Dual pattern of cholesterol-induced decoupling of residue-residue interactions of Kir2.2.

Cholesterol is a negative regulator of a variety of ion channels. We have previously shown that cholesterol suppresses Kir2.2 channels via residue-residue uncoupling on the inter-subunit interfaces within the close state of the channels (3JYC).

Point-of-Care Ultrasound, an Unexpected Cardiac Mass in a Neonate.

Neonatal cardiac masses are uncommon and often not obvious based on physical examination or plain radiography. The objective of this clinical case report is to demonstrate how cardiac point-of-care ultrasound was pivotal in the clinical course of a seemingly well neonate with vague symptoms. A 6-week-old male infant presented to the emergency department with fatigue and pallor that was reported to have resolved before arrival.

Development and validation of a LC-MS/MS method for analysis of vortioxetine in postmortem specimens. First data from an authentic case.

Vortioxetine is an antidepressant recently licensed in USA and EU for the treatment of major depressive disorder. Neither fatal case due to overdose nor data about postmortem concentrations on blood or other specimens have been reported. The aims of this study were the development and validation of a method for vortioxetine analysis by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) in postmortem samples and its application in an authentic case.

Effects of Nano and Microplastics on the Inflammatory Process: and Studies Systematic Review.

Background: Microplastics (MPs) and Nanoplastics (NPs) are plastic fragments that spread in the environment and accumulate in the human body, so they have been becoming a worldwide environmental concern because of their potential human health effects. The aim of this systematic review was to investigate the prospective impact of MPs and NPs on the inflammatory process.

Methods: Electronic article search was performed on PubMed, Scopus and Web of Science international databases from 1 Jan 2012 to 31 Dec 2021.

Innovative use of Protek Duo during bilateral lung transplant with Veno-Arterial Extracorporeal Membrane Oxygenation assistance.

V-A ECMO during bilateral lung transplantation is routinely used when extracorporeal support is needed, in particular in case of patients affected by pulmonary hypertension. We report the case of a patient successfully transplanted with V-A ECMO assistance using a percutaneous double lumen cannula as venous drainage (Protek Duo, CardiacAssist Inc., Pittsburgh, PA) and central aortic cannulation.

Cholesterol-induced suppression of Kir2 channels is mediated by decoupling at the inter-subunit interfaces.

Cholesterol is a major regulator of multiple types of ion channels. Although there is increasing information about cholesterol binding sites, the molecular mechanisms through which cholesterol binding alters channel function are virtually unknown. In this study, we used a combination of Martini coarse-grained simulations, a network theory-based analysis, and electrophysiology to determine the effect of cholesterol on the dynamic structure of the Kir2.

Heart rupture as an acute complication of cocaine abuse: A case report.

The purpose of this study is to show a very rare complication of acute cocaine poisoning, namely heart rupture. In the present case report, acute cocaine intoxication caused massive myocardial infarction, resulting in heart rupture and cardiac tamponade. A crime scene investigation found a dead body on the street in a drug dealing district.

Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a very complex pathophysiology differing from other causes of pulmonary hypertension (PH). It is an infrequent consequence of acute pulmonary embolism that is frequently misdiagnosed. Pathogenesis has been related to coagulation abnormalities, infection or inflammation, although these disturbances can be absent in many cases.

Development and Validation of a Method for the Detection and Quantification of Antidepressants and Antipsychotics in Bone Samples by GC-MS.

Bone marrow is the tissue contained inside the bones and can be considered one of the potential alternative tissues in forensic toxicology. This matrix could be particularly useful in those cases where the routine sample is not available due to an advanced state of decomposition or skeletonization of the corpse. The aim of this study was to develop, validate and apply an analytical method of extraction and analysis of different antidepressants and antipsychotics, commonly used in therapy, from spiked pig ribs.

Noncanonical function of long myosin light chain kinase in increasing ER-PM junctions and augmentation of SOCE.

Increased endothelial permeability leads to excessive exudation of plasma proteins and leukocytes in the interstitium, which characterizes several vascular diseases including acute lung injury. The myosin light chain kinase long (MYLK-L) isoform is canonically known to regulate the endothelial permeability by phosphorylating myosin light chain (MLC-P). Compared to the short MYLK isoform, MYLK-L contains an additional stretch of ~919 amino acid at the N-terminus of unknown function.

Modulation of Transient Receptor Potential C Channel Activity by Cholesterol.

Changes of cholesterol level in the plasma membrane of cells have been shown to modulate ion channel function. The proposed mechanisms underlying these modulations include association of cholesterol to a single binding site at a single channel conformation, association to a highly flexible cholesterol binding site adopting multiple poses, and perturbation of lipid rafts. These perturbations have been shown to induce reversible targeting of mammalian transient receptor potential C (TRPC) channels to the cholesterol-rich membrane environment of lipid rafts.

Toxicological investigations in a fatal and non-fatal accident due to hydrogen sulphide (HS) poisoning.

Hydrogen sulphide (HS) is one of the most toxic natural gas and represents a not rare cause of fatal events in workplaces. We report here a serious accidental poisoning by hydrogen sulphide inhalation involving six sailors. Three of them died while the other three survived and were transported to the emergency room.

Comparative docking analysis of cholesterol analogs to ion channels to discriminate between stereospecific binding vs. stereospecific response.

Cholesterol is a major component of the membrane and a key regulator of many ion channels. Multiple studies showed that cholesterol regulates ion channels in a stereospecific manner, with cholesterol but not its chiral isomers having a functional effect. This stereospecificity has been universally attributed to the specificity of cholesterol binding, with the assumption that only native cholesterol binds to the channels whereas its isomers do not.

Chiral Specificity of Cholesterol Orientation Within Cholesterol Binding Sites in Inwardly Rectifying K Channels.

Cholesterol is an integral component of cellular membranes and has been shown to be an important functional regulator for many different ion channels, including inwardly rectifying potassium (Kir) channels. Consequently, understanding the molecular mechanisms underlying this regulation represents a critical field of study. Broadly speaking, cholesterol can mediate ion channel function either directly by binding to specific sites or indirectly by altering surrounding membrane properties.

Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of Cholesterol Molecules.

Cholesterol is a major regulator of multiple types of ion channels, but the specific mechanisms and the dynamics of its interactions with the channels are not well understood. Kir2 channels were shown to be sensitive to cholesterol through direct interactions with "cholesterol-sensitive" regions on the channel protein. In this work, we used Martini coarse-grained simulations to analyze the long (μs) timescale dynamics of cholesterol with Kir2.

The influence of the trocar choice on post-operative acute pain after thoracoscopy.

Background: Acute post-operative pain following thoracic surgery procedures is still an unresolved problem despite the introduction of minimally invasive procedures such as video assisted surgery. Until now it is never investigated if different surgical instruments could influence post-operative pain. The aim of our study is to investigate the role of different type of trocar on post-operative pain in minimally invasive thoracic surgery.

Uniportal thoracoscopic resection of intralobar and extralobar pulmonary sequestration.

Pulmonary sequestration (PS) is a rare congenital malformation of the respiratory tract. Two main variants are described, the intralobar and the extralobar PS. Clinical manifestations vary from accidental findings to life threatening complications.

Differential Effects of Sterols on Ion Channels: Stereospecific Binding vs Stereospecific Response.

Numerous ion channels have been shown to be regulated by the level of membrane cholesterol, but the mechanisms responsible for these effects are still not well understood. The key question in the field is how to discriminate between the contributions of the two central mechanisms that might be responsible for the sensitivity of ion channels to cholesterol: specific sterol-protein interactions or regulation of channels by the bilayer physical properties. Comparative analysis of cholesterol and its isomers on the function of an ion channel is a powerful tool to achieve this goal.

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids.

The influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics was investigated computationally and experimentally. The truncated tail phospholipids, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), are two major oxidation products of the unsaturated phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine. A combination of coarse-grained molecular dynamics simulations, Laurdan multiphoton imaging, and atomic force microscopy microindentation experiments was used to determine the impact of POVPC and PGPC on the structure of a multicomponent phospholipid bilayer and to assess the consequences of their incorporation on membrane packing and endothelial cell stiffness.

Evaluation of the Role of Toxicological Data in Discriminating Between H S Femoral Blood Concentration Secondary to Lethal poisoning and Endogenous H S Putrefactive Production.

Hydrogen sulfide is a colorless gas and has a strong odor of rotten eggs. It is absorbed by the upper respiratory tract mucosa, and it causes histotoxic hypoxemia and respiratory depression by exerting an inhibitory effect on cytochrome oxidase. To evaluate the role of toxicological data in distinguishing between the H S blood concentration secondary to lethal poisoning and the endogenous H S produced during putrefaction, we compared the postmortem H S concentrations of six fatal H S poisoning cases (8.

The therapeutic use of cannabinoids: Forensic aspects.

Unlabelled: Since 2013 in the Italian market has been introduced the Nabiximols, a drug containing two of the main active cannabinoids: Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and cannabidiol (CBD). This drug has been approved in Italy in the treatment of Multiple Sclerosis (MS). It is an oral spray formulation and each puff of 100μl contains 2.

Domino effect: An unusual case of six fatal hydrogen sulfide poisonings in quick succession.

Hydrogen sulfide (H2S) is one of the most serious toxic gases encountered in forensic practice. Aside from being a by-product of many industrial processes, this gas is naturally produced during the putrefaction of organic substances. We report six autopsy cases of fatal H2S poisonings from inhalation of H2S gas after an occupational accident.