Homeobox gene-encoded transcription factors in development and mature circadian function of the rodent pineal gland.

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.

Research progress of circadian rhythm in cardiovascular disease: A bibliometric study from 2002 to 2022.

Background: Given that the circadian rhythm is intricately linked to cardiovascular physiological functions, the objective of this investigation was to employ bibliometric visualization analysis in order to scrutinize the trends, hotspots, and prospects of the circadian rhythm and cardiovascular disease (CVD) over the past two decades. Methods: A thorough exploration of the literature related to the circadian rhythm and CVD was conducted via the Web of Science Core Collection database spanning the years 2002-2022. Advanced software tools, including citespace and VOSviewer, were employed to carry out a comprehensive analysis of the co-occurrence and collaborative relationships among countries, institutions, journals, references, and keywords found in this literature. Furthermore, correlation mapping was executed to provide a visual representation of the data. Results: The present study encompassed a total of 3399 published works, comprising of 2691 articles and 708 reviews. The publications under scrutiny were primarily derived from countries such as the United States, Japan, and China. The most prominent research institutions were found to be the University of Vigo, University of Minnesota, and Harvard University. Notably, the journal Chronobiology International, alongside its co-cited publications, had the most substantial contribution to the research in this field. Following an exhaustive analysis, the most frequently observed keywords were identified as circadian rhythm, blood pressure, hypertension, heart rate, heart rate variability, and melatonin. Furthermore, a nascent analysis indicated that future research might gravitate towards topics such as inflammation, metabolism, oxidative stress, and autophagy, thereby indicating new directions for investigation. Conclusion: This analysis represents the first instance of bibliometric scrutiny pertaining to circadian rhythm and its correlation with cardiovascular disease (CVD) through the use of visualization software. Notably, this study has succeeded in highlighting the recent research frontiers and prominent trajectories in this field, thereby providing a valuable contribution to the literature.

The interplay between X-chromosome functional dosage and circadian regulation in females.

PURPOSE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes. METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus. RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation. CONCLUSION: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

Arrhythmia and Time of Day in Maintenance Hemodialysis: Secondary Analysis of the Monitoring in Dialysis Study.

Rationale & Objective: The incidence of arrhythmia varies by time of day. How this affects individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and timing of dialysis. Study Design: Secondary analysis of the Monitoring in Dialysis study, a multicenter prospective cohort study. Settings & Participants: Loop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months. Exposure: Time of day based on 6-hour intervals. Outcomes: Event rates of clinically significant arrhythmia. Analytical Approach: Negative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end-stage kidney disease with heart failure and end-stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis versus nondialysis day. Results: Rates of clinically significant arrhythmia peaked between 12:00 AM and 5:59 AM and were more than 1.5-fold as frequent during this interval than the rest of the day. In contrast, variations in atrial fibrillation peaked between 6:00 AM and 11:59 AM, but variations across the day were qualitatively small. Clinically significant arrhythmia occurred at numerically higher rate in individuals with end-stage kidney disease and heart failure (5.9 events/mo; 95% CI, 1.3-26.8) than those without heart failure (4.0 events/mo; 95% CI, 0.9-17.9). Although differences in overall rate were not significant, their periodicity was significantly different (P < 0.001), with a peak between 12:00 AM and 6:00 AM with kidney failure alone and between 6:00 AM and 11:59 AM in those with heart failure. Although the overall clinically significant arrhythmia rate was similar in morning compared with evening dialysis shifts (P = 0.43), their periodicity differed with a peak between 12:00 AM and 5:59 AM in those with AM dialysis and a later peak between 6:00 AM and 11:59 AM in those with PM shifts. Limitations: Post hoc analysis, unable to account for unmeasured confounders. Conclusion: Clinically significant arrhythmias showed strong diurnal patterns with a maximal peak between 12:00 AM and 5:59 AM and noon. Although overall arrhythmia rates were similar, the peak rate occurred overnight in individuals without heart failure and during the morning in individuals with heart failure. Further exploration of the influence of circadian rhythm on arrhythmia in the setting of hemodialysis is needed.

Arrhythmias occur with a high frequency in individuals with kidney failure. We sought to understand whether there were diurnal patterns for common types of arrhythmias in individuals with kidney failure. We used continuous rhythm data from 66 individuals on dialysis with implantable loop recorders. We found that clinically significant arrhythmias including bradycardia primarily occur overnight and in the early morning, whereas atrial fibrillation is more evenly distributed during the day.

Time of the day and season distribution among stroke code subtypes: differences between ischemic stroke, intracranial hemorrhage, and stroke mimic.

Background: Circadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients. Methods: This study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals. Results: A total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08-12 h and 12-16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4-8 h period (dawn), most of which were hypertensive, TIA in the 12-16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases. Conclusion: The present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon.

Circadian disruption dysregulates lung gene expression associated with inflammatory lung injury.

Rationale: Circadian systems drive the expression of multiple genes in nearly all cells and coordinate cellular-, tissue-, and system-level processes that are critical to innate immunity regulation. Objective: We examined the effects of circadian rhythm disorganization, produced by light shift exposure, on innate immunity-mediated inflammatory lung responses including vascular permeability and gene expression in a C57BL/6J murine model of inflammatory lung injury. Methods: A total of 32 C57BL/6J mice were assigned to circadian phase shifting (CPS) with intratracheal phosphate-buffered saline (PBS), CPS with intratracheal lipopolysaccharide (LPS), control (normal lighting) condition with intratracheal PBS, and control condition with intratracheal LPS. Bronchoalveolar lavage (BAL) protein, cell counts, tissue immunostaining, and differentially expressed genes (DEGs) were measured in lung tissues at 2 and 10 weeks. Measurements and results: In mice exposed to both CPS and intratracheal LPS, both BAL protein and cell counts were increased at both 2 and 10 weeks compared to mice exposed to LPS alone. Multiple DEGs were identified in CPS-LPS-exposed lung tissues compared to LPS alone and were involved in transcriptional pathways associated with circadian rhythm disruption, regulation of lung permeability, inflammation with Rap1 signaling, and regulation of actin cytoskeleton. The most dysregulated pathways included myosin light chain kinase, MAP kinase, profilin 2, fibroblast growth factor receptor, integrin b4, and p21-activated kinase. Conclusion: Circadian rhythm disruption results in exacerbated immune response and dysregulated expression of cytoskeletal genes involved in the regulation of epithelial and vascular barrier integrity-the mechanistic underpinnings of acute lung injury. Further studies need to explore circadian disorganization as a druggable target.

Causal dynamics of sleep, circadian rhythm, and mood symptoms in patients with major depression and bipolar disorder: insights from longitudinal wearable device data.

BACKGROUND: Sleep and circadian rhythm disruptions are common in patients with mood disorders. The intricate relationship between these disruptions and mood has been investigated, but their causal dynamics remain unknown. METHODS: We analysed data from 139 patients (76 female, mean age = 23.5 ± 3.64 years) with mood disorders who participated in a prospective observational study in South Korea. The patients wore wearable devices to monitor sleep and engaged in smartphone-delivered ecological momentary assessment of mood symptoms. Using a mathematical model, we estimated their daily circadian phase based on sleep data. Subsequently, we obtained daily time series for sleep/circadian phase estimates and mood symptoms spanning >40,000 days. We analysed the causal relationship between the time series using transfer entropy, a non-linear causal inference method. FINDINGS: The transfer entropy analysis suggested causality from circadian phase disturbance to mood symptoms in both patients with MDD (n = 45) and BD type I (n = 35), as 66.7% and 85.7% of the patients with a large dataset (>600 days) showed causality, but not in patients with BD type II (n = 59). Surprisingly, no causal relationship was suggested between sleep phase disturbances and mood symptoms. INTERPRETATION: Our findings suggest that in patients with mood disorders, circadian phase disturbances directly precede mood symptoms. This underscores the potential of targeting circadian rhythms in digital medicine, such as sleep or light exposure interventions, to restore circadian phase and thereby manage mood disorders effectively. FUNDING: Institute for Basic Science, the Human Frontiers Science Program Organization, the National Research Foundation of Korea, and the Ministry of Health & Welfare of South Korea.

Seasonal patterns in Chinese population: Validating the seasonal pattern assessment questionnaire and exploring associations with psychiatric diagnoses and biological rhythms.

Seasonal patterns (SP) exert a notable influence on the course and prognosis of patients with affective disorders, serving as a specifier in diagnosis. However, there is limited exploration of seasonality among psychotic patients, and the distinctions in seasonality among psychiatric patients remain unclear. In this study, we enrolled 198 psychiatric patients with anxiety and depressive disorders (A&D), bipolar disorder (BD), and schizophrenia (SZ), as well as healthy college students. Online questionnaires, including the Seasonal Pattern Assessment Questionnaire (SPAQ) for seasonality, the Morningness and Eveningness Questionnaire-5 (MEQ-5) for chronotypes, and the Pittsburgh Sleep Quality Index (PSQI), were administered. The validity and reliability of the Chinese version of the SPAQ were thoroughly analyzed, revealing a Cronbach's alpha of 0.896 with a two-factor structure. Results indicated that higher seasonality was correlated with poorer sleep quality and a more delayed chronotype (p < 0.05). Significant monthly variations were particularly evident in BD, specifically in mood, appetite, weight, social activities, and sleep dimensions (p < 0.001). In summary, the Chinese version of SPAQ is validated, demonstrating moderate correlations between seasonality, chronotype, and sleep quality. BD patients exhibited the strongest seasonality, while mood disorder patients displayed more delayed chronotypes than SZ.

Psychometric properties of the Turkish reduced morningness and eveningness questionnaire.

The aim of this study was to examine the psychometric properties of the 5-item Turkish Reduced Morningness-Eveningness Questionnaire (rMEQ) for the first time. The study involved 875 university students in an adaptation and validation study. Participants completed the rMEQ, MEQ, Depression Anxiety Stress Scale-21 (DASS-21), Insomnia Severity Index (ISI), Barratt Impulsiveness Scale Short Form (BIS-SF), and Oxford Happiness Questionnaire Short Form (OHQ-SF). The factor structure, convergent validity, internal consistency, sensitivity, and specificity of the rMEQ were examined. The confirmatory factor analysis showed that the rMEQ had a one-dimensional structure with good fit indices (χ2/df = 2.94, CFI = 0.990, TLI = 0.979, RMSEA = 0.047, and SRMR = 0.019). There was a significantly strong correlation between rMEQ and MEQ. In addition, we found a significantly weak correlation between rMEQ and DASS-21, ISI, BIS-SF, and OHQ-SF. The internal consistency coefficients of rMEQ were Cronbach's α = 0.706 and McDonald's ω = 0.740. The sensitivity and specificity of rMEQ were 83.3%-92.7% for morning types and 86.3%-87.3% for evening types. The Turkish rMEQ has adequate psychometric properties and can be used to assess an individual's chronotype.

Greater within- and between-day instability is associated with worse anxiety and depression symptoms.

BACKGROUND: Depression and anxiety affect hundreds of millions of people worldwide, and their prevalence increased during the COVID-19 pandemic as social schedules were disrupted. This study explores the associations between anxiety and depression and within- and between-day instability of affective, somatic, and cognitive symptoms during the early pandemic stages. METHODS: Participants (n = 153, ages 18-77, 72 % female) reported daily levels of affective (anxiety/sadness), somatic (appetite/sleepiness), and cognitive (concentration/energy) symptoms for 14-44 days at five timepoints: 0, 3, 6, 9, and 12 h after awakening. At the end of the study, participants completed validated scales for anxiety (GAD-7) and depression (PHQ-9). Symptom instability was assessed using the Absolute Real Variability (ARV) index. Regression models examined within-day instability (WD-I) and between-day instability (BD-I) with GAD-7 and PHQ-9 scores as outcomes. RESULTS: Greater instability (both WD-I and BD-I) of affective symptoms correlated with elevated GAD-7 and PHQ-9 scores. For somatic and cognitive symptoms, greater BD-I was associated with higher scores. LIMITATIONS: The study used retrospective daily data, which could benefit from real-time assessments for improved accuracy. CONCLUSIONS: This study provides empirical evidence of a connection between greater anxiety and depression severity and increased instability in daily mood and physiological symptoms. The findings underscore the importance of consistent symptom monitoring to understand overall mental health trajectories. Additionally, it highlights the role of daily routines in stabilizing the circadian system, potentially regulating physiological and psychological processes and reducing symptom instability.

Diurnal rhythmicity of infant fecal microbiota and metabolites: A randomized controlled interventional trial with infant formula.

Microbiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk. To compare microbiota development across feeding modes, this randomized controlled intervention study (German Clinical Trial DRKS00012313) longitudinally sampled infant stool during the first year of life, revealing similar fecal bacterial communities between formula- and breast-fed infants (N = 210) but differences across age. Infant formula containing GOS sustained high levels of bifidobacteria compared with formula containing B. longum and B. breve or placebo. Metabolite and bacterial profiling revealed 24-h oscillations and circadian networks. Rhythmicity in bacterial diversity, specific taxa, and functional pathways increased with age and was strongest following breastfeeding and GOS supplementation. Circadian rhythms in dominant taxa were further maintained ex vivo in a chemostat model. Hence, microbiota rhythmicity develops early in life and is impacted by diet.

Dietary fasting and time-restricted eating in Huntington's disease: therapeutic potential and underlying mechanisms.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein, resulting from a CAG repeat expansion in the huntingtin gene HTT. HD is characterized by a variety of debilitating symptoms including involuntary movements, cognitive impairment, and psychiatric disturbances. Despite considerable efforts, effective disease-modifying treatments for HD remain elusive, necessitating exploration of novel therapeutic approaches, including lifestyle modifications that could delay symptom onset and disease progression. Recent studies suggest that time-restricted eating (TRE), a form of intermittent fasting involving daily caloric intake within a limited time window, may hold promise in the treatment of neurodegenerative diseases, including HD. TRE has been shown to improve mitochondrial function, upregulate autophagy, reduce oxidative stress, regulate the sleep-wake cycle, and enhance cognitive function. In this review, we explore the potential therapeutic role of TRE in HD, focusing on its underlying physiological mechanisms. We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress-response pathways, and synchronize circadian rhythm activity. Understanding these mechanisms is critical for the development of targeted lifestyle interventions to mitigate HD pathology and improve patient outcomes. While the potential benefits of TRE in HD animal models are encouraging, future comprehensive clinical trials will be necessary to evaluate its safety, feasibility, and efficacy in persons with HD.

A critical role of Ca2+/calmodulin-dependent protein kinase II in coupling between evening and morning circadian oscillators in the suprachiasmatic nucleus.

Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) is widely expressed in the brain and is involved in various functions, including memory formation, mood and sleep. We previously reported that CaMKIIα is involved in the circadian molecular clock. Mice lacking functional CaMKIIα (K42R mice) exhibited a gradual increase in activity time (α decompression) of running-wheel (RW) activity due to a lengthened circadian period (τ) of activity offset under constant darkness (DD). In the present study, to investigate the functional roles of CaMKIIα in behavioural rhythms, we measured RW and general movements simultaneously under prolonged DD. Tau became longer as the relative intensity of behaviour activity within an activity time shifted from activity onset towards activity offset. In some K42R mice, α was gradually expanded with a marked reduction of RW activity, while general movements persisted without noticeable decline, which was followed by an abrupt shortening of α (α compression) with differential phase shifts of the activity onset and offset and recovery of RW activity. These results suggest that an internal coupling between the oscillators controlling activity onset and offset is bidirectional but with different strengths. The α compression occurred recurrently in 38% of K42R mice examined with an average interval of 37 days in association with attenuation of RW activity but never in the wild-type (WT) mice. Consistent with behavioural rhythms, the circadian period of the PER2::LUC rhythm in the cultured suprachiasmatic nucleus (SCN) slice was significantly longer in K42R than in WT. These findings are best interpreted by assuming that a loss of functional CaMKIIα attenuates the coupling between the onset and offset oscillators.

Neuronal E93 is required for adaptation to adult metabolism and behavior.

OBJECTIVE: Metamorphosis is a transition from growth to reproduction, through which an animal adopts adult behavior and metabolism. Yet the neural mechanisms underlying the switch are unclear. Here we report that neuronal E93, a transcription factor essential for metamorphosis, regulates the adult metabolism, physiology, and behavior in Drosophila melanogaster. METHODS: To find new neuronal regulators of metabolism, we performed a targeted RNAi-based screen of 70 Drosophila orthologs of the mammalian genes enriched in ventromedial hypothalamus (VMH). Once E93 was identified from the screen, we characterized changes in physiology and behavior when neuronal expression of E93 is knocked down. To identify the neurons where E93 acts, we performed an additional screen targeting subsets of neurons or endocrine cells. RESULTS: E93 is required to control appetite, metabolism, exercise endurance, and circadian rhythms. The diverse phenotypes caused by pan-neuronal knockdown of E93, including obesity, exercise intolerance and circadian disruption, can all be phenocopied by knockdown of E93 specifically in either GABA or MIP neurons, suggesting these neurons are key sites of E93 action. Knockdown of the Ecdysone Receptor specifically in MIP neurons partially phenocopies the MIP neuron-specific knockdown of E93, suggesting the steroid signal coordinates adult metabolism via E93 and a neuropeptidergic signal. Finally, E93 expression in GABA and MIP neurons also serves as a key switch for the adaptation to adult behavior, as animals with reduced expression of E93 in the two subsets of neurons exhibit reduced reproductive activity. CONCLUSIONS: Our study reveals that E93 is a new monogenic factor essential for metabolic, physiological, and behavioral adaptation from larval behavior to adult behavior.

Sleep and circadian rhythms in adolescents with attempted suicide.

Sleep and circadian rhythm disorders are very common in adolescents and have been linked to suicidal ideation. However, little is known about adolescent sleep before a suicide attempt (SA). The objectives of this study were to compare the sleep of adolescents aged 13 to 18 over a period of 4 weeks before a SA compared to a non-SA group, then to analyze the association between sleep, support social and well-being based on information from validated questionnaires. In 2015, 250 adolescents were included, 55 were recruited the day after a SA in French hospitals (before SA evaluations were retrospective). Logistic regression analyzes showed that during school days, bedtime was equivalent in both groups, but sleep onset latency was significantly longer in SA (86 min vs. 52 min, p = 0.016), and wake-up time was earlier (6 h 22 vs. 6 h 47, p = 0.002), resulting in a shorter total sleep time of 44 min (OR = 0.76, CI 95% [0.61-0.93]) the month preceding SA. Adolescents with longer sleep time performed better on perceived psychological well-being (p = 0.005), relationship with parents (p = 0.011) and school environment (p < 0.001). Results indicate a significant change in the quantity and quality of adolescents' subjective sleep in the 4 weeks preceding SA requiring objective measures to study the predictive properties of sleep in SA.

Impact of circadian clock protein Bmal1 on experimentally-induced periodontitis-associated renal injury.

OBJECTIVES: To investigate the mechanism of circadian clock protein Bmal1 (Bmal1) on renal injury with chronic periodontitis, we established an experimental rat periodontitis model. METHODS: Twelve male Wistar rats were randomly divided into control and periodontitis groups (n=6, each group). The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires, whereas the control group received no intervention measures. After 8 weeks, clinical periodontal parameters, including probing depth, bleeding index, and tooth mobility, were evaluated in both groups. Micro-CT scanning and three-dimensional image reconstruction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption. Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. Renal function indicators, such as creatinine, albumin, and blood urea nitrogen levels, and oxidative stress markers, including superoxide dismutase, glutathione, and malondialdehyde levels, were measured using biochemical assay kits. MitoSOX red staining was used to detect reactive oxygen species (ROS) content in the kidneys. The gene and protein expression levels of Bmal1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in rat renal tissues were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining. RESULTS: Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group. Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group. The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress, whereas the renal function levels showed abnormalities without statistical significance. MitoSOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group, and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1, Nrf2, and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend. CONCLUSIONS: Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Effects of Total Intravenous Anesthesia on Circadian Rhythms in Patients Undergoing Cardiac Transcatheter Closure.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

Bipolar Disorder, Circadian Rhythm and Clock Genes.

Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms such as melatonin and cortisol, clock genes, and circadian preference have shown the relationship between bipolar disorder and circadian rhythm. The results differed across different studies. In some studies, a delay in the circadian rhythm was observed in the depressive episode and advanced circadian rhythm was observed during the manic episode. In other studies, a delay in circadian rhythm was observed independent of mood episodes. Accordingly, circadian rhythm disorder was proposed as a trait marker for bipolar disorder. The altered circadian rhythm may represent a pathological mechanism that contributes to the mood episodes. However, a prospective cohort study is needed for further clarification.

OpsinLW2 serves as a circadian photoreceptor in the entrainment of circadian locomotor rhythm of a firebrat.

Photic entrainment is an essential function of the circadian clock, which enables organisms to set the appropriate timing of daily behavioral and physiological events. Recent studies have shown that the mechanisms of the circadian clock and photic entrainment vary among insect species. This study aimed to elucidate the circadian photoreceptors necessary for photic entrainment in firebrats Thermobia domestica, one of the most primitive apterygote insects. A homology search of publicly available RNA sequence (RNA-seq) data from T. domestica exhibited a cryptochrome 2 (cry2) gene and three opsin genes, opsin long wavelength 1 (opLW1), opLW2, and opUV, as candidate circadian photoreceptors. We examined the possible involvement of these genes in photic entrainment of firebrat locomotor rhythms. Firebrats had the highest entrainability to the light-dark cycle of green light. Treatment with dsRNA of the candidate genes strongly downregulated the respective targeted genes, and in the case of opsin genes, other untargeted genes were occasionally downregulated to various degrees. Under constant light, most control firebrats became arrhythmic, whereas a fraction of those treated with double RNAi of the two opLWs remained rhythmic. Behavioral experiments revealed that the transient cycles necessary for re-entrainment to shifted light cycles were lengthened when opLW2 expression was reduced. These results suggest that opLW2 is involved in the photic entrainment of circadian rhythm in firebrats.