Transcriptome analysis in animal models of mesial temporal lobe epilepsy

Orientadores: Íscia Teresinha Lopes Cendes, André Schwambach VieiraTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A epilepsia do lobo temporal mesial (ELTM) é uma doença neurológica crônica caracterizada pelo desenvolvimento de crises epiléticas e por anormalidades histopatológicas nas estruturas mediais do lobo temporal, principalmente a esclerose hipocampal (EH). O perfil de expressão gênica de tecido específico fornece informações biológicas relevantes sobre mecanismos moleculares potencialmente envolvidos em fenômenos biológicos complexos. Recentemente, devido à heterogeneidade da expressão gênica em diferentes subconjuntos de células, fica mais claro o quanto é importante a delimitação de regiões especificas, especialmente no sistema nervoso central. Utilizamos a técnica de RNAseq para determinar o perfil de expressão gênica no giro denteado (GD) do hipocampo e Cornu Ammonis 3 (CA3) em um modelo animal de epilepsia do lobo temporal induzido por pilocarpina. O sequenciamento de alto rendimento do RNA foi realizado a partir do tecido microdissecado do hipocampo, região dorsal e ventral do GD e CA3, assim como a intermediária de CA3, no modelo de pilocarpina em ratos Wistar. Avaliamos o perfil de expressão gênica e os processos biológicos enriquecidos a partir dos genes diferencialmente expressos. Os resultados indicam a presença de muitos genes regulados diferencialmente, dos quais, alguns foram específicos para cada sub-região do hipocampo nos ratos tratados com pilocarpina. No entanto, identificamos alguns importantes processos biológicos de sinalização que foram enriquecidos em todas os grupos celulares estudados e nas áreas examinadas, como, inflamação, navegação axonal, atividade neuronal e função sináptica. Os dados apresentados destacam a importância da análise de alto rendimento do transcriptoma no estudo de doenças complexas, como a epilepsia, e a vantagem de obter áreas delimitadas de tecido para analisar plenamente a grande heterogeneidade biológica de diferentes populações de células no sistema nervoso central. Nossos resultados sugerem uma predominância na região dorsal relacionada a atividade elétrica neuronal e orientação axonal, além de identificar uma interação entre vários componentes moleculares que levam à epileptogênese neste modelo animal que exibe dano hipocampal generalizadoAbstract: Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the development of seizures and by histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). It is well known that gene expression profile of specific tissue provides relevant biological information about molecular mechanisms potentially involved in complex biological phenomena. Recently, it has been recognized that due to the marked heterogeneity of gene expression in a different subset of cells, it is important to take sub-regional specificities when studying gene expression, especially in the central nervous system. We used RNA sequencing analysis to determine the profile of gene expression in the hippocampus dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of mesial temporal lobe epilepsy induced by pilocarpine. The high-throughput RNA sequencing was performed in tissue obtained from the dorsal and ventral DG and CA3, as well as the intermediate CA3, by laser-microdissection in Wistar rats. We evaluated the gene expression profile and the enriched signaling biological processes. Our results indicate that there were many differentially regulated genes, some of which were specific to each sub-regions of the hippocampus in the pilocarpine rats. However, we identified some major signaling biological processes that were enriched in all layers and areas examined, such as inflammation, axon guidance, neuronal activity and synaptic function. The data presented highlights the importance of high-throughput transcriptome analysis in the study of complex disorders such as epilepsy, and the advantage of obtaining tissue from delimitated areas to fully appreciate the large biological heterogeneity of different cell populations within the central nervous system. Our results suggest a predominance of the dorsal region in the neuronal electrical activity and axonal guidance. Furthermore, we identified an interaction among several molecular components leading to the epileptogenesis in this animal model that displays widespread hippocampal damageDoutoradoFisiopatologia MédicaDoutor em Ciências2013/8635-5FAPES

Partial Versus Total Trapeziectomy With Interposition Arthroplasty for Trapeziometacarpal Osteoarthritis Grade II to III Eaton-Littler : A Clinical Trial

Total trapeziectomy is the most widely used technique to treat isolated thumb trapeziometacarpal joint osteoarthritis. However, this technique has been associated with proximal migration of the thumb metacarpal, which has led some physicians to consider partial trapeziectomy as a valid alternative. The purpose of this study was to assess whether partial trapeziectomy improves final key pinch strength compared with total trapeziectomy. We randomized 34 patients with basal thumb osteoarthritis into 2 groups to undergo partial or total trapeziectomy with interposition arthroplasty. Key pinch strength at 12 months was the primary outcome measure. Other variables measured included trapezial space height, range of motion, grip strength, change in key pinch strength, patient-reported outcome measures, and pain. No difference between groups was detected regarding final pinch strength, trapezial space height, grip strength, range of motion, change in pinch strength, patient-reported outcomes (Quick -Disabilities of the Arm, Shoulder, or Hand), or pain. We cannot conclude that partial trapeziectomy provides an advantage over total trapeziectomy at 1 year after surgery. Although trapeziometacarpal space was substantially preserved in the partial trapeziectomy group at 12 months, this difference was not statistically or clinically significant. Diagnostic III

Development and implementation of a surgery management system aimed at a university hospital / Desenvolvimento e implementação de sistema de gerenciamento de cirurgias voltado a um hospital universitário

Objectives: To develop and implement the surgical management system containing the Surgical List and Surgical Map. Method: This study is of exploratory and descriptive nature of the applied methodological research type. The methodology used is based on the software development process based on the Pressman system development life cycle model. Results: The system was developed and made available on all hospital computers on its internal network. Implemented in all surgical areas and Surgical Center. Conclusion: The surgical management system provides real-time information on surgical patient information to all departments involved with surgical patients.Objetivos: Desarrollar e implementar el sistema de gestión de cirugías que contenga la Lista Quirúrgica y el Mapa Quirúrgico. Método: Este estudio es de naturaleza exploratoria y descriptiva del tipo investigación metodológica aplicada. La metodología utilizada se basa en el proceso de desarrollo de software fundamentada en el modelo de ciclo de vida de desarrollo de sistemas de Pressman. Resultados: El sistema fue desarrollado y puesto a disposición en todas las computadoras del hospital en su red interna. Implementado en todas las áreas quirúrgicas y el Centro Quirúrgico. Conclusión: El sistema de gestión de cirugías proporciona información en tiempo real de los pacientes quirúrgicos a todos los sectores involucrados con pacientes quirúrgicos.Objetivos: desenvolver e implementar o sistema de gerenciamento de cirurgias contendo a Lista Cirúrgica e Mapa Cirúrgico. Método: este estudo é de natureza exploratória e descritiva do tipo pesquisa metodológica aplicada. A metodologia utilizada baseia-se no processo de desenvolvimento de software fundamentada no modelo de ciclo de vida de desenvolvimento de sistemas de Pressman. Resultados: o sistema foi desenvolvido e disponibilizado em todos os computadores do hospital em sua rede interna. Implementado em todos as áreas cirúrgicas e Centro Cirúrgico. Conclusão: o sistema de gerenciamento de cirurgias disponibiliza informações em tempo real de informações dos pacientes cirúrgicos a todos setores envolvidos com pacientes cirúrgicos.

Predictions of the number of suspended surgeries using software Power BI® in a university hospital - Previsões do número de cirurgias suspensas utilizando o software Power BI® em um Hospital Universitário

Objective: To analyze the suspended surgeries, making future predictions of three months, starting in October 2022, through a line graph using the Power BI Software.  Method: We used the technique of weighted moving averages, simple exponential smoothing, using the Power BI® line graph tool, with a confidence interval of 95% and predictions of three months.  Results: The results showed that there are differences in the steps to construct predictions and some prerequisites must be fulfilled, the following predictions were found with their respective confidence intervals: November 134 (97,172), December 141 (102,180), January 147 (106,188).  Conclusion: The use of forecasts can be a useful tool for decision making, predicting problems and always necessary in the management of a hospital. and can even suppress expenses in anticipation of a variety of problems.Objetivo: Analizar las cirugías suspendidas, haciendo predicciones futuras de tres meses, a partir de octubre de 2022, a través de un gráfico lineal utilizando el software Power BI®.  Método: Se utilizó la técnica de medias móviles ponderadas, suavizado exponencial simple, utilizando la herramienta de gráfico de líneas de Power BI®, con un intervalo de confianza del 95% y predicciones de tres meses.  Resultados: Los resultados mostraron que existen diferencias en los pasos para construir predicciones y se deben cumplir algunos requisitos previos, se encontraron las siguientes predicciones con sus respectivos intervalos de confianza: noviembre 134 (97,172), diciembre 141 (102,180), enero 147 (106,188).  Conclusión: El uso de pronósticos puede ser una herramienta útil para la toma de decisiones, predicción de problemas y siempre necesaria en la gestión de un Hospital. e incluso puede suprimir gastos en previsión de una variedad de problemas.Objetivo: analisar as cirurgias suspensas, realizando previsões futuras de três meses, a partir de outubro de 2022, através de um gráfico de linhas utilizando o software Power BI®. Método: se utilizou a técnica de médias moveis ponderada, alisamento exponencial simples, utilizando a ferramenta gráfico de linhas do Power BI®, com intervalo de confiança de 95% e previsões de três meses. Resultados: os resultados demostraram que existem diferentes etapas para construir previsões e alguns pré-requisitos devem ser preenchidos, foram encontradas as seguintes previsões com seus respectivos intervalos de confiança: novembro 134(97,172), dezembro 141(102,180), janeiro 147(106.188). Conclusão: a utilização de previsões pode ser uma ferramenta útil para a tomada de decisão, prever problemas e sempre necessário na gestão de um hospital, podendo até suprimir gastos se antecipando a uma variedade de problemas.

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information

Little is known about the difference in gene expression between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts (NCFs) in colorectal cancer. Paired CAFs and NCFs were isolated from eight primary human colorectal carcinoma specimens. In culture conditions, soluble factors secreted by CAFs in the conditioned media increased clonogenicity and migration of epithelial cancer cells lines to a greater extent than did NCF. In vivo, CAFs were more competent as tumour growth enhancers than paired NCFs when co-inoculated with colorectal cell lines. Gene expression analysis of microarrays of CAF and paired NCF populations enabled us to identify 108 deregulated genes (38 upregulated and 70 downregulated genes). Most of those genes are fibroblast-specific. This has been validated in silico in dataset GSE39396 and by qPCR in selected genes. GSEA analysis revealed a differential transcriptomic profile of CAFs, mainly involving the Wnt signallingsignalling pathway, focal adhesion and cell cycle. Both deregulated genes and biological processes involved depicted a considerable degree of overlap with deregulated genes reported in breast, lung, oesophagus and prostate CAFs. These observations suggest that similar transcriptomic programs may be active in the transition from normal fibroblast in adjacent tissues to CAFs, independently of their anatomic demarcation. Additionally NCF already depicted an activated pattern associated with inflammation. The deregulated genes signature score seemed to correlate with CAF tumour promoter abilities in vitro, suggesting a high degree of heterogeneity between CAFs, and it has also prognostic value in two independent datasets. Further characterization of the roles these biomarkers play in cancer will reveal how CAFs provide cancer cells with a suitable microenvironment and may help in the development of new therapeutic targets for cancer treatment

Joc competitiu en línea per aprendre estadística

Un diagnòstic de les pràctiques d'estadística va portar a proposar per a una nova assignatura un joc competitiu en línia de presa de decisions basades en l'estadística. Aquest utilitza dades simulades i un web en què els estudiants adquireixen dades consumint un pressupost, hi introdueixen les decisions que prenen i fan el seguiment de la seva posició en el joc. El resultat final (PRESTON, PRàctiques d'ESTadística ON-line) ja s'ha utilitzat amb èxit a l'ETSEIB (2 quadrimestres, 400 estudiants).Peer Reviewe

Scientific production on computer-assisted numerical analysis in health / Produção científica sobre análise numérica assistida por computador em saúde

Objective: to evaluate the scientific production on computer-assisted numerical analysis in health, based on bibliometrics. Method: bibliometric research with a quantitative approach. The data were treated in the light of descriptive statistics, with the biblioshiny tool of the RStudio software. The terms used were "management, hospital material” and “barcode”. Results: 459 documents were recovered, in 274 titles, 445(96.95%) articles, 2458 authors, 81(3.30%) as sole authors. Age average number of documents was 8.91 years, co-authorship per document was 6.15. Conclusion: journals in zone 1 cannot be considered the most devoted to the subject. It was not possible to identify an elite group of authors.Objetivo: evaluar la producción científica sobre análisis numérico asistido por computadora en salud, con base en la bibliometría. Método: investigación bibliométrica con enfoque cuantitativo. Los datos fueron tratados a la luz de estadísticas descriptivo, con la herramienta biblioshiny del software RStudio. Los términos utilizados fueron "management, hospital material” y “barcode”. Resultados: se recuperaron 459 documentos, en 274 títulos, 445 (96,95%) artículos, 2458 autores, 81 (3,30%) como autor único. La edad promedio de documentos fue de 8,91 años, la coautoría por documento fue de 6,15. Conclusión: las revistas de la zona 1 no pueden considerarse las más dedicadas al tema. No fue possible identificar un grupo élite de autores.Objetivo: avaliar a produção científica sobre análise numérica assistida por computador em saúde, a partir da bibliometria. Método: pesquisa do tipo bibliométrica com abordagem quantitativa. Os dados foram tratados à luz da estatística descritiva, com a ferramenta biblioshiny do software RStudio. Os termos utilizados foram "management, hospital material” e “barcode”. Resultados: recuperou-se 459 documentos, em 274 títulos, 445(96,95%) artigos, 2458 autores, 81(3,30%) como autoria única. A idade média dos documentos foi de 8,91 anos, a coautoria por documento foi de 6,15. Conclusão: os periódicos da zona 1 não podem ser considerados os mais devotados ao assunto. Não foi possível identificar um grupo de elite de autores na temática analisada.

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.</p

Local hydrological conditions influence tree diversity and composition across the Amazon basin

Tree diversity and composition in Amazonia are known to be strongly determined by the water supplied by precipitation. Nevertheless, within the same climatic regime, water availability is modulated by local topography and soil characteristics (hereafter referred to as local hydrological conditions), varying from saturated and poorly drained to well-drained and potentially dry areas. While these conditions may be expected to influence species distribution, the impacts of local hydrological conditions on tree diversity and composition remain poorly understood at the whole Amazon basin scale. Using a dataset of 443 1-ha non-flooded forest plots distributed across the basin, we investigate how local hydrological conditions influence 1) tree alpha diversity, 2) the community-weighted wood density mean (CWM-wd) – a proxy for hydraulic resistance and 3) tree species composition. We find that the effect of local hydrological conditions on tree diversity depends on climate, being more evident in wetter forests, where diversity increases towards locations with well-drained soils. CWM-wd increased towards better drained soils in Southern and Western Amazonia. Tree species composition changed along local soil hydrological gradients in Central-Eastern, Western and Southern Amazonia, and those changes were correlated with changes in the mean wood density of plots. Our results suggest that local hydrological gradients filter species, influencing the diversity and composition of Amazonian forests. Overall, this study shows that the effect of local hydrological conditions is pervasive, extending over wide Amazonian regions, and reinforces the importance of accounting for local topography and hydrology to better understand the likely response and resilience of forests to increased frequency of extreme climate events and rising temperatures