Does enteral nutrition require continuity of management: a randomized controlled study.

Objective: To explore a set of enteral nutrition therapy continuity management programs for intensive care unit patients based on the theoretical study of circadian rhythm mechanism. Methods: The control group followed routine nursing management. Patients in the experimental group were implemented with an enteral nutrition continuity management program, and their eating behavior was adjusted 3 days before the end of tube feeding. Food intake was intermittent at 2, 3, and 4 h on the first day, the second day, and the third day of intervention, respectively, and all patients stopped eating at night. Abdominal distension assessment, appetite assessment, application of gastric motility drugs, and patient satisfaction were compared between the two groups after tube feeding. Results: Three days after the end of tube feeding, abdominal distention assessment, bowel sound auscultation, and appetite assessment were statistically different (P<0.05) between the two groups. There were differences in the first day (15 vs. 6, P<0.05), the second day (9 vs. 3, P<0.05), and the cumulative number (17 vs. 7, P<0.05) of gastrointestinal drugs, but no differences in the third day (2 vs. 1, P>0.05). There was a statistical difference in nursing intervention (6.0 vs. 7.0, P<0.05) and psychological nursing (6.0 vs. 7.0, P<0.05), but no statistical difference in health education, medical environment, and nursing attitude (P>0.05). Conclusion: Enteral nutrition continuity management program has a good preventive effect on the gastrointestinal symptoms of intensive care unit patients after the end of tube feeding.

Prevalence and outcomes of heart failure phenotypes in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. METHODS: AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. RESULTS: A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. CONCLUSIONS: The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF.

Real-world evidence of early rhythm control in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The favorable benefits of early rhythm control (ERC) therapy in newly diagnosed patients with atrial fibrillation (AF) have been demonstrated in the EAST-AFNET 4 trial. However, the generalizability and applicability of ERC in real-world clinical settings remain inconclusive. METHODS: We conducted a systematic search of the PubMed and Embase databases to identify observational studies published between January 2020 and February 2024 that focused on real-world evidence pertaining to ERC. The effectiveness and safety outcomes in our study were analogous to those evaluated in the EAST-AFNET 4 trial. RESULTS: A total of 4 observational studies that fulfilled the inclusion criteria of EAST-AFNET 4 were included, involving 130,970 patients with AF, 30.7% of whom received ERC therapy. In our pooled analysis using the fixed-effects model, compared with rate control, ERC significantly decreased the occurrence risk of the primary composite outcome (hazard ratio [HR] 0.86, 95% confidence interval[CI] 0.82-0.91), cardiovascular death (HR 0.87, 95% CI 0.78-0.98), stroke (HR 0.80, 95% CI 0.73-0.87), and hospitalization with worsening heart failure (HR 0.91, 95% CI 0.84-0.99) or acute coronary syndrome (HR 0.72, 95% CI 0.59-0.87). In terms of safety outcomes, there were no differences in the composite safety outcome (HR 1.00, 95% CI 0.95-1.05) and all-cause death (HR 0.93, 95% CI 0.82-1.06) between the two studied groups. CONCLUSIONS: ERC therapy showed favorable effectiveness outcomes compared with rate control, whereas the safety outcomes between the two therapeutic strategies did not differ significantly, supporting the benefits of ERC therapy over rate control in selected real-world patients with AF. REGISTRATION: The study protocol was registered to PROSPERO (CRD42023443569).

Predictors of Paroxysmal Atrial Fibrillation in Patients With a Cryptogenic Stroke: Selecting Patients for Long-Term Rhythm Monitoring.

BACKGROUND: After a cryptogenic stroke, patients will often require prolonged cardiac monitoring; however, the subset of patients who would benefit from long-term rhythm monitoring is not clearly defined. OBJECTIVE: Using significant predictors of AF using age, sex, comorbidities, baseline 12-lead electrocardiogram, short term rhythm monitoring and echocardiogram data, we created a risk score and compared it to previously published risk scores. METHODS: Patients admitted to Montefiore Medical Center between May 2017 and June 2022 with a primary diagnosis of cryptogenic stroke or TIA who underwent long-term rhythm monitoring with an implantable cardiac monitor were retrospectively analyzed. RESULTS: Variables positively associated with a diagnosis of clinically significant atrial fibrillation include age (p < 0.001), race (p = 0.022), diabetes status (p = 0.026), and COPD status (p = 0.012), the presence of atrial runs (p = 0.003), the number of atrial runs per 24 hours (p < 0.001), the total number of atrial run beats per 24 hours (p < 0.001) and the number of beats in the longest atrial run (p < 0.001), LA enlargement (p = 0.007) and at least mild mitral regurgitation (p = 0.009). We created a risk stratification score for our population, termed the "ACL score." The ACL score demonstrated superiority to the CHA2DS2-VASc score and comparability to the C2HEST score for predicting device-detected AF. CONCLUSION: The ACL score enables clinicians to better predict which patients are more likely to be diagnosed with device-detected AF after a cryptogenic stroke.

Sinus rhythm restoration reverses tricuspid regurgitation in patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Tricuspid regurgitation (TR) is a common valvular heart disease worldwide, and current guidelines for TR treatment are relatively conservative, as well as with detrimental outcomes. Restoration of sinus rhythm was reported to improve the TR severity in those TR patients with atrial fibrillation (AF). However, relevant research was limited. The aim of this meta-analysis was to evaluate the clinical outcomes of restoration of sinus rhythm in TR patients with AF. METHODS: In this study, PubMed, Web of Science, and Scopus databases were searched for study enrollment until July 2023. This study was designed under the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. These studies containing the patient's baseline characteristics, surgical procedure, and at least one of the clinical outcomes were included. The primary endpoint was TR grade during follow-up after restoration of sinus rhythm. RESULTS: Out of 1074 records, 6 were enrolled. Restoration of sinus rhythm is associated with a reduction of TR severity (TR grade, odds ratio 0.11, 95% confidence interval (CI): 0.01 to 1.28, P = 0.08, I2 = 83%; TR area, mean difference (MD) -2.19 cm2, 95% CI: -4.17 to -0.21 cm2, P = 0.03, I2 = 96%). Additionally, remolding of right heart with a significant reduction of tricuspid valve annulus diameter (MD -0.36 cm, 95%CI: -0.47 to -0.26 cm, P < 0.00001, I2 = 29%) and right atrium volume index (MD -11.10 mL/m2, 95%CI: -16.81 to -5.39 mL/m2, P = 0.0001, I2 = 79%) was observed during follow-up. CONCLUSIONS: In conclusion, rhythm-control therapy could reduce TR severity in AF patients with TR and is associated with right heart remodeling.

Exploring the Role of Circadian Rhythms in Sleep and Recovery: A Review Article.

Sleep is essential for every living organism. Humans spend about one-third of their lives sleeping. Sleep has been studied extensively, and the role of sleep in psychological, mental, and physical well-being is established to be the best. The rhythm of the brain between wakefulness and sleep is called the circadian rhythm, which is mainly controlled by melatonin and the pineal gland. The imbalance of this rhythm can lead to devastating effects on health. Vigorous workouts close to bedtime can interfere with falling asleep. Meal timing and composition can significantly affect sleep quality. It is advised to avoid large meals, caffeine, and alcohol before bedtime. Heavy meals close to bedtime can lead to poor sleep and hormone disruption. By following these guidelines enumerated in the article, individuals can improve sleep quality and overall health. Sleep cycles, especially rapid eye movement sleep, have a profound influence on mental and physical health. Adhering to recommended sleep practices enhances bodily restoration, fortifies the immune system, and upholds metabolic equilibrium. Sleep hygiene aligned with circadian rhythms is crucial for disease prevention and well-being. Healthcare professionals should prioritize sleep optimization strategies for patient care and public health.

Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

Outcome of tailored therapy in rheumatic heart disease with persistent atrial fibrillation (RHD-AF).

INTRODUCTION: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF. METHODS: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up. RESULTS: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. CONCLUSIONS: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations.

Circadian variations influence anxiety-related behaviour, olfaction, and hedonic response in male Sprague-Dawley rats.

INTRODUCTION: Despite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats. METHODS: Three behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats. RESULTS: Our findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects' active phase. DISCUSSION: This study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats' natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare.

Infants show systematic rhythmic motor responses while listening to rhythmic speech.

Rhythm is known to play an important role in infant language acquisition, but few infant language development studies have considered that rhythm is multimodal and shows strong connections between speech and the body. Based on the observation that infants sometimes show rhythmic motor responses when listening to auditory rhythms, the present study asked whether specific rhythm cues (pitch, intensity, or duration) would systematically increase infants' spontaneous rhythmic body movement, and whether their rhythmic movements would be associated with their speech processing abilities. We used pre-existing experimental and video data of 148 German-learning 7.5- and 9.5-month-old infants tested on their use of rhythm as a cue for speech segmentation. The infants were familiarized with an artificial language featuring syllables alternating in pitch, intensity, duration, or none of these cues. Subsequently, they were tested on their recognition of bisyllables based on perceived rhythm. We annotated infants' rhythmic movements in the videos, analyzed whether the rhythmic moving durations depended on the perceived rhythmic cue, and correlated them with the speech segmentation performance. The result was that infants' motor engagement was highest when they heard a duration-based speech rhythm. Moreover, we found an association of the quantity of infants' rhythmic motor responses and speech segmentation. However, contrary to the predictions, infants who exhibited fewer rhythmic movements showed a more mature performance in speech segmentation. In sum, the present study provides initial exploratory evidence that infants' spontaneous rhythmic body movements while listening to rhythmic speech are systematic, and may be linked with their language processing. Moreover, the results highlight the need for considering infants' spontaneous rhythmic body movements as a source of individual differences in infant auditory and speech perception.

Chinese self-report version of biological rhythms interview for assessment in neuropsychiatry (C-BRIAN-SR) - psychometric properties and prospective follow-up in patients with non-seasonal depression.

This study examined the psychometric properties and longitudinal changes of the self-reporting Traditional Chinese version of Biological Rhythms Interview for Assessment in Neuropsychiatry (C-BRIAN-SR) among healthy controls (HC) and patients with major depressive episode (MDE). Eighty patients with a current MDE and 80 HC were recruited. Assessments were repeated after two weeks in HC, and upon the discharge of MDE patients to examine the prospective changes upon remission of depression. The C-BRIAN-SR score was significantly higher in the MDE than HC group. The concurrent validity was supported by a positive correlation between scores of C-BRIAN-SR, Insomnia Severity Index and the Hospital Anxiety Depression Scale. C-BRIAN-SR negatively correlated MEQ in the MDE group (r = .30, p = 0.009), suggesting higher rhythm disturbances were associated with a tendency toward eveningness. A moderate test-retest reliability was found (r = .61, p < 0.001). A cut-off of 38.5 distinguished MDE subjects from HC with 82.9% of sensitivity and 81.0% of specificity. C-BRIAN-SR score normalized in remitted MDE patients but remained higher in the non-remitted. The C-BRIAN-SR is a valid and reliable scale for measuring the biological rhythms and may assist in the screening of patients with MDE.

Factors associated with chronotype, job burnout, and perceived stress among nurses in Chinese tertiary hospitals: A multicenter cross-sectional study.

Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.

Atrial fibrillation burden: a new outcome predictor and therapeutic target.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is not a dichotomous disease trait. Technological innovations enable long-term rhythm monitoring in many patients and can estimate AF burden. These technologies are already used to detect and monitor AF. This review describes the relation between AF burden and outcomes and potential effects of AF burden reduction. A lower AF burden is associated with a lower risk of stroke and heart failure in patients with AF: stroke risk without anticoagulation is lower in patients with device-detected AF and a low AF burden (stroke rate 1%/year) than in patients with persistent and permanent AF (stroke rate 3%/year). Paroxysmal AF shows intermediate stroke rates (2%/year). Atrial fibrillation burden-reducing interventions can reduce cardiovascular outcomes in patients with AF: early rhythm control reduces cardiovascular events including stroke and heart failure in patients with recently diagnosed AF and cardiovascular conditions. In patients with heart failure and AF, early rhythm control and AF ablation, interventions that reduce AF burden, reduce mortality and heart failure events. Recent technological innovations allow to estimate AF burden in clinical care, creating opportunities and challenges. While evidence remains limited, the existing data already suggest that AF burden reduction could be a therapeutic goal. In addition to anticoagulation and treatment of cardiovascular conditions, AF burden reduction emerges as a therapeutic goal. Future research will define the AF burden that constitutes a relevant risk of stroke and heart failure. Technologies quantifying AF burden need careful validation to advance the field.

Respiratory Function of Mitochondria in Patients with Coronary Heart Disease with Implantable Cardioverter-Defibrillator.

We studied the respiratory activity of mitochondria in peripheral blood leukocytes from 36 patients with coronary heart disease (CHD) and a history of ventricular tachyarrhythmias required cardioverter-defibrillator implantation. The measurements were carried out in incubation buffers with different oxidation substrates (succinate and pyruvate-malate mixture). In pyruvate-malate incubation buffer, oxygen consumption rate and respiratory control coefficients in patients with triggered device did not differ significantly from those in patients without cardioverter-defibrillator triggering. At the same time, respiratory control coefficients were below the reference values. In succinate buffer, values of mitochondrial parameters were significantly lower in patients with triggered devices. Our findings indicate that mitochondria of patients with non-triggered cardioverters-defibrillators have better functional and metabolic plasticity. It was concluded that activity of respiratory processes in mitochondria could be an indicator that should be taken into the account when assessing the risk of developing ventricular tachyarrhythmias.

Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.

A quantitative modeling framework to understand the physiology of the hypothalamic-pituitary-adrenal axis and interaction with cortisol replacement therapy.

Congenital adrenal hyperplasia (CAH) is characterized by impaired adrenal cortisol production. Hydrocortisone (synthetic cortisol) is the drug-of-choice for cortisol replacement therapy, aiming to mimic physiological cortisol circadian rhythm. The hypothalamic-pituitary-adrenal (HPA) axis controls cortisol production through the pituitary adrenocorticotropic hormone (ACTH) and feedback mechanisms. The aim of this study was to quantify key mechanisms involved in the HPA axis activity regulation and their interaction with hydrocortisone therapy. Data from 30 healthy volunteers was leveraged: Endogenous ACTH and cortisol concentrations without any intervention as well as cortisol concentrations measured after dexamethasone suppression and single dose administration of (i) 0.5-10 mg hydrocortisone as granules, (ii) 20 mg hydrocortisone as granules and intravenous bolus. A stepwise model development workflow was used: A newly developed model for endogenous ACTH and cortisol was merged with a refined hydrocortisone pharmacokinetic model. The joint model was used to simulate ACTH and cortisol trajectories in CAH patients with varying degrees of enzyme deficiency, with or without hydrocortisone administration, and healthy individuals. Time-dependent ACTH-driven endogenous cortisol production and cortisol-mediated feedback inhibition of ACTH secretion processes were quantified and implemented in the model. Comparison of simulated ACTH and cortisol trajectories between CAH patients and healthy individuals showed the importance of administering hydrocortisone before morning ACTH secretion peak time to suppress ACTH overproduction observed in untreated CAH patients. The developed framework allowed to gain insights on the physiological mechanisms of the HPA axis regulation, its perturbations in CAH and interaction with hydrocortisone administration, paving the way towards cortisol replacement therapy optimization.

Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

A leak K+ channel TWK-40 sustains the rhythmic motor program.

Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to the rhythmic defecation motor program (DMP) in Caenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function (gf) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.

Association between Circadian Rhythm-Disturbing Factors and Metabolic Syndrome in Korean Adults: Korea National Health and Nutrition Examination Survey (2016-2020).

Background: Circadian misalignment is associated with metabolic syndrome. This study aimed to examine the association between circadian rhythm-disturbing factors and metabolic syndrome. Methods: We used data from the 7th and 8th Korea National Health and Nutrition Examination Survey conducted between 2016 and 2020, which surveyed 16,253 individuals. Circadian rhythm-disturbing factors were defined as follows: sleep duration outside the reference group (6-8 hours), irregular breakfast, shift work, and physical inactivity. The adjusted odds ratio (aOR) for metabolic syndrome was calculated based on the number of circadian rhythm-disturbing factors present in adults over the age of 19 years. Results: Among a total of 16,253 participants (mean age 48.2±15 years), metabolic syndrome was found in 5,237 participants (29.3 %). The participants were classified into three categories based on the number of circadian rhythm-disturbing factors as follows: 2,627 (15.6%) did not have any factors, 6,406 (38.13%) had one factor, and 7,220 (46.3%) had two or more factors. Participants with a single circadian rhythm-disturbing factor were 21% more likely to have metabolic syndrome (aOR, 1.21; 95% confidence interval [CI], 1.08-1.36), and participants with two or more factors were 27% more likely to have metabolic syndrome (aOR, 1.27; 95% CI, 1.12-1.43). Conclusion: Circadian rhythm-disturbing factors were significantly associated with the prevalence of metabolic syndrome in Korean adults. This finding has potential clinical implications for maintaining circadian rhythms by avoiding certain factors to prevent metabolic syndrome. Further studies are required to confirm these findings.