BACKGROUND: Circadian rhythm disruptions are a common concern for poststroke patients undergoing rehabilitation and might negatively impact their functional outcomes.
OBJECTIVE: Our research aimed to uncover unique patterns and disruptions specific to poststroke rehabilitation patients and identify potential differences in specific rest-activity rhythm indicators when compared to inpatient controls with non-brain-related lesions, such as patients with spinal cord injuries.
METHODS: We obtained a 7-day recording with a wearable actigraphy device from 25 poststroke patients (n=9, 36% women; median age 56, IQR 46-71) and 25 age- and gender-matched inpatient control participants (n=15, 60% women; median age 57, IQR 46.5-68.5). To assess circadian rhythm, we used a nonparametric method to calculate key rest-activity rhythm indicators-relative amplitude, interdaily stability, and intradaily variability. Relative amplitude, quantifying rest-activity rhythm amplitude while considering daily variations and unbalanced amplitudes, was calculated as the ratio of the difference between the most active 10 continuous hours and the least active 5 continuous hours to the sum of these 10 and 5 continuous hours. We also examined the clinical correlations between rest-activity rhythm indicators and delirium screening tools, such as the 4 A\'s Test and the Barthel Index, which assess delirium and activities of daily living.
RESULTS: Patients who had a stroke had higher least active 5-hour values compared to the control group (median 4.29, IQR 2.88-6.49 vs median 1.84, IQR 0.67-4.34; P=.008). The most active 10-hour values showed no significant differences between the groups (stroke group: median 38.92, IQR 14.60-40.87; control group: median 31.18, IQR 18.02-46.84; P=.93). The stroke group presented a lower relative amplitude compared to the control group (median 0.74, IQR 0.57-0.85 vs median 0.88, IQR 0.71-0.96; P=.009). Further analysis revealed no significant differences in other rest-activity rhythm metrics between the two groups. Among the patients who had a stroke, a negative correlation was observed between the 4 A\'s Test scores and relative amplitude (ρ=-0.41; P=.045). Across all participants, positive correlations emerged between the Barthel Index scores and both interdaily stability (ρ=0.34; P=.02) and the most active 10-hour value (ρ=0.42; P=.002).
CONCLUSIONS: This study highlights the relevance of circadian rhythm disruptions in poststroke rehabilitation and provides insights into potential diagnostic and prognostic implications for rest-activity rhythm indicators as digital biomarkers.

UNASSIGNED: This single-arm, mixed-methods, pilot study examined the feasibility and preliminary efficacy of an adapted version of the transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) on multidimensional sleep health (MDSH) in a sample of adults with excess weight and suboptimal sleep health.
UNASSIGNED: Participants received up to eight, weekly, remotely delivered, tailored TranS-C sessions. At pre- and post-intervention, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and 7 days of Fitbit data were used to evaluate changes in sleep dimensions (regularity, alertness, timing, satisfaction, duration, and efficiency) and the composite MDSH score. Study feasibility examined recruitment, data collection, and intervention engagement (completion of core TranS-C sessions). Acceptability of the intervention was assessed with semi-structured interviews, which were analyzed using thematic analysis.
UNASSIGNED: From 85 referrals, 11 individuals were eligible, and 10 completed the study. All intervention participants completed the measures needed to calculate their composite MDSH score and completed the core intervention sessions. Themes from interviews support the intervention\'s remote delivery approach, applicability of the information provided, and impact on self-reported health. The intervention resulted in a large improvement in the mean composite MDSH score (Cohen\'s d = 1.17). Small-to-large effects were also observed for individual sleep health dimensions except for timing.
UNASSIGNED: Adapted TranS-C is acceptable for adults with excess weight and suboptimal sleep health and may be effective at improving short-term MDSH. With changes to recruitment methods, a larger study is feasible. Limitations include the small sample size and the lack of a control condition.

Eating disorders (ED) are psychological disorders characterized by dangerous eating behaviours, including protracted fasting and binge eating. Mental disorders comorbidities (e.g., anxiety and depression), as well as sleep difficulties, are common and might interfere with treatment response. This work investigated sleep quality, circadian preferences, and sleep disorders in ED patients compared to healthy controls (HC) and the impact of ED treatment on patients\' sleep. A literature search on Pubmed, Web of Science, Medline, and PsychInfo included 27 studies. Random effect analyses were performed (sample eating disorders = 711; sample healthy controls = 653) and subgroup analyses were calculated based on the ED subgroups: Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder. Whole sample analyses showed poorer physiological and subjective sleep quality in patients. Subgroup analyses showed that poorer physiological sleep was present only in anorexia nervosa. Two studies reporting circadian preferences and sleep disorders showed higher evening preference in patients and no differences in apnea prevalence between patients and healthy controls, respectively. Some studies suggested that specialized eating disorder treatments (e.g., Cognitive Behavioural Therapy for ED) can improve sleep quality in patients. Although these findings highlight poorer sleep in patients with ED compared to healthy controls, the mechanisms underlying sleep alterations in eating disorders remain to be identified.

Our study aimed to investigate the relationship between sleep-wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44-56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep-wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1-7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep-wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep-wake changes increases the risk of depressive symptoms in midlife women.

Time-restricted feeding (TRF) is a lifestyle intervention that aims to maintain a consistent daily cycle of feeding and fasting to support robust circadian rhythms. Recently, it has gained scientific, medical, and public attention due to its potential to enhance body composition, extend lifespan, and improve overall health, as well as induce autophagy and alleviate symptoms of diseases like cardiovascular diseases, type 2 diabetes, neurodegenerative diseases, cancer, and ischemic injury. However, there is still considerable debate on the primary factors that contribute to the health benefits of TRF. Despite not imposing strict limitations on calorie intake, TRF consistently led to reductions in calorie intake. Therefore, while some studies suggest that the health benefits of TRF are primarily due to caloric restriction (CR), others argue that the key advantages of TRF arise not only from CR but also from factors like the duration of fasting, the timing of the feeding period, and alignment with circadian rhythms. To elucidate the roles and mechanisms of TRF beyond CR, this review incorporates TRF studies that did not use CR, as well as TRF studies with equivalent energy intake to CR, which addresses the previous lack of comprehensive research on TRF without CR and provides a framework for future research directions.

Does time of day matter for cancer immunotherapy? Whereas the concept of optimizing the time of treatment is well documented for chemotherapy, whether it applies to immunotherapy, a revolutionizing treatment exploiting the power of immune cells to control tumors, has recently been addressed in a study published in Cell.

Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent data indicate that they play a central role in antitumor immunity, in both mice and humans. In this review, we discuss the evolving literature on circadian antitumor immune responses and the underlying mechanisms that control them. We further provide an overview of circadian treatment regimens-chrono-immunotherapies-that harness time-of-day differences in immunity for optimal efficacy. Our aim is to provide an overview for researchers and clinicians alike, for a better understanding of the circadian immune system and how to best harness it for chronotherapeutic interventions. This knowledge is important for a better understanding of immune responses per se and could revolutionize the way we approach the treatment of cancer and a range of other diseases, ultimately improving clinical practice.

The bidirectional relationship between cerebral structures and the gastrointestinal tract involving the microbiota embraces the scientific concept of the microbiota-gut-brain axis. The gut microbiome plays an important role in many physiological and biochemical processes of the human body, in the immune response and maintenance of homeostasis, as well as in the regulation of circadian rhythms. There is a relationship between the higher prevalence of a number of neurological disorders, sleep disorders and changes in the intestinal microbiota, which actualizes the study of the complex mechanisms of such correlation for the development of new treatment and prevention strategies. Environmental factors associated with excessive light exposure can aggravate the gut dysbiosis of intestinal microflora, and as a result, lead to sleep disturbances. This review examines the integrative mechanisms of sleep regulation associated with the gut microbiota (the role of neurotransmitters, short-chain fatty acids, unconjugated bile acids, bacterial cell wall components, cytokines). Taking into account the influence of gut dysbiosis as a risk factor in the development of various diseases, the authors systematize key aspects and modern scientific data on the importance of microflora balance to ensure optimal interaction along the microbiota-gut-brain axis in the context of the regulatory role of the sleep-wake cycle and its disorders.
Двустороння связь между церебральными структурами и желудочно-кишечным трактом с участием микробиоты охватывает научную концепцию оси мозг—кишечник—микробиом. Кишечный микробиом принимает важное участие во многих физиологических и биохимических процессах организма, в иммунном ответе и поддержании гомеостаза, а также в регуляции циркадианных ритмов. Отмечается взаимосвязь между более высокой распространенностью ряда неврологических расстройств, нарушений сна и изменениями в микробиоте кишечника, что актуализирует изучение сложных механизмов такой корреляции для разработки новых стратегий лечения и профилактики. Факторы внешней среды, связанные с избыточным световым воздействием, могут усугубить дисбиоз кишечной микрофлоры, и, как следствие, приводят к нарушениям сна. В настоящем обзоре рассматриваются интегративные механизмы регуляции сна, связанные с микробиотой кишечника (роль нейромедиаторов, короткоцепочечных жирных кислот, неконъюгированных желчных кислот, компонентов бактериальной клеточной стенки, цитокинов). Принимая во внимание влияние дисбиоза кишечника как фактора риска при развитии различных заболеваний, авторами систематизированы ключевые аспекты и современные научные данные о значении баланса микрофлоры для обеспечения оптимального взаимодействия по оси мозг—кишечник—микробиом в контексте с регулирующей ролью цикла сон—бодрствование и его нарушений.

Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain-including those involving serotonin and dopamine-exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in Tph2 knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in Tph2 knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.

Acrylamide (ACR) is a known carcinogen and neurotoxin. It is chronically consumed in carbohydrate-rich snacks processed at high temperatures. This calls for systematic research into the effects of ACR intake, best performed in an experimental model capable of detecting symptoms of its neurotoxicity at both high and low doses. Here, we study the influence of 10 µg/g (corresponding to the concentrations found in food products) and, for comparison, 60, 80 and 110 µg/g dietary ACR, on the fruit fly Drosophila melanogaster. We show that chronic administration of ACR affects lifespan, activity level and, most importantly, the daily and circadian pattern of locomotor activity of Drosophila. ACR-treated flies show well-defined and concentration-dependent symptoms of ACR neurotoxicity; a reduced anticipation of upcoming changes in light conditions and increased arrhythmicity in constant darkness. The results suggest that the rhythm-generating neural circuits of their circadian oscillator (biological clock) are sensitive to ACR even at low concentrations if the exposure time is sufficiently long. This makes the behavioural readout of the clock, the rhythm of locomotor activity, a useful tool for studying the adverse effects of ACR and probably other compounds.