Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

NOMPC ion channel hinge forms a gating spring that initiates mechanosensation.

The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the Drosophila mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate.

Cumulative incidence of chronic pain after visiting a Dutch emergency department with acute pain.

Background: Chronic pain is a substantial problem in modern healthcare resulting in health care overutilization. The cumulative incidence of developing chronic pain after visiting the emergency department with acute pain has been determined for specific patient groups only. If the cumulative incidence of chronic pain in emergency department patients with acute pain is high, more proactive measures are justified to limit development of chronic pain.

Efficacy of an erector spinae plane block for renal colic: a systematic review and meta-analysis.

Background And Aim: The passage of kidney stones through the ureter creates renal colic, a severe visceral abdominal pain. Renal colic is typically managed with non-steroidal anti-inflammatory drugs and opioids. Yet, these treatments often fail to provide adequate pain relief.

Characteristics and outcomes of emergency department patients across health care systems: an international multicenter cohort study.

Background: A wide variation of emergency medical system configurations across countries has limited the value of comparison of quality and performance measures in the past. Furthermore, lack of quantitative data on EDs prevents definition of the problems and possibilities for data driven improvement of quality of care. Therefore, the objective is to describe and compare Emergency Department (ED) populations and characteristics, and their outcomes in the Netherlands, Denmark and Australia, using a recently developed template for uniform reporting of standardized measuring and describing of care provided in the ED (structure, staffing and governance, population, process times and outcomes).