Coupling of Smoothened to inhibitory G proteins reduces voltage-gated K

SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric Gi proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic GiCT/TTA mice, in which Gi signaling is impaired, suggesting that the effect of SMO is mediated by Gi proteins. Investigation of the mechanism underlying the change in action potential kinetics revealed that activation of SMO selectively reduces outward voltage-gated K+ repolarizing (Kv) currents in isolated cardiomyocytes and that it induces a down-regulation of membrane levels of Kv4.3 in cardiomyocytes and intact hearts from WT but not from GiCT/TTA mice. Moreover, perfusion of intact hearts with Shh or purmorphamine increased the ventricular repolarization time (QT interval) and induced ventricular arrhythmias. Our data constitute the first report that acute, noncanonical Hh signaling mediated by Gi proteins regulates K+ currents density in cardiomyocytes and sensitizes the heart to the development of ventricular arrhythmias. © 2018 Cheng et al

Impact of hospital characteristics on implementation of a Pediatric Early Warning System in resource-limited cancer hospitals

BackgroundPediatric Early Warning Systems (PEWS) aid in identification of deterioration in hospitalized children with cancer but are underutilized in resource-limited settings. Proyecto EVAT is a multicenter quality improvement (QI) collaborative in Latin America to implement PEWS. This study investigates the relationship between hospital characteristics and time required for PEWS implementation.MethodsThis convergent mixed-methods study included 23 Proyecto EVAT childhood cancer centers; 5 hospitals representing quick and slow implementers were selected for qualitative analysis. Semi-structured interviews were conducted with 71 stakeholders involved in PEWS implementation. Interviews were recorded, transcribed and translated to English, then coded using a priori and novel codes. Thematic content analysis explored the impact of hospital characteristics and QI experience on time required for PEWS implementation and was supplemented by quantitative analysis exploring the relationship between hospital characteristics and implementation time.ResultsIn both quantitative and qualitative analysis, material and human resources to support PEWS significantly impacted time to implementation. Lack of resources produced various obstacles that extended time necessary for centers to achieve successful implementation. Hospital characteristics, such as funding structure and type, influenced PEWS implementation time by determining their resource-availability. Prior hospital or implementation leader experience with QI, however, helped facilitate implementation by assisting implementers predict and overcome resource-related challenges.ConclusionsHospital characteristics impact time required to implement PEWS in resource-limited childhood cancer centers; however, prior QI experience helps anticipate and adapt to resource challenges and more quickly implement PEWS. QI training should be a component of strategies to scale-up use of evidence-based interventions like PEWS in resource-limited settings

Calprotectina fecal: utilidad en el diagnóstico diferencial de enfermedad inflamatoria intestinal y síndrome intestino irritable en adultos

Differentiation between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can be complex as their symptoms are often similar and unspecific. Fecal biomarkers could be useful to select patients with suspected organic diseases for colonoscopy, with the aim to improve early diagnosis and to avoid unnecessary invasive studies. Fecal calprotectin (FC) is a protein found mainly in neutrophils that is released into the feces as a result of cell disruption and apoptosis. Currently, FC is a simple and non-invasive biomarker of intestinal inflammation. Inflammatory gastrointestinal disorders are associated with high levels of FC, as occurs in IBD. This review focuses on FC as a useful tool for differential diagnosis between IBS and IBD in adults

Péptidos inmunogénicos del gluten en deposiciones. Nuevo método para evaluar la adherencia a la dieta en pacientes celíacos

Celiac disease (CD) is an autoimmune pathology caused by the ingestion of gluten in genetically susceptible people, currently considered multisystemic. The treatment of CD is a lifelong strict Gluten-Free Diet (GFD), which allows a symptomatic improvement in most patients and achieve intestinal mucosa healing confirmed with histological study. The adherence to the GFD is variable, arguing as possible factors related to failure the economic, cultural, social aspects and the consumption of gluten inadvertently. The management of celiac patients contemplates instructing in the proper follow-up of GFD and evaluating their adherence. So far, the only way to assess adherence to GFD is through surveys, self-reports of eating habits and serology, being the main disadvantage the subjectivity factor. Recently the immunogenic gluten peptides have acquired relevance for the objective evaluation of the adherence to the GFD and the measurement appears as an efficient and sensitive option to determine the gluten intake, providing relevant information for the clinical management

Rol de la inflamación y medición de calprotectina fecal en síndrome de intestino irritable

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder mainly manifested as abdominal pain with correlated changed bowel habits. IBS pathophysiology is still not completely understood; recently, a lot of investigations suggest the role of inflammation and immune activation, most presenting as alteration of mast cells, lymphocytes and cytokines. Several biological markers of intestinal inflammation has been developed, there is not one ideal, but fecal calprotectin has great potential. In this review we will analyze the role of inflammation in IBS and the potential utility of fecal calprotectin

Ventajas de la medición de niveles plasmáticos de infliximab en pacientes con enfermedad inflamatoria intestinal

Inflammatory bowel disease includes Crohn ́s disease, ulcerative colitis and unclassified colitis. Conventional therapies used for treating these diseases are often insufficient or contraindicated and biological agents have proved to be effective and safe in these cases. Infliximab is a quimeric IgG1 monoclonal anti-tumor necrosis factor antibody that is capable of inducing and mantaining clinical remission in patients with inflammatory bowel disease. Despite its proven efficacy a considerable group of patients lose response requiring changes in therapy. Serum Infliximab trough levels are correlated with clinical response, endoscopic remission and mucosal healing in patients with inflammatory bowel disease. Monitoring and adjusting therapy guided by drug serum levels have proved to be more cost-effective and safer than empiric adjustments. Current international guidelines recommend the measurement of Infliximab trough levels in the global evaluation and management of these patients to improve treatment, avoid adverse events and unnecessary costs

Diagnóstico y propuestas de mejoramiento del rastro municipal de Zacoalco de Torres, Jalisco

En el presente Proyecto de Aplicación Profesional llamado San Pedro Valencia: Programa de Sustentabilidad Socioambiental para el Desarrollo Inclusivo, se presentaron las propuestas de mejora a corto, mediano y largo plazo para el Rastro municipal de Zacoalco de Torres, en este proyecto se identificó una problemática que se centra en la contaminación del medio ambiente específicamente en el suelo y mantos acuíferos a causa de la mala disposición de aguas residuales provenientes de procesos del Rastro Municipal. Esta mala gestión genera riesgos a la salud de viviendas aledañas por contaminación de agua potable y exposición a materia residual no tratada. Para poder proponer dichas propuestas de mejora fue necesario elaborar un diagnóstico/formulario en base a la normativa mexicana aplicable en los rastros municipales. De este modo se encontró un total de 22 Normas Oficiales Mexicanas, de las cuales solamente 5 involucran el manejo de las aguas residuales; Estas cinco normas son: NOM-008-ZOO-1994, NOM-009-ZOO-1994, NOM-194-SSA1-2004, NOM-001-SEMARNAT-1996, NOM-002-SEMARNAT-1996. De esta forma, una vez que se aplicó el diagnóstico/formulario al director del rastro, se logró identificar aquellas propuestas de mejora a corto, mediano y largo plazo para el rastro de Zacoalco de Torres. Con el diálogo se lograron establecer como viables algunas de las propuestas presentadas, para las cuales se buscaron proveedores y cotizaciones para poder implementarlas. Este documento fue presentado al Ayuntamiento con toda la información relevante para la implementación. Así mismo se identificó un área de oportunidad de proyecto, en el aspecto laboral en el rastro, ya que se considera que las condiciones laborales podrían mejorar y cumplir los reglamentos de acuerdo con lo que indica la ley laboral.ITESO, A.C

Clavigero. Comunidad de saberes, núm. 29: Movilidad urbana: hacia una ciudad posible

La movilidad urbana se relaciona con otras problemáticas como la pérdida de espacios naturales o verdes, la contaminación del aire, el acceso desigual al espacio público, la discriminación o la violencia en los trayectos de movilidad de las mujeres y disidencias sexo–genéricas, los siniestros viales que ponen en riesgo la vida de las personas, o la mala planeación urbana que afecta el derecho a la vivienda. Los textos de este número plantean un modelo de ciudad justo, a partir de una visión sistemática de la movilidad. Las y los autores incluyen la perspectiva de género, el cuidado de la vida y la sustentabilidad pero, sobre todo, colocan a las personas y al medio ambiente en el centro