3D finite element electrical model of larval zebrafish ECG signals

Assessment of heart function in zebrafish larvae using electrocardiography (ECG) is a potentially useful tool in developing cardiac treatments and the assessment of drug therapies. In order to better understand how a measured ECG waveform is related to the structure of the heart, its position within the larva and the position of the electrodes, a 3D model of a 3 days post fertilisation (dpf) larval zebrafish was developed to simulate cardiac electrical activity and investigate the voltage distribution throughout the body. The geometry consisted of two main components; the zebrafish body was modelled as a homogeneous volume, while the heart was split into five distinct regions (sinoatrial region, atrial wall, atrioventricular band, ventricular wall and heart chambers). Similarly, the electrical model consisted of two parts with the body described by Laplace’s equation and the heart using a bidomain ionic model based upon the Fitzhugh-Nagumo equations. Each region of the heart was differentiated by action potential (AP) parameters and activation wave conduction velocities, which were fitted and scaled based on previously published experimental results. ECG measurements in vivo at different electrode recording positions were then compared to the model results. The model was able to simulate action potentials, wave propagation and all the major features (P wave, R wave, T wave) of the ECG, as well as polarity of the peaks observed at each position. This model was based upon our current understanding of the structure of the normal zebrafish larval heart. Further development would enable us to incorporate features associated with the diseased heart and hence assist in the interpretation of larval zebrafish ECGs in these conditions

Observation of the rare decay K_S -> pi^0mu^+mu^-

A search for the decay K_S -> pi^0mu^+mu^- has been made by the NA48/1 Collaboration at the CERN SPS accelerator. The data were collected during 2002 with a high-intensity K_S beam. Six events were found with a background expectation of 0.22^+0.18_-0.11 event. Using a vector matrix element and unit form factor, the measured branching ratio is B(K_S -> pi^0mu^+mu^-)=[2.9^+1.5_-1.2(stat)+/-0.2(syst)]x10^{-9}.Comment: 19 pages, 8 figures, 4 tables. To be published in Physics Letters

Machine Learning Prediction of Cardiac Resynchronisation Therapy Response From Combination of Clinical and Model-Driven Data

Background: Up to 30–50% of chronic heart failure patients who underwent cardiac resynchronization therapy (CRT) do not respond to the treatment. Therefore, patient stratification for CRT and optimization of CRT device settings remain a challenge. Objective: The main goal of our study is to develop a predictive model of CRT outcome using a combination of clinical data recorded in patients before CRT and simulations of the response to biventricular (BiV) pacing in personalized computational models of the cardiac electrophysiology. Materials and Methods: Retrospective data from 57 patients who underwent CRT device implantation was utilized. Positive response to CRT was defined by a 10% increase in the left ventricular ejection fraction in a year after implantation. For each patient, an anatomical model of the heart and torso was reconstructed from MRI and CT images and tailored to ECG recorded in the participant. The models were used to compute ventricular activation time, ECG duration and electrical dyssynchrony indices during intrinsic rhythm and BiV pacing from the sites of implanted leads. For building a predictive model of CRT response, we used clinical data recorded before CRT device implantation together with model-derived biomarkers of ventricular excitation in the left bundle branch block mode of activation and under BiV stimulation. Several Machine Learning (ML) classifiers and feature selection algorithms were tested on the hybrid dataset, and the quality of predictors was assessed using the area under receiver operating curve (ROC AUC). The classifiers on the hybrid data were compared with ML models built on clinical data only. Results: The best ML classifier utilizing a hybrid set of clinical and model-driven data demonstrated ROC AUC of 0.82, an accuracy of 0.82, sensitivity of 0.85, and specificity of 0.78, improving quality over that of ML predictors built on clinical data from much larger datasets by more than 0.1. Distance from the LV pacing site to the post-infarction zone and ventricular activation characteristics under BiV pacing were shown as the most relevant model-driven features for CRT response classification. Conclusion: Our results suggest that combination of clinical and model-driven data increases the accuracy of classification models for CRT outcomes. Copyright © 2021 Khamzin, Dokuchaev, Bazhutina, Chumarnaya, Zubarev, Lyubimtseva, Lebedeva, Lebedev, Gurev and Solovyova.This work was supported by Russian Science Foundation grant no. 19-14-00134

Recruitment of SAC with V_SAC of −10 mV diminishes scroll wave breakup at low g_SAC.

<p>Changes in the CV restitution curves due to SAC opening for different values of λ_f. (A): g_SAC = 0.02 mS/µF, (B): g_SAC = 0.04 mS/µF and (C): g_SAC = 0.07 mS/µF. (D): Epicardial transmembrane potential distribution map on the anterior wall for V_SAC of −10 mV and g_SAC = 0.04 mS/µF when λ_f was assumed constant and equal to 1.2. Pink dot indicates the location of the phase singularity.</p

Effects of Mechano-Electric Feedback on Scroll Wave Stability in Human Ventricular Fibrillation

<div><p>Recruitment of stretch-activated channels, one of the mechanisms of mechano-electric feedback, has been shown to influence the stability of scroll waves, the waves that underlie reentrant arrhythmias. However, a comprehensive study to examine the effects of recruitment of stretch-activated channels with different reversal potentials and conductances on scroll wave stability has not been undertaken; the mechanisms by which stretch-activated channel opening alters scroll wave stability are also not well understood. The goals of this study were to test the hypothesis that recruitment of stretch-activated channels affects scroll wave stability differently depending on stretch-activated channel reversal potential and channel conductance, and to uncover the relevant mechanisms underlying the observed behaviors. We developed a strongly-coupled model of human ventricular electromechanics that incorporated human ventricular geometry and fiber and sheet orientation reconstructed from MR and diffusion tensor MR images. Since a wide variety of reversal potentials and channel conductances have been reported for stretch-activated channels, two reversal potentials, −60 mV and −10 mV, and a range of channel conductances (0 to 0.07 mS/µF) were implemented. Opening of stretch-activated channels with a reversal potential of −60 mV diminished scroll wave breakup for all values of conductances by flattening heterogeneously the action potential duration restitution curve. Opening of stretch-activated channels with a reversal potential of −10 mV inhibited partially scroll wave breakup at low conductance values (from 0.02 to 0.04 mS/µF) by flattening heterogeneously the conduction velocity restitution relation. For large conductance values (>0.05 mS/µF), recruitment of stretch-activated channels with a reversal potential of −10 mV did not reduce the likelihood of scroll wave breakup because Na channel inactivation in regions of large stretch led to conduction block, which counteracted the increased scroll wave stability due to an overall flatter conduction velocity restitution.</p> </div

The average number of filaments in the ventricular model with SAC of V_SAC of −10 mV for different g_SAC.

<p>The symbol * indicates that the average number of filaments is significantly smaller than that in the model without SAC representation (p<0.05).</p

The average number of filaments in the VF human ventricular electromechanical model with SAC of V_SAC of −60 mV for different g_SAC.

<p>The symbol * indicates that the average number of filaments is significantly smaller than that in the model without SAC representation (p<0.05).</p

Recruitment of SAC with V_SAC of −10 mV results in scroll wave breakup at large g_SAC.

<p>(A): Distribution of λ_f at 0.9 s after arrhythmia induction for the ventricular model with V_SAC of −10 mV; g_SAC = 0.07 mS/µF. (B): Scroll wave breakup in the region of large stretch (indicated by arrow). (C), (D) and (E) are plots of I_SAC, I_Na and V_m, respectively from the node indicated by the arrow in (B). The arrow denotes in (C): the large inward I_SAC during repolarization, in (D): inactivation of Na channels, (E): conduction block.</p

Лімфоцитома шкіри в практиці лікаря-патологоанатома: клініко-морфологічний аналіз випадку з практики

ABSTRACT. Background. Currently, lymphocytoma of the skin is not so rare, but it is still little known for doctors. Accordingto the modern concepts the skin lymphocytoma is considered as a benign process, which is based on the reactivepolyclonal lymphocytes proliferation, which arises in response to the action of various exogenous and endogenous factors.Objective. To analyze the literature data about the skin lymphocytoma and to bring a clinical and morphological analysis ofthe case from practice of this pathology. Methods. The authors studied the patient’s biopsy material. The microspecimenswere stained with hematoxylin and eosin, as well as with picrofuxin by the van Gieson and studied using microscope «OlympusВХ-41». Results. The authors noted that the analysis of clinical-anamnestic data and histological examination are importantfor the diagnosis of skin lymphocytoma. In the case from practice cited by the authors the cause of the skin lymphocytomadevelopment was the constant antigenic stimulation of the immunogenic components that make up the paints that wereused to perform the tattoo. Conclusion. The authors hope that the observation from practice of skin lymphocytoma will beinteresting and useful not only for dermatologists and pathologists, but also for physicians of other specialties.Реферат. В настоящее время лимфоцитома кожи является не такой большой редкостью, однако практикующим врачам она по-прежнему мало известна. В статье авторами проведен анализ данных литературы и описан случай наблюдения из практики лимфоцитомы кожи. По современным представлениям, лимфоцитома кожи рассматривается как доброкачественный процесс, в основе которого лежит реактивная поликлональная пролиферация лимфоцитов, возникающая в ответ на действие различных экзогенных и эндогенных факторов. В приведенном авторами случае из практики причиной развития лимфоцитомы кожи явилась ранее выполненная татуировка. В частности, в сосочковом и сетчатом слоях дермы определялся инфильтрат, который местами четко был отделен от эпидермиса слоем сосочкового слоя дермы (зоной Гренза), а местами прилежал к эпидермису и состоял из лимфоцитов и гистиоцитов. Вышеуказанные клеточные элементы располагались либо беспорядочно, либо в форме фолликулов, строение которых напоминало фолликулы лимфатического узла (гистиоциты в центре инфильтрата, лимфоциты вокруг них в виде периферического валика). Местами инфильтрат, состоящий из лимфоцитов и гистиоцитов, определялся вокруг сосудов и придатков кожи. Интересно то, что в области описанной инфильтрации было выявлено разрежение структур придатков кожи. В данном случае развитие лимфоцитомы кожи обусловлено, скорее всего, постоянной антигенной стимуляцией иммуногенных компонентов, входящих в состав красок, которые используют для выполнения татуировок.Реферат. В даний час лімфоцитома шкіри є не такою великою рідкістю, однак лікарям вона, як і раніше, мало відома. У статті авторами проведено аналіз даних літератури і описаний випадок спостереження з практики лімфоцитоми шкіри. За сучасними уявленнями лімфоцитома шкіри розглядається як доброякісний процес, в основі якого лежить реактивна поліклональна проліферація лімфоцитів, що виникає у відповідь на дію різних екзогенних та ендогенних факторів. У наведеному авторами випадку з практики причиною розвитку лімфоцитоми шкіри було раніше виконане татуювання. Зокрема, в сосочковому і сітчастому шарах дерми визначався інфільтрат, який місцями чітко був відділений від епідермісу шаром сосочкового шару дерми (зоною Гренза), а місцями прилягав до епідермісу і складався з лімфоцитів і гістіоцитів. Вищевказані клітинні елементи розташовувалися або безладно, або в формі фолікулів, будова яких нагадувала фолікули лімфатичного вузла (гістіоцити в центрі інфільтрату, лімфоцити навколо них у вигляді периферичного валика). Місцями інфільтрат, що складається з лімфоцитів і гістіоцитів, визначався навколо судин і придатків шкіри. Цікаво те, що в області описаної інфільтрації було виявлено розрідження структур придатків шкіри. В даному випадку розвиток лімфоцитоми шкіри обумовлено, швидше за все, постійною антигенною стимуляцією імуногенних компонентів, що входять до складу фарб, які використовують для виконання татуювань