Clocks & Sleep, Volume 7, Issue 4 (December 2025) – 11 articles

Critically ill patients are predisposed to developing cognitive dysfunction, excessive daytime sleepiness (EDS), and fatigue during their stay in the intensive care unit (ICU). Modafinil, a wakefulness-promoting agent, has demonstrated potential benefits in enhancing alertness, cognitive performance, and activity levels in various clinical populations. The present narrative review aims to systematically evaluate the existing literature regarding the administration of modafinil for the treatment of EDS and fatigue in the ICU context. A comprehensive literature search was performed using the Embase, MEDLINE, Web of Science, and Google Scholar databases, covering publications up to 20 June 2025. Studies investigating the use of modafinil to improve wakefulness in ICU patients were identified. A total of nine relevant studies were included, comprising two randomized controlled trials (RCTs), two case series, and five retrospective cohort studies (n = 950 patients). Four of these studies focused on patients with traumatic brain injury or post-stroke conditions, whereas the remaining studies addressed heterogeneous ICU populations. Preliminary evidence indicates that modafinil may enhance wakefulness in selected critically ill patients and potentially facilitate their participation in rehabilitative interventions, such as physical therapy. Nonetheless, robust conclusions regarding efficacy and safety remain limited by the small sample sizes and methodological constraints of the available studies. Consequently, further large-scale RCTs are warranted to elucidate the therapeutic role of modafinil in the management of EDS and hypoactivity among ICU patients. Full article

Circadian rhythm disruptions from shiftwork impact sleep quality and work performance, yet validated tools to assess circadian preferences in Arabic-speaking populations are scarce. This study aimed to translate and validate the 11-item Circadian Type Inventory (CTI-11) into Arabic (CTI-11A), evaluate its psychometric properties, and explore latent circadian profiles in relation to sleep quality. A cross-sectional survey in Bahrain involved 468 Arabic-speaking adults recruited via social media. The CTI-11A, assessing Languid/Vigorous (LV) and Flexible/Rigid (FR) subscales, and the Jenkins Sleep Scale (JSS) were administered. Confirmatory factor analysis (CFA), reliability tests, and latent class analysis (LCA) were conducted. Participants (mean age: 36.18 ± 10.35) showed CTI-11A total scores of 35.40 ± 6.61 and JSS scores of 5.76 ± 3.48. CFA confirmed the two-factor structure (RMSEA = 0.06, SRMR = 0.05, CFI = 0.93, TLI = 0.91), with Cronbach’s α of 0.72 (total CTI-11A). Test–retest reliability was high (ICC = 0.91). CTI-11A correlated moderately with JSS (r = 0.40, p < 0.001), with stronger FR-JSS (r = 0.36) than LV-JSS (r = 0.25) associations. LCA identified two classes (Class 1: 52%, vigorous/flexible; Class 2: 48%, languid/rigid), with Class 2 showing poorer sleep quality. The CTI-11A is a reliable and valid tool for assessing circadian preferences in Arabic-speaking populations, with distinct circadian profiles linked to sleep quality. While flexible/vigorous profiles associated with better sleep, languid/rigid profiles indicate higher sleep disturbance risk, informing targeted shiftwork interventions. Further refinement of the factor structure and broader regional validation are needed. Full article

Background: Shift work necessitates alterations in daily routines, which can be detrimental to workers’ health and may also influence the activity and rest patterns of their children. Aim: The aim of this study was to evaluate the concordance between activity and rest parameters of mothers and their children, according to the mothers’ work shift (day vs. night). Methods: Twelve mother–child dyads participated in this study, including six mothers working night shifts and six working day shifts. All mothers followed a 12/36 h rotating schedule (07:00–19:00 for day shifts; 19:00–07:00 for night shifts). Participants wore actigraphy devices for 10 consecutive days. Sleep and motor activity parameters were analyzed using the Bland–Altman method. Results: Analysis of the five least active hours (L5) revealed increased nocturnal activity among the night shift group. The period of the 10 most active hours (M10) suggested greater activity in the day shift group, with a smaller difference between mother and child in the day shift group. The relative amplitude (RA) in the night shift group was lower among mothers compared to the day group. Interdaily stability (IS) was lower, and intradaily variability (IV) was higher in the night shift group, suggesting more irregular activity patterns. Bedtime data showed greater variability in the night shift group, with night shift mothers typically going to bed later than their children—a pattern that was also observed for wake times. In the day shift group, total sleep time did not differ between mothers and children; however, in the night shift group, discrepancies increased proportionally with total sleep duration. Sleep efficiency was lower among mothers in both groups, but the difference between mother and child was more pronounced in the night shift group. Conclusions: Night shift work among mothers appears to negatively affect both their own and their children’s activity and sleep parameters when compared to those in the day shift group. Full article

Short sleep duration (≤6 h) is a public health concern linked to cardiometabolic disease and premature mortality. However, persistent disparities across sociodemographic, psychosocial, and structural domains remain underexplored in recent nationally representative samples. We analyzed 2022 Behavioral Risk Factor Surveillance System (BRFSS) data, including 228,463 adults (weighted N ≈ 122 million). Sleep duration was dichotomized as short (≤6 h) versus adequate (≥7 h). Complex samples logistic regression estimated associations between sociodemographic, psychosocial, behavioral, and structural determinants and short sleep, accounting for survey design. The weighted prevalence of short sleep was 33.2%. Non-Hispanic Black (AOR = 1.56, 95% CI: 1.46–1.65) and American Indian/Alaska Native adults (AOR = 1.46, 95% CI: 1.29–1.65) were disproportionately affected compared with non-Hispanic White adults. Psychosocial factors contributed strongly: life dissatisfaction, limited emotional support, and low social connectedness increased odds, whereas high connectedness was protective. Food insecurity and smoking were significant structural and behavioral risks, while binge drinking and urbanicity were not. One-third of U.S. adults report short sleep, with marked disparities across demographic, socioeconomic status, psychosocial stressors, and structural barriers. Findings highlight the multifactorial nature of sleep health inequities and the need for multilevel interventions addressing both individual behaviors and upstream determinants. Full article

Sleep disturbances and shift work are associated with increased cardiovascular risk, possibly through disruptions in endothelial and hemostatic function. While prior studies link acute sleep deprivation to vascular dysfunction, the impact of chronic sleep quality and circadian misalignment on endothelial health in healthy individuals, particularly shift workers, remains underexplored. The aim of this study was to examine the association between objectively measured sleep quality and endothelial/hemostatic function in healthy female hospital nurses, comparing shift and day workers, and considering time-of-day variation. In this repeated-measures study, 100 female nurses (51 shift, 49 day workers) aged 25–50 wore actigraphy devices for 7–14 days to assess total sleep time (TST), sleep efficiency (SEF), and wake after sleep onset (WASO). Endothelial function was measured using EndoPAT (Reactive Hyperemia Index—RHI). Hemostatic markers included plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), heparanase and heparanase procoagulant activity assessed by ELISA, and chromogenic assays in morning and evening. TST was not associated with any vascular outcomes. Poor sleep quality (low SEF, high WASO) was significantly associated with reduced RHI and elevated PAI-1 level, heparanase level, and heparanase procoagulant activity levels. Regression models revealed significant main effects of SEF and WASO on endothelial and coagulation markers, with some interactions depending on shift type and time of measurement. No significant associations were found for VWF. Impaired sleep quality, but not sleep duration, is associated with endothelial dysfunction and procoagulant activation, particularly among shift-working nurses. These findings suggest that sleep quality may play a critical role in vascular health and support the use of sleep-based interventions to reduce cardiovascular risk in shift-working populations. Full article

Academic performance in adolescence is influenced by both cognitive capacity and physiological factors such as sleepiness. However, the interaction between these dimensions remains understudied. This pilot study examined whether daytime sleepiness moderates the relationship between working memory and academic achievement in a sample of 601 schoolchildren aged 11 to 17 years. Participants completed a digital visuospatial working memory task and self-reported their daytime sleepiness using the Pediatric Daytime Sleepiness Scale (PDSS). Academic performance was assessed through official grades in Mathematics, Language, and Literature. Regression analyses showed that working memory (total score and average reaction time) and daytime sleepiness were independent predictors of academic performance. These findings support our hypotheses that cognitive and physiological factors each contribute to school success. However, no significant moderation effects were found in the full sample. Subgroup analyses revealed that working memory predicted academic outcomes only among students with normal sleepiness levels, whereas in high-sleepiness students, cognitive predictors lost significance and PDSS scores emerged as the dominant predictor. These results suggest that elevated daytime sleepiness can undermine the positive impact of working memory on academic performance. The findings highlight the importance of assessing both cognitive skills and physiological readiness when evaluating students. They also suggest that sleep-focused interventions may improve learning outcomes, especially during adolescence. Full article

Older adults are vulnerable to changes in sleep with age. Poor sleep quality is associated with self-reported cognitive changes, which can occur before the onset of objective cognitive decline associated with Mild Cognitive Impairment and Alzheimer’s disease. The objective of this study was to examine associations between self-reported sleep complaints, objective sleep quality, and self-reported cognitive changes and their relations to symptoms of depression and anxiety in a group of community-dwelling older adults. Adults aged ≥ 50 without dementia (n = 45) were recruited and completed 1–2 weeks of rest-activity monitoring using a wrist-worn device, underwent a test of global cognitive functioning (Mini-Mental State Examination; MMSE), and completed questionnaires assessing insomnia (Insomnia Severity Index; ISI), subjective sleep quality (Pittsburgh Sleep Quality Index; PSQI), self-reported cognitive changes (Cognitive Function Instrument; CFI), and symptoms of depression and anxiety (Beck Depression Inventory-II; BDI-II and Generalized Anxiety Disorder 7-item assessment; GAD-7). Pearson partial correlations assessed relations among subjective and objective sleep quality, insomnia ratings, CFI ratings, and global cognition, while controlling for BDI-II and GAD-7 ratings. Exploratory analyses examined the correlation between PSQI component scores and CFI ratings and global cognition. Greater ISI (r = 0.50, p ≤ 0.001) ratings significantly correlated with higher CFI scores. PSQI total ratings and actigraphy-based measures (n = 41) did not significantly correlate with CFI scores. Exploratory PSQI subscale analyses revealed that worse subjective sleep quality (r = 0.31, p = 0.048), shorter sleep duration (r = 0.32, p = 0.04), and greater use of sleep medications (r = 0.31, p = 0.048) correlated with higher CFI scores. Poorer sleep quality due to less time spent asleep, fragmented or disturbed sleep, and requiring medications to sleep, may be associated with greater memory concerns. Alternatively, worries about cognition may deleteriously affect sleep. Subjective measures of sleep quality may be useful to identify older adults at increased risk of cognitive decline. Full article

Ambient temperature and thermoregulation influence sleep quality. This study investigated the effects of a temperature-controlled mattress cover on sleep and perceptual outcomes in healthy adults. In a randomised, counterbalanced, crossover design, 34 healthy adults (20 F, 14 M; age, 30 ± 5 y) used a temperature-controlled mattress cover for 14 nights, following ≥3 nights of familiarisation. The temperature feature was on for 7 nights (POD) and off for 7 nights (CON). Sleep was assessed via wrist actigraphy, while heart rate (HR), heart rate variability (HRV), and respiratory rate (RR) were recorded by embedded sensors in the mattress cover. Participants completed daily and weekly questionnaires evaluating sleep quality, thermal comfort, and thermal sensation. Linear mixed models showed significant main effects of condition favouring POD over CON for all daily perceived outcomes (all p < 0.05). A large, significant improvement in perceived sleep quality was observed (p = 0.001, d = 0.92). No significant differences were found in objective sleep metrics or biometric measures (all p ≥ 0.05). A temperature-controlled mattress cover was associated with improved subjective sleep quality and thermal-related perceptions despite minimal changes in objective or biometric outcomes, which may in part reflect expectancy, or placebo effects. Further research is needed to explore whether these perceptual benefits lead to physiological improvements over time. Full article

The protein SNAIL has been widely studied for its roles in promoting cancer invasion and resistance to apoptosis. There are multiple contributors to its expression, including self- and circadian regulation, and it has been posited that SNAIL oscillates in a circadian manner. Given the multiple factors involved, we sought to determine whether this is indeed the case. We developed a luciferase reporter that was used to demonstrate SNAIL’s rhythmic nature (SNAIL:luc) in the circadian model cell line, U2OS. Considering SNAIL’s relevance in breast cancer, we also assessed its oscillations in cellular models representing different levels of aggression. We incorporated the SNAIL:luc reporter in MCF10A breast epithelial cells, and MCF7 and MDA-MB-231 breast cancer cell lines, which are less and more aggressive, respectively. We found that SNAIL oscillations were present but weak in MCF7 and arrhythmic in MDA-MB-231 cells, correlating with those of core clock genes (BMAL1 and PER2) in these models. Surprisingly, MCF10A cells, whose core clock genes possess robust circadian expression patterns, did not have rhythmic oscillations of SNAIL. Our findings suggest that SNAIL is under circadian control, but this is cell line/tissue dependent, setting the stage for additional studies to better understand the impacts of various factors contributing to its expression. Full article

Animal studies show that sleep regulation depends on subcortical networks, but whether the connectivity between subcortical areas contributes to human sleep variability remains unclear. We investigated whether the effective connectivity between the LC and hypothalamic subparts during wakefulness relates to sleep electrophysiology. Thirty-three younger (~22 y, 27 women) and 18 late middle-aged (~61 y, 14 women) healthy individuals underwent 7-Tesla functional MRI during wakefulness to assess LC–hypothalamus effective connectivity. Additionally, sleep EEG was recorded at night in the lab to examine the relationships between effective connectivity measures and REM sleep theta energy as well as sigma power prior to REM. Connectivity analyses revealed strong mutual positive influences between the LC and both the anterior–superior and posterior hypothalamus, consistent with animal studies. Aging was negatively associated with the connectivity from the anterior–superior hypothalamus (including the preoptic area) to the LC. In late middle-aged adults, but not younger adults, stronger effective connectivity from the anterior–superior hypothalamus to the LC was associated with lower REM theta energy. This association extended to other low-frequency bands during REM and NREM sleep. These findings highlight the age-dependent modulation of LC–hypothalamus interactions and their potential roles in sleep regulation, providing new insights into neural mechanisms underlying age-related sleep changes. Full article

Background: Circadian Syndrome (CircS) encompasses a range of cardiometabolic risk factors that contribute to an increased susceptibility to cardiovascular diseases and type 2 diabetes. Understanding the factors that underpin CircS is essential. This study primarily aims to examine the association between hypothyroidism and CircS in adults. A secondary analysis compares this association with that between hypothyroidism and Metabolic Syndrome (MetS). Additionally, the dose–response relationship between serum free thyroxine (FT4) levels and CircS probability is explored. Methods: This cross-sectional study includes 4050 National Health and Nutrition Examination Survey (NHANES) participants (2007–2012). Hypothyroidism was classified into (1) drug-managed, (2) non-drug-managed (NDM) primary, and (3) NDM central hypothyroidism, based on self-reported medication use and serum TSH/FT4 levels. CircS was defined as having ≥5 of its eight components, including MetS criteria, depression, short sleep, and non-alcoholic fatty liver disease. Results: Our results showed that hypothyroidism was significantly associated with CircS (OR: 1.58, 95% CI 1.26–1.98) and MetS (OR: 1.19, 95% CI 1.01–1.42). An inverse, non-linear relationship between serum FT4 levels and the probability of CircS was observed. Conclusions: The results underscore a significant association between hypothyroidism and CircS and MetS, with FT4 levels inversely related to CircS probability. These findings highlight hypothyroidism’s potential role in CircS pathogenesis and prevention. Full article