In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation.

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.

Structural heart transcatheter interventions in orthotopic cardiac transplant and left ventricular assist devices recipients: A nationwide study.

Background: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown.

Aims: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain.

Methods: Multicenter, ambispective, observational nationwide registry.

LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial.

Background: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA).

Direct Inhibition of BK Channels by Cannabidiol, One of the Principal Therapeutic Cannabinoids Derived from .

Cannabidiol (CBD), one of the main bioactive compounds, is utilized in the treatment of major epileptic syndromes. Its efficacy can be attributed to a multimodal mechanism of action that includes, as potential targets, several types of ion channels. In the brain, CBD reduces the firing frequency in rat hippocampal neurons, partly prolonging the duration of action potentials, suggesting a potential blockade of voltage-operated K channels.

Vagus Nerve Stimulation in the Carotid Triangle: An Effective Method for Monitoring the Recurrent Laryngeal Nerve in Thyroid and Parathyroid Surgery.

Objective: Our objective is the description of the technique of vagus nerve stimulation in carotid triangle in order to monitor the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery.

Methods: We stimulated the vagus nerve in the carotid triangle during 150 thyroid or parathyroid surgeries using a monopolar electromyography electrode inserted under the mastoid process towards the jugular foramen as a cathode, and using another subdermal electrode in the mastoid as an anode. Another complementary method of vagus stimulation was achieved with a pair of subdermal electrodes, placing the cathode at the mandibular angle and the anode at the mastoid.

A Combined Ligand- and Structure-Based Virtual Screening To Identify Novel NaV1.2 Blockers: In Vitro Patch Clamp Validation and In Vivo Anticonvulsant Activity.

Epilepsy is a neurological disorder characterized by recurrent seizures that arise from abnormal electrical activity in the brain. Voltage-gated sodium channels (NaVs), responsible for the initiation and propagation of action potentials in neurons, play a critical role in the pathogenesis of epilepsy. This study sought to discover potential anticonvulsant compounds that interact with NaVs, specifically, the brain subtype hNaV1.

Advanced Liquid Chromatography with Tandem Mass Spectrometry Method for Quantifying Glyphosate, Glufosinate, and Aminomethylphosphonic Acid Using Pre-Column Derivatization.

Analytical limitations make it challenging to develop effective methodologies for understanding glyphosate-based herbicide levels in drinking water and groundwater. Due to their lack of chromophores and zwitterionic nature, glyphosate-based herbicides are difficult to detect using traditional methods. This paper offers a straightforward method for quantifying glyphosate, glufosinate, and aminomethylphosphonic acid (AMPA) via 9-fluorenylmethylchloroformate (FMOC-Cl) pre-column derivatization and analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Clinical outcomes of TAVI with the Myval balloon-expandable valve for non-calcified aortic regurgitation.

Background: Transcatheter aortic valve replacement (TAVR) in non-calcified aortic regurgitation (NCAR) is an off-label procedure. The balloon-expandable Myval includes extra-large sizes (30.5 mm and 32 mm) of interest in this setting.

Transcatheter valve-in-valve or valve-in-ring implantation with a novel balloon-expandable device in patients with bioprosthetic left side heart valves failure: 1-year follow-up from a multicenter experience.

Background: Transcatheter aortic and mitral valve-in-valve (ViV) or valve-in-ring (ViR) implantation into failed bioprosthetic heart valves (BHVs) or rings represents an appealing, less invasive, treatment option for patients at high surgical risk. Nowadays, few data have been reported on the use of balloon-expandable Myval (Meril Life Science, Vapi, India) transcatheter heart valve (THV) for the treatment of degenerated BHVs or rings. We aimed at evaluating the early and mid-term clinical outcomes of patients with left side heart bioprosthesis deterioration treated with transcatheter ViV/ViR implantation using Myval THV.

Novel Dimeric hHv1 Model and Structural Bioinformatic Analysis Reveal an ATP-Binding Site Resulting in a Channel Activating Effect.

The human voltage-gated proton channel (hHv1) is a highly selective ion channel codified by the gene. It plays a fundamental role in several physiological processes such as innate and adaptive immunity, insulin secretion, and sperm capacitation. Moreover, in humans, a higher hHv1 expression/function has been reported in several types of cancer cells.

Structure-Based Virtual Screening Identifies Novobiocin, Montelukast, and Cinnarizine as TRPV1 Modulators with Anticonvulsant Activity .

The transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel, known to be involved in the regulation of many important physiological and pathological processes. In the last few years, it has been proposed as a promising target to develop novel anticonvulsant compounds. However, thermoregulatory effects associated with the channel inhibition have hampered the path for TRPV1 antagonists to become marketed drugs.

Myval versus alternative balloon- and self-expandable transcatheter heart valves: A central core lab analysis of conduction disturbances.

Background: Several studies have compared surface electrocardiographic changes following different self-expandable (SE) (Evolut (Medtronic, USA); Acurate (Boston Scientific, USA); Portico (Abbott, USA); and Allegra (NVT, Germany)) and balloon-expandable (BE) Sapien-3 (Edwards Lifesciences, USA) transcatheter heart valves. We aimed to compare these prosthesis with the novel Myval BE prosthesis (Meril Life, India).

Methods: Academic European registry of consecutive patients with severe aortic stenosis who received any of the 6 aforementioned valves.

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.

Aim: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes.

Volatile composition and sensory properties of wines from vineyards affected by iron chlorosis.

Recent studies have shown that mild to moderate iron chlorosis can have positive effects on grape quality potential, including volatile profile. The main objective of this work was to investigate, for the first time, how moderate iron stress in grapevines affects the presence of volatile organic compounds (VOCs) in wines. The study was carried out during 2018-2019 seasons, in 20 Tempranillo vineyard subzones with different degree of iron deficiency, located in Ribera del Duero (North-Central Spain).

Intra-Day Solar Power Forecasting Strategy for Managing Virtual Power Plants.

Solar energy penetration has been on the rise worldwide during the past decade, attracting a growing interest in solar power forecasting over short time horizons. The increasing integration of these resources without accurate power forecasts hinders the grid operation and discourages the use of this renewable resource. To overcome this problem, Virtual Power Plants (VPPs) provide a solution to centralize the management of several installations to minimize the forecasting error.

Next-generation balloon-expandable Myval transcatheter heart valve in low-risk aortic stenosis patients.

Objectives: We aimed to describe hemodynamic performance and clinical outcomes at 30-day follow-up of the balloon-expandable (BE) Myval transcatheter heart valve (THV) in low-risk patients.

Background: The results of the next-generation BE Myval THV in low-risk aortic stenosis (AS) patients are still unknown.

Methods: Retrospective registry performed in nine European centers including patients with low predicted operative mortality risk according to Society of thoracic surgeons (STS) and European system for cardiac operative risk evaluation (EuroSCORE-II) scores.

Early clinical and haemodynamic matched comparison of balloon-expandable valves.

Objectives: The balloon-expandable Sapien-3 valve demonstrated superior results in terms of residual aortic regurgitation when compared with self-expandable devices. We aimed to compare for the first-time early outcomes of Sapien-3 transcatheter heart valve (THV) with the balloon-expandable Myval device.

Methods: Consecutive real-world patients from nine European institutions with symptomatic severe aortic stenosis treated either with Sapien-3 or Myval THV devices after June 2018 were compared.

Turning Base Transceiver Stations into Scalable and Controllable DC Microgrids Based on a Smart Sensing Strategy.

This paper describes a practical approach to the transformation of Base Transceiver Stations (BTSs) into scalable and controllable DC Microgrids in which an energy management system (EMS) is developed to maximize the economic benefit. The EMS strategy focuses on efficiently managing a Battery Energy Storage System (BESS) along with photovoltaic (PV) energy generation, and non-critical load-shedding. The EMS collects data such as real-time energy consumption and generation, and environmental parameters such as temperature, wind speed and irradiance, using a smart sensing strategy whereby measurements can be recorded and computing can be performed both locally and in the cloud.

Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit.

Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca- and voltage-dependent K channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD).

Relationships between chlorophyll content of vine leaves, predawn leaf water potential at veraison, and chemical and sensory attributes of wine.

Background: Water deficit and iron deficiency (iron chlorosis) are common environmental stresses that affect grapevine production in the Mediterranean area. Studies on the impact of both stresses, when they act simultaneously, are rare. The main objective of this investigation was to evaluate the combined effects of the incidence of iron chlorosis and the vine water status on quality of Tempranillo wine.

Parabens inhibit hNa 1.2 channels.

Propylparaben, a commonly used antimicrobial preservative, has been reported as an anticonvulsant agent targeting neuronal Na channels (Na). However, the specific features of the Na channel inhibition by this agent have so far not been extensively studied. Moreover, it is still unclear if it shares this pharmacological activity with other parabens.

Differential expression of the long and truncated Hv1 isoforms in breast-cancer cells.

Metabolic reprogramming of cancer cells results in a high production of acidic substances that must be extruded to maintain tumor-cell viability. The voltage-gated proton channel (Hv1) mediates highly selective effluxes of hydronium-ion (H ) that prevent deleterious cytoplasmic acidification. In the work described here, we demonstrated for the first time that the amino-terminal-truncated isoform of Hv1 is more highly expressed in tumorigenic breast-cancer-cell lines than in nontumorigenic breast cells.