A gut-secreted peptide suppresses arousability from sleep.

Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.

Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut.

The view that sleep is essential for survival is supported by the ubiquity of this behavior, the apparent existence of sleep-like states in the earliest animals, and the fact that severe sleep loss can be lethal. The cause of this lethality is unknown. Here we show, using flies and mice, that sleep deprivation leads to accumulation of reactive oxygen species (ROS) and consequent oxidative stress, specifically in the gut. ROS are not just correlates of sleep deprivation but drivers of death: their neutralization prevents oxidative stress and allows flies to have a normal lifespan with little to no sleep. The rescue can be achieved with oral antioxidant compounds or with gut-targeted transgenic expression of antioxidant enzymes. We conclude that death upon severe sleep restriction can be caused by oxidative stress, that the gut is central in this process, and that survival without sleep is possible when ROS accumulation is prevented. VIDEO ABSTRACT.

Completion Rates and Timeliness of Diagnostic Colonoscopies for Rectal Bleeding in Primary Care.

BACKGROUND: Rectal bleeding is the most common presenting symptom of colorectal cancer, and guidelines recommend timely follow-up, usually with colonoscopy to ensure timely diagnoses of colorectal cancer. OBJECTIVE: Identify loop closure rates and vulnerable process points for patients with rectal bleeding. DESIGN: Retrospective cohort study, using medical record review of patients aged ≥ 40 with index diagnosis of rectal bleeding at 2 primary practices-an urban academic practice and affiliated community health center, between January 1, 2018, and December 31, 2020. Patients were classified as having completed recommended follow-up workup ("closed loop") vs. not ("open loop"). Open loop patient cases were categorized into six types of process failures. PARTICIPANTS: A total of 837 patients had coded diagnoses of rectal bleeding within study window. Sixty-seven were excluded based on prior colectomy, clinical presentation more consistent with upper GI bleed, no rectal bleeding documented on chart review, or expired during the follow-up period, leaving 770 patients included. MAIN MEASURES: Primary outcomes were percentages of patient cases classified as "open loops" and distribution of these cases into six categories of process failure that were identified. KEY RESULTS: 22.3% of patients (N = 172) failed to undergo timely recommended workup for rectal bleeding. Largest failure categories were patients for whom no procedure was ordered (N = 62, 36%), followed by patients with procedures ordered but never scheduled (N = 44, 26%) or scheduled but subsequently cancelled or not kept (N = 31, 18%). While open loops increased after the onset of the COVID-19 pandemic, this difference was not significant within our study period. CONCLUSIONS: Significant numbers of patients presenting to primary care with rectal bleeding fail to undergo recommended workup. The majority either have no procedure ordered, or procedure ordered but never scheduled or cancelled and not kept, suggesting these are important failure modes to target in future interventions. Ensuring reliable ordering and processes for timely scheduling and completion of procedures represent critical areas for improving the diagnostic process for patients with rectal bleeding in primary care.