Circadian Research Articles

Evidence of a circadian variation in 10-km laboratory running time-trial performance, where a standardised approach has been employed

ABSTRACT Diurnal variations in time-trial performance have been shown in people living normally, where a “standardised protocol” has been employed to reduce bias. We tested the hypothesis that a circadian variation exists for a 10-km running laboratory-based time-trial, where such a standardised approach is used. Twelve recreationally active adult males were recruited. The participants completed three familiarisation time-trials to the best of their ability at a self-selected pace and six 10-km time-trials at 06:00, 10:00, 14:00, 18:00, 22:00 and 02:00 h. Each session was separated by 7-days. Participants were allocated into 6 groups due to finish times (FT); sessions were counterbalanced in order of administration. A cosine fit for resting intra-aural temperature and FT both showed a significant circadian rhythm (p < 0.05) with mesor, amplitude and acrophases of 36.61°C vs 2994 s, 0.34°C vs 149 s; and 17:29 vs 18:44 h:min, respectively. The parallelism of temperature and FT agrees with previously published research. The finding of a 24-h rhythm in 10-km FT (5.0%, d = 0.80; power = 100%) concurs with that of a shorter distance where “standardised protocols” have been employed (4-km, 2.6%, d = 0.34). This finding has implications for scheduling of competition and training. Whether this variation is apparent in other populations, however, is unclear.

Circadian rhythm and the influence of light on parameters related to calcium metabolism in stroke patients admitted for rehabilitation.

Hospitalized stroke patients are at high risk of developing circadian disruption due to lack of natural sunlight. This may affect the circadian rhythm of the calcium metabolism. This study is a secondary explorative analysis from a Randomized Controlled Trial. Acute stroke patients requiring a minimum of two weeks of rehabilitation were randomized to an Intervention unit (IU) equipped with naturalistic light or a Control unit (CU) with standard indoor lighting. Blood was drawn across 24 h at inclusion and discharge in 45 patients, 25 from the IU and 20 from the CU. Calcium showed significant rhythmicity at inclusion and discharge in both groups. Alkaline phosphatase, parathyroid hormone (PTH), and Vitamin D exhibited no significant rhythmicity at inclusion or discharge in either group while phosphate exhibited rhythmicity at discharge in the CU. PTH levels were elevated in the CU group compared to the IU group at time of discharge. Of the measured parameters, only calcium exhibited circadian rhythmicity after stroke. Naturalistic light did not have any influence on the rhythmicity, indicating that light may not be the main circadian regulator of the circadian oscillations that regulate calcium metabolism. PTH seems to be decreased by naturalistic light.

Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms

Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms

Improved intensive care lighting and staff wellbeing: A pilot feasibility service evaluation

Background: The lighting environment in intensive care units (ICUs) is markedly different from natural light, potentially disrupting patients’ circadian rhythms and impacting staff wellbeing. New lighting technologies may mitigate these effects. Methods: A mixed methods service evaluation was conducted in a London ICU using Dyson Lightcycle™ luminaires (DLs) to evaluate staff wellbeing. Wellbeing assessments and user perceptions of the built environment were conducted using validated questionnaires before, during, and after DL deployment. Existing ambient light usage was measured using HOBO devices installed on the ceiling. Additionally, data on DL usage (including spectral data) were collected continuously using Raspberry Pi™ sensors. Results: DL usage was high (&gt;70% per 24 h), primarily as supplementary lighting. Users found DLs easy to control and beneficial for clinical and administrative tasks. Participants assigned a 12.5% higher satisfaction score rated from 0 to 8 of lighting overall during deployment compared to pre-deployment (6.06 ± 0.29 and 5.06 ± 0.60, respectively; p = 0.20). Control variables for the built environment (noise, temperature and air quality) remained unchanged. Staff reported improvements in mood (38%, p &lt; 0.001), fatigue (17.7%, p &lt; 0.001), and sleep quality (21.2%, p = 0.01) during DL use. Discussion: In the first pilot feasibility service evaluation of its kind, the relationship between ICU lighting quality and staff wellbeing was investigated using DLs. We show that it is feasible to equip an ICU with a novel mode of lighting to evaluate both illuminance and user-centred outcomes. The study suggests a positive association between DL use and staff wellbeing, with notable improvements in mood, fatigue and sleep quality. The nature of the emitted light may enhance the space rather than simply illuminate, thus further adding to a feeling of wellbeing. These findings support data from studies which report effects of light brightness and colour on mood. Additionally, there appears to be a signal towards benefit to the user when additional lighting is provided, compared to the current overhead fluorescent luminaires prevalent in most ICUs. In this service evaluation these benefits were demonstrated in ICU staff operating the device. However, it is conceivable that effects such as improved mood and reduced sleep disturbance may have patient benefits too. Conclusion: Local lighting systems like DLs show promise in enhancing ICU staff wellbeing. Their impact on patient outcomes and the potential for broader implementation deserve further investigation in appropriately designed and powered larger-scale trials.

Circadian rhythm related genes signature in glioma for drug resistance prediction: a comprehensive analysis integrating transcriptomics and machine learning

BackgroundGliomas, 24% of all primary brain tumors, have diverse histology and poor survival rates, with about 70% recurring due to acquired or de novo resistance. Insomnia in patients is correlated strongly with circadian rhythm disruptions. The correlation between circadian rhythm disorders and drug resistance of some tumors has been proved. However, the precise mechanism underlying the relationship between glioma and circadian rhythm disorders has not been elucidated.MethodsCircadian rhythm-related genes (CRRGs) were identified using the least absolute shrinkage and selection operator (LASSO) regression, and stochastic gradient descent (SGD) was performed to form a circadian rhythm-related score (CRRS) model. The studies of immune cell infiltration, genetic variations, differential gene expression pattern, and single cell analysis were performed for exploring the mechanisms of chemotherapy resistance in glioma. The relationship between CRRGs and chemosensitivity was also confirmed by IC 50 (half maximal inhibitory concentration) analysis.ResultSignatures of 16 CRRGs were screened out and identified. Based on the CRRS model, an optimal comprehensive nomogram was created, exhibiting a favorable potential for predicting drug resistance in samples. Immune infiltration, cell–cell communication, and single cell analysis all indicated that high CRRS group was closely related to innate immune cells. IC50 analysis showed that CRRG knockdown enhanced the chemosensitivity of glioma.ConclusionA significant correlation between CRRGs, drug resistance of glioma, and innate immune cells was found, which might hold a significant role in the drug resistance of glioma.

The Prognostic Significance of Sleep and Circadian Rhythm for Myocardial Infarction Outcomes: Case-Control Study.

Myocardial infarction (MI) is a medical emergency resulting from coronary artery occlusion. Patients with acute MI often experience disturbed sleep and circadian rhythm. Most previous studies assessed the premorbid sleep and circadian rhythm of patients with MI and their correlations with cardiovascular disease. However, little is known about post-MI sleep and circadian rhythm and their impacts on prognosis. The use of actigraphy with different algorithms to evaluate sleep and circadian rhythm after acute MI has the potential for predicting outcomes and preventing future disease progression. We aimed to evaluate how sleep patterns and disrupted circadian rhythm affect the prognosis of MI, using actigraphy and heart rate variability (HRV). Nonparametric analysis of actigraphy data was performed to examine the circadian rhythm of patients. Patients with MI in the intensive care unit (ICU) were enrolled alongside age- and gender-matched healthy controls. Actigraphy was used to evaluate sleep and circadian rhythm, while HRV was monitored for 24 hours to assess autonomic nerve function. Nonparametric indicators were calculated to quantify the active-rest patterns, including interdaily stability, intradaily variability, the most active 10 consecutive hours (M10), the least active 5 consecutive hours (L5), the relative amplitude, and the actigraphic dichotomy index. Follow-ups were conducted at 3 and 6 months after discharge to evaluate prognosis, including the duration of current admission, the number and duration of readmission and ICU admission, and catheterization. Independent sample t tests and analysis of covariance were used to compare group differences. Pearson correlation tests were used to explore the correlations of the parameters of actigraphy and HRV with prognosis. The study included 34 patients with MI (mean age 57.65, SD 9.03 years) and 17 age- and gender-matched controls. MI patients had significantly more wake after sleep onset, an increased number of awakenings, and a lower sleep efficiency than controls. Circadian rhythm analysis revealed significantly lower daytime activity in MI patients. Moreover, these patients had a lower relative amplitude and dichotomy index and a higher intradaily variability and midpoint of M10, suggesting less sleep and wake activity changes, more fragmentation of the rest-activity patterns, and a more delayed circadian rhythm. Furthermore, significant correlations were found between the parameters of circadian rhythm analysis, including nighttime activity, time of M10 and L5, and daytime and nighttime activitySD, and patient prognosis. Patients with acute MI experienced significantly worse sleep and disturbed circadian rhythm compared with healthy controls. Our actigraphy-based analysis revealed a disturbed circadian rhythm, including reduced daytime activities, greater fluctuation in hourly activities, and a weak rest-activity rhythm, which were correlated with prognosis. The evaluation of sleep and circadian rhythm in patients with acute MI can serve as a valuable indicator for prognosis and should be further studied.

Unveiling the novel role of circadian rhythms in sepsis and septic shock: unexplored implications for chronotherapy

Circadian rhythms are critical to coordinating body processes to external environmental cues, such as light and feeding, to ensure efficiency and maintain optimal health. These rhythms are controlled by ‘clock’ transcription factors, such as Clock, Bmal1, Per1/2, Cry1/2, and Rev-erbs, which are present in almost every tissue. In modern society, disruptions to normal circadian rhythms are increasingly prevalent due to extended lighting, shift work, and long-distance travel. These disruptions misalign external cues to body processes and contribute to diseases such as obesity and non-alcoholic fatty liver disease. They also exacerbate pre-existing health issues, such as depression and inflammatory bowel disease. The normal inflammatory response to acute infection displays remarkable circadian rhythmicity in humans with increased inflammatory activity during the normal night or rest period. Severe bloodborne infections, exemplified in sepsis and the progression to septic shock, can not only disrupt the circadian rhythmicity of inflammatory processes but can be exacerbated by circadian misalignment. Examples of circadian disruptions during sepsis and septic shock include alteration or loss of hormonal rhythms controlling blood pressure and inflammation, white blood cell counts, and cytokine secretions. These changes to circadian rhythms hinder sepsis and septic shock recovery and also increase mortality. Chronotherapy and chronopharmacotherapy are promising approaches to resynchronise circadian rhythms or leverage circadian rhythms to optimise medication efficacy, respectively, and hold much potential in the treatment of sepsis and septic shock. Despite knowledge of how circadian rhythms change in these grave conditions, very little research has been undertaken on the use of these therapies in support of sepsis management. This review details the circadian disruptions associated with sepsis and septic shock, the influence they have on morbidity and mortality, and the potential clinical benefits of circadian-modulating therapies.

The impact of circadian rhythm disruption on oxaliplatin tolerability and pharmacokinetics in Cry1-/-Cry2-/- mice under constant darkness.

Circadian rhythms, the 24-h oscillations of biological activities guided by the molecular clock, play a pivotal role in regulating various physiological processes in organisms. The intricate relationship between the loss of circadian rhythm and its influence on the tolerability and pharmacokinetic properties of anticancer drugs is poorly understood. In our study, we investigated the effects of oxaliplatin, a commonly used anticancer drug, on Cry1-/- and Cry2-/- mice (Cry DKO mice) under darkness conditions, where they exhibit free-running phenotype. We administered oxaliplatin at a dosage of 12mg/kg/day at two distinct circadian times, CT8 and CT16, under constant darkness conditions to Cry DKO mice and their wild type littermates. Our results revealed a striking disparity in oxaliplatin tolerance between Cry DKO mice and their wild-type counterparts. Oxaliplatin exhibited severe toxicity in Cry DKO mice at both CT8 and CT16, in contrast to the wild type mice. Pharmacokinetic analyses suggested that such toxicity was a result of high concentrations of oxaliplatin in the serum and liver of Cry DKO mice after repeated dose injections. To understand the molecular basis of such intolerance, we performed RNA-seq studies using mouse livers. Our findings from the RNA-seq analysis highlighted the substantial impact of circadian rhythm disruption on gene expression, particularly affecting genes involved in detoxification and xenobiotic metabolism, such as the Gstm gene family. This dysregulation in detoxification pathways in Cry DKO mice likely contributes to the increased toxicity of oxaliplatin. In conclusion, our study highlights the crucial role of an intact molecular clock in dictating the tolerability of oxaliplatin. These findings emphasize the necessity of considering circadian rhythms in the administration of anticancer drugs, providing valuable insights into optimizing treatment strategies for cancer patients.

Quality of Daylighting in Childcare Facilities: A Comparative Study of Polish Regulations with International Sustainability Rating Systems

This study examines the quality and availability of daylight in childcare facilities, focusing on compliance with Polish Technical Conditions (TCs) and comparing them with international certification systems such as BREEAM, LEED, and WELL. Polish regulations regarding sunlight exposure require revisions to support the sustainable development of buildings, impacting children’s well-being, their health, and the building’s energy efficiency. Daylight’s significance for children’s health and development underpins the investigation, highlighting its impact on the circadian rhythm, cognitive abilities, and well-being. The research utilized computational simulations with Rhinoceros 7 and Ladybug and Honeybee plugins to model a preschool room’s daylight performance under various window configurations and orientations. Quantitative and qualitative analyses were conducted, focusing on parameters such as Daylight Factor (DF), Daylight Autonomy (DA), and Useful Daylight Illuminance (UDI). The findings revealed that while the TCs’ requirements ensure minimum daylight access, they result in nonoptimal lighting quality as defined by international standards. Almost half of the surveyed rooms in the case with a WFR of one-eighth did not meet the condition for having acceptable daylight levels, as defined in the study. In the same study, only about one-third of the analyzed variants achieved the threshold for good daylight quality. At a WFR of one-eighth, no room variant reached the level considered to indicate excellent daylight quality. The results show the need for revised regulations incorporating comprehensive metrics like Climate-Based Daylight Modeling (CBDM). This study suggests that integrating advanced methods of assessing daylight quality could significantly improve daylight conditions in childcare environments. This research is a starting point for discussing the need to modernize the Polish Technical Conditions (TC) to support the sustainable development of childcare facilities in Poland.

Interactions Between Anesthesia and Sleep: Optimizing Perioperative Care to Improve Sleep Quality and Surgical Recovery Outcomes.

Sleep is a fundamental physiological process that supports immunity, cognition, memory, and metabolism, making it essential for overall health and well-being. Poor-quality sleep is associated with the onset of many diseases, including cardiovascular and mental health disorders. When using anesthesia, it is essential to have a thorough understanding of the metabolic dysfunction and immunosuppression linked to sleep loss to ensure appropriate perioperative management. Commonly used agents like propofol, sevoflurane, and ketamine affect consciousness, pain levels, and autonomic responses. Inhaled anesthetics (e.g., sevoflurane and isoflurane) and intravenous anesthetics (propofol) act on gamma-aminobutyric acid (GABA) receptors and influence stages of sleep and circadian rhythms. Ketamine may uniquely preserve some aspects of restorative sleep, while most anesthetics affect rapid eye movement (REM) and slow wave sleep (SWS), altering cognitive and physical recovery. Modifying anesthetic regimes depending on the patient's sleep history and risk factors can maximize sleep health and postoperative patient outcomes. The physiological effects of anesthesia on the central nervous system persist beyond the perioperative period by influencing sleep quality, circadian regulation, and postoperative outcomes. Effective pain management is a significant component in addressing sleep quality. Opioids, while effective for pain relief, disrupt sleep architecture by reducing REM and SWS, increasing awakening frequency, and potentially causing respiratory depression. Multimodal pain therapy, including non-opioid analgesics, can reduce dependence, improve sleep quality, and lower adverse effects. Anesthetic agents can influence the body's internal clock, leading to mood changes, fatigue, and cognitive deficits. This review exploits the relationship between sleep and anesthesia, detailing the effect of anesthetic agents on the quality, architecture, and recovery of sleep patterns post-surgery. It also explores how these agents influence sleep stages, such as REM and non-REM sleep, and their implications for patient outcomes. Incorporating sleep optimization techniques can enhance recovery timelines and patient well-being. Researching anesthetic techniques that support postoperative sleep health is essential for further improving patient outcomes.

Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation

Misregulation of the activity of GCN2, the kinase that phosphorylates and inactivates translation initiation factor eIF2α, has been implicated in several health disorders, underscoring the need to determine the mechanisms controlling GCN2 activation. During nutrient starvation, increased uncharged tRNA levels trigger GCN1 and GCN20 proteins to mediate the binding of uncharged tRNA to GCN2 to activate the kinase to phosphorylate eIF2α. Under constant conditions, activation of the Neurospora crassa homolog of GCN2, CPC-3, is controlled by the circadian clock. However, how the circadian clock controls the rhythmic activity of CPC-3 was not known. We found that the clock regulates CPC-3 and GCN1 interaction with ribosomes and show that these interactions are necessary for clock regulation of CPC-3 activity. CPC-3 activity rhythms, and the rhythmic interaction of CPC-3 and GCN1 with ribosomes, are abolished in a temperature-sensitive valyl-tRNA synthetase mutant (un-3ts) that has high levels of uncharged tRNAVal at all times of the day. Disrupting the interaction between GCN1 and uncharged tRNA in the absence of GCN20 altered rhythmic CPC-3 activity, indicating that the clock controls the interaction between uncharged tRNA and GCN1. Together, these data support that circadian rhythms in mRNA translation through CPC-3 activity require rhythms in uncharged tRNA levels that drive the rhythmic interaction between CPC-3 and GCN1 with ribosomes. This regulation uncovers a fundamental mechanism to ensure temporal coordination between peak cellular energy levels and the energetically demanding process of mRNA translation.

Unveiling Photoperiod-Responsive Regulatory Networks in Tropical Maize Through Transcriptome Analysis

Background/Objectives: Maize (Zea mays L.), a crop of worldwide importance, owes its adaptability to diverse environments to its genetic variation. However, tropical maize exhibits intrinsic photoperiod sensitivity, limiting its adaptability to temperate regions. Photoperiod sensitivity significantly affects the flowering time and other agronomic traits, but the underlying molecular mechanisms remain poorly understood. In this study, the aim is to elucidate the transcriptional regulatory networks mediating photoperiod responses in tropical maize inbred line Su65, providing insights into improving photoperiod adaptability. Methods: RNA-seq analysis was carried out to investigate photoperiod-responsive genes and pathways in tropical line Su65 exposed to varying photoperiod conditions. Differential expression analysis, functional enrichment, and the construction of protein–protein interaction (PPI) networks were carried out to investigate transcriptional dynamics. Additionally, qRT-PCR was employed to confirm the expression patterns of key candidate genes and generate detailed temporal expression profiles. Results: A total of 1728 differentially expressed genes (DEGs) were identified, with significant enrichment in pathways such as stress responses, redox homeostasis, and secondary metabolite biosynthesis. A set of new key hub genes (such as Zm00001d048531, Zm00001d018821, Zm00001d034892, etc.) were identified through PPI network analysis. Temporal expression profiling of ZmPHYB1, ZmPHYC1, ZmFKF2, ZmGI2, and ZmPRR37a, the key genes involved in circadian rhythms, revealed distinct regulatory patterns of photoperiod-sensitive genes at different time points, highlighting their roles in flowering time regulation and developmental transitions. Conclusions: In this study, critical molecular networks underlying photoperiod sensitivity in tropical maize are uncovered and a foundation is provided for improving photoperiod adaptability through genetic improvement. By integrating RNA-seq and qRT-PCR, the research offers valuable insights into transcriptional dynamics and their role in maize development under photoperiodic regulation.

Rest-Activity Rhythms, Their Modulators, and Brain-Clinical Correlates in Opioid Use Disorder.

Sleep and circadian disruptions are highly prevalent in opioid use disorder (OUD) and are a barrier to successful treatment and recovery; yet few objective data are available, especially for individuals in OUD treatment with opioid agonist therapy. If disruptions remain present despite OUD treatment, this information would yield potential new targets for adjunctive therapy. To systematically investigate different aspects of rest-activity rhythms (RAR), including sleep, physical activity, circadian rhythmicity, and brain functional correlates in individuals with OUD. This cross-sectional study conducted from October 12, 2017, through January 11, 2024, recruited participants with OUD from treatment programs or the community in the District of Columbia, Maryland, and Virginia area. Participants included individuals with OUD treated with methadone or buprenorphine, individuals with OUD who remained abstinent without medications, and healthy controls (HCs). Healthy participants were recruited from advertisements. Statistical analyses were conducted between March 1 and May 31, 2024. In total, 21 RAR features were derived from 1-week actigraphy data, and principal components were used to extract independent RAR components. Modulators and brain and clinical correlates of RAR were also examined. This study included 73 participants (46 [63%] male; mean [SD] age, 43.5 [11.3] years). Among 42 patients with OUD (16 [38%] female; mean [SD] age, 42.7 [11.4] years), 33 receiving medications for opioid use disorder (MOUD) exhibited greater sleep-wake irregularity than 9 patients without MOUD (mean difference, 0.85 [95% CI, 0.00-1.69]) or 31 age- and sex-matched HCs (11 [36%] female; mean [SD] age, 44.5 [11.3] years; mean difference, 0.75 [95% CI, 0.19-1.31). Among participants receiving MOUD, greater sleep irregularity was associated with longer heroin use history (r26 = 0.45; P = .02) and lower daytime light exposure (r33 = -0.57; P < .001). Compared with HCs, participants with OUD exhibited lower fractional occupancy (percentage of occurrence) in a default mode network-dominated brain state, with individuals experiencing more pronounced sleep-wake irregularities displaying exacerbated impairments (r23 = -0.55; P = .007). Findings of this cross-sectional study showed that sleep irregularity in participants with OUD receiving opioid agonist medications correlated with years of opioid misuse and shorter daylight exposures and was associated with impaired brain state dynamics. These findings suggest that interventions increasing light exposure may improve sleep-wake irregularity and brain functional network dynamics in individuals with OUD receiving opioid agonist medications.

Melatonin-Mediated Circadian Rhythm Signaling Exhibits Bidirectional Regulatory Effects on the State of Hair Follicle Stem Cells

The development and regulation of hair are widely influenced by biological rhythm signals. Melatonin plays a crucial role as a messenger in transmitting biological rhythm signals, and its impact on hair development has been well documented. During the process of hair follicle reconstruction, hair follicle stem cells (HFSCs) are the most important cell type, but the regulatory effect of melatonin on the state of HFSCs is still not fully understood. Therefore, it is necessary to conduct a more comprehensive characterization of the effects of melatonin on the state of hair follicle stem cells. The research results indicate that HFSCs express retinoic acid receptor-related orphan receptor alpha (Rorα), and melatonin inhibits the expression level of RORA. Experimental results from CUT&amp;Tag, CUT&amp;RUN, and dual luciferase reporter assays demonstrate that Foxc1 is a downstream target gene of RORA, with RORA regulating Foxc1 expression by binding to the promoter region of Foxc1. The CCK-8 assay results show that low doses of melatonin upregulate the survival rate of hair follicle stem cells, while high doses have the opposite effect. The knockdown of Foxc1 reverses the inhibitory effect of high-dose melatonin on the survival rate of hair follicle stem cells. Based on these findings, we believe that melatonin-mediated circadian signals exert a bidirectional regulatory effect on the state of HFSCs.

Effect of sleep deprivation on gait complexity.

Gait complexity is considered an indicator of adaptability, reflecting the complex interaction between multiple components of the neuromuscular system. Previous research provided evidence that chronobiology, which reflects the individual expression of circadian rhythms, affects the regulation of gait dynamics. The literature also suggests the disruption of these circadian rhythms affects multiple human physiological systems. Considering the association between chronobiology and gait complexity, and its clinical relevance, it would be important to investigate whether the disruption of sleep-wake cycle could affect gait complexity. This study aimed to investigate the effect of 1 night of sleep deprivation on gait complexity and variability of healthy individuals, exploring potential implications for motor control. Seventeen healthy and young male adults underwent an in-lab supervised 24-hr sleep deprivation protocol, with gait complexity and variability assessed using detrended fluctuation analysis and coefficient of variation, respectively. Chronotype was also assessed through the Morningness-Eveningness Questionnaire. We observed a loss of gait complexity with sleep deprivation (PRE: 0.8 ± 0.13; POST24: 0.62 ± 0.08, p < 0.001), while gait variability remained unaltered (p = 0.132). Additionally, we demonstrated an association between gait complexity's relative changes and chronotype (r = -0.665, p = 0.004). Overall, our findings suggest sleep deprivation induces a decrease in the neuromuscular system's ability to flexibly adapt gait output. Moreover, we also highlight the importance of chronobiology in motor control, as we observed the more morning-type an individual is, the greater the loss of complexity following 1 night of sleep deprivation. Altogether, our findings underscore the potential impact of sleep deprivation on central processes underlying gait complexity.

Deletion of Arntl, a component of the molecular clock, in adipocytes leads to cellular hypertrophy by increasing insulin sensitivity via FGF21

Brain and muscle Arnt-like protein 1 (BMAL1), encoded by Aryl hydrocarbon receptor nuclear translocator like 1 (Arntl) gene, is a transcription factor that regulates the circadian rhythm of the expressions of several genes. The link between the loss of BMAL1 function in adipose tissue and obesity has been reported. Although these previous studies have suggested that dysregulation of lipolysis is a contributing factor, but the detailed mechanism has not been fully understood. This study aimed to elucidate the role of BMAL1 in adipocytes using adipocyte-specific Arntl deficient (AAKO) mice. Deletion of Arntl in adipocytes leads to increased cellular insulin sensitivity, which in turn, inhibited lipolysis in adipocytes and caused cellular hypertrophy. The expression levels of Fgf21 in adipose tissue were significantly elevated in AAKO mice compared to Arntlflox/flox mice. Double knockout of Arntl and Fgf21 in adipocytes abolished metabolic phenotypes such as decreased circulating non-esterified fatty acid levels, adipocyte hypertrophy, and increased insulin sensitivity in AAKO mice. These results indicated that BMAL1 regulates fat mobilization and insulin signaling in adipocytes via FGF21 during the stationary phase. This is the possible mechanism by which disruption of circadian rhythm induces obesity.

Sleep and respiratory infections.

Sleep disorders that involve circadian rhythm disruption and sleep-disordered breathing (SDB) such as obstructive sleep apnea (OSA) are closely linked to respiratory infections. SDB leads to a proinflammatory state due to intermittent hypoxia, sleep fragmentation, increased oxidative stress, and elevation of inflammatory mediators such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and C-reactive protein (CRP). Furthermore, inflammatory mediator levels correlate with SDB severity, especially in people with OSA. Nocturnal microaspiration, gastroesophageal reflux, and associated comorbidities (e.g. obesity) increase the risk of community-acquired pneumonia, viral infections such as SARS-CoV-2, respiratory complications, and death. OSA has been associated with post-COVID syndrome. It also increases the risk of postoperative complications in both adults and children. Circadian rhythm disorders such as insomnia predispose to immune disorders and increase the risk of infection. Chronic conditions such as bronchiectasis, with or without concomitant cystic fibrosis, can lead to structural sleep changes and increase the risk of OSA due to chronic cough, arousals, aspirations, hypoxia, upper airway edema, and overexpression of proinflammatory cytokines. The protective effect of treatment for sleep disorders against respiratory infection is currently unknown. However, in people presenting with respiratory infection, it is important to test for SDB to prevent complications.

A review of integrative dynamic lighting and associated well-being impact for people living with dementia

Integrative lighting considers light for both visual and non-visual impact and can therefore benefit human health and well-being. More specifically, it can benefit circadian-related well-being, an umbrella term which within dementia cohorts considers factors such as sleep, rest-activity, mood, agitation and activities of daily living. As people living with dementia experience disruptions to their circadian rhythms and spend large amounts of time indoors, the understanding of how integrative interior lighting could influence their body clock could help support their well-being. A review of 18 studies found that papers are difficult to compare due to unsystematic study designs and reporting of study characteristics, light characteristics and participant characteristics. The findings at most imply that indoor integrative lighting could be beneficial to these aspects of well-being. This review finds suggestion that for this cohort there may be a relationship between colour variation and mood and agitation, alongside a relationship between intensity variation and sleep, and that the influence on rest-activity may be more unpredictable. These findings are inferred and due to heterogeneous study designs they are inconclusive. The outcome of this review therefore recommends future studies that follow systematic checklists for study designs which seek to test these inferred hypotheses within this cohort.

Investigating the Relationship Between Circadian Rhythm and Learning-Memory

Investigating the Relationship Between Circadian Rhythm and Learning-Memory

SLEEP, CIRCADIAN RHYTHMS, AND LUNG CANCER.

Lung cancer is the leading cause of cancer-related mortality worldwide, with the prevalence of the disease continually rising. Therefore, identifying disease-modifying risk factors is critical, with increasing recognition of the impact of sleep quality/sleep disorders. This narrative review summarizes the evidence on the role of five domains of sleep on lung cancer incidence and progression: (i) sleep quality/duration, (ii) sleep disordered breathing, (iii) circadian rhythm disturbances, (iv) sleep-related movement disorders and (v) personal, environmental and social factors that modulate each of these associations. Epidemiological evidence supports reduced sleep duration, increased sleep duration, poor sleep quality, insomnia, obstructive sleep apnea, evening chronotype, peripheral limb movements in sleep, and less robustly for night shift work and restless leg syndrome to be associated with increased risk of lung cancer development, with potential impacts on cancer survival outcomes. Proposed mechanisms underlying the biological plausibility of these epidemiological associations are also explored, with common theories relating to immune dysregulation, metabolic alterations, reductions in melatonin, sympathetic overactivation, increased reactive oxygen species, production of protumorigenic exosomes and inflammation. We also summarized potential treatments addressing impaired sleep quality/sleep disorders and their ability to attenuate the risk of lung cancer and cancer survival. While evidence on reversibility is inconsistent, there are trends toward positive outcomes. Future research should focus on clinical trials to confirm cause and effect relationships, large epidemiologic studies for incidence/prognosis, clarification on the relative efficacy of treatment modalities, and more in vivo animal models to establish the molecular mechanisms underlying these relationships.