ANALYSIS OF ELECTRICAL BURNS IN ALBANIA: A FOUR-YEAR REVIEW.

This is an epidemiological review of electrical burns admitted to the Service of Burns and Plastic Surgery, UHC "Mother Theresa" of Tirana, Albania, covering a four-year period, from 2019 to 2022. Twenty-seven patients were identified as having sustained an electrical burn injury, all of them males and most of them, namely 85%, belonging to the "working force" age group 19-65 years old. Most of the accidents, 70% of them, occurred at work, and these were all high voltage electrical burns. A total 65% of the cases had at least one of the upper limbs involved and the mean surface area burned was estimated at around 20% TBSA, mortality rate 11.1%, and all the fatal cases were from occupational burns. Serum level of BUN, creatinine and liver enzymes were evaluated on admission and at least 7 days after, with no significant changes. WBC count was found to be elevated in almost all the patients, and remained elevated in the second week and even longer for patients with sepsis. Four of our patients needed amputations. Besides these, no other serious complications were registered.

Nous présentons une étude épidémiologique des 37 patients admis dans le service des brûlés et de chirurgie plastique du CHU Mère Teresa de Tirana entre 2019 et 2022. Il s'agissait exclusivement d'hommes dont 85% en âge de travailler (19 à 65 ans). Il s'agissait dans la plupart (70%) des cas d'accidents du travail (AT) et dans ces cas toujours d'atteintes à haut voltage. Au moins un des membres supérieurs était atteint dans 65% des cas. La surface brûlée moyenne était de 20% SCT, la mortalité de 11,1% (toujours après AT). Urée, créatinine et enzymes hépatiques étaient mesurées à l'entrée et au moins 1 fois, à J7, sans changement notable. On observait une hyperleucocytose initiale, persistant pendant la deuxième semaine voire plus longtemps en cas de sepsis. Aucune complication sévère n'a été observée chez les survivants, hormis des amputations chez 4 patients.

An unidentified yet notable modification on I Na and I K (DR) caused by ramelteon.

Despite advancement in anti-seizure medications, 30% of patients continue to experience recurrent seizures. Previous data indicated the antiepileptic properties of melatonin and its agonists in several animal models. However, the underlying mechanisms of melatonin and its agonists on cellular excitability remain poorly understood. In this study, we demonstrated the electrophysiological changes of two main kinds of ion channels that are responsible for hyperexcitability of neurons after introduction of melatonin agonists- ramelteon (RAM). In Neuro-2a cells, the amplitude of voltage-gated Na+ (I Na) and delayed-rectifier K+ currents (I K (DR)) could be suppressed under RAM. The IC50 values of 8.7 and 2.9 µM, respectively. RAM also diminished the magnitude of window Na+ current (I Na (W)) elicited by short ascending ramp voltage, with unchanged the overall steady-state current-voltage relationship. The decaying time course of I Na during a train of depolarizing pulses arose upon the exposure to RAM. The conditioning train protocol which blocked I Na fitted the recovery time course into two exponential processes and increased the fast and slow time constant of recovery the presence of RAM. In pituitary tumor (GH3) cells, I Na amplitude was also effectively suppressed by the RAM. In addition, GH3-cells exposure to RAM decreased the firing frequency of spontaneous action potentials observed under current-clamp conditions. As a result, the RAM-mediated effect on INa was closely associated with its ability to decrease spontaneous action potentials. Collectively, we found the direct attenuation of I Na and I K (DR) caused by RAM besides the agonistic action on melatonin receptors, which could partially explain its anti-seizure activity.

A Case Report of an Atypical Presentation of Morvan Syndrome.

Morvan syndrome, also known as Morvan's fibrillary chorea, is a rare paraneoplastic neurological syndrome presenting with central nervous system (CNS) symptoms, peripheral nerve hyperexcitability, and autonomic nervous system (ANS) manifestations. The etiology and severity of the disease are not well understood. An adult female presented with a sudden onset of chest pain, unilateral extremity weakness, blepharospasms, and muscle spasms, with positive voltage-gated potassium channel (VGKC) antibody and positive neuronal antibody (amphiphysin) in serum. Morvan syndrome can be diagnosed in patients with myokymia, positive VGKC antibody, and neuropsychiatric symptoms with a high clinical index of suspicion. This atypical presentation of Morvan syndrome in a female identifies a novel association of amphiphysin positivity in this rare disease.

Application value of individualized tube voltage, contrast injection, and adaptive statistical iterative reconstruction V algorithm based on body mass index in renal computed tomography angiography for radiation and iodinated contrast dose reduction.

OBJECTIVES: To explore the application value of body mass index (BMI)-based kilovoltage peak (kVp) selection and contrast injection protocol combined with different adaptive statistical iterative reconstruction V (ASIR-V) strengths in renal computed tomography angiography (CTA) in reducing radiation and contrast medium (CM) doses. METHODS: One-hundred renal CTA patients were prospectively enrolled and were divided into individualized kVp group (group A, n = 50) and conventional 100 kVp group (group B, n = 50), both with automatic tube current modulation and CM of Iohexol at 350 mgI/mL concentration. Group A: 70 kVp, noise index (NI) of 18 and CM dose rate of 17 mgI/kg/s for 10 s for BMI <25 kg/m2 patients; 80 kVp, NI = 17, and CM dose rate of 19 mgI/kg/s for 10 s for 25 kg/m2≤BMI≤30 kg/m2 patients. Group B: 100 kVp, 50 mL of CM at the flow rate of 4.5 mL/s. The objective image quality, effective radiation dose, CM dose, injection rate, and image quality were compared between the 2 groups. RESULTS: There was no significant difference in patient characteristics between the 2 groups (P > .05). Compared to group B, group A significantly reduced effective radiation dose by 28.4%, CM dose by 27.2%, and injection rate by 22.7% (all P < .001). The 2 groups had similar SD values in erector spine (P > .05). Group A had significantly higher CT values, SNR, and CNR values of the renal arteries than group B (all P < .001). The 2 radiologists had excellent agreement (Kappa value > 0.8) in the subjective scores of renal CTA images and showed no statistically significant difference between the 2 groups (4.57 ± 0.42 vs 4.41 ± 0.49) (P > .05). CONCLUSIONS: BMI-based scan and reconstruction protocol in renal CTA significantly reduces radiation and contrast doses while maintaining diagnostic image quality. ADVANCES IN KNOWLEDGE: (i) BMI-based individualized tube voltage selection and contrast injection protocol in renal CTA reduces both radiation and contrast doses over conventional protocol. (ii) The combination of lower kVp and higher weight ASIR-V maybe used to improve image quality in terms of contrast enhancement and image noise under lower radiation and contrast dose conditions. (iii) Renal CTA of normal size (BMI ≤ 30 kg/m2) patients acquired at low radiation dosage and low iodine contrast dose through the combination of low tube voltage and ASIR-V algorithm achieves excellent diagnostic image quality with a good inter-rater agreement.

Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms.

The KCNH family of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K+ channels, but the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains of KCNH channels play a crucial role in gating that is still only partly understood. Using KCNH1(KV10.1) as a model, we have characterized the behavior of a series of modified channels that could not be explained by the current models. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the uncovering of an open state can explain the behavior of the mutants. This open state, which is not detectable in wild-type channels, appears to lack the rapid flicker block of the conventional open state. Because it is accessed from deep closed states, it elucidates intermediate gating events well ahead of channel opening in the wild type. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca2+-Calmodulin and generate a model that describes the characteristic features of KCNH channels gating.

Experimental investigation of zinc ferrite/insulation oil nanofluid natural convection heat transfer, AC dielectric breakdown voltage, and thermophysical properties.

Improving the thermal and dielectric properties of insulation oil (INO) with nanoadditives is an important challenge, and achieving dispersion stability in these nanofluids is quite challenging, necessitating further investigation. The main goal of this study is the synthesis and use of the hydrophobicity of zinc ferrite (ZnFe2O4) nanoparticles, which can improve both the thermal and dielectric properties of the INO. This oil is made from distillate (petroleum), including severely hydrotreated light naphthenic oil (75-85%) and severely hydrotreated light paraffinic oil (15-25%). A comprehensive investigation was carried out, involving the creation of nanofluids with ZnFe2O4 nanoparticles at various concentrations, and employing various characterization methods such as X-ray diffraction (XRD), Fourier-transform infrared (FTIR), scanning electron microscopy, energy dispersive X-ray (EDX), zeta potential analysis, and dynamic light scattering (DLS). The KD2 Pro thermal analyzer was used to investigate the thermal characteristics, including the thermal conductivity coefficient (TCC) and volumetric heat capacity (VHC). Under free convection conditions, the free convection heat transfer coefficient (FCHTC) and Nusselt numbers (Nu) were evaluated, revealing enhancements ranging from 14.15 to 11.7%. Furthermore, the most significant improvement observed in the AC Breakdown voltage (BDV) for nanofluids containing 0.1 wt% of ZnFe2O4 amounted to 17.3%. The most significant finding of this study is the improvement in the heat transfer performance, AC BDV, and stability of the nanofluids.

Gliosarcoma associated with bilateral hippocampal sclerosis in a cat presenting complex partial seizures with orofacial involvement: A case report.

Key Clinical Message: Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. Abstract: A 16-year-old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill-defined, round, intra-axial mass in the right piriform lobe, showing hyperintensity on T2W, T2-FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2-FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1-antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody-associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1-antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high-grade glioma.

Follicle-stimulating hormone promotes atrial fibrosis in menopausal women with atrial fibrillation.

BACKGROUND: Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared with men. However, the underlying mechanism remains unclear. OBJECTIVE: The purpost of this study was to investigate the mechanism through which menopause promotes atrial fibrosis. METHODS: In a prospective cohort of women with AF, regression analyses were conducted to assess the relationship between low-voltage area (LVA) and sex hormone levels. CREM-IbΔC-X mice, a spontaneous AF model, underwent bilateral ovariectomy (OVX). Electrocardiograms, echocardiograms, and Masson staining were performed. Follicle-stimulating hormone (FSH) stimulation was applied in male mice for 3 months. OVX was also applied in an angiotensin II (Ang II)-induced pressure overload mouse model, after programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms. RESULTS: Women demonstrated a significantly higher LVA burden than men (P < .001). A positive correlation was observed between LVA burden and FSH level (P = .002). Mice in the OVX group exhibited a significantly higher incidence of AF (P = .040) and atrial fibrosis (P = .021) compared with the Sham group, which could be attenuated by adeno-associated virus encoding small interfering RNA against Fshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P = .035) and atrial fibrosis (P = .002). In Ang II-induced female mice, OVX prompted atrial fibrosis, increased AF inducibility, and shortened atrial effective refractory period, which could be attenuated with knockdown of Fshr. RNA-seq indicated mitochondrial dysfunction. CONCLUSION: Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.

Clinical efficacy of radiofrequency ablation guided by high-density mapping on persistent atrial fibrillation.

Objective: The study aimed to explore the clinical efficacy of radiofrequency ablation (RFA) guided by high-density mapping on persistent atrial fibrillation (PsAF). Method: A total of 190 patients with PsAF undergoing RFA were divided into a routine group (n = 105) and a high-density mapping group (n = 85). The indicators of therapeutic efficacy were collected and compared. Results: A statistically significant difference was found in the overall rate of post-operative recurrence between the two groups (11.58% vs. 23.81%, χ2 = 5.055, p = 0.025). The effects of different treatment methods on SF-36 score varied (FSF-36 treatment = 43.142, p < 0.05), and SF-36 scores at 3, 6, and 12 months of both groups were in the same order: the high-density mapping group > the routine group. While surgery guided by high-density substrate mapping (odds ratio = 0.453, 95% confidence interval: [0.232-0.784], p < 0.001) was a protective factor for recurrence. Conclusion: For patients with PsAF, more accurate mapping is conducted on the atrial substrate using a PentaRay electrode, which further verifies that the success rate of individualized ablation strategy is like mainstream procedures, and it significantly improves the subsequent health status of patients and reduces their incidence of adverse reactions.

Objetivo: Explorar la eficacia clínica de la ablación por radiofrecuencia guiada por mapeo de alta densidad en el tratamiento de la fibrilación auricular persistente. Método: Ciento noventa pacientes con fibrilación auricular persistente que recibieron ablación por radiofrecuencia se dividieron en dos grupos: convencional (n = 105) y mapeo de alta densidad (n = 85). Se recopilaron y compararon los indicadores de eficacia. Resultados: La diferencia en la tasa total de recurrencia posoperatoria entre los dos grupos fue estadísticamente significativa (11,58% vs. 23,81%; χ2 = 5055; p = 0.025). Los efectos de los diferentes métodos de tratamiento en el puntaje SF-36 variaron (FSF-36 tratamiento = 43.142, p < 0.05), y los puntajes SF-36 a los 3, 6 y 12 meses de ambos grupos siguieron el mismo orden: grupo de mapeo de alta densidad > grupo convencional. Por su parte, la cirugía guiada por mapeo de matriz de alta densidad (OR: 0.453; IC95%: 0.232-0.784; p < 0.001) es un factor protector contra la recurrencia. Conclusión: Para los pacientes con fibrilación auricular persistente, el uso de electrodos Pentaray para mapear con mayor precisión en la matriz auricular verificó aún más que la tasa de éxito de la estrategia de ablación individualizada es similar a la de la cirugía convencional, mejorando significativamente el estado de salud posterior del paciente y reduciendo la incidencia de reacciones adversas.

Ether-Based Gel Polymer Electrolyte for High-Voltage Potassium Ion Batteries.

Low-concentration ether electrolytes cannot efficiently achieve oxidation resistance and excellent interface behavior, resulting in severe electrolyte decomposition at a high voltage and ineffective electrode-electrolyte interphase. Herein, we utilize sandwich structure-like gel polymer electrolyte (GPE) to enhance the high voltage stability of potassium-ion batteries (PIBs). The GPE contact layer facilitates stable electrode-electrolyte interphase formation, and the GPE transport layer maintains good ionic transport, which enabled GPE to exhibit a wide electrochemical window and excellent electrochemical performance. In addition, Al corrosion under a high voltage is suppressed through the restriction of solvent molecules. Consequently, when using the designed GPE (based on 1 m), the K||graphite cell exhibits excellent cycling stability of 450 cycles with a capacity retention of 91%, and the K||FeFe-Prussian blue cell (2-4.2 V) delivers a high average Coulombic efficiency of 99.9% over 2200 cycles at 100 mA g-1. This study provides a promising path in the application of ether-based electrolytes in high-voltage and long-lasting PIBs.

Voltage mapping and right ventriculography to guide ablation for arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia: a case report.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a family inherited cardiomyopathy associated with ventricular arrhythmias. With the development of molecular biology, histology, imaging, and other diagnostic techniques, the diagnosis rate and incidence of ARVC have gradually increased. However, ARVC remains rare in clinical practice. Currently, the diagnosis and management of ARVC is far from satisfactory in clinical practice. In the case report, we described a clinical case of radiofrequency ablation guided by voltage mapping and right ventriculography in the treatment of ARVC with ventricular tachycardia and discussed the relevant literatures.

Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.

Electrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer.

Effect of Synthetic Vitreous Fiber Exposure on TMEM16A Channels in a Xenopus laevis Oocyte Model.

Many years ago, asbestos fibers were banned and replaced by synthetic vitreous fibers because of their carcinogenicity. However, the toxicity of the latter fibers is still under debate, especially when it concerns the early fiber interactions with biological cell membranes. Here, we aimed to investigate the effects of a synthetic vitreous fiber named FAV173 on the Xenopus laevis oocyte membrane, the cell model we have already used to characterize the effect of crocidolite asbestos fiber exposure. Using an electrophysiological approach, we found that, similarly to crocidolite asbestos, FAV173 was able to stimulate a chloride outward current evoked by step membrane depolarizations, that was blocked by the potent and specific TMEM16A channel antagonist Ani9. Exposure to FAV173 fibers also altered the oocyte cell membrane microvilli morphology similarly to crocidolite fibers, most likely as a consequence of the TMEM16A protein interaction with actin. However, FAV173 only partially mimicked the crocidolite fibers effects, even at higher fiber suspension concentrations. As expected, the crocidolite fibers' effect was more similar to that induced by the co-treatment with (Fe3+ + H2O2), since the iron content of asbestos fibers is known to trigger reactive oxygen species (ROS) production. Taken together, our findings suggest that FAV173 may be less harmful that crocidolite but not ineffective in altering cell membrane properties.

Linking performance to dynamic migration of biofilm ecosystem reveals the role of voltage in the start-up of hybrid microbial electrolysis cell-anaerobic digestion.

Applied voltage is a crucial parameter in hybrid microbial electrolysis cells-anaerobic digestion (MEC-AD) systems for enhancing methane production from waste activated sludge (WAS). This study explored the impact of applied voltage on the initial biofilm formation on electrodes during the MEC-AD startup using raw WAS (Rr) and heat-pretreated WAS (Rh). The findings indicated that the maximum methane productivity for Rr and Rh were 3.4 ± 0.5 and 3.4 ± 0.2 mL/gVSS/d, respectively, increasing 1.5 times and 2.6 times over the productivity at 0 V. The biomass on electrode biofilms for Rr and Rh at 0.8 V increased by 70 % and 100 % compared to 0 V. The core functional microorganisms in the cathode biofilm were Methanobacterium and Syntrophomonas, and Geobacter in the anode biofilm, enhancing methane production through syntrophism and direct interspecies electron transfer, respectively. These results offer academic insights into optimizing AD functional electrode biofilms by applying voltage.

Aluminum Corrosion Chemistry in High-Voltage Lithium Metal Batteries with LiFSI-Based Ether Electrolytes.

High-voltage Li metal batteries (LMBs) based on ether electrolytes hold potential for achieving high energy densities exceeding 500 Wh kg-1, but face challenges with electrolyte oxidative stability, particularly concerning aluminum (Al) current collector corrosion. However, the specific chemistry behind Al corrosion and its effect on electrolyte components remains unexplored. Here, our study delves into Al corrosion in the representative LiFSI-DME electrolyte system, revealing that low-concentration electrolytes exacerbate Al current collector corrosion and solvent decomposition. In contrast, high-concentration electrolytes mitigate these issues, enhancing long-term stability. Remarkably, LiFSI-0.7DME electrolyte demonstrates exceptional stability with up to 1000 cycles at high voltage without significant capacity decay. These findings offer crucial insights into Al corrosion mechanisms in ether-based electrolytes, advancing our comprehension of high-voltage LMBs and facilitating their development for practical applications.

Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings.

Cellular electrophysiology is the foundation of many fields, from basic science in neurology, cardiology, oncology to safety critical applications for drug safety testing, clinical phenotyping, etc. Patch-clamp voltage clamp is the gold standard technique for studying cellular electrophysiology. Yet, the quality of these experiments is not always transparent, which may lead to erroneous conclusions for studies and applications. Here, we have developed a new computational approach that allows us to explain and predict the experimental artefacts in voltage-clamp experiments. The computational model captures the experimental procedure and its inadequacies, including: voltage offset, series resistance, membrane capacitance and (imperfect) amplifier compensations, such as series resistance compensation and supercharging. The computational model was validated through a series of electrical model cell experiments. Using this computational approach, the artefacts in voltage-clamp experiments of cardiac fast sodium current, one of the most challenging currents to voltage clamp, were able to be resolved and explained through coupling the observed current and the simulated membrane voltage, including some typically observed shifts and delays in the recorded currents. We further demonstrated that the typical way of averaging data for current-voltage relationships would lead to biases in the peak current and shifts in the peak voltage, and such biases can be in the same order of magnitude as those differences reported for disease-causing mutations. Therefore, the presented new computational pipeline will provide a new standard of assessing the voltage-clamp experiments and interpreting the experimental data, which may be able to rectify and provide a better understanding of ion channel mutations and other related applications.

Serotonin (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride improves detrusor sphincter dyssynergia by inhibiting L-type voltage-gated calcium channels in spinal cord injured rats.

AIMS: To explore the role of voltage-gated calcium channels (VGCC) in 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5-hydroxy tryptamine (5-HT) 2A receptors and VGCCs in lumbosacral cord after SCI. METHODS: Female Sprague-Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS-EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS-EMG. Rats were euthanized and L6-S1 spinal cord were acquired for immunofluorescence. RESULTS: In SCI rats, intrathecal administration of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride or L-type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high-frequency oscillations. They could also prolong EUS bursting activity duration on EUS-EMG. Moreover, the effect of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride can be eliminated with the combined administration of L-type VGCC agonist, (±)-Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T-type VGCC blocker TTA-P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5-HT2A receptor and Cav1.2 immunolabeling-positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats. CONCLUSIONS: Our study demonstrated that 5-HT2A/2C agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride may improve SCI-induced DSD by inhibiting the L-type voltage-gated calcium channel in lumbosacral cord motoneurons.

Core myopathy in two siblings with a biallelic variant in the CACNA1S gene-A case series study.

Homozygous variants of Calcium Voltage-Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation were previously identified as causes of periodic paralysis and congenital early-onset myopathy, while it could be manifested as a late-onset congenital core myopathy. Abstract: Calcium Voltage-Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core-like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late-onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C > A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core-like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S-related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.

Lysosomal iron accumulation and subsequent lysosomes-mitochondria iron transmission mediate PFOS-induced hepatocyte ferroptosis.

Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5-24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.