Search Results (3,424)

Monoclonal gammopathies of clinical significance (MGCSs) are entities in which a small hematological clone produces a monoclonal immunoglobulin capable of causing organ damage. Neurological involvement remains difficult to diagnose and treat, especially in the context of incidental monoclonal gammopathy of undetermined significance (MGUS)–peripheral neuropathy (PN) associations. We conducted a single-center retrospective study at Fundeni Clinical Institute, Bucharest, from January 2015 to December 2025. The reference population included 300 patients with MGUS. The diagnosis of MGNS was established clinically and/or electrophysiologically, with the exclusion of alternative causes of neuropathy. In total, 35 patients with MGNS were identified (prevalence 11.7%). Neuropathy was more common in IgM MGUS (36.7%) compared to IgG (15%), IgA (14.3%), or light chain MGUS (16.7%), with an increased risk for IgM (OR 3.27, p < 0.001). A total of 88.5% of patients received hematological treatment; neurological response was noted in the majority of treated patients. Mortality was 14.3%, and median OS was not reached. Our findings confirm the dissociation between low clonal load and the severity of organ involvement. IgM MGUS is associated with a significantly increased risk of neuropathy, supporting the need for systematic screening for MGUS in patients with PN and for a multidisciplinary approach. Full article

Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article

Neuronal activity and cerebral blood flow are tightly coupled to support the high metabolic demands of the brain. Disruption of neurovascular coupling is a defining feature of many neurodegenerative disorders such as Alzheimer’s disease, stroke, small vessel disease, Parkinson’s disease, and aging. Progress in understanding the mechanisms underlying neurovascular coupling requires experimental approaches that can simultaneously measure neuronal activity and vascular dynamics with high spatial and temporal resolution, while also enabling targeted perturbations of the system. Here, we present a methodological framework that combines chronic electrophysiological recordings with two-photon imaging of cerebral blood flow and optogenetic manipulation of the vasculature in vivo. Using a chronically implanted flexible electrode array, we obtain measurements of the single- and multi-unit spiking activity, as well as local field potentials. Concurrently, two-photon microscopy enables high-resolution measurements of vessel diameter and blood flow within individual vascular segments. In addition, optogenetic control of vascular smooth muscle cells allows for rapid and reversible manipulation of the vessel diameter through the same cranial window while simultaneously recording the neural and vascular activity. We provide detailed protocols for surgical implantation, data acquisition, and analysis, and discuss experimental considerations and limitations. This combined platform offers a powerful tool for mechanistic studies of neurovascular coupling and its dysfunction in disease models. Full article

Background: H1-antihistamines are widely used for allergic and upper respiratory conditions; however, several agents included in this class have been associated with cardiac electrophysiological adverse effects, including QT interval prolongation and torsades de pointes (TdP). These effects are largely exposure-dependent and mechanistically linked to inhibition of cardiac ion channels. Chlorpheniramine maleate (CPM), a first-generation H1-antihistamine, has been implicated in arrhythmic events primarily under conditions of increased systemic exposure, prompting interest in whether alternative routes of administration may lower cardiac risk. Methods: This narrative review integrates mechanistic, preclinical, clinical, pharmacokinetic, and regulatory evidence. Information was extracted from PubMed, Google Scholar, and Scielo using search terms such as cardiotoxicity, chlorpheniramine, QT prolongation, intranasal administration, and cardiac arrhythmias, with no language restriction. Results: Comparative pharmacokinetic evidence shows that, on a dose-normalized basis, intranasal and oral chlorpheniramine exhibit comparable bioavailability; however, in a clinical context, intranasal doses (1.12–2.24 mg) are lower than oral daily doses (4–12 mg/day), resulting in a lower systemic exposure (Cmax and AUC) with intranasal administration. Available pharmacovigilance or epidemiological data have not specifically evaluated intranasal chlorpheniramine, and the number of dedicated safety trials remains limited. Conclusions: Preclinical, in vitro, mechanistic studies suggest that intranasal administration of chlorpheniramine should confer superior cardiac safety compared to the oral route. However, clinical data from human studies directly comparing the cardiac safety of intranasal chlorpheniramine versus systemic chlorpheniramine is extremely limited. More data from clinical trials, case–control studies, and regulatory databases are needed to validate these theoretical claims. Full article

Background and Objectives: Idiopathic ventricular arrhythmias commonly occur in patients without structural heart disease and most often present as premature ventricular contractions (PVCs). Although generally considered benign, a high PVC burden may cause symptoms, reduce quality of life, and lead to reversible PVC-induced cardiomyopathy. This study aimed to evaluate long-term outcomes after radiofrequency catheter ablation of idiopathic outflow tract PVCs. Materials and Methods: This single-center retrospective study included 101 patients with idiopathic PVCs who underwent radiofrequency catheter ablation. PVC burden and clinical outcomes were assessed at baseline and during follow-up at 3 months, 12 months, and 5 years. Procedural success, predictors of success, and changes in antiarrhythmic drug therapy were analyzed. Results: During follow-up, a marked reduction in PVC burden was observed compared with baseline values. The median PVC burden decreased from 21.89% at baseline to 0.79% at 3 months, 0.23% at 12 months, and 0.09% at the 5-year follow-up after ablation. Acute procedural success was achieved in 88.1% of patients. Long-term success at 5 years was observed in 80.2% of patients. The use of antiarrhythmic drugs decreased during follow-up. Left ventricular ejection fraction remained stable, with no significant difference between baseline and 5-year values. Monomorphic PVC morphology and procedural success at 12 months were identified as independent predictors of long-term success. Conclusions: Radiofrequency catheter ablation provides effective and sustained reduction in PVC burden in patients with idiopathic outflow tract PVCs, with high acute success rates, durable long-term outcomes, and reduced reliance on antiarrhythmic drug therapy. Full article

Background/Objectives: Schizophrenia is one of the most extensively studied yet conceptually unstable disorders in the history of medicine and brain sciences. Since its formalization at the turn of the twentieth century, the disorder has been repeatedly redefined, reflecting changes in clinical observation, diagnostic philosophy, and neuroscientific models of brain function. The objective of this review is to critically examine the historical evolution of schizophrenia as a medical construct and to analyze how shifts in diagnostic systems have shaped the search for biological and molecular biomarkers. Methods: A narrative-historical review of the literature was conducted, integrating classical psychiatric texts, diagnostic manuals, and contemporary neuroscientific studies. Key milestones in the conceptualization of schizophrenia were analyzed alongside the development of biological hypotheses, including neurochemical, electrophysiological, neuroimaging, genetic, immunological, omics-based, and digital approaches. Emphasis was placed on identifying conceptual continuities, ruptures, and methodological limitations across historical periods. Results: The analysis reveals that the evolution of schizophrenia has been characterized by increasing diagnostic standardization accompanied by growing biological heterogeneity. While successive biological models have provided valuable insights into specific aspects of the disorder, none have yielded single, robust diagnostic biomarkers. Instead, findings consistently reflect partial overlaps between clinical phenotypes and biological signals, strongly influenced by historically derived diagnostic categories. Conclusions: The persistent absence of definitive diagnostic biomarkers for schizophrenia reflects not only technical limitations but also the historical construction of the disorder as a heterogeneous clinical category. Understanding this historical context is essential for interpreting current findings in brain sciences. Future research is likely to benefit from stratification-based, dimensional, and integrative frameworks that move beyond categorical diagnosis while preserving clinical relevance. Full article

Lipidomics has emerged as a transformative discipline in biomedical research, providing high-resolution insights into metabolic signaling and disease pathophysiology. The R programming language provides a widely adopted framework for extensible analysis of complex lipidomic datasets due to its robust biostatistical infrastructure. Herein, we present a comprehensive roadmap for lipidomics in R, structured around a standardized analytical lifecycle: from raw data acquisition and preprocessing to structural annotation, statistical modeling and functional interpretation. We critically contextualize and integrate a curated suite of widely adopted R packages (version 4.3.0), including xcms and MSnbase for feature extraction, LipidMS 3.0 for fragmentation-based identification, and lipidr for quality control and normalization. Furthermore, we demonstrate how advanced tools such as mixOmics and clusterProfiler can be integrated to bridge the gap between differential lipid abundance and systems-level biological insights. Particular emphasis is placed on reproducibility, nomenclature standardization and the emerging role of machine learning in biomarker discovery. By synthesizing these resources into a coherent pipeline, this guide provides a structured reference for researchers. Further discussion addresses methodological pitfalls, statistical assumptions and reproducibility constraints that frequently compromise lipidomics studies. Ultimately, this structured approach facilitates systematic tool selection, accelerating the translation of complex lipidomic signatures into reproducible and clinically meaningful discoveries. Full article

Background: Crocodilians rarely develop cancer despite long lifespans and continuous exposure to environmental carcinogens, suggesting robust natural anti-tumor defense mechanisms. Methods: We investigated the anti-cancer activity of sera derived from the phylogenetically related species—alligators, crocodiles, and chickens, and studied their underlying immune mechanisms. The anti-tumor activity of alligator serum was tested in murine models of melanoma and lymphoma. Results: Alligator serum (AS) and its (NH₄)₂SO₄-precipitated fraction (ASa) showed rapid and potent cytotoxicity toward multiple murine and human cancer cell lines while sparing non-malignant human cells. Importantly, ASa attenuated melanoma and lymphoma tumor growth in mice. Electrophysiological analyses in PN71 cancer cells treated with ASa revealed rapid membrane depolarization and formation of high-conductance pores consistent with Complement-mediated membrane attack complex (MAC) activity. Proteomic analyses identified the Complement component C5 as a major protein enriched in active fractions, implicating the Complement system in cancer cell killing. Based on phylogenetic similarity of C5, crocodile and chicken sera exhibit alligator-like comparable anti-cancer activity. Mechanistic studies in chicken serum showed that the anti-cancer activity depends on Ca²⁺ and Mg²⁺ ions, terminal Complement components (C5–C8), and IgM antibodies that initiate Complement activation. Immunodepletion of IgM from CSa significantly reduced cytotoxicity, whereas purified chicken IgM activated human Complement to induce cancer cell death. Conclusions: These findings identify a conserved IgM–Complement immune mechanism capable of selectively targeting malignant cells. The evolutionary conservation and cross-species functionality of this pathway highlight its potential as a bio-inspired strategy for developing novel Complement-based cancer immunotherapies. Full article

Background/Objectives: Goal-directed praxis actions (GOPAs) integrate perception, motor planning, and executive control. While neural correlates of single actions are known, less is understood about how complexity conditions and their hierarchical organization into elementary tasks shape neural dynamics during ecologically manual assembly tasks. This study tested how electrophysiological (EEG) activity reflects global complexity and selective engagement of executive and sensorimotor systems across GOPAs. Methods: 38 healthy young adults completed two assembly conditions differing in complexity (basic and advanced) decomposed into four elementary tasks: identification, handling, alignment, and joining. EEG was recorded across five frequency bands (delta, theta, alpha, beta, and gamma) and four regions of interest (ROI): frontal, fronto-central, temporo-central, and parieto-occipital. Results: Neural activity varied significantly depending on different complexity, elementary task, and ROI. The advanced-complexity condition elicited stronger neural responses compared to the basic-complexity condition, reflecting greater cognitive, and sensorimotor demands. A task-related gradient emerged, with joining showing the highest activity, followed by alignment, while identification and handling showed lower activation. Frontal regions, particularly in theta activity, were more involved under higher complexity, suggesting increased executive control. In contrast, beta and gamma activity predominated in temporo-central and parieto-occipital regions, supporting visuomotor and sensorimotor integration. Conclusions: EEG oscillatory dynamics during ecological GOPAs are selectively modulated by complexity condition and hierarchical task organization. Neural activity tracks functional demands of specific action phases rather than general arousal, highlighting dynamic coordination between executive and sensorimotor systems during complex manual behavior. Full article

Galeruca daurica (Joannis) (Coleoptera: Chrysomelidae) is an oligophagous pest in which both adults and larvae prefer to feed on Allium forage grasses of the Liliaceae family. In this study, we identified gustatory receptor (GR) genes based on the transcriptome data of G. daurica; analyzed the expression profiles of these GR genes across different larval instars and various tissues of male and female adults using quantitative real-time PCR (qRT-PCR); detected the electrophysiological responses of the mouthparts of male and female G. daurica adults to flavonoids and carbohydrates using single sensillum recording (SSR); and recorded the changes in food consumption of G. daurica adults after feeding on six host plant-derived metabolites. A total of 26 GR genes were identified from the transcriptome data of adult and larval of G. daurica. Phylogenetic analysis was performed to screen candidate functional gustatory receptor genes, including four sugar receptors (GdauGR7, GdauGR10, GdauGR14 and GdauGR28), seven bitter receptors (GdauGR11, GdauGR16~17, GdauGR22, GdauGR25~26 and GdauGR30), and two CO₂ receptors (GdauGR15 and GdauGR20). Larval expression profiling of GdauGRs in G. daurica revealed that the relative expression levels of 17 genes exhibited dynamic changes during larval growth and development. GdauGRs were expressed to varying degrees in the antennae, mouthparts, brain, gut, and forelegs of adult G. daurica, with sex-specific differences. Notably, the expression levels of GdauGR4, GdauGR9 and GdauGR16 in the gut were extremely significantly higher than those in other tissues. In the SSR test, the six tested flavonoids and one carbohydrate were able to induce robust electrophysiological responses in the gustatory sensilla on the antennae and mouthparts of adult G. daurica at specific concentrations. In addition, the supplementation of several host-derived metabolites altered the food consumption of adult G. daurica. These findings lay a solid foundation for elucidating the molecular mechanisms underlying gustatory recognition and host adaptation in G. daurica. Full article

The global spread of COVID-19 led to the rapid authorization of remdesivir as the first antiviral therapy. However, accumulating clinical evidence has linked its use to cardiac adverse effects. Understanding the mechanisms underlying remdesivir-induced cardiotoxicity is critical for optimizing its clinical use and ensuring patient safety. This study investigates the electrophysiological and molecular features underlying remdesivir-induced cardiac toxicity in male and female guinea pigs, aiming to elucidate the sex-dependent differences in cardiac dysfunction and the role of mitochondria in mediating these effects. A cardiac injury model was established via intraperitoneal administration of remdesivir. In vivo telemetry and ex vivo electrocardiography were used for continuous monitoring of cardiac electrical activity, while optical mapping enabled the assessment of action potential parameters and conduction properties. The histopathological alterations and mitochondrial ultrastructure were examined by hematoxylin–eosin staining and transmission electron microscopy. ELISA and Western blot analyses were performed to explore the inflammatory signaling, apoptosis, and mitochondrial dynamics. Remdesivir induced distinct sex-specific patterns of cardiac toxicity. Compared with female guinea pigs, male guinea pigs had significantly more severe myocardial injury, which was characterized by extensive inflammatory cell infiltration, marked mitochondrial disruption, and a higher incidence of sustained ventricular tachyarrhythmia. Overall, remdesivir was associated with sex-dependent cardiac toxicity, accompanied by mitochondrial impairment and inflammatory activation. Male guinea pigs were more susceptible to electrophysiological instability and mitochondrial dysfunction. These findings highlight the importance of carefully evaluating remdesivir’s cardiac effects and support the need for individualized, sex-specific considerations in its clinical administration. Full article

Increasing recognition of the clinical impact of isolated tricuspid regurgitation has led to rapid expansion of surgical and transcatheter tricuspid valve interventions. Given the close anatomic relationship between the tricuspid valve and the atrioventricular conduction system, both surgical and transcatheter approaches carry a significant risk of new conduction disturbances and permanent pacemaker implantation. A three-dimensional understanding of the atrioventricular conduction axis is essential to anticipate and mitigate these complications. This review provides a comprehensive overview of conduction system anatomy and physiology in the context of tricuspid valve interventions, highlighting the mechanisms underlying procedure-related conduction abnormalities. We also discuss contemporary management strategies, including approaches to pre-existing transvalvular leads, valve-sparing pacing alternatives, and the evolving role of electrophysiologists within the multidisciplinary heart team. Full article

Anxiety, a common mental disorder, is epidemiologically linked to high dietary sugar intake. However, the underlying neural mechanisms remain poorly understood. Here, using male C57BL/6 mice (n ≥ 10 per group), we show that two-week consumption of sugar-sweetened drinks reliably induced anxiety-like behavior, characterized by reduced center time in the open field test and less open arm exploration in the elevated plus maze. Notably, consumption of sucrose, glucose, or the non-metabolizable glucose analog methyl-α-D-glucopyranoside induced anxiety-like behavior, whereas intake of the artificial sweetener acesulfame potassium (Ace-K) did not. Moreover, after two weeks of exposure to sucrose or glucose but not to Ace-K, c-Fos expression was elevated in glutamatergic neurons of the nucleus of the solitary tract (NTS). Mechanistically, high glucose activated intrinsic excitability and the amplitude of spontaneous excitatory postsynaptic currents in NTS glutamatergic neurons; congruently, selective activation of NTS glutamatergic neurons mimicked anxiety-like behavior in mice, while chemogenetic silencing of these neurons abolished glucose-induced anxiety. Together, our findings demonstrate that NTS glutamatergic neurons activation mediates sugar-induced anxiety. These results suggest that this anxiogenic effect is driven by glucose-related signaling rather than artificial sweet taste perception alone, shedding light on a novel clinical therapy against anxiety. Full article

In this paper, we present a multi-parallel restricted additive Schwarz (MP-RAS) preconditioner construction method for cardiac electrophysiology simulation. This method is designed to address the need for solving large-scale linear systems in realistic cardiac electrophysiology simulations and can provide a more efficient computational tool for patient-specific electrical propagation modeling, arrhythmia studies, and the evaluation of ablation strategies. The proposed preconditioner is suitable for the finite element simulation of the anisotropic cardiac monodomain model. In particular, we construct the subdomains based on Morton code sorting, build submatrices by indices and decompose the formula for parallel computing. Given that the computing of each subdomain is relatively independent, the iteration can be extended to N-parallel. Numerical experiments indicate that for matrices of the same size and under the same number of partitions, Morton code sorting is at least 105 times faster than METIS, while the memory usages are reduced by 12∼32%. The iteration number is reduced by approximately two times compared with the Jacobi and block Jacobi preconditioned conjugate gradient (PCG) method. Comparative experiments with other solvers further demonstrate that the MP-RAS solver is highly efficient for solving this parabolic partial differential equation and have strong parallel scalability. Full article

Exogenous application of plant hormones has been considered a short-term and effective strategy to alleviate deleterious effects of water stress on plants. However, whether exogenous gibberellic acid (GA₃) directly enhances nitrogen accumulation and thereby alleviates drought stress in soybean (Glycine max (Linn.) Merr.) remains to be investigated. This study set three water treatments (75% CK, 50% MD, 25% SD), with half of the plants at each level sprayed with 10⁻⁶ mol·L⁻¹ GA₃, measuring growth, photosynthesis, nitrogen content, water status, and electrophysiological parameters and calculating cellular metabolic electronic energy (ΔG_B) based on Nernst equation. The results showed that drought reduced soybean nitrogen accumulation, photosynthesis, growth and yield. GA₃ increased soybean nitrogen accumulation, improving photosynthesis and yield under CK, which enhanced the consumption of intracellular stored energy and reduced ΔG_B. Under MD, GA₃ improved leaf water status, promoted soybean nitrogen accumulation and photosynthesis and reduced ΔG_B by allocating more energy to drought resistance; it could therefore mitigate the moderate drought stress on plants. ΔG_B negatively correlated with total nitrogen content and yield, indicating that ΔG_B was a potential indicator associated with nitrogen accumulation, which can guide the optimization of GA₃ spraying strategies. Further studies on GA₃ application details are necessary to improve the soybean yields under drought conditions. Full article