24-hour Rhythm Research Articles

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

A Digital Health Intervention to Stabilize the 24-Hour Rhythm of Sleep, Meals, and Physical Activity for Reducing Depression Among Older Bereaved Spouses: Protocol for a Randomized Controlled Trial

A Digital Health Intervention to Stabilize the 24-Hour Rhythm of Sleep, Meals, and Physical Activity for Reducing Depression Among Older Bereaved Spouses: Protocol for a Randomized Controlled Trial

Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge.

For billions of years before electric light was invented, life on Earth evolved under the pattern of light during the day and darkness during the night. Through evolution, nearly all organisms internalized the temporal rhythm of Earth's 24-hour rotation and evolved self-sustaining biological clocks with a ~24-hour rhythm. These internal rhythms are called circadian rhythms, and the molecular constituents that generate them are called molecular circadian clocks. Alignment of molecular clocks with the environmental light-dark rhythms optimizes physiology and behavior. This phenomenon is particularly true for reproductive function, in which seasonal breeders use day length information to time yearly changes in fertility. However, it is becoming increasingly clear that light-induced disruption of circadian rhythms can negatively impact fertility in nonseasonal breeders as well. In particular, the luteinizing hormone surge promoting ovulation is sensitive to circadian disruption. In this review, we will summarize our current understanding of the neuronal networks that underlie circadian rhythms and the luteinizing hormone surge.

Ultradian rhythms of AKT phosphorylation and gene expression emerge in the absence of the circadian clock components Per1 and Per2.

Rhythmicity of biological processes can be elicited either in response to environmental cycles or driven by endogenous oscillators. In mammals, the circadian clock drives about 24-hour rhythms of multitude metabolic and physiological processes in anticipation to environmental daily oscillations. Also at the intersection of environment and metabolism is the protein kinase—AKT. It conveys extracellular signals, primarily feeding-related signals, to regulate various key cellular functions. Previous studies in mice identified rhythmicity in AKT activation (pAKT) with elevated levels in the fed state. However, it is still unknown whether rhythmic AKT activation can be driven through intrinsic mechanisms. Here, we inspected temporal changes in pAKT levels both in cultured cells and animal models. In cultured cells, pAKT levels showed circadian oscillations similar to those observed in livers of wild-type mice under free-running conditions. Unexpectedly, in livers of Per1,2−/− but not of Bmal1−/− mice we detected ultradian (about 16 hours) oscillations of pAKT levels. Importantly, the liver transcriptome of Per1,2−/− mice also showed ultradian rhythms, corresponding to pAKT rhythmicity and consisting of AKT-related genes and regulators. Overall, our findings reveal ultradian rhythms in liver gene expression and AKT phosphorylation that emerge in the absence of environmental rhythms and Per1,2−/− genes.

Indications, Contraindications, and Clinical Significance of Holter Monitoring Device

Holter electrocardiogram monitoring devices are mainly indicated to assess the 24-hour heart rate and rhythm, enabling clinicians and physicians to evaluate the underlying disorders, possibly arrhythmias. The clinical significance of these modalities was apparent in different clinical events, including cardiac and non-cardiac ones. Many applications and clinical advantages were reported since the device was first reported, which changed the way how healthcare settings deal with and monitor cardiac rhythm and associated abnormalities. Evidence shows that Holter monitoring devices are useful in the appropriate patient populace and are very efficacious in diagnosing and following cardiac arrhythmias and other different cardiac conditions, which can significantly enhance the prognosis and management of cardiovascular patients. In this context, it has been shown that primary healthcare physicians should always be aware that many patients might be present with asymptomatic cardiac arrhythmias. However, not many studies have adequately assessed them in the non-cardiac population, which calls for conducting more future investigations. In the present literature review study, we aim to discuss the indications, contraindications, and clinical significance of using the Holter monitoring device based on data from the relevant studies in the literature.

Rest-Activity Rhythm Patterns and Physical Functional Performance in Community-Dwelling Older Men

Sleep and activity patterns have been linked to physical performance in older adults. Traditional parametric models of 24-hour activity rhythms fail to adequately capture specific diurnal sleep and wake patterns; functional principal components analysis (fPCA) is a non-parametric approach that addresses this limitation. Using fPCA, we modeled accelerometry data from n = 2,960 participants in the Osteoporotic Fractures in Men (MrOS) ancillary sleep study (mean age 77y) and examined cross-sectional associations with gait speed and grip strength measurements. Lower daytime activity (expected difference = -0.049 [-0.072, -0.028] m/s), increased sleep duration and a reduced midday dip in activity (-0.015 [-0.035, 0.006] m/s) were modestly associated with worsening gait speed. A modest association between both later sleep and wake times and increased sleep duration with worsening grip strength outcomes was observed (-1.11 [-1.90, -0.32] kg). Specific daily activity patterns may serve as predictive biomarkers for changing physical function in aging populations.

Functional approach to sleep disturbance in chronic fatigue: chronic fatigue and sleep disturbance

Sleep is closely related to health behaviors and is also a crucial lifestyle in itself. In this regard, sleep health should be a part of assessing and managing chronic fatigue in the clinical field. First, it is vital to get in the early morning sun and improve sleep hygiene for proper melatonin secretion. Second, relaxation, meditation, or nutritional supplementation can be helpful to prevent sympathetic nervousness in the evening. Third, it is important to re-recognize and regain the health blessings of rapid eye movement sleep in the early morning. Lastly, meals tailored according to the biological clock (chrono-nutrition) can facilitate gut microbiota s healthy flourishing and the 24-hour circadian rhythm. When assessing and treating patients with chronic fatigue, functional medicine approaches are another essential step for improving the quality of life and advanced health care, based on a broad understanding of sleep science.

Abstract 14361: Time Restricted Feeding Modifies Day-Night Rhythms in Heart Rate and Cardiac Conduction

Background: Heart rate and cardiac conduction cycle with periodicity of 24-hours. The balance of circadian output from the autonomic nervous system and cardiomyocyte clock differentially regulates the sinoatrial (SA) and atrioventricular (AV) node, which could render the cardiac rate and conduction sensitive to internal misalignment and increase cardiac arrhythmogenicity. Hypothesis: The light-dark cycle entrains the circadian clock in the suprachiasmatic nucleus whereas the timing of feeding entrains circadian clocks in the peripheral organs. We determined whether time restricted feeding (TRF) to the light (inactive) cycle in mice caused misalignment in heart rate and conduction. Methods: Telemetry was used to record the electrocardiogram (ECG) in wild type (WT) mice housed in 12-hour light and 12-hour dark cycles. Day-night rhythms in ECG recordings were calculated by fitting data to a cosine function in ad libitum feeding conditions (ALF), 24 hours or 2-weeks after switching to TRF. Phase is reported as the peak rhythm relative to lights on (ZT = 0h). Results: During ALF, WT mice showed aligned 24-hour rhythms in the RR- and PQ-intervals that peaked at the beginning of the light cycle (ZT=4.4±0.5h and 4.6±0.3h, n=6). Switching to TRF for 24 hours caused a sudden and large phase shift in the peaks of 24-hour rhythms to the dark cycle (ZT=21.6±0.6h and 20.0±0.5h, p<0.05 compared to ALF). After 2 weeks of TRF, the RR- and PQ-intervals still peaked together at ZT=19.5±0.2h and 20.5±0.2h (p<0.05 compared to ALF). TRF also increased the 24-hour rhythm amplitude in the RR- and PQ-intervals by 161% and 118% after 24 hours of TRF, and by 109% and 80% after 2 weeks of TRF. That is due to significant increase peak of RR- (ALF 126.4 ± 2.6 ms, 24 hours after TRF 174.8 ± 7.3 ms, 2-weeks after TRF 167.2 ± 9.4 ms, p<0.01) and PQ-intervals (37.0 ± 1.3 ms, 41.5 ± 1.8 ms, 40.0 ± 1.1 ms, p<0.01) in dark cycle. Conclusion: TRF does not cause internal misalignment between the 24-hour rhythms of the RR- and PQ-intervals. TRF does cause a dramatic phase shift and increases the RR- and PQ-interval rhythm amplitudes along with their peak value. TRF could represent an underrecognized electrophysiological modifier in the day-night rhythms for heart rate and cardiac conduction.

Retraction: 24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex.

Retraction: 24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex.

Feeding and Eating Disorders in the Context of Circadian Rhythms.

A circadian rhythm is a 24-hour rhythm controlled by a master clock, the suprachiasmatic nucleus, and driven by synchronizing internal/external zeitgebers. Food intake is one of the most important external cues/zeitgebers. Studies in humans and animals have shown that misalignment of food intake leads to chronodisruption, which is associated with metabolic disruption, obesity, and disordered eating attitudes. The term chronotype, which expresses the circadian typology, has been classified into 3 main types that represent the differences in the reflection of circadian rhythms shown in human studies on daily behaviors. It has been reported that evening-type individuals are more prone to disrupted eating attitudes, such as skipping meals, eating at night, and consuming a calorie-rich diet. In addition, eating disorders up to the diagnostic level is associated with the evening type. The bidirectional relationship between impaired circadian rhythms and disordered eating attitudes has brought chronotherapeutic interventions, which are biological rhythm-oriented treatment approaches, to the agenda. Bright light therapy has been found to reduce bulimic eating behaviors and night eating symptoms. More evidence is needed regarding the effect of chronotherapeutic approaches on metabolic disorders, disordered eating attitudes, and eating disorders associated with obesity.

Tag-Nacht-Schwankungen des Augeninnendrucks als eigenständiger Risikofaktor für das primäre Offenwinkelglaukom

Purpose. Purpose: In addition to the static observation of intraocular pressure at an arbitrary time point, the dynamic observation of intraocular pressure in the 24-hour rhythm is considered to be clinically useful in order to better assess the extent of day-night fluctuations. Material and Methods. The literature review includes the current state of knowledge regarding the 24-hour fluctua- tions in intraocular pressure as an independent risk factor for primary open-angle glaucoma. The literature search was performed with PubMed. Results. The intraocular pressure is neuronally regulated and is involved in the circadian regulation via the nucleus supra- chiasmaticus; the normal fluctuation in intraocular pressure is 5 mmHg. In the context of systemic neurodegeneration in primary open-angle glaucoma, there is also a disturbance of the cir- cadian rhythm. The fluctuations in intraocular pressure can be 10 mmHg or more and are an independent risk factor for glaucoma progression. Conclusion. Thus, the goal of successful glaucoma therapy is not only to achieve an individual target pressure range, but also to normalise abnormal circadian intraocular pressure fluctuations. Keywords glaucoma, circadian rhythm, neurodegeneration, oxidative stress

The Effects of Different Hormones on Supraventricular and Ventricular Premature Contractions in Healthy Premenopausal Women.

Background and Objectives: The effects of gender differences on cardiac parameters have been well-established. In this study, we aimed to evaluate the possible associations of plasma levels of different sex hormones with premature atrial or ventricular contractions in premenopausal women. Materials and Methods: We conducted a prospective study which included women in late reproductive age who presented with palpitations during an eight-month period. A 12-lead electrocardiography, a transthoracic echocardiogram, blood samples, and 24-hour rhythm Holter were conducted on the third day of the menstrual cycle. Results Overall, 93 healthy premenopausal women with a median age of 42 years were enrolled. QTc interval was within normal limits in all patients. The 24 h range of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) was 0–6450 and was 0–21,230, respectively. The median number of PVCs was 540 and the median number of PACs was 212, respectively. In total, 51 patients (54.8%) had a frequency of PVCs > 500/24 h and 37 patients (39.8%) had a frequency of PACs > 500/24 h, respectively. No statistically significant association was shown between any hormone and the frequency of PACs. Regarding PVCs, patients with a PVCs frequency > 500/24 h had higher estradiol levels compared to patients with PVCs less than 500/24 h (median 60 pg/mL versus 42 pg/mL, p = 0.02, OR: 1.01). No association was found between PVCs and other hormones. Conclusions: In premenopausal healthy women, higher estradiol levels are independently associated with increased PVCs. This suggests that estradiol in late reproductive stages may exert proarrhythmic effects.

P060 Hypoxia-induced overexpression of Rev-Erb-alpha and NPAS2 proteins in obstructive sleep apnea patients - possible mechanism of DM2 development

Abstract Circadian clocks are endogenous coordinators of 24-hour behavioral and molecular rhythms, which disruption may be caused by obstructive sleep apnea (OSA). It is composed of a set of genes, function as activators (CLOCK, BMAL) or repressors (PER, CRY). Neuronal PAS Domain Protein 2 (NPAS2) can substitute CLOCK in its function. Orphan nuclear receptor (Rev-Erb-α) is another protein supporting the CLOCK-BMAL1 complex, forming the loop which helps to regulate their expression. There are studies suggesting the significant influence of circadian disruption mediated via NPAS2 and Rev-Erb-α on DM2 development. The aim of the study was to determine the role of NPAS2 and Rev-Erb-α in DM2 for OSA patients. All participants underwent polysomnography (PSG) examination. Based on apnea-hypopnea index accompanied by clinical data the recruited individuals (n=40) were assigned to one from 3 groups: OSA (severe OSA, no DM2; n=17), DM2 (severe OSA + DM2; n=7) and control group (no OSA, no DM2; n=16). Serum protein levels of Rev-Erb-α and NPAS2 were assessed with ELISA immunoassay. Analysis between the groups revealed the statistically significant difference only in NPAS2 protein level (p=0.037). Further post-hoc analysis revealed significant differences between OSA and the control group (p=0.017). Moreover, a statistically significant correlation between AHI and NPAS2 serum protein level was observed (r=-0.478, p=0.002). NPAS2 protein levels are associated with a number of apneas and hypopneas during the REM phase of sleep and might have a significant role in the development of OSA complications. However, further studies are needed to understand its role.

Deep-coverage spatiotemporal proteome of the picoeukaryote Ostreococcus tauri reveals differential effects of environmental and endogenous 24-hour rhythms

The cellular landscape changes dramatically over the course of a 24 h day. The proteome responds directly to daily environmental cycles and is additionally regulated by the circadian clock. To quantify the relative contribution of diurnal versus circadian regulation, we mapped proteome dynamics under light:dark cycles compared with constant light. Using Ostreococcus tauri, a prototypical eukaryotic cell, we achieved 85% coverage, which allowed an unprecedented insight into the identity of proteins that facilitate rhythmic cellular functions. The overlap between diurnally- and circadian-regulated proteins was modest and these proteins exhibited different phases of oscillation between the two conditions. Transcript oscillations were generally poorly predictive of protein oscillations, in which a far lower relative amplitude was observed. We observed coordination between the rhythmic regulation of organelle-encoded proteins with the nuclear-encoded proteins that are targeted to organelles. Rhythmic transmembrane proteins showed a different phase distribution compared with rhythmic soluble proteins, indicating the existence of a circadian regulatory process specific to the biogenesis and/or degradation of membrane proteins. Our observations argue that the cellular spatiotemporal proteome is shaped by a complex interaction between intrinsic and extrinsic regulatory factors through rhythmic regulation at the transcriptional as well as post-transcriptional, translational, and post-translational levels.

Desynchronized circadian clock and exposures to xenobiotics are associated with differentiated disease phenotypes: The interface of desynchronized circadian clock and exposures to xenobiotics would lead to adverse response and recovery.

A paradigm shift in the human chronotoxicity of xenobiotics would study two-sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems-based networks are under the influence of well-synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24-hour (periodic) diurnal rhythms and answering whether these disruptions in synchronization would affect response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system's elements. Desynchronized interfaces during critical life windows or in time-repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes.

Diel cycle of sea spray aerosol concentration

Sea spray aerosol (SSA) formation have a major role in the climate system, but measurements at a global-scale of this micro-scale process are highly challenging. We measured high-resolution temporal patterns of SSA number concentration over the Atlantic Ocean, Caribbean Sea, and the Pacific Ocean covering over 42,000 km. We discovered a ubiquitous 24-hour rhythm to the SSA number concentration, with concentrations increasing after sunrise, remaining higher during the day, and returning to predawn values after sunset. The presence of dominating continental aerosol transport can mask the SSA cycle. We did not find significant links between the diel cycle of SSA number concentration and diel variations of surface winds, atmospheric physical properties, radiation, pollution, nor oceanic physical properties. However, the daily mean sea surface temperature positively correlated with the magnitude of the day-to-nighttime increase in SSA concentration. Parallel diel patterns in particle sizes were also detected in near-surface waters attributed to variations in the size of particles smaller than ~1 µm. These variations may point to microbial day-to-night modulation of bubble-bursting dynamics as a possible cause of the SSA cycle.

Abstract P199: Circadian Contributions To Blood Pressure Variation Under Constant Conditions

The circadian clock is an endogenous biological timekeeper that responds to environmental changes and governs various physiological processes over a 24-hour cycle. Blood pressure (BP) variation is thought to be controlled by the circadian clock, but few studies have examined circadian control of BP in humans. Moreover, it is unknown whether nighttime BP dipping is driven by the circadian system or by external factors. We investigated whether the circadian system drives 24-hour rhythms in BP, including nighttime BP dipping, using a 30-hour constant routine (CR) protocol. The CR protocol controls for external factors, allowing circadian rhythms to be isolated and measured, by having participants lie in a semi-recumbent posture in dim light (<10 lux) at a constant temperature, consume isocaloric snacks every 2 hours, and maintain wakefulness. To measure the BP rhythm, ambulatory BP was measured every 30 minutes (SpaceLabs 90227), and to measure the central circadian rhythm, core body temperature was measured every 10 seconds using an ingestible, wireless sensor (HQInc Core Body Temperature Wireless Data Record and Sensor). To date, 17 normotensive African American participants (13 females and 4 males), with a mean age of 37 (± 11.3) years and body mass index (BMI) of 32.5 kg/m 2 , have completed the study. Approximately 59% of participants (10 of 17) had non-dipping systolic BP at screening, defined as a <10% decrease in mean systolic BP from daytime to nighttime. Under constant conditions, 94% of participants (16 of 17) had a non-dipping BP phenotype. Median systolic BP dipping was 0.8% for females and 2.2% for males. There was a robust rhythm in participants’ core body temperature but not BP, suggesting that the circadian clock may not contribute substantially to a nighttime decrease in BP in normotensive African Americans. Instead, the non-dipping BP phenotype is likely more so a result of behavioral and/or physiological sleep-related processes. Future research and interventions for non-dipping BP may need to target these underlying behavioral and physiological processes.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. Emens JS, St Hilaire MA, Klerman EB, etal. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Is heart rate variability a risk factor for premature ejaculation?

The purpose of this study is to assess the parameters of heart rate variability, which is an indicator of the change in autonomic nervous system (ANS) activity, in individuals with premature ejaculation (PE). This study was performed by comparing 40 patients with PE (mean age, 31.2±4.1years) and 40 healthy individuals (mean age, 30.4±4.8years) without PE from May 2018 to December 2019. HRV parameters were compared between men with PE and healthy controls in 24-hour heart rhythm Holter examination. In the time domain analysis, which is a subgroup of HRV, square root of differences between consecutive normal NN intervals (RMSSD), which is an indicator of parasympathetic activity, was lower in patients with PE compared with controls (P=.025). Moreover, within the frequency domain analysis, high frequency (HF), another indicator of parasympathetic activity, was lower in patients compared with controls (P=.032). Finally, the LF/HF ratio, reflecting sympathetic/parasympathetic activity ratio, was significantly higher in patients compared with controls (P=.008). Furthermore, the multivariate logistic regression analysis showed that LF/HF ratio is independently associated with PE (P=.005). The ROC curve analysis showed that the optimal cut-off value of LF/HF above 2.7 predicted PE at a sensitivity of 77.5% and specificity of 82.5% (positive predictive value: 81.5% and negative predictive value: 78.5%). Different HRV parameters were exhibited in the comparison of patients with PE and normal controls. It suggests that the change in HRV parameters will be an indicator of imbalance in ANS and this imbalance may cause PE. Therefore, HRV analysis can be a diagnostic tool to assess altered ANS activity in patients with PE and may be considered as a rapid screening tool.

Patient preferences for ambulatory blood pressure monitoring devices: Wrist-type or arm-type?

BackgroundAmbulatory blood pressure monitoring (ABPM) is important in evaluating average 24-hour blood pressure (BP) levels, circadian rhythm, sleeping BP and BP variability but many patients are reluctant to use standard ABPM devices.MethodsWe compared two validated ABPM devices, the BPro tonometric wrist monitor and the A&D TM-2430 oscillometric upper arm monitor, for agreement of recordings and acceptability in 37 hypertensive patients (aged 55±9 years).ResultsSuccessful BP measurements were less frequent with the wrist-type than the arm-type device during the sleeping (66.3% vs. 92.9%, P <0.01) and awake periods (56.2% vs. 86.5%, P <0.01). Comparable paired readings showed no significant difference in systolic BP but diastolic BP (DBP) values were higher with the wrist compared to the arm monitor (24-hour 89±13 vs. 85±14 mmHg, P <0.01) with similar differences awake and sleeping. Bland-Altman analysis showed some large discrepancies between individual arm and wrist monitor measurements. More patients found the wrist monitor more comfortable to use than the arm monitor.ConclusionsDespite the difference in individual BP measurements and the systematic overestimation of DBP values with the BPro device, wrist monitors with good patient acceptability may be useful to facilitate ABPM in some patients to provide additional information about cardiovascular risk and response to antihypertensive therapies.