Nuevas estrategias docentes en Histología. Más aprendizaje y menos enseñanza: Uso de microscopios virtuales e Historrelatos.

Current teaching at the University needs novel methodologies to increase students’ motivation. Here, we present two approaches to engage the student body to Human Histology subject at the University of Malaga. Virtual teaching was propelled by the COVID-19 crisis and confinement. The software for the study of histological/histopathological samples has become a valuable tool. Moreover, digital competences are in high demand within the biomedical field but students usually do not receive sufficient training. For these reasons, we have implemented the use of virtual microscopy (VM, Olympus), sharing 66 digitalized slides accessible under a username/password. VM provides real-time dynamic microscopy and offers an innovative experience at exceptionally high resolution. VM allows students to explore the samples online from anywhere, favoring autonomy and self-learning. Moreover, VM enables capturing specific tissue areas using these pictures to ask specific questions. On the other hand, transversal competences such as reading and writing skills, along with synthesis capability can be underdeveloped in our students. We initiated the activity of writing stories about histology contents (Histostories). Professional graphic designers from a webpage of scientific divulgation (masscience.com) illustrated the first story about erythrocytes. We conducted a survey among medical students to analyze the impact of this narration on their learning. Most of them welcome the initiative, considering it as an appropriate and enjoyable instrument for summarizing and revising the concepts. Immunity was among the topics more demanded between the students. Finally, we encouraged our students to write their own Histostories mentored by our teaching staff. These stories are shared through the virtual campus and on masscience website. So far, two medical students are collaborating with us in this experimental project that we expect it will bring more benefits to both readers and participants.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

New teaching strategies in Histology. More learning and less teaching

Las transformaciones de la educación Médica conciernen a la Histología, ocasionando reducciones en la carga docente y asignación de créditos, redefinición de competencias y objetivos de aprendizaje, así como una creciente orientación médica de sus contenidos y una disminución de las clases magistrales. Por ello se hace necesario el empleo de nuevos métodos que se aproximen más al aprendizaje que a la enseñanza, pero que no supongan ni un aumento de la carga docente del alumnado ni un incremento de los ya hipertrofiados planes de estudios. En la Facultad de Medicina de Málaga hemos implementado nuevas metodologías docentes: orientación médica , clase inversa, ABP, microscopia virtual, HistolCasts), HistolWord, Instagram, Historrelatos), y evaluación continua . Sobre estas actividades los estudiantes han mostrado un alto grado de participación y satisfacción, estimulando su interés y motivación por la Histología y mejorando el rendimiento académico. Adicionalmente, muchas de estas estrategias se pueden extrapolar a otras áreas de la educación médica, tanto para estudiantes como para residentes y formación continuada. Algunas de estas metodologías ya han sido ya presentadas y otras lo serán por algunos de mis compañeros. Me voy a referir a continuación al HistolWord. Se trata de una actividad de gamificación basada en el juego del pasapalabra, empleando términos histológicos. Se formaron 32 equipos de 5 estudiantes que compitieron en un sistema de eliminatorias desde dieciseisavos de final, confeccionándose 70 roscos de palabras. Todo se desarrollaba en un aula con casi 200 estudiantes, donde se leían las preguntas y se proyectaba el rosco, de manera que no solo participaban los dos equipos que se enfrentaban en ese momento, sino todos los presentes. Los estudiantes indicaron la utilidad de HistolWord como motivación para el estudio, complemento de las clases, revisión y aplicaciones médicas, existiendo una correlación positiva con las calificaciones.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion

Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 ◦C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.Andalusian Society of Cardiology with a “beca de Investigación general

Impact of first year renal replacement therapy on the hospital admissions of a regional public health system

Introducción y objetivos: La enfermedad renal crónica tiene una alta prevalencia y coste, así como un mayor riesgo de ingreso. Disponemos de registros públicos y obligatorios, pero no hay referencias recientes para estimar el impacto que el tratamiento sustitutivo renal (TSR) tiene en la actividad hospitalaria. Métodos: Tras las autorizaciones pertinentes, hemos integrado las bases de datos REMER (2013-2014) y CMBDH (2013-2015) para analizar la actividad hospitalaria durante el primer an˜ o de TSR. Resultados: Un total de 767 pacientes iniciaron TSR en los 7 hospitales de tercer nivel de la Comunidad de Madrid. Más de una tercera parte lo hicieron de forma no programada durante un ingreso. Este inicio es más frecuente en HD que en DP, pero existen diferencias clínicas relevantes en edad y en comorbilidad. Descartando este primer episodio, casi el 60% de pacientes ingresan durante el primer an˜ o. La tasa de ingreso es de 1,2 ingresos/paciente, más alta en HD que en TX y DP; la estancia media es de 8,6 días. El coste agregado de los ingresos del primer an˜ o es de 12.006 D /paciente. Nuestro análisis asegura la inclusión exhaustiva de todos los episodios y la estimación precisa de costes. Conclusiones: El impacto del TSR en la actividad hospitalaria ha sido infraestimado y es una parte importante del coste global del TSR. Los resultados de la literatura internacional no pueden extrapolarse a nuestro país por las diferencias en el modelo sanitario y perfil de paciente. La integración de bases de datos clínicas es técnicamente viable y podría abrir una vía inmensa de información que solo requiere apoyo institucional para su desarrollo.Introduction and objectives: Chronic kidney disease has a high prevalence and economic impact, and an increased risk of hospitalization. Although there are public regional and country registries, we have not found references to estimate the impact of renal replacement therapy (RRT) on hospital admissions. Methods: We obtained authorization from the ethics committee and health authorities to integrate the REMER [Madrid Kidney Disease Registry] (2013-2014) and Minimum Basic Data Set (2013-2015) databases and to analyze the admissions during the first year of RRT. Results: 767 patients started RRT in all the hospitals of our region across all RRT modalities. More than a third of the patients start dialysis during a hospital admission. This unplanned start, more common in HD than PD, shows relevant differences in patient profile or admission characteristics. Without considering this initial episode, almost 60% of patients were admitted during their first year. The hospitalization rate was 1.2 admissions/patient, higher in HD than in TX or PD; the mean length of stay was 8.6 days. The estimated cost of admissions during the first year is D 12,006/patient. Our analysis ensures the exhaustive inclusion of all episodes and accurate estimation based on the discharge form. Conclusion: The impact of RRT on hospitals has been underestimated and is very relevant when calculating the total cost of RRT. Results from other countries cannot be extrapolated due to differences in the health system and patient profile. The integration of clinical databases could open up an opportunity that needs only institutional support for its development

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.The authors thank the Centro Nacional de Investigaciones Cardiovasculares (CNIC) Viral Vectors Unit for producing the adeno-associated virus serotype 9. Confocal experiments were conducted at the CNIC Microscopy and Dynamic Imaging Unit. The authors thank the CNIC Bioinformatics Unit for generating the in silico homology modeling simulations, F-function analysis, and helpful discussions. The authors also thank the Centro de Supercomputación de Galicia for the use of the Finis Terrae III supercomputer to perform molecular dynamics studies. The CNIC was supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). This work was supported by the National heart, Lung and Blood Institute under National Institutes of Health (NIH) grant R01HL163943; the La Caixa Banking Foundation project code HR18-00304 (grant LCF/PR/HR19/52160013); grants PI-FIS-2020, PI20/01220, PI-FIS-2023, and PI23/01039 from the Instituto de Salud Carlos III and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER) and the European Union, respectively; grants PID2020-116935RB-I00 and BFU2016-75144-R funded by MICIU/AEI/10.13039/501100011033; the Fundación La Marató de TV3 (736/C/2020) amb el suport de la Fundació La Marató de TV3; the CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (grant CB16/11/00458); the European Union’s Horizon 2020 grant agreement GA-965286; and the Program S2022/BMD7229-CM ARCADIACM funded by the Comunidad de Madrid to J. Jalife; grant PID2021-126423OB-C22 (to M. Martín-Martínez) funded by MICIU/AEI/10.13039/501100011033; and European Regional Development Fund (ERDF) grant PID2022-137214OB-C22 (to M. Gutierrez-Rodríguez) funded by MICIU/AEI/10.13039/501100011033. The imaging studies were performed in the TRIMA@CNIC (Infraestructura de Imagen Traslacional Avanzada del CNIC) node of the ICTS ReDIB (Infraestructuras Científicas y Técnicas Singulares: Red Distribuida de Imagen Biomédica) grant ICTS-2018- 04-CNIC-16 funded by MICIU/AEI/10.13039/501100011033 and ERDF, and project EQC2018-005070-P funded by MICIU/AEI/10.13039/501100011033 and FEDER. A.I. Moreno-Manuel holds an formación profesional universitaria (FPU) contract (FPU20/01569) from the Ministerio de Universidades. J.M. Ruiz Robles holds an FPU contract (FPU22/03253) from the Ministerio de Universidades. L.K. Gutiérrez holds an FPI contract (PRE2018-083530) from the Ministerio de Economía y Competitividad de España cofunded by the Fondo Social Europeo, attached to project SEV-2015-0505-18-2. I. Martínez-Carrascoso holds a PFIS (Contratos predoctorales de formación en investigación en salud) contract (FI21/00243) funded by Instituto de Salud Carlos III and the Fondo Social Europeo Plus cofunded by the European Union. M.L. Vera-Pedrosa held contract PEJD-2019-PRE/BMD15982 funded by the Consejería de Educación e Investigación de la Comunidad de Madrid y Fondo Social Europeo.S

GACETA SANITARIA in 2017. Improving the quality of our journal

Empezamos este año 2018 con nuestra Nota editorial anual, en la cual pretendemos compartir con los/las lectores/as, personas autoras y la sociedad la actividad realizada por el equipo editorial de la revista a lo largo del año anterior. El documento también permite analizar los avances y las áreas de mejora en marcha de la revista. A continuación, presentaremos brevemente las actividades realizadas durante el año 2017, así como la información sobre el desempeño de la revista. Muchas de estas actividades se ven reflejadas también en el blog del comité editorial de Gaceta Sanitaria

Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia

Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7,500–3,500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up

GACETA SANITARIA in 2018. Strengthening the presence in Latin America and promoting the publication of essential issues for the National Health System

Una vez más, presentamos el informe de la actividad realizada por el equipo editorial a lo largo del año anterior y los datos de desempeño de la revista, con el fin de rendir cuentas a nuestros/as lectores/as, a las personas socias de SESPAS y a la sociedad. El documento permite analizar los avances y las áreas de mejora de la revista, así como los logros alcanzados más relevantes. Este año queremos destacar el fortalecimiento de la presencia en Latinoamérica y la promoción de la publicación de temas esenciales para el Sistema Nacional de Salud