Electrophysiological Characteristics Research Articles

Ventricular arrhythmias in association with athletic cardiac remodelling.

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs) and sudden cardiac death is less well established. Thus, it is unclear whether the 'athlete's heart' promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse. The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete's heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point toward a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete. This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance and approach to the management of athletes with VAs.

The cumulative effect of compound heterozygous variants in TRPV3 caused Olmsted syndrome

BackgroundOlmsted syndrome (OS) is a rare genodermatosis predominantly inherited in an autosomal dominant manner, typically arising from gain-of-function (GOF) variants in the transient receptor potential channel vanilloid 3 (TRPV3). ObjectiveThis study aims to investigate potential mechanisms underlying OS in two cases presenting with an autosomal recessive inheritance pattern. MethodsNext-generation sequencing panel was employed to identify TRPV3 variants. TRPV3 plasmids carrying specific point variations were generated and transiently transfected into HEK293T cells. Electrophysiological patch-clamp techniques were utilized to record voltage-activated and ligand-activated currents. Celltiter-Glo luminescent assay was employed to analyze the cell viabilities. ResultsCompound heterozygous variants, c.1563G>C (p.W521C) and c.1376C>T (p.S459L), as well as c.1773G>C (p.L591F) and c.2186G>A (p.R729Q), were identified in the two OS patients respectively. Electrophysiological analysis of ligand-induced activation of TRPV3 variants demonstrated the closest correlation with clinical manifestations. All four variants displayed GOF channel activity characterized by increased sensitivity. Notably, W521C and L591F exhibited both heightened sensitivity and lower EC50 values for the TRPV3 agonist. Co-transfection with wild-type TRPV3 plasmids significantly rescued these effects. Cells co-transfected with the corresponding compound heterozygous variants exhibited intermediate electrophysiological characteristics. ConclusionsIn this study, we present two cases of OS by autosomal-recessive inheritance of TPRV3 variants. This study presents a notable observation of compound heterozygous GOF variants in TRPV3, highlighting their cumulative impact on clinical manifestations. Additionally, we advocate for the use of ligand-dependent ion channel activity assays to assess the pathogenicity of TRPV3 variants in OS.

Cellular calcium handling and electrophysiology are modulated by chronic physiological pacing in human induced pluripotent stem cell-derived cardiomyocytes.

Electric pacing of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) has been increasingly used to simulate cardiac arrhythmias in vitro and to enhance cardiomyocyte maturity. However, the impact of electric pacing on cellular electrophysiology and Ca2+ handling in differentiated hiPSC-CM is less characterized. Here we studied the effects of electric pacing for 24 h or 7 days at a physiological rate of 60 beats/min on cellular electrophysiology and Ca2+ cycling in late-stage, differentiated hiPSC-CM (>90% troponin+, >60 days postdifferentiation). Electric culture pacing for 7 days did not influence cardiomyocyte cell size, apoptosis, or generation of reactive oxygen species in differentiated hiPSC-CM compared with 24-h pacing. However, epifluorescence measurements revealed that electric pacing for 7 days improved systolic Ca2+ transient amplitude and Ca2+ transient upstroke, which could be explained by elevated sarcoplasmic reticulum Ca2+ load and SERCA activity. Diastolic Ca2+ leak was not changed in line-scanning confocal microscopy, suggesting that the improvement in systolic Ca2+ release was not associated with a higher open probability of ryanodine receptor (RyR)2 during diastole. Whereas bulk cytosolic Na+ concentration and Na+/Ca2+ exchanger (NCX) activity were not changed, patch-clamp studies revealed that chronic pacing caused a slight abbreviation of the action potential duration (APD) in hiPSC-CM. We found in whole cell voltage-clamp measurements that chronic pacing for 7 days led to a decrease in late Na+ current, which might explain the changes in APD. In conclusion, our results show that chronic pacing improves systolic Ca2+ handling and modulates the electrophysiology of late-stage, differentiated hiPSC-CM. This study might help to understand the effects of electric pacing and its numerous applications in stem cell research including arrhythmia simulation.NEW & NOTEWORTHY Electric pacing is increasingly used in research with human induced pluripotent stem cell cardiomyocytes (hiPSC-CM), for example to simulate arrhythmias but also to enhance maturity. Therefore, it is mandatory to understand the effects of pacing itself on cellular electrophysiology in late-stage, matured hiPSC-CM. This study provides an electrophysiological characterization of the effects of chronic electric pacing at a physiological rate on differentiated hiPSC-CM.

Polyethyleneimine facilitates the growth and electrophysiological characterization of iPSC-derived motor neurons.

Induced pluripotent stem cell (iPSC) technology, in combination with electrophysiological characterization via multielectrode array (MEA), has facilitated the utilization of iPSC-derived motor neurons (iPSC-MNs) as highly valuable models for underpinning pathogenic mechanisms and developing novel therapeutic interventions for motor neuron diseases (MNDs). However, the challenge of MN adherence to the MEA plate and the heterogeneity presented in iPSC-derived cultures raise concerns about the reproducibility of the findings obtained from these cellular models. We discovered that one novel factor modulating the electrophysiological activity of iPSC-MNs is the extracellular matrix (ECM) used in the coating to support in vitro growth, differentiation and maturation of iPSC-MNs. The current study showed that two coating conditions, namely, Poly-L-ornithine/Matrigel (POM) and Polyethyleneimine (PEI) strongly promoted attachment of iPSC-MNs on MEA culture dishes compared to three other coating conditions, and both facilitated the maturation of iPSC-MNs as characterized by the detection of extensive electrophysiological activities from the MEA plates. POM coating accelerated the maturation of the iPSC-MNs for up to 5weeks, which suits modeling of neurodevelopmental disorders. However, the application of PEI resulted in more even distribution of the MNs on the culture dish and reduced variability of electrophysiological signals from the iPSC-MNs in 7-week cultures, which permitted the detection of enhanced excitability in iPSC-MNs from patients with amyotrophic lateral sclerosis (ALS). This study provides a comprehensive comparison of five coating conditions and offers POM and PEI as favorable coatings for in vitro modeling of neurodevelopmental and neurodegenerative disorders, respectively.

CardioMEA: comprehensive data analysis platform for studying cardiac diseases and drug responses

IntroductionIn recent years, high-density microelectrode arrays (HD-MEAs) have emerged as a valuable tool in preclinical research for characterizing the electrophysiology of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs). HD-MEAs enable the capturing of both extracellular and intracellular signals on a large scale, while minimizing potential damage to the cell. However, despite technological advancements of HD-MEAs, there is a lack of effective data-analysis platforms that are capable of processing and analyzing the data, particularly in the context of cardiac arrhythmias and drug testing.MethodsTo address this need, we introduce CardioMEA, a comprehensive data-analysis platform designed specifically for HD-MEA data that have been obtained from iPSCCMs. CardioMEA features scalable data processing pipelines and an interactive web-based dashboard for advanced visualization and analysis. In addition to its core functionalities, CardioMEA incorporates modules designed to discern crucial electrophysiological features between diseased and healthy iPSC-CMs. Notably, CardioMEA has the unique capability to analyze both extracellular and intracellular signals, thereby facilitating customized analyses for specific research tasks.Results and discussionWe demonstrate the practical application of CardioMEA by analyzing electrophysiological signals from iPSC-CM cultures exposed to seven antiarrhythmic drugs. CardioMEA holds great potential as an intuitive, userfriendly platform for studying cardiac diseases and assessing drug effects.

Interleukin-6 levels in atrium and onset of spontaneous atrial fibrillation: is there a causal relationship

Abstract Background Cumulative evidence suggests that atrial interleukin-6 (IL-6) may play a significant role in the development of spontaneous postoperative atrial fibrillation (sPOAF) in coronary artery bypass grafting (CABG) patients. Our previous studies found that the IL-6 produced by the atrium is positively related to the development of sPOAF. However, the causal relationship between IL-6 and sPOAF is not established. Purpose This study aims to explore the potential causality between atrial IL-6 and spontaneous AF(sAF), alongside assessing the impact of IL-6 on the electrophysiological properties of atrial myocytes (AM). Methods To determine the causal link between IL-6 and sAF, mice were randomly divided into eight groups: seven receiving injections of varying doses of recombinant IL-6 protein groups (15ng/kg to180ng/kg) into the left atrial wall, and one control group (vehicle). Mice were monitored for sAF for 7 days using implanted telemetry device. At 48 hrs post-injection, the left atrial appendages of another set of mice were collected for analyzing levels of IL-6, Myeloperoxidase (MPO), Transforming Growth Factor-β1 (TGF-β1), and Tumor Necrosis Factor-α (TNF-α). To assess the effect of IL-6 on the electrophysiological characteristics of AM, AMs were isolated from the hearts of 12-week-old mice and divided into experimental and control groups for electrophysiological testing. The experimental group was perfused with extracellular solutions containing 100 ng/mL of IL-6 while the control group was perfused with standard extracellular solutions. The measurements focused on action potential (AP), transient outward potassium current (Ito), and inward rectifier potassium current (Ik1) after a 30-minute perfusion. Results As depicted in Fig. 1A, a dose-response relationship between IL-6 levels and sAF occurrence was observed, with incidence increasing from 0% at 15 ng/kg to 75% at 180 ng/kg (χ²= 16.691, P = 0.005). The injection of IL-6 also induced the production of MPO, TGF-β1, and TNF-α with a dose-dependent effects (Fig. 2). In comparison to control, the AP duration at 90% (APD90) and APD50 of repolarization of atrial myocytes were significantly shortened in IL-6 group (Fig. 1B). For voltages from -10mV to +70mV, atrial myocytes in the IL-6 group showed significantly lower Ito current density than those in the control (Fig. 1C). No significant alterations were observed in the impact of IL-6 on Ik1 current density in atrial myocytes (Fig.1D). Conclusion To the best of our knowledge, this is the first study that experimentally tested the causal relation between IL-6 and sAF. The injection of IL-6 could cause the onset of sAF and produce MPO, TGF-β1, and TNF-α with a significant dose-dependent effect. The effect of IL-6 on inducing sAF might be through its effect on reducing APD and Ito current density in mouse atrial myocytes. This suggests that inhibition of atrial IL-6 might be a potential novel sPOAF prevention strategy.

Right ventricular outflow tract arrhythmias in patients with obstructive sleep apnea- electrophysiological insights

Abstract Background Obstructive sleep apnea (OSA) was associated with atrial fibrillation and heart failure. Furthermore, the arrhythmic sudden death during sleep in patients with OSA raises serious concerns. Non-ischemic ventricular arrhythmias arise frequently from the right ventricular outflow tract (RVOT). The involvement of obstructive sleep apnea in the genesis of arrhythmia (premature ventricular contraction or tachycardia) originating specifically in the RVOT is not yet coherently established. Purpose This study aims to demonstrate the possible relationship between untreated obstructive sleep apnea and the occurrence of RVOT arrhythmia and to follow the electrophysiological features and outcomes after radiofrequency catheter ablation (RFA) in patients carrying this double burden. Methods One-hundred-twelve (112) consecutive asymptomatic and symptomatic patients admitted with RVOT arrhythmia ((PVCs and VTs) underwent a sleep study (polysomnography). Apnea was set out as the cessation of breathing and hypopnea was defined as shallow, slow, and restricted breathing occurring in episodes of ten seconds or more. The patients had normal left and right ventricle ejection fractions and no structural cardiovascular disease or other known extracardiac arrhythmia predisposing conditions. No significantly elevated systolic pressure in the pulmonary artery was assessed at echocardiography. Every patient was investigated by electrophysiologic study (EPS) and RFA of the clinical ventricular arrhythmia was immediately performed. Practicing and former professional athletes were excluded. Results Seventy-eight (69 %) of the included patients had an apnea-hypopnea index > 10/h. The included patients had the following characteristics: mean age 52 ± 8 years, 62% males, 81% had a BMI >30kg/m². The cardiac electrophysiologic study did not induce sustained VTs. The distribution of the PVCs and non-sustained VTs evidenced a predilection for the superior, septal and anterior (68%) and also superior and anterolateral aspects of the RVOT (23%). Radiofrequency catheter ablation (RFA) guided by activation mapping, precocity (the site of earliest activation > 30 ms before the setting of the QRS complex) and pace-mapping were performed in all patients. Immediate success was obtained in 98 patients (88%). After a mean follow-up of 24± 6 months, 28 patients (28%) from the success arm had a recurrence of the PVCs or the non-sustained VTs, 22 patients (22%) with and 6 patients (6%) without sleep apnea. Conclusions RVOT arrhythmia genesis and relapse after successful RFA seem highly associated with sleep apnea. Furthermore, patients with sleep apnea are more prone to have recurrent arrhythmias after radiofrequency catheter ablation in the absence of appropriate control of OSA.

Multi-modality deep learning prediction of heart age: insights from UK-Biobank

Abstract Background Identification of apparently healthy individuals at high cardiovascular risk who may benefit from targeted preventive strategies remains challenging. Predicted heart age, the chronological age of individuals with similar absolute cardiovascular disease (CVD) risk but with no risk factors, has been proposed to appropriately describe the absolute CVD risk over conventional prediction tools. Purpose To develop multi-modality based deep learning predictors for heart age in UK-Biobank individuals. Methods We used deep learning to develop a heart age predictor based on videos from heart magnetic resonance imaging (MRI) (anatomical dimension), electrocardiograms (ECG) (electrical dimension) or both from 45000 individuals of the UK Biobank cohort (age range 45-81 years) (Figure). We estimated the heritability of heart aging and identified single-nucleotide polymorphisms associated with accelerated heart aging. We performed X-wide association study to identify non-genetic factors potentially associated with accelerated heart aging. Results We predicted age with a mean absolute error (MAE) of 2.5±0.03 years (R2=85.6±0.6%) and found that accelerated heart aging is heritable at more than 35%. MRI-based anatomical features predicted age better than ECG-based electro-physiological features (MAE=2.29±0.03 years versus 4.90±.0.08 years), and heart anatomical and electrical aging were weakly correlated (Pearson correlation=0.249±0.002). Our attention maps highlighted the aorta, the mitral valve, and the interventricular septum as key anatomical features driving heart age prediction in videos that capture the entire heartbeat cycle. We found accelerated anatomical and electrical heart aging to be genetically correlated (Pearson correlation=0.508±0.089). The most significant locus was in TTN (Titin) and it was associated with heart anatomical aging. Cardiovascular diseases, general health status, and mental health disorders were highly associated with accelerated heart aging. Conclusions A multi-modality based deep learning approach was highly predictive of heart age. Accelerated heart age has a complex biological basis with genetic and environmental correlates. Leveraging of the described pipeline to predict survival and the onset of age-related cardiovascular diseases may shed light on heart aging role in health outcomes and effectively guide personalized preventive strategies.

Surgical treatment of long-term epilepsy-associated tumors guided by stereoelectroencephalography

PurposeAccurate detection and resection of the epileptogenic zone (EZ) in patients with long-term epilepsy-associated tumors (LEATs) are significantly correlated with favorable seizure prognosis. However, the relationship between tumors and the EZ remains unknown. This study aimed to evaluate the spatial relationship between LEATs and the EZ, as well as the electrophysiological features of LEATs.MethodsWe retrospectively studied five patients with LEATs who underwent deep electrode implantation and EZ resection in the hospital. The clinical characteristics, surgical outcomes, localizing features and intracranial SEEG results were reviewed.ResultsOne female and four males (mean age: 25.2 years; median age: 24 years; range: 13–45 years) were included in the study. Five-to-eleven electrodes (mean: 8.4) were implanted per patient. The EZ was located in the tumor and nearby cortex in three cases and in the tumor and distant areas in two cases. Pathological examination revealed ganglioglioma in four cases, two of which were associated with hippocampal sclerosis, and the other case showed a multinodular and vacuolating neuronal tumor with gliosis. All patients were seizure-free for at least 24 months postoperatively.ConclusionsSEEG provides valuable insights into the electrophysiological mechanisms of LEATs. The EZ often contains brain tissue around the tumor. However, only a few cases, particularly those with temporoparietal occipital (TPO) area involvement, a long history of epilepsy and other abnormalities on MRI, such as hippocampal sclerosis and focal cortical dysplasia, may include distant areas.

Molecular mechanisms underlying glucose-dependent insulinotropic polypeptide secretion in human duodenal organoids.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by enteroendocrine K cells in the proximal small intestine. This study aimed to explore the function of human K cells at the molecular and cellular levels. CRISPR-Cas9 homology-directed repair was used to insert transgenes encoding a yellow fluorescent protein (Venus) or an Epac-based cAMP sensor (Epac-S-H187) in the GIP locus in human duodenal-derived organoids. Fluorescently labelled K cells were purified by FACS for RNA-seq and peptidomic analysis. GIP reporter organoids were employed for GIP secretion assays, live-cell imaging of Ca2+ using Fura-2 and cAMP using Epac-S-H187, and basic electrophysiological characterisation. The G protein-coupled receptor genes GPR142 and CASR were knocked out to evaluate roles in amino acid sensing. RNA-seq of human duodenal K cells revealed enrichment of several G protein-coupled receptors involved in nutrient sensing, including FFAR1, GPBAR1, GPR119, CASR and GPR142. Glucose induced action potential firing and cytosolic Ca2+ elevation and caused a 1.8-fold increase in GIP secretion, which was inhibited by the sodium glucose co-transporter 1/2 (SGLT1/2) blocker sotagliflozin. Activation of the long-chain fatty acid receptor free fatty acid receptor 1 (FFAR1) induced a 2.7-fold increase in GIP secretion, while tryptophan and phenylalanine stimulated secretion by 2.8- and 2.1-fold, respectively. While CASR knockout blunted intracellular Ca2+ responses, a CASR/GPR142 double knockout was needed to reduce GIP secretory responses to aromatic amino acids. The newly generated human organoid K cell model enables transcriptomic and functional characterisation of nutrient-sensing pathways involved in human GIP secretion. Both calcium-sensing receptor (CASR) and G protein-coupled receptor 142 (GPR142) contribute to protein-stimulated GIP secretion. This model will be further used to identify potential targets for modulation of native GIP secretion in diabetes and obesity.

Differential electrographic seizure patterns in malformations of cortical development, early life brain injury, and later life brain injury

Structural epilepsy is a chronic neurologic condition that may be caused by in utero malformations of cortical development (MCD) or post-natal brain injuries resulting in encephalomalacia. We hypothesized that the timing of epileptogenic insult would lead to distinct electrographic seizure patterns. Specifically, we predicted that later life insults would lead to longer duration seizures with higher proportion of focal: focal to bilateral tonic-clonic (FBTC) seizures and low rates of bihemispheric onset seizures, as compared to early life insults. We performed a retrospective chart review of 70 adult patients – 33 with epilepsy secondary to brain injury (9 with injury occurring before 16 years and 24 with injury occurring at or after 16 years) with resultant encephalomalacia on MR imaging and 37 with epilepsy secondary to MCD – admitted to the University of Pittsburgh Epilepsy Monitoring Unit for presurgical evaluation. There were no significant differences in duration of epilepsy or number of trialed seizure medications between the groups. We examined scalp EEG data for all patients, as well as intracranial EEG data in a subset. We analyzed seizure duration, seizure frequency, and seizure type (focal, FBTC, and bihemispheric onset) in three cohorts: MCD patients, patients with brain injury occurring in early life (<16 years old), and patients with brain injury occurring in later life (≥16 years old). Patients with later life brain injury had significantly longer and less frequent seizures as compared to MCD cohorts. There were no differences between MCD and early life brain injury cohorts. Seizure duration findings were corroborated in a subset of patients who additionally underwent intracranial EEG monitoring. Additionally, later life brain injury patients had significantly different seizure types as compared to MCD cohorts, with high rates of FBTC and low rates of bihemispheric onset. Again, there was no significant differences in seizure type between early life brain injury and MCD cohorts. These novel findings indicate the relevance of timing of epileptogenic insult on the electrophysiological characteristics of structural epilepsies.

Phenotypic, Electrophysiologic, and Imaging Spectrum of Hirayama Disease from Northern India.

Cervical flexion-induced myelopathy, also known as Hirayama disease (HD), is a lower motor neuron disorder seen mainly in adolescents and young adults, affecting the C7-T1 myotomes, presenting as asymmetric weakness with wasting of one or both the distal upper limbs. We aimed to describe the clinical features, electrophysiology, and radiologic features of HD in a tertiary care institute in northern India. One hundred and forty patients between 2017 and 2022 with clinical and imaging features consistent with HD were retrospectively reviewed from the All India Institute of Medical Sciences-Comprehensive Neuromuscular Diseases center database. Majority were males with the mean age of onset of illness being 17.8 years. The median duration of the symptoms was 3 (1.5-4) years. Sixty-nine (49%) patients had unilateral involvement, and the disease was actively progressing in 88 (63%) patients at presentation. Two families had history of HD in two (1.4%) siblings. Electromyography showed abnormal findings in the clinically involved limb in all the patients and in the clinically uninvolved limb in 17/50 (34%) patients. Flexion magnetic resonance imaging (MRI) demonstrated forward dural displacement in 134 (96%) patients and asymmetric cord flattening in 124 (88.5%) patients. Disability was graded as mild, moderate, and severe; 12 (13%) had severe disability. The majority were managed conservatively, and four underwent surgery for HD. A high index of suspicion of HD needs to be kept in a young male presenting with distal upper limb weakness and atrophy. Dynamic MRI of the cervical spine in young adults presenting with hand wasting is inevitable. This disease needs to be managed aggressively and early to prevent serious dysfunction and loss of productivity.

Palytoxin Evokes Reversible Spreading Depolarization in the Locust CNS.

Spreading depolarization (SD) describes the near-complete depolarization of CNS neural cells as a consequence of chemical, electrical, and metabolic perturbations. It is well-established as the central mechanism underlying insect coma and various mammalian neurological dysfunctions. Despite significant progress in our understanding, the question remains: which cation channel, if any, generates SD in the CNS? Previously, we speculated that the sodium-potassium ATPase (NKA) might function as a large-conductance ion channel to initiate SD in insects, potentially mediated by a palytoxin (PLTX)-like endogenous activator. In the current study, we evaluate the effectiveness and properties of PLTX as an SD initiator in L. migratoria. Whereas bath-applied PLTX failed to ignite SD, direct injection into the neuropil triggered SD in 57% of the preparations. Notably, PLTX-induced SD onset was significantly more rapid compared to ouabain injection and azide controls, though their electrophysiological features remained similar. Furthermore, PLTX-induced SD was recoverable and resulted in a greater frequency of repetitive SD events compared to ouabain. Surprisingly, prior PLTX treatment disrupted the onset and recovery of subsequent SD evoked by other means. PLTX injection could attenuate the amplitude and even completely inhibit the onset of azide-induced SD at higher doses. These results show that PLTX can trigger repetitive and reversible SD-like events in locusts and simultaneously interfere with anoxic SD occurrence. We suggest that the well-documented NKA pump conversion into an open non-selective cationic channel is a plausible mechanism of SD activation in the locust CNS, warranting additional investigations.

Progress of Conductivity and Conduction Velocity Measured in Human and Animal Hearts.

Cardiac conduction velocity (CV) is a critical electrophysiological characteristic of the myocardium, representing the speed at which electrical pulses propagate through cardiac tissue. It can be delineated into longitudinal, transverse, and normal components in the myocardium. The CV and its anisotropy ratio are crucial to both normal electrical conduction and myocardial contraction, as well as pathological conditions where it increases the risk of conduction block and reentry. This comprehensive review synthesizes longitudinal and transverse CV values from clinical and experimental studies of human infarct hearts, including findings from the isthmus and outer loop, alongside data derived from animal models. Additionally, we explore the anisotropic ratio of conductivities assessed through both animal and computational models. The review culminates with a synthesis of scientific evidence that guides the selection of CV and its corresponding conductivity in cardiac modeling, particularly emphasizing its application in patient-specific cardiac arrhythmia modeling.

The spectrum of rippling muscle disease.

Rippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability. It is characterized by rippling wave-like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion-induced rapid muscle contraction (PIRC), and percussion-induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune-mediated (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1/ polymerase I and transcript release factor (CAVIN1/PTRF). CAV3 pathogenic variants are autosomal dominant or less frequently recessive while CAVIN1/PTRF pathogenic variants are autosomal recessive. CAV3-RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin-3 immunoreactivity is often absent or diffusely reduced in CAV3-RMD. CAVIN1/PTRF-RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra-skeletal muscle manifestations. Muscle cavin-1/PTRF immunoreactivity is absent or reduced while caveolin-3 immunoreactivity is reduced, often in a patchy way, in CAVIN1/PTRF-RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker while the mosaic expression of caveolin-3 and cavin-4 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.

The impact of Parkinson’s disease on striatal network connectivity and corticostriatal drive: An in silico study

Abstract Striatum, the input stage of the basal ganglia, is important for sensory-motor integration, initiation and selection of behavior, as well as reward learning. Striatum receives glutamatergic inputs from mainly cortex and thalamus. In rodents, the striatal projection neurons (SPNs), giving rise to the direct and the indirect pathway (dSPNs and iSPNs, respectively), account for 95% of the neurons, and the remaining 5% are GABAergic and cholinergic interneurons. Interneuron axon terminals as well as local dSPN and iSPN axon collaterals form an intricate striatal network. Following chronic dopamine depletion as in Parkinson’s disease (PD), both morphological and electrophysiological striatal neuronal features have been shown to be altered in rodent models. Our goal with this in silico study is twofold: (a) to predict and quantify how the intrastriatal network connectivity structure becomes altered as a consequence of the morphological changes reported at the single-neuron level and (b) to investigate how the effective glutamatergic drive to the SPNs would need to be altered to account for the activity level seen in SPNs during PD. In summary, we predict that the richness of the connectivity motifs in the striatal network is significantly decreased during PD while, at the same time, a substantial enhancement of the effective glutamatergic drive to striatum is present.

Electrophysiological Characteristics Associated With Spontaneous Termination of Ventricular Fibrillation.

Electrophysiological Characteristics Associated With Spontaneous Termination of Ventricular Fibrillation.

Current opinion: optimize radiofrequency ablation through electrophysiological principles, modeling, and clinical recommendations.

This article aims to empower the interventional pain physician to utilize RFA effectively by explaining the technical and electrophysiological features of monopolar, bipolar, and internally cooled RFA. Scientific data are used to provide advice on the effective, well tolerated, and rational application of these techniques. Moreover, physicians need to know how to analyze and generalize ex-vivo and in-vivo models to the clinical setting to optimize clinical outcomes. Recent studies suggest that there are many ways to enhance the technical effectiveness of interventional pain medicine RFA through adjustments in the equipment selection and settings and the local tissue conditions specific to the targeted anatomical area. These modifications could assist in improving clinical and safety outcomes. To optimize both the efficacy and safety of RFA, physicians must understand, conceptualize, interpret, and clinically translate the basic science of RFA. This knowledge is crucial for optimizing equipment selection and settings based on target location to enhance clinical outcomes and limit technical failures.

Sensory Neuronopathies: Clinical Presentation, Management, and Outcome.

Sensory neuronopathies (SNNs) are a rare group of pure sensory disorders causing asymmetrical, multifocal pattern of sensory loss with distinct clinical and electrophysiological features. We aimed to study the clinical features and etiology and share the experience of treating SNN from our center. A prospective observational study was conducted over 3 years. Patients with predominant sensory complaints and electrophysiological evidence of neuropathy were evaluated. Possible/probable SNN was diagnosed using Camdessanch´e criteria. Detailed workup was done to determine the etiology and treatment given accordingly. Follow-up was done and response to treatment was assessed using modified Rankin Scale grading at 12 months. Fourteen patients with SNN were studied. Two (14.3%) patients were diagnosed with Sjogren's syndrome (SS-SNN), two (14.3%) with paraneoplastic syndrome, one (7.1%) with leprous ganglionitis, and nine (64.3%) were idiopathic sensory neuronopathy (I-SNN) cases. Improvement occurred in nine (64.3%), stability in three (21.4%), and worsening in two (14.3%) patients. Out of 11 SS-SNN and I-SNN patients, eight showed improvement on follow-up, seven with injection rituximab (RTX) and one with azathioprine. We found positive correlation between RTX treatment and improvement on follow-up (P = 0.0256). Six (66.66%) out of nine I-SNN patients had early initiation of immunotherapy, of which all improved. There was positive correlation between early treatment initiation time in I-SNN patients and improvement (P = 0.0119). Promising results were noted in SS-SNN and I-SNN patients with intensive treatment approach using RTX. Hit hard and early treatment approach is crucial for achieving improvement in sensory neuronopathies.

Visual interpretation of deep learning model in ECG classification: A comprehensive evaluation of feature attribution methods

Feature attribution methods can visually highlight specific input regions containing influential aspects affecting a deep learning model's prediction. Recently, the use of feature attribution methods in electrocardiogram (ECG) classification has been sharply increasing, as they assist clinicians in understanding the model's decision-making process and assessing the model's reliability. However, a careful study to identify suitable methods for ECG datasets has been lacking, leading researchers to select methods without a thorough understanding of their appropriateness. In this work, we conduct a large-scale assessment by considering eleven popular feature attribution methods across five large ECG datasets using a model based on the ResNet-18 architecture. Our experiments include both automatic evaluations and human evaluations. Annotated datasets were utilized for automatic evaluations and three cardiac experts were involved for human evaluations. We found that Guided Grad-CAM, particularly when its absolute values are utilized, achieves the best performance. When Guided Grad-CAM was utilized as the feature attribution method, cardiac experts confirmed that it can identify diagnostically relevant electrophysiological characteristics, although its effectiveness varied across the 17 different diagnoses that we have investigated.