Stability Of Rhythm Research Articles

Алгоритм количественной оценки кардиореспираторной синхронизации для характеристики функционального состояния и межсистемных взаимодействий у спортсменов

Introduction. The rhythm of the heart (heart rate, HR) is closely related to the rhythm of breathing. The phenomenon of respiratory sinus arrhythmia (an increase in heart rate during inhalation and a decrease during exhalation) is well known. Cardiorespiratory interactions and synchronization of these two signals are evaluated differently in the literature. The purpose of this work was to propose and test an approach to assess cardiorespiratory synchronization – the calculation of the cross-correlation coefficient between heart rate and respiration curve, for a more objective characterization of an athlete’s bodily states. Methods. A photoplethysmogram and respiration were recorded in 45 healthy athletes (18-25 years old) in three situations: rest, paced breathing at 6 times per minute (resonant frequency) and the performance of a sensorimotor task (tapping with the rhythmic metronome sounds and then reproducing a given rhythm from memory). For the HR and respiration curves, filtering and smoothing algorithms using the Savitsky-Goley method were applied sequentially, and then the cross-correlation coefficient between the two curves was calculated. The spectral parameters of heart rate variability (LF and HF) were also obtained, since during spontaneous breathing its contribution to the HR is reflected in HF band, and when breathing at a resonant frequency, a peak occurs at a frequency of 0.1 Hz in the LF band. Results. The cross-correlation coefficient, as well as the peak of HR spectral power at 0.1 Hz, increases significantly when breathing at a resonant frequency. The relationship between these indicators is most accurately described not by a linear, but by a logarithmic dependence. When performing a sensorimotor task, the so-called respiratory waves in the heart rhythm spectrum (HF) do not change from rest to tapping by a metronome and then to holding the rhythm by memory. At the same time, the cross-correlation coefficient demonstrates significant changes between these situations. In addition, a significant correlation was found between the change in the cross-correlation coefficient and the stability of rhythm maintenance (from memory): an increase in the cardiorespiratory synchronization leads to a decrease in motor rhythm stability. Conclusion. Assessment of cardiorespiratory synchronization due to the peculiarities of both signals (changes in heart rate and respiratory phases) requires preliminary preparation of data arrays: filtering and smoothing the stepped curve of heart rate dynamics. The calculation of the cross-correlation coefficient can be used to assess cardiorespiratory synchronization in real time and is likely to be applicable in short time fragments to assess emotional reactions and other short-term fluctuations in psychophysiological conditions, where the classical method of assessing changes in heart rhythm in the frequency or time domains is not applicable.

Association between rest-activity rhythm and diabetic retinopathy among US middle-age and older diabetic adults.

The disruption of circadian rhythm has been reported to aggravate the progression of diabetic retinopathy (DR). Rest-activity rhythm (RAR) is a widely used method for measuring individual circadian time influencing behavior. In this study, we sought to explore the potential association between RAR and the risk of DR. Diabetic participants aged over 40 from 2011-2014 National Health and Nutrition Examination Survey (NHANES) were enrolled. Data from the wearable device ActiGraph GT3X was used to generate RAR metrics, including interdaily stability (IS), intradaily variability (IV), most active 10-hour period (M10), least active 5-hour period (L5), and Relative amplitude (RA). Weighted multivariable logistic regression analysis and restricted cubic spline analysis were conducted to examine the association between RAR metrics and DR risk. Sensitivity analysis was also conducted to examine the robustness of the findings. An unsupervised K-means clustering analysis was conducted to identify patterns in IV and M10. A total of 1,096 diabetic participants were enrolled, with a DR prevalence of 20.53%. The mean age of participants was 62.3 years, with 49.57% being male. After adjusting covariates, IV was positively associated with DR (β: 3.527, 95%CI: 1.371-9.073). Compared with the lowest quintile of IV, the highest quintile of IV had 136% higher odds of DR. In contrast, M10 was negatively associated with DR (β: 0.902, 95%CI: 0.828-0.982), with participants in the highest M10 quintile showing 48.8% lower odds of DR. Restricted cubic spline analysis confirmed that these associations were linear. Meanwhile, sensitivity analysis confirmed the robustness. K-means clustering identified three distinct clusters, with participants in Cluster C (high-IV, low-M10) had a significantly higher risk of DR comparing with Cluster A (low-IV, high-M10). A more fragmented rhythm and lower peak activity level might be associated with an increased risk of DR. These findings indicate that maintaining a more rhythmic sleep-activity behavior might mitigate the development of DR. Further research is necessary to establish causality and understand the underlying mechanisms, and focus on whether interventions designed to enhance daily rhythm stability and increase diurnal activity level can effectively mitigate the risk of progression of DR.

Abstract Mo051: Phototherapy to stimulate carnosine activity and enhance global heart function: A promising adjunctive therapy for congestive heart failure (CHF)

Background: The emerging field of cardiac optogenetics uses pulses of light to stimulate optically-sensitive proteins in the heart, influencing cellular physiology with unprecedented spatiotemporal resolution. Effects include increased glutathione and carnosine activity, and promotion of ATP synthesis. Clinical benefits include improved functional capacity, heart rhythm stability, and relief form congestive heart failure (CHF). Transcutaneous phototherapy devices are now available (LifeWave Inc, San Diego, USA), which may provide these benefits without the requirement for an external power source. Objective: To investigate whether upregulation of carnosine activity using a wearable cutaneous phototherapy device may improve echocardiographic measures of global heart function, cardiac contractility, and hemodynamics. Methods: The Carnosine ® adhesive skin patch (34 mm outside diameter) contain an organic crystalline material that reflects back specific frequencies of infra-red light known to activate carnosine dipeptides throughout the body. These function as a high-energy phosphate system known to enhance muscle function. Study participants (n=12 healthy volunteers (7 male, 5 female), 40-66 years of age) underwent a focused baseline echocardiogram, which included atrial (A) and early (E) mitral valve inflow, peak tissue velocity (E’) at both the lateral and septal mitral annulus, and left ventricular ejection fraction (LVEF). 10-14 patches were then applied along the sternum and across the left thorax (3 rd -5 th interspace), incorporating the anterior axilla. The echocardiogram was repeated 20-30 minutes after patch application. Results: LVEF was improved following application of the phototherapy device, increasing from 59.8±6.3% to 66.65±5.8% (Δ 6.3%, p<0.05), indicating an improvement in overall cardiac function. Septal E’ also increased, from 7.3±0.7 cm/s to 8.2±0.6 cm/s (Δ 0.89 cm/s, p<0.05), indicating a direct effect on contractility. E and A wave velocities increased from 63.7 cm/s to 66.1 cm/s (Δ 2.5±0.4 cm/s, p<0.08) and from 56.8 cm/s to 62.6 cm/s (Δ 5.7±0.7 cm/s, p<0.1), indicating augmented hemodynamics trending towards significance. Conclusion: Self-powered wearable phototherapy devices may enhance myocardial contractility and overall cardiac function. Such technologies represent a promising therapy for CHF.

Variability in sleep architecture and alterations in circadian rhythms in patients with acute cerebral infarction accompanied by sleep-disordered breathing.

To continuously and dynamically monitor the sleep status of patients in the acute phase of cerebral infarction, and to investigate the characteristics of acute cerebral infarction(ACI)associated with sleep-disordered breathing (SDB), variations in sleep structure, and changes in sleep circadian rhythms. Patients with ACI within 48h of onset who were admitted to the Department of Neurology at Kailuan General Hospital from November 2020 to December 2022 were selected. Detailed baseline information such as age, gender, smoking history, drinking history, were recorded for the selected participants. From the beginning of their hospitalization, the selected participants were monitored for their sleep status continuously for 5 days using the Intelligent Mattress-based Sleep Monitoring Platform System(IMSMPS). Based on the heart rate data obtained from the monitoring, the interdaily stability (IS) and intradaily variability (IV) of the sleep circadian rhythm were calculated. 1,367 patients with ACI were selected. Monitoring results over 5 days indicated 147 cases (10.75%) without SDB, and 1,220 cases (89.25%) with SDB. Among the group with SDB, there were 248 cases (18.14%) with continuous mild SDB, 395 cases (28.90%) with moderate SDB, 295 cases (21.58%) with severe SDB, and 282 cases (20.63%) that fluctuated between different severity levels. Within this fluctuating group, 152 cases (53.90%) fluctuated between two severity levels, 120 cases (42.55%) between three levels, and 10 cases (3.55%) among all four levels. There were statistically significant differences (P < 0.05) in the sleep latency, sleep efficiency, non-rapid eye movement stages 1-2, rapid eye movement, proportion of non-rapid eye movement, proportion of rapid eye movement, wake after sleep onset, time out of bed, number of awakenings, respiratory variability index, and heart rate variability index among patients with ACI monitored from day 1 to 5. However, other monitored sleep structure parameters did not show statistically significant differences (P > 0.05). The coefficient of variation for all sleep monitoring parameters ranged between 14.54 and 36.57%. The IV in the SDB group was higher than in the group without SDB (P < 0.05), and the IS was lower than in the group without SDB (P < 0.05). Patients in the acute phase of cerebral infarction have a high probability of accompanying SDB. The sleep structure of these patients shows significant variability based on the onset time of the stroke, and some patients experience fluctuations among different severity levels of SDB. ACI accompanied by SDB can further reduce the IS of a patient's sleep circadian rhythm and increase its IV.

Seasonal Stability of the Circadian Rhythm in Patients with Type I Myocardial Infarction.

A circadian rhythm of myocardial infarction has been described but there is little data on its relation with seasons and months. From June 2013 to June 2018, we analyzed the alerts for acute ST-segment elevation myocardial infarction (STEMI) in a Spanish region with 6.64 million inhabitants, universal health coverage, and an organized STEMI reperfusion network. We selected those patients which an identifiable culprit plaque. We recruited 6765 cases of STEMI due to type I acute myocardial infarction (type-I AMI), with mean age of 63.2 years (range 17-101, standard deviation [SD] 13.7), 5238 were males (77.4%) and 2801 (41.9%) were 65 years or older. The hourly distribution followed a fixed pattern in all months, with most of the events occurring between 6:00 AM and 4:00 PM, a peak at approximately 01:00 PM and a valley between 10:00 PM and 06:00 AM. No significant difference was found when comparing the mean time to first medical contact between July (the month with more daylight hours) and December (the month with shortest days). No significant differences were found between male and female patients, or between patients aged 65 years or older and younger patients. There was a close correlation between the number of events per month and the number of events occurring during the day (6 AM to 6 PM, r = 0.988, p = 0.001) and during the night (6 PM to 6 AM, r = 0.944, p 0.001), with different slopes of the regression lines (t-test, p 0.001), so that the difference between day-night occurrences increased with the total incidence. There is a circadian pattern in the presentation of STEMI that is not influenced by sex and age. The different incidence of STEMI at different times of the year does not affect the circadian pattern in terms of the shape of the curve or the mean time of presentation, although diurnal events increase more than nocturnal events, suggesting that triggers are most likely to act during vulnerable periods as determined by a circadian-based rhythm.

Comparing Human-Smartphone Interactions and Actigraphy Measurements for Circadian Rhythm Stability and Adiposity: Algorithm Development and Validation Study.

This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. We hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. We enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. Sleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. Our findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.

Factors associated with the fragmentation and stability of the rest-activity rhythm in adults and older adults

ABSTRACT This cross-sectional study aimed to identify factors related to the fragmentation and stability of the rest-activity rhythm (RAR) in adults and older adults. It is part of a larger research project investigating aspects concerning sleep duration, quality, and disorders in a representative subsample of the population. Sociodemographic data, lifestyle, health habits and subjective sleep variables were obtained; RAR records were collected by means of actigraphy and analyzed using non-parametric variables (IS, IV, M10, L5, RA, sL5, and sM10). Study participants were 313 individuals with complete actigraphy records. There was a prevalence of older adults (50.2%) and females (51.1%). Females, individuals with 4–8 y of education, and those who used alcohol abusively exhibited lower RAR fragmentation. Higher fragmentation was observed in individuals who napped and those reporting poor sleep quality. Greater rhythm stability was evident in females, older adults, those with 4–8 y of education, and those who had a partner. Smokers demonstrated lower RAR stability. These findings may contribute valuable insights for decision-making aimed at preventing and treating issues related to fragmentation and instability of the rhythm and its possible consequences to health.

Factors Related to Masticatory Rhythm in Patients with Oral Tumors.

Background: Older adults who have undergone surgery for oral tumors are at increased risk of impaired masticatory rhythm. This study investigated the correlations between masticatory rhythm, objective masticatory performance, and subjective masticatory performance as well as factors related to masticatory rhythm. Methods: The participants were 44 adults (24 men, 20 women; age range 42~90 years old) who had undergone maxillectomy, mandibulectomy, or glossectomy and were rehabilitated with a maxillofacial prosthesis. The number of functional contact teeth pairs was confirmed by intraoral examination. Chewing rate, cycle duration, coefficient of variation (CV) for cycle duration (reflecting the stability of masticatory rhythm), and mixing ability were measured simultaneously using a mastication movement rhythm tracking device during gum chewing. Maximum occlusal force was measured using the dental prescale system. Patients' perception of chewing ability was rated using a questionnaire. Results: The Spearman's rank correlation test revealed that mixing ability, patient-rated masticatory scores, cycle duration, CV for cycle duration, and maximum occlusal force showed significant correlations with chewing rate. Multiple linear regression analysis identified mixing ability and the CV for cycle duration as significant predictors of masticatory rhythm. Conclusions: Factors associated with a faster chewing rate were higher mixing ability and masticatory scores, greater maximum occlusal force, shorter cycle duration, and smaller CV for cycle duration. Stable masticatory rhythm and mixing ability are significant predictors of chewing rate. Poor masticatory performance and unstable masticatory rhythm can result in slower chewing and thus a higher risk of inadequate dietary intake.

Robotic-Assisted Epicardial Hybrid Ablation and Left Appendage Closure in Persistent Atrial Fibrillation: First European Experience.

Background: Pulmonary vein isolation is currently considered to be the gold standard for ablating paroxysmal atrial fibrillation. However, its efficacy is limited in patients with persistent atrial fibrillation. The convergent procedure has emerged as a hybrid ablation. This study aims, for the first time in the literature, to introduce a hybrid approach that includes epicardial ablation with cutting-edge robotic technology and subsequent electrophysiological study to verify and an endocardial ablation to complete the ablation lines. Methods: We present 18 cases of robotic-assisted epicardial hybrid ablation performed between April and December 2023 on patients with long-standing persistent atrial fibrillation (mean age: 64 ± 5 years; mean duration: 4 ± 2 years). All of the procedures were performed at "Humanitas Gavazzeni Hospital", Bergamo, Italy. Robot-assisted epicardial ablation performed using the "Epi-Sense AtriCure" device was guided by monitoring electrogram morphology and point-by-point impedance drop. This approach also included left atrial appendage occlusion and the disconnection of the ligament of Marshall. An electrophysiological study and endocardial ablation were planned three months after the procedure. Results: The procedure was successfully executed in all patients with no major complications and a mean operative time of 142 ± 22 min. None of the cases required conversion to full sternotomy or minithoracotomy. The procedure was performed in all cases without extracorporeal circulation and on a beating heart. Fifteen patients (83%) were extubated in the operating room. The length of stay in the intensive care unit was less than 24 h. Acute restoration of sinus rhythm was achieved in 12 out of the 18 patients (67%); the median duration of their hospital stay was two days. In the electrophysiological study, seven pts had sinus rhythm, two had atrial fibrillation, and one patient developed atrial flutter at 3-month follow-up. Patients underwent transcatheter ablation to complete the lesion set and, at the time of discharge, were all in sinus rhythm. Conclusions: In our initial experience, surgical atrial fibrillation ablation consisting of a unilateral thoracoscopic technique facilitated by a robotic platform and continuous EGM monitoring has proven to be safe and feasible. For the electrophysiological study at 3 months, completing the gaps in the surgical ablation lines could improve the clinical results of the technique in terms of sinus rhythm stability. However, mid- and long-term follow-up is required to demonstrate this.

Is rest-activity rhythm prospectively associated with all-cause mortality in older people regardless of sleep and physical activity level? The 'Como Vai?' Cohort study.

This study aims to test the association of rest-activity rhythm (intradaily variability and interdaily stability) with all-cause mortality in an older adult cohort in Brazil. It also assesses whether the amount of time spent at each intensity level (i.e., physical activity and nocturnal sleep) interferes with this association. This cohort study started in 2014 with older adults (≥60 years). We investigated deaths from all causes that occurred until April 2017. Rest-activity rhythm variables were obtained using accelerometry at baseline. Intradaily variability indicates higher rhythm fragmentation, while interdaily stability indicates higher rhythm stability. Cox proportional-hazard models were used to test the associations controlling for confounders. Among the 1451 older adults interviewed in 2014, 965 presented valid accelerometry data. During the follow-up period, 80 individuals died. After adjusting the analysis for sociodemographic, smoking, morbidity score, and number of medicines, an increase of one standard deviation in interdaily stability decreased 26% the risk of death. The adjustment for total sleep time and inactivity did not change this association. On the other hand, the association was no longer significant after adjusting for overall physical activity and moderate to vigorous physical activity. Rest-activity rhythm pattern was not associated with mortality when physical activity was considered, possibly because this pattern could be driven by regular exercise. Promoting physical activity remains a relevant strategy to improve population health.

Genomic investigation of duplication, functional conservation, and divergence in the LRR-RLK Family of Saccharum

BackgroundSugarcane (Saccharum spp.) holds exceptional global significance as a vital crop, serving as a primary source of sucrose, bioenergy, and various by-products. The optimization of sugarcane breeding by fine-tuning essential traits has become crucial for enhancing crop productivity and stress resilience. Leucine-rich repeat receptor-like kinases (LRR-RLK) genes present promising targets for this purpose, as they are involved in various aspects of plant development and defense processes.ResultsHere, we present a detailed overview of phylogeny and expression of 288 (495 alleles) and 312 (1365 alleles) LRR-RLK genes from two founding Saccharum species, respectively. Phylogenetic analysis categorized these genes into 15 subfamilies, revealing considerable expansion or reduction in certain LRR-type subfamilies. Compared to other plant species, both Saccharum species had more significant LRR-RLK genes. Examination of cis-acting elements demonstrated that SsLRR-RLK and SoLRR-RLK genes exhibited no significant difference in the types of elements included, primarily involved in four physiological processes. This suggests a broad conservation of LRR-RLK gene function during Saccharum evolution. Synteny analysis indicated that all LRR-RLK genes in both Saccharum species underwent gene duplication, primarily through whole-genome duplication (WGD) or segmental duplication. We identified 28 LRR-RLK genes exhibiting novel expression patterns in response to different tissues, gradient development leaves, and circadian rhythm in the two Saccharum species. Additionally, SoLRR-RLK104, SoLRR-RLK7, SoLRR-RLK113, and SsLRR-RLK134 were identified as candidate genes for sugarcane disease defense response regulators through transcriptome data analysis of two disease stresses. This suggests LRR-RLK genes of sugarcane involvement in regulating various biological processes, including leaf development, plant morphology, photosynthesis, maintenance of circadian rhythm stability, and defense against sugarcane diseases.ConclusionsThis investigation into gene duplication, functional conservation, and divergence of LRR-RLK genes in two founding Saccharum species lays the groundwork for a comprehensive genomic analysis of the entire LRR-RLK gene family in Saccharum. The results reveal LRR-RLK gene played a critical role in Saccharum adaptation to diverse conditions, offering valuable insights for targeted breeding and precise phenotypic adjustments.

Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation.

Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.

Associations of 24‐h rest‐activity patterns with plasma markers of neurodegeneration and Alzheimer’s disease pathology in cognitively unimpaired individuals

AbstractBackgroundAltered 24‐h rest‐activity rhythms have been previously associated with higher burden of Alzheimer’s disease (AD) pathological hallmarks, as measured with positron emission tomography or cerebrospinal fluid collection. Recent developments in fluid biomarkers now allow to non‐invasively measure levels of AD‐related pathology in the plasma. Here, we examined whether actigraphy‐derived 24‐h rest‐activity patterns could be linked to plasma markers of neurodegeneration and AD pathology in a sample of cognitively unimpaired participants.MethodNinety‐three asymptomatic individuals (mean age = 59.73 ± 13.74 y., range = 30 – 85 y., 48 females, Table 1) underwent 10 days of actigraphic recordings, and blood drawing. Standard non‐parametric indices of 24‐h rest‐activity rhythm fragmentation (intradaily variability, IV) and stability (interdaily stability, IS) were extracted using the GGIR package (v2.8‐2) in R. Plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), 40 and 42 amino acid‐long amyloid‐β (Aβ40 and Aβ42, respectively), total tau, and phosphorylated tau at threonine 181 (pTau181) or threonine 231 (pTau231) were measured using Single molecule array technology.ResultMultiple linear regression models adjusted for age, sex, education, and body mass index, showed that worse rest‐activity rhythm fragmentation, as indicated by higher IV values, was strongly associated with elevated levels of plasma NfL (t = 4.53, p &lt; .0001, Figure 1), but also with higher levels of plasma GFAP (t = 2.44, p = .02, Figure 2) and lower plasma Aβ42/40 ratio (t = ‐2.23, p = .03, Figure 2). Similarly, increased day‐to‐day rest‐activity rhythm stability, as indicated by higher IS values, was associated with lower levels of plasma NfL (t = ‐2.37, p = .02, Figure 1). By contrast, no significant relationships were found between IV or IS values and total tau or phosphorylated tau plasma biomarkers (all p &gt; .27).ConclusionThese findings provide further evidence that disrupted rest‐activity patterns, in particular fragmentation of rest‐activity rhythms, may constitute a sensitive marker of incipient AD pathology and neurodegeneration in cognitively unimpaired individuals. Our study therefore highlights the clinical utility of monitoring rest‐activity patterns for improved detection of individuals at‐risk for neurodegenerative diseases, including AD.

Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial

ObjectivePerform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DesignSecondary analysis of a randomized controlled trial with convenience age subsamples (younger (20–49 year; n = 52) versus and older (50–71 years; n = 35)). SettingCommunity mental health clinics. ParticipantsEighty-seven adults with serious mental illness. InterventionTranS-C versus treatment as usual (TAU). MeasurementsOutcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). ResultsDepression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = −0.40, 95% confidence interval (CI): −0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: −0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = −0.52, n = 15, p = 0.049). ConclusionConfirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. Brief article summaryThe authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults).A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

Atrial fibrillation and high-grade functional mitral regurgitation - what is the chicken, what is the egg?

Abstract Background Atrial fibrillation (AF) and mitral valve regurgitation (MR) represent highly prevalent and intimately linked comorbidities with shared and interacting pathophysiological mechanisms [1]. The first-time and simultaneous occurrence of high-grade functional MR (fMR) and AF therefore often poses a chicken-or-egg dilemma, rendering clinical decision making on which of the two conditions should prioritized challenging. To date, data regarding the rationale and the timing of MR therapy in this cohort are lacking. Purpose The aim of the present study was to identify predictors of persistence of de novo high-grade fMR after rhythm control of concomitant de novo AF in order to provide guidance for the early clinical management of this relevant cohort of patients. Methods In a single center observational cohort study, consecutive patients presenting with first diagnosed MR and AF undergoing acute rhythm control of AF were identified and patients with non-high-grade MR, primary MR, simultaneous cardiogenic shock, prior mitral valve repair or replacement, endocarditis, intracardiac thrombi and/or concomitant relevant pathology of the aortic valve were excluded. Clinical and echocardiographic parameters at baseline and follow-up (FU) were assessed and predictors of persistence of high-grade fMR at FU were identified via multivariable logistic regression analyses. Results A total of 780 consecutive patients were identified between 2016 and 2022, of whom 100 patients were enrolled in the study. Acute rhythm control of AF was achieved predominantly by electrocardioversion (90%, 90/100) and in a minority by pulmonary vein isolation (10%, 10/100). After a median FU period of 318 days (IQR 849 days), 59% (59/100) patients showed mild to moderate fMR and 41% (41/100) patients presented with persisting high-grade fMR, of whom 44% (18/41) and 39% (16/41) underwent surgical or percutaneous MR therapy, respectively. The remaining 17% (7/41) were conservatively treated. AF/AT recurrence was not associated with persistent high-grade MR (Odds ratio [OR] 2.4, 95% confidence interval [CI] 0.6-4.5, p = 0.2), whereas concomitant first degree AV block (OR 1.4, 95%-CI 1.1-1.7, p=0.005), pulmonary hypertension (OR 1.3, 95%-CI 1.1-1.6, p=0.004) and NYHA functional class IV (OR 1.4, 95%-CI 1.1-1.6, p=0.02) at the time of first presentation were found to be predictors of persistent high-grade MR during FU in multivariable logistic regression. Conclusion Patients with de novo high-grade MR and AF presenting with concomitant first degree AV block, NYHA functional class IV or pulmonary hypertension are more likely to have persistent high-grade MR after early rhythm control of AF regardless of sinus rhythm stability during FU. In this constellation, early definitive therapy for MR should be prioritized. Larger, prospective studies are needed to confirm the results and to investigate the impact of early interventional rhythm control strategies on MR reversibility.

54 Sleep and Circadian Rhythms in Premanifest Huntington’s disease: Relationship with Cognition

Objective:Huntington’s disease (HD) is a neurodegenerative disease characterised by motor, psychiatric and cognitive decline. Currently, no treatments have been identified in HD for slowing down cognitive decline or improving cognitive function. We are interested in identifying potentially modifiable factors in HD that can be targeted to improve or maintain cognitive function. Sleep and circadian disruption stand out as possible modifiable targets because sleep and circadian symptoms are common in HD, and such disruptions are known to impact cognition in the general population. Despite some emerging evidence that sleep quality correlates with cognition in manifest HD, whether these same relationships exist in the premanifest period is unknown. Further, whether circadian rhythms relate to cognition in premanifest HD remains open. Therefore, we aimed to determine whether sleep and circadian parameters relate to cognitive performance in premanifest HD.Participants and Methods:To date, we have recruited 27 premanifest HD participants to a two-week remote sleep study. During the study, participants wore an Actiwatch-2 and completed a sleep diary for 14 consecutive days to assess their sleep and rest-activity patterns. Participants also completed online sleep and mood questionnaires and a cognitive assessment using videoconference. We calculated Pearson correlations to examine whether cognitive performance relates to subjective sleep quality, objective sleep parameters and circadian rest-activity rhythms. Thus far, we have analysed data from 15 female participants with premanifest HD (Mage = 43.20, SD = 11.58).Results:Preliminary results indicate that measures of subjective sleep quality, insomnia severity, daytime sleepiness, and fatigue severity in premanifest HD do not correlate with cognitive performance. Increases in objectively measured sleep efficiency, however, strongly correlated with better performance on the Hopkins-Verbal Learning Test-Revised (HVLT-R) immediate (r = 0.562, p &lt; 0.05) and delayed recall trials (r = 0.597, p &lt; 0.05) and the Trail Making Test Part B (TMT-B; r = 0.550, p &lt; 0.05). More time spent awake (i.e., wake after sleep onset) was strongly linked to reduced performance on the TMT-B (r = -0.542, p &lt; 0.05) and Symbol Digit Modalities Test (r = -0.556, p &lt; 0.05). Further, increases in total sleep time were associated with better performance on the HVLT-R immediate (r = 0.682, p &lt; 0.05) and delayed recall trial (r = 0.616, p &lt; 0.05). For our circadian parameters, less fragmented day-today rest-activity rhythms (i.e., higher intra-daily variability) strongly correlated with higher scores on the HVLT-R immediate (r = 0.768, p &lt; 0.001) delayed recall trials (r = 0.7276, p &lt; 0.05) and TMT-B (r = 0.516, p &lt; 0.05), whereas consistent and stable day-to-day rest-activity rhythms (i.e., higher inter-daily stability) was associated with poorer performance on ERT (r = -0.587, p &lt; 0.05).Conclusions:Preliminary results suggest that fragmented sleep, sleep inefficiency, reduced total sleep time, rest-activity rhythm stability and fragmentation relate to poorer cognitive performance in people with premanifest HD. Should analysis of our whole sample confirm these preliminary findings, targeting sleep in HD (e.g., through sleep hygiene and/or psychoeducation) may be a useful strategy to improve or maintain cognition.

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

Chronotype-Dependent Sleep Loss Is Associated with a Lower Amplitude in Circadian Rhythm and a Higher Fragmentation of REM Sleep in Young Healthy Adults.

In modern society, the time and duration of sleep on workdays are primarily determined by external factors, e.g., the alarm clock. This can lead to a misalignment of the intrinsically determined sleep timing, which is dependent on the individual chronotype, resulting in reduced sleep quality. Although this is highly relevant given the high incidence of sleep disorders, little is known about the effect of this misalignment on sleep architecture. Using Fitbit trackers and questionnaire surveys, our study aims to elucidate sleep timing, sleep architecture, and subjective sleep quality in young healthy adults (n = 59) under real-life conditions (average of 82.4 ± 9.7 days). Correlations between variables were calculated to identify the direction of relationships. On workdays, the midpoint of sleep was earlier, the sleep duration was shorter, and tiredness upon waking was higher than on free days. A higher discrepancy between sleep duration on workdays and free days was associated with a lower stability of the circadian rhythm of REM sleep and also with a higher fragmentation of REM sleep. Similarly, a higher tiredness upon waking on free days, thus under intrinsically determined sleep timing conditions, was associated with a lower proportion and a higher fragmentation of REM sleep. This suggests that the misalignment between extrinsically and intrinsically determined sleep timing affects the architecture of sleep stages, particularly REM sleep, which is closely connected to sleep quality.

Abstract P1125: Development Of A Multicellular Sinoatrial Node Organoid For Modeling Robust Pacemaking And Conduction

The prevalence and healthcare burden of sinoatrial (SA) node dysfunction have been continuously increasing due to the growth in the elderly population, emphasizing the need for more detailed studies of SA node functions to enable effective therapy for treating and preventing SA node dysfunction. However, current SA node or pacemaker models are limited to isolated single cell-type cells or cell clusters, leaving a gap in the ability to model autonomous cardiac contraction. In contrast, the SA node is a natural organoid with elaborate insulated architecture and heterogeneous cellular composition. Furthermore, current single cell-type pacemakers have worsened heart rhythm stability during one-month in vivo integration, limiting their application as clinically viable biological pacemakers that can generate robust pacemaking and conduction. To address the current limitations of SA node models, we developed a three-dimensional multicellular SA node organoid by reproducing the human SA node's multicellular tissue structure and fail-safe mechanisms. First, inspired by the SA node's partial electrical insulation, we structurally isolated a group of cardiomyocytes with a single exit pathway that allowed for electrical connection to neighboring cardiomyocytes. We found that the geometrically isolated cardiomyocytes successfully activated neighboring quiescent cardiomyocytes without any pacemaker-related gene expression, and they maintained the rhythm for three months. Second, the overexpression of HCN4, a key pacemaker channel, in these isolated cardiomyocytes further improved heart rhythm variability down to the millisecond level, suggesting the interplay between pacemaker gene expression and nodal architecture for long-term, high-fidelity pacing. Finally, we successfully fabricated and integrated the SA node organoid into our 3D pacemaker organoid-myocardium platform, and the integrated organoid dominated rhythm control in 3D cardiac muscle constructs for 30 days. These studies will help define if tissue-level architecture and multicellular compositions mediate SA node's robust pacemaking and conduction and may reveal a high-fidelity tissue-level biological pacemaker as a novel therapeutic strategy for SA node dysfunctions.

Effects of blue-enriched white light with same correlated colour temperature on visual fatigue

Visual fatigue has become a public health issue, while the relevant retinal mechanism and characteristics of blue light that induce visual fatigue have been rarely studied. In the retina, both short wavelength-sensitive (S) cones and melanopsin-containing intrinsically photoreceptive retinal ganglion cells (ipRGCs) are sensitive to blue light, and their responses are opposite in pupil mediation. Thus, effects of blue-enriched white light with different S-cone-opic Equivalent Daylight Illuminance (EDI) on visual fatigue was investigated, maintaining the same melanopic EDI to avoid interferences of melanopsin-containing ipRGCs. Two white illuminants (one with low S-cone-opic EDI, the other with high S-cone-opic EDI) were characterized based on α-opic EDI with the same correlated colour temperature and illuminance. Melanopic EDI was lower than S-cone-opic EDI of these two illuminants. Psychological, visual, physiological and cognitive performances were measured to investigate visual fatigue. Results showed that blue-enriched white light with high S-cone-opic EDI can induce visual fatigue. Participants felt more discomfort in their eyes under high S-cone-opic EDI along with the decline of tear film stability and changes of heart rhythm. Furthermore, the reaction time in a memory task increased significantly under high S-cone-opic EDI. The findings provide new insights into the optimization of indoor lighting environments for human health.