Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.

AIMS: Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP). METHODS AND RESULTS: First, 24-h electrical pacing at 3 Hz was used to investigate whether AF-associated remodelling in iPSC-aCM and aEHM would ensue. Compared to controls (24 h, 1 Hz pacing) TP-stimulated iPSC-aCM presented classical hallmarks of AF-associated remodelling: (i) decreased L-type Ca2+ current (ICa,L) and (ii) impaired activation of acetylcholine-activated inward-rectifier K+ current (IK,ACh). This resulted in action potential shortening and an absent response to the M-receptor agonist carbachol in both iPSC-aCM and aEHM subjected to TP. Accordingly, mRNA expression of the channel-subunit Kir3.4 was reduced. Selective IK,ACh blockade with tertiapin reduced basal inward-rectifier K+ current only in iPSC-aCM subjected to TP, thereby unmasking an agonist-independent constitutively active IK,ACh. To allow for long-term TP, we developed iPSC-aCM and aEHM expressing the light-gated ion-channel f-Chrimson. The same hallmarks of AF-associated remodelling were observed after optical-TP. In addition, continuous TP (7 days) led to (i) increased amplitude of inward-rectifier K+ current (IK1), (ii) hyperpolarization of the resting membrane potential, (iii) increased action potential-amplitude and upstroke velocity as well as (iv) reversibly impaired contractile function in aEHM. CONCLUSIONS: Classical hallmarks of AF-associated remodelling were mimicked through TP of iPSC-aCM and aEHM. The use of the ultrafast f-Chrimson depolarizing ion channel allowed us to model the time-dependence of AF-associated remodelling in vitro for the first time. The observation of electrical remodelling with associated reversible contractile dysfunction offers a novel platform for human-centric discovery of antiarrhythmic therapies.

Visibilidad de la Revista Médica Herediana: Una revisión mediante Google Scholar / Visibility of the Revista Medica Herediana: A Google Scholar review

Objetivo: Identificar los artículos más citados y los autores más productivos de la Revista Médica Herediana (RMH). Material y métodos: Estudio bibliométrico descriptivo. Se recuperaron los artículos de la RMH y se seleccionaron los trabajos que recibieron al menos una cita en el período 2009 - 2013 mediante Google Scholar. Resultados: Se comparó el impacto de la RMH con otras revistas publicadas por la Universidad Peruana Cayetano Heredia (UPCH); se analizaron 710 documentos, permitiendo identificar 176 artículos con al menos una cita recibida en Google Scholar. Conclusiones: Se identificó 15 (8,5%) artículos que recibieron 10 o más citaciones y el artículo más citado obtiene 36 citas. Dos (3,5%) investigadores concentran la mayor cantidad de colaboraciones de esta publicación en este período de análisis. (AU)

Objectives: To identify the most cited manuscripts and more productive authors of Revista Medica Herediana. Methods: A descriptive bibliometric study was performed. Articles that had at least one citation from 2009-2013 were selected using Google Scholar. Results: 710 documents were reviewed identifying 176 manuscripts with at least one citation. Conclusions: Fifteen manuscripts (8.5%) received more than 10 citations, the most cited manuscript received 36 citations. Two authors (3.5%) concentrated the highest number of contributions during the study period. (AU)

Factores demográficos asociados con el conocimiento sobre salud en una muestra de mujeres de la ciudad de Lima (Perú) en 2008: resultados del cuestionario SAHLSA-50 / Demographic factors associated with health literacy in a sample of females residing in Lima, Peru in 2008: results from the SAHLSA-50 test

Objetivo: identificar el porcentaje de sujetos con un adecuado conocimiento sobre la salud y determinar las variables demográficas que predicen un apropiado conocimiento de la misma. Metodología: estudio de cohorte transversal en el que se aplicó la prueba SAHLSA-50 en una muestra de 49 mujeres en edad fértil, usuarias del servicio ginecológico del Hospital Dos de Mayo de la ciudad de Lima (Perú). Para someter a prueba la hipótesis se empleó el coeficiente de correlación de Pearson y el análisis de regresión lineal. Resultados: de acuerdo con lo obtenido, el rango de valores del puntaje de la prueba SAHLSA estuvo entre 22 y 50 puntos con un promedio de 37 ±7, 15 puntos. Dichos resultados se vieron reflejados en 43% de las encuestadas, las cuales consiguieron un puntaje inferior al promedio en la prueba de conocimiento sobre salud (n=21). Igualmente, se encontró que la escolaridad es predictora del nivel de conocimiento sobre la salud (p < 0,05). Conclusiones: los resultados muestran que las pacientes con menor grado de instrucción podrían tener pocas oportunidades de entender los mensajes escritos que provengan de sus servicios de salud.

Objective: the objectives were to identify the percentage of subjects having appropriate health literacy and determine the demographic variables predicting appropriate health literacy in females. Methodology: this was a cross-sectional study in which the short assessment of health literacy for Spanish adults (SAHLSA-50) test was given to a sample of 49 reproductive-aged females who were attending the gynaecological service at Dos de Mayo Hospital in Lima, Peru. Linear regression analysis and Pearson’s coefficient of correlation were used to test the hypothesis. Results: SAHLSA test scores ranged from 22 to 50 points, averaging 37 + 7.15 points; 43% of the females surveyed obtained a score lower than the average on the health literacy test (n=21). It was found that the level of schooling was a predictor for health literacy level (p<0.05). Conclusions: these findings showed that patients who have had lower levels of schooling would have little opportunity of understanding written messages/instructions issued by local or state health services.