Periodic ER-plasma membrane junctions support long-range Ca signal integration in dendrites.

Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II.

Predictors of quality of life and resilience in patients with ovarian cancer during the COVID-19 pandemic: a cross-sectional study.

Purpose: The aim of this cross-sectional study was to investigate the psychosocial burdens of patients with ovarian cancer during the COVID-19 pandemic.

Methods: Ovarian cancer patients answered a quantitative survey assessing their resilience (BRS) and quality of life (FACT-G7) as well as clinical (first- vs. ≥ second-line treatment), demographic (age < 65 vs.

The overlooked burden of persistent physical symptoms: a call for action in European healthcare.

Regardless of their cause, persistent physical symptoms are distressing somatic complaints that occur on most days for at least several months. They are common in patients with somatic diseases, functional somatic disorders, mental disorders, and undiagnosed medical conditions and are often associated with significant impairment and medical costs. Despite their prevalence and impact, persistent physical symptoms are often overlooked in medical care.

Discovery, synthesis and SAR of 2-acyl-1-biarylmethyl pyrazolidines, dual orexin receptor antagonists designed as fast and short-acting sleeping drugs.

Dual orexin receptor antagonists (DORAs) are approved for the treatment of sleep onset and/or sleep maintenance insomnia. In the present disclosure, we report the discovery of a new class of DORAs designed to treat sleep disorders requiring a fast onset and a short duration of action (<4 h). We used early human pharmacokinetic-pharmacodynamic (PK-PD) predictions and in vivo experiments to identify DORAs eliciting this specific hypnotic profile.

ChatGPT as an Information Source for Patients with Migraines: A Qualitative Case Study.

Migraines are one of the most common and expensive neurological diseases worldwide. Non-pharmacological and digitally delivered treatment options have long been used in the treatment of migraines. For instance, migraine management tools, online migraine diagnosis or digitally networked patients have been used.