Objective: Several lines of evidence support a relationship between circadian rhythms disruption in the onset, course, and maintenance of mental disorders. Despite the study of circadian phenotypes promising a decent understanding of the pathophysiologic or etiologic mechanisms of psychiatric entities, several questions still need to be addressed. In this review, we aimed to synthesize the literature investigating chronobiologic theories and their associations with psychiatric entities. Methods: The Medline, Embase, PsycInfo, and Scopus databases were comprehensively and systematically searched and articles published between January 1990 and October 2019 were reviewed. Different combinations of the relevant keywords were polled. We first introduced molecular elements and mechanisms of the circadian system to promote a better understanding of the chronobiologic implications of mental disorders. Then, we comprehensively and systematically reviewed circadian system studies in mood disorders, schizophrenia, and anxiety disorders. Results: Although subject characteristics and study designs vary across studies, current research has demonstrated that circadian pathologies, including genetic and neurohumoral alterations, represent the neural substrates of the pathophysiology of many psychiatric disorders. Impaired HPA-axis function-related glucocorticoid rhythm and disrupted melatonin homeostasis have been prominently demonstrated in schizophrenia and other psychotic disorders, while alterations of molecular expressions of circadian rhythm genes including CLOCK, PER, and CRY have been reported to be involved in the pathogenesis of mood disorders. Discussion: Further translational work is needed to identify the causal relationship between circadian physiology abnormalities and mental disorders and related psychopathology, and to develop sound pharmacologic interventions.

Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. Management of sleep-wake circadian disorders (SWCD) includes education to sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e. positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially, or can be a combination of several forms of therapy. Drugs used for SWCD include traditional sleep or wake-promoting agents, chronotherapeutic agents. Recently, novel medications, which are more precisely acting on specific neurochemical systems (i.e. orexin system) important for sleep and wake, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

Background and Objectives: Light therapy (LT) is used as an adjunctive treatment for sleep problems. This study evaluates the impact of LT on sleep quality and sleep-related parameters in patients with sleep disorders. Materials and Methods: We performed a pilot randomized, open-label clinical trial. Fourteen patients aged 20–60 years with sleep disorders for more than three months were randomized into the control and LT groups (1:1 ratio). The LT group was instructed to use a device that provides bright LT (6000 K, 380 lux, wavelength 480 nm) for at least 25 minutes before 09:00 am for two weeks. A self-reported questionnaire was used to evaluate circadian preference, mood, and sleep-related parameters. We analyzed serum cortisol levels and clock genes expression. Results: The Epworth Sleepiness Scale (ESS), insomnia severity index, and Pittsburgh Sleep Quality index were significantly improved within the LT group only after the two-week period. When comparing the two groups, only the change in ESS significant was significant (mean difference; control: -0.14 vs LT: -1.43, p=0.021) after adjusting for baseline characteristics. There were no significant differences in serum cortisol or clock genes expression. Conclusions: LT can improve daytime sleepiness in patients with sleep disorders; however, further well-designed studies are warranted to confirm its efficacy.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

REV-ERBα and its paralog, REV-ERBβ encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock that can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes were controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provided strong evidence for isoform-dependent actions. For example, REV-ERBα were more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components required REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways, despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators may help treat metabolic disturbances and certain types of cancer.

Adverse childhood experiences are known to program children for disrupted biological cycles, premature aging, microbiome dysbiosis, immune-inflammatory misregulation, and chronic disease multimorbidity. To date, the microbiome has not been a major focus of deprogramming efforts despite its emerging role in every aspect of ACE-related dysbiosis and dysfunction. This article examines: 1) the utility of incorporating microorganism-based, anti-aging approaches to combat ACE-programmed chronic diseases (also known as noncommunicable diseases and conditions, NCDs) and 2) microbiome regulation of core systems biology cycles that affect NCD comorbid risk. In this review microbiota influence over three key cyclic rhythms (circadian cycles, the sleep cycle, and the lifespan/longevity cycle) as well as tissue inflammation and oxidative stress are discussed as an opportunity to deprogram ACE-driven chronic disorders. Microbiota, particularly those in the gut, have been shown to affect host-microbe interactions regulating the circadian clock, sleep quality, as well as immune function/senescence and regulation of tissue inflammation. The microimmunosome is one of several systems biology targets of gut microbiota regulation. Furthermore, correcting misregulated inflammation and increased oxidative stress is key to protecting telomere length and lifespan/longevity and extending what has become known as the healthspan. This review article concludes that to reverse the tragedy of ACE-programmed NCDs and premature aging, managing the human holobiont microbiome should become a routine part of healthcare and preventative medicine across the life course.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Current patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, SI-compliant standard provides a way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert-scientific consensus and expressed according to this new measurement standard. These recommendations are supported by a comprehensive analysis of the sensitivity of human ‘non-visual’ responses to ocular light, are centred on an easily measured quantity (melanopic equivalent daylight (D65) illuminance), and provide a straightforward framework to inform lighting design and practice.

Background: Blood pressure (BP) is characterized by a circadian rhythm (Circr), with lower nighttime values, called dipping. Non-dipping is associated with higher CVD risk. The Circr of urinary sodium excretion (NaCle), peaking during the day, is linked to BP patterns. Physical ac-tivity (PA) is known to improve BP control and enhance the dipping phenomenon, but its possi-ble effect on NaCle remains unclarified. Objectives: This study aimed to investigate the correla-tion between PA and the Circr of NaCle and to determine if the relationship is independent of age, sex, BP values, dipping pattern, and salt intake. Methods: A cross-sectional analysis was conducted using data from the Ticino Epidemiological Stiffness Study, involving 953 participants in Switzerland. Data collection included standardized questionnaires, blood samples, 24-hour urine collections, and ambulatory BP monitoring. Participants were categorized into sedentary, partially active, and active. The effect of PA, NaCl intake, and dipping on the day/night NaCle ratio, was assessed with multivariable linear regressions. Results: Participants median age 49 years, with 78% having normal BP values and 47% exhibiting a dipping pattern. 51% were classi-fied as sedentary and 22% as partially active. The median NaCl intake was 7.9 g/day. The youngest subjects had a higher hourly NaCle ratio compared to older subjects. Higher NaCl in-take correlated with increased BP, phenomenon more pronounced in men and younger subjects. The hourly day/night NaCle ratio positively correlates with dipping; however, PA did not show a significant correlation with the NaCle ratio. Conclusion: This study indicates that while the day/night NaCle ratio correlates with the dipping pattern, PA is unrelated to the circadian rhythm of renal sodium handling. The beneficial effects of PA on BP and cardiovascular health thus appear to be mediated through mechanisms other than NaCle. These are explorative find-ings only, but relativize the need for further investigations on the topic.

In mice, mutations or targeted disruptions of the core circadian gene Bmal1 have been implicated in early onset of ocular pathologies, including premature/congenital cataract development. The aim of the present study was to analyze probands of consanguineous Pakistani cataract families to identify the novel pathogenic variants in the BMAL1 gene. We have studied 21 congenital cataract families. Ophthalmic examination was performed for the probands and available family members. Genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing was performed for the entire coding region of the BMAL1 gene. Targeted Sanger sequencing of BMAL1 revealed a heterozygous variant c.41A>T; p.(Asp14Val) in one proband, but it did not co-segregate with the disease phenotype in the family. In addition, a nonsynonymous variant (rs2290037) was identified in five probands. Our study is the first one to analyze the role of BMAL1 gene mutations in humans for their association with congenital cataract. Although we were unable to find the variants associated with congenital cataract families from Pakistan, more studies from other populations will be informative to further prove the role of BMAL1 with the disease.

Circadian rhythms misalignment is associated with hypertension. The aim of the study was to evaluate the concentration of selected clock proteins- cryptochrome 1 (CRY1) and circadian locomotor output cycles kaput (CLOCK) and to determine their relationships with biochemical and anthropometric parameters and lifestyle elements (diet, physical activity, quality of sleep) in hypertensive patients. In 25 female with hypertension (HT) and 49 non-hypertensive women (NHT), the CRY1 and CLOCK concentrations, total antioxidant status (TAS), lipid profile and glycemia were conducted. Blood pressure and anthropometric measurements, nutritional, exercise and sleep analyses were performed. In HT the CRY1 level was 40.2% lower than in the NHT. No differences were noted in CLOCK concentration between groups. The study showed no relationship between CRY1 or CLOCK concentrations and glucose or lipids profile, amount of physical activity and sleep quality, although CRY1 was associated with some anthropometric parameters. There was a negative correlation between the CLOCK concentration and the amount of saturated fatty acids consumed (24h) in HT. That indicates the possible influence of the diet on the CLOCK level. In a detailed prognosis of the risk of hypertension, it is worth considering the measurement of the level of CRY1 in populations with abnormal anthropometric indices.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first- and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical popu-lation of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: The Korean ver-sion of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression In-ventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experi-encing their first episode (n=22, mean age: 15.09±1.44 years) and those with recurrent episodes (n=39, mean age: 15.95±1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first-episode 26.18±10.54 and recurrent episode 25.90±10.59, STAI-S: first-episode 56.91±12.12 and recurrent episode 57.49±11.93, STAI-T: first-episode 60.36±11.63 and recurrent episode 59.09±12.10, SPAQ-total: first-episode 6.59±4.86 and recurrent episode 6.77±5.23, KtCS: first-episode 30.32±5.83 and recurrent episode 28.13±7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r=0.26), KtCS (r=-0.48), K-BRIAN-sleep (r=0.58), K-BRIAN-activity (r=0.64), K-BRIAN-social (r=0.71) and K-BRIAN-eating (r=0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized, due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment and pause release are two critical regulatory steps that determine the status of Pol II pausing. Recently, we showed that Pol II pausing exhibits genomewide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms. We also discuss the possible mechanisms for daily changes in Pol II pausing and the critical involvement of Pol II pausing regulation in generating rhythmic transcription output.

The calmodulin-binding transcription activators (CAMTAs) mediate transcriptional regulation of development, growth, and responses to various environmental stresses in plants. To characterize the biological processes of soybean CAMTA (GmCAMTA) family members in response to abiotic stress, we identified 15 GmCAMTA genes from soybean (Glycine max L.) and investigated their roles in the abiotic stress response. The transcriptions of GmCAMTAs exhibited distinct circadian regulation patterns and were expressed differently in response to salt, drought, and cold stresses, except ABA. Interestingly, the expression levels of GmCAMTA2, GmCAMTA8, and GmCAMTA12 were higher in stem tissue than in other soybean tissues. To determine the roles of GmCAMTAs in the regulation of developmental processes and stress responses, we isolated GmCAMTA2 and GmCAMTA8 cDNAs from soybean and generated Arabidopsis overexpressing transgenic plants. The GmCAMTA2-OX and GmCAMTA8-OX plants showed hypersensitivity to drought stress. The water in the leaves of GmCAMTA2-OX and GmCAMTA8-OX plants was lost faster than that in WT plants under drought stress conditions. In addition, stress-responsive genes in the GmCAMTA2-OX and GmCAMTA8-OX plants were down-regulated under drought stress conditions. Our results suggest that GmCAMTA2 and GmCAMTA8 genes are regulated by circadian rhythms and function as negative regulators in development and drought stress responses.

With the development of social economy, the quality of national life has been rapidly improved, along with the accelerated aging of the population and the continued prevalence of metabolic risk factors. Cardiometabolic diseases (CMDs) have become a major disease burden for both urban and rural residents in China, and most of them are related to lifestyle changes in modern society, especially circadian rhythm disorders. Circadian rhythm regulating the activity of metabolism, such as carbohydrates, lipids, and other nutrients, is the most important pathway modulating the health. Nowadays, studies have shown that the interaction between circadian rhythmicity and gut microbiota counts for the homeostasis of metabolic health, while circadian rhythm disruption is associated with gut microbiota dysbiosis and metabolic diseases. However, there is a lack of research on the topic of gut microbiota mechanisms regulating circadian rhythm disruption leading to CMDs. With increased burden of CMDs prevention and treatment, as well as the demand of healthcare resource allocation, it prompts us to put forward a new strategy to solve this problem. This review focuses on the interactions between circadian rhythm and gut microbiota to elucidate the potential mechanisms of circadian rhythm disruption induced CMDs, providing a solid support for further prevention and treatment.

Sleep is an essential component of a healthy lifespan, influencing both physical and mental well-being along with good quality of life. Adequate sleep quality and quantity are associated with a host of health advantages, including enhanced immune function, learning and memory, emotional well-being, and cardiovascular health. Chronic sleep deprivation, or poor sleep quality, is associated with a variety of negative health outcomes, including an increased risk of obesity, diabetes, hypertension, depression, cancer, and even premature death. One compelling argument in favor of sleep as a predictor of a healthy lifespan is its effect on cellular repair and regeneration. During sleep, the body goes through important activities such as tissue repair, muscular growth, and memory consolidation. Sleep also helps the brain eliminate toxins and metabolic waste, which contributes to its optimal functioning. Without adequate sleep, these important processes are jeopardized, resulting in accelerated aging and greater susceptibility to chronic illnesses. Furthermore, sleep is essential for maintaining hormone balance, particularly those involved in appetite regulation and metabolism. Sleep disturbances can disrupt the regulation of these hormones, resulting in weight gain, metabolic diseases, and, ultimately, a shorter life span. Finally, prioritizing optimal sleep is pivotal for increasing longevity and general health. Emphasizing the importance of sleep hygiene and treating sleep-related dysfunctions should be part of the modern approach to extending healthy life.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

In conclusion, the present study demonstrated the safety of practicing WFM at different TOD. Furthermore, it appears that practicing WF in the evening is safer, as indicated by HRR60s, [Gl], and MBP findings. The utilization of digital biomarkers for monitoring health status during WFM has been shown to be efficient.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Light enables vision and exerts widespread effects on physiology and behaviour, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in a controlled physiological and behavioural state. Proper consideration of light during experimentation - both when it is explicitly employed as an independent variable and as a general feature of the environment - has the potential to provide more informative experimental designs and more reliable outcomes, contributing to Reduction and Refinement, helping to ensure more ethical animal use, and improving data quality. As such, it is unfortunate that ambient light for animals is typically quantified in units (lux) designed for human observers. We report the consensus views of an expert working group, with expertise spanning mammalian photobiology, neurobiology and animal husbandry and welfare, convened in February 2023 to agree upon metrics for light appropriate for non-human mammals and their application to improve animal welfare and the quality of animal research. We conclude that species-specific versions of the recently standardised a-opic metrology represent the best available approach to quantifying light. We provide methods for measuring these quantities; practical guidance for their implementation in husbandry and experimentation; and quantitative guidance on appropriate light exposure for laboratory mammals.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

The western flower thrips, Frankliniella occidentalis, is invasive and polyphagous. Its visual signal plays a crucial role in host location, suggesting that thrips has diurnal behavior. However, any diel rhythmicity of the thrips behavior is not yet well understood. This study analyzed the diurnal rhythmicity of the feeding and mating behaviors of thrips, and the patterns were explained in terms of diel rhythmicity by assessing the expression of genes associated with the circadian clock. Most feeding behaviors were observed during photophase in both larvae and adults. In mating behavior, which is mainly exhibited in 2~3 days-old young adults after emergence, most adults copulated at photophase. This diurnal pattern of the mating behavior was further supported by the analysis of a temporal calling behavior for mating, which was biased toward photophase. Four genes associated with the circadian clock were predicted in the F. occidentalis genome: period (PER), Timeless (TIM), Doubletime (DBT), and clock (CLK). All these genes exhibited a characteristic diel pattern in their gene expressions in a 24 h-period. The high expression peaks of these genes except for DBT were observed at photophase. To confirm the functional association of these genes with the feeding and mating behaviors, individual RNA interference specific to each gene was executed by feeding the gene-specific double-stranded RNA. Aside from DBT, suppression of these gene expressions resulted in significant deviations of the diel rhythms of the behaviors. These results suggest that the genetic components of the diel rhythmicity mediate the diurnal feeding and mating behaviors of F. occidentalis.

Patients with cancer experience insomnia or sleep disturbances. This study aimed to explore whether the discrepancy between a patient's desired time in bed and total sleep time (DBST) index is a measurement tool for insomnia severity or sleep onset latency [SOL] in patients with cancer. This retrospective medical records review study gathered clinical information and rating scale scores including Insomnia Severity Scale (ISI), Cancer-related Dysfunctional Beliefs about Sleep scale (C-DBS), Patient Health Questionnaire-9 items (PHQ-9), State subcategory of State and Trait Anxiety Inventory, and Short form of Fear of Progression Questionnaire. Sleep indices of time variables (bedtime, sleep onset time, and wake-up time), duration variables [SOL, time in bed (TIB), time in bed for 24 hours (TIB/d), and duration from wake-up time to bedtime (WTB)], and the DBST index were calculated. The ISI score was predicted by PHQ-9 (β=0.34, P<0.001), C-DBS (β=0.17, P=0.034), and DBST index (β=0.22, P=0.004) with a significant correlation with the DBST index (r=0.19, p=0.020). The DBST index was significantly correlated with long SOL (r=0.23, P=0.005). Long SOL was predicted by early bedtime (β=0.18, P=0.045), short WTB (β=-0.26, P=0.004), and high DBST index (β=0.19, P=0.013). The DBST index was significantly correlated with a predicting variable each for insomnia severity and SOL in patients with cancer.

Gliomas are solid tumors of the Central Nervous System (CNS) that originated from different glial cells. The World Health Organization (WHO) classified these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as a grade IV. GBM are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.

The aim of the study is to obtain a more complete picture of the blood plasma melatonin concentration in the donkey species. To this purpose sampling and statistical processing were carried out in such a way that allowed to establish the annual and daily rhythm. Based on human observations, according to the hypothesis of the authors, the blood plasma melatonin concentration of pregnant individuals rises during late gestational period, before parturition. To confirm this, the melatonin concentration of pregnant and non-pregnant mares was monitored and compared. In regard to the circannual rhythm, the significantly lowest midnight melatonin value (27.67 pg/ml) is typical for the summer solstice. Under consideration of circadian changes, a significantly strongest melatonin production (45.16 pg/ml) can be observed on the night of the winter solstice (p < 0.001). Considering the gestational age, the blood plasma melatonin concentration (around 38 pg/ml) does not change as pregnancy progresses (p = 0.136). The results obtained in the study population of the domestic ass usefully expand the little knowledge previously gathered about the development of blood plasma melatonin concentration of this species.

(1) Background: The aim of this study was to investigate the circadian rhythms of tongue features according to the effects of physiological phases over a 24-hour period. (2) Methods: Fifteen healthy participants aged 20 to 69 years were recruited. The participants did not have current chronic diseases or past diseases and had to meet the inclusion and exclusion criteria. The participants stayed at the Gil Hospital for a duration of 2 nights and 3 days. On the first day, at 18:00, they consumed their allocated portions of food and water and then completed a questionnaire. At approximately 21:00, their tongue images were acquired using a computerized tongue image acquisition system, following which they slept for 8 hours, commencing at 23:00. Measurements were taken from 07:00 through 21:00 on the second day, and the final acquisition was taken at 07:00 on the following morning, resulting in a total of eight images. The circadian rhythm was authenticated and quantified utilizing the single cosinor analysis, a technique for periodic regression analysis for fitting a 24-hour cosine curve. (3) Results: Cosinor analysis revealed that all tongue features were significantly related to circadian rhythm. (4) Conclusions: The results of this study may be important for considering the time of day at which the tongue is observed and tongue status is evaluated.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

Drosophila circadian circuit is one of the best described neural circuits but is complex enough to obscure our understanding of how it actually works. Animals’ rhythmic behavior, the seemingly simple outcome of their internal clocks, relies on the interaction of heterogeneous clock neurons that are spread across the brain. Direct observations of their coordinated network interactions can bring us forward in understanding the circuit. The current challenge is to observe activity of each of these neurons over a long span of time –hours to days– in live animals. Here we review the progress in circadian circuit interrogation powered by in vivo calcium imaging.

We investigated if the abnormal sleep-wake rhythms in infants are related to the future development of autism spectrum disorder (ASD), using questionnaire from September to October 2016. The parents of a total 160 children with ASD (male, n=123; female, n=37) recruited from the two hospitals in K and H cities and as a control group, 145 children (male, n=75; female, n=70) recruited from four nursery schools in T city. Fisher’s exact test was used for the comparison of categorical variables. The associations of bedtime and waking time on weekdays and holidays in infancy, at 1-3≦ (1-3) years of age and at 3-5 ≦ (3-5)years of age with the prevalence of ASD were analyzed using a multivariable logistic regression analysis. Especially by 3 years of age, the following factors were associated with an increased risk of developing ASD in the future: 1) short sleep (<8h), 2) long time to fall asleep (>60min), 3) sleep onset time after 22:00h, 4) wake-up time after 07:00h and/or 08:00h on weekdays and holidays, respectively, 5) frequent (>3 times) and long-term awakening (>60min). Misalignment and/or shift of the sleep-wake circadian rhythm in infant may be one of the precursors and/or risk factor to the future development of ASD.

The circadian clock regulates daily changes in behavioral, endocrine and metabolic activities in mammals. Circadian rhythms in cellular physiology are significantly affected by aging. In particular, we previously found that aging has profound impact on daily rhythms in mitochondrial functions, leading to increased oxidative stress. However, this is unlikely due to malfunction of molecular clocks in the suprachiasmatic nucleus or peripheral tissues, as robust clock oscillations are observed therein in old animals. Nonetheless, aging induces changes in gene expression levels and rhythms in various peripheral and probably central tissues. In this article, we review findings on the roles of the circadian clock and aging in regulating mitochondrial rhythms and redox homeostasis. Chronic sterile inflammation is implicated in mitochondrial dysfunction and increased oxidative stress during aging. In particular, upregulation of CD38 by inflammatory response can disturb mitochondrial functions in multiple ways.

Huntington’s disease (HD) causes progressive movement disorders and cognitive deficits. Besides, sleep disturbances and emotional distress are prominent clinical signatures of HD. The experimental subjects and HD human brains display altered regenerative plasticity resulting from aberrant neurogenic and nonneurogenic areas. Sleep disorders, emotional disruption, and cognitive deficits have been linked to impaired cell cycle events of neural stem cells (NSC) in neurodegenerative disorders. In a physiological state, circadian clock gene pathways play important roles in the regulation of the proliferation and differentiation of NSC, whereas the irregular circadian clock pathway is attributed to impairment in the neurogenic process. The recent advancement of chemogenetic-based approaches represents a potential scientific tool to rectify the abnormal circadian clock which may aid in mitigating neurogenic failure in the brain. Notably, GABAergic vasoactive intestinal peptide (VIP)-expressing neurons in the brain plays a key role in the regulation of neuroplasticity and circadian rhythm. Thus, this conceptual review article addresses the potential link between sleep disorder and aberrant neurogenic events in HD and proposes chemogenetic kindling of vasoactive intestinal peptide (VIP) -expressing GABAergic neurons in the brain as a therapeutic strategy for reprogramming the clock gene pathways in mitigating the neurodegenerative failure in HD.

The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years; its original publication has been cited 1,240 times (Google Scholar, May 2019); its online version, which was available until July 2017, has produced almost 300,000 entries from all over the world (MCTQ database). The MCTQ has gone through several versions, has been translated into 13 languages and has been validated against other more objective measures of daily timing in several independent studies. Besides being used as a method to correlate circadian features of human biology with other factors – ranging from health issues to geographical factors – the MCTQ gave rise to quantifying old wisdoms, like “teenagers are late” and has produced new concepts, like social jetlag. Some like the MCTQ’s simplicity and some view it critically; it is time to have a self-critical view on the MCTQ, to address some misunderstandings and give some definitions about MCTQ-derived chronotype and the concept of social jetlag.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

Circadian rhythm (CR) influences various physiological functions, including physical and cognitive performance, which fluctuate throughout the day. The present study aimed to investigate the combined and separate effects of CR and physical fatigue on cognitive and physical performance. A sample of 18 amateur athletes was subjected to a series of tests at three different times of the day: morning, afternoon, and evening. Fatigue was induced following isokinetic concentric exercise combined with a 20-minute treadmill run, followed by assessments of selected physical and cognitive tasks. Repeated measures ANOVA did not reveal an interaction between CR and fatigue in cognitive performance (p &gt; 0.05). However, a significant main effect of fatigue was observed in visual reaction time (VisRT) across all three time points. Moreover, peak torque (PT) and peak torque fatigue index (PTFI) showed significant differences between the three times of the day, peaking in the evening. Although we found no interaction between CR and physical fatigue state on selected cognitive parameters at the three times of day, a separate effect of fatigue on cognitive performance was identified. Additionally, physical parameters exhibited peak values occurring in the evening hours. Future research should further explore underlying mechanisms that potentially influence cognitive performance at different times of the day.

Background: Anxiety disorders can be both an independent risk factor of many somatic conditions and the cause of complications of various organic disorders leading to poor prognosis. Objectives: The purpose of this study is to compare the heart rate variability (HRV) recorded both during the day and at night in patients with anxiety disorders and healthy individuals. Methods: The study was conducted on fifty consecutive outpatients with anxiety disorders who participated in intensive group psychotherapy. The diagnosis was made according to DSM-IV-TR criteria using the PSE-10 questionnaire. Out of 50 patients under study, 17 were diagnosed with panic disorder (PD) and 21 with generalized anxiety disorder (GAD). The control group consisted of 40 healthy people. The resulting three groups were compared in terms of circadian HRV using the Oxford Medilog Suprima Holter System. Results: The HRV analysis showed the nocturnal falls in the time and frequency parameters related to parasympathetic activity (rMSSD, pNN50, HF). The most unfavourable alterations were observed in the PD group, which comprised the disappearance of day vs. night amplitude of the majority of HRV parameters. Hence, the PD group was particularly susceptible to the arrhythmic events. It was noticeable that nocturnal vagotonia in the PD group was significantly lower as compared with the GAD and control group. Conclusions: The innovative aspect of the present study was to find a distinct profile of HRV with regard to the types of anxiety disorders because of the existing considerable differences between the nature of PD and GAD.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM). Sixty male C57BL/6J mice were divided initially to two groups, the shifted group (n=30) exposed to circadian shifts for three months and the non-shifted group (n=30) under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 hour light-dark cycle followed by another five days under reversed light-dark cycle. At the end of the three months a colitis was induced by 2 % DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n=15 per group), sham group non-shifted (Sham-NS), sham group shifted (Sham-S) and DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition by DNA extraction followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, GM composition was also modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings shows a possible interplay between circadian rhythm disruption, GM dynamics, and colitis pathogenesis.

An autonomous endogenous time-keeping is ubiquitous across many living organisms known as circadian clock when it has a period of about 24 hours. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus \textit{Neurospora crassa} is a well established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of \textit{Neurospora} is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedbacks among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 hrs. Our model reveals a switch between WC1 induced transcription and FFC assisted inactivation of WC1. Using the new model we also study possible mechanisms of glucose compensation. A fairly simple model with just 3 non-linearities helps to elucidate clock dynamics revealing a mechanism of rhythms production. The model can further be utilized to study entrainment and temperature compensation.

The impact of cyclic heat stress (CHS) and lighting events on pig feeding behavior (FB) was investigated. The FB of 90 gilts was recorded in real time under two ambient temperatures (AT): thermoneutrality (TN, 22 °C) or CHS (22°/35 °C). The day was divided into four periods: PI (06-08 h); PII (08-18 h); PIII (18-20 h); and PIV (20-06 h). Automatic and Intelligent Precision Feeders recorded each feed event for each pig. An estimated meal criterion (49 minutes) was used to calculate the FB variables. Feed behavior in both ATs followed a circadian pattern. The CHS reduced the feed intake by 6.9%. Pigs prioritized feed intake during the coolest hours of the day; however, nocturnal cooling did not allow the pigs to compensate for the reduced meal size due to CHS. The highest meal size and most of the meals were observed during the lighting-on period. Pigs reduced their interval between meals during periods II and III. The lighting program increased the meal size when the lights were switched on and reduced the meal size when the lights were switched off. Thus, the dynamics of the FB were largely influenced by AT, while the meal size was affected by the lighting program.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Hospitalized patients frequently have disordered and poor-quality sleep due to a variety of both intrinsic and extrinsic factors. These include frequent nighttime intrusions, insomnia related to pain and unfamiliar environments, dark conditions during the day with loss of natural light, and disruption of natural sleep cycle due to illness. Sleep wake disturbances can result in deleterious consequence on physical, emotional and cognitive status, which may impact patient satisfaction, clinical recovery, and hospital length of stay. Despite this, clinicians frequently fail to document sleep disturbances and are generally unaware of best practices to improve sleep quality in the hospital. The purpose of this review is to discuss sleep disturbances in hospitalized patients with a focus on causes of sleep disturbance, effect of poor quality sleep, high risk populations, considerations for surveillance and prevention, as well as pharmacologic and non-pharmacologic options for treatment.

The circadian and stress-realizing systems are interconnected, and the balance of their interaction determines the state of human health. The objective of this study was to investigate the modulating effect of activating the circadian system on heart rate variability in female medical students with high anxiety while performing a cognitive task. After 20 minutes of adequate stimulation of circadian photoreceptors with a monochromatic blue light, the cognitive task performance resulted in a decrease in sympathetic impact. During the session of using Blue Sky Pro glasses, a trend of increasing heart rate variability was observed in a state of relative rest (especially in the first 5 minutes). A comparative analysis of the parameters of the letter cancellation test before and after light exposure revealed a statistically significant increase in the indexes reflecting mental productivity, work accuracy, and concentration of attention. The results suggest an essential physiological role of the human circadian system in modulating the autonomic and psycho-emotional conditions, as well as cognitive functions of individuals with high anxiety. Our findings indicate the possibility of quickly correcting the balance in human systemic regulatory mechanisms using the activation of retinal circadian photoreceptors by blue light.

Sleep disorders (SD) have a complex aetiology, and socioeconomic status (SES) as determined by social class, household income, ethnicity and education plays an important role in their development. As SD are associated with cognitive impairment and mood disorders, they in turn impact SES. Socioeconomic status also influences allostatic load caused by chronic accumulation of stress throughout life. Environmental and psychological stressors have a direct effect on SD, and they are modulated by SES, in combination with comorbidities like obesity and cardiovascular disease. This review explores the recent theories about the influence of SES on the development of SD in the general population, whether or not occurring with comorbidities, and also focusses on the interplay between socioeconomic status, circadian rhythms, aging and clinical outcomes like metabolic diseases and cancer.

Melatonin is an important hormone with a methoxy-indole structure. It is secreted regularly by the pineal gland of mammals. It takes part in many chemical, biological, and physiological activities of the body. Melatonin, acts as a basic hormone, and is responsible for circadian rhythm regulation and sleep control. It has been shown to occur in the highest concentration in organisms during the night times. In living organisms, many activities that have physiological, biological, hormonal, and psychological characteristics follows a certain rhythm. Body temperature, hormone levels, sleep-wakefulness, and some other cognitive functions in humans also change with the circadian rhythm. Its synthesis and release begin with darkness and end with light. This review aims to explore the functions of melatonin such as its stimulating effects on antioxidant enzymes, reducing lipid peroxidation, and protecting brain tissue from oxidative damage. It also has properties that stop the proliferation of cancer cells and prevent tumor growth. Melatonin, which was previously known only as an animal hormone, has been found to also exist in plants. Research has shown that melatonin is present in almost all plant species analyzed to date and that it performs functions similar to those in animals. In plants, it plays a vital role in dealing with various abiotic and biotic stresses. Melatonin acts as an important antioxidant in post-harvest technology and extends the post-harvest life of fruits and vegetables. It also takes part in the regulation of stress-specific genes and the activation of pathogenesis-related proteins and antioxidant enzymes. The most prominent roles of melatonin in plants include regulating circadian rhythm, growth, and development, and increasing tolerance to a wide range of environmental stress factors. The review reveals the effects of melatonin as an extremely important secondary metabolite, on human, animal, and plant metabolism. The use of PRISMA guidelines was used for reporting, search, selection, and synthesis. Information up to 2024 was searched from search engines for the occurrence, nature and function of melatonin. Key words such as structural function, hormonal function, secretion and metabolism were used in the search of publications.

Running at odds with the timing imposed by the circadian clock plays an important role in the process that leads to communicable and non communicable diseases. The primary objective of this study was to analyse whether early dinner eater children were at lower risks of acute respiratory infections than late dinner eater children, during the COVID-19 pandemic. Methods: This cross sectional study was conducted from July to December 2020 on children attending Majorcan emergency services. Clinical data collected included timing, symptoms, laboratory tests and imaging studies of current illness. Each diagnosis was validated by general paediatricians. Our survey on dinner time habits was carried out by using self-administered questionnaires. Results: A total of 669 children under age 18 were included in the study. The median of dinner time was 8:30 pm. Late dinner eaters accounted for a higher proportion of acute otitis media than early dinner eaters (7% vs 3%; P=0.028). Other infectious diseases were not associated with dinner time habits. Conclusions: We make a preliminary estimate of the link between late dinner habits and acute otitis media in children. However, no conclusions about causality can be established due to the observational design of the study.

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients’ quality of life. The disease is caused by genetic irregularities affected by the epigenetic and environmental factors. Some of these factors may include the seasonal changes, such as solar radiation, air pollution and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis.

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of Autism Spectrum Disorder (ASD) and inherited intellectual disability (ID). Besides ASD, ID and other issues, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, present excellent model for research in the FXS field. During this study, sleep pattern and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography in integration with a highly-customized version of software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1 B55 male mutants can be considered weak rhythmic flies rather than totally arrhythmic, and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of videography and software used in the current study should be recommended as a gold-standard methodology for such further research.

Exposure of experimental rodents to controlled cycles of light, food, and temperature is important when investigating alterations in circadian cycles that profoundly influence health and disease. However, applying such stimuli simultaneously is difficult in practice. Our aim was to design, build, test, and open-source describe a simple device that subjects a conventional mouse cage to independent cycles of physiologically relevant environmental variables. The device is based on a box enclosing the rodent cage to modify the light, feeding, and temperature environments. The device provides temperature-controlled air conditioning (heating or cooling) by a Peltier module and includes programmable feeding and illumination. All functions are set by a user-friendly front panel for independent cycle programming. Bench testing with a model simulating the CO2 production of mice in the cage showed: a) suitable air renewal (by measuring actual ambient CO2), b) controlled realistic illumination at the mouse enclosure (measured by a photometer), c) stable temperature control, and d) correct cycling of light, feeding, and temperature. The cost of all the supplies (retail purchased by e-commerce) was &lt; 300 US$). Detailed technical information is open-source provided, allowing for any user to reliably reproduce or modify the device. This approach can considerably facilitate circadian research since using one of the described low-cost devices for any mouse group with a given light-food-temperature paradigm allows for all the experiments to be performed simultaneously, thereby requiring no changes in the light/temperature of a general-use laboratory.

Despite the strong links between sleep, circadian rhythms, and mental health, sleep education has been neglected in mental healthcare provider training programs. The current pilot study examined the potential efficacy and acceptability of a sleep education workshop for trainee psychologists, called the Sleep Psychology Workshop. Eleven students completing their Master of Psychology degrees (90% female, 24.4 ± 1.6 years old) attended the Sleep Psychology Workshop as part of their Health Psychology course, delivered as three, two-hour lectures (total six hours). Trainees’ sleep psychology knowledge quiz scores (% correct) demonstrated significant improvement from pre- (M = 60%, SD = .09) to post-workshop (M = 79%, SD = .08), t (6) = -5.18, p = .002. Trainees also reported increased self-efficacy to use common sleep-related assessment instruments and empirically supported interventions to manage sleep and circadian rhythm disturbances, along with increased confidence to manage insomnia disorder in clinical practice (all p<.02). Trainees also endorsed the workshop as an acceptable sleep education program for trainee psychologists via a post-workshop feedback survey, focus group, and six-month follow-up survey. This pilot study provides preliminary evidence for the Sleep Psychology Workshop as an effective and acceptable sleep education program for trainee psychologists.

We examined whether the ambient illuminance during extended wakefulness modulates the homeostatic increase in human deep sleep [i.e. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA)] in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e. sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800K), and once under either white light (WL: 250 lux, 2800K) or blue-enriched white light (BL: 250 lux, 9000K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

GIGANTEA (GI) is a gene involved in multiple biological functions, which were analysed and are partially conserved in a series of mono- and dicotyledonous plant species. The identified biological functions include control over the circadian rhythm, light signalling, cold tolerance, hormone signalling and photoperiodic flowering. The latter function is a central role of GI, as it involves a multitude of pathways, both dependent and independent of the gene CONSTANS(CO) as well as on the basis of interaction with miRNA. The complexity of gene function of GI increases due to the existence of paralogs showing changes in genome structure as well as incidences of sub- and neofunctionalization. We present an updated report of the biological function of GI, integrating late insights into its role in floral initiation, flower development and flower volatile production.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Understanding user challenges with light dosimeters is crucial for designing more acceptable devices and advancing light exposure research. We systematically evaluated the usability and acceptability of the lido (light dosimeter) by 29 participants who wore the dosimeter near the corneal plane of the eye for 5 days. Common reasons for not wearing the dosimeter included exercise, recharging, wet environments, public settings, and discomfort. Despite these issues, participants adhered to using the dosimeter, with high compliance (89% of recording time). Our findings reveal a significant discrepancy between mean melanopic Equivalent Daylight Illuminance (300 lxmEDI) and median values (51 lxmEDI). This discrepancy indicates that, for most of the time, participants experienced significantly lower light levels. Specifically, participants were exposed to light levels above 250 lxmEDI for only 14% of their wearing time. This highlights the need for increased exposure to recommended light levels. In the evening, participants' light exposure was below the recommended 10 lxmEDI for 58% of the wear time, which is in line with the guidelines for reducing light exposure before sleep. This study highlights the critical need for strategies to enhance daily light exposure, aligning better with circadian health recommendations.

It is often said in human society that it all starts from the mind, and this is true. The answer to the question “Why is it that pets require much fewer years to fully develop than humans?” could be headed to the Theory of Relativity and the perceived time according to the levels of instinct and rationality. It is perhaps no wonder that the French language translates the word “mind” as “l’esprit”, which also means “spirit” in the English language. Given that the Theory of Relativity applies to all physical matter, the theory applies to chemistry, biology and psychology as well. The level of instinct is proportional with the perceived speed of time and implicitly, to the speed of time itself for the whole organism, given that the nervous system coordinates all bodily functions. A pet may experience a few years as humans experience over a decade, making their perceived lifetime to be approximately equal to the human’s. The same applies to the perception of space and its components. This aspect would emphasise upon the fact that all life on Earth shows the same degree of value with regards to uniqueness. Nevertheless, the values represented by the hierarchy of competences among living organisms at the same time differs based on species. Honour of uniqueness and hierarchy of competences represent two scientific concepts that never overcross. As a result, there is no evidence to suggest that scientific facts as such constitute a form of contradiction to philosophical and religious ideas, given that religion refers to animals as companions of humans. With regards to the clock of the living organism; there are three kinds of clocks in a living organism: the emotional clock, the cognitive clock and the molecular clock. These three categories actually constitute the temporal layers of our dimension, so they are in a relationship of interdependence. When one has a feeling that time is slower or quicker, they are not fully experiencing that change in the time speed, but only partially. And one can profoundly experience the change of perceived time speed when they experience profound feelings, which sweep them away from reality. Complete, deep mental focus can bring about this profound change in perception, which will make the individual feel as if they are in a different form of reality. When one is more instinctive, the person in cause perceives time as slower and sees more opportunities within the same frame of time and space. When one experiences the “Fight or flight” mode, the person in the cause finds themselves to be in danger and has two options; to try to prevail over the danger or to flee it. Whilst experiencing such a mode, people are much more alert and therefore, time passes more slowly and the physical space dilates. When people are relaxed, however, time and space become smaller, and when they are in a deep state of resting, they become very small. And where there is a smaller dimension, there is a greater speed, just as the circulating air gains speed when it crosses narrow passages.

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.