Search Results (1,147)

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K⁺) and calcium (Ca²⁺) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K⁺ currents and voltage-dependent Ca²⁺ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K⁺ current profiles: SK4+/EAG−/Kir−, SK4−/EAG+/Kir−, and SK4−/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from −20 mV to −70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca²⁺ conductance observed. Their activation threshold (~−30 mV) and half-activation voltage (V/2 ≈ −12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1). Full article

Mucins are highly glycosylated proteins that form the structural basis of mucus and represent a key component of innate immunity at mucosal surfaces, particularly in the respiratory tract. Beyond their mechanical barrier function, mucins actively participate in pathogen trapping, regulation of mucociliary clearance, modulation of inflammatory responses, and maintenance of epithelial homeostasis. Dysregulation of mucin synthesis, composition, or transport contributes to mucus hypersecretion, impaired airway clearance, and chronic inflammation in respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. This review summarizes current insights into mucin biology, including their biosynthesis, structure, classification, and regulation, with emphasis on the gel-forming mucins MUC5AC and MUC5B. The role of mucins in mechanical protection, host–pathogen interactions, control of inflammation, and coordination of innate immune responses is reviewed. Attention is given to the interplay between mucins, immune cells, and microbial communities in maintaining airway barrier integrity. The article further examines mucoactive therapeutic strategies aimed at restoring mucus barrier function. Expectorants, mucolytics, mucoregulators, and mucokinetic agents are reviewed with respect to their mechanisms of action and clinical relevance. Established drugs, including N-acetylcysteine, carbocysteine, dornase alfa, ambroxol, and hypertonic solutions, are considered alongside emerging molecular targets such as NF-κB-dependent regulation of mucin expression, calcium-activated chloride channels, MARCKS-mediated mucin exocytosis, purinergic signaling pathways, and NO/cGMP signaling. Non-pharmacological approaches, including airway clearance techniques and respiratory rehabilitation, are covered concisely. Conclusions: Overall, this review highlights mucins as dynamic regulators of innate immunity and underscores the need for mechanism-based, personalized mucoactive therapies to improve outcomes in chronic inflammatory airway diseases. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with drug resistance representing the primary barrier to effective treatment. Current research has largely focused on individual signaling pathways or isolated organelle functions, yet a comprehensive understanding of how these subcellular structures coordinate to drive resistance remains lacking. This review synthesizes current knowledge through the perspective of subcellular structural homeostasis, the dynamic balance maintained by intracellular organelles. We examine how key subcellular structures, the cell membrane, mitochondria, endoplasmic reticulum, ribosomes, lysosomes, exosomes, and stress granules, undergo functional remodeling to promote drug resistance. It is crucial that these organelles do not work independently but form an integrated and dynamic communication network. Mitochondria serve as the intracellular signaling hub, integrating calcium signals, metabolic progress, and stress responses, while exosomes function as intercellular messengers that spread the anti-drug-resistant phenotype between cells. This framework reveals why targeting individual structures often fails and highlights the therapeutic potential of disrupting inter-organelle communication. We discuss emerging clinical strategies targeting subcellular structures and identify critical knowledge gaps, including the need for non-invasive biomarkers and combination approaches that target multiple network nodes. By shifting the focus from isolated organelles to their coordinated interplay, this review offers a new paradigm for overcoming drug resistance in PDAC. Full article

Groundwater is the primary source of irrigation in many semi-arid hard-rock aquifer regions. Yet, its suitability assessment is often hindered by the nonlinear hydrochemical dynamics that traditional bivariate tools, such as the U.S. Salinity Laboratory (USSL) diagram, cannot adequately resolve. To overcome this limitation, we developed an explainable artificial intelligence (XAI) framework that predicts irrigation suitability categories directly from hydrochemical variables, without relying on calculated indices. Using 1872 post-monsoon groundwater samples from Telangana, India, we trained three ensemble tree-based classifiers (Random Forest, LightGBM, and XGBoost) on 11 hydrochemical variables (Na⁺, K⁺, Ca²⁺, Mg²⁺, HCO₃⁻, Cl⁻, F⁻, NO₃⁻, SO₄²⁻, pH, and total hardness). Class imbalance was addressed using the Synthetic Minority Over-sampling Technique (SMOTE), and model hyperparameters were optimized with Optuna. Among the tested models, LightGBM achieved the best performance (balanced accuracy = 0.938). Model interpretability was enabled using Shapley Additive Explanations (SHAP), supported by Piper and Gibbs diagrams, revealing a critical distinction between sodicity-driven salinity and hardness-driven mineralization, identifying calcium-saturated waters for which gypsum amendment can be chemically futile. To bridge the gap between algorithmic accuracy and operational simplicity, we distilled SHAP explanations into linear heuristics and quantified the trade-off between accuracy and simplicity. Accordingly, we proposed a tiered hydrochemical triage framework in which quantitative heuristics handled approximately 62.5% of the routine samples, while XAI resolved the complex and ambiguous cases. Overall, the proposed framework transforms classic suitability assessment tools into an adaptable, evidence-informed, proactive decision-support system for sustainable agricultural water management under increasing environmental stress. Full article

Medical literature is replete with diagrammatic representations of systems, yet lacks standardised nomenclature and consistent symbolic conventions. In an introductory system dynamics course for health science students, causal loop diagrams (CLDs) are used to support systems thinking. Notwithstanding recognised limitations, CLDs provide a coherent heuristic for representing multivariate systems with feedback. We studied 55 first-year volunteers enrolled in the course to compare understanding of systems presented as CLDs versus typical journal diagrams. Two endocrine systems were selected from open-access, peer-reviewed literature: calcium homeostasis and glucose homeostasis. Participants were shown either the original journal diagram for one system and a CLD for the other, or vice versa, and answered twelve true/false questions—six per system. A mixed-model, two-way repeated measures ANOVA revealed a significant interaction between Diagram (CLD vs. journal diagram) and System (Calcium vs. Glucose). Post hoc comparisons showed significantly higher performance with CLDs for both Calcium (0.84 vs. 0.38) and Glucose (0.83 vs. 0.63), p < 0.001. A Fisher’s Exact Test also indicated a higher proportion of questions favouring CLDs. These findings suggest that training in CLDs may enhance understanding of complex systems compared to standard journal diagrams. Further work is needed to address limitations including the small sample size, use of a single cohort, and a restricted set of diagrams. Full article

Objectives: To evaluate the physicochemical properties of a novel strontium silicate-based root canal sealer (C-Root SP) in comparison with a calcium silicate-based sealer (TotalFill BC) and an epoxy resin-based sealer (AH Plus). Methods: Setting time, net mass change (apparent solubility behavior), pH changes, and surface characteristics were assessed based on ISO 6876 and ANSI/ADA Specification No. 57, with minor methodological modifications. Net mass change and pH were evaluated over 28 days. Surface morphology and elemental composition were analyzed after dry and aqueous aging in deionized water using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Data were analyzed using one-way and repeated-measures ANOVA with Tukey’s post hoc test (α = 0.05). Results: AH Plus exhibited the longest initial and final setting times (10.93 ± 0.65 h and 37.33 ± 0.13 h), whereas TotalFill BC showed the shortest (7.98 ± 0.32 h and 30.18 ± 0.20 h); C-Root SP demonstrated intermediate values (9.35 ± 0.38 h and 32.75 ± 0.57 h) (p < 0.001). C-Root SP exhibited positive net mass change values (indicative of net mass loss), ranging from 5.32 ± 4.72% at 24 h to 6.83 ± 5.55% at 28 days, significantly higher than AH Plus and TotalFill BC (p < 0.001), which showed negative values indicative of apparent mass gain. All sealers demonstrated alkaline conditions, with C-Root SP maintaining the highest apparent pH values throughout the evaluation period (p < 0.001). Surface and compositional changes were observed in the bioceramic sealers following aqueous aging, with increased detectable strontium content in C-Root SP. Conclusions: C-Root SP exhibited physicochemical behavior consistent with a strontium-modified calcium silicate-based sealer, characterized by hydration-driven hydroxyl ion release resulting in apparent alkalinity and ion exchange-associated behavior, and dynamic surface changes consistent with those reported for bioceramic materials. Clinical Significance: Strontium incorporation may influence hydration-mediated physicochemical behavior; however, further in vitro and in vivo studies are required to determine its clinical relevance. Full article

HIV latency, driven by a complex interplay of host factors, remains a key barrier to viral clearance. Current latency-reversing agents (LRAs) demonstrate limited efficacy and specificity, and none have been approved for clinical use. Although natural products have shown promise as LRAs, the therapeutic potential of fungal metabolites remains underexplored. Candida albicans, a prevalent human commensal and opportunistic pathogen, produces diverse secondary metabolites that can influence host pathways, affecting latency dynamics. This study aimed to investigate the latency-modulating potential of secondary metabolites of C. albicans using an integrative network pharmacology and computational pipeline. C. albicans secondary metabolites were retrieved from the literature, screened for drug-likeness, and mapped to human targets and biological pathways annotated in HIV latency. Key metabolites, hub genes, and pathways were systematically characterized through network and computational analyses. Six drug-like candidates, identified from 185 absorption, distribution, metabolism, excretion, and toxicity (ADMET)-screened metabolites, collectively mapped to 369 human genes with a 6.5% overlap in HIV latency (176 shared and 20 hub genes). These overlapping genes were significantly enriched for signal transduction, membrane localization, and adaptive responses to chemical stimuli. Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed oncogenic diseases (non-small cell lung, pancreatic, and prostate cancers) and latency-associated cascades, including PD-L1/PD-1, HIF-1, Ras, PI3K-Akt, calcium, and cAMP signaling. Six hub targets (MAPK1, PIK3CA, MAPK3, EGFR, MTOR, and AKT1) were consistently annotated within the top 30 KEGG pathways and displayed strong binding affinities for MET 15 and MET 119. Molecular dynamics (MD) simulations confirmed favorable binding free energies (BFEs) and stable conformational dynamics for the top-ranked metabolite MET 15. C. albicans secondary metabolites preferentially target oncogenic signaling networks central to HIV latency maintenance, notably PI3K/AKT/MTOR and MAPK/ERK, which regulate cell survival, metabolic homeostasis, and viral transcriptional repression. MET 15 is a top-ranked candidate metabolite for HIV latency-reversing therapeutics and warrants experimental validation in established latency models. Full article

Background: Short-term facilitation (STF) is a key form of synaptic plasticity driven by activity-dependent increases in presynaptic release probability. However, estimating core synaptic parameters—quantal size ($q$), vesicle pool size ($N$), and release probability ($p_i$)—remains challenging due to nonlinear dynamics and unobservable presynaptic states, limiting the applicability of conventional methods. Methods: We developed a fast analytical framework based on first- and second-order statistical moments of evoked EPSCs, including mean, variance, and cross-stimulus covariance. By constructing composite moment relationships, latent variables were algebraically eliminated, yielding closed-form estimators of synaptic parameters. To improve robustness under strong facilitation, a Tsodyks–Markram (T–M) model-based calibration step was introduced to refine $N$ and $p_i$ using the estimated $q$ as a constraint. Results: Applied to hippocampal CA3–CA1 synapses, the method produced accurate and stable estimates of q across varying noise and sampling conditions. Incorporation of cross-stimulus covariance enabled effective characterization of structured variability that is neglected in classical approaches. While direct estimates of $N$ and $p_i$ showed dispersion, T–M calibration significantly improved stability and physiological consistency. Compared with mean–variance analysis, the proposed method achieved superior performance under facilitating conditions. Conclusions: This hybrid framework enables rapid and reliable estimation of synaptic parameters in STF synapses by exploiting second-order statistical structure. It provides a practical tool for investigating presynaptic mechanisms and may facilitate quantitative studies of synaptic dysfunction in neurological and psychiatric disorders. Full article

Human transglutaminases (hTGs) are Ca²⁺-dependent enzymes that catalyze protein crosslinking, deamidation and other post-translational modifications, thus acting as key stabilizers of tissue architecture and modulators of protein function across diverse physiological contexts. This family comprises eight catalytically active members, TG1-7, the blood coagulation factor FXIII, and the inactive structural protein Band 4.2 of the erythrocyte membrane. Recent structural and biochemical advances have refined our understanding of the molecular principles governing transglutaminase function. Thus, current evidence reveals how domain organization and catalytic architecture integrate calcium binding, nucleotide-dependent regulation in TG2 and proteolytic activation in selected isoforms to control enzymatic activity. In this review, we provide an updated and comprehensive overview of the active hTGs, combining structural, biochemical and functional data to explain how closely related enzymes achieve isoform-specific regulation and distinct biological roles. We further examine how disruption of these mechanisms contributes to human pathology, highlighting representative examples in autoimmunity, inherited disorders and complex diseases. By integrating recent biochemical and structural findings with disease-associated evidence, we aim to offer a coherent framework for understanding how TG regulation underlies their diverse biological functions and clinical relevance. Full article

Cyantraniliprole, a second-generation diamide insecticide, exhibits broad-spectrum efficacy against numerous insect pests due to its selective activation of insect ryanodine receptors (RyRs). This activation triggers uncontrolled calcium release from the sarcoplasmic reticulum, resulting in sustained muscle contraction, paralysis, and ultimately death. Its unique mode of action, which is different from that of organophosphates, carbamates, pyrethroids, and neonicotinoids, helps minimize cross-resistance, making it a valuable component of integrated pest management (IPM). However, continuous field use has led to the development of resistance, primarily mediated by target-site mutations within the RyR transmembrane domain (e.g., G4946E, I4743M, and I4790K) and by enhanced metabolic detoxification via cytochrome P450 monooxygenases, carboxylesterases, and glutathione S-transferases. These mechanisms often confer cross-resistance to other diamide insecticides, thereby complicating resistance management. Moreover, sublethal exposures can disrupt insect growth, development, and reproduction, potentially accelerating resistance evolution. In addition, cyantraniliprole poses ecological risks due to its toxicity to non-target organisms such as aquatic species, including zebrafish and water fleas, pollinators such as honeybees, and soil fauna, as well as the environmental persistence of its major metabolite, J9Z38. This review comprehensively integrated current knowledge on the molecular mechanisms of action, genetic and metabolic bases of resistance, sublethal effects, and ecotoxicological impacts of cyantraniliprole, along with its environmental fate, plant uptake and translocation, and residue dynamics in agricultural systems. Finally, we discuss potential risk-mitigation strategies, including formulation optimization, application-method improvements, and resistance monitoring. Overall, this review aims to provide a comprehensive scientific foundation for the sustainable use, resistance management, and regulatory assessment of this widely used insecticide. Full article

Elemental migration and enrichment are important processes influencing tea plant growth and the assembly of rhizosphere bacterial communities within the rock–soil–plant continuum. This study explores how soil parent materials (granite, quartz schist, and sericite schist) are potentially associated with these processes and their observed associations with the elemental composition of tea leaves. Exploratory statistical analyses revealed distinct, lithology-specific biogeochemical patterns that serve as a foundation for hypothesis generation. In granite soils, chlorite correlated with the mobility of Cr, Pb, Cu, Ni, Mg, and Na, coinciding with shifts in the relative abundances of Verrucomicrobia, Armatimonadetes, and Chloroflexi. In quartz schist, kaolinite exhibited notable correlations with the dynamics of Pb, Cr, Ni, Zn, and As, which were statistically linked to Planctomycetes, Proteobacteria, and Acidobacteria. Complex mineral–microbe interactions were observed in sericite schist soils, where clay minerals (e.g., chlorite, illite) were closely associated with the migration of multiple elements (Pb, K, Ca, Cd, As, Al, Fe, Zn), paralleling structural variations in communities of Actinobacteria, Planctomycetes, Chloroflexi, and Proteobacteria. Potassium (K), calcium (Ca), and manganese (Mn) showed bioaccumulation tendencies in tea leaves across all lithologies, with an enrichment capacity order of Ca > K > Mn > Mg > Na > Al. Exploratory Classification and Regression Tree (CART) analysis suggested that the migration of K, Ca, Cu, Zn, and Hg corresponded most closely with their soil concentrations. Manganese (Mn) exhibited a mineral-associated trend, with kaolinite content as a potential correlate, while cadmium (Cd) migration was statistically linked to the relative abundance of Armatimonadetes. These findings highlight potential candidate relationships between mineralogy, microbes, and elemental mobility rather than confirming causal mechanisms, emphasizing the need for further validation in larger or experimental datasets. Full article

Glycolysate and glycerolysate—organic substances recovered from the chemical recycling of polyurethane waste—were investigated as sustainable plasticizers for acrylonitrile-butadiene rubber composites filled with 30 phr of calcium lignosulfonate or kraft lignin. The study evaluated the impact of these recycled plasticizers (added at 10 and 15 phr) on the curing process, morphology, rheology, mechanical and dynamic mechanical performances. Rheological analysis confirmed that both plasticizers significantly reduced the complex viscosity of the rubber compounds, with the effect being most pronounced at the 15 phr loading. While the incorporation of glycolysate and glycerolysate slightly extended the optimum cure time and decelerated the curing process, the cross-link density remained consistently within the range of 3.5–4 × 10⁻⁴ mol·cm⁻³. Morphological studies revealed that the plasticizers facilitated better dispersion of both lignin types and improved interfacial adhesion. However, the mechanical response differed significantly depending on the filler type. A consistent increase in elongation at break was observed only for composites filled with kraft lignin, where values rose from 341% for the reference up to 571% for the sample with 15 phr of glycolysate. In contrast, the application of plasticizers to calcium lignosulfonate-filled composites led to an initial decrease in both tensile strength and elongation at break. Notably, kraft lignin-filled composites exhibited superior overall mechanical performance, with glycolysate effectively maintaining tensile strength levels comparable to the reference. While both recovered substances performed effectively as processing aids, they had a negligible effect on the glass transition temperature. The results demonstrated that these recovered polyurethane derivatives are highly effective, sustainable alternatives to conventional plasticizers, showing a clear synergistic effect particularly with kraft lignin. Full article

Traumatic brain injury (TBI) initiates a cascade of molecular and cellular reactions leading to long-term disturbances of neuronal and glial homeostasis. One of the key mechanisms of secondary injury is a pathological increase in intracellular Ca²⁺ concentration. Parvalbumin (PV) plays an important role in the regulation of Ca²⁺ homeostasis in neurons. In turn, connexin 43 (Cx43) is the principal protein of astrocytic gap junctions (GJs), which ensure neuroglial communication. The spatiotemporal changes in these proteins and the mechanisms of their interaction after TBI remain insufficiently studied. In the present study, a comprehensive analysis of the expression, localization, and spatial organization of PV and Cx43 in the cerebral cortex following TBI was performed. In intact tissue, PV was localized predominantly in neurons, whereas Cx43 formed typical punctate structures of astrocytic GJs. Twenty-four hours after TBI, a sharp activation of PV with pronounced nuclear translocation was observed against the background of a catastrophic decrease in Cx43 expression, accompanied by a reduction in the number of NeuN⁺ neurons and signs of apoptosis. However, after 7 days, a mirror-opposite effect was detected, characterized by decreased PV expression and increased Cx43 levels with its aggregation into cluster-like structures, as well as partial restoration of NeuN immunoreactivity. In addition, molecular dynamics simulations demonstrated that the stability of the PV–Cx43 complex is determined by the presence of Ca²⁺ and physiological pH, whereas acidosis and Ca²⁺ overload destabilize their interaction. Taken together, these results reveal a phase-dependent mirror-opposite pattern of PV and Cx43 expression and localization and emphasize the key role of Ca²⁺- and pH-dependent neuroglial interactions in TBI. Full article

This study evaluated the effects of dietary protein levels during late gestation on nutrient digestibility, plasma amino acid profiles in jennies, and donkey foal growth performance. Twenty-four pregnant jennies were randomly assigned to one of three diets with different crude protein (CP) contents during late gestation: 12.48% (HP), 11.52% (MP), and 10.54% (LP) on a dry matter basis. All animals received the same diet immediately after parturition for a duration of 30 days. During the trial, two digestion experiments were conducted, blood samples were collected at 28 and 7 days prepartum, and weekly weight measurements of jennies and foals were recorded. The results indicated that the dietary protein level did not significantly affect feed intake in late gestation. However, apparent nutrient digestibility of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and ether extract (EE), and calcium (Ca) and phosphorus (P) was generally higher in the MP and LP groups than in the HP group, with MP showing the most consistent improvements across nutrients and timepoints (p < 0.05). Although the HP diet increased plasma concentrations of certain amino acids, including glutamic acid (Glu), valine (Val), methionine (Met), leucine (Leu), essential amino acids (EAAs), functional amino acids (FAAs), and branched chain amino acids (BCAAs), and elevated serum levels of glucose (GLU), blood urea nitrogen (BUN), and creatinine (CRE), it failed to improve postpartum weight recovery in jennies, highlighting that weight dynamics during this period are governed by factors beyond dietary protein content alone. Specifically, the LP group exhibited significantly higher cumulative postpartum weight loss over weeks 1–4 than the HP group (p = 0.004). Regarding offspring performance, both HP and MP diets improved foal birth weight, weekly body weight up to 4 weeks, average daily gain, and body height compared to the LP group (p < 0.05), with no significant differences observed between the HP and MP groups. In conclusion, for jennies under the current confined feeding system, a late-gestation diet containing 11.52% CP was adequate to support higher nutrient digestibility in the jennies and better growth performance in their foals, compared to a lower protein level (10.54% CP). However, increasing the dietary CP to 12.48% provided no additional benefits in nutrient utilization or overall productivity. Full article

Background: Valproic acid (VPA) poisoning has a dynamic clinical course and may require extracorporeal toxin removal (ECTR) in severe cases. Intermittent hemodialysis is the preferred ECTR technique; however, clinical experience with expanded hemodialysis (HDx) using medium cut-off (MCO) membranes in acute VPA intoxication is scarce. We describe a case of severe VPA poisoning managed with intermittent HDx and outline the clinical rationale and kinetic response. Case Report: A 54-year-old woman presented to the emergency department after accidental presumably ingesting approximately 4 g of VPA, with depressed consciousness (Glasgow Coma Scale 7) and metabolic acidosis (pH 7.10, HCO₃⁻ 13 mmol/L, PCO₂ 50 mmHg, lactate 2.8 mmol/L, ionized calcium 0.8 mmol/L, elevated anion gap). Initial plasma VPA was 262.99 µg/mL, ammonia was 14 µmol/L, and cranial computed tomography showed no acute abnormalities. ECTR was initiated in the intensive care unit as intermittent HDx using an MCO dialyzer for 4 h. Serial VPA concentrations were obtained before treatment, at 2 h, and at the end of the session to guide real-time prescription adjustment, with an increase in blood flow from 200 to 230 mL/min. Results: VPA decreased from 262.99 µg/mL pre-HD to 141.48 µg/mL at 2 h (46.2% reduction) and 97.81 µg/mL at 4 h (62.8% reduction), with clear improvement in the level of consciousness. A mild post-dialysis rebound was observed (100.07 µg/mL at 14 h). The patient recovered without additional ECTR and was discharged with normalized VPA levels on follow-up. Conclusions: In this patient, intermittent HDx with an MCO membrane was feasible, well tolerated, and associated with rapid VPA clearance and neurological recovery. Serial drug monitoring enabled bedside optimization of the dialysis prescription and post-treatment evaluation. A single HDx session was sufficient, and VPA therapy was safely reintroduced under close monitoring. Full article