A bexiga neurogênica é uma disfunção vesical decorrente principalmente da lesão medular. O cateterismo vesical intermitente é o tratamento mais indicado na atualidade, deve ser realizado de 4 a 6 vezes ao dia, durante toda a vida, visando a proteção do trato urinário superior e a aquisição da continência urinária. Na reabilitação desses indivíduos, a autocateterização vesical é um desafio enfrentado na busca pela autonomia, privacidade, inserção social e participação. Os vídeos educativos são utilizados para o aprendizado do autocateterismo em vários países, por serem de fácil utilização e acesso via internet. Apesar disso, não existem vídeos realizados para o contexto brasileiro, levando em consideração os cateteres urinários e a técnica utilizada no Brasil. Este estudo teve como objetivo desenvolver e validar um vídeo educativo para a realização do autocateterismo vesical intermitente limpo. Trata-se de um estudo quantitativo, desenvolvido em duas fases: 1ª fase com a avaliação de vídeos educativos públicos direcionados para a aprendizagem do autocateterismo vesical intermitente com a técnica limpa; e 2ª Fase, com o desenvolvimento e validação de um vídeo educativo voltado para aprendizagem do autocateterismo. O levantamento dos vídeos utilizou um site de compartilhamento de vídeos utilizando o descritor \"autocateterismo\". Os vídeos foram avaliados por três juízes da área de saúde. O processo de desenvolvimento e validação do roteiro do vídeo educativo utilizou questionários previamente ratificados. Participaram dessas etapas, respectivamente, 18 e 17 juízes experts em reabilitação e/ou no ensino em saúde. O levantamento mostrou que apenas 3,5% (172) do total de vídeos disponíveis no site pesquisado eram voltados para o aprendizado do autocateterismo no contexto brasileiro. Seis vídeos eram específicos para o autocateterismo, dos quais quatro tinham informações desatualizadas ou incorretas, apenas dois atingiram a pontuação aceitável. Na validação do roteiro observou-se um predomínio de participantes do sexo feminino (94,44%), com idade de 30 a 60 anos, dos quais 72,22% possuíam mestrado e 50% atuavam há mais de cinco anos na área de reabilitação. O roteiro foi considerado validado com 96,29% das respostas dos juízes \"concordo\" ou \"concordo totalmente\" nas questões referentes ao quesito objetivo, 91,09% para quesito conteúdo, 98,12% em relação ao quesito relevância, 75% quanto ao quesito ambiente, 71,11% no quesito linguagem verbal e 92,70% referente à inclusão de tópicos. A produção do vídeo contou com uso de tecnologia 3D e apoio de uma equipe técnica especializada. No que se refere à validação do conteúdo do vídeo educativo, o conteúdo do vídeo foi considerado validado com 100% dos juízes que responderam \"concordo\" ou \"concordo totalmente\" nas questões referentes à funcionalidade, 86,27% referentes à usabilidade, 97,06% no quesito eficiência, 100% para técnica audiovisual, 94,11% quanto ao ambiente e 97,05% procedimento. O vídeo educativo foi avaliado positivamente tanto pela qualidade das informações quanto pela didática do ensino, mostrando a relevância da validação de materiais educativos. A expectativa é disseminar o vídeo educativo em diferentes centros de reabilitação e Universidades, visando propagar e tornar o conhecimento sobre a temática mais acessível à sociedade e aos profissionais de saúde, em especial os de reabilitação. Além de incentivar e embasar metodologicamente o desenvolvimento de outros vídeos educativos na área da saúde / The neurogenic bladder is a vesical dysfunction mainly due to spinal cord injury. Clean intermittent catheterization is currently the best treatment and it should be performed 4-6 times a day, during the entire lifetime, in order to protect the upper urinary tract and the acquisition of urinary continence. The rehabilitation of the affected people, by the use of self-catheterization is a challenge, which has to be faced to maintain autonomy, privacy, social inclusion and participation. Educational videos on self-catheterization are used in several countries because of its handling and wide accessibility via Internet. However, there are no videos concerning Brazilian context, considering the urinary catheters and catheterization techniques used in Brazil. This study aimed to develop and validate an educational video on how to perform intermittent self- catheterization in Brazilian context. It is a quantitative study, divided in two phases: The 1st phase including the evaluation of existing public educational videos with the aim to learn the intermittent self-catheterization using a clean technique and the 2nd phase with the development and validation of an educational video with the objective to learn the self-catheterization. Educational videos have been gathered searching the keyword \"self- catheterization\" on a video- sharing Website. Three judges of the healthcare area evaluated the videos. The development and validation process of the storyboard of the educational video used previously evaluated questionnaires. In these phases, respectively, 18 and 17 judges, who are experts in rehabilitation and/or health education took part. The first evaluation showed that only 3.5% of all videos available (172) on the website had learning self-catheterization as content in Brazilian context. Six videos were specific about self-catheterization, of which four had outdated or incorrect information and only two achieved an acceptable score. In the evaluation of the storyboard participated mainly female specialists (94.44%), aged between 30 and 60 years, of which 72.22% had a master\'s degree and 50% worked for more than five years in the area of rehabilitation. The judges rated the storyboard with 96.29% of the responses being \"agree\" or \"fully agree\" regarding the purpose of the video, 91.09% regarding the content, 98.12% in relation to the relevance, 75% regarding the ambience, 71 11% regarding the verbal language and 92.70% in relation to the query inclusion of topics. The production of the video used 3D technology and was supported by a specialized technical team. With regard to the validation of educational video, the video content was considered validated with 100% of the judges responded \"agree\" or \"fully agree\" on issues related to functionality, 86.27% for usability, 97.06% in the query efficiency, 100% on the visual technique, 94.11% to the environment query and 97.05% for the procedure. Regarding the educational video validation, it was considered validated with 100% of respondents \"agree\" or \"strongly agree\" on issues related to functionality, 86.27% respondents to the query usability, 97.06% related to efficiency, 100% in the visual technique, 94.11% to the environment and 97.05% for the procedure. Both, the quality of information and the teaching didactic of the educational video was evaluated positively, showing the importance of validation of educational materials. The ambition is to spread the educational video in different rehabilitation centers and universities, in order to share the knowledge and make it accessible to the society and the health professionals, especially those working the area of rehabilitation. In addition, the goal is to encourage and consolidate the methodological development of other educational videos in the healthcare area

L'analyse de données d'expression montre qu'il est avantageux d'analyser les processus biologiques en termes de modules plutôt que simplement considérer les gènes un par un. Dans ce projet nous avons conduit une analyse non supervisée des données d'expression de gènes de plusieurs cohortes de tumeurs urothéliales en appliquant la méthode d'Analyse en Composantes Indépendantes. Plusieurs études ont démontré les meilleures performances de l'ACI par rapport à l'ACP et les méthodes de clustering, pour obtenir une décomposition plus réaliste des données d'expression en patterns d'expression pertinents et associés avec le phénotype d'intérêt.Les tumeurs urothéliales apparaissent et évoluent selon deux voies distinctes dont la probabilité de progression en cancer musculo-invasif diffère radicalement. Excepté la mutation de FGFR3 dans le groupe le moins agressif, les processus moléculaires sous-jacents n'ont pas été complètement identifiés. Le principal objectif de cette thèse était dédié aux interprétations biologiques des différentes composantes indépendantes pour aider à confirmer et étendre la liste des processus biologiques connus pour être impliqués dans le cancer de vessie.Chaque composante indépendante est caractérisée par une liste de projections de gènes et de contributions pondérées d'échantillons tumoraux . En combinant expertise biologique et comparaison des listes de gènes à des voies existantes et en étudiant conjointement l'association des composantes aux annotations cliniques et moléculaires, nous avons pu différencier les CIscausées par des facteurs techniques, tels que le prélèvement chirurgical de celles ayant des interprétations biologiques pertinentes. De plus, parmi les signaux pertinents biologiquement, cette analyse nous a permis de différencier les signaux provenant du stroma, comme la réponse immunitaire médiée par les lymphocytesB&T, de ceux produits par les tumeurs elles-mêmes, comme les signaux reliés à la prolifération ou à la différenciation. La classification des tumeurs selon leurs contributions à certaines CIs a pu être étroitement associée à des annotations anatomo-cliniques, et a mis en évidence de nouveaux sous-types de tumeur spotentiels, qui suggèrent l'existence de voies de progression supplémentaires dans le cancer de vessie. De façon similaire, l'étude des contributions de groupes de tumeurs basés sur des annotations cliniques ou moléculaires a montré différents niveaux de contamination par le stroma entre les tumeurs mutées et nonmutées pour FGFR3. La reproductibilité des composantes a été étudiée en utilisant des graphes de corrélation. La majeure partie des CIs interprétées a été validée sur trois jeux de données indépendants, et plusieurs d'entre elles ont aussi détectées dans un jeu de données de lignées cellulaires.Une deuxième étude sur le rétinoblastome a montré que nous pouvions tirer partie de l'ACI dans des contextes variés. Le rétinoblastome est initié par la perte des deux alléles du gène suppresseur de tumeur RB1. D'autres évènements génomiques non identifiés sont nécessaires à la progression de la maladie. Nous avons observé une association entre âge des patients et altérations génomiques. Les patients jeunes présentant moins d'altérations que les patients âgés, ces derniers présentant des gains du 1q et des pertes du 16q. Cette séparation des tumeurs selon l'âge est également observée sur les données d'expression, notamment en appliquant l'ACI dont l'une des composantes discrimine les patients selon leur âge. Ces résultats suggèrent l'existence de deux voies de progression dans le rétinoblastome. L'analyse des données à haut débit fournit de nombreuses listes de gènes. Afin de les interpréter, une possibilité est d'extraire les dernières publications groupées par sujets prédéfinis (fonction, localisation,...). / Practice of gene expression data analysis shows that it is advantageous to analyze biologicalprocesses in terms of modules rather than simply consider gene one by one. In this project, we conducted anunsupervised analysis of the gene expression data of several cohorts of urothelial tumors, applying theIndependent Component Analysis method. Several studies demonstrated the outperformance of ICA overPCA and clustering-based methods in obtaining a more realistic decomposition of the expression data intoconsistent patterns of coexpressed genes associated with the studied phenotypes[1, 2, 3, 4].Urothelial tumors arise and evolve through two distinct pathways which radically differ on their probabilityof progression to muscle invasion. Except the mutation of FGFR3 in the less aggressive group, theunderlying molecular processes have not been completely identified. The first and main objective of the PhDthesis was dedicated to the biological interpretation of the different independent components to help toconfirm and extend the list of biological processes known to be involved in bladder cancer.Each independent component (IC) is characterized by a list of gene projections on the one hand and weightedcontributions of tumor samples on the other hand. By combining biological expertise and comparison of theassociated list of genes to known pathways, and jointly studying the association of the components tomolecular and clinical annotations, we have been able to differentiate components that were caused bytechnical factors, such as surgical sampling, from those having consistent biological interpretationin terms of tumor biology. Moreover, among the biologically meaningful signals, this analysis allowed us todifferentiate the signals from stroma of the tumor, like immune response mediated by B- and T-lymphocytes,from the signals produced by the tumors themselves, like signals related to proliferation, or differentiation.The clustering of the tumor samples according to their contributions on some ICs can be closely associated toanatomo-clinical annotations, and highlighted new potential subtypes of tumors which suggest existence ofadditional pathways of bladder cancer progression. Similarly, the study of the contributions of preestablishedgroups of tumors based on clinical or molecular criteria showed different levels of stromacontamination between FGFR3 non-mutated and mutated tumors. The reproducibility of the components wasinvestigated using correlation graphs. The major part of the interpreted ICs was validated on threeindependent bladder cancer datasets, and several of them were also identified in an urothelial cancer celllines data set.A second study about retinoblastoma gave us the occasion to show that we can take advantage ofICA in various contexts. Retinoblastoma is initiated by the loss of both alleles of the RB1 tumor suppressorgene. Although necessary for initiation, other genomic events, that remain to be identified, are needed for theprogression of the disease [5]. We observed, as it was previously described [6], an association between age ofthe patients and levels of genomic aberrations, the younger patients having fewer alterations than the olderpatients, which generally present gain of 1q and loss of 16q. We showed that this tendency of the tumors tobe clustered into two groups of age can also be observed on the expression data by applying ICA whose oneof the component was highly correlated to the age of the patients. These results suggest the existence of twopathways of progression in retinoblastoma.The analysis of high throughput data provides many lists of genes. To interpret them, a possibility isto study the latest related publications grouped by pre-defined group of topics (function, cellular location...).To that aim, in a third study, we introduced a web-based Java application tool named GeneValorization whichgives a clear and handful overview of the bibliography corresponding to one particular gene list [7].

Les tumeurs de vessie suivent deux voies de progression tumorale. La voie des carcinomes in situ (CIS) qui progressent pour envahir la membrane basale puis le muscle, et la voie des tumeurs papillaires de bas grade qui progressent peu mais qui récidivent fréquemment. Environ 65% des tumeurs papillaires de bas grade présentent une mutation du gène FGFR3 et récemment des protéines de fusion FGFR3-TACC3 ont été observées dans les tumeurs de vessie (dans 10% des tumeurs invasives). Le rôle oncogénique du récepteur FGFR3 muté et de FGFR3-TACC3 a été démontré in vivo et in vitro. Cependant, les voies de signalisation du récepteur FGFR3 muté ou de FGFR3-TACC3 sont à l’heure actuelle très peu caractérisées. Dans ce contexte, deux approches ont été mises en place pour caractériser ces voies de signalisation. La première s’appuie sur l’étude de la phosphorylation des protéines p38, AKT et ERK1/2 par le récepteur FGFR3 muté (S249C) ou sauvage dans la lignée cellulaire fibroblastique NIH3T3, et a permis d’identifier les protéines p38 et AKT comme activées par le récepteur FGFR3 muté et nécessaire pour induire la transformation cellulaire. L’étude de l’activation de ces deux voies de signalisation a été réalisée dans des lignées cellulaires dérivées de tumeurs de vessie exprimant le récepteur FGFR3 muté ou FGFR3-TACC3 de manière endogène et a montré que leur activation était dépendante de celle du récepteur FGFR3. De plus nous avons montré que les protéines p38 et AKT sont impliquées dans le maintien d’une boucle de rétro-contrôle positive entre FGFR3 et MYC : l’activation de FGFR3 induit une surexpression de MYC qui en retour promeut l’expression de FGFR3. La seconde approche est basée sur une étude visant à identifier les partenaires protéiques de FGFR3 par spectrométrie de masse après immunoprécipitation de celui-ci qui avait été réalisée précédemment au laboratoire. L’analyse des données a permis l’obtention d’une liste de 60 protéines identifiées comme partenaires protéiques de FGFR3 avec une grande confiance. La construction d’un réseau à partir de cette liste n’a pas été possible (trop peu d’interactions existant entre ces protéines), nous avons donc développé un algorithme (PEPPER) en collaboration avec un étudiant en bio-informatique au laboratoire, Rémy Nicolle, pour proposer un réseau de signalisation de FGFR3.Les deux approches mises en place au cours de cette thèse nous ont permis de mieux caractériser les voies de signalisation du récepteur FGFR3. L’identification d’une boucle de rétrocontrôle entre FGFR3 et MYC a permis de mieux comprendre pourquoi le récepteur FGFR3 possède des propriétés oncogéniques, et de proposer les protéines p38 et AKT comme cibles thérapeutiques potentielles pour traiter les tumeurs de vessie exprimant le récepteur FGFR3 altéré. La construction du réseau de signalisation de FGFR3 via PEPPER donne une vue d’ensemble des voies de signalisation de FGFR3 et ouvre de nouvelles pistes à étudier. / Bladder cancer progression can be divided in two main pathways. The pathway of In Situ Carcinoma (CIS) which progress through an invasion of the basement membrane and then the muscle and the pathway of Ta papillary tumors which change little but recur frequently after tumor resection. Approximately 65% of Ta papillary tumors harboring a FGFR3 mutation and recently FGFR3-TACC3 fusion proteins have been observed in bladder tumors (about 10% of bladder tumors). The oncogenic role of the mutated FGFR3 receptor and of the FGFR3-TACC3 fusion protein has been demonstrated in vivo and in vitro. However signaling pathways activated by the mutated FGFR3 receptor or by the FGFR3-TACC3 fusion protein are currently poorly characterized.In this context, two approaches have been developed to characterize these signaling pathways. The first is based on the study of p38, AKT and ERK1/2 phosphorylation by the mutated receptor (S249C) or the wild type receptor in the NIH3T3 fibroblastic cell line. This study allowed identifying p38 and AKT as activated by the mutated FGFR3 receptor. Moreover, activation of p38 and AKT by the mutated receptor is critical for cell transformation. Study of the activation of these two signaling has been realized in human bladder cancer cell lines endogenously expressing the mutated FGFR3 receptor or the FGFR3-TACC3 fusion protein. Moreover, we showed that p38 and AKT are involved in the maintenance of a FGFR3/MYC feedback positive loop: FGFR3 activation induce MYC over expression which in turns promotes FGFR3 expression. The second approach is based on a study whose aim was to identify FGFR3 proteins partners by mass spectrometry after a FGFR3 immunoprecipitation, which has been previously realized in the lab. Data analyze led to the obtaining of a list of 60 proteins identified has FGFR3 protein partners with a high confidence. Construction of a FGFR3 network with this list was not possible (too little interactions existing between these proteins), so we developed an algorithm (PEPPER) in collaboration with a student in bioinformatics in the lab, Remy Nicolle, to propose a FGFR3 signaling network.The two approaches developed during this thesis allowed us to better characterize the FGFR3 signaling pathways. Identification of a FGFR3/MYC feedback loop allowed us to better understand why the altered FGFR3 has oncogenic properties and to propose p38 and AKT as news promising therapeutic targets, to treat human bladder tumors harboring the altered FGFR3 receptor. Construction of the FGFR3 signaling network with the algorithme PEPPER give an overview of the FGFR3 signaling pathways and open new tracks to explore.

O bairro do Bexiga foi resultado de um processo político e econômico mais amplo pelo qual passava o país desde a segunda metade do século XIX, com o desenvolvimento da economia cafeeira e a inserção do estado de São Paulo no mercado exportador, envolvendo a Abolição da Escravidão, a instauração da República e a readequação das práticas urbanas de acordo com os parâmetros europeus de urbanização e industrialização. Nesse processo, iniciativas orientadas por um zoneamento e especialização de usos e funções explícitos e implícitos na legislação foram adotados com o objetivo de adequar a capital paulista ao novo papel. Assim, parte das moradias e dos segmentos do comércio de gêneros alimentícios, bem como oficinas, depósitos e fábricas e serviços menos nobres deslocaram-se em direção dos bairros vizinhos ao perímetro central. A especialização das funções urbanas implicou não somente no redesenho das zonas de exercício das atividades produtivas, como também das áreas de moradias exclusivas para determinados grupos sociais. Nesse contexto, em função da demanda, surgiram empreendimentos imobiliários de loteamentos destinados a abrigar moradores e atividades produtivas essenciais à cidade em expansão, dando origem a novos bairros, sendo o Bexiga um caso exemplar desse fenômeno. Esta tese se propõe a conhecer e compreender de que maneira o bairro do Bexiga se inseriu no movimento de reespacialização social e das funções urbanas - seu papel na reconfiguração da cidade -, assim como suas conexões com o espaço urbano mais amplo. De outro lado, no decorrer do século XX, alguns estereótipos foram construídos como traços determinantes do bairro, conferindo ao Bexiga um caráter de uniformidade funcional, social, étnica e arquitetônica. Assim, outro objetivo desta tese é desconstruir a visão estereotipada do Bexiga como um bairro homogêneo em todas as suas instâncias, destacando: a diversidade das atividades produtivas ali desenvolvidas, a presença e coexistência de diferentes camadas sociais, a presença de grupos étnicos diversos e as diferentes formas de moradia envolvendo bem mais do que as \"casas operárias\". / The quarter of Bexiga was a result of a wider economic and political process through which the country had undergone since the second half of 19th century, with the development of coffee economy and the insertion of the state of São Paulo in the export market, involving the Abolition of Slavery, the establishment of the Republic and the readaptation of the urban practices according to the European parameters of urbanization and industrialization. In this process, initiatives oriented by a zoning and specialization of use and functions explicit and implicit in the legislation were adopted with the objective of adjusting the São Paulo capital to the new role. Thus, part of the dwellings and the commerce of foodstuff, as well as workshops, store houses, factories and less noble services moved towards the neighborhoods of central areas. The specialization of urban functions resulted not only in the redesign of the productive activities zones, but also of the areas of dwellings exclusive for certain social groups. In this context, according to the demand, real state enterprises of housing development arose, aimed at sheltering dwellers and productive activities essential for the expanding city, giving rise to new quarters, and Bexiga was an exemplary case of this phenomenon. The present thesis aims at knowing and comprehending how the quarter of Bexiga became part of the movement of social and urban functions respatialization - its role in the reconfiguration of the city - , as well as its connections with the wider urban spaces. On the other hand, throughout the 20th century, some stereotypes were built as determining features of the quarter, giving Bexiga a quality of functional, social, ethnic and architectural uniformity. Thus, another objective of this thesis is deconstructing the stereotyped vision of Bexiga as a homogeneous quarter considering all of its aspects, highlighting: the diversity of productive activities developed there, the presence and coexistence of different social strata, the presence of diverse ethnic groups and the different forms of dwellings involving much more than the \"proletarian houses\".

Orientador: Maria Luiza Cotrim Sartor de Oliveira / Banca: Carlos Márcio Nóbrega de Jesus / Banca: Heidge Fukumasu / Não disponível / Abstract: Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that in a previous longterm study with Wistar rats fed at 2,500 ppm concentration showed high incidence of urothelial tumors in both genders. Accordingly, USEPA categorized Diuron as a "known/likely" human carcinogen. The accepted non-genotoxic mode of action (MOA) of Diuron encompasses urothelial necrosis induced by direct cytotoxicity, followed by regenerative cell proliferation and sustained urothelial hyperplasia that may favor neoplasia development. Scanning electron microscopy (SEM), light microscopy and labeling index are essentials tools for identification and classification of cytotoxic and proliferative changes in the bladder. The present study evaluated the dose-response of Diuron regarding urothelial lesions. Sixty male Wistar rats were fed Diuron for 20 weeks mixed in the diet at 0, 60, 125, 500, 1,250, or 2,500 ppm. Simple hyperplasia was significantly increased in the Diuron 1,250 and 2,500 ppm groups, and the cell proliferation at 2,500 ppm group. By SEM, the incidences and severity of lesions were significantly greater in the 500 and 1,250 ppm. Although numerically increased, the incidence of lesions in the 2,500 ppm group did not differ significantly from the control. The present study documented a doseresponse influence of Diuron on the rat urothelium, with a no observed effect level (NOEL) of 125 ppm. / Mestre

A lesão medular (LM) é um evento catastrófico e incapacitante com importante impacto físico e psicológico, influenciando significativamente a qualidade e expectativa de vida das pessoas acometidas. Nos últimos anos, com o crescimento progressivo da violência urbana e da sobrevida das pessoas, houve um aumento importante dos casos de LM, com aproximadamente 2,5 milhões de pessoas afetadas no mundo, sendo 130.000 casos novos ao ano. As complicações decorrentes da LM são diversas, dentre elas, as disfunções do trato urinário merecem destaque, por serem responsáveis pela maior parte das morbidades e por cerca de 10% a 15% de mortalidade dessa população. No Brasil, não há instrumento específico para coleta de dados amplos para LM, como propõem os Data Sets da Spinal Cord Injury Association (ISCoS). Assim, considerando o desafio da reabilitação vesical enfrentado por esta população , o presente estudo objetivou realizar o processo de tradução, adaptação e validação do Data Set do trato urinário inferior. Tratou-se de estudo quantitativo, metodológico, de delineamento transversal, dividido nas fases de tradução, realizado segundo as recomendações da ISCoS, e teste de confiabilidade inter e intraexaminadores, testado a partir do índice AC1 proposto por Gwet e o índice Kappa, contando com uma amostra de 50 participantes. Como resultado da fase de tradução, das nove questões que compunham o instrumento, apenas quatro termos apresentaram divergências e tiveram que ser revistos; e destes, um necessitou do acionamento do comitê da ISCoS. O perfil geral dos participantes foi composto de homens , com idade média de 39 anos, com LM de etiologia traumática e tempo de lesão inferior a dois anos. A confiabilidade interexaminadores mostrou-se adequada com valores acima de 0,5 em 100% das questões testadas com índice AC1 de Gwet; para o Kappa, o índice permaneceu acima de 0,5 em 70,5% das questões e foi observado que o índice AC1 de Gwet se mostrou superior ao Kappa em relação à prevalência de respostas com alta concordância. A avaliação da confiabilidade intraexaminador mostrou que o índice AC1 de Gwet, em oito das 17 questões avaliadas, ficou abaixo de 0,5. Já o índice Kappa ficou abaixo de 0,5 em cinco das 17 questões. Isso foi atribuído às temáticas das questões que tratavam dos temas de incontinência urinária e uso de dispositivos para incontinência e ao fato de os participantes estarem inseridos em programas de reabilitação, o que ocasionou mudanças no trato urinário durante o intervalo entre entrevistas, que foi de aproximadamente duas semanas. Foi observado ainda um alto índice de participantes que realizavam o cateterismo urinário (70%) e com uso de dispositivos para incontinência urinária (64%), assim é preciso avançar em estudos para o tratamento das disfunções que promovam também a continência urinária. Este estudo realizou a tradução e a validação para o português brasileiro do Data Set do trato urinário inferior segundo as recomendações da ISCoS, corroboradas pela literatura científica, gerando um instrumento confiável de coleta de dados clínicos sobre o trato urinário inferior para ser utilizado no Brasil, contribuindo para a reabilitação das pessoas com LM / Spinal cord injury (SCI) is a catastrophic and disabling event with an important physical and psychological event, significantly influencing the quality and life expectancy of the person involved. In recent years, due to the progressive growth of urban violence and the survival of the people, there was a significant increase in cases of SCI, with approximately 2.5 million people affected worldwide, with 130,000 new cases a year. Complications arising from the SCI are numerous, and among them, the dysfunctions related to the urinary tract deserve prominence, since they are responsible for the majority of the morbidity and 10% to 15% of the mortality in this population. In Brazil, there is no specific instrument for the collection of comprehensive data for spinal cord injury, as it is the proposal presented by the Data Sets of the Spinal Cord Injury Association (ISCoS). Thus, taking into account the challenge of rehabilitation of the bladder faced by people with SCI, this study was aimed at carrying out the process of translation, adaptation and validation of the Data Set of the lower urinary tract. It was a methodological, quantitative study of transversal design, divided into phases of translation, carried out according to the recommendations of the ISCoS, and inter and intra examiners reliability test, tested from the AC1 index proposed by Gwet and the Kappa index, with a sample of 50 participants. As a result of the stage of translation, from the nine themes that make up the instrument, only four terms presented differences; and of these, only one needed actions of the Committee of ISCoS. The profile of the participants was of men, with average age of 39, with SCI of traumatic etiology and time of injury inferior to two years. Inter examiners reliability was adequate with values greater than 0.5 in 100% of the questions proven with AC1 Gwet index; for the Kappa, the index remained higher than 0.5 in 70.5% of the questions and it was observed that Gwet index AC1 was shown to be superior to the Kappa in relation to the prevalence of answers with high concordance. The evaluation of reliability Intra examiner showed that the AC1 index of Gwet, in eight of the 17 questions evaluated stayed below 0.5. The Kappa index stayed below 0.5 in five of the 17 questions. This was attributed to questions dealing with incontinence and use of devices for incontinence and also to the fact that the participants were still inserted in rehabilitation programs, which caused changes in the urinary tract during the interval between interviews, which was of approximately two weeks. A high rate of participants was observed performing urinary catheterization (70%) and use of devices for incontinence (64%), thus it is necessary to advance in the studies for the treatment of disorders which also promote continence. The present study performed the translation and validation to Brazilian Portuguese of the Data Set of the lower urinary tract according to the recommendations of the ISCoS, supported by the scientific literature, creating a reliable instrument for the collection of clinical data on the lower urinary tract to be used in Brazil, contributing to the rehabilitation of people with spinal cord injuries

O diagnóstico de câncer e a necessidade de passar por vários tratamentos geram impactos e transformações na vida da pessoa. A reação individual para lidar com o itinerário da doença sofre influência do contexto sociocultural e repercute no modo de lidar com os sentimentos existenciais da experiência. Esses sentimentos podem ser expressos por termos diversos, entre eles, a depressão. O objetivo deste estudo foi interpretar os significados da depressão atribuídos pelos pacientes com câncer de bexiga em seguimento terapêutico, construídos com base em dados narrativos. Empregou-se a abordagem metodológica qualitativa, embasado pelo referencial teórico-metodológico da antropologia médica e do método da narrativa. Após aprovação ética para a pesquisa e consentimento das chefias da instituição coparticipante, foram convidados 12 participantes com câncer de bexiga, sem diagnóstico de depressão, em seguimento terapêutico no Ambulatório de Urologia Oncológica de um serviço de saúde de alta complexidade do interior do Estado de São Paulo, para participar do estudo. A coleta de dados ocorreu no período de janeiro 2014 a fevereiro de 2015, por meio de entrevistas semiestruturadas gravadas, observação direta e registros no diário de imersão, realizadas nos domicílios dos participantes e no serviço de saúde. Obteve-se uma amostra representativa do grupo, não intencional, homogênea quanto ao sexo, sendo a maioria acima de 60 anos, casados, com mais de sete anos de estudos e aposentados. Para tratamento, todos realizaram RTU com associação da BCG para a maioria, e houve três cistectomizados. A análise dos dados narrativos apoiou-se nos pressupostos da análise temática pelo processo indutivo. Identificaram-se as categorias com as quais elaboramos as unidades de sentidos do processo vivido com o câncer de bexiga e a depressão, compondo os modelos explanatórios dos pacientes. As unidades de sentidos serviram de guia para a construção de duas sínteses narrativas e seus significados: \"O paradoxo da vida com câncer de bexiga\" e \"A depressão como emoção no câncer de bexiga em seguimento terapêutico\". A primeira síntese aborda as dificuldades com o processo da doença e tratamento enquanto rupturas na vida, futuro incerto pela possibilidade de recidiva da doença, necessidade de continuidade do tratamento para o controle da doença e a lógica compensatória de controle emocional, relacionando-se com as ponderações contraditórias da vida atual. Assim, o significado desta síntese narrativa é de paradoxo. A segunda síntese aborda a incorporação do termo depressão ao senso comum, o qual revela a dimensão sociocultural da condição de ser sobrevivente oncológico em seguimento terapêutico. O seu significado revela a depressão no câncer como prática social e expressão de subjetividade, por meio da emoção de tristeza. Esta investigação permitiu-nos interpretar os significados da depressão atribuídos pelos adoecidos com câncer de bexiga segundo suas experiências. Como considerações finais, destacamos a importância dos enfermeiros em darem atenção à saúde mental do adoecido pelo câncer, pela escuta das suas subjetividades para promoveram intervenções adequadas, objetivando a integralidade do cuidado / The diagnosis of cancer and the need to undergo several treatments cause impact and change in the people\'s life. The personal reaction in coping with the itinerary of the disease suffers influence of the sociocultural context affecting the way of dealing with existential feelings from experience. These feelings can be related through different terms, among them, depression. The aim of study was to interpret the meanings of the depression attributed by patients with bladder cancer under therapeutic follow-up, based on their narratives. It was used the qualitative methodological approach, supported by theoretical-methodological referential of medical anthropology and narrative method. After ethical approval for the research and agreement of the heads of institutions, as coparticipants, 12 individuals were invited to participate of the study, they all with bladder cancer, without depression diagnosis, under therapeutic follow-up at the Oncological Urology Clinic that provide health service of high complexity in the countryside of São Paulo state . The data collection occurred from January 2014 to February 2015, through recorded semi-structured interviews, direct observations and it were registered in the immersion diary. These activities were held at the patients´ residences and in the health service. It was obtained a representative sample of the group, non-intentional, homogeneous regard to sex, being the most part of the patients over 60 years old, married, with more seven years of schooling and retired. For treatment, they all were submitted to TUR, with BCG association for the greater part and three of them by cystectomy. The analysis of narratives data was supported on the assumptions of thematic analysis by inductive process. The categories were identified and used to elaborate the units of senses of the experienced process by bladder cancer and depression as well as built the explanatory models of the patients. These units of senses served as guide for construction of two narratives syntheses and their meanings: \"The paradox of life with bladder cancer\" and \"The depression as emotion with bladder cancer under therapeutic follow-up\". The first synthesis addresses the difficulties with disease process and treatment as rupture of life, an uncertain future on the possibility of recurrence of the disease, the need of continuous treatment to control the disease and compensatory logic of the emotional control relating to contradictories considerations of the current life. Thus, the meaning of this narrative synthesis is paradox. The second synthesis approaches the incorporation of the depression term to common sense, which exposes the sociocultural dimension of the condition of being cancer survivor under therapeutic follow-up; its meaning reveals depression in cancer as social practice and subjectivity expression through emotion of sadness. This research allowed us to interpret the meanings of depression attributed by patients with bladder cancer according to their experiences. As final consideration, we emphasize the importance of the nurses to give attention to the mental health of the patients with cancer, by listening to their subjectivities to promote appropriate interventions, aiming care completeness

O diagnóstico de câncer e a necessidade de passar por vários tratamentos geram impactos e transformações na vida da pessoa. A reação individual para lidar com o itinerário da doença sofre influência do contexto sociocultural e repercute no modo de lidar com os sentimentos existenciais da experiência. Esses sentimentos podem ser expressos por termos diversos, entre eles, a depressão. O objetivo deste estudo foi interpretar os significados da depressão atribuídos pelos pacientes com câncer de bexiga em seguimento terapêutico, construídos com base em dados narrativos. Empregou-se a abordagem metodológica qualitativa, embasado pelo referencial teórico-metodológico da antropologia médica e do método da narrativa. Após aprovação ética para a pesquisa e consentimento das chefias da instituição coparticipante, foram convidados 12 participantes com câncer de bexiga, sem diagnóstico de depressão, em seguimento terapêutico no Ambulatório de Urologia Oncológica de um serviço de saúde de alta complexidade do interior do Estado de São Paulo, para participar do estudo. A coleta de dados ocorreu no período de janeiro 2014 a fevereiro de 2015, por meio de entrevistas semiestruturadas gravadas, observação direta e registros no diário de imersão, realizadas nos domicílios dos participantes e no serviço de saúde. Obteve-se uma amostra representativa do grupo, não intencional, homogênea quanto ao sexo, sendo a maioria acima de 60 anos, casados, com mais de sete anos de estudos e aposentados. Para tratamento, todos realizaram RTU com associação da BCG para a maioria, e houve três cistectomizados. A análise dos dados narrativos apoiou-se nos pressupostos da análise temática pelo processo indutivo. Identificaram-se as categorias com as quais elaboramos as unidades de sentidos do processo vivido com o câncer de bexiga e a depressão, compondo os modelos explanatórios dos pacientes. As unidades de sentidos serviram de guia para a construção de duas sínteses narrativas e seus significados: \"O paradoxo da vida com câncer de bexiga\" e \"A depressão como emoção no câncer de bexiga em seguimento terapêutico\". A primeira síntese aborda as dificuldades com o processo da doença e tratamento enquanto rupturas na vida, futuro incerto pela possibilidade de recidiva da doença, necessidade de continuidade do tratamento para o controle da doença e a lógica compensatória de controle emocional, relacionando-se com as ponderações contraditórias da vida atual. Assim, o significado desta síntese narrativa é de paradoxo. A segunda síntese aborda a incorporação do termo depressão ao senso comum, o qual revela a dimensão sociocultural da condição de ser sobrevivente oncológico em seguimento terapêutico. O seu significado revela a depressão no câncer como prática social e expressão de subjetividade, por meio da emoção de tristeza. Esta investigação permitiu-nos interpretar os significados da depressão atribuídos pelos adoecidos com câncer de bexiga segundo suas experiências. Como considerações finais, destacamos a importância dos enfermeiros em darem atenção à saúde mental do adoecido pelo câncer, pela escuta das suas subjetividades para promoveram intervenções adequadas, objetivando a integralidade do cuidado / The diagnosis of cancer and the need to undergo several treatments cause impact and change in the people\'s life. The personal reaction in coping with the itinerary of the disease suffers influence of the sociocultural context affecting the way of dealing with existential feelings from experience. These feelings can be related through different terms, among them, depression. The aim of study was to interpret the meanings of the depression attributed by patients with bladder cancer under therapeutic follow-up, based on their narratives. It was used the qualitative methodological approach, supported by theoretical-methodological referential of medical anthropology and narrative method. After ethical approval for the research and agreement of the heads of institutions, as coparticipants, 12 individuals were invited to participate of the study, they all with bladder cancer, without depression diagnosis, under therapeutic follow-up at the Oncological Urology Clinic that provide health service of high complexity in the countryside of São Paulo state . The data collection occurred from January 2014 to February 2015, through recorded semi-structured interviews, direct observations and it were registered in the immersion diary. These activities were held at the patients´ residences and in the health service. It was obtained a representative sample of the group, non-intentional, homogeneous regard to sex, being the most part of the patients over 60 years old, married, with more seven years of schooling and retired. For treatment, they all were submitted to TUR, with BCG association for the greater part and three of them by cystectomy. The analysis of narratives data was supported on the assumptions of thematic analysis by inductive process. The categories were identified and used to elaborate the units of senses of the experienced process by bladder cancer and depression as well as built the explanatory models of the patients. These units of senses served as guide for construction of two narratives syntheses and their meanings: \"The paradox of life with bladder cancer\" and \"The depression as emotion with bladder cancer under therapeutic follow-up\". The first synthesis addresses the difficulties with disease process and treatment as rupture of life, an uncertain future on the possibility of recurrence of the disease, the need of continuous treatment to control the disease and compensatory logic of the emotional control relating to contradictories considerations of the current life. Thus, the meaning of this narrative synthesis is paradox. The second synthesis approaches the incorporation of the depression term to common sense, which exposes the sociocultural dimension of the condition of being cancer survivor under therapeutic follow-up; its meaning reveals depression in cancer as social practice and subjectivity expression through emotion of sadness. This research allowed us to interpret the meanings of depression attributed by patients with bladder cancer according to their experiences. As final consideration, we emphasize the importance of the nurses to give attention to the mental health of the patients with cancer, by listening to their subjectivities to promote appropriate interventions, aiming care completeness

A lesão medular (LM) é um evento catastrófico e incapacitante com importante impacto físico e psicológico, influenciando significativamente a qualidade e expectativa de vida das pessoas acometidas. Nos últimos anos, com o crescimento progressivo da violência urbana e da sobrevida das pessoas, houve um aumento importante dos casos de LM, com aproximadamente 2,5 milhões de pessoas afetadas no mundo, sendo 130.000 casos novos ao ano. As complicações decorrentes da LM são diversas, dentre elas, as disfunções do trato urinário merecem destaque, por serem responsáveis pela maior parte das morbidades e por cerca de 10% a 15% de mortalidade dessa população. No Brasil, não há instrumento específico para coleta de dados amplos para LM, como propõem os Data Sets da Spinal Cord Injury Association (ISCoS). Assim, considerando o desafio da reabilitação vesical enfrentado por esta população , o presente estudo objetivou realizar o processo de tradução, adaptação e validação do Data Set do trato urinário inferior. Tratou-se de estudo quantitativo, metodológico, de delineamento transversal, dividido nas fases de tradução, realizado segundo as recomendações da ISCoS, e teste de confiabilidade inter e intraexaminadores, testado a partir do índice AC1 proposto por Gwet e o índice Kappa, contando com uma amostra de 50 participantes. Como resultado da fase de tradução, das nove questões que compunham o instrumento, apenas quatro termos apresentaram divergências e tiveram que ser revistos; e destes, um necessitou do acionamento do comitê da ISCoS. O perfil geral dos participantes foi composto de homens , com idade média de 39 anos, com LM de etiologia traumática e tempo de lesão inferior a dois anos. A confiabilidade interexaminadores mostrou-se adequada com valores acima de 0,5 em 100% das questões testadas com índice AC1 de Gwet; para o Kappa, o índice permaneceu acima de 0,5 em 70,5% das questões e foi observado que o índice AC1 de Gwet se mostrou superior ao Kappa em relação à prevalência de respostas com alta concordância. A avaliação da confiabilidade intraexaminador mostrou que o índice AC1 de Gwet, em oito das 17 questões avaliadas, ficou abaixo de 0,5. Já o índice Kappa ficou abaixo de 0,5 em cinco das 17 questões. Isso foi atribuído às temáticas das questões que tratavam dos temas de incontinência urinária e uso de dispositivos para incontinência e ao fato de os participantes estarem inseridos em programas de reabilitação, o que ocasionou mudanças no trato urinário durante o intervalo entre entrevistas, que foi de aproximadamente duas semanas. Foi observado ainda um alto índice de participantes que realizavam o cateterismo urinário (70%) e com uso de dispositivos para incontinência urinária (64%), assim é preciso avançar em estudos para o tratamento das disfunções que promovam também a continência urinária. Este estudo realizou a tradução e a validação para o português brasileiro do Data Set do trato urinário inferior segundo as recomendações da ISCoS, corroboradas pela literatura científica, gerando um instrumento confiável de coleta de dados clínicos sobre o trato urinário inferior para ser utilizado no Brasil, contribuindo para a reabilitação das pessoas com LM / Spinal cord injury (SCI) is a catastrophic and disabling event with an important physical and psychological event, significantly influencing the quality and life expectancy of the person involved. In recent years, due to the progressive growth of urban violence and the survival of the people, there was a significant increase in cases of SCI, with approximately 2.5 million people affected worldwide, with 130,000 new cases a year. Complications arising from the SCI are numerous, and among them, the dysfunctions related to the urinary tract deserve prominence, since they are responsible for the majority of the morbidity and 10% to 15% of the mortality in this population. In Brazil, there is no specific instrument for the collection of comprehensive data for spinal cord injury, as it is the proposal presented by the Data Sets of the Spinal Cord Injury Association (ISCoS). Thus, taking into account the challenge of rehabilitation of the bladder faced by people with SCI, this study was aimed at carrying out the process of translation, adaptation and validation of the Data Set of the lower urinary tract. It was a methodological, quantitative study of transversal design, divided into phases of translation, carried out according to the recommendations of the ISCoS, and inter and intra examiners reliability test, tested from the AC1 index proposed by Gwet and the Kappa index, with a sample of 50 participants. As a result of the stage of translation, from the nine themes that make up the instrument, only four terms presented differences; and of these, only one needed actions of the Committee of ISCoS. The profile of the participants was of men, with average age of 39, with SCI of traumatic etiology and time of injury inferior to two years. Inter examiners reliability was adequate with values greater than 0.5 in 100% of the questions proven with AC1 Gwet index; for the Kappa, the index remained higher than 0.5 in 70.5% of the questions and it was observed that Gwet index AC1 was shown to be superior to the Kappa in relation to the prevalence of answers with high concordance. The evaluation of reliability Intra examiner showed that the AC1 index of Gwet, in eight of the 17 questions evaluated stayed below 0.5. The Kappa index stayed below 0.5 in five of the 17 questions. This was attributed to questions dealing with incontinence and use of devices for incontinence and also to the fact that the participants were still inserted in rehabilitation programs, which caused changes in the urinary tract during the interval between interviews, which was of approximately two weeks. A high rate of participants was observed performing urinary catheterization (70%) and use of devices for incontinence (64%), thus it is necessary to advance in the studies for the treatment of disorders which also promote continence. The present study performed the translation and validation to Brazilian Portuguese of the Data Set of the lower urinary tract according to the recommendations of the ISCoS, supported by the scientific literature, creating a reliable instrument for the collection of clinical data on the lower urinary tract to be used in Brazil, contributing to the rehabilitation of people with spinal cord injuries

<p>Cancer immunotherapy aims at reversing the immunosuppressive tumor environment and enhancing anti-tumor immunity. This thesis comprises studies on murine models for prostate (TRAMP-C2) and bladder (MB49) cancer with the aim to explore if the introduction of an adenoviral vector expressing CD40 ligand (AdCD40L) can induce anti-tumor immune responses.</p><p>We show in subcutaneous mouse models that AdCD40L treatment suppresses tumor growth. Bladder cancer is known to secrete immunosuppressive IL-10 which may inhibit T cell function. We show that introducing AdCD40L into mouse bladder tumors inhibits IL-10 production and reverses immunosuppression. AdCD40L-transduced mouse prostate cancer cells showed caspase activation and reduced cell viability. Vaccination with CD40L-modified prostate cancer cells induces anti-tumor responses and protects mice against rechallenge with native TRAMP-C2 cells. In order to enhance AdCD40L therapy, we explored the possibility of combining it with the histone deacetylase inhibitor FK228, also known as depsipeptide. We show that FK228 upregulates coxsackie and adenovirus receptor expression and thereby enhances adenoviral-mediated CD40L expression in both murine and human prostate cancer cells. Increasing amounts of FK228 or AdCD40L reduces prostate cancer cell viability, while the combined treatment gives at least an additive therapeutic effect. Moreover, we show that AdCD40L transduction of prostate cancer cells induces endogenous CD40 expression and sensitize them for CD40L-mediated therapy.</p><p>In order to conduct prostate-specific gene therapy, prostate-specific promoters can be used to drive transgene expression. However, there are no reports on prostate-specific promoters that are transcriptionally active in mouse cells. Here we show that by using the two-step transcription activation system (TSTA), we can enhance the activity of a recombinant human promoter sequence and obtain activity in mouse prostate cancer cells as well. This finding paves the way for future studies of prostate-specific gene therapy in immunocompetent mouse models.</p>