High beta-amyloid(1-40) cerebrospinal fluid concentrations precede increase of serum biomarkers in a case with severe HELLP syndrome.

Beta-amyloid peptides and tau protein concentrations were analysed at second and third trimester pregnancy in cerebrospinal fluid in a 27-year old woman who developed severe HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome. Contrary to a healthy pregnant control the beta-amyloid(1-40) load was much higher and the ratios beta-amyloid peptides(1-42/1-40) and phospho-tau/tau had increased before delivery. We observed that in early HELLP syndrome increased beta-amyloid levels preceded vascular biomarker changes.

Ryanodine receptor stabilization therapy suppresses Ca- based arrhythmias in a novel model of metabolic HFpEF.

Heart Failure with preserved ejection fraction (HFpEF) has a high rate of sudden cardiac death (SCD) and empirical treatment is ineffective. We developed a novel preclinical model of metabolic HFpEF that presents with stress-induced ventricular tachycardia (VT). Mechanistically, we discovered arrhythmogenic changes in intracellular Ca handling distinct from the changes pathognomonic for heart failure with reduced ejection fraction.

Electro-metabolic signaling.

Precise matching of energy substrate delivery to local metabolic needs is essential for the health and function of all tissues. Here, we outline a mechanistic framework for understanding this critical process, which we refer to as electro-metabolic signaling (EMS). All tissues exhibit changes in metabolism over varying spatiotemporal scales and have widely varying energetic needs and reserves.

When health care sickens the health care worker: Commentary on Park et al. (2023).

In their survey, Park and colleagues (2023) reported that many health care and hospital workers perceived that their safety was not a priority during the COVID-19 pandemic, with 33.9% of responders feeling betrayed by institutional leaders. Employees of the health care system reported being viewed more as servants than specialists during the pandemic, and they noted that critical assessment and the expression of one's own opinion were unwelcome (Lederer, 2023).

Ryanodine Receptor Stabilization Therapy Suppresses Ca -Based Arrhythmias in a Novel Model of Metabolic HFpEF.

Heart Failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure worldwide and its significant mortality is associated with a high rate of sudden cardiac death (SCD; 30% - 40%). Chronic metabolic stress is an important driver of HFpEF, and clinical data show metabolic stress as a significant risk factor for ventricular arrhythmias in HFpEF patients. The mechanisms of SCD and ventricular arrhythmia in HFpEF remain critically understudied and empirical treatment is ineffective.

Na /K ATPase-Ca 1.2 nanodomain differentially regulates intracellular [Na ], [Ca ] and local adrenergic signaling in cardiac myocytes.

Background: The intracellular Na concentration ([Na ] ) is a crucial but understudied regulator of cardiac myocyte function. The Na /K ATPase (NKA) controls the steady-state [Na ] and thereby determines the set-point for intracellular Ca . Here, we investigate the nanoscopic organization and local adrenergic regulation of the NKA macromolecular complex and how it differentially regulates the intracellular Na and Ca homeostases in atrial and ventricular myocytes.

Structural Analysis of Mitochondria in Cardiomyocytes: Insights into Bioenergetics and Membrane Remodeling.

Mitochondria in mammalian cardiomyocytes display considerable structural heterogeneity, the significance of which is not currently understood. We use electron microscopic tomography to analyze a dataset of 68 mitochondrial subvolumes to look for correlations among mitochondrial size and shape, crista morphology and membrane density, and organelle location within rat cardiac myocytes. A tomographic analysis guided the definition of four classes of crista morphology: lamellar, tubular, mixed and transitional, the last associated with remodeling between lamellar and tubular cristae.

Calcium and bicarbonate signaling pathways have pivotal, resonating roles in matching ATP production to demand.

Mitochondrial ATP production in ventricular cardiomyocytes must be continually adjusted to rapidly replenish the ATP consumed by the working heart. Two systems are known to be critical in this regulation: mitochondrial matrix Ca ([Ca]) and blood flow that is tuned by local cardiomyocyte metabolic signaling. However, these two regulatory systems do not fully account for the physiological range of ATP consumption observed.

Arterial Occlusion Effectiveness of Space Blanket‒Improvised Tourniquets for the Remote Setting.

Introduction: Control of severe extremity hemorrhage by tourniquet can save lives. In remote areas or in mass casualty incidents with multiple severely bleeding victims, lack of conventional tourniquets may make it necessary to improvise tourniquets.

Methods: Occlusion of the radial artery and delayed onset of capillary refill time resulting from windlass-type tourniquets were experimentally investigated by comparing a commercial tourniquet and a space blanket‒improvised tourniquet with a carabiner as a rod.

Disruption of P2Y2 signaling promotes breast tumor cell dissemination by reducing ATP-dependent calcium elevation and actin localization to cell junctions.

The tumor microenvironment and wound healing after injury both contain extremely high concentrations of the extracellular signaling molecule, adenosine triphosphate (ATP) compared to normal tissue. P2Y2 receptor, an ATP-activated purinergic receptor, is typically associated with pulmonary, endothelial, and neurological cell signaling. Here we report its role and importance in breast epithelial cell signaling and how it is altered in metastatic breast cancer.

Detecting Hexafluoroisopropanol Using Soft Chemical Ionization Mass Spectrometry and Analytical Applications to Exhaled Breath.

Here we explore the potential use of proton transfer reaction/selective reagent ion-time-of-flight-mass spectrometry (PTR/SRI-ToF-MS) to monitor hexafluoroisopropanol (HFIP) in breath. Investigations of the reagent ions HO, NO, and O are reported using (relative humidity (rH) ≈ 0%) and (rH ≈ 100%)) nitrogen gas containing traces of HFIP, i.e.

Pericytes and the Control of Blood Flow in Brain and Heart.

Pericytes, attached to the surface of capillaries, play an important role in regulating local blood flow. Using optogenetic tools and genetically encoded reporters in conjunction with confocal and multiphoton imaging techniques, the 3D structure, anatomical organization, and physiology of pericytes have recently been the subject of detailed examination. This work has revealed novel functions of pericytes and morphological features such as tunneling nanotubes in brain and tunneling microtubes in heart.

Understanding Calmodulin Variants Affecting Calcium-Dependent Inactivation of L-Type Calcium Channels through Whole-Cell Simulation of the Cardiac Ventricular Myocyte.

Mutations in the calcium-sensing protein calmodulin () have been linked to two cardiac arrhythmia diseases, Long QT Syndrome 14 (LQT14) and Catecholaminergic Polymorphic Ventricular Tachycardia Type 4 (CPVT4), with varying degrees of severity. Functional characterization of the mutants most strongly associated with LQT14 show a clear disruption of the calcium-dependent inactivation (CDI) of the L-Type calcium channel (LCC). CPVT4 mutants on the other hand are associated with changes in their affinity to the ryanodine receptor.

Rescue Blankets as Multifunctional Rescue Equipment in Alpine and Wilderness Emergencies-A Narrative Review and Clinical Implications.

The utilization of rescue blankets in pre-hospital emergency medicine exceeds protection from hypothermia and enhanced visibility by far. In this narrative review, we focus on emphasizing the alternative applications of these fascinating multifunctional tools in the pre-hospital setting. A literature search in PubMed and Web of Science yielded 100 results (last update was on 8 July 2022), a total number of 26 of which were included in this narrative review.

Electromagnetic Interference from Heated Gloves May Compromise Avalanche Transceiver Function.

Introduction: Rapid location of avalanche victims by companions using avalanche transceivers is of utmost importance to prevent asphyxiation. The objective was to determine whether electromagnetic interference from heating elements in gloves worn by rescuers or victims can impair the receiving or transmitting function of avalanche beacons.

Methods: Commercially available heated gloves from 3 different manufacturers were examined during a simulated search with 3 common brands of avalanche transceivers.

Thin foil body-shield resuscitation barrier device to protect from blood: an experimental study.

In times of collective concern about pandemics, body-shield resuscitation barrier devices are more and more considered to protect against transmission of different pathogens between rescuers and patients. The objective of this experimental study was to investigate the characteristics of blood drops dispersed on the surface of four different foils suitable for blanketing patients during resuscitation. We analyzed run-off characteristics of blood stains depending on surface properties of polyvinyl chloride, polyethylene, polyethylene terephthalate and aluminum-coated polyethylene terephthalate.

[Effects of automated external defibrillators on hands-off intervals in lay rescuers].

Background: Survival chances after out-of-hospital cardiac arrests caused by hyperdynamic electric cardiac rhythms can be significantly improved by early defibrillation with automated external defibrillators (AEDs). As postulated in international guidelines, the resulting hands-off intervals should not exceed 10 s.

Objectives: We investigated delay in onset of chest compressions and the length of hands-off intervals during defibrillation associated with the application of AEDs.

Critical Requirements for the Initiation of a Cardiac Arrhythmia in Rat Ventricle: How Many Myocytes?

Cardiovascular disease is the leading cause of death worldwide due in a large part to arrhythmia. In order to understand how calcium dynamics play a role in arrhythmogenesis, normal and dysfunctional Ca signaling in a subcellular, cellular, and tissued level is examined using cardiac ventricular myocytes at a high temporal and spatial resolution using multiscale computational modeling. Ca sparks underlie normal excitation-contraction coupling.

Camera-based Measurements of Intracellular [Na+] in Murine Atrial Myocytes.

Intracellular sodium concentration ([Na]i) is an important regulator of intracellular Ca. Its study provides insight into the activation of the sarcolemmal Na/Ca exchanger, the behavior of voltage-gated Na channels and the Na,K-ATPase. Intracellular Ca signaling is altered in atrial diseases such as atrial fibrillation.

Understanding the Dynamics of the Transient and Permanent Opening Events of the Mitochondrial Permeability Transition Pore with a Novel Stochastic Model.

The mitochondrial permeability transition pore (mPTP) is a non-selective pore in the inner mitochondrial membrane (IMM) which causes depolarization when it opens under conditions of oxidative stress and high concentrations of Ca. In this study, a stochastic computational model was developed to better understand the dynamics of mPTP opening and closing associated with elevated reactive oxygen species (ROS) in cardiomyocytes. The data modeled are from "photon stress" experiments in which the fluorescent dye TMRM (tetramethylrhodamine methyl ester) is both the source of ROS (induced by laser light) and sensor of the electrical potential difference across the IMM.