Sleep regularity is an important but under-measured dimension of sleep health. Objective indices from actigraphy or wearables are robust but resource-intensive. The Sleep Regularity Questionnaire (SRQ) offers a brief subjective tool, but its validity against objective and diary-based indices in healthy adults is unclear.In Part 1, 31 adults wore a smart ring continuously for 21 nights. Device-derived regularity metrics included the Sleep Regularity Index (SRI), interdaily stability (IS), social jetlag (SJL), composite phase deviation (CPD), and the standard deviation of sleep onset and wake time. In Part 2, 52 adults completed a one-week sleep diary, from which variability in sleep timing, total sleep time (TST), SJL and nightly perceived sleep quality were derived. All participants completed the SRQ and Brief Pittsburgh Sleep Quality Index (B-PSQI).In Part 1, associations between SRQ scores and device-derived SRI, IS, SJL, CPD and timing variability were small (absolute r ≤ 0.36). Higher SRQ Global and Sleep Continuity scores were moderately associated with better B-PSQI global scores (r –0.37 to –0.44). In Part 2, SRQ Global and Circadian Regularity showed small-to-moderate associations with higher diary-rated sleep quality and lower bedtime variability (r ≈ 0.40 and –0.32 to –0.34), while correlations with other diary metrics and B-PSQI were weak (absolute r ≤ 0.25).The SRQ shows modest convergent validity with diary-based timing variability and perceived sleep quality, but only weak correspondence with smart ring-based sleep regularity indices. It is likely to complement, rather than replace, objective monitoring in healthy adults with relatively regular sleep–wake patterns.

The hypothalamic suprachiasmatic nucleus (SCN), the circadian pacemaker of the mammalian brain, integrates both environmental and endogenous information to modulate various physiological and behavioral processes. Both light and physical activity entrain SCN circadian rhythmicity, but the underlying molecular mechanisms for physical activity remain elusive. Repetitive neuronal stimulation results in accumulation of the stable transcription factor ΔFOSB, that has been implicated in long-term brain plasticity, altered neuronal excitability, and changes in behavior. In rodents, voluntary wheel running (VWR) mimics aspects of exercise training and increases ΔFOSB in several brain regions. Whether VWR also alters ΔFOSB in the SCN is unexplored. Here, young-adult male and female Wistar rats were housed sedentary or allowed to run for four weeks followed by quantification of ΔFOSB in the SCN. VWR lowered SCN ΔFOSB-positive cell numbers in males and females compared to sedentary housing. Total running distance did not correlate with ΔFOSB suppression. Analysis taking estrous cycle into account revealed that ΔFOSB-positive cell numbers were cyclic in sedentary females, being lowest during proestrus and highest during diestrus. Remarkably, this cyclicity was absent in runners, where ΔFOSB-positive cell numbers remained comparable to those observed during proestrus in sedentary controls. Finally, estradiol replacement following ovariectomy in sedentary females lowered SCN ΔFOSB-positive cell numbers. Thus, VWR and estrous cycle, via, at least in part, estradiol, modulate SCN ΔFOSB. Given its role in long-term plasticity and behavioral adaptations, ΔFOSB may provide a molecular link between VWR and/or estrous cycle and the output of the SCN and its related behavioral adaptations.

The human circadian timing system depends on the light/dark cycle as its main cue to synchronize with the environment, and thus with solar time. However, human activities depend also on social time, i.e. the set of time conventions and restrictions dictated by society, including Daylight Saving Time (DST), which adds an hour to any degree of desynchrony between social and solar time. Here, we used Google Trends as a data source to analyze diurnal variation, if any, and the daily peak in the relative search volume of 26 Google search queries in relation to the transitions to/from DST in Italy from 2015 to 2020. Our search queries of interest fell into three categories: sleep/health-related, medication and random non sleep/health-related. After initial rhythm and phase analysis, 11 words were selected to compare the average phase of the 15 days before and after the transition to/from DST. We observed an average phase advance after the transition to DST, and a phase delay after the transition to civil time, ranging from 25 to 60 minutes. Advances or delays shorter than 60 minutes, which were primarily observed in the sleep/health-related category, may suggest that search timing for these queries is at least partially driven by the endogenous circadian rhythm. Finally, a significant trend in phase anticipation over the years was observed for virtually all words. This is most likely related to an increase in age, and thus in earlier chronotypes, amongst Google users.

The circadian clock is adjusted by light inputs via the retinohypothalamic tract. Because environmental light is controllable for modern humans at the individual’s preference although under social schedules, individual differences in time-related psychology and behavior may be associated with morningness-eveningness preference (M-E preference). To examine this hypothesis, we used the Time Management Scale and Time Anxiety Scale to quantify time-related psychology and behavior. These scales aim to evaluate “awareness of effective time management and utilization” and “anxiety about uncontrollable time schedule and unexpected time-related outcome”, respectively. According to our correlation analysis using mid-sleep time as a marker for M-E preference, we obtained results supporting our hypothesis in the correlation between the M-E preference values and the Time Management Scale scores, with larger “time estimation” and “taking each moment as it comes” scores associated with more morningness and eveningness, respectively. Considering that modern humans likely become night owls under artificial light conditions, it appears plausible that lower awareness of time management leads to more eveningness.

Shift work is an inconsistent and atypical work schedule. This study aimed to investigate the influence of shift work on the Quality of Sleep (QOS) and Executive Functions (EF). Thirty shift workers and thirty day workers first completed a demographic questionnaire. They then were tested using the Pittsburgh Sleep Quality Index (PSQI) and EF tests, including the Corsi Block-Tapping Task (CBTT), Berg’s Card Sorting Task (BCST), and the Continuous Performance Task (CPT). Results were subjected to non-parametric Chi-Square Tests, the Mann-Whitney U Test, and Independent T-Tests. Shift workers had significantly poorer sleep quality than day workers, which was shown in PSQI global scale (p = 0.001), sleep duration (p = 0.042), habitual sleep efficiency (p = 0.021), and sleep disturbance (p = 0.021). Concerning EF tests, shift workers performed significantly poorer on CBTT (p = 0.019) and BCST (p = 0.015, 0.047) compared with day workers. Significant differences were also observed between shift workers and day workers in terms of variables of omission errors (p = 0.037) and commission errors (p = 0.041) on CPT, but no significant difference was found between shift workers and day workers in reaction time (p = 0.561). Shift work impaired EF. These findings are related to shift workers’ poorer sleep and its detrimental effects on areas of the brain, which are critical for EF, such as the prefrontal area. Our results suggest the evaluation and implication of practices and policies to assuage the consequences of working in shifts.

In mammals, circadian rhythmicity is sustained via a transcriptional/translational feedback loop referred to as the canonical molecular circadian clock. Circadian rhythm is absent in undifferentiated embryonic stem cells; it begins only after differentiation. We used pluripotent P19 embryonal carcinoma stem cells to check the biological clock before and after differentiation into neurons using retinoic acid. We show that the central clock genes ARNTL (Bmal), Per2 and Per3, and the peripheral clock genes Rev-erb-α and ROR-α, oscillate before and after differentiation, as does the expression of the neuronal differentiation markers Hes5, β-3-tubulin (Tubb3) and Stra13, but not Neurod1. Furthermore, the known clock-modulating compounds ERK, EGFR, Pi3K, p38, DNA methylation and Sirtiun inhibitors, in addition to Rev-erb-α ligands, modulate the expression of central and peripheral clock genes. Interestingly Sirtinol, Sirt1 and Sirt2 inhibitors had the greatest significant effect on the expression of clock genes, and increased Hes5 and Tubb3 expression during neuronal differentiation. Our findings reveal a new frontier of circadian clock research in stem cells: contrary to what has been published previously, we have shown the clock to be functional and to oscillate, even in undifferentiated stem cells. Modulating the expression of clock genes using small molecules could affect stem cell differentiation.

Previous work from our laboratory has shown that a measure of attention to emotionally-charged stimuli, the late positive potential (LPP) event related potential (ERP), distinguished neutral from emotional pictures on a baseline day, but not after sleep deprivation. Here we sought to extend these findings and address the uncertainty about the effect of time-of-day on emotion processing by testing a morning group (8:00–10:00 a.m., n = 30) and an evening group (8:00–10:00 p.m., n = 30). We also examined the extent of diurnal changes in cortisol related to the emotion processing task. Results from this study mirrored those found after one night of sleep deprivation. Compared to the morning group, the LPP generated by the evening group (who had a greater homeostatic sleep drive) did not distinguish neutral from emotionally-charged stimuli. New to this study, we also found that there was a time-of-day effect on positive, but not negative pictures. While, as expected, cortisol levels were higher in the morning relative to the evening group, there was no relationship between cortisol and the LPP ERP emotion measure. In addition, neither time-of-day preference nor sleep quality was related to the LPP measure. These findings show that, similar to what occurs after sleep deprivation, increased sleep pressure throughout the day interferes with attention processing to emotional stimuli.

Background: Circadian rhythms are daily changes in our physiologyand behavior that are manifested as patterns of brain wave activity, periodichormone production, recurring cell regeneration, and other oscillatorybiological activities. Their importance to human health is becoming apparent;they are deranged by shift work and jet-lag and in disparate conditions such asinsomnia, sleep syndromes, coronary heart attacks, and depression, and areendogenous factors that contribute to cancer development and progression.Discussion: As evidence of the circadian connection to human healthhas grown, so has the number of Americans experiencing disruption of circadianrhythms due to the demands of an industrialized society. Today, there is agrowing work force that experiences night shift work and time-zone shiftsshaping the demands on physicians to best meet the needs of patients exposed tochronic circadian disruptions. The diverse range of illness associated withaltered rhythms suggests that physicians in various fields will see its impactin their patients. However, medical education, with an already full curriculum,struggles to address this issue.Summary: Here, we emphasize the need for incorporating the topic ofcircadian rhythms in the medical curriculum and propose strategies to accomplishthis goal.

BackgroundThe relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice.MethodsGeneral activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed.ResultsFree-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups.ConclusionsSince athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics.

BackgroundIn university health care settings, students with psychosomatic complaints often have chronotypic problems. For this reason, we investigated a potential connection between psychosomatic complaints and circadian rhythm irregularity assessed by salivary levels of melatonin and growth hormone.MethodsFifteen healthy students between 21 and 22 years of age were examined for physiological parameters of chronotypes based on melatonin and growth hormone secretion patterns, using a fluorescence enzyme immunoassay. Salivary samples were collected from subjects at home five times each day (20:00, 24:00, 04:00, 08:00, and 12:00 h). In addition, the subjects rated their psychosomatic symptoms twice (at 08:00 and 20:00 h).ResultsA group with irregular circadian rhythm of melatonin (ICR) showed more psychosomatic complaints than a group with the regular circadian rhythm (RCR), especially for anxiety.ConclusionPsychosomatic symptoms, particularly anxiety, may be associated with irregularity in melatonin and growth hormone rhythms, which can be altered by basic lifestyle habits even in healthy students.