Sleep Disruption and Bone Health.

PURPOSE OF REVIEW: Review recent literature investigating the relationship between bone health and sleep/circadian disruptions (e.g., abnormal sleep duration, night shift work). RECENT FINDINGS: Short and long sleep are associated with low bone mineral density (BMD). Recent data from observational studies identified an increased risk of fracture in women with short sleep. Studies suggest that age, sex, weight change, and concurrent circadian misalignment may modify the effects of sleep restriction on bone metabolism. Interventional studies demonstrate alterations in bone metabolism and structure in response to circadian disruption that could underlie the increased fracture risk seen with night shift work. The effects of sleep and circadian disruption during adolescence may have lifelong skeletal consequences if they adversely impact bone modeling. Data suggest that short sleep and night shift work negatively impact bone metabolism and health. Rigorous studies of prevalent sleep and circadian disruptions are needed to determine mechanisms and develop prevention strategies to optimize lifelong skeletal health.

Examining the Relationships Between Sleep Physiology and the Gut Microbiome in Preclinical and Translational Research: Protocol for a Scoping Review.

BACKGROUND: Sleep is an instrumental behavioral state with evidence supporting its active role in brain function, metabolism, immune function, and cardiovascular systems. Research supports that there are pathways underlying the bidirectional communication between the brain and gastrointestinal system, also known as the "gut-brain axis." Primary research examining sleep and gut microbiome relationships continues to increase. Although current data include both preclinical and clinical research, gut microbiome results are reported through a wide range of metrics (alpha diversity, beta diversity, and bacterial compositional changes), which makes cross-study comparison challenging. Therefore, a synthesis of the research examining sleep and gut microbiome relationships is necessary to understand the state of the science and address gaps in the literature for future research. OBJECTIVE: In this paper, we outline a scoping review protocol to evaluate and synthesize preclinical and clinical primary research focused on the associations between sleep and the gut microbiome. METHODS: The search strategy was facilitated through a medical research librarian and involved electronic databases including PubMed/MEDLINE, Embase, Scopus, Web of Science, CENTRAL trials database, BIOSIS Citation Index, and the Zoological Record. Gray literature sources including medRxiv and bioRxiv preprint servers were also searched. Studies were screened according to the aims and exclusion and inclusion criteria of the protocol. After screening, data will be extracted and synthesized from the included studies according to predefined sleep and microbiome methodology metrics. RESULTS: The search strategy yielded 4622 references that were imported for study screening, and source screening was completed in May 2022 by 2 independent investigators, resulting in a total of 93 sources for data extraction and synthesis. The data synthesis table is expected to be completed by August 2022, and the results will be disseminated through paper submission by December 2022 and presented at conferences related to neuroscience, sleep physiology, bioinformatics, and the microbiome. CONCLUSIONS: A scoping review of preclinical and clinical research is needed to synthesize the growing data focused on the relationships between sleep and the gut microbiome. We expect the results of this synthesis will identify gaps in the literature and highlight pathways linking the gut-brain axis and sleep physiology to stimulate future research questions. TRIAL REGISTRATION: Open Science Framework 69TBR; https://osf.io/69tbr. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38605.

K-complexes are a sensitive marker of noise-related sensory processing during sleep: a pilot study.

STUDY OBJECTIVES: The primary aim of this study was to examine dose-response relationships between sound pressure levels (SPLs) and K-complex occurrence probability for wind farm and road traffic noise. A secondary aim was to compare K-complex dose-responses to manually scored electroencephalography arousals and awakenings. METHODS: Twenty-five participants underwent polysomnography recordings and noise exposure during sleep in a laboratory. Wind farm and road traffic noise recordings of 20-sec duration were played in random order at 6 SPLs between 33 and 48 dBA during established N2 or deeper sleep. Noise periods were separated with periods of 23 dBA background noise. K-complexes were scored using a validated algorithm. K-complex occurrence probability was compared between noise types controlling for noise SPL, subjective noise sensitivity, and measured hearing acuity. RESULTS: Noise-induced K-complexes were observed in N2 sleep at SPLs as low as 33 dBA (Odds ratio, 33 dBA vs 23 dBA, mean (95% confidence interval); 1.75 (1.16, 2.66)) and increased with SPL. EEG arousals and awakenings were only associated with noise above 39 dBA in N2 sleep. K-complexes were 2 times more likely to occur in response to noise than EEG arousals or awakenings. Subjective noise sensitivity and hearing acuity were associated with the K-complex occurrence, but not arousal or awakening. Noise type did not detectably influence K-complexes, EEG arousals, or awakening responses. CONCLUSION: These findings support that K-complexes are a sensitive marker of sensory processing of environmental noise during sleep and that increased hearing acuity and decreased self-reported noise sensitivity increase K-complex probability.

REM sleep behavior disorder in narcolepsy: A secondary form or an intrinsic feature?

Disrupted nighttime sleep is one of the pentad of symptoms defining Narcolepsy. REM sleep behavior disorder (RBD) largely contributes to night sleep disruption and narcolepsy is the most common cause of secondary RBD. However, RBD linked to narcolepsy (N-RBD) has been insufficiently characterized, leaving unsolved a number of issues. Indeed, it is still debated whether N-RBD is an intrinsic feature of narcolepsy, as indubitable for cataplexy, and therefore strictly linked to the cerebrospinal fluid hypocretin-1 (CSF hcrt-1) deficiency, or an associated feature, with a still unclear pathophysiology. The current review aims at rendering a comprehensive state-of-the-art of N-RBD, highlighting the open and unsettled topics. RBD reportedly affects 30-60% of patients with Narcolepsy type 1 (NT1), but it may be seen also in Narcolepsy type 2 (NT2). When compared to idiopathic/isolated RBD (iRBD), N-RBD has been reported to be characterized by less energetic and quieter episode, which however occur with the same probability in the first and the second part of the night and sometime even subcontinuously. N-RBD patients are generally younger than those with iRBD. N-RBD has been putatively linked to wake-sleep instability due to CSF hcrt-1 deficiency, but this latter by itself cannot explain completely the phenomenon as N-RBD has not been universally linked to low CSF hcrt-1 levels and it may be observed also in NT2. Therefore, other factors may probably play a role and further studies are needed to clarify this issue. In addition, therapeutic options have been poorly investigated.

Hypocretin-1 Levels Associate with Fragmented Sleep in Patients with Narcolepsy Type 1.

STUDY OBJECTIVES: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. METHODS: Actigraphy recording of 1-2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31-79 pg/mL. RESULTS: According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. CONCLUSIONS: Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep.