Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GR beta) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR(iKO)) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker

Experiencia en la creación de registros con fines de Investigación Clínica

RESUMEN: La legislación en Chile ha regulado el desarrollo de investigación clínica aplicada. Actualmente, es posible utilizar los datos de la ficha clínica de los pacientes, con fines de investigación, previa autorización del sujeto a través del proceso de consentimiento informado respectivo. La gran cantidad de datos clínicos acumulados en los registros de salud representan una oportunidad para el desarrollo de investigación, más aún cuando los registros son electrónicos.En el año 2012, la Subdirección de Investigación en conjunto con el Comité de Ética de Clínica Las Condes, elaboraron un documento para regular, orientar y potenciar el uso de registros con fines de investigación biomédica por los profesionales de la salud de la institución.El objetivo de este artículo es compartir la experiencia en la creación de registros con fines de investigación científica, su desarrollo y la modalidad de funcionamiento en base a la regulación ético-legal chilena. ABSTRACT: Legislation in Chile has regulated the development of clinical research. At present, it is possible to use patient's health clinical records for research purposes, with prior authorization of the subject through the respective informed consent process. The large amount of clinical data accumulated in health records represents an opportunity for research development, especially when the records are electronic.In 2012, the Academic Research Unit and the Ethics Committee of Clínica Las Condes, developed a Protocol to regulate, guide and enhance the use of health clinical records for biomedical research purposes by healthcare professionals of the institution.The aim of this article is to share the experience of the development of clinical registries for scientific research, based on the local ethics and legal regulation. Palabras clave: Investigación, registros en salud, ficha clínica, base de datos, Keywords: Biomedical research, electronic health records, registries, data collectio

Planificación y factibilidad de un proyecto de investigación clínica

RESUMEN: La investigación científica se ha consolidado como el mejor modo de generar conocimiento confiable, válido, verificable y reproducible. En el ámbito de la salud humana, la investigación biomédica ha permitido ampliar la comprensión de las enfermedades y avanzar en su prevención y en el tratamiento y rehabilitación de las personas en situación de enfermedad. El método científico es un sistema ordenado de generación de conocimiento mediante pasos secuenciales, que brindan mayor certidumbre a un resultado y permiten obtener conclusiones válidas, que aporten verosimilitud al nuevo conocimiento generado. Al planificar un proyecto de investigación, se debe tener presente que existe el riesgo de dilapidar tiempo, energía y recursos para finalmente obtener resultados pobres, decepcionantes y a veces inútiles. Para minimizar estos riesgos, la planificación ofrece un modo de anticipar eventos y obstáculos, a la vez de reconocer alternativas que hagan del proyecto, un producto útil, que logre su objetivo y que sea eficiente en el uso de los recursos. Respecto a estos recursos, el análisis de factibilidad del proyecto permitirá conocer en detalle los recursos necesarios para su mejor ejecución y cumplir así, los objetivos del estudio. ABSTRACT: Scientific research is the best way to generate reliable, valid, verifiable and reproducible knowledge. In human health, biomedical research has allowed a better understanding of human diseases and to make progress in the prevention, treatment and rehabilitation of persons suffering from diseases. The scientific method is a sorted and structured system of generation of knowledge, through a series of sequential steps, that provide greater certainty to a result and allows to obtain valid conclusions, that provide credibility to new knowledge. When planning a research project, it should be noted that, there is actual risk to waste time, energy and resources to finally get a poorer, disappointing and sometimes useless outcome than expected. To minimize these risks, the planning gives a way of anticipating events and obstacles, and at the same time recognizing alternatives that make project, a useful product, which achieved its objective and to be efficient in the use of resources. With respect to these resources, the project feasibility analysis allows to recognize in detail the resources needed for its best execution and to meet the objectives of the study. Palabras clave: Proyecto, investigación, planificación, factibilidad, ejecución, Keywords: Project, research, planning, implementing, executio

Fecal microbiota transplantation in recurrent Clostridium difficile infection. Report of one case Trasplante de microbiota fecal en infección recurrente por Clostridium difficile. Experiencia local a partir de un caso clínico

© 2015, Sociedad Medica de Santiago. All rights reserved. Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat recurrent Clostridium difficile infection, with near 90% of success. We report a 57 years old woman who developed an antibiotic associated diarrhea with a positive polymerase chain reaction test for Clostridium Difficile toxin. She was successfully treated with Vancomycin trice but diarrhea recurred. Therefore a fecal microbiota transplant was performed using solid stools from a relative, diluted in saline and instilled in the distal ileon, with a good clinical response, without recurrence of diarrhea, during a 6-month follow-up

LA ENFERMERÍA Y LA INVESTIGACIÓN

RESUMEN: La enfermería es una profesión y como tal, profesa una vocación con una misión. Esta es, proveer el cuidado del paciente, cumpliendo los mejores estándares de calidad y seguridad en salud disponibles. La gestión y ejecución de los cuidados de enfermería deben estar sustentadas y justificadas en evidencia científica y por lo tanto, se hace necesario que las enfermeras(os) desarrollen investigación, para contribuir en los fundamentos de su quehacer.Los profesionales de enfermería entregan gran parte de su tiempo de trabajo a la labor asistencial y de gestión del cuidado, lo que dificulta detenerse a reflexionar algunos conceptos en los cuales está basada su profesión. Se hace necesario meditar sobre las bases y cimientos deontológicos de la profesión de enfermería, y considerar las responsabilidades éticas y jurídicas, todo lo cual obliga a ejercer una labor profesional consecuente a éstas. Esto implica una permanente autoevaluación y mejoramiento de su labor asistencial y a la vez, fundamentar los procedimientos en la evidencia científica. Por consiguiente, en este artículo, se describirán cómo la investigación es parte estructural y básica para la excelencia del cuidado, los campos de desarrollo de la enfermería en la investigación, las competencias del profesional de enfermería que le permiten desarrollar estudios de investigación y la relevancia del equipo para la creación, desarrollo y ejecución de la investigación. SUMMARY: Nursing is a profession and, as such a vocation with a mission. This is to provide patient care and comply with the best quality standards and greater safety. The management and execution of nursing care must be supported and justified in scientific evidence, therefore, it is necessary for nurses to develop research and to contribute in the construction of the foundations of their work.Professional nurses dedicate a large part of their time work, to caring and managing care, which makes it difficult to think over some concepts on which their profession is based. This article is a call to remind the foundations of the nursing profession, their ethical and legal responsibilities and to execute their professional work consistent with these. This implies a permanent self-evaluation and the constant improvement of their care work, basing their procedures on scientific evidence. That is the reason why this article describes how research is the bedrock to the excellence of care, shows the fields where nursing research can be develop, the professional competencies that allow it and the relevance of the research group for the creation, development and execution of investigation. Palabras clave: Investigación, enfermería, excelencia, cuidado, evidencia científica enfermería, capacidad de investigación., Keywords: Nursing research, excellence of care, nursing scientific evidence, research capacity

Transition to adulthood of adolescents with inflammatory bowel disease Transición del adolescente con enfermedad inflamatoria intestinal desde la atención pediátrica a la del adulto

© 2015, Sociedad Medica de Santiago. All rights reserved. Inflammatory bowel disease (IBD) is a prevalent chronic disorder, often diagnosed during childhood. Studies have suggested that the incidence of IBD in this group of patients is increasing. Children and adolescents with IBD frequently have more extensive and severe disease than adults. Transition is an important concept to ensure optimal health care management of adolescents and young adult patients with chronic physical and medical conditions. During this process there is a change in knowledge, attitudes and behavior towards the disease with a responsibility that gradually shifts from parents to the patient. The success of the transition process depends on the patient, pediatric and adult gastroenterologists. Thus, providers need to understand how to start, maintain and finish this process. When transition process is coordinated, staged and well planned, the adolescent and young adult will acquire the tools needed to successfu