74 research outputs found
Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.
CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC
Reliability and validity study of the Spanish adaptation of the “Wijma Delivery Expectancy/Experience Questionnaire” (W-DEQ-A)
The Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ-A) is an instrument that evaluates fear of childbirth through the expectations of women in relation to childbirth and their experience during the birth. The objective of this study was to translate the W-DEQ-A into Spanish and analyse its reliability and validity. The study was carried out in two phases: (1) adapting the questionnaire to Spanish and (2) a transversal study in a sample of 273 pregnant women in the Sexual and Reproductive Health centres in the Metropolitan Northern Barcelona in Catalonia (Spain). The psychometric properties were analysed in terms of reliability and construct validity. The confirmatory factorial analysis did not confirm the unidimensionality of the original structure of the WDEQ-A, as happened with the other studies in which it has previously been validated. The result of the exploratory factorial analysis suggests four factors, or dimensions, very similar but not identical to those obtained in other analysis studies of the W-DEQ-A. The Cronbach alpha and the omega scale were also adequate for all the scales and for each of the dimensions. The results of this study confirm the findings of other studies that suggest that the W-DEQ-A is multi-dimensional. In the Spanish version of the W-DEQ-A four dimensions have been identified to explore fear of childbirth in pregnant women. The Spanish version of the WDEQ-A (WDEQ-A-Sp) is reliable and valid for the measurement of fear of childbirth in clinical practice and for use in future research
Validity and reliability of the Spanish version of the “Wijma Delivery Expectancy/Experience Questionnaire” (W-DEQ-B)
The Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ-B) is an instrument that allows the experiences around fear of childbirth to be examined after the birth. It is currently the most widely used to measure different aspects related to the fear of childbirth and enables healthcare and additional assistance to women after birth to be adapted according to their needs. The objective of this study was to translate the W-DEQ-B into Spanish and analyse its reliability and validity. The study was carried out in two phases: (1) transcultural adaption of the questionnaire to Spanish and (2) a transversal study in a sample of 190 postpartum women from Sexual and Reproductive Health Clinics in the province of Barcelona (Spain). The psychometric properties were examined in terms of reliability (internal consistency and temporal stability) and construct validity (confirmatory factorial analysis [CFA] and exploratory factorial analysis [EFA]). The results of the CFA did not confirm unidimensionality of the W-DEQ-B questionnaire. The EFA suggested four very similar, but not identical, dimensions to those obtained in other studies in which the W-DEQ-B has been evaluated. Both the Cronbach's alpha and the omega coefficient were adequate for the total questionnaire and for each of the four dimensions. The results of this study confirm that the W-DEQ-B is multi-dimensional. In the Spanish version of the W-DEQ-B-Sp four dimensions have been identified that allow the experiences around fear of childbirth to be examined after the birth. The Spanish version of the WDEQ-B (WDEQ-B-Sp) is reliable and valid for the measurement of fear of childbirth in clinical practice and for use in future research
GuĂa de Práctica ClĂnica para el diagnĂłstico de compromiso orgánico en amiloidosis: parte 3/3 año 2020
MĂ©todos: Se generĂł un listado de preguntas con el formato PICO centradas en la especificidad y sensibilidad de las pruebas diagnĂłsticas en amiloidosis. Se realizĂł la bĂşsqueda en PubMed durante julio-agosto del 2019, en inglĂ©s y español. Los niveles de evidencia y los grados de recomendaciĂłn se basan en el sistema GRADE (http://www.gradeworkinggroup.org/index.htm). Las recomendaciones se graduaron segĂşn su direcciĂłn (a favor o en contra) y segĂşn fuerza (fuertes y dĂ©biles). Las recomendaciones finales fueron evaluadas con la herramienta GLIA para barreras y facilitadores en la implementaciĂłn de Ă©stas. InterpretaciĂłn de recomendaciones: Las recomendaciones fuertes indican alta confianza, ya sea a favor o en contra, de una intervenciĂłn. En esta guĂa se utiliza el lenguaje “se recomienda” cuando se define una recomendaciĂłn fuerte. Las recomendaciones dĂ©biles indican que los resultados para una intervenciĂłn, favorable o desfavorable, son dudosos. En este caso, se utiliza el lenguaje “se sugiere”, cuando se define una recomendaciĂłn dĂ©bil. CĂłmo utilizar estas pautas: Las recomendaciones deben ser interpretadas en el contexto de la atenciĂłn especializada, con estudios diagnĂłsticos validados y realizados por mĂ©dicos entrenados. Se asume que el mĂ©dico tratante tiene alto nivel de sospecha de amiloidosis. No asume condiciones coexistentes que modifican el curso de la enfermedad. Asume que los estudios diagnĂłsticos son realizados por mĂ©dicos entrenados con mĂ©todos validados y estandarizados. Esta guĂa es relevante para los profesionales de la salud y los involucrados en las polĂticas sanitarias, para ayudar a asegurar que existan los acuerdos necesarios para brindar la atenciĂłn adecuada
IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi Infection by Recruiting Suppressive IL-10-Producing Neutrophils
Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-Îł and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-Îł production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-Îł concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-Îł production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-Îł-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils
Rúbrica elaborada per avaluar la Competència “Pensament Reflexiu” (PR)
Projecte: 2016PID-UB/028[cat] El projecte en el qual s’emmarca aquest instrument respon a una comunitat de prà ctica com a base del treball cooperatiu, el desenvolupament professional interdisciplinari i la millora de la prà ctica docent a partir d’una xarxa entre els membres integrants procedents de cinc universitats (UB, UAB, UCLM, UBU i UVEG- La Florida Universitaria). Fruit d’aquest treball, es va aprofundir en el marc teòric sobre les activitats d’ensenyament i d’aprenentatge reflexiu a la Universitat a través de les metodologies narratives. Això va permetre l’elaboració de dispositius per facilitar el pensament reflexiu sobre el procés de construcció del coneixement, l’aprenentatge realitzat i el desenvolupament competencial per part de l’alumnat en el marc de les diferents assignatures implicades en el projecte. Paral.lelament, va permetre el disseny d’un sistema d’avaluació formativa coherent amb les tasques d’aprenentatge proposades, en forma de rúbriques. La proposta de la definició de pensament reflexiu com a competència comuna, aixà com de les dimensions i els indicadors amb els corresponents nivells de domini és el que es presenta en el present document.[spa] El proyecto en el cual se enmarca este instrumento responde a una comunidad de práctica como base del trabajo cooperativo, el desarrollo profesional
interdisciplinario y la mejora de la práctica docente a partir de una red entre los miembros integrantes procedentes de cinco universidades (UB, UAB, UCLM,
UBU y UVEG- La Florida Universitaria).
Fruto de este trabajo, se profundizó en el marco teórico sobre las actividades de enseñanza y de aprendizaje reflexivo en la Universidad a través de las
metodologĂas narrativas. Esto permitiĂł la elaboraciĂłn de dispositivos para facilitar el pensamiento reflexivo sobre el proceso de construcciĂłn del conocimiento,
el aprendizaje realizado y el desarrollo competencial por parte del alumnado en el marco de las diferentes asignaturas implicadas en el proyecto. Paralelamente,
permitió el diseño de un sistema de evaluación formativa coherente con las tareas de aprendizaje propuestas, en forma de rúbricas. La propuesta de la definición
de pensamiento reflexivo como competencia común, asà como de las dimensiones y los indicadores con los correspondientes niveles de dominio se presenta a continuación.Recurs elaborat en el marc del projecte concedit a la convocatòria de Projecte d’innovació docent del Programa de Millora i Innovació Docent, “El pensament reflexiu i el desenvolupament competencial a l'educació superior” (2016PID-UB/028)
Activation of Different Signals Identified with Glia Cells Contribute to the Progression of Hyperalgesia
El pensamiento reflexivo a travĂ©s de las metodologĂas narrativas: experiencias de innovaciĂłn en educaciĂłn superior
CoordinaciĂł: Marta Sabariego PuigEste cuaderno es fruto de dos proyectos concedidos en las convocatorias de ayudas a la investigaciĂłn en docencia universitaria (REDI- CE14-1511 y REDICE16-1660). Están centrados en el estudio de las metodologĂas de carácter narrativo y (auto)biográfico (Suárez, 2011) sobre el pensamiento reflexivo para el desarrollo personal y profesional del alumnado universitario. Ambos proyectos han permitido la consolidaciĂłn de una comunidad de práctica, una red interuniversitaria e interdisciplinar de profesorado docente e investigador que tiene como finalidad profundizar en la base teĂłrica, la sistematizaciĂłn y la validaciĂłn de las experiencias de innovaciĂłn para el fomento del pensamiento reflexivo a travĂ©s de las metodologĂas narrativas. El cuaderno es el producto del análisis colectivo de las experiencias desarrolladas y los resultados obtenidos, vinculando la investigaciĂłn con la innovaciĂłn para una docencia de calidad que nos lleve a pensar sobre el valor de una de las vĂas más importantes para construir y reconstruir significados en las actividades de enseñanza y aprendizaje que se plantean en el espacio universitario: la reflexiĂłn.
El texto está organizado en dos secciones. La primera recoge tres apartados teĂłricos sobre la fundamentaciĂłn conceptual del pensamiento reflexivo, las caracterĂsticas de los espacios de aprendizaje favorables al desarrollo de esta competencia básica para el aprendizaje en la Universidad y el valor de los dispositivos narrativos diseñados. La segunda secciĂłn engloba diez experiencias innovadoras que ilustran el desarrollo de un aprendizaje más reflexivo en el alumnado vĂa escritura narrativa. Finalmente, el cuaderno concluye con propuestas para contribuir a la renovaciĂłn y validaciĂłn de una actividad docente organizada y estructurada a este efecto en la educaciĂłn superio
Selenium biochemistry and its role for human health
Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases
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