Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.

Heart failure causes sleepless nights.

Cardiac dysfunction triggers immune-mediated loss of pineal gland melatonin release.

Circadian gene × environment perturbations influence alcohol drinking in Cryptochrome-deficient mice.

Alcohol use disorder (AUD) is a widespread addiction disorder with severe consequences for health. AUD patients often suffer from sleep disturbances and irregular daily patterns. Conversely, disruptions of circadian rhythms are considered a risk factor for AUD and alcohol relapses. In this study, we investigated the extent to which circadian genetic and environmental disruptions and their interaction alter alcohol drinking behaviour in mice. As a model of genetic circadian disruption, we used Cryptochrome1/2-deficient (Cry1/2-/- ) mice with strongly suppressed circadian rhythms and found that they exhibit significantly reduced preference for alcohol but increased incentive motivation to obtain it. Similarly, we found that low circadian SCN amplitude correlates with reduced alcohol preference in WT mice. Moreover, we show that the low alcohol preference of Cry1/2-/- mice concurs with high corticosterone and low levels of the orexin precursor prepro-orexin and that WT and Cry1/2-/- mice respond differently to alcohol withdrawal. As a model of environmentally induced disruption of circadian rhythms, we exposed mice to a "shift work" light/dark regimen, which also leads to a reduction in their alcohol preference. Interestingly, this effect is even more pronounced when genetic and environmental circadian perturbations interact in Cry1/2-/- mice under "shift work" conditions. In conclusion, our study demonstrates that in mice, disturbances in circadian rhythms have pronounced effects on alcohol consumption as well as on physiological factors and other behaviours associated with AUD and that the interaction between circadian genetic and environmental disturbances further alters alcohol consumption behaviour.

Nurses' experiences and preferences around shift patterns: A scoping review.

OBJECTIVE: To explore the evidence on nurses' experiences and preferences around shift patterns in the international literature. DATA SOURCES: Electronic databases (CINHAL, MEDLINE and Scopus) were searched to identify primary studies up to April 2021. METHODS: Papers reporting qualitative or quantitative studies exploring the subjective experience and/or preferences of nurses around shift patterns were considered, with no restrictions on methods, date or setting. Key study features were extracted including setting, design and results. Findings were organised thematically by key features of shift work. RESULTS: 30 relevant papers were published between 1993 and 2021. They contained mostly qualitative studies where nurses reflected on their experience and preferences around shift patterns. The studies reported on three major aspects of shift work: shift work per se (i.e. the mere fact of working shift), shift length, and time of shift. Across all three aspects of shift work, nurses strive to deliver high quality of care despite facing intense working conditions, experiencing physical and mental fatigue or exhaustion. Preference for or adaptation to a specific shift pattern is facilitated when nurses are consulted before its implementation or have a certain autonomy to self-roster. Days off work tend to mitigate the adverse effects of working (short, long, early or night) shifts. How shift work and patterns impact on experiences and preferences seems to also vary according to nurses' personal characteristics and circumstances (e.g. age, caring responsibilities, years of experience). CONCLUSIONS: Shift patterns are often organised in ways that are detrimental to nurses' health and wellbeing, their job performance, and the patient care they provide. Further research should explore the extent to which nurses' preferences are considered when choosing or being imposed shift work patterns. Research should also strive to better describe and address the constraints nurses face when it comes to choice around shift patterns.

Human circadian variations.

Circadian rhythms, present in most phyla across life, are biological oscillations occurring on a daily cycle. Since the discovery of their molecular foundations in model organisms, many inputs that modify this tightly controlled system in humans have been identified. Polygenic variations and environmental factors influence each person's circadian rhythm, contributing to the trait known as chronotype, which manifests as the degree of morning or evening preference in an individual. Despite normal variation in chronotype, much of society operates on a "one size fits all" schedule that can be difficult to adjust to, especially for certain individuals whose endogenous circadian phase is extremely advanced or delayed. This is a public health concern, as phase misalignment in humans is associated with a number of adverse health outcomes. Additionally, modern technology (such as electric lights and computer, tablet, and phone screens that emit blue light) and lifestyles (such as shift or irregular work schedules) are disrupting circadian consistency in an increasing number of people. Though medical and lifestyle interventions can alleviate some of these issues, growing research on endogenous circadian variability and sensitivity suggests that broader social changes may be necessary to minimize the impact of circadian misalignment on health.

Demographic, psychological, chronobiological, and work-related predictors of sleep disturbances during the COVID-19 lockdown in Italy.

The first COVID-19 contagion wave caused unprecedented restraining measures worldwide. In Italy, a period of generalized lockdown involving home confinement of the entire population was imposed for almost two months (9 March-3 May 2020). The present is the most extensive investigation aimed to unravel the demographic, psychological, chronobiological, and work-related predictors of sleep disturbances throughout the pandemic emergency. A total of 13,989 Italians completed a web-based survey during the confinement period (25 March-3 May). We collected demographic and lockdown-related work changes information, and we evaluated sleep quality, insomnia and depression symptoms, chronotype, perceived stress, and anxiety using validated questionnaires. The majority of the respondents reported a negative impact of confinement on their sleep and a delayed sleep phase. We highlighted an alarming prevalence of sleep disturbances during the lockdown. Main predictors of sleep disturbances identified by regression models were: female gender, advanced age, being a healthcare worker, living in southern Italy, confinement duration, and a higher level of depression, stress, and anxiety. The evening chronotype emerged as a vulnerability factor, while morning-type individuals showed a lower predisposition to sleep and psychological problems. Finally, working from home was associated with less severe sleep disturbances. Besides confirming the role of specific demographic and psychological factors in developing sleep disorders during the COVID-19 pandemic, we propose that circadian typologies could react differently to a particular period of reduced social jetlag. Moreover, our results suggest that working from home could play a protective role against the development of sleep disturbances during the current pandemic emergency.

Deciphering the Interacting Mechanisms of Circadian Disruption and Alzheimer's Disease.

Alzheimer's disease (AD) is one of the crucial causative factors for progressive dementia. Neuropathologically, AD is characterized by the extracellular accumulation of amyloid beta plaques and intracellular neurofibrillary tangles in cortical and limbic regions of the human brain. The circadian system is one of the many affected physiological processes in AD, the dysfunction of which may reflect in the irregularity of the sleep/wake cycle. The interplay of circadian and sleep disturbances inducing AD progression is bidirectional. Sleep-associated pathological alterations are frequently evident in AD. Understanding the interrelation between circadian disruption and AD may allow for earlier identification of AD pathogenesis as well as better suited approaches and potential therapies to combat dementia. In this article, we examine the existing literature related to the molecular mechanisms of the circadian clock and interacting mechanisms of circadian disruption and AD pathogenesis.

Effects of work organization on the occurrence and resolution of sleep disturbances among night shift workers: a longitudinal observational study.

This study aimed to investigate the association between work organization and the trajectories of insomnia patterns among night shift workers in a hospital. The health examination data of hospital workers, recorded from January 2014 to December 2018, were collected; 6765 records of 2615 night shift workers were included. Insomnia was defined as a score of ≥ 15 on the Insomnia Severity Index (ISI). Participants were categorized into five groups according to insomnia patterns derived from the analysis of their ISI scores. Work organization and socio-demographic characteristics were also investigated. Generalized estimating equation models and linear mixed models were constructed to analyze the longitudinal data. Of the total participants, 53.0% reported insomnia at least once during the follow-up period. The lack of nap opportunities and work-time control was associated with the occurrence of insomnia, whereas more than 5 years of shift work experience was related to the resolution of insomnia. All work-related factors were significantly related to insomnia risk; however, the effects were not significant in the sustained insomnia group. Although sleep problems are inevitable in night shift workers, well-designed work schedules and better work organization can help reduce the occurrence of insomnia among them.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r = -.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = -.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

A field investigation of the relationship between rotating shifts, sleep, mental health and physical activity of Australian paramedics.

Paramedics working on a rotating shift are at an increased risk of developing chronic health issues due to continuous circadian rhythm disruption. The acute effects of shift rotation and objectively measured sleep have rarely been reported in paramedics. This study investigated the relationships between a rotating shift schedule and sleep (using actigraphy), subjective reports of sleepiness, mood, stress and fatigue. Galvanic Skin Response, energy expenditure and physical activity (BodyMedia SenseWear Armband) were also recorded across the shift schedule. Paramedics were monitored for a period of eight consecutive days across pre-shift, day shift, night shift, and 2 days off. Fifteen paramedics (M age = 39.5 and SD = 10.7 years) who worked rotational shifts experienced sleep restriction during night shift compared to pre-shift, day shift and days off (p < 0.001). Night shift was also associated with higher levels of stress (p < 0.05), fatigue (p < 0.05), and sleepiness (p < 0.05). One day off was related to a return to pre-shift functioning. Such shift-related issues have a compounding negative impact on an already stressful occupation with high rates of physical and mental health issues. Therefore, there is an urgent need to investigate methods to reduce rotating shift burden on the health of paramedics. This could be through further research aimed at providing recommendations for shift work schedules with sufficient periods for sleep and recovery from stress.

Optimising sleep and performance during night float: A systematic review of evidence and implications for graduate medical education trainees.

Graduate medical education (GME) training commonly requires residents and fellows to engage in night float shift work. This review aims to assess the effectiveness of interventions for trainees when preparing for, completing, and recovering from working night float shifts. We reviewed all available studies published prior to September 2019 using PubMed, Scopus, CINAHL, the Cochrane library, PsycINFO, and Google Scholar databases. We included all original, primary research articles assessing either non-pharmacological or pharmacological interventions on the chronobiological and physiological effects of night float shift work among GME trainees. Five studies (n = 179 patients) met inclusion criteria. Interventions included melatonin in the morning before sleep after night float shifts, napping during night float shifts, modafinil after a night of sleep deprivation, and caffeinated energy drinks after 6 consecutive night float shifts. Melatonin improved one measure of attention. A 2-hr nap was associated with improved speed related to task switching. Modafinil improved performance in tests of cognition. Caffeinated energy drinks led to improvement in select driving performance variables and reaction time. Effect sizes for outcome variables were calculated. Heterogeneity among the studies precluded combining the data in a meta-analysis. According to GRADE criteria, the quality of the evidence in these studies was low or very low. Our findings suggest GME trainees may benefit from utilising a limited number of interventions when preparing for or recovering from night float shift work. More investigation is needed to identify interventions that could help GME trainees adapt to and recover from working night float shifts.

Ageing shift workers' sleep and working-hour characteristics after implementing ergonomic shift-scheduling rules.

We studied whether implementing binding ergonomic shift-scheduling rules change ageing (≥45 years) social and healthcare employees' (mean age 52.5 years, 95% women) working-hour characteristics (e.g. weekly working hours, number and length of night shifts, and short shift intervals) and sleep. We compared an intervention group (n = 253) to a control group (n = 1,234) by survey responses (baseline 2007/2008, follow-up 2012) and objective working-hour characteristics (intervention group n = 159, control group n = 379) from 91 days preceding the surveys. Changes in working-hour characteristics were analysed with repeated measures general linear models. The fully adjusted model (sociodemographics and full-/part-time work) showed that proportion of short shift intervals (<11 hr, p = .033) and weekend work (p = .01) decreased more in the intervention than in the control group. Changes in sleep outcomes were analysed with generalised logit model to binomial and multinomial variables. The fully adjusted model (sociodemographics, full-/part-time work, job strain, health behaviours, and perceived health) revealed higher odds in the intervention group for long sleep (≥9 hr; odds ratio [OR] 5.53, 95% confidence interval [CI] 2.21-13.80), and lower odds of short sleep (<6 hr; OR 0.72, 95% CI 0.57-0.92), having at least two sleep difficulties often (OR 0.55, 95% CI 0.43-0.70), and more specifically difficulties in falling asleep (OR 0.56, 95% CI 0.41-0.77), waking up several times per night (OR 0.43, 95% CI 0.34-0.55), difficulties in staying asleep (OR 0.64, 95% CI 0.49-0.82), and non-restorative sleep (OR 0.70, 95% CI 0.54-0.90) than the control group. In conclusion, implementation of ergonomic shift-scheduling rules resulted in minor changes in ageing employees' objective working hours and a consistent buffering effect against worsening of sleep.

Short sleep duration and high exposure to quick returns are associated with impaired everyday memory in shift workers.

PURPOSE: To investigate the relationship between self-reported everyday memory problems the last month, and: (a) shift work schedule, (b) night shifts and quick returns worked the last year, and (c) sleep duration the last month. METHODS: In all, 1,275 nurses completed the Everyday Memory Questionnaire - revised, and answered questions about shift work exposure and sleep duration. We performed multiple linear regression analyses with memory score as dependent variable, and the shift work exposure variables as well as sleep duration as predictors, while adjusting for potential confounders. FINDINGS: High exposure to quick returns (ß = .10, p < .05) and short sleep duration (ß = .10, p < .05) were both positively associated with memory problems, whereas shift work schedule, long sleep duration, night shift exposure, and low and moderate exposure to quick returns were not. DISCUSSION: Frequent insufficient time for rest between shifts as well as short sleep was associated with poorer everyday memory.

Accelerometry-assessed sleep duration and timing in late childhood and adolescence in Scottish schoolchildren: A feasibility study.

Children and adolescents commonly suffer from sleep and circadian rhythm disturbances, which may contribute to poorer mental health and wellbeing during this critical developmental phase. Many studies however rely on self-reported sleep measures. This study assessed whether accelerometry data collection was feasible within the school setting as a method for investigating the extent of sleep and circadian disruption, and associations with subjective wellbeing, in Scotland. Fourteen days of wrist-worn accelerometry data were collected from 69 pupils, aged 10-14 years. Objective measures of sleep timing, sleep duration and circadian rest-activity patterns were derived. Questionnaires assessed subjective sleep timing, depressive symptoms, and experiences of wearing the accelerometer. Pupils slept on average less than 8 hours per night, failing to meet standard age-specific recommendations. Sleep timing was later and duration longer on weekends compared to weekdays (B = 0.87, 95% confidence interval (CI) 0.70, 1.04; B = 0.49, 95% CI 0.29, 0.69), indicating social jetlag. Lower daytime activity was correlated with higher depressive symptoms (r = -0.84, p = 0.008). Compared to primary school pupils, secondary pupils had shorter sleep window duration and lower circadian relative amplitude. Over half of participants reported some discomfort/inconvenience wearing the accelerometer. These data highlight that inadequate sleep is prevalent in this sample of schoolchildren. Future, larger scale investigations will examine in more detail the associations between sleep, circadian function and physical activity with mental health and wellbeing.

Home-EEG assessment of possible compensatory mechanisms for sleep disruption in highly irregular shift workers - The ANCHOR study.

STUDY OBJECTIVES: While poor sleep quality has been related to increased risk of Alzheimer's disease, long-time shift workers (maritime pilots) did not manifest evidence of early Alzheimer's disease in a recent study. We explored two hypotheses of possible compensatory mechanisms for sleep disruption: Increased efficiency in generating deep sleep during workweeks (model 1) and rebound sleep during rest weeks (model 2). METHODS: We used data from ten male maritime pilots (mean age: 51.6±2.4 years) with a history of approximately 18 years of irregular shift work. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). A single lead EEG-device was used to investigate sleep in the home/work environment, quantifying total sleep time (TST), deep sleep time (DST), and deep sleep time percentage (DST%). Using multilevel models, we studied the sleep architecture of maritime pilots over time, at the transition of a workweek to a rest week. RESULTS: Maritime pilots reported worse sleep quality in workweeks compared to rest weeks (PSQI = 8.2±2.2 vs. 3.9±2.0; p<0.001). Model 1 showed a trend towards an increase in DST% of 0.6% per day during the workweek (p = 0.08). Model 2 did not display an increase in DST% in the rest week (p = 0.87). CONCLUSIONS: Our findings indicated that increased efficiency in generating deep sleep during workweeks is a more likely compensatory mechanism for sleep disruption in the maritime pilot cohort than rebound sleep during rest weeks. Compensatory mechanisms for poor sleep quality might mitigate sleep disruption-related risk of developing Alzheimer's disease. These results should be used as a starting point for future studies including larger, more diverse populations of shift workers.

Circadian misalignment increases mood vulnerability in simulated shift work.

Night shift work can associate with an increased risk for depression. As night workers experience a 'misalignment' between their circadian system and daily sleep-wake behaviors, with negative health consequences, we investigated whether exposure to circadian misalignment underpins mood vulnerability in simulated shift work. We performed randomized within-subject crossover laboratory studies in non-shift workers and shift workers. Simulated night shifts were used to induce a misalignment between the endogenous circadian pacemaker and sleep/wake cycles (circadian misalignment), while environmental conditions and food intake were controlled. Circadian misalignment adversely impacted emotional state, such that mood and well-being levels were significantly decreased throughout 4 days of continuous exposure to circadian misalignment in non-shift workers, as compared to when they were under circadian alignment (interaction of "circadian alignment condition" vs. "day", mood: p < 0.001; well-being: p < 0.001; adjusted p-values). Similarly, in shift workers, mood and well-being levels were significantly reduced throughout days of misalignment, as compared to circadian alignment (interaction of "circadian alignment condition" vs. "day", mood: p = 0.002; well-being: p = 0.002; adjusted p-values). Our findings indicate that circadian misalignment is an important biological component for mood vulnerability, and that individuals who engage in shift work are susceptible to its deleterious mood effects.

Changes in performance and bio-mathematical model performance predictions during 45 days of sleep restriction in a simulated space mission.

Lunar habitation and exploration of space beyond low-Earth orbit will require small crews to live in isolation and confinement while maintaining a high level of performance with limited support from mission control. Astronauts only achieve approximately 6 h of sleep per night, but few studies have linked sleep deficiency in space to performance impairment. We studied crewmembers over 45 days during a simulated space mission that included 5 h of sleep opportunity on weekdays and 8 h of sleep on weekends to characterize changes in performance on the psychomotor vigilance task (PVT) and subjective fatigue ratings. We further evaluated how well bio-mathematical models designed to predict performance changes due to sleep loss compared to objective performance. We studied 20 individuals during five missions and found that objective performance, but not subjective fatigue, declined from the beginning to the end of the mission. We found that bio-mathematical models were able to predict average changes across the mission but were less sensitive at predicting individual-level performance. Our findings suggest that sleep should be prioritized in lunar crews to minimize the potential for performance errors. Bio-mathematical models may be useful for aiding crews in schedule design but not for individual-level fitness-for-duty decisions.

Relationship between Sleep and Hedonic Appetite in Shift Workers.

Short and/or poor sleep are established behavioral factors which can contribute to excess food intake, and emerging evidence suggests that disturbed circadian rhythms may also impact food intake regulation. Together, disturbed sleep and circadian rhythms may help explain the excess risk for obesity seen in shift workers. To date, however, the details of how shift work may impact food intake regulation are still not fully defined. Here we examined the relationship between sleep characteristics and hedonic control of appetite in shift workers. A total of 63 shift workers (mean (M) age: 36.7 years, standard deviation (SD): 12.0; 59% women) completed an online survey comprising self-reported measures of body weight regulation, sleep (Pittsburgh Sleep Quality Index, Sleep Hygiene Index), and hedonic control of appetite (Food Craving Inventory, Power of Food Scale). Seventy-one percent reported some weight change since starting shift work, and 84% of those reported weight gain (M = +11.3 kg, SD = 9.1). Worse sleep quality and shorter sleep duration were associated with more food cravings, and worse sleep quality and hygiene were associated with higher appetitive drive to consume palatable food (greater hedonic drive). This preliminary study suggests hedonic pathways are potentially contributing to weight gain in shift workers with disturbed sleep.

Sleep in autism: A biomolecular approach to aetiology and treatment.

People with autism spectrum disorder (ASD) commonly experience other comorbidities. Studies indicate that between 50% and 83% of individuals with ASD have sleep problems or disorders. The most commonly reported sleep problems are: (a) insomnia symptoms including the inability to get to sleep or stay asleep; and (b) circadian rhythm sleep-wake disorders, defined as a misalignment between the timing of endogenous circadian rhythms and the external environment. The circadian system provides timing information for the sleep-wake cycle that is regulated by the interaction of an endogenous processes (circadian - Process C, and homeostatic - Process S) and synchronizing agents (neurohormones and neurotransmitters), which produce somnogenic activity. A clinical priority in ASD is understanding the cause of these sleep problems in order to improve treatment outcomes. This review approaches sleep in autism from several perspectives: Sleep-wake mechanisms and problems, and brain areas and molecules controlling sleep (e.g., GABA and melatonin) and wake maintenance (e.g., serotonin, acetylcholine and glutamate). Specifically, this review examines how altered sleep structure could be related to neurobiological alterations or genetic mutations and the implications this may have for potential pharmacological treatments in individuals with ASD.

Circadian Rhythm Sleep-Wake Disorders.

PURPOSE OF REVIEW: This article provides an overview of circadian physiology and discusses common presentations and treatment strategies for the circadian rhythm sleep-wake disorders. RECENT FINDINGS: Circadian rhythms are present throughout the body, and appreciation for the role that circadian dysregulation plays in overall health is increasing, with mounting associations between circadian disruption and cardiometabolic disease risk. SUMMARY: It is important to recognize the ubiquitous role that circadian rhythms play throughout the brain and body. An understanding of circadian neurophysiology will provide insight into the means by which patients with a variety of neuropathologies at the level of the retina, optic nerve, or hypothalamus may also be at risk for circadian dysfunction.