The constrained disorder principle defines the existence and function of living organisms. The principle specifies that biological systems comprise a disorder within constrained random boundaries. Per this principle, living organisms are machines with a degree of error that do not strive to optimize. Their differentiator from non-living organisms is their intrinsic disorder within personalized dynamic random boundaries. The constrained disorder is mandatory for the systems\' existence and proper operation. It provides living organisms the flexibility and adaptability required for operating under continuously changing internal and external milieus. The constrained disorder principle defines health and disease states by specifying the degree of the disorder and the arbitrary boundaries of biological systems. Disturbed systems lose their disorder or operate out of the disorder boundaries leading to diseases. The principle provides a platform for applying the constrained disorder to correct systems disturbances and improve disease outcomes.

UNASSIGNED: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient\'s medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise.
UNASSIGNED: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO2) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland-Altman method was used to confirm similarity.
UNASSIGNED: VO2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO2: r = 0.647, HR: r = 0.534). The Bland-Altman plot revealed no bias between the mean values (e.g., 19 min; VO2: -0.22 mL/kg/min; HR: -0.07/min).
UNASSIGNED: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

UNASSIGNED: This study sought to determine the feasibility of collecting physiologic data in thoracic surgery residents and whether it would correlate with burnout and burnout with performance.
UNASSIGNED: This was a prospective study of thoracic surgery residents over a 5-month period. Participants were evaluated with a wearable biometric device (heart rate variability and sleep) and the Maslach Burnout Inventory. Resident performance was quantified using Accreditation Council for Graduate Medical Education Milestones (scale, 1-5) normalized to program-designated targets (3 for postgraduate year 6 or lower residents and 4 for postgraduate year 7 residents).
UNASSIGNED: The cohort consisted of 71% female participants (5/7) with 86% of residents having 1 or more children. High levels of emotional exhaustion (median, 30 [interquartile range, 20-36], where >26 is high) and high levels of depersonalization (median, 16 [interquartile range, 14-22], where >12 is high) were common, but personal accomplishment was also uniformly high (median, 43 [interquartile range, 41-46], where >38 is high). There was a significant correlation between heart rate variability and emotional exhaustion (r(12) = 0.65, P = .01) but not depersonalization (P = .28) or personal accomplishment (P = .24). Depersonalization and personal accomplishment did not correlate with resident performance (P = .12 and P = .75, respectively); however, increased emotional exhaustion showed a significant correlation with higher resident performance during periods when burnout was reported (r(6) = 0.76, P = .047).
UNASSIGNED: Dynamic measurement of resting heart rate variability may offer an objective measure of burnout in thoracic surgery residents. Thoracic surgery residents who report high levels of burnout in this cohort maintained the ability to meet program-designated milestones at or above the level expected of their postgraduate year.

UNASSIGNED: The previous metanalysis found that Mind-body intervention (MBI) improves neuropsychologic well-being and may increase brain-derived growth factor (BDNF). BDNF is a neurotrophic factor related to neuroplasticity.
UNASSIGNED: To evaluate the effect of the short intensive MBI compared to control-relaxation on Site on BDNF and examine if this change is related to mitochondria function or stress-related neurohormonal activity.
UNASSIGNED: Randomized, controlled, two-period cross-over trial conducted in a medical center in Thailand. Healthy-meditation naive Nurse and Occupational Therapy Students, 23 assigned randomly to MBI, and 24 relaxations at the site for 8 h during the weekend. The wash-out period was three months between the two periods. All volunteers took the blood test for BDNF, mitochondrial oxidative phosphorylation (OXPHOS), Cortisol, and Heart rate variability (HRV) measurement before and Visual Analogue Scale for Anxiety (VAS-A), forward and backward digit span after each period.
UNASSIGNED: A total of 40 participants finished the trials. The cross over trial analysis showed a significant treatment effect between MBI and Relaxation on-site for the mean VAS-A as 9.89 (95% CI 4.81 to 19.47; P = 0.001), serum BDNF as 1.24 (95% CI 0.16 to 2.32; P = 0.04), and OXPHOS complex-1 was decreased 0.41 (95% CI 0.03-0.29 p = 0.03). There were no significant differences for digit span, cortisol, and HRV.
UNASSIGNED: In healthy meditation naïve females, even a short period of MBI may increase serum BDNF and reduce anxiety more than relaxation on-site. The more reduction of OXPHOS complex-1 in the mindfulness group suggests oxidative stress may be a more sensitive indicator than stress-related neurohormonal activity.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund\'s SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.

Pre-eclampsia (PE) is a multisystem progressive disorder affecting 3-5% of pregnancies. PE independently increases the risk for premature cardiovascular disease (CVD) in mothers and their children long-term. The effectiveness of a family-centered lifestyle intervention to lower CVD risk in PE families has not previously been evaluated. In the current FINNCARE study, we prospectively compare CVD risk and CVD progression in PE families (mother, father and child) in a cross-sectional study setting 8-12 years from delivery with non-PE control families of comparable age. Furthermore, we evaluate the effectiveness and feasibility of an interactive web-based behavioral 12-month lifestyle intervention to reduce blood pressure and the CVD risk profile overall in a randomized controlled trial. In total, 300 PE families will be randomized 1:1 to a PE-intervention or a PE-control group, and the 100 non-PE control families similarly followed-up at 12 months. Primary outcome is 24-hour mean systolic BP change from baseline in mother and child. Study aims to provide information on CVD progression and CVD risk management in the family following PE.

BACKGROUND: Disruption in circadian rhythms is associated with cardiovascular disease and may play a role in socioeconomic differences in cardiovascular disease prevalence. However, it is unclear whether low SES is associated with a lower diurnal rhythm in autonomic activity markers. We investigated the association between SES and the amplitude of the daily fluctuation of heart rate.
METHODS: We included data of 450 participants of a HELIUS sub-study in Amsterdam, the Netherlands. Participants wore an Actiheart monitor (CamNtech), a chest-worn monitor which measures heart rate every 15 s for several days. Cosinor analysis was performed on the time series of heart rate within each participant. We analyzed the association between the cosinor parameters (amplitude, midline and peak time of the diurnal HR rhythm) and SES indicators (education, occupational class and a proxy of income) in multivariate linear regression models, adjusting for age, sex and ethnicity.
RESULTS: There was a clear diurnal rhythm in the average heart rates, with a peak between noon and 18:00 and a trough between 04:00 and 06:00. This rhythm was present for all categories of education, occupation and income proxy. The estimates for the cosinor parameters did not differ consistently and significantly between categories of education, occupation or income proxy.
CONCLUSIONS: We did not find any consistent evidence to support our hypothesis of a diminished amplitude in the diurnal variation of heart rate in individuals with lower SES. Future studies should explore SES differences in the diurnal variation in markers of autonomic activity other than heart rate.

The genesis of neuropathic pain is complex, as sensory abnormalities may differ between patients with different or similar etiologies, suggesting mechanistic heterogeneity, a concept that is largely unexplored. Yet, data are usually grouped for analysis based on the assumption that they share the same underlying pathogenesis. Sex is a factor that may contribute to differences in pain responses. Neuropathic pain is more prevalent in female patients, but pre-clinical studies that can examine pain development in a controlled environment have typically failed to include female subjects. This study explored patterns of development of hyperalgesia-like behavior (HLB) induced by noxious mechanical stimulation in a neuropathic pain model (spared nerve injury, SNI) in both male and female rats, and autonomic dysfunction that is associated with chronic pain. HLB was analyzed across time, using both discrete mixture modeling and rules-based longitudinal clustering. Both methods identified similar groupings of hyperalgesia trajectories after SNI that were not evident when data were combined into groups by sex only. Within the same hyperalgesia development group, mixed models showed that development of HLB in females was delayed relative to males and reached a magnitude similar to or higher than males. The data also indicate that sympathetic tone (as indicated by heart rate variability) drops below pre-SNI level before or at the onset of development of HLB. This study classifies heterogeneity in individual development of HLB and identifies sexual dimorphism in the time course of development of neuropathic pain after nerve injury. Future studies addressing mechanisms underlying these differences could facilitate appropriate pain treatments.

UNASSIGNED: In autonomic units, patients perform several short Valsalva maneuvers (VMs) while learning the procedure. The effects of repeated VMs on cardiovascular elicited responses were assessed.
UNASSIGNED: 14 healthy volunteer subjects were selected (aged 22-26). VMs were performed every 3 min up to 6 times in a reclined sitting position. Changes in blood pressure (BP), heart rate (HR) and baroreflex sensitivity indexes were evaluated. Subjects were classified according to their adrenergic response patterns.
UNASSIGNED: VMs repetitions evoked a progressive decrease in BP during phases II and III and a reduced increase in mean BP at late phase II. Increased bradycardia at early phase II and IV was also observed. Last two VMs showed a significant increase in Valsalva ratio, while other indexes remained unaltered. Subjects with balanced adrenergic responses presented extended pressure recovery time from the third repetition and lower BP values than those with augmented or suppressed adrenergic responses.
UNASSIGNED: Significant changes in BP and HR at certain phases were observed when consecutive VMs were performed in young subjects in a reclined position. The most affected baroreflex index was the Valsalva ratio. Adrenergic response patterns showed differences that should be considered in order to avoid false positives.
UNASSIGNED: We recommend not repeating the VM more than 4 times and revisiting the role and reliability of the Valsalva ratio.

There is an increasing recognition of the importance of interactions between the heart and the autonomic nervous system in the pathophysiology of arrhythmias. These interactions play a role in both the initiation and maintenance of arrhythmias and are important in both atrial and ventricular arrhythmia. Given the importance of the autonomic nervous system in the pathophysiology of arrhythmias, there has been notable effort in the field to improve existing therapies and pioneer additional interventions directed at cardiac-autonomic targets. The interventions are targeted to multiple and different anatomic targets across the neurocardiac axis. The purpose of this review is to provide an overview of the rationale for neuromodulation in the treatment of arrhythmias and to review the specific treatments under evaluation and development for the treatment of both atrial fibrillation and ventricular arrhythmias.