Search Results (720)

Background: Persistent neuromuscular deficits following anterior cruciate ligament reconstruction (ACLR) are frequently attributed to arthrogenic muscle inhibition (AMI). The type of autologous graft used may influence the trajectory of neuromuscular recovery. Objective: To investigate the influence of graft type—bone–patellar tendon–bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT)—on the contractile properties of periarticular knee muscles over a 9-month post-operative period. Hypothesis: Each graft type would result in distinct recovery patterns of muscle contractility, as measured by tensiomyography (TMG). Methods: Thirty-one patients undergoing ACLR with BPTB (n = 8), HT (n = 12), or QT (n = 11) autografts were evaluated at 3, 6, and 9 months post-operatively. TMG was used to measure contraction time (Tc) and maximal displacement (Dm) in the rectus femoris, vastus medialis, vastus lateralis, and biceps femoris. Results: Significant within-group improvements in Tc and Dm were observed across all graft types from 3 to 9 months (Tc: p < 0.001 to p = 0.02; Dm: p < 0.001 to p = 0.01). The QT group showed the most pronounced Tc reduction in RF (from 30.16 ± 2.4 ms to 15.44 ± 1.6 ms, p < 0.001) and VM (from 31.05 ± 2.6 ms to 18.65 ± 1.8 ms, p = 0.004). In contrast, HT grafts demonstrated limited Tc recovery in BF between 6 and 9 months compared to BPTB and QT (p < 0.001), indicating a stagnation phase. BPTB exhibited persistent bilateral deficits in both quadriceps and BF at 9 months. Conclusions: Autograft type significantly influences neuromuscular recovery patterns after ACLR. TMG enables objective, muscle-specific monitoring of contractile dynamics and may support future individualized rehabilitation strategies. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

The electrical ventricular storm (VES) is defined as multiple sustained ventricular arrhythmias arising in a short time, often refractory to standard antiarrhythmic treatment. The three pillars of the physiopathogenesis of the VES are autonomic dysfunction, triggers, and an altered ventricular substrate. Incessant or highly recurrent ventricular arrhythmia impacts the hemodynamic status by worsening heart failure and increasing mortality. A stepwise, team-based, and tailored therapeutic approach is required to stop ventricular arrhythmia and regain the hemodynamic and electric stability of the patient. The authors focused on describing all currently available therapeutic approaches for VES, intending to establish the best VES therapeutic approaches. This process involves considering the patient’s specific condition, responses to previous treatments, and the potential risks and benefits of each approach. The options range from adjusting antiarrhythmic therapy to reprogramming of the ICD, sedation, epidural anaesthesia, stellate ganglia anaesthetic block, and the use of ECMO or left ventricular assist devices and radiofrequency catheter ablation. Particular attention is paid to the detailed management of genetic primary arrhythmia syndromes like long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and Wolff–Parkinson–White syndrome, early repolarisation syndrome, right ventricular arrhythmogenic dysplasia, and idiopathic ventricular fibrillation. After overcoming the acute events of VES and obtaining hemodynamic stability, the treatment should shift toward an optimal balance of heart failure therapy, controlling the substrate by revascularisation procedures and resolving other pathology-generating ventricular arrhythmias. This article provides a comprehensive overview of ESV’s current management options using the most efficient strategies known to date. Full article

New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II clinical trials, events of QT prolongation or proarrhythmia were not observed. Here, we utilized cardiac NAMs to evaluate the functional consequences of vanoxerine treatment on human cardiac excitation–contraction coupling. The cardiac MPS used in this study was a microfabricated fluidic culture platform with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) capable of evaluating voltage, intracellular calcium handling, and contractility. Likewise, the hiPSC-CM comprehensive in vitro proarrhythmia assay (CiPA) was employed based on multielectrode array (MEA). Vanoxerine treatment delayed repolarization in a concentration-dependent manner and induced proarrhythmic events in both NAM platforms. The complex cardiac MPS displayed a frequency-dependent vanoxerine response such that EADs were eliminated at a faster pacing rate (1.5 Hz). Moreover, exposure analysis revealed a 99% vanoxerine loss in the cardiac MPS. TdP risk analysis demonstrated high to intermediate TdP risk at clinically relevant concentrations of vanoxerine and frequency-independent EAD events in the hiPSC-CM CiPA model. These findings demonstrate that nonclinical cardiac NAMs can recapitulate clinical outcomes, including detection of vanoxerine-induced delayed repolarization and proarrhythmic effects. Moreover, this work provides a foundation to evaluate the safety and efficacy of novel compounds to reduce the dependence on animal studies. Full article

Background: The cardiovascular effects of SARS-CoV-2, including autonomic dysregulation, are becoming increasingly recognized, even following mild infections. However, long-term electrocardiographic (ECG) changes remain poorly characterized. Methods: We conducted a prospective study of 151 unvaccinated healthcare workers with RT-PCR-confirmed mild to moderate SARS-CoV-2 infection. Standard 12-lead ECGs were recorded before infection (T0) and at 6–12 months (T1) and >12 months (T2) after infection. Key parameters included heart rate (HR), PR interval, QRS duration, and corrected QT interval (QTc). Results: Heart rate (HR) increased transiently at T1 (p < 0.05) and normalized by T2. Mild but persistent PR interval shortening was observed at both follow-ups (p < 0.01). There were no significant changes in QRS or QTc intervals. No arrhythmias or conduction blocks occurred. ECG alterations were not associated with sex or age, except for greater PR shortening in males. Conclusions: Mild SARS-CoV-2 infection can result in transient sinus tachycardia and subtle PR shortening, which is likely to be a post-viral autonomic effect. Long-term ECG surveillance appears unnecessary in asymptomatic cases. Full article

A facile method was adopted to fabricate β-C₃N₄, and it was then doped with manganese and tellurium to obtain novel 10%MnTeO₃@β-C₃N₄ (10%MnTe@β) and 20%MnTeO₃@β-C₃N₄ (20%MnTe@β) nanohybrids. The β-C₃N₄, 10%MnTe@β, and 20%MnTe@β showed surface areas of 85.86, 97.40, and 109.54 m² g⁻¹, respectively. Using ciprofloxacin (CIP) as a pollutant example, 10%MnTe@β and 20%MnTe@β attained equilibrium at 60 and 45 min with q_t values of 48.88 and 77.41 mg g⁻¹, respectively, and both performed better at pH = 6.0. The kinetic studies revealed a better agreement with the pseudo-second-order model for CIP sorption on 10%MnTe@β and 20%MnTe@β, indicating that the sorption was controlled by a liquid film mechanism, which suggests a high affinity of CIP toward 10%MnTe@β and 20%MnTe@β. The sorption equilibria outputs indicated better alignment with the Freundlich and Langmuir models for CIP removal by 10%MnTe@β and 20%MnTe@β, respectively. The thermodynamic analysis revealed that CIP removal by 10%MnTe@β and 20%MnTe@β was exothermic, which turned more spontaneous as the temperature decreased. Applying 20%MnTe@β as the best sorbent to groundwater and seawater spiked with CIP resulted in average efficiencies of 94.8% and 91.08%, respectively. The 20%MnTe@β regeneration–reusability average efficiency was 95.14% within four cycles, which might nominate 20%MnTe@β as an efficient and economically viable sorbent for remediating CIP-contaminated water. Full article

To realize accurate ladle pouring, an analytical model of the constant flow rate pouring was established. By integrating a user-defined function (UDF), a CFD simulation model of the constant flow rate pouring was established to investigate the liquid steel pouring behavior under different inner wall inclination angle α, initial liquid volume V_c, and target flow rate q. Finally, the accuracy of the analytical model and the simulation model was verified through experiments. The results show that the experimental results agree well with the theoretical and simulation results, which verify the accuracy of the analytical model and the simulation model. Moreover, the simulation results indicate that increasing both α and V_c leads to an increase in the pouring flow rate. To achieve a stable pouring process and a constant flow rate value, a proper α, V_c and q_t should be selected. In this study α = 7.5° V_c = 70% V_capacity and q in the range of 0.10–0.12 m³/s are proper. To realize constant flow rate pouring, a time-variant ladle angular velocity is obtained and it can be adjusted by the motor speed. Therefore, different constant flow rates could be acquired by adjusting the motor speed, which provide guidance to the casting technology. Full article

This paper presents a technique for extracting the initial parameters of the longitudinal phase space of freshly injected bunches in an electron storage ring. This technique combines simulation of single-bunch longitudinal phase space evolution with a bunch-by-bunch data acquisition and processing system, enabling high-precision determination of initial phase space parameters during electron storage ring injection—including the initial phase, initial bunch length, initial energy offset, initial energy spread, and initial energy chirp. In our experiments, a high-speed oscilloscope captured beam injection signals, which were then processed by the bunch-by-bunch data acquisition system to extract the evolution of the injected bunch’s phase and length. Additionally, a single-bunch simulation software package was developed, based on mbtrack2 and PyQt5, that is capable of simulating the phase space evolution of bunches under different initial parameters after injection. By employing a genetic algorithm to iteratively align simulation results with experimental data, the remaining initial phase space parameters of the injected bunch can be accurately determined. Full article

Background: Pulmonary embolism (PE) increases right ventricular (RV) afterload, potentially leading to myocardial stress and electrocardiographic abnormalities. Although QTc prolongation has been suggested as a marker of RV dysfunction, its prevalence, clinical significance, and prognostic value in acute PE remain poorly defined. Objective: The objective of this study is to evaluate the prevalence and clinical implications of QTc prolongation in patients with intermediate–high and high-risk acute PE. Methods: We retrospectively analyzed 95 consecutive patients admitted with intermediate–high or high-risk PE between September 2021 and December 2023. QTc prolongation was defined as ≥470 ms in males and ≥480 ms in females. Clinical, imaging, and laboratory data were compared between patients with normal and prolonged QTc intervals. QTc was assessed at admission, after treatment, and prior to discharge. Results: QTc prolongation was observed in 28.4% of patients at presentation. This group had significantly higher lactate levels (2.3 vs. 1.8 mmol/L, p = 0.03) and a non-significant trend toward elevated troponin and lower oxygen saturation. No differences were observed in echocardiographic or CT-based RV dysfunction parameters. QTc values normalized by discharge irrespective of treatment modality. There was no association between QTc prolongation and in-hospital or long-term mortality. A trend toward more aspiration thrombectomy was noted in the prolonged QTc group (29.6% vs. 11.8%, p = 0.06). Conclusions: QTc prolongation is common in acute intermediate–high and high-risk PE and may reflect transient myocardial stress. While not predictive of clinical outcomes, it should be considered in the differential diagnosis of QTc prolongation in patients presenting with dyspnea and chest pain. Full article

Background/Objectives: ST-segment deviation (STD) on electrocardiography (ECG) may reflect myocardial injury in critically ill patients. However, its prognostic significance in non-cardiac intensive care unit (ICU) populations remains unclear. We aimed to assess the association between STD on ICU admission and 30-day mortality and to evaluate its incremental prognostic value beyond the SOFA score. Methods: In this retrospective single-center study, we included 307 consecutive ICU patients (median age: 64.0 years; 65.5% men). Patients with acute cardiac conditions were excluded. STD was defined as ≥1 mm ST elevation or depression in any lead on standard 12-lead ECG performed on admission. The primary outcome was 30-day all-cause mortality. Prognostic associations were assessed using multivariable Cox regression adjusted for SOFA score. Discriminative performance was evaluated by comparing ROC curves for models with and without STD, with bootstrap-based testing (1000 iterations) to assess significance. Results: STD was present in 126 patients (41.0%) and occurred more frequently in non-survivors (47.6% vs. 36.5%, p = 0.033. In Cox regression, STD was independently associated with 30-day mortality (HR = 1.534; 95% CI: 1.081–2.177; p = 0.017), even after adjustment for SOFA score. This association remained statistically robust in bootstrap validation. The addition of STD amplitude to the SOFA score modestly improved model discrimination with a borderline significant difference between the areas under the curve (ΔAUC = 0.005, p = 0.0581). Conclusions: ST-segment deviation on the admission ECG is an independent predictor of 30-day mortality in non-cardiac critically ill patients and may enhance risk stratification beyond the SOFA score. Full article

Objectives: With the growing importance of mobile technology and artificial intelligence (AI) in healthcare, the development of automated cardiac diagnostic systems has gained strategic significance. This review aims to summarize the current state of knowledge on the use of AI in the analysis of electrocardiographic (ECG) signals obtained from wearable devices, particularly smartwatches, and to outline perspectives for future clinical applications. Methods: A narrative literature review was conducted using PubMed, Web of Science, and Scopus databases. The search focused on combinations of keywords related to AI, ECG, and wearable technologies. After screening and applying inclusion criteria, 152 publications were selected for final analysis. Conclusions: Modern AI algorithms—especially deep neural networks—show promise in detecting arrhythmias, heart failure, prolonged QT syndrome, and other cardiovascular conditions. Smartwatches without ECG sensors, using photoplethysmography (PPG) and machine learning, show potential as supportive tools for preliminary atrial fibrillation (AF) screening at the population level, although further validation in diverse real-world settings is needed. This article explores innovation trends such as genetic data integration, digital twins, federated learning, and local signal processing. Regulatory, technical, and ethical challenges are also discussed, along with the issue of limited clinical evidence. Artificial intelligence enables a significant enhancement of personalized, mobile, and preventive cardiology. Its integration into smartwatch ECG analysis opens a path toward early detection of cardiac disorders and the implementation of population-scale screening approaches. Full article

Voltage-gated potassium channels Kv7.1, encoded by the gene KCNQ1, play critical roles in various physiological processes. In cardiomyocytes, the complex Kv7.1-KCNE1 mediates the slow component of the delayed rectifier potassium current that is essential for the action potential repolarization. Over 1000 KCNQ1 missense variants, many of which are associated with long QT syndrome, are reported in ClinVar and other databases. However, over 600 variants are of uncertain clinical significance (VUS), have conflicting interpretations of pathogenicity, or lack germline information. Computational prediction of the damaging potential of such variants is important for the diagnostics and treatment of cardiac disease. Here, we collected 1750 benign and pathogenic missense variants of Kv channels from databases ClinVar, Humsavar, and Ensembl Variation and tested 26 bioinformatics tools in their ability to identify known pathogenic or likely pathogenic (P/LP) variants. The best-performing tool, AlphaMissense, predicted the pathogenicity of 195 VUSs in Kv7.1. Among these, 79 variants of 66 wildtype residues (WTRs) are also reported as P/LP variants in sequentially matching positions of at least one hKv7.1 paralogue. In available cryoEM structures of Kv7.1 with activated and deactivated voltage-sensing domains, 52 WTRs form intersegmental contacts with WTRs of ClinVar-listed variants, including 21 WTRs with P/LP variants. ClinPred and paralogue annotation methods consistently predicted that 21 WTRs of KCNE1 have 34 VUSs with damaging potential. Among these, 8 WTRs are contacting 23 Kv7.1 WTRs with 13 ClinVar-listed variants in the AlphaFold3 model. Analysis of intersegmental contacts in CryoEM and AlphaFold3 structures suggests atomic mechanisms of dysfunction for some VUSs. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

Bedaquiline is known to shorten the duration of therapy of tuberculosis but has limitations, e.g., poor solubility and adverse effects such as prolongation of the QT interval. In this study, bedaquiline was incorporated into an inherently targeted nanosystem for improved permeation of the drug, with ex vivo diffusion studies performed to investigate its penetration. The bedaquiline-loaded mannan–chitosan oligosaccharide lactate nanoparticles were prepared by a one-step ionic gelation probe sonication method. A PermeGear 7-in-line flow-through diffusion system was used for the ex vivo diffusion studies across porcine and human pericardia. Bedaquiline-loaded nanoparticles with a particle size and potential of 192.4 nm and 40.5 mV, respectively, were obtained. The drug-loaded mannan–chitosan nanoparticles had an encapsulation efficacy of 98.7% and drug loading of 0.6%. Diffusion data indicated a steady-state flux of 2.889 and 2.346 µg.cm⁻².min⁻¹ for porcine and human pericardia, respectively. The apparent permeability coefficients were calculated to be 2.66 × 10⁻⁴ cm.min⁻¹ and 2.16 × 10⁻⁴ cm.min⁻¹ for porcine and human pericardia, respectively. The lag phases were 52.72 min and 0 min for porcine and human pericardia, respectively. The drug permeation indicated a consistent and linear diffusion pattern across both porcine and human pericardia, additionally approving the porcine pericardium as a great comparable tissue to human tissue for pericardial studies. This study is the first to demonstrate ex vivo diffusion of bedaquiline-loaded, macrophage-targeted chitosan–mannan nanoparticles across both human and porcine pericardia, representing a novel platform for disease-targeted, localized treatment of TB pericarditis. Full article

Background/Objectives: Long QT Syndrome type 2 (LQT2) is a cardiac channelopathy linked to pathogenic variants in the KCNH2 gene, which encodes the Kv11.1 potassium channel, essential for cardiac repolarization. Variants affecting splice sites disrupt potassium ion flow, prolong QT interval, and increase the risk of arrhythmias and sudden cardiac death (SCD). Understanding genotype–phenotype correlations is key, given the variability of clinical manifestations even within families sharing the same variant. We aimed to evaluate new pathogenic variants by analyzing genotype–phenotype correlations in informative families. Methods: Genetic and clinical assessments were performed on index cases and family members carrying KCNH2 pathogenic variants, referred for genetic testing between 2010 and June 2023. The next-generation sequencing (NGS) of 210 cardiovascular-related genes was conducted. Clinical data, including demographic details, family history, arrhythmic events, electrocardiographic parameters, and treatments, were collected. Results: Among 390 patients (152 probands) tested for LQTS, only 2 KCNH2 variants had over 5 carriers. The detailed clinical information of 22 carriers of this KCNH2 p.Ser261fs. has already been reported by our research group. Moreover, we identified 12 carriers of the KCNH2 c.77-2del variant, predicted to disrupt a splice site and not previously reported. Segregation analysis showed its high penetrance, supporting its classification as pathogenic. Conclusions: The newly identified KCNH2 c.77-2del variant is a pathogenic, as strongly supported by the segregation analysis. Our findings underscore the importance of further research into splice site variants to enhance clinical management and genetic counseling for affected families. Full article