Clocks & Sleep最新文献

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.

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.

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.

Diagnosis and monitoring of daytime sleepiness remain challenging and are strongly reliant on subjective assessments. To revisit common monitoring tools and explore new assessment modalities, we investigated the response of daily and momentary subjective measures of sleepiness and fatigue and skin temperature to sleep restriction, assessed between- and within-day variations in these responses, and studied their convergence. Seventeen healthy participants (aged 19-32 years, seven females, ten males) participated in a field study employing ecological momentary assessment. After a one-week baseline, two sleep conditions (4 h/night vs. 7-9 h/night, actigraphy-controlled; three nights each) were counterbalanced across participants. During the experimental conditions, sleepiness and fatigue were assessed using subjective rating scales administered in daily diary questionnaires and experience sampling questionnaires (10 notifications per day), while distal and proximal skin temperatures were continuously recorded. Results revealed significant effects of sleep restriction on distal and proximal skin temperature and daily reports of sleepiness and fatigue, independent of the number of sleep-restricted nights. The effects on momentary assessments were moderated by day, reflecting a cumulative effect of the sleep restriction from Days 1 to 3. The effects of sleep restriction on momentary sleepiness and fatigue ratings or hourly skin temperature metrics were not significantly moderated by time of day. Hourly skin temperatures (distal skin temperature and temperature gradient) were significantly related to subjective sleepiness and fatigue. In conclusion, all self-reports were sensitive to the sleep restriction, but momentary assessments illustrate the manipulation's cumulative effects and captured temporal dynamics in sleepiness and fatigue within days. This investigation showed overlap between sleepiness and fatigue experiences as reflected in medium to strong associations. Skin temperature correlates with momentary subjective sleepiness (and fatigue); however, considering it a proxy for daytime sleepiness remains exploratory.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent disorder in the pediatric population. Furthermore, there appears to be a special relationship between ADHD and Restless Legs Syndrome (RLS). The objective of this review was therefore to provide an updated overview of the current literature regarding the prevalence of RLS and its potential clinical impact in pediatric ADHD subjects (<18 years). A systematic literature review was carried out in May 2025 in the PubMed-Medline database according to PRISMA criteria. After evaluation by two readers of the 147 identified articles, 9 articles investigating the prevalence of RLS with or without assessment of its potential clinical impact were selected for this systematic literature review. The prevalence of RLS in children and adolescents with ADHD showed significant variation, ranging from 11% to 54%. One study found a significant impact of RLS on academic performance and life skills in pediatric ADHD subjects. Three studies highlighted higher severity of ADHD complaints in subjects with comorbid RLS. One study reported higher RLS severity scores in the ADHD+RLS group and significantly more severe scores in the "hyperactive-impulsive" ADHD subtype. Two studies identified a significant association between a family history of RLS and RLS+ADHD comorbidity. Compared with the general pediatric population, the prevalence of RLS appears to be higher in pediatric ADHD subjects. Finally, this comorbid sleep disorder could worsen the severity of ADHD symptoms and complicate its clinical management.

Sleep in intensive care unit (ICU) patients is frequently disrupted, which may adversely affect their overall health and recovery. Despite the implementation of various strategies to promote sleep, accurately assessing its quality remains complex. This pilot study aimed to evaluate both the quality and quantity of sleep in ICU patients using actigraphy (ACT) and the Richards-Campbell Sleep Questionnaire (RCSQ) and to compare the diagnostic performance of these two tools. We conducted a prospective observational study including 228 ICU patients. Sleep was assessed using both RCSQ and ACT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the discriminative ability of each tool (Area Under the Curve [AUC], sensitivity, specificity), with optimal cut-off points determined using Youden's Index. The Mann-Whitney U test was used to compare sleep parameters between patients classified as having good or poor sleep based on ACT measurements. The mean RCSQ score was 38.16 ± 17.09, indicating poor perceived sleep quality. Sleep onset latency (based on RCSQ) was 35.71 ± 21.44 min, with a mean of 40.32 ± 20.03 awakenings. According to ACT, sleep latency was 39.23 ± 22.09 min, and total sleep duration was 198.15 ± 128.42 min (approximately 3 h and 18 min), which is significantly below recommended levels. The average number of awakenings recorded was 24.85. In terms of diagnostic performance, the RCSQ demonstrated excellent discriminative ability (AUC = 1.00 for the total score), while ACT showed more variable results: total sleep duration had a good AUC of 0.91, while sleep latency showed a lower performance with an AUC of 0.50. The RCSQ proved to be more reliable than ACT in assessing sleep quality in ICU patients, providing consistent results across multiple parameters, including sleep depth, latency, and number of awakenings. Conversely, ACT yielded less consistent findings, particularly regarding sleep latency and nighttime interruptions. Further studies are warranted to refine objective tools for evaluating sleep in critically ill patients.

Individuals with neurodevelopmental disorders (NDDs) often experience sleep disturbances and are frequently exposed to light during nighttime hours. Our previous studies using the Contactin-associated protein-like 2 (Cntnap2) knockout (KO) mouse model of NDDs demonstrated that nighttime light exposure adversely affected behavioral measures. In this study, we exposed wild-type (WT) and Cntnap2 KO mice to an ultradian lighting cycle (T7), which alternates 3.5 h of light and 3.5 h of darkness, hypothesizing that this lighting protocol would mimic the impact of nighttime light exposure seen in standard light-dark cycles with dim light at night (DLaN). However, adult WT and Cntnap2 KO mice held under the T7 cycle did not show the increased grooming behavior or reduced social interaction observed in Cntnap2 KO mice exposed to DLaN. The T7 cycle lengthened the circadian period and weakened the rhythm amplitude without abolishing rhythmicity in either genotype. Finally, opposite to DLaN, neither the T7 cycle nor constant darkness (DD) elicited an increase in cFos expression in the basolateral amygdala. These results demonstrate that the adverse effects of nighttime light exposure in an NDD model depend on the extent of the circadian disruption rather than light exposure alone, emphasizing the importance of circadian stability as a protective factor in NDDs.

The school and university periods represent a critical phase in individuals' cognitive, emotional, and behavioural development. Numerous lifestyle factors can influence executive functions and high-level cognitive processes crucial for learning and behavioural adaptation. Sleep and physical activity are two variables that influence executive functions and that could be modified through behavioural interventions. Numerous scientific studies suggest that adequate sleep quality and duration are linked to improved cognitive performance. Similarly, regular physical exercise correlates with neurocognitive benefits. However, these two aspects of lifestyle are often compromised in students, resulting in attention difficulties, reduced working memory, and difficulty in inhibitory control, all aspects of non-optimal executive functioning. Even though the scientific literature separately explores "sleep and executive functions" and "physical activity and executive functions", few studies have integrated the two factors to assess their combined effect on executive functioning, particularly within the student population. The present narrative review aims to outline an integrated theoretical framework of existing scientific literature and to identify any knowledge gaps that may guide future research. It could provide relevant insights for designing preventive or promotional interventions to enhance students' cognitive performance and mental well-being.

Concussions significantly impact sleep quality among adolescents. Despite increasing recognition of these effects, the complex relationship between adolescent concussions and sleep disturbances is still not fully understood and presents mixed findings. Here, we conducted a systematic review and meta-analysis to assess how concussions affect sleep-related symptoms in adolescents. We included papers presenting Pittsburgh Sleep Quality Index (PSQI) differences following concussion in high school and collegiate patients, with sleep measures recorded following concussion. Animal studies, research on participants with conditions other than concussion, non-English articles and papers failing to present PSQI data were excluded. We searched MEDLINE^®, Embase^®, CINAHL, Web of Science™, PsycINFO^®, Google Scholar, and Cochrane Central Register of Controlled Trials databases until 23 August 2024. In addition, we performed hand-searching of relevant reference lists and conference proceedings to identify further studies. Risk of bias was assessed using the Newcastle-Ottawa scale. In total, we considered 4477 studies, with nine meeting the inclusion criteria. Our analysis involved 796 participants, 340 of whom had experienced a concussion. Analysis was carried out using the meta and metafor packages in R (version 4.0.0). We showed a deterioration in sleep quality post-concussion, as evidenced by increased PSQI (standardised mean difference 0.84; 95% CI 0.53-1.16; p < 0.0001). Subgroup and quality assessments confirmed the consistency of these findings. Since poor sleep quality impacts daytime activities, we analysed the relationship between concussion and daytime dysfunction. We showed that concussion is associated with a significant worsening of the daytime dysfunction score by 0.55 (95% CI 0.24-0.70; p = 0.006). We conclude that concussions impair both sleep quality and daytime functioning in adolescents. Our research underscores the need for systematic inclusion of sleep quality assessments in post-concussion protocols and calls for targeted interventions to manage sleep disturbances post-concussion to mitigate their broader impacts on daily functioning.

The circadian rhythm of the central brain clock in the suprachiasmatic nucleus (SCN) is synchronized by light. White adipose tissue (WAT) is one of the metabolic endocrine organs containing a molecular clock, and it is synchronized by the SCN. Excess WAT is a risk factor for health issues including type 2 diabetes mellitus (DM2). We hypothesized that bright-light exposure would affect the human WAT transcriptome. Therefore, we analyzed WAT biopsies from two previously performed randomized cross-over trials (trial 1: n = 8 lean, healthy men, and trial 2: n = 8 men with obesity and DM2). From 7:30 h onwards, all the participants were exposed to either bright or dim light. Five hours later, we performed a subcutaneous abdominal WAT biopsy. RNA-sequencing results showed major group differences between men with obesity and DM2 and lean, healthy men as well as a differential effect of bright-light exposure. For example, gene sets encoding proteins involved in oxidative phosphorylation or respiratory chain complexes were down-regulated under bright-light conditions in lean, healthy men but up-regulated in men with obesity and DM2. In addition to evident group differences between men with obesity and DM2 and healthy lean subjects, autonomic or neuroendocrine signals resulting from bright-light exposure also differentially affect the WAT transcriptome.