Clocks & Sleep, Volume 4, Issue 4 (December 2022) – 19 articles

Circadian rhythms of physiological processes, constantly being in a state of dynamic equilibrium and plastically associated with changes in environmental conditions, are the basis of homeostasis of an organism of human and other mammals. Violation of circadian rhythms due to significant disturbances in parameters of main environmental effectors (desynchronosis) leads to the development of pathological conditions and a more severe course of preexisting pathologies. We conducted the study of the ultrastructure of cells of mice transplantable malignant melanoma B16 under the condition of normal (fixed) lighting regime and under the influence of constant lighting. Results of the study show that melanoma B16 under fixed light regime represents a characteristic picture of this tumor—predominantly intact tissue with safe junctions of large, functionally active cells with highly irregular nuclei, developed organelles and a relatively low content of melanin. The picture of the B16 melanoma tissue structure and the ultrastructure of its cells under the action of constant lighting stand in marked contrast to the group with fixed light: under these conditions the tumor exhibits accelerated growth, a significant number of cells in the state of apoptosis and necrosis, ultrastructural signs of degradation of the structure and functions, and signs of embryonization of cells with the background of adaptation to oxygen deficiency. Full article

Background and Aim: Sleep-disordered breathing (SDB) is an extremely common disorder with a high impact on morbidity and mortality. The purpose of this study was to compare overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) and to highlight and understand the differences between them. Material and Methods: The study was conducted retrospectively on 132 subjects selected by consecutive sampling from those attending our unit for suspected SDB. After clinical evaluation as well as functional and sleep investigations, the population was divided according to diagnosis in OS and OHS; then, the clinical parameters of two groups were compared with different statistical analysis. Results: The subjects with OHS were younger and reported higher rated daytime sleepiness (p = 0.005). In addition, they presented more nocturnal respiratory events (apnea-hypopnea index (AHI) 63.61 ± 22.79 events·h⁻¹ vs. AHI_OS 42.21 ± 22.91 events·h⁻¹, p < 0.0001) at the sleep investigation as worse gas exchange during sleep leading to a higher percentage of nocturnal hypoxemia (p < 0.0001). In contrast, subjects with OS had more an impaired respiratory function. With regard to night-time ventilatory therapy, more subjects with OS were effectively treated with continuous positive airway pressure (CPAP) (p = 0.011), while more OHS were treated with auto-adjusting PAP (APAP) (14% vs. 1%, p = 0.008). Conclusions: The present study tried to establish a framework for OS and OHS because proper management of the two disorders would reduce their burden on healthcare. Full article

The cortisol awakening response (CAR) is a distinct rise in cortisol that occurs upon awakening that is thought to contribute to arousal, energy boosting, and anticipation. There is some evidence to suggest that inadequate sleep may alter the CAR, but the relationship between sleep duration and CAR has not been systematically examined. Healthy males (n = 111; age: 23.0 ± 3.6 yrs) spent 10 consecutive days/nights in a sleep laboratory. After a baseline night (9 h time in bed), participants spent either 5 h (n = 19), 6 h (n = 23), 7 h (n = 16), 8 h (n = 27), or 9 h (n = 26) in bed for seven nights, followed by a 9 h recovery sleep. The saliva samples for cortisol assay were collected at 08:00 h, 08:30 h and 08:45 h at baseline, on experimental days 2 and 5 and on the recovery day. The primary dependent variables were the cortisol concentration at awakening (08:00 h) and the cortisol area under the curve (AUC). There was no effect of time in bed on either the cortisol concentration at awakening or cortisol AUC. In all the time in bed conditions, the cortisol AUC tended to be higher at baseline and lower on experimental day 5. Five consecutive nights of mild to moderate sleep restriction does not appear to affect the CAR in healthy male adults. Full article

Sleep medicine classes and teachings are usually deficient and insufficient during undergraduate medical education. In order to circumvent the educational deficits in sleep medicine, students at a Brazilian Medical School created a sleep medicine interest group—an academic organization for teaching purposes whose administration is carried out by the undergraduate students themselves. This study aims to describe the establishment of a sleep medicine interest group, as well as to evaluate the results of its first edition on the knowledge about sleep medicine among undergraduate medical students. Classes were taken biweekly and consisted of lectures by invited professors, presentation of clinical cases, and discussion with the students. By the end of the course, both attendees and non-attendees were invited to fill out a questionnaire including an objective assessment of knowledge (15 multiple choice questions). The questionnaire was filled out by 32 participants, of which 18 were attendees and 14 were non-attendees. The average result on the final exam was significantly higher among the attendees (6.1 ± 1.2) in comparison with non-attendees (4.9 ± 1.3—p = 0.015). The results demonstrate that an interest group proved to be feasible as a source of complementary information to undergraduate medical students and a valid alternative to circumvent the educational deficits. Full article

Knowledge of the impact of sleep problems in the periconceptional period is scarce. Since this period is the most sensitive time window for embryonic and placental development, we aim to study the impact of maternal sleep problems in the periconceptional period on both mother and offspring. We systematically searched various databases up until September 2021 for studies reporting on maternal sleep in the periconceptional period and any outcome in mother and offspring. We included observational studies describing maternal sleep problems in the periconceptional period and associations with either maternal and/or offspring outcomes. The search produced 8596 articles, of which we selected 27 studies. Some associations were found between sleep problems and lower fertility, more hypertensive disorders, more mood disorders in mothers, higher risk of preterm birth and low birth weight, and more sleep and behavior problems in offspring, with associations with maternal mood disorders being most consistent. This systematic review shows that maternal sleep problems in the periconceptional period are associated with a higher risk of various adverse outcomes in both mother and offspring, although not consistently. It shows that good sleep during pregnancy is crucial, starting as early as before conception, especially for maternal mood. Therefore, it is important for clinicians to pay attention to sleep problems in the periconceptional period and provide adequate treatment for potential sleep problems, even before pregnancy. Full article

This study aimed to evaluate the effectiveness of glasses that emit blue light in reducing the need for recovery, general fatigue, and stress levels in security guards who work night shifts. Light manipulation is seen as a promising strategy to mitigate complaints related to shift work, such as sleepiness and impaired cognitive performance. In a randomized controlled cross-over study design, 86 Dutch security guards used light-emitting glasses (exposure duration: 30 min) during night shifts in a five week period versus a five week control period without glasses. Measurements (Need for Recovery Scale; Checklist Individual Strength; stress level assessed by a fitness tracker) were performed at baseline, at five weeks, and again at 11 weeks. The chronotype was measured at baseline as a potential covariate. A mixed model for repeated measure analyses showed no significant reduction in the need for recovery, nor a reduction in general fatigue scores, during the intervention period. Paired Samples T-Test analyses showed no significant changes in stress levels for the intervention period. Conclusively, blue light exposure using light-emitting glasses for security guards during night shifts showed no directly measurable effect on the reduced need for recovery, overall fatigue, and stress levels. Full article

Variability in the timing of daily sleep is increasingly recognized as an important factor in sleep and general physical health. One potential driver of such daily variations in sleep timing is different work and social obligations during the “working week” and weekends. To investigate the nature of weekday/weekend differences in the timing of sleep offset, we examined actigraphy records of 79,161 adult participants in the UK Biobank who wore an actiwatch for 1 week. The time of sleep offset was found to be on average 36 min later on weekends than on weekdays, and when this difference was expressed as an absolute value (i.e., irrespective of sleep offset being either later or earlier on weekends), it was 63 min. Younger age, more socioeconomic disadvantage, currently being in employment, being a smoker, being male, being of non-white ethnicity and later chronotype were associated with greater differences in sleep offset between weekdays and weekend days. Greater differences in sleep offset timing were associated with age-independent small differences in cardiometabolic health indicators of BMI and diastolic blood pressure, but not HbA1c or systolic blood pressure. In a subset of participants with Type 2 Diabetes Mellitus, weekday/weekend sleep offset differences were associated weakly with BMI, systolic blood pressure and physical activity. Overall, this study demonstrates potentially substantive differences in sleep offset timings between weekdays and weekends in a large sample of UK adults, and that such differences may have public health implications. Full article

Introduction: In 2009, the World Health Organization identified vehicle crashes, both injury-related and fatal, as a public health hazard. Roadway lighting has long been used to reduce crashes and improve the safety of all road users. Ocular light exposure at night can suppress melatonin levels in humans. At sufficient light levels, all visible light wavelengths can elicit this response, but melatonin suppression is maximally sensitive to visible short wavelength light. With the conversion of roadway lighting to solid state sources that have a greater short wavelength spectrum than traditional sources, there is a potential negative health impact through suppressed melatonin levels to roadway users and those living close to the roadway. This paper presents data on the impact of outdoor roadway lighting on salivary melatonin in three cohorts of participants: drivers, pedestrians, and those experiencing light trespass in their homes. Methods: In an outdoor naturalistic roadway environment, healthy participants (N = 29) each being assigned to a cohort of either pedestrian, driver, or light trespass experiment, were exposed to five different solid state light sources with differing spectral emissions and one no lighting condition. Salivary melatonin measurements were made under an average roadway luminance of 1.0 cd/m² (IES RP-18 Roadway Lighting Requirements for expressway roads) with a corneal melanopic Equivalent Daylight Illuminances (EDI) ranging from 0.22 to 0.86 lux. Results: The results indicate that compared to the no roadway lighting condition, the roadway light source spectral content did not significantly impact salivary melatonin levels in the participants in any of the cohorts. Conclusions: These data show that recommended levels of street lighting for expressway roads do not elicit an acute suppression of salivary melatonin and suggest that the health benefit of roadway lighting for traffic safety is not compromised by an acute effect on salivary melatonin. Full article

Sleep loss induces performance impairment and fatigue. The reactivation of human herpesvirus-6, which is related to the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), is one candidate for use as an objective biomarker of fatigue. Phosphorylated eIF2α is a key regulator in integrated stress response (ISR), an intracellular stress response system. However, the relation between sleep/sleep loss and ISR is unclear. The purpose of the current study was to evaluate the effect of prolonged sleep deprivation and recovery sleep on ISR-related gene expression in rat liver. Eight-week-old male Sprague–Dawley rats were subjected to a 96-hour sleep deprivation using a flowerpot technique. The rats were sacrificed, and the liver was collected immediately or 6 or 72 h after the end of the sleep deprivation. RT-qPCR was used to analyze the expression levels of ISR-related gene transcripts in the rat liver. The transcript levels of the Atf3, Ddit3, Hmox-1, and Ppp15a1r genes were markedly increased early in the recovery sleep period after the termination of sleep deprivation. These results indicate that both activation and inactivation of ISRs in the rat liver occur simultaneously in the early phase of recovery sleep. Full article

Future automotive interior lighting might have the potential to go beyond decorative purposes by influencing alertness, circadian physiology, and sleep. As the available space in the interior of an automobile for lighting applications is limited, understanding the impact of various luminous surface sizes on non-image-forming effects is fundamental in this field. In a laboratory study using a within-subject design, 18 participants were exposed to two bright light conditions with different solid angles and one dim light condition in a balanced, randomized order during the course of the evening. Our results demonstrate that both light conditions significantly increased subjective alertness and reduced salivary melatonin concentration but not cognitive performance compared to dim light. The solid angle of light exposure at constant corneal illuminance only affected visual comfort. While subjective alertness can be increased and melatonin can be attenuated with rather small luminaires, larger solid angles should be considered if visual comfort is a priority. Full article

Nonrestorative sleep (NRS) is a common sleep disorder. It is associated with several unhealthy lifestyle factors, such as skipping breakfast and lack of exercise. However, the associations between alcohol drinking, smoking, and NRS are unclear. This study examined the prevalence of NRS within the Japanese general population and the relationships among alcohol drinking, smoking, and NRS. We analyzed an anonymized dataset from a 2013 nationwide population survey (35,717 men and 39,911 women). NRS was assessed through a single-item question, and socio-demographic and lifestyle factors were assessed through self-reports. Multivariable logistic regression analyses were used to examine the associations between alcohol drinking, smoking, and NRS. The total prevalence of NRS was 22.2% (95% CI 21.8–22.7) in men and 23.4% (95% CI 23.0–23.8) in women. Further, we found that sleep duration and prevalence of NRS shared an inverse J-shaped relationship. Heavy alcohol drinking was significantly associated with NRS in both sexes. Short sleep duration and certain socioeconomic factors modified the effect of smoking on NRS in men. These results could be useful in the development of more effective sleep health policies to establish better sleep hygiene. Full article

Light is an influential regulator of behavioural and physiological state in mammals. Features of cognitive performance such as memory, vigilance and alertness can be altered by bright light exposure under laboratory and field conditions. However, the importance of light as a regulator of performance in everyday life is hard to assess and has so far remained largely unclear. We set out to address this uncertainty by developing a tool to capture measures of cognitive performance and light exposure, at scale, and during everyday life. To this end, we generated an app (Brighter Time) which incorporated a psychomotor vigilance (PVT), an N-back and a visual search task with questionnaire-based assessments of demographic characteristics, general health, chronotype and sleep. The app also measured illuminance during task completion using the smartphone’s intrinsic light meter. We undertook a pilot feasibility study of Brighter Time based on 91-week-long acquisition phases within a convenience sample (recruited by local advertisements and word of mouth) running Brighter Time on their own smartphones over two study phases in winter and summer. Study compliance was suitable (median = 20/21 requested task completions per subject). Statistically significant associations were observed between subjective sleepiness and performance in all tasks. Significant daily variations in PVT and visual search performance were also observed. Higher illuminance was associated with reduced reaction time and lower inverse efficiency score in the visual search. Brighter Time thus represents a viable option for large-scale collection of cognitive task data in everyday life, and is able to reveal associations between task performance and sleepiness, time of day and current illuminance. Brighter Time’s utility could be extended to exploring associations with longer-term patterns of light exposure and/or other light metrics by integrating with wearable light meters. Full article

Background: Pre-sleep intentions to react to stimuli during sleep affect sleep processes in spite of reductions in conscious awareness. Here, we compare influences of sounds presented during sleep (with and without intentions to react) with the effect of pre-sleep intentions on sleep (with and without sounds being present during sleep). Methods: Twenty-six young, healthy participants spent two experimental nights in the sleep laboratory. On one night, they were instructed to react to sounds during sleep (“on call”); on the other night, not (“neutral”). Unknown to the subjects, sounds were presented at a low volume in both nights in one group. No sound was presented in any of the two nights in the other group. Results: The instruction of being “on call” decreased objective sleep efficiency independently of sounds being present or not. In addition, event-related responses to sounds as well as slow-wave activity were reduced when being “on call”. Conclusions: Pre-sleep intentions to react impair sleep independently of sounds actually being present and influence brain responses to sounds during sleep. Our results highlight the importance of subjective relevance for reducing negative impact of external noise sources such as traffic or church bells. Full article

Objective/Background: Phenotyping of non-rapid-eye-movement (NREM) parasomnias is currently poorly undertaken. This study aimed to determine whether there are differences phenotypically among childhood-, adolescent-, and adult-onset NREM parasomnias continuing into and presenting in adulthood. Patients/Methods: A retrospective, cohort study of patients presenting with NREM parasomnia between 2008 and 2019 (n = 307) was conducted. Disorders included sleepwalking (n = 231), night terrors (n = 150), sexualised behaviour in sleep (n = 50), and sleep-related eating disorder (n = 28). Results: Compared to the adult-onset NREM behaviours group, the childhood- and adolescent-onset groups were more likely to have a family history of NREM behaviours (p < 0.001), experience a greater spectrum of NREM disorders (p = 0.001), and report a history of sleep-talking significantly more frequently (p = 0.014). Atopy was most prevalent in the childhood-onset group (p = 0.001). Those with childhood-onset NREM parasomnias were significantly more likely to arouse from N3 sleep on video polysomnography (p = 0.0003). Psychiatric disorders were more likely to be comorbid in the adult-onset group (p = 0.012). A history of trauma coinciding with onset of NREM behaviours was significantly more common in the childhood- and adolescent-onset groups (p < 0.001). Conclusions: Significant differences exist across childhood-, adolescent-, and adult-onset NREM parasomnia presenting in adulthood. This study suggests that adult-onset slow-wave sleep disorders may be confounded by psychiatric disorders resulting in nocturnal sleep disruption and that unresolved traumatic life experiences perpetuate NREM disorders arising in childhood and comprise one of the strongest external risk factors for triggering and perpetuating these disorders in adolescence. Full article

The STOP-Bang questionnaire is an easy-to-administer scoring model to screen and identify patients at high risk of obstructive sleep apnea (OSA). However, its diagnostic utility has never been tested with First Nation peoples. The objective was to determine the predictive parameters and the utility of the STOP-Bang questionnaire as an OSA screening tool in a First Nation community in Saskatchewan. The baseline survey of the First Nations Sleep Health Project (FNSHP) was completed between 2018 and 2019. Of the available 233 sleep apnea tests, 215 participants completed the STOP-Bang score questionnaire. A proportional odds ordinal logistic regression analysis was conducted using the total score of the STOP-Bang as the independent variable with equal weight given to each response. Predicted probabilities for each score at cut-off points of the Apnea Hypopnea Index (AHI) were calculated and plotted. To assess the performance of the STOP-Bang questionnaire, sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and area under the curve (AUC) were calculated. These data suggest that a STOP-Bang score ≥ 5 will allow healthcare professionals to identify individuals with an increased probability of moderate-to-severe OSA, with high specificity (93.7%) and NPV (91.8%). For the STOP-Bang score cut-off ≥ 3, the sensitivity was 53.1% for all OSA and 72.0% for moderate-to-severe OSA. For the STOP-Bang score cut-off ≥ 3, the specificity was 68.4% for all OSA and 62.6% for moderate-to-severe OSA. The STOP-Bang score was modestly superior to the symptom of loud snoring, or loud snoring plus obesity in this population. Analysis by sex suggested that a STOP-Bang score ≥ 5 was able to identify individuals with increased probability of moderate-to-severe OSA, for males with acceptable diagnostic test accuracy for detecting participants with OSA, but there was no diagnostic test accuracy for females. Full article

This study aimed to examine the sleep habits in pairs of Japanese high school students and their mothers in the summer and autumn. Nineteen pairs of high school students and their mothers participated in this study. Wrist actigraphy, subjective sleep evaluations, and bedroom environmental measurements (temperature, humidity, and light) were performed for a duration of one week. The results of a split-plot analysis of variance revealed no significant difference in the actigraphically evaluated time spent in bed (TIB) between the seasons and between the mothers and students. The TIB was approximately 6 h on weekdays, and significantly lengthened to approximately 7 h on weekends (p < 0.05). The average sleep efficiency values recorded were higher than 90%. The mothers showed significantly advanced sleep phases compared to those of the students (p < 0.05). In addition, the waking time on Monday morning was significantly correlated between the mothers and students in the summer and autumn (p < 0.05). A perceived sleep loss “almost every day” or “several times per week” was reported by approximately half of the mothers and students in each season. The students occasionally fell into nocturnal sleep with the room light turned on. These results suggest that sleep hygiene education considering life habit characteristics is required to ensure sufficient sleep time. Full article

We examined the immediate impact of a social media outage on nomophobia and associated symptoms using a longitudinal cohort design. Data were collected at two timepoints, baseline (T1) and during the social media outage of 4 October 2021 (T2). T1 was collected in August–September 2021 as part of the baseline of an ongoing study. The nomophobia questionnaire (NMP-Q), Generalized Anxiety Disorder-7 scale (GAD-7), and Athens insomnia scale (AIS) were administered to 2706 healthy participants from the general Bahraini population (56% females, mean age 33.57 ± 11.65 years). Approximately one month later, during the social media outage, 306 of the study participants were opportunistically assessed using the NMP-Q. At baseline, we found that nomophobia levels strongly correlated positively with both insomnia (p = 0.001) and anxiety symptoms (p = 0.001). This is the first report to examine the impact of a social media outage on nomophobia. Our findings indicate that symptoms of nomophobia increased significantly during a social media outage. Baseline insomnia scores predicted a surge in the global scores of nomophobia symptoms during a social media outage. Full article

The purpose of this study is to characterize the impact of the timing and duration of missing actigraphy data on interdaily stability (IS) and intradaily variability (IV) calculation. The performance of three missing data imputation methods (linear interpolation, mean time of day (ToD), and median ToD imputation) for estimating IV and IS was also tested. Week-long actigraphy records with no non-wear or missing timeseries data were masked with zeros or ‘Not a Number’ (NaN) across a range of timings and durations for single and multiple missing data bouts. IV and IS were calculated for true, masked, and imputed (i.e., linear interpolation, mean ToD and, median ToD imputation) timeseries data and used to generate Bland–Alman plots for each condition. Heatmaps were used to analyze the impact of timings and durations of and between bouts. Simulated missing data produced deviations in IV and IS for longer durations, midday crossings, and during similar timing on consecutive days. Median ToD imputation produced the least deviation among the imputation methods. Median ToD imputation is recommended to recapitulate IV and IS under missing data conditions for less than 24 h. Full article

While the energizing effect of light has been known since the early years of light therapy, its reliable detection using objective measures is still not well-established. This review aims to ascertain the immediate energizing effect of light and determine its best indicators. Sixty-four articles published before July 2022 were included in the review. The articles described 72 (sub-)studies performed in healthy individuals. Fourteen measures were analyzed. The analysis showed that light causes an energizing effect that can be best documented by measuring core (rectal) body temperature: the proportion of the studies revealing increasing, unchanging, and decreasing rectal temperature was 13/6/1. The second most suitable indicator was heart rate (10/22/1), which showed concordant changes with rectal temperature (a trend, seven mutual studies). There is no evidence from the reviewed articles that oxygen consumption, skin conductance, blood pressure, heart rate variability, non-rectal inner temperature (combined digestive, tympanic, and oral), skin temperature, or cortisol levels can provide light effect detection. Four other measures were found to be unsuitable as well but with less certainty due to the low number of studies (≤3): skin blood flow, noradrenaline, salivary alpha-amylase, and thyroid-stimulating hormone levels. On the other hand, light exposure had a noticeable effect on sympathetic nerve activity measured using microneurography; however, this measure can be accepted as a marker only tentatively as it was employed in a single study. The analysis took into account three factors—study limitation in design/analysis, use of light in day- or nighttime, and relative brightness of the light stimulus—that were found to significantly influence some of the analyzed variables. The review indicates that the energizing effect of light in humans can be reliably detected using rectal temperature and heart rate. Full article