BACKGROUND: The associations between sleep patterns or behaviors and the risk of cirrhosis and the influence of genetic susceptibility on these associations among NAFLD participants remain inadequately elucidated.
METHODS: This study conducted a prospective follow-up of 112,196 NAFLD participants diagnosed at baseline from the UK Biobank cohort study. Five sleep behaviors were collected to measure a healthy sleep score. Five genetic variants were used to construct a polygenic risk score. We used Cox proportional hazard model to assess hazard ratios (HR) and 95% confidence intervals (CIs) for incidence of cirrhosis.
RESULTS: During the follow-up, 592 incident cirrhosis cases were documented. Healthy sleep pattern was associated with reduced risk of cirrhosis in a dose-response manner (ptrend < 0.001). Participants with favourable sleep score (versus unfavourable sleep score) had an HR of 0.55 for cirrhosis risk (95% CI 0.39-0.78). Multivariable-adjusted HRs (95% CIs) of cirrhosis incidence for NAFLDs with no frequent insomnia, sleeping for 7-8 h per day, and no excessive daytime dozing behaviors were 0.73 (0.61-0.87), 0.79 (0.66-0.93), and 0.69 (0.50-0.95), respectively. Compared with participants with favourable sleep pattern and low genetic risk, those with unfavourable sleep pattern and high genetic risk had higher risks of cirrhosis incidence (HR 3.16, 95% CI 1.88-5.33). In addition, a significant interaction between chronotype and genetic risk was detected for the incidence of cirrhosis (p for multiplicative interaction = 0.004).
CONCLUSIONS: An association was observed between healthy sleep pattern and decreased risk of cirrhosis among NAFLD participants, regardless of low or high genetic risk.

BACKGROUND: Unhealthy sleep behaviors are associated with higher risks of osteoporosis (OP), while prospective evidence is limited. This study aimed to prospectively investigate this association, quantify the attributable burden of OP incidence reduction due to unhealthy sleep behaviors, and explore potential modifications by genetic risk factors.
METHODS: This longitudinal cohort study was conducted utilizing data from the UK Biobank, comprising 293,164 participants initially free of OP and with requisite sleep behaviors data at baseline. We followed the participants after recruitment until November 30, 2022, to ascertain incident OP. We assessed the associations of five sleep behaviors including sleep duration, chronotype, insomnia, daytime napping, and morning wake-up difficulties, as well as sleep behavior patterns identified based on the above sleep behaviors, with the risk of OP, using Cox models adjusted for multiple confounders. The analyses were then performed separately among individuals with different OP susceptibility, indexed by standard polygenetic risk scores(PRS) for OP. Our secondary outcome was OP with pathologic fracture. Subgroup and sensitivity analyses were performed. Additionally, attributable risk percent in the exposed population (AR%) and population attributable fraction (PAF) of sleep behaviors were calculated.
RESULTS: Over a median follow-up of 13.7 years, 8253 new-onset OP cases were documented. Unhealthy sleep behaviors, such as long or short sleep duration, insomnia, daytime napping, morning wake-up difficulties, and unhealthy sleep patterns, were associated with elevated risks of OP (HRs ranging from 1.14 to 1.46, all P-value <0.001) compared to healthy sleep behaviors. Similar associations were observed for OP with pathologic fractures. Insomnia exhibited the largest AR% of 39.98 % (95%CI: 36.46, 43.31) and PAF of 33.25 % (95%CI: 30.00, 36.34) among healthy sleep patterns and components. A statistically significant multiplicative interaction was noted between sleep behaviors and OP PRS on OP risk (all P-interaction <0.001).
CONCLUSIONS: Four unhealthy sleep behaviors and sleep behavior patterns were associated to increased OP risk, with insomnia contributing the most to OP incidence, while genetic risk for OP modified this association. These findings underscore the crucial role of adhering to healthy sleep behaviors for effective OP prevention.

UNASSIGNED: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.
UNASSIGNED: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
UNASSIGNED: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
UNASSIGNED: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
UNASSIGNED: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.

UNASSIGNED: Although previous studies of sleep-related behaviors in relation to primary open-angle glaucoma (POAG) have been noted, the causal relationship remains unclear. The purpose of our present study was to investigate the relationships of genetically predicted sleep traits with POAG using a two-sample bidirectional Mendelian randomization (MR) method.
UNASSIGNED: Summary-level data collected from publicly available genome-wide association studies (GWAS) of European decent were applied for the bidirectional MR analysis. After quality control steps, independent single-nucleotide polymorphisms for eight sleep behaviors and POAG were selected as the genetic instruments. The inverse-variance weighted (IVW) approach was adopted as the primary method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy. Multivariable MR (MVMR) was used to assess the direct effect of sleep traits on POAG, after adjusting for several confounding factors.
UNASSIGNED: Our investigation revealed a positive correlation between genetically predicted ease of getting up in the morning and sleep duration and POAG using the IVW method (odds ratio (OR)=1.78, 95% confidence interval (CI):1.29-2.46, P = 4.33× 10-4; OR = 1.66, 95% CI:1.18-2.34, P = 3.38×10-3, respectively). Other supplementary MR methods also confirmed similar results. Moreover, the MVMR results also revealed that the adverse effects of these two sleep traits on POAG persisted after adjusting for body mass index, smoking, drinking, and education (all P < 0.05). Conversely, the relationships between genetic liability of POAG and different sleep behaviors were not statistically significant in the reverse-direction MR estimate (all P > 0.05).
UNASSIGNED: Our study demonstrated that genetic prediction of getting up easily in the morning or sleep duration were associated with a higher risk of POAG, but not vice versa, in a European population. Further validation and clinical interventions are required to offer potential strategies to prevent and manage POAG.

A negative attitude toward sleep has greatly affected sleep habits. In addition to contributing to physical and metabolic disorders, poor sleep quality may cause emotional disturbances. This study aimed to measure sleep behavior and factors contributing to poor sleep quality in the Madinah region, Saudi Arabia. We also assessed whether the use of sleeping aids improved peoples sleep. Three hundred and ninety-nine adults in the Madinah region of Saudi Arabia participated in this cross-sectional study. Three data domains were collected using an online questionnaire between 30 January and 26 April 2022. In the first domain, the characteristics of participants were discussed. In the second domain, questions about sleep behavior were asked. In the third domain, we examined the types, frequency, and impact of sleep aid use. Out of the 399 participants, 154 (38.59%) reported sleep problems. A total of 64.94% of the 154 participants blamed stress as the leading cause of their sleep disorders, and 74.68% of those with sleep problems reported reduced productivity. Among those who reported having sleep problems, 46.10% used sleep aids, with Panadol night (antihistamine) being the most used, 49.30%, followed by Melatonin at 39.44%. Sleep quality improved by 67.6% among those who used sleep aids. A total of 71.8% of the participants think it is not safe to use sleep aids in the long term. Our findings suggest that sleep problems are a prevalent concern in Madinah, Saudi Arabia, and even though the use of sleep aids improved sleep quality, it should be considered an emerging and important public health objective in Saudi Arabia. Further studies are needed to evaluate sleep quality and the level of sleep aid usage among other Saudi Arabian regions.

Sleep insufficiency is associated with increased risk of morbidity and mortality. Bedtime procrastination, or the needless and voluntary delay in sleep, is a sleep-related behavior which may interfere with sleep health. The objective of this study is to comprehensively examine the daily associations among bedtime procrastination and measures of sleep regularity, satisfaction, timing, efficiency, and duration.
Two hundred and eighty young adult participants (79% female; Mage=24.4) completed daily sleep diaries and measures of bedtime procrastination and sleep restoration over 14days, in addition to measures of chronotype. Multilevel models were constructed to examine the associations between bedtime procrastination and sleep health.
Greater bedtime procrastination was associated with poorer sleep health, including poorer self-reported sleep restoration, later sleep timing, less efficient sleep, and shorter sleep duration. These associations were significant at both within- and between-person levels, and persisted after statistically adjusting for individuals\' chronotypes.
This study offers bedtime procrastination as a putative mechanism for poor sleep health and finds that the associated risk of poor sleep from bedtime procrastination is independent of chronotype. Results presented here suggest that bedtime procrastination may be a relevant behavior in the development or maintenance of sleep and sleep-related disorders.

UNASSIGNED: Vitamin D has been known to be associated with asthma, particularly in children, while the evidence among adults is limited and inconclusive. This study aimed to investigate the association between serum, vitamin D concentrations, and the incidence of adult-onset asthma and also the modified effect caused by sleep patterns and genetic risks.
UNASSIGNED: A prospective cohort study with 307,872 participants aged between 37 and 73 years was conducted based on the UK Biobank, with a median follow-up of 12 years. The Cox proportional hazard model was applied to evaluate the association between vitamin D status and incident adult-onset asthma, and the modified effect was investigated by conducting stratified analysis according to sleep pattern score and genetic risk score, and subgroup analyses were performed by sex, age, BMI, and smoking status as well.
UNASSIGNED: Individuals with optimal vitamin D concentration were associated with 11.1% reduced risk of incident asthma compared to those participants with deficient vitamin D (HR = 0.889; 95% CI: 0.820-0.964; p = 0.005). Moreover, stratification analysis demonstrated that the protective effect of vitamin D on asthma risk was modified by sleep patterns or genetic susceptibility, with the strongest protective effect being observed in the subpopulation with a moderate sleep pattern (HR = 0.883; 95% CI: 0.797-0.977; p = 0.016) and a moderate genetic risk (HR = 0.817; 95% CI: 0.711-0.938; p = 0.004). In subgroup analyses, the protective effect of optimal vitamin D levels was only significant among men, individuals younger than 60 years of age, overweight individuals, and current or previous smokers.
UNASSIGNED: Increased serum vitamin D levels were associated with a lower risk of incident adult-onset asthma, and this association was modified by sleep patterns and genetic predisposition to some extent.

The association between sleep behaviors and gout risk remains uncertain. We aimed to evaluate the relationship of sleep patterns based on a combination of five major sleep behaviors with the risk of new-onset gout, and to explore whether genetic risks of gout may modify this association in the general population.
403,630 participants without gout at baseline in UK Biobank were included. A healthy sleep score was created by combining five major sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Genetic risk score for gout was calculated based on 13 single nucleotide polymorphisms (SNPs) with independently significant genome-wide association with gout. The primary outcome was new-onset gout.
During a median follow-up duration of 12.0 years, 4270 (1.1%) participants developed new-onset gout. Compared to participants with poor sleep patterns (0 ≤ healthy sleep score ≤ 1), those with healthy sleep patterns (4 ≤ healthy sleep score ≤ 5) had a significantly lower risk of new-onset gout (HR, 0.79; 95% CI: 0.70-0.91). Moreover, the significantly lower risk of new-onset gout associated with healthy sleep patterns were mainly found in those with low (HR, 0.68; 95%CI: 0.53-0.88), or intermediate genetic risks of gout (HR, 0.78; 95%CI: 0.62-0.99), but not in participants with high genetic risks of gout (HR, 0.95; 95%CI: 0.77-1.17) (P for interaction =0.043).
Among the general population, a healthy sleep pattern was associated with a significant lower of new-onset gout risk, especially in those with lower genetic risks of gout.

Bedtime procrastination, or delays in bedtime not attributable to external obligations, is a behavioral tendency that undermines sleep and is conceptualized as a consequence of poor self-regulation. Prior studies investigating the mechanistic role of self-regulation in bedtime procrastination relied on cross-sectional methods and self-reported self-regulation. The present study examined the association between bedtime procrastination and both objective and self-reported executive functioning (EF) as indices of self-regulation, as well as the moderating role of chronotype, using methods that examined these associations at the daily level.
A total of 273 young adult participants (78% female; Mage = 24.4) completed daily measures of objective EF (i.e., Stroop task), self-reported EF (i.e., self-reported cognitive, behavioral, and emotional regulation difficulties), and bedtime procrastination over 14 days, in addition to measures of chronotype. Multilevel models were constructed to examine the associations between bedtime procrastination and EF, as well as EF-chronotype interactions.
Poorer daily objective EF and self-reported behavioral regulation were associated with greater same-night bedtime procrastination. Additionally, poorer subjective cognitive and emotional regulation were associated with greater average bedtime procrastination across 14 days. Later chronotypes reported greater bedtime procrastination than early chronotypes.
The present study provides support for the association between EF and bedtime procrastination, but finds no evidence for the moderating role of chronotype in this association. Results suggest that some EF processes may be more relevant to bedtime procrastination than others. Current findings have implications for assessment and intervention for this consequential sleep-relevant behavioral tendency.

BACKGROUND: We aimed to investigate the prospective association of individual and combined sleep behaviors and mental health (psychological distress and neuroticism) with incident irritable bowel syndrome (IBS).
METHODS: A total of 302,839 participants without prior IBS in the UK Biobank were enrolled. A healthy sleep score was created according to five sleep factors and defined the low-risk groups as follows: sleep 7-8 h/day, early chronotype, never/rarely insomnia, no snoring, and no frequent excessive daytime sleepiness. Psychological distress and neuroticism were ascertained using the Patient Health Questionnaire and the Eysenck Personality Questionnaire-Revised Short Form, respectively. The primary outcome was incident IBS, based on self-report or linkage to death register and/or primary care and/or hospital admission data.
RESULTS: During a median follow-up of 12.0 years, 5574 participants developed IBS. Overall, low-risk sleep behaviors and a healthy sleep score (per one point increment, HR, 0.81, 95%CI, 0.79-0.83) were associated with a lower risk of incident IBS, 29.4 %-32.4 % of which was mediated by mental health. Psychological distress (per one point increment, HR, 1.16, 95%CI, 1.14-1.17) and neuroticism (HR, 1.11, 95%CI, 1.10-1.12) were positively associated with incident IBS, and healthy sleep scores mediated 8.3 %-9.7 % of the association. Moreover, participants with lowest healthy sleep score/highest mental health score and higher genetic risk of IBS showed the highest risk of incident IBS.
CONCLUSIONS: Sleep behaviors and mental health were assessed by self-reported questionnaires.
CONCLUSIONS: Healthy sleep scores and low psychological distress/neuroticism were associated with a lower risk of IBS, regardless of genetic predisposition.