Circadian clock genes and cell survival in bipolar disorder: Insights into lithium responsiveness and molecular mechanisms in patient-derived neural progenitor cells and mouse neurons.

Bipolar disorder (BD) is characterized by disrupted circadian rhythms and neuronal loss. Lithium amplifies circadian rhythms and is neuroprotective, indicating mechanistic overlap across cellular systems. We examined the role of neuroprotection in determining lithium response and how circadian clock genes regulate apoptosis.

Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study.

Background: Nerinetide is a neuroprotectant effective in preclinical models of acute ischaemic stroke when administered within 3 h of onset. However, the clinical evaluation of neuroprotectants in this short timeframe is challenging. We sought to establish the feasibility, safety, and effectiveness of nerinetide when given before hospital arrival within 3 h of symptom onset of suspected stroke.

Phages carry orphan antitoxin-like enzymes to neutralize the DarTG1 toxin-antitoxin defense system.

The astounding number of anti-phage defenses encoded by bacteria is countered by an elaborate set of phage counter-defenses, though their evolutionary origins are often unknown. Here, we report the discovery of an orphan antitoxin counter-defense element in T4-like phages that can overcome the bacterial toxin-antitoxin phage defense system, DarTG1. The DarT1 toxin, an ADP-ribosyltransferase, modifies phage DNA to prevent replication while its cognate antitoxin, DarG1, is a NADAR superfamily ADP-ribosylglycohydrolase that reverses these modifications in uninfected bacteria.

Disrupted callosal connectivity underlies long-lasting sensory-motor deficits in an NMDA receptor antibody encephalitis mouse model.

N-methyl-d-aspartate (NMDA) receptor-mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long-term effects of exposure to a patient-derived GluN1-specific mAb during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity.

Relationship between Shoulder Pain, Trunk and Lower Limb Pain in Overhead Athletes: A Systematic Review with Meta-analysis.

Background: Forty-nine percent of overhead athletes suffer from shoulder pain. Throwing movements require the participation of all components of the kinetic chain to reduce risk for shoulder overuse. Thus, limited lower limb range of motion or weakness has been identified as a risk factor for shoulder pain in overhead athletes.