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A presente tese de doutorado ? composta de quatro artigos emp?ricos, com dois importantes eixos para avalia??o neuropsicol?gica. O primeiro, a avalia??o dos comportamentos comunicativos desviantes do discurso conversacional em diferentes faixas et?rias; e o segundo, a constru??o e os resultados preliminares do Programa de Capacita??o em Neuropsicologia do Envelhecimento para Equipes de Sa?de (CENEES). O primeiro estudo ?Age-related differences in Conversational Discourse Abilities: a comparative study? compara o desempenho de adultos jovens e idosos no discurso conversacional. Os resultados demonstraram que os participantes adultos jovens em geral apresentaram melhor desempenho nas habilidades comunicativas. No entanto, o grupo de idosos apresentou melhores ?ndices em vari?veis associadas ao engajamento do discurso. Salienta-se que os itens associados ao planejamento da fala e auto monitoramento n?o apresentaram diferen?as entre os grupos. J? para o segundo estudo, ?Desempenho do processamento conversacional entre subgrupos cl?nicos no cont?nuo do envelhecimento?, a avalia??o do discurso foi utilizada na compara??o entre grupos cl?nicos. Diferen?as significativas foram encontradas nos aspectos de: coer?ncia, coes?o, compreens?o e pros?dia lingu?stica e emocional. Dentre as vari?veis analisadas, o destaque maior ? para ?Tem velocidade de fala diminu?da? em que todos os grupos cl?nicos se diferenciaram, sendo que o DA leve teve maiores m?dias de aparecimento. O terceiro estudo, ?Constru??o do Programa de Capacita??o em Neuropsicologia do Envelhecimento para Equipes de Sa?de (CENEES)?, apresentou os processos e etapas do CENEES. A constru??o do CENEES teve a participa??o de 4 ju?zes especialistas com ?ndice de validade de conte?do de 0,785. O programa foi constru?do em duas fases de cinco e uma etapa, respectivamente. A vers?o final do CENEES foi dividida em 8 encontros, com 4 m?dulos, sendo: 1. Pilares do conhecimento; 2. Mem?ria; 3. Fun??es executivas, 4. Comunica??o, e um ?ltimo encontro de revis?o para retomada dos t?picos aprendidos. Por ?ltimo, o estudo quatro ?Efeito e Efetividade do Programa de Capacita??o em Neuropsicologia do Envelhecimento para Equipes de Sa?de (CENEES)? foi a aplicabilidade de fato do programa constru?do. Participaram 7 agentes comunit?rios de sa?de (ACS) de uma Unidade B?sica de Sa?de da regi?o metropolitana de Porto Alegre. Os resultados demonstraram que os m?dulos de ?Mem?ria? e ?Comunica??o? foram de f?cil entendimento para os participantes e os m?dulos ?Pilares do conhecimento? e ?Fun??es executivas? foram mais dif?ceis de serem acompanhados. A an?lise qualitativa foi de extrema import?ncia para que os participantes demonstrassem o quanto foi importante a participa??o no CENEES. Essa tese de doutorado contribui para a pr?tica de avalia??o e interven??o neuropsicol?gica em espec?fico para os eixos de comunica??o e capacita??o de profissionais da equipe de sa?de. Por ?ltimo, salienta-se a necessidade da continuidade de todos estudos envolvidos nessa tese, a import?ncia dos eixos te?ricos aqui descritos para diagn?stico precoce e preciso de pacientes com alguma patologia cognitiva associada. The presente thesis is composed of four empirical articles, with two important topics for neuropsychological evaluation. The first topic, includes the discourse assessment using the frequency of impaired communicative behaviors comparing young and older adults; The second topic, involves the development and preliminary results of the ?Training Program in Neuropsychology of Aging for Health Team?. The firs article ?Age-related differences in Conversational Discourse Abilities: a comparative study? compares the discourse performance of young and older adults. The results showed that young adult participants generally presented better performance in communicative skills. However, the elderly group was better in variables associated with speech engagement. It should be noted that the aspects associated with speech planning and self-monitoring did not show differences between groups. To the second article ?Conversational Discourse among clinical subgroups in aging?, was used the discourse assessment comparing clinical subgroups. Significant differences were found in the aspects of: coherence, cohesion, comprehension and linguistic and emotional prosody. It is noted that some variables such as ?Has an abnormal speech rate ? decreased? revealed worse outcome to the azlheimer desease group. The third article, ?Development of the Psycoeducation in Neuropsychology of Aging for Health Staff?, showed all the phases to development the material. The program was judged by four neuropsychologic experts and had a validity index of 0.785. The program was done in two phases with five steps. The final version was splited in 8 meetings, composing 4 subjects: 1. General knowledge about neurosciences; 2. Memory; 3. Executive Functions; 4. Communication and another meeting for revision. Finally, the fourth study ?Effect and Effectiveness of Psycoeducation in Neuropsychology of Aging for Health Staff? was the applicability of the program. Seven community health agents participated and the result showed that ?Memory? and ?Communication? meetings were easily understood by participants. The ?General knowledge about neurosciences? and ?Executive function? meetings were more difficult to the agents. The qualitative analysis was extremely important for the participants to demonstrate how important participation in program was. This doctoral thesis contributes to the practice of evaluation and neuropsychological intervention in communication and training of health team. Finally, the need for continuity of all studies involved in this thesis is stressed, the importance of the theoretical axes described here for early and accurate diagnosis of patients with some associated cognitive pathology. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

El traumatismo craneoencefálico (TCE) puede conllevar impactantes cambios en la vida cotidiana, que incluyen alteraciones a nivel social, profesional, comunicativo y cognitivo (dificultades atencionales, mnemónicas y ejecutivas). Este estudio tuvo por objeto caracterizar la ocurrencia de déficits neuropsicológicos post-TCE y constatar el impacto ocasionado por el nivel de severidad del trauma en el desempeño cognitivo de los pacientes. Participaron 96 adultos en la muestra total, que fue dividida en dos grupos para evaluar el nivel de severidad del trauma: TCE leve (n=39) y TCE grave (n=77). La gravedad de la lesión se clasificó por medio de la Escala de Coma de Glasgow, por la duración de la pérdida de consciencia, o por la amnesia post-traumática. No había diferencias entre la edad y la escolaridad de los participantes. Para la comparación entre los grupos en cuanto a la distribución de ocurrencia de déficits neuropsicológicos, se utilizó el Chi-cuadrado. Se utilizó una batería de evaluación neuropsicológica flexible conformada por tareas verbales y visoespaciales de habilidades lingüísticas, mnemónicas y ejecutivas. Los grupos no se diferenciaron en cuanto a las variables sociodemográficas. Los pacientes con TCE leve tuvieron mejores puntajes comparados con los de TCE grave (número de errores y categorías completadas del Test de clasificación de tarjetas de Wisconsin- [WCST, por sus siglas en inglés]; errores en la parte B del Test de Hayling; y en la interferencia retro y proactiva del Test de aprendizaje auditivo verbal de Rey [RAVLT, por sus siglas en inglés]. El nivel de severidad del trauma parece mostrar diferencias en los individuos en cuanto al desempeño en memoria episódica de información nueva y en el control de interferencia entre los recuerdos; lo mismo se aplica a las funciones de flexibilidad e inhibición. Estos resultados sugieren que es necesaria una mayor inversión en acciones de políticas públicas, priorizando intervenciones neurocognitivas reeducativas y métodos de prevención de accidentes relacionados con lesiones traumáticas que tengan alta incidencia de secuelas. El traumatismo craneoencefálico (TCE) puede conllevar impactantes cambios en la vida cotidiana, que incluyen alteraciones a nivel social, profesional, comunicativo y cognitivo (dificultades atencionales, mnemónicas y ejecutivas). Este estudio tuvo por objeto caracterizar la ocurrencia de déficits neuropsicológicos post-TCE y constatar el impacto ocasionado por el nivel de severidad del trauma en el desempeño cognitivo de los pacientes. Participaron 96 adultos en la muestra total, que fue dividida en dos grupos para evaluar el nivel de severidad del trauma: TCE leve (n=39) y TCE grave (n=77). La gravedad de la lesión se clasificó por medio de la Escala de Coma de Glasgow, por la duración de la pérdida de consciencia, o por la amnesia post-traumática. No había diferencias entre la edad y la escolaridad de los participantes. Para la comparación entre los grupos en cuanto a la distribución de ocurrencia de déficits neuropsicológicos, se utilizó el Chi-cuadrado. Se utilizó una batería de evaluación neuropsicológica flexible conformada por tareas verbales y visoespaciales de habilidades lingüísticas, mnemónicas y ejecutivas. Los grupos no se diferenciaron en cuanto a las variables sociodemográficas. Los pacientes con TCE leve tuvieron mejores puntajes comparados con los de TCE grave (número de errores y categorías completadas del Test de clasificación de tarjetas de Wisconsin- [WCST, por sus siglas en inglés]; errores en la parte B del Test de Hayling; y en la interferencia retro y proactiva del Test de aprendizaje auditivo verbal de Rey [RAVLT, por sus siglas en inglés]. El nivel de severidad del trauma parece mostrar diferencias en los individuos en cuanto al desempeño en memoria episódica de información nueva y en el control de interferencia entre los recuerdos; lo mismo se aplica a las funciones de flexibilidad e inhibición. Estos resultados sugieren que es necesaria una mayor inversión en acciones de políticas públicas, priorizando intervenciones neurocognitivas reeducativas y métodos de prevención de accidentes relacionados con lesiones traumáticas que tengan alta incidencia de secuelas. Traumatic brain injury (TBI) can lead to significant changes in daily life, as well as in social, labor, communicative, and cognitive domains (attention, memory and executive functions). This study aimed to characterize the occurrence of post-TBI neuropsychological deficits as well as to determine whether there is an impact related to the level of severity of the trauma on the patient's performance. Ninety-six adults participated in the study, who were divided in two groups to assess the trauma's level of severity: mild TBI (n=39) and severe TBI (n=57). This severity was classified by the Glasgow Coma Scale, by the duration of consciousness loss, or by post-traumatic amnesia. There were no differences between the groups regarding variables of age and years of schooling. A Chi- square test was used to do a comparison between the two groups in terms of occurrence of neuropsychological deficits. Verbal, visuospatial, mnemonic, linguistic and executive tests composed a flexible neuropsychological battery. Patients with mild TBI had better scores compared to those with severe TBI (number of errors and in completed categories of the Modified Wisconsin Card Sorting Test (MWCST); errors in Part B of The Hayling Test; and proactive and retroactive interference in the Rey Auditory Verbal Learning Test (RAVLT). The severity of the trauma seems to differentiate individual's performance on episodic memory of new information and in the control of interference between memories; the same is applied to flexibility and inhibition functions. These results suggest the need for more investments in public health policy actions, prioritizing neurocognitive remedial intervention and prevention methods for such condition with high incidence of sequelae.

El traumatismo craneoencefálico (TCE) puede conllevar impactantes cambios en la vida cotidiana que incluyen alteraciones a nivel social - profesional - comunicativo y cognitivo (dificultades atencionales. mnemónicas y ejecutivas). Este estudio tuvo por objeto caracterizar la ocurrencia de déficits neuropsicológicos post-TCE y constatar el impacto ocasionado por el nivel de severidad del trauma en el desempeño cognitivo de los pacientes. Participaron 96 adultos en la muestra total que fue dividida en dos grupos para evaluar el nivel de severidad del trauma: TCE leve (n=39) y TCE grave (n=77). La gravedad de la lesión se clasificó por medio de la Escala de Coma de Glasgow por la duración de la pérdida de consciencia o por la amnesia postraumática. No había diferencias entre la edad y la escolaridad de los participantes. Para la comparación entre los grupos en cuanto a la distribución de ocurrencia de déficits neuropsicológicos se utilizó el Chi-cuadrado. Se empleó una batería de evaluación neuropsicológica flexible conformada por tareas verbales y viso espacial de habilidades lingüísticas mnemónicas y ejecutiva. Los grupos no se diferenciaron en cuanto a las variables sociodemográficas. Los pacientes con TCE leve tuvieron mejores puntajes comparados con los de TCE grave (número de errores y categorías completadas del Test de clasificación de tarjetas de Wisconsin [WCST. por sus siglas en inglés]; errores en la parte B del Test de Hayling; y en la interferencia retro y proactiva del Test de aprendizaje auditivo verbal de Rey [RAVLT. por sus siglas en inglés]. El nivel de severidad del trauma parece mostrar diferencias en los individuos en cuanto al desempeño en memoria episódica de información nueva y en el control de interferencia entre los recuerdos; lo mismo se aplica a las funciones de flexibilidad e inhibición. Estos resultados sugieren que es necesaria una mayor inversión en acciones de políticas públicas priorizando intervenciones neurocognitivas reeducativas y métodos de prevención de accidentes relacionados con lesiones traumáticas que tengan alta incidencia de secuelas. Traumatic brain injury (TBI) can lead to significant changes in daily life as well as in social labor communicative and cognitive domains (attention. memory and executive functions). This study aimed to characterize the occurrence of post-TBI neuropsychological deficits as well as to determine whether there is an impact related to the level of severity of the trauma on the patient’s performance. Ninety-six adults participated in the study who were divided in two groups to assess the trauma’s level of severity: mild TBI (n=39) and severe TBI (n=57). This severity was classified by the Glasgow Coma Scale by the duration of consciousness loss or by post-traumatic amnesia. There were no differences between the groups regarding variables of age and years of schooling. A Chi- square test was used to do a comparison between the two groups in terms of occurrence of neuropsychological deficits. Verbal. Visuospatial – mnemonic - linguistic and executive tests composed a flexible neuropsychological battery. Patients with mild TBI had better scores compared to those with severe TBI (number of errors and in completed categories of the Modified Wisconsin Card Sorting Test (MWCST); errors in Part B of The Hayling Test; and proactive and retroactive interference in the Rey Auditory Verbal Learning Test (RAVLT). The severity of the trauma seems to differentiate individual’s performance on episodic memory of new information and in the control of interference between memories; the same is applied to flexibility and inhibition functions. These results suggest the need for more investments in public health policy actions prioritizing neurocognitive remedial intervention and prevention methods for such condition with high incidence of sequels.

A presente disserta??o de mestrado compreende dois artigos emp?ricos que pretendem explorar a avalia??o dos processamentos comunicativos e executivos de pacientes adultos com traumatismo cranioencef?lico (TCE) em dois momentos ap?s a les?o cerebral: no momento da interna??o (inpatients) e ap?s alta hospitalar (outpatients). O primeiro estudo objetiva comparar os processamentos discursivo, pragm?tico, l?xico-sem?ntico, de leitura e de escrita de pacientes adultos p?s TCE do tipo inpatients (TCEi), comparando o desempenho com indiv?duos sem les?o cerebral. Os resultados indicaram que os participantes se diferenciaram nos quatro processamentos comunicativos sendo que o grupo com TCE teve pior desempenho. O segundo estudo teve como objetivo verificar se existem diferen?as entre pacientes p?s-TCE - do tipo outpatients com gravidades leve e grave - e indiv?duos saud?veis, quanto ao desempenho nos processamentos comunicativos e executivos, al?m de identificar se associa??es e dissocia??es existem na amostra de TCE. Encontraram-se diferen?as entre grupos nos escores do discurso conversacional e narrativo e nas habilidades executivas de planejamento, flexibilidade cognitiva, mem?ria de trabalho, velocidade de processamento e inibi??o. Tais achados, de forma geral, indicam que pacientes com menor les?o e teoricamente melhor progn?stico, podem apresentar desempenho discursivo abaixo do esperado. Al?m disso, as tarefas indicaram diferen?as nas habilidades executivas entre os tr?s grupos. pacientes com TCE grave tiveram pior desempenho do que controles e pacientes com TCE leve, ainda TCE leve diferenciou-se dos graves nos dois estudos. Por ?ltimo, dissocia??es entre os grupos de TCE foram encontradas nos itens de manuten??o de regras e velocidade de processamento e associa??es encontradas nos itens de planejamento. Os resultados dos dois estudos emp?ricos contribuem para a comunidade cient?fica em entender um perfil cont?nuo de dificuldades mesmo em pacientes com o menor ?ndice de gravidade de les?o. As an?lises apresentadas nessa disserta??o de mestrado s?o poss?veis de serem implementadas nos servi?os p?blicos para avalia??o mais apurada desses pacientes e para identificar melhor progn?stico j? que algumas dificuldades podem afetar globalmente o funcionamento dos pacientes e dificultar, inclusive, o per?odo de recupera??o p?s les?o cerebral. This dissertation contains two empirical articles which investigated the communication skills and executive functions of adults with traumatic brain injury (TBI) upon hospital admission (inpatients) and after hospital discharge (outpatients). The aim of the first study was to compare discursive, pragmatic, lexical-semantic, reading and writing skills between inpatients with TBI (iTBI) and adults with no neurological damage. Our results showed between-group differences on all parameters evaluated, with control participants outperforming the iTBI group across all measures used in the study. The aim of the second investigation was to identify differences between outpatients with mild or severe TBI (oTBI) and healthy adults on communicative and executive functions, as well as to investigate associations and dissociations between patterns of impairment in the oTBI sample. The two groups differed in their performance on conversational and narrative discourse tasks, as well as on the following executive functions: planning, cognitive flexibility, working memory, processing speed and inhibitory control. Overall, the findings suggested that even subjects with relatively mild lesions and a theoretically good prognosis may experience impairments in discourse processing. The patient group was then further divided according to TBI severity, and differences in executive functions were identified between these two subgroups, as well as between each of these categories and the control group. Patients with severe TBI performed worse than control participants and subjects with mild TBI, and differences between patients with mild and severe TBI were identified in both studies. Lastly, the TBI groups showed dissociations between impairments in rule maintenance and processing speed, and associations between cognitive performance on planning tasks. These findings contributed to the current literature on the continuum of communicative and executive impairment profiles across all levels of TBI severity. The analyses performed in this dissertation may be used in public health services to perform a more accurate assessment of patients with TBI and improve prognostic accuracy, since some impairments may have an impact on global functioning and affect the length of the post-TBI recovery period. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Lentiviral vectors containing the green fluorescent protein gene have been successfully used to select transgenic embryos before transfer to a surrogate mother. However, there are apparently no reports regarding early detection of transgenic embryos using a lentiviral vector carrying an additional transcription unit for tissue-specific expression of a valuable protein. In this study, two HIV-based lentiviral vectors were constructed. The first one contained the green fluorescent protein (GFP) coding sequence driven by the early SV40 promoter (Lv-G), whereas the other contained an additional transcription unit for the expression of E2 glycoprotein from classical swine fever virus, driven by a 1.5 kb αS1casein promoter from water buffalo (Lv-αS1cE2hisG). Microinjection of single-cell mouse embryos with Lv-G lentiviral vector rendered embryos which were GFP-positive, beginning at the four-cell stage. Of 33 mice born, 28 (81%) carried the transgene DNA and 15 (55.5%) were GFP-positive. Microinjection of Lv-αS1cE2hisG lentiviral vector yielded 28 mice born; although 24 (85%) carried the transgene DNA, none were GFP-positive, suggesting that the tissue-specific expression cassette interfered with expression of the ubiquitous trancriptional unit. In Lv-αS1cE2hisG transgenic mice, E2his was expressed in milk as a homodimer (at concentrations ≤ 0.422 mg/mL). This was apparently the first report of expression of a recombinant protein in the milk of transgenic animals generated by lentiviral transgenesis.

Traumatic brain injury (TBI) can lead to significant changes in daily life, as well as in social, labor, communicative, and cognitive domains (attention, memory and executive functions). This study aimed to characterize the occurrence of post-TBI neuropsychological deficits as well as to determine whether there is an impact related to the level of severity of the trauma on the patient's performance. Ninety-six adults participated in the study, who were divided in two groups to assess the trauma's level of severity: mild TBI (n=39) and severe TBI (n=57). This severity was classified by the Glasgow Coma Scale, by the duration of consciousness loss, or by post-traumatic amnesia. There were no differences between the groups regarding variables of age and years of schooling. A Chi- square test was used to do a comparison between the two groups in terms of occurrence of neuropsychological deficits. Verbal, visuospatial, mnemonic, linguistic and executive tests composed a flexible neuropsychological battery. Patients with mild TBI had better scores compared to those with severe TBI (number of errors and in completed categories of the Modified Wisconsin Card Sorting Test (MWCST); errors in Part B of The Hayling Test; and proactive and retroactive interference in the Rey Auditory Verbal Learning Test (RAVLT). The severity of the trauma seems to differentiate individual's performance on episodic memory of new information and in the control of interference between memories; the same is applied to flexibility and inhibition functions. These results suggest the need for more investments in public health policy actions, prioritizing neurocognitive remedial intervention and prevention methods for such condition with high incidence of sequelae.