La enseñanza basada en proyectos interdisciplinares en ciencias y matemáticas en el Grado de Educación Primaria

Memoria ID-0170. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Jornadas de Startup y educación en la Escuela Universitaria de Educación y Turismo de Ávila

Memoria ID-0214. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses

Bandas miloníticas plegadas en los materiales metamórficos del sur de Segovia

RESUMEN: En los materiales metamórficos del Sur de Segovia la segunda fase de deformación hercínica da lugar a bandas miloníticas de extensión kilométrica. Estas bandas están plegadas por la tercera fase; mediante criterios estructurales se deducen en esta zona una sinforma y una antiforma como las estructuras más notables de esta fase

Tako-tsubo Syndrome and Heart Failure: Long-term Follow-up

Introduction and objectives: Tako-tsubo syndrome produces a variable degree of transient left ventricular dysfunction. Our objective was to determine the short- and long-term prognosis of this syndrome, the incidence of and risk factors for the development of heart failure, and the influence on heart failure on the long-term outcome in our patient population. Methods: We prospectively recorded the clinical features and events during the hospital stay and follow-up of 100 patients with tako-tsubo syndrome. The risk factors for heart failure during hospital stay, considered as Killip class≥II, were assessed. Results: Most of the patients were women (89%), with a mean age of 68 years. The distribution according to Killip class was: Killip I, 70 patients; Killip II, 15; Killip III, 5; and Killip IV, 10. Cardiovascular risk factors, including diabetes, were common in the overall group, but were more so in the heart failure cohort. The left ventricular ejection fraction was lower in the heart failure group (51% vs 42%; P<.01). There were no differences in preadmission medications or biomarkers of necrosis. Over a median follow-up of 1380 days, the incidence of events reported during the hospital stay and long-term follow-up, both for death and the combined endpoints, was higher in the heart failure cohort. Conclusions: Although the prognosis in tako-tsubo syndrome is usually good, heart failure occurs quite frequently, mainly in patients with a greater number of comorbidities and poorer previous functional class. Moreover, heart failure is associated with a higher number of early and late adverse events. The overall long-term prognosis is good.Fundación Mutua MadrileñaDepto. de MedicinaFac. de MedicinaTRUEpu

Impact of delirium in acute cardiac care unit after transcatheter aortic valve replacement

El delirium es un trastorno cognitivo que se produce con frecuencia durante la hospitalización en unidades de cuidados agudos cardiológicos (UCAC), pero su efecto tras la sustitución percutánea de la válvula aórtica (TAVI) no ha sido bien evaluado. El objetivo de este estudio es determinar la incidencia, los factores predictivos y el impacto pronóstico del delirium tras el implante de una TAVI. Métodos: Se incluyeron 501 pacientes consecutivos ingresados en una UCAC tras el implante de TAVI. Se utilizó el método de evaluación de la confusión para evaluar el delirium durante la estancia en la UCAC. Se evaluaron los factores de riesgo, el tratamiento farmacológico preventivo, las características periprocedimiento y las complicaciones. Se registraron los acontecimientos clínicos con una mediana de seguimiento de 24 meses. Resultados: La incidencia de delirium tras TAVI fue del 22,0% (n = 110). El deterioro cognitivo previo (OR 4,17; IC 95%: 1,11-15,71; p = 0,035), la enfermedad arterial periférica (OR 4,54; IC 95%: 1,79-11,54; p = 0,001), el uso de anestesia general (OR 2,55; IC 95%: 1,32-4,90; p = 0,005) y la ventilación mecánica prolongada (OR 18,86; IC 95%: 1,85-192,58; p = 0,013) se asociaron significativamente con el desarrollo de delirium. Los pacientes con delirium tuvieron una mayor estancia hospitalaria (7,5 [5,5-13,5] frente a 5,6 [4,6-8,2] días, y mayor mortalidad intrahospitalaria (OR 2,68; IC 95% 1,02-6,99; p = 0,045), a 1 año (HR 2,09; IC 95% 1,13-3,87; p = 0,018) y a 2 años (HR 1,94; IC 95% 1,12-3,34; p = 0,017). Conclusiones: El delirium es una complicación frecuente en los pacientes ingresados en la UCAC tras el implante de una TAVI, y se asocia con una estancia hospitalaria prolongada y una mayor mortalidad intrahospitalaria y a medio plazo.Depto. de MedicinaFac. de MedicinaTRUEpu

El enalapril intravenoso no evita el desarrollo de remodelado eléctrico auricular agudo secundario a estimulación rápida

Introducción y objetivos. Estudios recientes sugieren un efecto antiarrítmico de los inhibidores de la enzima de conversión de la angiotensina en la prevención de la fibrilación auricular. Un estudio realizado en animales sugirió que estos fármacos evitan el desarrollo del perjudicial remodelado eléctrico auricular agudo secundario a crisis de taquiarritmias auriculares. El presente estudio analiza en pacientes si el enalapril intravenoso en dosis convencionales previene el desarrollo de dicho remodelado. Pacientes y método. Analizamos a 16 pacientes sin cardiopatía estructural remitidos para estudio electrofisiológico por taquicardias supraventriculares. En la fase control cuantificamos el remodelado eléctrico agudo midiendo los períodos refractarios efectivos (PRE) en ambas aurículas antes y después de 10 min de estimulación auricular rápida (250 ms). Tras la recuperación de los PRE hasta valores basales, administramos enalaprilato intravenoso (0,015 mg/kg) y repetimos la secuencia previa de mediciones y estimulación para cuantificar el remodelado en fase enalapril. Resultados. En fase de control, tras la estimulación rápida se indujo una significativa reducción del 14% en los PRE derechos (p < 0,01) y del 8% en los izquierdos (p < 0,01) respecto a sus valores basales. En la fase enalapril, los PRE descendieron un 15% (p < 0,01) y un 7% (p < 0,01), respectivamente. Comparando ambas fases, no hubo diferencias significativas en el grado de remodelado ni en su evolución temporal. El número de episodios de fibrilación auricular inducidos inintencionadamente durante las mediciones de los PRE no varió de manera significativa entre ambas fases. Conclusiones. El enalapril intravenoso no evita el desarrollo de remodelado eléctrico auricular agudo, no modifica su duración ni dificulta la inducción de fibrilación auricula

Impact of Clopidogrel and Aspirin Treatment on the Expression of Proteins in Platelets from Type-2 Diabetic Patients with Stable Coronary Ischemia

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone.Fondo de Investigacion de la Seguridad SocialDepto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEpu

Epicardial Connections Between the Pulmonary Veins and Left Atrium: Relevance for Atrial Fibrillation Ablation

Epicardial Connections Between PVs and the LA. Introduction: Some observations support the existence of epicardial connections (ECs) between ipsilateral pulmonary veins (vein to vein ECs [VVECs]), and we have observed venoatrial ECs inserted at distance from the pulmonary vein ostium (vein to atrium ECs [VAECs]). Our aim was to determine the prevalence of ECs and their relevance for pulmonary vein isolation. Methods and Results: We studied 100 consecutive patients with drug-refractory atrial fibrillation who underwent ostial pulmonary vein isolation by cooled radiofrequency catheter ablation. A VVEC was identified if pulmonary vein pacing activated the ipsilateral vein before the atrium, requiring ablation of both venous ostia to isolate either pulmonary vein. A VAEC was identified if pacing produced atrial breakthrough located at distance from the venous ostium, requiring extraostial ablation to isolate the pulmonary vein. Patients with ECs (20%) were younger (P = 0.02) and had a higher prevalence of structural heart disease (P = 0.01) than patients without ECs. VVECs and VAECs were identified in 32 pulmonary veins (10%) and VAECs in 10 veins (3%). Veins with ECs had a higher rate of early recurrence of conduction following isolation (29% vs 11%; P = 0.01). Conclusion: Twenty percent of patients with atrial fibrillation had ECs resistant to ostial ablation in one or more pulmonary veins. Isolating veins with ECs may require a different ablation approach. These connections are associated with an increased rate of early recurrence of conduction.Depto. de MedicinaFac. de MedicinaTRUEpu