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Background: The objective of this pilot study was to identify frequencydependent effects of respiratory-gated auricular vagus afferent nerve stimulation (RAVANS) on the regulation of blood pressure and heart rate variability in hypertensive subjects and examine potential differential effects by sex/gender or race. Methods: Twenty hypertensive subjects (54.55 ± 6.23 years of age; 12 females and 8 males) were included in a within-person experimental design and underwent five stimulation sessions where they received RAVANS at different frequencies (i.e., 2 Hz, 10 Hz, 25 Hz, 100 Hz, or sham stimulation) in a randomized order. EKG and continuous blood pressure signals were collected during a 10-min baseline, 30-min stimulation, and 10-min poststimulation periods. Generalized estimating equations (GEE) adjusted for baseline measures were used to evaluate frequency-dependent effects of RAVANS on heart rate, high frequency power, and blood pressure measures, including analyses stratified by sex and race. Results: Administration of RAVANS at 100 Hz had significant overall effects on the reduction of heart rate (b = 􀀀2.03, p = 0.002). It was also associated with a significant reduction of diastolic (b = 􀀀1.90, p = 0.01) and mean arterial blood pressure (b = 􀀀2.23, p = 0.002) in Black hypertensive participants and heart rate in female subjects (b = 􀀀2.83, p = 0.01) during the post-stimulation period when compared to sham. Conclusion: Respiratory-gated auricular vagus afferent nerve stimulation exhibits frequency-dependent rapid effects on the modulation of heart rate and blood pressure in hypertensive patients that may further differ by race and sex. Our findings highlight the need for the development of optimized stimulation protocols that achieve the greatest effects on the modulation of physiological and clinical outcomes in this population. [ABSTRACT FROM AUTHOR]

Objective Respiratory-gated Auricular Vagal Afferent Nerve stimulation (RAVANS) is a safe nonpharmacological approach to managing chronic pain. The purpose of the current study was to examine (1) the feasibility and acceptability of RAVANS, combined with mindful meditation (MM) for chronic low back pain (CLBP), (2) the potential synergy of MM+RAVANS on improving pain, and (3) possible moderators of the influence of MM+RAVANS on pain. Design Pilot feasibility and acceptability study. Setting Pain management center at large academic medical center. Subjects Nineteen adults with CLBP and previous MM training. Methods Participants attended two sessions during which they completed quantitative sensory testing (QST), rated pain severity, and completed a MM+stimulation session. Participants received RAVANS during one visit and sham stimulation during the other, randomized in order. Following intervention, participants repeated QST. Results MM+RAVANS was well tolerated, acceptable, and feasible to provide relief for CLBP. Both MM+stimulation sessions resulted in improved back pain severity, punctate pain ratings, and pressure pain threshold. Individuals with greater negative affect showed greater back pain improvement from MM+RAVANS while those with greater mindfulness showed greater back pain improvement from MM+sham. Conclusions Results suggest that for CLBP patients with prior MM training, the analgesic effects of MM may have overshadowed effects of RAVANS given the brief single session MM+RAVANS intervention. However, those with greater negative affect may benefit from combined MM+RAVANS. [ABSTRACT FROM AUTHOR]

Major depressive disorder has been associated with a significant risk for the development and progression of cardiovascular disease. The impact of depression on cardiovascular morbidity and mortality is sex-dependent, with women having a greater risk for this comorbidity and poorer clinical outcomes. Although management of depressive symptomatology has been associated with a better prognosis in patients with comorbid depression and cardiovascular disease, a significant proportion remained undertreated, are refractory to antidepressant medications, or present cardiovascular side effects and drug interactions. The development and validation of novel, nonpharmacological interventions targeting the comorbidity of depression and cardiovascular disease in a sex-dependent manner may have a significant impact on the improvement of depressive symptomatology and cardiovascular outcomes with a better safety profile and broader applicability. The aim of this review is to evaluate existing nonpharmacologic therapeutics used for the management of this comorbidity and to review emerging interventions with potential sex-dependent effects on this population. [Psychiatr Ann. 2022;52(1):14–19.] [ABSTRACT FROM AUTHOR]

Background: Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases, such as cardiovascular disease (CVD), metabolic syndrome, and breast and colon cancers, and shortens life expectancy. We aimed to determine the effects of moderate (MCT)- versus high-intensity interval training (HIT) on vascular function parameters in physically inactive adults. We hypothesized that individualized HIT prescription would improve the vascular function parameters more than the MCT in a greater proportion of individuals. Methods: Twenty-one inactive adults were randomly allocated to receive either MCT group (60–75% of their heart rate reserve, [HRR] or HIT group (4 min at 85–95% of peak HRR), 3 days a week for 12 weeks. Vascular function (brachial artery flow-mediated dilation, FMD [%], normalized brachial artery flow-mediated dilation, FMDn [%], aortic pulse wave velocity, PWV [m·s− 1], AIx, augmentation index: aortic and brachial [%]), were measured at baseline and over 12 weeks of training. In order for a participant to be considered a responder to improvements in vascular function parameters (FMDn and PWV), the typical error was calculated in a favorable direction. Results: FMD changed by − 1.0% (SE 2.1, d = 0.388) in the MCT group, and + 1.8% (SE 1.8, d = 0.699) in the HIT group (no significant difference between groups: 2.9% [95% CI, − 3.0 to 8.8]. PWV changed by + 0.1 m·s− 1 (SE 0.2, d = 0.087) in the MCT group but decreased by − 0.4 m·s− 1 in the HIT group (SE 0.2, d = 0.497), with significant difference between groups: − 0.4 [95% CI, − 0.2 to − 0.7]. There was not a significant difference in the prevalence of no-responder for FMD (%) between the MCT and HIT groups (66% versus 36%, P = 0.157). Regarding PWV (m·s− 1), an analysis showed that the prevalence of no-responder was 77% (7 cases) in the MCT group and 45% (5 cases) in the HIT group (P = 0.114). Conclusions: Under the conditions of the present study, both groups experienced changed in vascular function parameters. Compared to MCT group, HIT is more efficacious for improving FMD and decreasing PWV, in physically inactive adults. Trial registration: ClinicalTrials.gov NCT02738385 registered on 23 March 2016. [ABSTRACT FROM AUTHOR]

Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain. [ABSTRACT FROM AUTHOR]

Objective Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have demonstrated altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system and its role in both somatic and nonsomatic FM symptoms. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity and to explore how sustained, evoked deep tissue pain modulates this connectivity. Methods We acquired functional magnetic resonance imaging and electrocardiography data on FM patients and healthy controls during rest (the rest phase) and during sustained mechanical pressure-induced pain over the lower leg (the pain phase). Functional connectivity associated with different S1 subregions was calculated, while S1leg connectivity (representation of the leg in the primary somatosensory cortex) was contrasted between the rest phase and the pain phase and was correlated with clinically relevant measures in FM. Results During the rest phase, FM patients showed decreased connectivity between multiple ipsilateral and cross-hemispheric S1 subregions, which was correlated with clinical pain severity. Compared to the rest phase, the pain phase produced increased S1leg connectivity to the bilateral anterior insula in FM patients, but not in healthy controls. Moreover, in FM patients, sustained pain-altered S1leg connectivity to the anterior insula was correlated with clinical/behavioral pain measures and autonomic responses. Conclusion Our study demonstrates that both somatic and nonsomatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are closely linked with the degree to which evoked deep tissue pain alters S1 connectivity to salience/affective pain-processing regions. Additionally, diminished connectivity between S1 subregions during the rest phase in FM may result from ongoing widespread clinical pain. [ABSTRACT FROM AUTHOR]

Nonlinear digital signal processing methods that address system complexity have provided useful computational tools for helping in the diagnosis and treatment of a wide range of pathologies. More specifically, nonlinear measures have been successful in characterizing patients with mental disorders such as Major Depression (MD). In this study, we propose the use of instantaneous measures of entropy, namely the inhomogeneous point-process approximate entropy (ipApEn) and the inhomogeneous point-process sample entropy (ipSampEn), to describe a novel characterization of MD patients undergoing affective elicitation. Because these measures are built within a nonlinear point-process model, they allow for the assessment of complexity in cardiovascular dynamics at each moment in time. Heartbeat dynamics were characterized from 48 healthy controls and 48 patients with MD while emotionally elicited through either neutral or arousing audiovisual stimuli. Experimental results coming from the arousing tasks show that ipApEn measures are able to instantaneously track heartbeat complexity as well as discern between healthy subjects and MD patients. Conversely, standard heart rate variability (HRV) analysis performed in both time and frequency domains did not show any statistical significance. We conclude that measures of entropy based on nonlinear point-process models might contribute to devising useful computational tools for care in mental health. [ABSTRACT FROM AUTHOR]

BACKGROUND The link between inflammation, obesity, and cardiovascular disease (CVD) has been described in adult populations but few data are available with respect to children. The aim of this study was to describe the inter-relationships between adiposity, C-reactive protein (CRP) plasma concentrations, and blood pressure levels in a Hispanic pediatric population. METHODS We included 325 schoolchildren (mean age, 10.0 years) selected from the school population of Bucaramanga, Colombia. Blood pressure, lipid profile, glucose, and CRP plasma concentration were measured using standard procedures. Body mass index (BMI) was used for evaluating the children's nutritional condition. Correlation coefficients were calculated for all the variables using Spearman's test. RESULTS As expected, a positive correlation was found between BMI and systolic blood pressure (SBP) in both genders, and between CRP and SBP levels in boys. After a multivariate regression analysis, the association between adiposity and blood pressure remained significant, whereas the CRP concentrations were no longer associated with SBP. CONCLUSIONS The results obtained in our study of Hispanic school-age children show that adiposity is correlated with CRP concentrations and SBP values as has been earlier described in Caucasian populations. However, we failed to find a significant relationship between low-grade inflammation and SBP levels. Further studies are needed in order to explore alternative pathophysiological mechanisms linking obesity and high blood pressure in children and to define the impact of these associations on the cardiovascular risk of our pediatric population. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to determine whether the beneficial effect of oral supplementation with calcium and conjugated linoleic acid (CLA) in the reduction of the incidence of pregnancy-induced hypertension (PIH) is related with changes in plasma levels of prostanoids, renin, angiotensin II, calciotropic hormones, and plasma and intracellular ionized free calcium. Methods: These mediators were determined using the blood samples obtained from a randomized, double-blind, placebo-controlled trial that included 48 healthy primigravidas with a family history of preeclampsia and with diastolic notch, recruited from four outpatient clinics from two developing countries. Participants were randomized to daily oral doses of elemental calcium and CLA or lactose-starch placebo from week 18 to week 22 of gestation until delivery. Results: The incidence of PIH was significantly reduced in women receiving the supplement (2 women [8.3%]) compared with placebo (10 women [41.7%]) (relative risk = 0.20, 95% confidence interval 0.05–0.82, P = .01). There were no significant differences in the plasma concentrations of ionized calcium, prostaglandin E2, renin, angiotensin II, parathormone,and calcitonine. The concentration of intracellular ionized free calcium presented a significant reduction after interventions (92.0 nmol/L [range 62.5 to 220 nmol/L] v 62.5 nmol/L [range 28 to 200 nmol/L; P = .01) in the supplemented group but not in the placebo group. The women who developed PIH (n = 12) presented a significant increase in the concentrations of intracellular calcium after interventions (120 nmol/L [range 89.2 to 240 nmol/L] v 137.5 nmol/L [range 89.2 to 138 nmol/L; P = .02). Conclusions: Calcium and CLA supplementation during pregnancy reduces the incidence of PIH, and decreases the intracellular concentration of ionized free calcium in peripheral blood lymphocytes. [Copyright &y& Elsevier]

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson's Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity. [ABSTRACT FROM AUTHOR]