A5009600398- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Cardiac pacing and defibrillation studies
- Cardiac Arrhythmias and Treatments
- ECG Monitoring and Analysis
- Atrial Fibrillation Management and Outcomes
- Indoor and Outdoor Localization Technologies
- Heart Rate Variability and Autonomic Control
- Potassium and Related Disorders
- Receptor Mechanisms and Signaling
- Electrochemical Analysis and Applications
- Pluripotent Stem Cells Research
- Hemodynamic Monitoring and Therapy
- Dialysis and Renal Disease Management
- Non-Invasive Vital Sign Monitoring
- Neuroscience and Neuropharmacology Research
- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Analytical Chemistry and Sensors
- Energy Efficient Wireless Sensor Networks
- EEG and Brain-Computer Interfaces
- Underwater Vehicles and Communication Systems
- Heart Failure Treatment and Management
- Genetic and Kidney Cyst Diseases
University of Bologna
2016-2025
Laboratori Guglielmo Marconi (Italy)
2016-2025
Marconi University
2016-2025
Azienda-Unita' Sanitaria Locale Di Cesena
2008-2021
Constructor University
2011-2018
Ritsumeikan University
2018
Karlsruhe Institute of Technology
2018
Universidad Autónoma de Madrid
2018
University of Amsterdam
2017
Amsterdam UMC Location University of Amsterdam
2017
Human-based modelling and simulations are becoming ubiquitous in biomedical science due to their ability augment experimental clinical investigations. Cardiac electrophysiology is one of the most advanced areas, with cardiac simulation being considered for virtual testing pharmacological therapies medical devices. Current models present inconsistencies data, which limit further progress. In this study, we design, development, calibration independent validation a human-based ventricular model...
Key points We constructed a comprehensive mathematical model of the spontaneous electrical activity human sinoatrial node (SAN) pacemaker cell, starting from recent Severi–DiFrancesco rabbit SAN cells. Our is based on electrophysiological data isolated cells and closely matches action potentials calcium transient that were recorded experimentally. Simulated ion channelopathies explain clinically observed changes in heart rate corresponding mutation carriers, providing an independent...
Calmodulin (CaM) is a small protein, encoded by three genes (CALM1-3), exerting multiple Ca2+-dependent modulatory roles. A mutation (F142L) affecting only one of the six CALM alleles associated with long QT syndrome (LQTS) characterized recurrent cardiac arrests. This phenotypic severity unexpected from predicted allelic balance. In this work, effects heterozygous CALM1-F142L have been investigated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained LQTS...
Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward reduced outward currents, their role in promoting repolarisation abnormalities remains unknown. The goal this study to identify key ionic driving human HCM, evaluate anti-arrhythmic effects single multichannel current blocks.
Computational models of the electrical activity sinoatrial cells (SANCs) have been proposed to gain a deeper understanding cellular basis cardiac pacemaking. However, they fail reproduce number experimental data, among which are effects measured after modifications 'funny' (If) current. We developed novel SANC mathematical model by updating description membrane currents and intracellular mechanisms on acquisitions, in an attempt pacemaker its physiological pharmacological modulation. Our...
This white paper presents principles for validating proarrhythmia risk prediction models regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food Drug Administration–sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate progress in development new cardiac safety paradigm, Comprehensive Vitro Proarrhythmia Assay (CiPA). opinions regarding these reflect collective views...
Background . Although sudden death is one of the most frequent causes in haemodialysis (HD) patients, problem cardiac arrhythmias, major cause these outcomes, has been little discussed.
The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or preliminary cardiotoxicity tests, generated better understanding hiPSC-CM biophysical mechanisms great amount action potential calcium transient data. In this paper, we propose a new in silico model, with particular attention to Ca2+ handling. We used i) the Paci2013 model starting point, ii)...
Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) silico human adult ventricular cardiomyocyte (hAdultV-CM) models. Their combination was recently proposed as a potential replacement for the present hERG-based QT study pharmacological assessments. Here, we systematically compared effects of selective ionic current block hiPSC-CM hAdultV-CM action potentials...
High-throughput in vitro drug assays have been impacted by recent advances human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) technology and contact-free all-optical systems simultaneously measuring action potentials (APs) Ca2+ transients (CaTrs). Parallel computational shown that silico simulations can predict effects with high accuracy. We combine these technologies demonstrate the utility of high-throughput experimental data to refine hiPSC-CM populations explain...
Sodium channel blockers are used as gene-specific treatments in long-QT syndrome type 3, which is caused by mutations the sodium gene (SCN5A). Response to treatment influenced biophysical properties of mutations.We sought investigate unexpected deleterious effect mexiletine a mutation combining gain-of- function and trafficking abnormalities.A 3 child experienced paradoxical QT prolongation worsening arrhythmias after treatment. The SCN5A F1473S expressed HEK293 cells presented right-ward...
BackgroundHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are in vitro models with the clear advantages of their human origin and suitability for disease investigations. However, limitations include incomplete characterization variability reported different cell lines laboratories.ObjectiveThe purpose this study was to investigate silico ionic mechanisms potentially explaining phenotypic hiPSC-CMs long QT syndrome type 3 (LQT3) response antiarrhythmic...
KCNQ1 and KCNE1 encode Kv7.1 KCNE1, respectively, the pore-forming accessory subunits of slow delayed rectifier potassium current, IKs. mutations are associated with long short QT syndrome. The aim this study was to characterize biophysical cellular phenotype a missense mutation, F279I, found in 23-year-old man corrected interval (QTc) 356 ms family history sudden cardiac death. Experiments were performed using perforated patch-clamp, western blot, co-immunoprecipitation, biotinylation,...
Cardiac Purkinje cells (PCs) are implicated in lethal arrhythmias caused by cardiac diseases, mutations, and drug action. However, the pro-arrhythmic mechanisms PCs not entirely understood, particularly humans, as most investigations conducted animals. The aims of this study to present a novel human electrophysiology biophysically-detailed computational model, disentangle ionic Purkinje-related electrophysiology, pacemaker activity arrhythmogenicity. new Trovato2020 model incorporates...
The importance of electrolyte concentrations for cardiac function is well established. Electrolyte variations can lead to arrhythmias onset, due their important role in the action potential (AP) genesis and maintaining cell homeostasis. However, most human AP computer models available literature were developed with constant concentrations, fail simulate physiological changes induced by variations. This especially true Ca2+, even O'Hara-Rudy model (ORd), one widely used electrophysiology....
Background. Alterations of ventricular repolarization duration, as measured by the QT interval, are frequently observed in haemodialysis (HD) patients. The nature and sign these changes not yet fully understood. Methods. Different dialysate K + Ca 2+ levels, leading to different end-HD plasma concentrations patient, have been tested present study terms their impact on QTc. A model human cardiomyocyte action potential (AP) has used assess silico whether were able justify at cellular level...
The Na+ channel mutation (p.S216L), previously associated with type 3 long-QT syndrome (LQT3) phenotype, and a common polymorphism (p.H558R) were detected in patient an intermittent Brugada (BS) ECG pattern. study was aimed to assess the p.S216L electrical its modulation by p.H558R, identify abnormalities compatible mixed BS-LQT3 phenotype. expressed alone (S216L channels), or combination (S216L–H558R mammalian cell line (TSA201). Functional analysis included standard voltage clamp dynamic...
In recent years, binary coding of image features, such as local patterns and phase quantization, have become popular in a large variety quantification tasks. Lately, some non-binary codings, ternary pattern, been proposed to improve the performance these based approaches. methods it is very important correctly choose thresholds applied for building used represent given its features by feature vector. Keywords: Machine learning, coding, stem cell image, sub-cellular support vector machine,...
Both biomedical research and clinical practice rely on complex datasets for the physiological genetic characterization of human hearts in health disease. Given complexity variety approaches recordings, there is now growing recognition need to embed computational methods cardiovascular medicine science analysis, integration prediction. This paper describes a Workshop Computational Cardiovascular Science that created an international, interdisciplinary inter-sectorial forum define next steps...
Abstract Blood potassium concentration ([K + ]) influences the electrocardiogram (ECG), particularly T-wave morphology. We developed a new method to quantify [K ] from analysis and tested its clinical applicability on data dialysis patients, in whom varies significantly during therapy. To elucidate mechanism linking T-wave, we also analysed long QT syndrome type 2 (LQT2) testing hypothesis that our would have underestimated these patients. Moreover, computational model was used explore...
Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse dependent agents greater at slow heart rates, resulting in both reduced arrhythmia suppression fast rates and increased risk rates. opposite property, forward dependence, would theoretically overcome these parallel problems, yet (FRD) antiarrhythmics remain elusive. Moreover, there evidence an intrinsic perturbations to AP. We have...
<b><i>Objective:</i></b> To characterize the clinical features of a new type X-linked mental retardation associated with MECP2 mutation in index family. <b><i>Background:</i></b> mutations, originally described high percentage patients classic Rett syndrome, were considered lethal men. The authors recently novel A140V missense an Italian family semidominant retardation. <b><i>Methods:</i></b> neurologic six symptomatic relatives (two women and four men) carrying compiled. Laboratory...