o teste de Tukey (pós-teste) e o teste de correlação de Spearman. Os resultados mostraram que 55,5% dos participantes com TEA leve apresentam indicativo de ao menos um distúrbio de sono, sendo os maiores percentuais encontrados em distúrbios de hiperidrose de sono, distúrbios respiratórios de sono e distúrbios de início e manutenção de sono. O grupo que recebeu melatonina apresentou os menores percentuais de distúrbios de sono com exceção do distúrbio de hiperidrose do sono. A análise da actigrafia mostrou que: o grupo TEA leve melatonina apresentou maior tempo total de sono em comparação aos outros grupos. Houve divergência sobre o ritmo atividade-repouso entre os parâmetros de fragmentação e amplitude do ritmo, sendo encontrado que o grupo TEA leve melatonina apresentou: ritmo menos fragmentado segundo o Aczcm e o IVm; e maior amplitude de ritmo segundo RAd e menor amplitude de ritmo segundo Sumpim. Os resultados do inventário de comportamento indicaram que as crianças com TEA leve apresentam os maiores escores classificados como clínico em problemas de pensamento, ansiedade, retraimento, comportamentos internalizantes e comportamentos externalizantes. O grupo que recebeu melatonina apresentou menores percentuais de escores classificados como clínico pelo inventário CBCL. A média de acertos no teste de fluência verbal fonêmica no grupo TEA leve foi de 13,9 ± 1,6. Quando separado por letras, o resultado foi P= 5,4 ± 0,7, T= 4,3 ± 0,5, L= 4,6 ± 0,6. Houve correlação entre os distúrbios totais de sono e os problemas somáticos de comportamento apresentados pelo grupo TEA leve. Estes dados mostram que crianças com TEA leve apresentam alta incidência de distúrbios de sono assim como no TEA sem especificação de grau, porém em menor escala. Estes distúrbios afetam aspectos comportamentais destas crianças e o tratamento com melatonina pode levar a melhora deste quadro. A fluência verbal de crianças com TEA grau leve é similar a de crianças com desenvolvimento típico. / The features common to the ASD highlighted by the DSM-5 are: communication deficit, difficulty making friends or relating, routine dependence, resistance to change, inappropriate items obsession. Such behavior can be verified since childhood, but with individual variations, which led the ASD to be considered as a "continuum" ranging from less committed (mild) to very committed (serious). Among the complex symptoms of ASD there is the high prevalence of sleep disorders, with a negative influence on behavioral changes, mood instability, deficits in neurocognitive functions including memory, attention, verbal creativity, cognitive flexibility and abstract reasoning. As a possible cause of sleep disorders in this population is the deficit of the melatonin production, hormone that modulates the sleep quality. In order to collaborate with future treatments that improving the life quality of ASD individuals, this study aimed to investigate parameters of sleep wake rhythm, behavior and verbal fluency before and after exogenous melatonin use in mild ASD individuals. For this, mild ASD individuals of both genders, 7-18 years were assessed by Sleep Disturbance Scale for Children (SDSC), actigraphy, Child Behavior Checklist (CBCL) and phonemic verbal fluency test before and after oral melatonin (3 mg). Descriptive statistical analysis was analyzed by mean and standard error or by percentage of the different parameters and inferential statistical analysis was performed by ANOVA with Tukey test (post-test) and Spearman correlation test. The results showed that 55,5% of mild ASD participants showed at least one sleep disorder, with the highest percentages found in sleep hyperhidrosis, sleep-breathing disorders and disorders of initiating and maintaining sleep. The group receiving melatonin had the lowest percentage of sleep disorders with the exception of sleep hyperhidrosis disorder. The actigraphy showed that: the mild ASD melatonin group showed higher total time of sleep than other groups. There was disagreement about between fragmentation parameters and amplitude of the activity-rest rhythm, since was found that the group of mild ASD melatonin showed: less fragmented rhythm according to Aczcm and IVm; and greater amplitude following Rad and lower amplitude rhythm following Sumpim. The results of behavior indicated that children with mild ASD have the high scores classified as clinical problems in thinking, anxiety, withdrawal, internalizing behaviors and externalizing behaviors. The group receiving melatonin had lower percentages of scores classified as clinical CBCL inventory. The mean score on the verbal fluency test in the group of mild ASD was 13,9 ± 1,6. When separated by letter, the result was P= 5,4 ± 0,7, T= 4,3 ± 0,5, L= 4,6 ± 0,6. There was a correlation between total sleep disorders and somatic behavior problems presented by mild ASD group. These data show that children with mild ASD have a high incidence of sleep disorders as well as in the ASD level without specification, but to a lesser extent. These disorders affect behavioral aspects of these children and the treatment with melatonin can improve of the clinical condition. Verbal fluency of children with ASD mild is similar to typically developing children.

ABSTRACT The Golgi apparatus has always been an interesting organelle of study because of its unique morphology as well as the critical roles it plays in cell biology. It is situated next to the endoplasmic reticulum and secreted proteins must pass through the Golgi vesicular pathway for modifications and targeting. In addition, the Golgi apparatus plays an essential role in establishing cellular polarity. Cell polarity refers to difference in orientation of cell structures spatially, and is involved in establishing functionality. The Golgi apparatus establishes cell polarity in various ways including orienting itself spatially, biasing vesicular trafficking within the cell, and most importantly through its role as a microtubule organizing center. The cytoskeleton provides the structural framework for cells. Microtubules nucleated from the Golgi-dependent microtubule organizing center result in an asymmetric cytoskeleton. An asymmetric cytoskeleton is essential to establishing cell polarity. Neurons require cell polarity to establish the essential structures such as the axon and dendrites. The Golgi apparatus establishes neuronal polarity through its extensive network of associated proteins. In this review, we will discuss the growing evidence supporting the role of the Golgi apparatus in establishing neuronal polarity.

Orientadores: Maria Valeriana Leme de Moura-Ribeiro, Silvia Maria Ciasca / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T12:07:58Z (GMT). No. of bitstreams: 1 Riechi_TatianaIzabeleJarorskideSa_D.pdf: 7337748 bytes, checksum: 0efb01b99750b80257e9ddb8bcd6d435 (MD5) Previous issue date: 2008 / Resumo: O objetivo deste estudo foi avaliar o impacto do nascimento pré-termo e com baixo peso (PT-BPN) no neurodesenvolvimento, na formação das funções mentais superiores e conseqüentemente na aprendizagem acadêmica, de crianças e adolescentes em idade escolar. A intensificação dos cuidados pré e peri natais e a evolução técnico-profissional das Unidades de Terapia Intensiva Neonatal melhorou as condições de sobrevivência dos bebês PT-BPN, gerando o aumento progressivo das taxas de sobrevivência neonatal e com elas, novas expectativas quanto às morbidades resultantes ao longo da infância, juventude e até, a fase adulta. Questões relativas a quais alterações longitudinais, cognitivo-comportamentais, poderiam ser assinaladas como possíveis efeitos da interrupção abrupta e precoce do processo gestacional. Mediante a vulnerabilidade do Sistema Nervoso Central (SNC), alterações estruturais e funcionais podem ocorrer, gerando circuitos cerebrais alternativos e/ou compensatórios, que resultam em Transtornos do Desenvolvimento como, o Distúrbio de Aprendizagem. Foi desenvolvido um estudo transversal caso controle em 120 escolares com idades entre 06 anos e 15 anos e 11 meses, regularmente matriculados no Ensino Fundamental e pareados sócio-economicamente. Todos foram submetidos ao protocolo de Avaliação Neuropsicológica, Neurológica e Escolar. O Grupo Propósito (GP) foi formado por 60 escolares nascidos no CAISM-FCM/UNICAMP com idade gestacional < 37 semanas e peso < 2.500 g. O Grupo Controle (GC) foi composto de 24 escolares irmãos dos sujeitos GP e, 36 escolares vizinhos colegas dos sujeitos GP, ambos nascidos com peso = 2.500g e idade gestacional = 37 semanas. Entre os instrumentos utilizados estão: WISC III, Teste Guestáltico Visomotor Bender, Trail Making Test, Figura Complexa de Rey, Teste Neuropsicológico Luria Nebraska-C, Escala Comportamental A2 de Rutter, Lista de Verificação Comportamental para Crianças e Adolescentes (CBCL) e Teste de Desempenho Escolar. Foram encontradas diferenças estatisticamente significativas entre GP e GC, com resultados inferiores para GP indicando comprometimento de: Coordenação Viso-Motora (86,7%), Desenvolvimento Psicomotor Geral (75,0%), Habilidade Viso-Construtiva (73,3%), Raciocínio Matemático (66,1%), Habilidade Tátil-Cinestésica (65,0%) e Memória Visual (60,0%), todos com p-valor=0,001. O QI dos sujeitos do GP mostrou-se na média, em geral, 10 pontos abaixo do GC. Observou-se prevalência no GP de: Distúrbios de Aprendizagem (33,3%), Dificuldade Escolar (35,0%), Lateralidade Cruzada (46,6%) e problemas Psicológicos e/ou Psiquiátricos (61,7%). Os escolares brasileiros PT-BPN desta pesquisa apresentaram alterações funcionais cerebrais específicas, associadas a transtornos cognitivo-comportamentais e de aprendizagem, mais expressivos do que os sujeitos do GC e também dos resultados descritos na literatura internacional / Abstract: The objective of this study was to evaluate the impact of preterm birth and low birth weight (PT-LBW) on neurodevelopment, on the formation of high mental functions, and, consequently, on the academic learning of school-age children and teenagers. The intensification of pre- and peri-natal cares and the technical-professional evolution of Newborn Intensive Care Units have improved the survival conditions of PT-LBW babies, therefore generating a progressive increase of newborn survival rates and, with that, new expectations regarding the resultant morbidities through childhood, youth and even the adult phase. Issues regarding which longitudinal, cognitive-behavioral alteration could be branded as possible effects of the abrupt and premature interruption of the gestational process. Through the vulnerability of the Central Nervous System (CNS), structural and functional alterations might occur, generating alternative and/or compensational brain circuits, which result on Development Derangements such as the Learning Disorder. A cross-sectional case-control study was conducted on 120 school-age children with ages between 06 years-old and 15 years-old and 11 months, regularly enrolled at Elementary Schools and socio-economically paired. All were submitted to the Neuropsychological, Neurological and Academic Assessment protocol. The Purpose Group (PG) was formed by 60 school-age children born at the CAISM-FCM/UNICAMP having gestational ages lower than 37 weeks and birth weight lower than 2,500 g. The Control Group (CG) was composed by 24 school-age children siblings of the PG subjects and 36 school-age children neighbors and colleagues of the PG subjects, all born with weights higher or equal 2,500 g and gestational ages higher or equal 37 weeks. Among the research instruments used we find: WISC III, Bender Visual-Motor Gestalt Test, Trail Making Test, Rey Complex Figure, Luria Nebraska-C Neuropsychological Test, Rutter¿s Behavioral Scale A2, the Child Behavior Checklist (CBCL) and Test of School Performance. Statistically significant differences were found between PG and CG, PG having lower results that indicate impairments of: Visual-Motor Coordination (86,7%), General Psychomotor Development (75,0%), Visual-Constructive Skill (73,3%), Mathematical Thinking (66,1%), Tactile-Kinesthetic Skill (65,0%) and Visual Memory (60,0%), all with a p-value = 0,001. The IQ of the PG subjects was, generally, in an average of 10 points lower than CG¿s. On the PG the prevalence of the following was observed: Learning Disorders (33,3%), School Learning Problem (35,0%), Crossed Laterality (46,6%) and Psychological and/or Psychiatric Problems (61,7%). The Brazilian PT-LBW school-age subjects of this research displayed specific brain functional alterations, associated to cognitive-behavioral and learning disorders, which are more outstanding than those of the CG subjects, and also than results described on international literature about the matter / Doutorado / Neurologia / Doutor em Ciências Médicas

O nascimento prematuro constitui-se em um fator de risco ao desenvolvimento. Por um lado a hospitalização em Unidade de Terapia Intensiva Neonatal (UTIN) pode proteger o bebê nascido pré-termo, por outro lado este sobrevive em um ambiente adverso, em que é exposto a estímulos estressores e dolorosos inerentes aos cuidados intensivos. Os objetivos do estudo foram: a) caracterizar e comparar o desenvolvimento neurocomportamental de bebês nascidos pré-termo, diferenciados pela idade gestacional; b) examinar associações entre os eventos estressores da UTIN e o desenvolvimento neurocomportamental. A amostra foi composta por 45 recém-nascidos pré-termo (RNPT) nascidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, distribuídos em três grupos: G1, 10 RNPT de 23 a 28 semanas de idade gestacional (IG); G2, 10 RNPT de 29 a 32 semanas de IG; G3, 25 RNPT de 34 a 37 semanas de IG (grupo controle). Apenas os neonatos G1 e G2 foram internados na UTIN. Os neonatos foram avaliados pela Neurobehavioral Assessment of the Preterm Infant (NAPI), antes de atingir 37 semanas de idade pós-concepcional (IPC). Os neonatos G1 e G2 foram avaliados em dois momentos (aos 32 e 35 semanas de IPC) e os G3 foram avaliados apenas nesta última idade. Na avaliação dos eventos estressores da UTIN foram realizadas a observação direta dos bebês e a análise diária do prontuário dos pacientes, durante a internação. Os resultados mostraram que, quanto ao desenvolvimento neurocomportamental na fase de 35 semanas de IPC, os neonatos G3 apresentaram os melhores resultados em relação aos neonatos G1 e G2. Os piores resultados na NAPI foram encontrados nos neonatos G2, com menores escores nos domínios motor e vigor e irritabilidade, em comparação aos neonatos G1 e G3. Além disso, destaca-se que a evolução do neurodesenvolvimento, de 32 para 35 semanas de IPC, foi melhor nos neonatos G1 quando comparados aos G2. Considerando-se a associação entre o neurodesenvolvimento e os eventos estressores da UTIN, observou-se que, aos 32 semanas de IPC, quanto maior o número de eventos de ventilação assistida, mais choro na avaliação neurocomportamental nos neonatos G1. Nos neonatos G2, por sua vez, quanto maior era o número de acessos periféricos, mais alerta e ativado os bebês se mantiveram, mais choro e melhor era o sinal de cachecol. Além disso, neste grupo, quanto mais exames médicos realizados mais alerta e chorando os bebês se mantiveram na avaliação NAPI. Na idade de 35 semanas IPC, nos G1 e G2, quanto maior era o número de acessos periféricos, mais tempo os bebês se mantiveram em estado de alerta na avaliação NAPI. A avaliação neurodesenvolvimental inicial na fase neonatal antes de atingir a idade do termo permitiu a identificação de riscos e recursos nos neonatos pré-termo. Apesar de extrema prematuridade, os neonatos G1 apresentaram mais recursos neurocomportamentais do que os neonatos pré-termo moderado, com 35 semanas de IPC. Os eventos estressores de manuseio dos neonatos e procedimentos dolorosos na UTIN mostraram associações com estados comportamentais ativados, o que interfere negativamente nos processos de regulação desenvolvimental dos bebês prematuros. / Preterm birth is a risk factor for development. On one hand hospitalization in the Neonatal Intensive Care Unit (NICU) can protect the preterm infants, on the other hand they survive in an adverse environment, where they are exposed to stressful and painful stimuli inherent in the intensive care. The objectives of the study were: a) to characterize and to compare the neurobehavioral development of preterm infants at different gestational ages; b) to examine associations between stressful events in NICU and the neurobehavioral development. The sample was composed of 45 preterm neonates (PT) born in the Hospital of Clinics, Faculty of Medicine at Ribeirão Preto - USP, divided into three groups: G1, 10 PT of 23-28 weeks of gestational age (GA), G2, 10 PT of 29-32 weeks GA, and G3, 25 PT of 34-37 weeks GA (control group). Only the G1 and G2 neonates were admitted to the NICU. The neonates were evaluated through Neurobehavioral Assessment of the Preterm Infant test (NAPI), prior reach 37 weeks of post-conceptional age (PCA). The G1 and G2 neonates were assessed at two time points (at 32 and 35 weeks of PCA) and G3 neonates were evaluated only in this last age. The assessment of the stressful events in the NICU was performed through direct observation of the infants and the daily analysis of the inpatients` charts during the hospitalization. The results showed that on the neurobehavioral development at 35 weeks of PCA, the G3 neonates showed better results in comparison to the G1 and G2 neonates. The worst results of NAPI were found in the G2 neonates, indicating lower scores in motor force and irritability, compared to the G1 and G3 neonates. Furthermore, the neurodevelopment evolution from 32 to 35 weeks of PCA was better in the G1 neonates than the G2 ones. Concerning the associations between the neurodevelopmental and the stressful events in the NICU, it was observed that, at 32 weeks of PCA, the greater the number of assisted ventilation events, the more crying happened in the neurobehavioral evaluation of the G1neonates. In the G2 neonates, in turn, the greater the number of peripheral access, the more alert and active the infants remained, the more crying and the best was the scarf sign. Moreover, in this group, the more medical examinations, the more alert and crying the infants remained during the NAPI assessment. In both groups of neonates at 35 weeks PCA, the greater the number of peripheral access, the longer the infants remained on alert state during the NAPI assessment. The initial neurodevelopmental assessment in the neonatal phase before reaching the age of term allowed the identification of risks and resources in preterm neonates. Although the G1 neonates presented extreme prematurity, they exhibit more neurobehavioral resources than the moderate preterm neonates at 35 weeks of PCA. The stressors stimuli of handling the neonates and painful procedures in the NICU setting were associated with more infants` activated behavioral states, which could impair the regulation developmental process of premature infants.

Tourette’s is currently considered a neurodevelopmental genetic disorder. Georges Gilles de la Tourette is given primary credit for the diagnoses of the disorder in the late 1800s. Clear answers have been elusive although modern research and improvements to neuroimaging have enabled the causal factors of Tourette’s Disorder (TD) to be examined with greater scrutiny. Currently, there is no known cure or pharmaceutical treatment that has been proven 100% effective for all patients and symptoms of Tourette’s. Anecdotally, there have been recent media and self-reports of people diagnosed with Tourette’s finding relief from their symptoms through involvement in focus-based activities such as video games, athletic endeavors and musical engagement, albeit little empirical evidence exists on these subjects. The author is seeking empirical data showing the influence of musical engagement on the symptoms of Tourette’s. This research does not focus on the receptive activity of listening to music, but engagement. This performance-based music making or engagement can be described as the body being physically involved in the creation and production of music which comes from such activities as playing a musical instrument or singing. This study seeks to answer the question, “does musical engagement influence the symptoms of Tourette’s?” A self-reported survey instrument was generated to question those claiming to be musicians who have been diagnosed with TD to explore what effect engaging in a musical activity has on their symptoms. Participants’ responses to ten questions were analyzed. The survey apex involved a Likert-type scale asking to what extent these musicians experienced changes in their symptoms. One hundred eighty-three (N = 183) respondents rated their perceptions from one to five where one equaled drastic symptoms increase by engaging in a musical activity and five equaled drastic symptoms decrease. The mean response from the scale was 4.45, clearly showing that these musicians with TD experienced a great deal of relief when engaged in their activity. This study presents evidence and support for research into neurodevelopmental and musical training correlations and a strong case for childhood music education as a means to facilitate this training.