CO, Pb++ and SO2 effects on L-type calcium channel and action potential in human atrial myocytes. In silico study

La exposición a contaminantes atmosféricos, como el monóxido de carbono (CO), plomo (Pb++) y dióxido de azufre (SO2), promueve la aparición de enfermedades cardiovasculares. Estudios experimentales han demostrado que el CO, el Pb++ y el SO2 bloquean los canales de calcio tipo L, disminuyendo la corriente de calcio (ICaL) y la duración del potencial de acción (APD), favoreciendo el inicio de arritmias auriculares. El objetivo es estudiar los efectos del CO, Pb++ y SO2 a diferentes concentraciones, sobre ICaL y el potencial de acción auricular mediante simulación computacional. Para ello, se desarrollaron modelos matemáticos de los efectos de los contaminantes atmosféricos sobre el canal de calcio auricular tipo L y se incorporaron en un modelo matemático de células auriculares humanas. Los resultados sugieren que el CO, el Pb++ y el SO2, bloquean la corriente ICaL en una fracción que aumenta a medida que aumenta, la concentración, generando un acortamiento del APD. Estos resultados son consistentes con estudios experimentales. El efecto combinado de los tres contaminantes atmosféricos generó un acortamiento del APD, lo cual es considerado un efecto pro-arrítmico.Exposure to air pollutants like carbon monoxide (CO), lead (Pb++) and sulfur dioxide (SO2) promotes the occurrence of cardiovascular diseases. Experimental studies have shown that CO, Pb++ and SO2 block L-type calcium channels, reducing the calcium current (ICaL) and the action potential duration (APD), which favors the initiation of atrial arrhythmias. The goal is to study the effects of CO, Pb++ and SO2 at different concentrations on ICaL and action potential using computational simulation. For this purpose, models of the effects of the air pollutants on the atrial L-type calcium channel were developed and were incorporated into a mathematical model of a human atrial cell. The results suggest that CO, Pb++ and SO2 block the ICaL current in a fraction that increases along with the concentration, generating an APD shortening. These results are consistent with experimental studies. The combined effect of the three air pollutants produced an APD shortening, which is considered to be a pro-arrhythmic effect

Complexity of Atrial Fibrillation Electrograms Through Nonlinear Signal Analysis: In Silico Approach

Identification of atrial fibrillation (AF) mechanisms could improve the rate of ablation success. However, the incomplete understanding of those mechanisms makes difficult the decision of targeting sites for ablation. This work is focused on the importance of EGM analysis for detecting and modulating rotors to guide ablation procedures and improve its outcomes. Virtual atrial models are used to show how nonlinear measures can be used to generate electroanatomical maps to detect critical sites in AF. A description of the atrial cell mathematical models, and the procedure of coupling them within two‐dimensional and three‐dimensional virtual atrial models in order to simulate arrhythmogenic mechanisms, is given. Mathematical modeling of unipolar and bipolar electrogramas (EGM) is introduced. It follows a discussion of EGM signal processing. Nonlinear descriptors, such as approximate entropy and multifractal analysis, are used to study the dynamical behavior of EGM signals, which are not well described by a linear law. Our results evince that nonlinear analysis of EGM can provide information about the dynamics of rotors and other mechanisms of AF. Furthermore, these fibrillatory patterns can be simulated using virtual models. The combination of features using machine learning tools can be used for identifying arrhythmogenic sources of AF

Atrial proarrhythmic effect of lead as one of the PM10 metal components of air pollution. An in-silico study

[EN] Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.This work was supported by Ministerio de Ciencia, Tecnologi a e Innovacion MINCIENCIAS from Colombia, through grant No. 120677757994; and by the Direccion General de Politica Cientifica de la Generalitat Valenciana PROMETEO/2020/043.Palacio, LC.; Pachajoa, DC.; Durango-Giraldo, G.; Zapata-Hernández, C.; Ugarte, JP.; Saiz Rodríguez, FJ.; Buitrago-Sierra, R.... (2021). Atrial proarrhythmic effect of lead as one of the PM10 metal components of air pollution. An in-silico study. PLoS ONE. 16(10):1-17. https://doi.org/10.1371/journal.pone.0258313S117161

Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans

The serotonergic system has been hypothesized to contribute to the biological susceptibility to type 2 diabetes mellitus (T2DM) and body-mass index (BMI) categories. We investigate a possible association of 5-HTTLPR polymorphism (L and S alleles) in the promoter region of the serotonin transporter gene (SLC6A4) with the development of T2DM and/or higher BMI by analyzing a sample of 138 individuals diagnosed with T2DM and 172 unrelated controls from the Mexican general population. In the total sample genotypes were distributed according to Hardy-Weinberg equilibrium, and S allele frequency was 0.58. There was no statistical association between 5-HTTLPR polymorphism and the development of T2DM in this Mexican population sample (p = 0.12). Nevertheless, logistic regression analysis of the L allele and increased BMI disclosed an association, after adjusting for age, sex and T2DM (p = 0.02, OR 1.74, 95% CI: 1.079-2.808)

Influence of hypothermia on right atrial cardiomyocyte apoptosis in patients undergoing aortic valve replacement

BACKGROUND: There is increasing evidence that programmed cell death can be triggered during cardiopulmonary bypass (CPB) and may be involved in postoperative complications. The purpose of this study was to investigate whether apoptosis occurs during aortic valve surgery and whether modifying temperature during CPB has any influence on cardiomyocyte apoptotic death rate. METHODS: 20 patients undergoing elective aortic valve replacement for aortic stenosis were randomly assigned to either moderate hypothermic (ModHT group, n = 10, 28°C) or mild hypothermic (MiHT group, n = 10, 34°C) CPB. Myocardial samples were obtained from the right atrium before and after weaning from CPB. Specimens were examined for apoptosis by flow cytometry analysis of annexin V-propidium iodide (PI) and Fas death receptor staining. RESULTS: In the ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative) decreased after CPB, while early apoptotic (annexin positive, PI negative) and late apoptotic or necrotic (PI positive) cells increased. In contrast, no change in the different cell populations was observed over time in the MiHT group. Fas expression rose after reperfusion in the ModHT group but not in MiHT patients, in which there was even a trend for a lower Fas staining after CPB (p = 0.08). In ModHT patients, a prolonged ischemic time tended to induce a higher increase of Fas (p = 0.061). CONCLUSION: Our data suggest that apoptosis signal cascade is activated at early stages during aortic valve replacement under ModHT CPB. This apoptosis induction can effectively be attenuated by a more normothermic procedure

Implementación del Proyecto Planta de Alimentos para la Integración Social de la Universidad Nacional de La Plata (PAIS-UNLP)

En el marco de la crisis alimentaria global, durante el bienio 2016-2018 cerca de 14.2 millones de argentinos padecían inseguridad alimentaria, moderada o grave, valor que duplicaba lo registrado para el bienio anterior (FAO, 2019). En este aspecto el INDEC informó que, para 2021, existían en nuestro país casi 12 millones de personas por debajo de la línea de pobreza, de los cuales 3 millones se encontraban por debajo de la línea de indigencia. En la ciudad de La Plata, entre 2018 y 2019, el Consejo Social llevó adelante un relevamiento de Sitios de Distribución de Alimentos del Gran La Plata, encontrando también datos alarmantes: casi un 41% de la población por debajo de la línea de pobreza y un 13.5% por debajo de la línea de indigencia. Frente a este panorama, la Universidad Nacional de La Plata (UNLP) priorizó la necesidad de un accionar urgente planteando nuevas herramientas. Por este motivo, en el marco del Plan Argentina Contra el Hambre, en 2019, la UNLP puso a disposición toda su capacidad científica y técnica y se propuso como objetivo principal la creación de la Planta de Alimentos para la Integración Social (P.A.I.S) con el propósito de generar productos de alta calidad nutricional, de fácil acceso para las personas más vulnerables, que permitan articular las capacidades productivas del Cinturón Hortícola Platense fortaleciendo el sistema productivo local y en particular la cadena de valor alimentaria.Facultad de Ingenierí

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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