ABSTRACT: Fluctuations of the human heart beat constitute a complex system that has been studied mostly under resting conditions using conventional time series analysis methods. During physical exercise, the variability of the fluctuations is reduced, and the time series of beat-to-beat RR intervals (RRIs) become highly non-stationary. Here we develop a dynamical approach to analyze the time evolution of RRI correlations in running across various training and racing events under real-world conditions. In particular, we introduce dynamical detrended fluctuation analysis and dynamical partial autocorrelation functions, which are able to detect real-time changes in the scaling and correlations of the RRIs as functions of the scale and the lag. We relate these changes to the exercise intensity quantified by the heart rate (HR). Beyond subject-specific HR thresholds the RRIs show multiscale anticorrelations with both universal and individual scale-dependent structure that is potentially affected by the stride frequency. These preliminary results are encouraging for future applications of the dynamical statistical analysis in exercise physiology and cardiology, and the presented methodology is also applicable across various disciplines.
Project description:In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained-handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05).Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05).The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod.German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do.
Project description:<h4>Background</h4>Trailrunning is becoming very popular. However, the risk and burden of running-related injuries (RRI) in trailrunning is not well established.<h4>Objective</h4>To investigate the prevalence, injury rate, severity, nature, and economic burden of RRIs in Dutch trailrunners.<h4>Methods</h4>This prospective cohort study included 228 trailrunners aged 18 years or over (range 23-67), and was conducted between October 2013 and December 2014. After completing the baseline questionnaire, the Oslo Sports Trauma Research Center Questionnaire on Health Problems was administered every 2 weeks to collect data on RRIs. Participants who reported RRIs were asked about healthcare utilization (direct costs) and absenteeism from paid work (indirect costs). RRI was defined as disorders of the musculoskeletal system or concussions experienced or sustained during participation in running.<h4>Results</h4>The mean prevalence of RRIs measured over time was 22.4 % [95 % confidence interval (CI) 20.9-24.0], and the injury rate was 10.7 RRIs per 1000 h of running (95 % CI 9.4-12.1). The prevalence was higher for overuse (17.7 %; 95 % CI 15.9-19.5) than for acute (4.1 %; 95 % CI 3.3-5.0) RRIs. Also, the injury rate was higher for overuse (8.1; 95 % CI 6.9-9.3) than for acute (2.7; 95 % CI 2.0-3.4) RRIs. The median of the severity score was 35.0 [25-75 %, interquartile range (IQR) 22.0-55.7], and the median of the duration of RRIs was 2.0 weeks (IQR 2.0-6.0) during the study. The total economic burden of RRIs was estimated at €172.22 (95 % CI 117.10-271.74) per RRI, and €1849.49 (95 % CI 1180.62-3058.91) per 1000 h of running. An RRI was estimated to have a direct cost of €60.92 (95 % CI 45.11-94.90) and an indirect cost of €111.30 (95 % CI 61.02-192.75).<h4>Conclusions</h4>The health and economic burden of RRIs presented in this study are significant for trailrunners and for society. Therefore, efforts should be made in order to prevent RRIs in trailrunners.
Project description:We present RISE (http://rise.zhanglab.net), a database of RNA Interactome from Sequencing Experiments. RNA-RNA interactions (RRIs) are essential for RNA regulation and function. RISE provides a comprehensive collection of RRIs that mainly come from recent transcriptome-wide sequencing-based experiments like PARIS, SPLASH, LIGR-seq, and MARIO, as well as targeted studies like RIA-seq, RAP-RNA and CLASH. It also includes interactions aggregated from other primary databases and publications. The RISE database currently contains 328,811 RNA-RNA interactions mainly in human, mouse and yeast. While most existing RNA databases mainly contain interactions of miRNA targeting, notably, more than half of the RRIs in RISE are among mRNA and long non-coding RNAs. We compared different RRI datasets in RISE and found limited overlaps in interactions resolved by different techniques and in different cell lines. It may suggest technology preference and also dynamic natures of RRIs. We also analyzed the basic features of the human and mouse RRI networks and found that they tend to be scale-free, small-world, hierarchical and modular. The analysis may nominate important RNAs or RRIs for further investigation. Finally, RISE provides a Circos plot and several table views for integrative visualization, with extensive molecular and functional annotations to facilitate exploration of biological functions for any RRI of interest.
Project description:The origin of slow intrinsic oscillations in resting states of functional magnetic resonance imaging (fMRI) signals is still a matter of debate. The present study aims to test the hypothesis that slow blood oxygenation level-dependent (BOLD) oscillations with frequency components greater than 0.10 Hz result from a central neural pacemaker located in the brain stem. We predict that a central oscillator modulates cardiac beat-to-beat interval (RRI) fluctuations rapidly, with only a short neural lag around 0.3 s. Spontaneous BOLD fluctuations in the brain stem, however, are considerably delayed due to the hemodynamic response time of about ?2-3 s. In order to test these predictions, we analyzed the time delay between slow RRI oscillations from thorax and BOLD oscillations in the brain stem by calculating the phase locking value (PLV). Our findings show a significant time delay of 2.2 ± 0.2 s between RRI and BOLD signals in 12 out of 23 (50%) participants in axial slices of the pons/brain stem. Adding the neural lag of 0.3 s to the observed lag of 2.2 s we obtain 2.5 s, which is the time between neural activity increase and BOLD increase, termed neuro-BOLD coupling. Note, this time window for neuro-BOLD coupling in awake humans is surprisingly of similar size as in awake head-fixed adult mice (Mateo et al., 2017).
Project description:RATIONALE:Sleep-disordered breathing (SDB) is strongly linked to adverse cardiovascular outcomes (cardiovascular diseases (CVD)). Whether heart rate changes measured by nocturnal R-R interval (RRI) dips (RRI dip index (RRDI)) adversely affect the CVD outcomes is unknown. OBJECTIVES:To test whether nocturnal RRDI predicts CVD incidence and mortality in the Wisconsin Sleep Cohort study (WSCS), independent of the known effects of SDB on beat-to-beat variability. METHODS:The study analysed electrocardiograph obtained from polysomnography study to assess the nocturnal total RRDI (the number of RRI dips divided by the total recording time) and sleep RRDI (the number of RRI dips divided by total sleep time). A composite CVD risk as a function of total and sleep RRDI was estimated by Cox proportional hazards in the WSCS. RESULTS:The study sample consisted of 569 participants from the WSCS with no prior CVD at baseline were followed up for up to 15 years. Nocturnal total RRDI (10-unit change) was associated with composite CVD event(s) (HR, 1.24 per 10-unit increment in RRDI (95% CI 1.10 to 1.39), p<0.001). After adjusting for demographic factors (age 58±8 years old; 53% male; and body mass index 31±7 kg/m2), and apnoea-hypopnoea index (AHI 4%), individuals with highest total nocturnal RRDI category (≥28 vs<15 dips/hour) had a significant HR for increased incidence of CVD and mortality of 7.4(95% CI 1.97 to 27.7), p=0.003). Sleep RRDI was significantly associated with new-onset CVD event(s) (HR, 1.21 per 10-unit increment in RRDI (95% CI 1.09 to 1.35), p<0.001) which remained significant after adjusting for demographic factors, AHI 4%, hypoxemia and other comorbidities. CONCLUSION:Increased nocturnal RRDI predicts cardiovascular mortality and morbidity, independent of the known effects of SDB on beat-to-beat variability. The frequency of RRDI is higher in men than in women, and is significantly associated with new-onset CVD event(s) in men but not in women.
Project description:BACKGROUND: Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. METHODS/DESIGN: The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event.During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. DISCUSSION: The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners. TRIAL REGISTRATION: The Netherlands National Trial Register NTR1906. The NTR is part of the WHO Primary Registries.
Project description:Objective: To test whether women with metabolic syndrome (MS) have impairments in the on- and off-transients during an incremental test and to study whether any of the MS components are independently associated with the observed responses. Research Design and Methods: Thirty-six women aged 35-55 years were divided into a group with MS (MSG, n = 19) and a control group (CG, n = 17). R-R intervals (RRi) and heart rate variability (HRV) were calculated on a beat-to-beat basis and the heart rate (HR) at the on- and off-transient were analyzed during an incremental cardiopulmonary exercise test (CPET). Results: MSG showed lower aerobic capacity and lower parasympathetic cardiac modulation at rest compared with CG. HR values in on-transient phase were significantly lower in MSG compared with CG. The exponential amplitudes "amp" and the parameters "τ" [speed of heart rate recovery (HRR)] were lower in MSG. MSG exhibited higher HR values in comparison to CG during the off-transient indicating a slower HRR. In MSG, there was an inverse and significant correlation between fasting plasma vs. ΔF and glucose vs. exponential "τ" of HRR dynamics. Conclusion: MS is associated with poor heart rate kinetics. The altered HR kinetics seems to be related to alterations in cardiac parasympathetic modulation, and glucose metabolism seems to be the major determinant.
Project description:The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1-58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.
Project description:This family study from Oman (n?=?1231) explored the heritability and genetic and environmental correlations of heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS) with ambulatory and beat-to-beat blood pressure (BP). Ambulatory BP was measured for 24?hours to calculate mean values for daytime and sleep separately. Time and frequency domain HRV indices, BRS, office beat-to-beat BP, and heart rate (HR) were measured for 10?minutes at rest. SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age2, sex, their interactions and BMI. Heritability of SBP and DBP ranged from 16.8% to 40.4% for daytime, sleeping, 24-hour and office beat-to-beat measurements. HR and BRS showed a heritability of 31.9% and 20.6%, respectively, and for HRV indices heritability ranged from 11.1% to 20.5%. All HRV measurements and BRS were found to be negatively correlated with BP, but phenotypic correlation coefficients were relatively weak; HR was positively correlated with BP. None of the genetic correlations were statistically significant while environmental factors explained most of the correlations for all HRV indices with BP. Our study found consistent but weak correlations among HRV, HR, BRS and ambulatory/office beat-to-beat BP. However, environmental rather than genetic factors contributed most to those correlations.
Project description:Low-frequency oscillations with a dominant frequency at 0.1 Hz are one of the most influential intrinsic blood-oxygen-level-dependent (BOLD) signals. This raises the question if vascular BOLD oscillations (originating from blood flow in the brain) and intrinsic slow neural activity fluctuations (neural BOLD oscillations) can be differentiated. In this study, we report on two different approaches: first, on computing the phase-locking value in the frequency band 0.07-0.13 Hz between heart beat-to-beat interval (RRI) and BOLD oscillations and second, between multiple BOLD oscillations (functional connectivity) in four resting states in 23 scanner-naïve, anxious healthy subjects. The first method revealed that vascular 0.1-Hz BOLD oscillations preceded those in RRI signals by 1.7 ± 0.6 s and neural BOLD oscillations lagged RRI oscillations by 0.8 ± 0.5 s. Together, vascular BOLD oscillations preceded neural BOLD oscillations by ~90° or ~2.5 s. To verify this discrimination, connectivity patterns of neural and vascular 0.1-Hz BOLD oscillations were compared in 26 regions involved in processing of emotions. Neural BOLD oscillations revealed significant phase-coupling between amygdala and medial frontal cortex, while vascular BOLD oscillations showed highly significant phase-coupling between amygdala and multiple regions in the supply areas of the anterior and medial cerebral arteries. This suggests that not only slow neural and vascular BOLD oscillations can be dissociated but also that two strategies may exist to optimize regulation of anxiety, that is increased functional connectivity between amygdala and medial frontal cortex, and increased cerebral blood flow in amygdala and related structures.