Muscle Network Connectivity Study in Diabetic Peripheral Neuropathy Patients.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.

Influence of genetic mutations to atria vulnerability to atrial fibrillation: An in-silico 3D human atria study.

BACKGROUND AND OBJECTIVE: Personalized 3D computer models of atria have been extensively implemented in the last yearsas a tool to facilitate the understanding of the mechanisms underlying different forms of arrhythmia, such as atrial fibrillation (AF). Meanwhile, genetic mutations acting on potassium channel dynamics were demonstrated to induce fibrillatory episodes in asymptomatic patients. This research study aims at assessing the effects and the atrial susceptibility to AF of three gain-of-function mutations - namely, KCNH2 T895M, KCNH2 T436M, and KCNE3-V17M - associated with AF outbreaks, using highly detailed 3D atrial models with realistic wall thickness and heterogenous histological properties. METHODS: The 3D atrial model was generated by reconstructing segmented anatomical structures from CT scans of an AF patient. Modified versions of the Courtemanche human atrial myocyte model were used to reproduce the electrophysiological activity of the WT and of the three mutant cells. Ectopic foci (EF) were simulated in sixteen locations across the atrial mesh using an S1-S2 protocol with two S2 basic cycle lengths (BCL) and eleven coupling intervals in order to induce arrhythmias. RESULTS: The three genetic mutations at 3D level reduced the APD90. The KCNE3-V17M mutation provoked the highest shortening (55 % in RA and LA with respect to WT), followed by KCNH2 T895M (14 % in RA and 18 % LA with respect to WT)and KCNH2 T436M (7 % in RA and 9 % LA with respect to WT). The KCNE3-V17M mutation led to arrhythmia in 67 % of the cases simulated and in 94 % of ectopic foci considered, at S2 BCL equal to 100 ms. The KCNH2 T436M and KCNH2 T895M mutations increased the vulnerability to AF in a similar way, leading to arrhythmic episodes in 7 % of the simulated conditions, at S2 BCL set to 160 ms. Overall, 60 % of the arrhythmic events generated arise in the left atrium. Spiral waves, multiple rotors and disordered electrical pattern were elicited in the presence of the KCNE3-V17M mutation, exhibiting an instantaneous mean frequency of 7.6 Hz with a mean standard deviation of 1.12 Hz. The scroll waves induced in the presence of the KCNH2 T436M and KCNH2 T895M mutations showed steadiness and regularity with an instantaneous mean frequencies in the range of 4.9 - 5.1 Hz and a mean standard deviation within 0.19 - 0.53 Hz. CONCLUSIONS: The pro-arrhythmogenicity of the KCNE3-V17M, KCNH2 T895M and KCNH2 T436M mutations was studied and proved on personalized 3D cardiac models. The three genetic mutations were demonstrated to increase the predisposition of atrial tissue to the formation of AF-susceptible substrate in different ways based on their effects on electrophysiological properties of the atria.

Experimentally validated modeling of dynamic drug-hERG channel interactions reproducing the binding mechanisms and its importance in action potential duration.

BACKGROUND AND OBJECTIVE: Assessment of drug cardiotoxicity is critical in the development of new compounds and modeling of drug-binding dynamics to hERG can improve early cardiotoxicity assessment. We previously developed a methodology to generate Markovian models reproducing preferential state-dependent binding properties, trapping dynamics and the onset of IKr block using simple voltage clamp protocols. Here, we test this methodology with real IKr blockers and investigate the impact of drug dynamics on action potential prolongation. METHODS: Experiments were performed on HEK cells stably transfected with hERG and using the Nanion SyncroPatch 384i. Three protocols, P-80, P0 and P 40, were applied to obtain the experimental data from the drugs and the Markovian models were generated using our pipeline. The corresponding static models were also generated and a modified version of the O´Hara-Rudy action potential model was used to simulate the action potential duration. RESULTS: The experimental Hill plots and the onset of IKr block of ten compounds were obtained using our voltage clamp protocols and the models generated successfully mimicked these experimental data, unlike the CiPA dynamic models. Marked differences in APD prolongation were observed when drug effects were simulated using the dynamic models and the static models. CONCLUSIONS: These new dynamic models of ten well-known IKr blockers constitute a validation of our methodology to model dynamic drug-hERG channel interactions and highlight the importance of state-dependent binding, trapping dynamics and the time-course of IKr block to assess drug effects even at the steady-state.

Factores predictores de resultado en tratamiento de tabaquismo en población de adultos mayores de la Comunidad Valenciana / Predictors of smoking treatment outcome in a population of older adults in the Valencian Community

El consumo de tabaco es uno de los más importantes factores de riesgo de enfermedad y muerte en España. Por ello, el objetivo de este estudio fue investigar las características epidemiológicas de 239pacientes fumadores mayores de 50 años en una unidad hospitalaria de deshabituación de tabaco, así como analizar los principales factores predictores que pueden influir en sus intentos de cese a losdoce meses. Es un estudio analítico transversal con tratamiento multicomponente combinando terapia psicológica e intervención farmacológica. Para comparar el éxito de abandono de los pacientes yconocer los posibles factores predictores, se llevó a cabo un análisis multivariante y de regresión logística binaria. De todos los pacientes, el 49,7% estableció el día D y la tasa de abandono final fue de 41,4%. Los predictores de intentos de abandono significativos fueron: índice paquetes-año entre 30 y 60, valor de cooximetría ≤ 10ppm, con una o más veces de intentos previos, tiempo máximo de cese superior a tres meses y grado alto en el test de Richmond. La escala de Minnesota con un valor inferior a 5 puntos fue el único predictor de abstinencia puntual a los doce meses. Los pacientes que consumieron menos tabaco y manifestaron intentos previos y alto grado de motivación tuvieron mayor posibilidad de tomar la decisión con éxito para dejar de fumar. Además, controlar el síndrome de abstinencia fue el aspecto más importante para tratar y reducir la tasa de recaída. (AU)

Tobacco consumption is one of the most important risk factors for disease and death in Spain. Therefore, the aim of this study was to investigate the epidemiological characteristics of 239 smoking patients over 50 years of age in a hospital smoking cessation unit, as well as to analyse the main predictors that may influence their cessation attempts at 12 months. It is a cross-sectional analytical study with multicomponent treatment combining psychological therapy and pharmacological intervention. A multivariate and binary logistic regression analysis was carried out to compare patients’ cessation success and to identify possible predictors. Of all patients, 49.7% established D-day and the final quit rate was 41.4%. Significant predictors of quit attempts were: pack-year index between 30 and 60, cooximetry value ≤ 10ppm, with one or more times of previous attempts, maximum cessation time greater than three months and high grade on the Richmond test. The Minnesota scale with a value of less than 5 points was the only predictor of timely abstinence at 12 months. Patients who used less tobacco and reported previous attempts and high motivation were more likely to make a successful decision to quit smoking. In addition, controlling the withdrawal syndrome was the most important aspect to treat and reduce the relapse rate. (AU)

Estilos de vida, adherencia a la dieta mediterránea, características antropométricas en un colectivo de universitarios de ciencias de la salud / Lifestyle, adherence to Mediterranean diet, anthropometric characteristics in a group of university health sciences students

Fundamentos: Los estudiantes universitarios viven importantes cambios de estilo de vida, patrón de adherencia a dieta mediterránea y estado nutricional. El objetivo de este estudio fue conocer las características de estos factores en universitarios valencianos y las asociaciones de estos entre sí. Métodos: Estudio descriptivo transversal en estudiantes universitarios de 18 a 27 años. Se evaluaron las características de estilos de vida, valores antropométricos, por género y edad, así como la asociación entre ellos mediante análisis descriptivo univariante y bivariante, incluyendo el test de U-Mann Whitney y la correlación de Spearman. Resultados: Entre los 682 estudiantes estudiados hay una baja prevalencia de obesidad (1,5%). Las mujeres presentan mayor nivel de consumo de tabaco (32,5%), mientras que los hombres muestran mayores frecuencias en la falta de desayuno (7,1%). Asimismo, el grupo de menores de 23 años destaca por una baja adherencia a la dieta mediterránea. Se observó una correlación positiva entre IMC, consumo de tabaco (p=0,001) y adherencia a la dieta mediterránea (p<0,0001). Existe correlación negativa entre IMC y frecuencia de desayuno (p=0,007), almuerzo (p=0,002) y merienda (p=0,006). Conclusiones: Los alumnos universitarios presentan mayoritariamente un IMC adecuado con baja prevalencia de obesidad. Existe margen de mejora en la adherencia a dieta mediterránea, en el hábito de desayuno y en los estilos de vida saludable (AU)

Background: University students are facing important changes of lifestyle, the pattern of adherence to Mediterranean Diet and nutritional status. The objective of this study was to know the characteristics of these factors implemented in university students of Valencia and their associations. Methods: A cross-sectional study on University students aged 18 to 27 years. We evaluated the characteristics of lifestyles and anthropometric values by gender and age and the association between them by univariate and bivariate analysis, including the Mann-Whitney U-test and Spearman correlations. Results: Of a total of 682 students we observed a low prevalence of obesity (1.5%). Women presented higher levels of tobacco consumption (32.5%), while men were more prone to skip breakfast showed higher frequencies in the lack of breakfast (7.1%). The younger age group (≤23) had a lower adherence to the Mediterranean diet. A positive correlation was observed between BMI, smoking (p=0.001) and adherence to the Mediterranean diet (p< 0.0001). There is also negative correlation between BMI and the frequency of breakfast (p=0.007), lunch (p=0.002) and snack (p=0.006). Conclusions: The university students present mainly a suitable BMI with a low prevalence of obesity. There is room for improvement in the adherence to a Mediterranean Diet, the habit of eating breakfast and healthy lifestyles (AU)

¿Qué operan los residentes españoles durante la residencia?: análisis de la aplicabilidad del programa de la especialidad de Cirugía General y Digestiva al finalizar el periodo de residencia / The surgical experience of general surgery residents: An analysis of the applicability of the specialty program in General and Digestive Surgery

El entrenamiento quirúrgico siguiendo un periodo de residencia ha conseguido que los residentes en nuestro país posean una formación homogénea y satisfactoria para el desarrollo de su actividad profesional. Ello se debe a la existencia de planes de formación específicos para cada especialidad. El plan vigente promulgado en 2007 detallaba el número mínimo de intervenciones quirúrgicas y procedimientos que un cirujano debía haber efectuado para completar su periodo de formación. El objetivo de este estudio es conocer la aplicación del programa de la especialidad en cuanto al número de intervenciones practicadas durante el periodo de residencia. MATERIAL Y MÉTODOS: Se diseñó una hoja de recogida de datos que incluía la relación de intervenciones enunciada en el programa de la especialidad, que fue remitida en abril de 2014 a todos los hospitales que disponen de unidades acreditadas para la formación de residentes. En septiembre de 2014 se tabularon las respuestas remitidas y se efectuó un estudio estadístico descriptivo general, y un subanálisis en función del sexo del residente y de la comunidad autónoma. A la vez se analizó la actividad efectuada en función del número de residentes que existiera en cada unidad docente acreditada. RESULTADOS: La encuesta se remitió a los 117 hospitales con unidades acreditadas, que incluyen un total de 190 plazas ofertadas. De ellas se obtuvieron 91 respuestas (53%). La formación ofrecida se adapta en líneas generales a la propuesta por el plan de la especialidad. El número global de intervenciones practicadas de acuerdo a las diferentes subáreas, en cirugía laparoscópica y de urgencias, cumple o supera las cifras previstas, excepto en cirugía esofagástrica y HPB. El subanálisis de la actividad quirúrgica según la comunidad autónoma no evidencia diferencias significativas en el número total de intervenciones, sin embargo, sí se objetivan diferencias en cirugía endocrina (p = 0,001) y de la mama (p = 0,042). Un 55% de los residentes eran mujeres, sin diferencias significativas en cuanto a su distribución en las comunidades autónomas. Sin embargo, las cirujanas operan más que los cirujanos durante la residencia (625 ± 244 vs 527 ± 209; p < 0,01). También se observa que el número de residentes adscrito a cada unidad docente se correlaciona con el número de intervenciones realizadas: han efectuado más intervenciones los cirujanos que están solos en su unidad que aquellos que tienen compañeros de su mismo año (669 ± 237 vs. 527 ± 209; p = 0,004). CONCLUSIÓN: La actividad quirúrgica efectuada por los cirujanos españoles se adecua a la propuesta por el plan actual de la especialidad, excepto en cirugía HPB y esofagogástrica. La distribución es homogénea de acuerdo a las comunidades autónomas, aunque existen diferencias en función del número de residentes por hospital y el sexo del residente. Esta información es esencial para evaluar la idoneidad del plan de formación y el diseño de nuevos planes formativos

Residents in our country have achieved a homogenous surgical training by following a structured residency program. This is due to the existence of specific training programs for each specialty. The current program, approved in 2007, has a detailed list of procedures that a surgeon should have performed in order to complete training. The aim of this study is to analyze the applicability of the program with regard to the number of procedures performed during the residency period. MATERIAL AND METHODS: A data collection form was designed that included the list of procedures from the program of the specialty; it was sent in April 2014 to all hospitals with accredited residency programs. In September 2014 the forms were analysed, and a general descriptive study was performed; a subanalysis according to the resident's sex and Autonomous region was also performed. The number of procedures performed according to the number of residents in the different centers was also analyzed. RESULTS: The survey was sent to 117 hospitals with accredited programs, which included 190 resident places. A total of 91 hospitals responded (53%). The training offered adapts in general to the specialty program. The total number of procedures performed in the different sub-areas, in laparoscopic and emergency surgery is correct or above the number recommended by the program, with the exception of esophageal-gastric and hepatobiliary surgery. The sub-analysis according to Autonomous region did not show any significant differences in the total number of procedures, however, there were significant differences in endocrine surgery (P = .001) and breast surgery (P = .042). A total of 55% of residents are female, with no significant differences in distribution in Autonomous regions. However, female surgeons operate more than their male counterparts during the residency period (512 ± 226 vs. 625 ± 244; P < .01). The number of residents in the hospital correlates with the number of procedures performed; the residents with more procedures trained in hospitals where there were less residents (669 ± 237 vs. 527 ±2 09; P = .004). CONCLUSION: The surgical activity performed by spanish surgeons is adequate to the specialty program, except in hepatobiliary and esophageal-gastric surgery. The distribution is homogeneous in the different autonomous regions, although there are differences that depend on the number and sex the of residents in each hospital. This information is essential to evaluate the quality of the specialty program and to design new training programs

PATRONES SIMPLES DE ABLACIÓN PARA LA TERMINACIÓN DE ROTORES EN FIBRILACIÓN AURICULAR CRÓNICA. ESTUDIO DE SIMULACIÓN / SIMPLE ABLATION PATTERNS FOR TERMINATING ROTORS IN CHRONIC ATRIAL FIBRILLATION. A SIMULATION STUDY / PADRÕES SIMPLES ABLAÇÃO DE RESCISÃO DE ROTORES COM FIBRILAÇÃO ATRIAL CRÔNICA. ESTUDO DE SIMULAÇÃO

La fibrilación auricular (FA) es la arritmia más común en la práctica clínica y por la que más se consulta en los servicios médicos. Recientemente, se ha propuesto un mecanismo de mantenimiento de la FA, el cual consiste en la existencia de uno o varios rotores que activan el tejido a alta frecuencia. La ablación es uno de los tratamientos para la FA, en FA crónica son necesarios patrones de ablación complejos, por lo que actualmente se busca el patrón ideal con un mínimo número de líneas de ablación. En este trabajo se simula la actividad de un rotor en un modelo 2D de tejido auricular humano, bajo condiciones de FA crónica y se localiza su centro de giro (tip). Se proponen y evalúan seis diferentes patrones simples de ablación compuestos por un número reducido de líneas. El estudio demostró que aquellos patrones que atraviesan o encierran el tip del rotor y que adicionalmente se prolongan hasta una frontera de conducción son eficaces en la terminación del rotor.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and the most consulted in medical services. Recently it has been proposed a mechanism for maintaining the AF, which consists in one or more rotors activating the tissue at high frequency. Ablation is one of the treatments for AF, for chronic AF is needed complex ablation patterns, so currently it has been looking for an ideal pattern with a minimum number of ablation lines. In this work activity of a rotor was simulated in a 2D model of human atrial tissue, under chronic AF conditions, and the center of rotation (tip) was located. Six different simple ablation patterns composed of a limited number of lines were proposed and evaluated. The study showed that those patterns that passed through or encloses the tip of the rotor and additionally were extended to a conduction boundary are effective in the termination of the rotor.

A fibrilação atrial (FA) é a arritmia mais comum na prática clínica e na consulta que a maioria dos serviços médicos. Recentemente, é proposto um mecanismo para a manutenção da FA, que é a existência de um ou mais rotores que activam o tecido com elevada frequência. A ablação é um tratamento para fibrilação atrial em padrões crônicos de ablação de FA necessárias são complexas, por isso eles estão atualmente buscando o padrão ideal, com um número mínimo de linhas de ablação. Neste documento, a actividade de um rotor é simulada em um modelo em 2D do tecido atrial humano, sob condições de AF crónica e o seu centro de rotação (ponta) está localizado. São propostos e avaliados seis diferentes padrões de ablação individuais compostos de um pequeno número de linhas. O estudo mostrou que as que passam através de padrões ou encerram a ponta do rotor e se estendem para além de um limite de condução são eficazes na cessação do rotor.

Cardiovascular fitness in youth; association with obesity and metabolic abnormalities / Entrenamiento cardiovascular en la juventud; asociación con obesidad y anomalías metabólicas

Therapies currently implemented for obesity are focused on nutritional aspects and on physical activity. In order to make physical activity a positive therapy instead of triggering disabilities it is relevant to accurately assess cardiovascular fitness. Objective: To assess the cardiovascular fitness by measuring the peak oxygen consumption and to asses their relationship with classical cardiometabolic parameters. Methods: A modified Balke protocol was applied to one hundred and twenty-six Caucasians (60% males), ranging between 9 and 16 years old, who underwent an assessment of obesity. The non-obese group consisted of healthy age and sex matched subjects who were invited to participate from the general population. Results: Significant differences in consumption of oxygen peak between non-obese and obese individuals were observed. In contrast, no significant differences existed between the categories of obesity. Furthermore in obese subjects consumption of oxygen peak was inversely correlated with parameters of cardiometabolic risk, particularly insulin and HOMA index. In addition, two predictive equations of consumption of oxygen peak, with an R2 of 0.74 and 0.84, respectively, have been developed. Conclusion: The consumption of oxygen peak is a relevant clinical parameter that should be included in the routine clinical assessment of obese subjects. Therefore, it is crucial to make exercise tests more affordable which can be achieved by employing predictive equations (AU)

Las terapias que se implantan actualmente para la obesidad se centran en los aspectos nutricionales y sobre la actividad física. Con el fin de hacer que la actividad física sea una terapia positiva en vez de un desencadenador de discapacidades, es relevante evaluar de forma precisa el entrenamiento cardiovascular. Objetivo: evaluar el entrenamiento cardiovascular midiendo el consumo máximo de oxígeno y evaluar su relación con los parámetros cardiometabólicos clásicos. Métodos: se aplicó el protocolo modificado de Balke a 126 individuos caucásicos (60 % de varones), con edades entre 9 y 16 años, que se sometieron a una evaluación de obesidad. El grupo de no obesos consistía de individuos sanos, de la población general, emparejados por edad y sexo y a los que se les invitó a participar. Resultados: se observaron diferencias significativas en el consumo máximo de oxígeno entre los individuos obesos y no obesos. Por contra, no existían diferencias significativas entre las categorías de obesidad. Además, en los sujetos obesos, el consumo máximo de oxígeno se correlacionó de forma inversa con los parámetros de riesgo cardiometabólico, particularmente con la insulina y el índice HOMA. Además, se han desarrollado dos ecuaciones predictivas del consumo máximo de oxígeno con una R2 de 0,74 y de 0,84, respectivamente. Conclusión: el consumo máximo de oxígeno es un parámetro clínico relevante que debería incluirse en la evaluación clínica rutinaria de los sujetos obesos. Por lo tanto, es crucial hacer que las pruebas de esfuerzo sean más asequibles, que puedan alcanzarse empleando las ecuaciones predictivas (AU)

Arritmias cardiacas generadas por heterogeneidad electrofisiológica: estudio mediante simulación / Cardiac arrhythmias generated by electrophysiological heterogeneity: simulation study

Las arritmias ventriculares usualmente se presentan como consecuencia de isquemia miocárdica aguda, lo cual causa la mayoría de las muertes súbitas. La heterogeneidad cardiaca tanto funcional (diferente comportamiento eléctrico en los miocitos) como bioquímica (diferentes concentraciones iónicas en isquemia), altera el comportamiento eléctrico del ventrículo y genera dispersión en la repolarización del potencial de acción, por lo que se convierte en sustrato funcional para la generación de arritmias fatales. En este trabajo se revisan las técnicas experimentales para el estudio y la detección de arritmias por reentrada, y se valida un modelo geométrico de isquemia, en presencia de heterogeneidad eléctrica en la región transmural de la pared ventricular. Para ello se utilizaron simulaciones bidimensionales de un modelo biofísicamente detallado y se obtuvieron reentradas lobulares en diferentes configuraciones de las células M de la pared ventricular.

Ventricular arrhythmias usually appear as consequence of acute myocardial ischemia, responsible for most of sudden deaths. Functional (different electrical behavior of myocytes) as well as biochemical (different ionic concentrations during ischemia) cardiac heterogeneity alter the ventricle electric performance and generate dispersion in the action potential repolarization that turns into functional substrate for the generation of fatal arrhythmias. In this work the experimental techniques for the study and detection of arrhythmias by re-entry are reviewed and a geometrical model of ischemia is validated in the presence of electrical heterogeneity in the trans-mural region of the ventricular wall. For this purpose, bi-dimensional simulations of a detailed biophysical model were used and lobular re-entries in different configurations of the M cells of the ventricular wall were obtained.