Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury.

Animal studies have demonstrated beneficial effects of therapeutic hypothermia on myocardial function, yet exact mechanisms remain unclear. Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90 minutes with consecutive reperfusion. 30 minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60 minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure

A superconducting-nanowire 3-terminal electronic device

In existing superconducting electronic systems, Josephson junctions play a central role in processing and transmitting small-amplitude electrical signals. However, Josephson-junction-based devices have a number of limitations including: (1) sensitivity to magnetic fields, (2) limited gain, (3) inability to drive large impedances, and (4) difficulty in controlling the junction critical current (which depends sensitively on sub-Angstrom-scale thickness variation of the tunneling barrier). Here we present a nanowire-based superconducting electronic device, which we call the nanocryotron (nTron), that does not rely on Josephson junctions and can be patterned from a single thin film of superconducting material with conventional electron-beam lithography. The nTron is a 3-terminal, T-shaped planar device with a gain of ~20 that is capable of driving impedances of more than 100 k{\Omega}, and operates in typical ambient magnetic fields at temperatures of 4.2K. The device uses a localized, Joule-heated hotspot formed in the gate to modulate current flow in a perpendicular superconducting channel. We have characterized the nTron, matched it to a theoretical framework, and applied it both as a digital logic element in a half-adder circuit, and as a digital amplifier for superconducting nanowire single-photon detectors pulses. The nTron has immediate applications in classical and quantum communications, photon sensing and astronomy, and its performance characteristics make it compatible with existing superconducting technologies. Furthermore, because the hotspot effect occurs in all known superconductors, we expect the design to be extensible to other materials, providing a path to digital logic, switching, and amplification in high-temperature superconductors

Is the pain just physical? The role of psychological distress, quality of life, and autistic traits in ehlers–danlos syndrome, an internet-based survey in italy

Background: Ehlers–Danlos syndromes (EDS) have been associated with psychological distress, comorbid psychiatric disorders, and worsening in quality of life (QoL). Among the neurodevelopmental disorders, autism spectrum disorders (ASD) have shown the highest rates of co-occurrence with EDS. The reasons for these associations are unknown and a possible role of pain in increasing the risk of psychiatric disorders in EDS has been suggested. However, a detailed picture of an Italian EDS sample is still lacking. Methods: We conducted a web-based survey in a third level center for the diagnosis of EDS in northern Italy, to investigate psychological distress, QoL, and the presence of autistic traits. Furthermore, we correlated the psychometric data with some clinical variables. Results: We observed a high rate of psychological distress with 91% of the responders at high risk of common mental disorders, low QoL, and high prevalence of autistic traits in EDS patients. Specifically, patients lacking a specific genetic test, diagnosed as suspects of EDS appeared to be at greater risk and reported worse psychological QoL. Pain was significantly associated with both psychological distress and worse QoL. Conclusions: Our findings support the need of further research and of a multi-disciplinary approach to EDS including psychological and psychiatric liaison

Correction to: Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study (Neurotherapeutics, (2021), 18, 2, (1127-1136), 10.1007/s13311-020-01004-3)

This article has been updated to add the author Richard S. Finkel. The original article has been corrected

Health Impacts of Catastrophic Climate Change: Expert Workshop. Avoid Dangerous Climate Change (AVOID)

Climate change is likely to have serious and significant impacts on human population health. The mechanisms by which climate change may affect health are becoming better understood. Current quantitative methods of estimating future health impacts rely on disease-specific models that primarily describe relationships between mean values of weather variables and health outcomes and do not address the impacts of extreme events or weather disasters. Extreme events have the potential to disrupt community function, which is of concern for decision-makers. Estimating the magnitude and extent of impacts from low probability high impact events is challenging because there is often no analogue that can provide relevant evidence and that take into account the complexity of factors determining future vulnerability and health impacts (the social determinants of health)

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET)

Background. Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E’ and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. Methods. EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. Results. Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E’ that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E’ but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E’ and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E’, p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E’ of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. Conclusion. Age and HTN have a synergic negative effect on E/E’ and TAPSE at peak exercise in hypertensive subjects

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

The Euro Area Crisis Management Framework – Consequences and Institutional Follow-Ups

The current instruments in the EU to deal with debt and liquidity crises include among others the European Financial Stability Facility (EFSF) and the European Financial Stabilisation Mechanism (EFSM). Both are temporary in nature (3 years). In terms of an efficient future crisis management framework one has to ask what follows after the EFSF and the EFSM expire in 3 years time. In this vein, this briefing paper addresses the question of the political and economic medium-to long-term consequences of the recent decisions. Moreover, we assess what needs to be done using this window of opportunity of the coming 3 years. Which institutions need to be formalized, into what format, in order to achieve a coherent whole structure? This briefing paper presents and evaluates alternatives as regards the on-going debate on establishing permanent instruments to support the stability of the euro. Among them are the enhancement of the effectiveness of the Stability and Growth Pact combined with the introduction of a European semester and a macroeconomic surveillance and crisis mechanism, fiscal limits hard-coded into each country's legislation in the form of automatic, binding and unchangeable rules and, as the preferred solution, the European Monetary Fund