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Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states.

Aim Methods Results Conclusions This study assessed the effects of hand‐bathing on sympathetic nervous activity exacerbated by psychological stress. Participants immersed one hand in warm water for 2 min while exposed to noise, and changes in blood flow and skin temperature of the non‐immersed hand were observed.Twenty‐nine healthy university students aged 20 years or older were randomly assigned to either the hand‐bathing group (n = 14) or the control group (n = 15). After a brief rest in a quiet environment, participants were exposed to noise for 6 min. Those in the hand‐bathing group submerged their left hand in a 40°C thermostatic bath for 2 min, starting 2 min into the noise exposure. The tympanic temperature, blood flow, and skin temperature of the non‐immersed hand were continuously measured, along with blood pressure and subjective evaluations before and after the noise exposure.Both groups experienced a decrease in fingertip skin temperature at the start of the noise exposure, persisting longer in the control group. Conversely, the hand‐bathing group showed increased fingertip skin temperature after 150 s, significantly higher after the noise exposure than the control group (p = .04). Participants in the hand‐bathing group reported significantly increased overall body warmth, thermal comfort, and relaxation during hand‐bathing (p = .007, p = .01, p < .001).The 2‐min hand‐bathing intervention reversed the pronounced vasoconstrictive response induced by noise exposure and elicited heightened sensations of overall body warmth, thermal comfort, and relaxation. Hand‐bathing may mitigate heightened sympathetic nervous activity associated with psychological stress induced by noise exposure. [ABSTRACT FROM AUTHOR]

Background: Sympathetic nerve activity (SNA) plays a central role in the pathogenesis of several diseases such as sepsis and chronic kidney disease (CKD). Activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) has been implicated in SNA. The mechanisms responsible for the adverse prognosis observed in sepsis associated with CKD remain to be determined. Therefore, we aimed to clarify the impact of increased SNA resulting from microglial activation on hemodynamics and organ damage in sepsis associated with CKD. Methods and results: In protocol 1, male Sprague–Dawley rats underwent either nephrectomy (Nx) or sham surgery followed by cecal ligation and puncture (CLP) or sham surgery. After CLP, Nx-CLP rats exhibited decreased blood pressure, increased heart rate, elevated serum creatinine and bilirubin levels, and decreased platelet count compared to Nx-Sham rats. Heart rate variability analysis revealed an increased low to high frequency (LF/HF) ratio in Nx-CLP rats, indicating increased SNA. Nx-CLP rats also had higher creatinine and bilirubin levels and lower platelet counts than sham-CLP rats after CLP. In protocol 2, Nx-CLP rats were divided into two subgroups: one received minocycline, an inhibitor of microglial activation, while the other received artificial cerebrospinal fluid (CSF) intracerebroventricularly via an osmotic minipump. The minocycline-treated group (Nx-mino-CLP) showed attenuated hypotensive and increased heart rate responses compared to the CSF-treated group (Nx-CSF-CLP), and the LF/HF ratio was also decreased. Echocardiography showed larger left ventricular dimensions and inferior vena cava in the Nx-mino-CLP group. In addition, creatinine and bilirubin levels were lower and platelet counts were higher in the Nx-mino-CLP group compared to the Nx-CSF-CLP group. Conclusions: In septic rats with concomitant CKD, SNA was significantly enhanced and organ dysfunction was increased. It has been suggested that the mechanism of exacerbated organ dysfunction in these models may involve abnormal systemic hemodynamics, possibly triggered by activation of the central sympathetic nervous system through activation of microglia in the PVN. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) primarily arises in children who are <10 years of age, and originates from developing sympathetic nervous system, which results in tumors in adrenal glands and/or sympathetic ganglia. The diagnosis of NB involves a combination of laboratory and imaging tests, and biopsies. Small extracellular vesicles (sEVs) have gained attention as potential biomarkers for various types of tumors. Here, we performed proteomic analysis of serum sEVs and identified potential biomarkers for NB. Methods: Label-free proteomics of serum sEVs were performed in the discovery phase. A bulk RNA-seq dataset of NB tissues was used to analyze the association between genes encoding sEVs proteins and prognosis. Potential biomarkers were validated via multiple reaction monitoring (MRM) or western blot analysis in the validation phase. A public single-cell RNA-seq (scRNA-seq) dataset was integrated to analyze the tissue origin of sEVs harboring biomarkers. Results: A total of 104 differentially expressed proteins were identified in NB patients with label-free proteomics, and 26 potential biomarkers were validated with MRM analysis. Seven proteins BSG, HSP90AB1, SLC44A1, CHGA, ATP6V0A1, ITGAL and SELL showed the strong ability to distinguish NB patients from healthy controls and non-NB patients as well. Integrated analysis of scRNA-seq and sEVs proteomics revealed that these sEVs-derived biomarkers originated from different cell populations in tumor tissues. Conclusion: sEVs-based biomarkers may aid the molecular diagnosis of NB, representing an innovative strategy to improve NB detection and management. [ABSTRACT FROM AUTHOR]

• Metabolic syndrome or cardiovascular-kidney-metabolic (CKM) syndrome is a growing epidemic affecting more than one-fourth of the general population with increasing prevalence rates over the years. • Activation of the renin-angiotensin-aldosterone system, sympathetic nervous system, elevated leptin levels, mitochondrial dysfunction, oxidative stress, and pro-inflammatory cytokines are the major causes of renal dysfunction in patients with CKM syndrome. • Despite high rates of chronic kidney disease among patients with CKM syndrome, such patients are less likely to undergo kidney transplantation. • Post-transplant CKM syndrome is a complex pathological entity related to pre-transplant risk factors and patient status, immunosuppressive regimens, and infectious diseases. Such condition is associated with poor patient and allograft outcomes. Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Aim: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)‐neuregulin 4 (NRG4)‐ErbB4 axis, with somatotopic dependence. Materials and methods: We established a high‐fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c‐Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B‐NRG4‐ErbB4 axis was verified by peripheral specific antagonism of ErbB4. Results: ES at the forelimb and abdomen regions significantly up‐regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD‐induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. Conclusion: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4‐ErbB4 signaling pathway. [ABSTRACT FROM AUTHOR]

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk. [ABSTRACT FROM AUTHOR]

The mechanism of vasovagal syncope (VVS) is multifaceted and involves a delicate balance within the autonomic nervous system (ANS). This review delves into the complex interplay between the ANS and VVS, elucidating the pivotal role that autonomic imbalance plays in the pathophysiology of this condition. Through a comprehensive exploration of the sympathetic and parasympathetic branches of the ANS, this review provides insights into the mechanisms that underlie VVS. In addition, this article discusses established and emerging research on the management of VVS. [ABSTRACT FROM AUTHOR]

Decabrominated diphenyl ether (BDE‐209) is a typical persistent organic pollutant that can cross the placental barrier, increasing the exposure risk for offspring. Norepinephrine (NE) from nerve terminals and acetylcholine (Ach) can bind to specific receptors on immune cells, inhibit the immune function of the body then cause immunotoxicity. However, whether maternal exposure to BDE‐209 could lead to immunotoxicity in the offspring by acting on the sympathetic and parasympathetic nervous systems remains unclear. In view of this, the pregnancy and lactation rat BDE‐209 exposure model was established and the results demonstrated that pregnancy and lactation BDE‐209 exposure could induce immunotoxicity to female offspring via affecting immunopathology (hematological and biochemical parameters, organ indices, and spleen histopathological), decreasing humoral immunity (serum hemolysin, immunoglobulins, and cytokine productions), damaging cellular immunity (splenic lymphocytes and spleen cytokine productions), and restraining nonspecific immunity. Moreover, a dramatically significant correlation was observed between spleen nerve indices and immunity indices. Additionally, the mechanism revealed that maternal BDE‐209 exposure caused offspring immunotoxicity through (1) activating MHC/PKCθ/NF‐κB pathway; (2) promoting sympathetic nervous pathway, by upregulating the expression of β2AR protein, which in turn elevating cAMP, following activate PKA and phosphorylate CREB, ultimately leading to immunotoxicity;(3) activating parasympathetic nerve pathway by reducing the binding with Ach and α7nAchR, upregulating the expression of JAK2 and phosphorylating STAT3, induced immunotoxicity of female offspring. [ABSTRACT FROM AUTHOR]

Hypertension is a globally prevalent disease, but the pathogenesis remains largely unclear. AMP-activated protein kinase (AMPK) is a nutrition-sensitive signal of cellular energy metabolism, which has a certain influence on the development of hypertension. Previously, we found a down-regulation of the phosphorylated (p-) form of AMPK, and the up-regulation of the angiotensin II type 1 receptor (AT1-R) and that of p-ERK1/2 in the hypothalamic paraventricular nucleus (PVN) of hypertensive rats. However, the exact mechanism underlying the relationship between AMPK and AT1-R in the PVN during hypertension remains unclear. Thus, we hypothesized that AMPK modulates AT1-R through the ERK1/2-NF-κB pathway in the PVN, thereby inhibiting sympathetic nerve activity and improving hypertension. To examine this hypothesis, we employed a renovascular hypertensive animal model developed via two-kidney, one-clip (2K1C) and sham-operated (SHAM). Artificial cerebrospinal fluid (aCSF), used as vehicle, or 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR, an AMPK activator, 60 μg/day) was microinjected bilaterally in the PVN of these rats for 4 weeks. In 2K1C rats, there an increase in systolic blood pressure (SBP) and circulating norepinephrine (NE). Also, the hypertensive rats had lowered expression of p-AMPK and p-AMPK/AMPK, elevated expression of p-ERK1/2, p-ERK1/2/ERK1/2 and AT1-R, increased NF-κB p65 activity in the PVN compared with the levels of these biomarkers in SHAM rats. Four weeks of bilateral PVN injection of AMPK activator AICAR, attenuated the NE level and SBP, increased the expression of p-AMPK and p-AMPK/AMPK, lessened the NF-κB p65 activity, decreased the expression of p-ERK1/2, p-ERK1/2/ERK1/2 and AT1-R in the PVN of 2K1C rats. Data from this study imply that the activation of AMPK within the PVN suppressed AT1-R expression through inhibiting the ERK1/2-NF-κB pathway, decreased the activity of the sympathetic nervous system, improved hypertension. [ABSTRACT FROM AUTHOR]

Background: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. Methods: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. Results: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. Conclusion: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system controls bodily functions including vascular tone, cardiac rhythm, and the "fight-or-flight response". Sympathetic chain ganglia develop in parallel with preganglionic motor nerves extending from the neural tube, raising the question of whether axon targeting contributes to sympathetic chain formation. Using nerve-selective genetic ablations and lineage tracing in mouse, we reveal that motor nerve-associated Schwann cell precursors (SCPs) contribute sympathetic neurons and satellite glia after the initial seeding of sympathetic ganglia by neural crest. Motor nerve ablation causes mispositioning of SCP-derived sympathoblasts as well as sympathetic chain hypoplasia and fragmentation. Sympathetic neurons in motor-ablated embryos project precociously and abnormally towards dorsal root ganglia, eventually resulting in fusion of sympathetic and sensory ganglia. Cell interaction analysis identifies semaphorins as potential motor nerve-derived signaling molecules regulating sympathoblast positioning and outgrowth. Overall, central innervation functions both as infrastructure and regulatory niche to ensure the integrity of peripheral ganglia morphogenesis. How tissues interact to help each other grow is a major question for biologists. Here, the authors show that motor innervation controls positioning of sympathetic progenitor cells to ensure correct shaping of ganglia in the peripheral nervous system. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS), also known as the broken-heart syndrome, is a reversible condition typically observed in female patients presenting for acute coronary syndromes (ACS). Despite its increasing incidence, TTS often remains undiagnosed due to its overlap with ACS. The pathophysiology of TTS is complex and involves factors such as coronary vasospasm, microcirculatory dysfunction, increased catecholamine levels, and overactivity of the sympathetic nervous system. Diagnosing TTS requires a comprehensive approach, starting with clinical suspicion and progressing to both non-invasive and invasive multimodal tests guided by a specific diagnostic algorithm. Management of TTS should be personalized, considering potential complications, the presence or absence of coronary artery disease (CAD), diagnostic test results, and the patient's clinical course. The current data primarily derive from case series, retrospective analyses, prospective registries, and expert opinions. In recent years, there has been growing recognition of gender differences in the pathophysiology, presentation, and outcomes of TTS. This review provides an updated overview of gender disparities, highlighting the importance of tailored diagnostic and management strategies. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as an attractive option for patients with relapsed or refractory high-risk neuroblastoma (HRNB). Neuroblastoma (NB), a sympathetic nervous system cancer arising from an embryonic neural crest cell, is heterogeneous clinically, with outcomes ranging from an isolated abdominal mass that spontaneously regresses to a widely metastatic disease with cure rates of about 50% despite intensive multimodal treatment. Risk group stratification and stage-adapted therapy to achieve cure with minimal toxicities have accomplished major milestones. Targeted immunotherapeutic approaches including monoclonal antibodies, vaccines, adoptive cellular therapies, their combinations, and their integration into standard of care are attractive therapeutic options, although curative challenges and toxicity concerns remain. In this review, we provide an overview of immune approaches to NB and the tumor microenvironment (TME) within the clinical translational framework. We propose a novel T cell-based therapeutic approach that leverages the unique properties of tumor surface antigens such as ganglioside GD2, incorporating specific monoclonal antibodies and recent advancements in adoptive cell therapy. [ABSTRACT FROM AUTHOR]

Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia‐induced fatal cardiac arrhythmias. To test this hypothesis, adult, non‐diabetic Sprague–Dawley rats were subjected to hyperinsulinemic‐severe hypoglycemic clamps (3 h, 10–15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5‐fold increase in third‐degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third‐degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of central α2‐adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2‐adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg−1; maintenance infusion of 0.1–0.5 µg kg h−1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats−1, P = 0.003) most strongly for medium‐sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats−1; P < 0.001). Dexmedetomidine progressively de‐recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de‐recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats−1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ –0.09 ± 0.07 to Δ –0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium‐sized APs (normalized cluster 2: –6.0 ± 5 to –1.6 ± 2 % mmHg−1; P = 0.008). These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. Key points: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear.This microneurographic study investigated the impact of a dexmedetomidine infusion (α2‐adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns.Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre.Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre.These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho‐excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory–sympathetic coupling and sympathetic transduction to BP are important for short‐ and longer‐term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory‐coupled BP variability. Resting MSNA, respiration and beat‐to‐beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal‐averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11 mmHg, P = 0.046), greater Traube–Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1 mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. Key points: Respiratory–sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short‐ and longer‐term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete.We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D.Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase.T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory‐related BP excursions (Traube–Hering waves) and BP variability.Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population. [ABSTRACT FROM AUTHOR]

In modern animal husbandry, stress can be viewed as an automatic response triggered by exposure to adverse environmental conditions. This response can range from mild discomfort to severe consequences, including mortality. The poultry industry, which significantly contributes to human nutrition, is not exempt from this issue. Although genetic selection has been employed for several decades to enhance production output, it has also resulted in poor stress resilience. Stress is manifested through a series of physiological reactions, such as the identification of the stressful stimulus, activation of the sympathetic nervous system and the adrenal medulla, and subsequent hormonal cascades. While brief periods of stress can be tolerated, prolonged exposure can have more severe consequences. For instance, extreme fluctuations in environmental temperature can lead to the accumulation of reactive oxygen species, impairment of reproductive performance, and reduced immunity. In addition, excessive noise in poultry slaughterhouses has been linked to altered bird behaviour and decreased production efficiency. Mechanical vibrations have also been shown to negatively impact the meat quality of broilers during transport as well as the egg quality and hatchability in hatcheries. Lastly, egg production is heavily influenced by light intensity and regimens, and inadequate light management can result in deficiencies, including visual anomalies, skeletal deformities, and circulatory problems. Although there is a growing body of evidence demonstrating the impact of environmental stressors on poultry physiology, there is a disproportionate representation of stressors in research. Recent studies have been focused on chronic heat stress, reflecting the current interest of the scientific community in climate change. Therefore, this review aims to highlight the major abiotic stressors in poultry production and elucidate their underlying mechanisms, addressing the need for a more comprehensive understanding of stress in diverse environmental contexts. [ABSTRACT FROM AUTHOR]

In frail older adults (mean age 85 years old), a 3-month supplementation with a low dose (6 g/day) of medium-chain triglycerides (MCTs; C8:0 and C10:0) given at a meal increased muscle mass and function, relative to supplementation with long-chain triglycerides (LCTs), but it decreased fat mass. The reduction in fat mass was partly due to increased postprandial energy expenditure by stimulation of the sympathetic nervous system (SNS). However, the extracellular signals to ameliorate sarcopenia are unclear. The following three potential extracellular signals to increase muscle mass and function after MCT supplementation are discussed: (1) Activating SNS—the hypothesis for this is based on evidence that a beta2-adrenergic receptor agonist acutely (1–24 h) markedly upregulates isoforms of peroxisomal proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNAs, promotes mitochondrial biogenesis, and chronically (~1 month) induces muscle hypertrophy. (2) An increased concentration of plasma acyl-ghrelin stimulates growth hormone secretion. (3) A nitrogen-sparing effect of ketone bodies, which fuel skeletal muscle, may promote muscle protein synthesis and prevent muscle protein breakdown. This review will help guide clinical trials of using MCTs to treat primary (age-related) sarcopenia. [ABSTRACT FROM AUTHOR]

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS. The regulation of energy homeostasis by centrally-produced GLP-1 is not yet fully understood. Here, authors show that GLP-1 neuronal circuitry in the olfactory bulb reduces food intake and enhances insulin secretion in obese mice. The increase in insulin secretion is mediated by a GABA-dependent relay in the paraventricular hypothalamus and decreased sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

Introduction: The pupil light reflex (photomotor reflex) has a duration of 3.5 s and is a highly reproducible measurement. Conventionally, the autonomic nervous system (ANS) activity evaluated by this reflex does not consider the viscoelasticity of the iris muscles. This study aims to detect differences in reflex autonomic activity in a supine position with parameters derived from the Kelvin-Voigt viscoelastic model in two distinct groups of elite athletes. Method: Groups formed using a dendrogram analysis based on basal autonomic activity assessed with heart rate variability. Heart rate variability was measured, and the photomotor reflex was modeled. Results: The model showed a high degree of adjustment to the photomotor reflex (r2 = 0.99 ± 0.01). The impulse 3, an indicator of reflex sympathetic activity, revealed a significantly higher activity (1= 0.05) in the [sympa/para]+ group compared to the [sympa/para] group. This result was further supported by a greater relative total redilation amplitude (1 = 0.05) and a shorter duration of 75% redilation (= 0.01). Finally, the relative total redilation amplitude exhibited a significant correlation with the linear stiffness constant (= 0.001) and the maximum redilation speed with restoring force (1 = 0.001). Discussion: These results indicate that (i) the photomotor reflex can detect an alteration of the reflex autonomic activity specific to each of the two branches of the ANS (ii) the viscoelastic properties of the iris muscles play a significant role in the energy storage-restitution mechanisms during the photomotor reflex. This approach could allow athletes to benefit from reduced time spent in the analysis of ANS activity, potentially making it an almost daily and automated process. [ABSTRACT FROM AUTHOR]

Light is fundamental for biological life, with most mammals possessing light-sensing photoreceptors in various organs. Opsin3 is highly expressed in adipose tissue which has extensive communication with other organs, particularly with the brain through the sympathetic nervous system (SNS). Our study reveals a new light-triggered crosstalk between adipose tissue and the hypothalamus. Direct blue-light exposure to subcutaneous white fat improves high-fat diet-induced metabolic abnormalities in an Opsin3-dependent manner. Metabolomic analysis shows that blue light increases circulating levels of histidine, which activates histaminergic neurons in the hypothalamus and stimulates brown adipose tissue (BAT) via SNS. Blocking central actions of histidine and denervating peripheral BAT blunts the effects of blue light. Human white adipocytes respond to direct blue light stimulation in a cell-autonomous manner, highlighting the translational relevance of this pathway. Together, these data demonstrate a light-responsive metabolic circuit involving adipose-hypothalamus communication, offering a potential strategy to alleviate obesity-induced metabolic abnormalities. Light is essential for biological life. Here, the authors show blue light activates the photoreceptor Opsin3 in white fat, triggering a light-responsive metabolic circuit involving adipose-hypothalamus communication, which could potentially alleviate obesity-induced metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Obesity is a chronic and debilitating disorder that originates from alterations in energy-sensing brain circuits controlling body weight gain and food intake. The dysregulated syntheses and actions of lipid mediators in the hypothalamus induce weight gain and overfeeding, but the molecular and cellular underpinnings of these alterations remain elusive. In response to changes in the nutritional status, different lipid sensing pathways in the hypothalamus direct body energy needs in a Yin-Yang model. Endocannabinoids orchestrate the crosstalk between hypothalamic circuits and the sympathetic nervous system to promote food intake and energy accumulation during fasting, whereas bile acids act on the same top-down axis to reduce energy intake and possibly storage after the meal. In obesity, the bioavailability and downstream cellular actions of endocannabinoids and bile acids are altered in hypothalamic neurons involved in body weight and metabolic control. Thus, the onset and progression of this disease might result from an imbalance in hypothalamic sensing of multiple lipid signals, which are possibly integrated by common molecular nodes. In this viewpoint, we discuss a possible model that explains how bile acids and endocannabinoids may exert their effects on energy balance regulation via interconnected mechanisms at the level of the hypothalamic neuronal circuits. Therefore, we propose a new conceptual framework for understanding and treating central mechanisms of maladaptive lipid action in obesity. • Endocannabinoids and bile acids act as Yin-Yang regulators of the body energy needs. • Master lipid sensors in the brain could integrate the actions of multiple lipid signals. • Obesity might originate from dysregulation of master lipid sensors in the brain. [ABSTRACT FROM AUTHOR]

Short and insufficient sleep are prevalent and associated with cardiovascular disease, with the sympathetic nervous system as a suspected mediator. The purpose of the present study was to investigate the association between objective, actigraphy-based total sleep time (TST), sleep efficiency (SE), and cardiovascular and sympathetic regulation in healthy adults. We hypothesized that short TST and low SE would be associated with elevated resting blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA). Participants included 94 individuals [46 males, 48 females, age: 30 ± 15 yr, body mass index (BMI): 26 ± 4 kg/m2]. All participants underwent at least 7 days of at-home, wristwatch actigraphy monitoring (avg: 10 ± 3 days). Seated blood pressures were assessed using brachial blood pressure measurements, followed by a 10-minute supine autonomic testing session consisting of continuous HR (electrocardiogram), beat-by-beat blood pressure (finger plethysmograph), and MSNA (microneurography) monitoring. Partial correlations were used to determine the relationship between sleep and cardiovascular parameters while accounting for the influence of age, sex, and BMI. TST was not associated with MAP (R = −0.105, P = 0.321), HR (R = 0.093, P = 0.383), or MSNA burst frequency (BF; R = −0.168, P = 0.112) and burst incidence (BI; R = −0.162, P = 0.124). Similarly, SE was not associated with MAP (R = −0.088, P = 0.408), HR (R = −0.118, P = 0.263), MSNA BF (R = 0.038, P = 0.723), or MSNA BI (R = 0.079, P = 0.459). In contrast to recent preliminary findings, our results do not support a significant association between actigraphy-based sleep duration or efficiency and measures of resting blood pressure, heart rate, and MSNA. NEW & NOTEWORTHY: The present study investigated the independent association between actigraphy-based sleep duration, efficiency, and measures of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in adult males and females. Contrary to our hypothesis, the findings do not support an independent association between habitual sleep and cardiovascular or sympathetic neural activity. However, these findings do not preclude a potential association between these parameters in populations with sleep disorders and/or cardiovascular disease. [ABSTRACT FROM AUTHOR]

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients. [ABSTRACT FROM AUTHOR]

The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex and sympathetic transduction in the peripheral vasculature. These mechanisms interact, and both may be altered with aging and impacted by menopause. Although age-related decreases in sympathetic transduction have been demonstrated in women, it remains unclear whether sympathetic baroreflex sensitivity (BRS) is impaired in postmenopausal women (POST). We tested the hypothesis that sympathetic BRS would be enhanced in POST compared with premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22 ± 2 yr, 22 ± 3 kg/m2) and 12 POST (57 ± 5 yr, 24 ± 2 kg/m2) during 10 min of rest. Spontaneous sympathetic BRS was quantified as the slope of a linear regression between MSNA burst incidence and diastolic BP. Sympathetic transduction to mean arterial pressure (MAP) for the 10 cardiac cycles following spontaneous MSNA bursts was assessed via signal averaging method. Resting MAP was similar (PRE: 82 ± 8 vs. POST: 85 ± 8 mmHg, P = 0.43), whereas resting MSNA was elevated in POST (PRE: 10 ± 6 vs. POST: 45 ± 16 bursts/100 heart beats, P < 0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: −2.0 ± 1.2 vs. POST: −5.2 ± 1.9 bursts/beat/mmHg, P < 0.0005). Sympathetic transduction to MAP was attenuated in POST (time: P < 0.001, group: P < 0.001, interaction: P < 0.01). These data suggest that sympathetic BRS may be enhanced in POST. Consistent with recent hypotheses, enhanced sensitivity of the arterial baroreflex's neural arc may signify a compensatory response to reduced efficiency of the peripheral arterial baroreflex arc (i.e., sympathetic transduction) to preserve BP buffering capacity. NEW & NOTEWORTHY: Studies examining sympathetic baroreflex function with aging remain equivocal, with some studies showing an increase, decrease, or no change in sympathetic baroreflex sensitivity (BRS) in older adults compared with younger adults. With aging, women experience unique physiological changes due to menopause that influence autonomic function. For the first time, we show that postmenopausal women exhibit a greater sympathetic BRS compared with young premenopausal women. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate cardiac autonomic modulation using short‐term heart rate variability (HRV) and compare it among frailty statuses in older Indian adults. Methods: A total of 210 subjects aged 60 years and above were recruited into three groups: frail (n = 70), pre‐frail (n = 70), and non‐frail (n = 70) from the outpatient department of Geriatric Medicine at a tertiary care hospital in India. Frailty status was assessed using the Rockwood frailty index (FI) criteria. HRV was derived from a 5‐min ECG recording of standard limb leads and assessed using time domain, frequency domain, and nonlinear analysis of cardiac interval variability. Results: The HRV parameters indicative of parasympathetic modulation such as SDNN, SDSD, rMSSD, NN50, pNN50, absolute HF power, and SD1 were significantly lower in frail subjects compared with both pre‐frail and non‐frail subjects (P < 0.05). Absolute LF power and SD2 were also lower in frail subjects compared with pre‐frail and non‐frail subjects (P < 0.05). Measures of sympatho‐vagal balance (LF/HF and SD1/SD2 ratios) did not show statistical significance. The FI demonstrated negative correlations with all HRV parameters. Conclusions: Frail individuals exhibit decreased sympathetic and parasympathetic modulation compared with pre‐frail and non‐frail individuals, although maintaining a balanced sympatho‐vagal state. Furthermore, autonomic modulation declines progressively with increasing frailty. [ABSTRACT FROM AUTHOR]

Background Sympathetic-mediated vasoconstriction from the superior cervical ganglion (SCG) is a significant contributor to cerebral vasospasm. Inhibition of the SCG has been shown to improve cerebral blood flow and reverse cerebral vasospasm in swine models. We evaluated the efficacy of a novel minimally invasive endovascular approach to target and pharmacologically inhibit the SCG, using a Micro-Infusion Device for transmural drug delivery. Methods Eight SCGs in four Yorkshire swine were surgically identified. After confirming appropriate sympathetic-mediated intracranial vasoconstriction response with SCG stimulation, an endovascular Micro- Infusion Device was used for transmural targeting of the SCG and delivery of 1.5--2 mL of 1% lidocaine-contrast mixture to the perivascular space. Digital subtraction angiography was obtained at: (1) baseline; (2) with SCG stimulation; and (3) after lidocaine delivery to the SCG using the Micro-Infusion Device with concurrent SCG stimulation. Vessel diameters were measured and compared. Results Endovascular transmural delivery of lidocaine to the SCG and carotid perivascular tissue using the Micro-Infusion Device successfully inhibited sympathetic-mediated vasoconstriction response. Measured vessel diameters after lidocaine delivery were comparable to baseline despite SCG stimulation. Conclusion A novel endovascular technique of transmural delivery of lidocaine to the SCG and carotid artery perivascular tissues successfully inhibits the sympathetic input to the cerebral vasculature and modulates sympathetic-mediated cerebral vasospasm. These results suggest promising steps towards translation to potential clinical use for patients suffering from cerebral vasospasm. [ABSTRACT FROM AUTHOR]

Introduction Heart rate variability (HRV) serves as a non-invasive marker to assess autonomic nervous system (ANS) modulation on cardiac rhythm. Its link with sleep quality, particularly in the context of insomnia, posits HRV as a potential indicator of autonomic state variations during sleep disturbances. The prevalence of insomnia, affecting up to 20% of the general population, emphasizes the need to understand its extensive impact. Material and Methods For this review - 41 relevant titles from 1985 to 2024 were selected Analysis of the Literature: Recent studies highlight a bidirectional relationship between insomnia and ANS function, with increased sympathetic activity indicated by physiological and subjective measures in individuals with insomnia. The role of medications like beta-blockers in disrupting ANS and leading to sleep deprivation further connects measurable and perceived aspects of sleep quality, impacting health negatively. Moreover, HRV's application has expanded beyond professional athletics to daily activity and sleep quality monitoring by the general population, emphasizing its potential in evaluating stress and training intensity. Conclusion: The complex interplay between HRV, insomnia, and health outcomes necessitates further research. However, integrating HRV measurements into clinical and everyday monitoring may offer a promising avenue for improving sleep disorder management and enhancing quality of life. [ABSTRACT FROM AUTHOR]

Aims: Compensatory mechanisms in heart failure (HF) are triggered to maintain adequate cardiac output. Among them, hyperactivation of the sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS, and we can evaluate it through pupillometry. The aim of the study was to compare the differences in pupillary reflex between patients with acute HF and controls and to analyse whether these differences in pupillary reflex may offer a new and easy prognostic factor in such patients. Methods and results: We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 h after admission and prior to discharge. The results were compared with those of a group of 100 healthy volunteers who also underwent pupillometry. The maximum baseline pupil size (MBPS) and the minimum pupil diameter (MPD) were measured. Patients with decompensated HF have a higher MBPS (3.64 ± 0.81) and higher MPD (2.60 ± 0.58) than HF patients at discharge and in the control group (P‐value = 0.01 and 0.01, respectively). Also, HF patients presented an improvement in pupillometric values at discharge [MBPS (3.47 ± 0.79) and MPD (2.51 ± 0.58)] and showed no differences compared with the control group [MBPS (3.34 ± 0.82) and MPD (2.40 ± 0.53)] (P‐value = 0.19 and 0.14, respectively). In addition, MBPS provides a good independent predictor of in‐hospital and 1 month mortality in patients admitted with HF. Six patients (5.61%) died during hospital admission, and 11 patients (10.2%) died in the first month after discharge. Also, four patients (3.74%) were readmitted within 1 month of discharge. The receiver operating characteristic (ROC) curve for predicting in‐hospital mortality through MBPS was 0.823. No patient with an MBPS < 3.7 mm died. The ROC curve for predicting combined mortality or readmission within the first month for MBPS was 0.698. Conclusions: Pupillometry may be a new, non‐invasive, and simple tool to determine the status of SNS, help in the prognostic stratification of acute HF patients, and improve therapeutic management. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions The US Headache Consortium developed evidence‐based guidelines for the treatment of migraine and found grade A evidence in support of behavior therapy (BT). Understanding the mechanisms of BT may improve the management of migraine and reduce its burden.We performed a narrative review to define the current evidence of BT and determine its usefulness in migraine management.The information was obtained from 116 publications, with 56 of them retrieved through direct searches in PubMed (2011–2020) and the remainder selected by the authors to complete the content. BT might reduce migraine impact by decreasing the sympathetic nervous system's response to stress and increasing pain tolerance. Acting in headache‐related surroundings can be improved, together with headache duration and self‐efficacy. Applications such as mobile health and electronic health applications can help to carry out healthier lifestyle patterns. Regarding medication overuse, BT seems to be a good choice, with similar results to pharmacological prophylaxis. Advantages of using BT are the lack of adverse effects and the unrestricted use in children, where BT is postulated to be even more effective than the standardized pharmacopeia.BT is an interesting tool that can be used as an add‐on therapy in migraine. Through BT, the autonomy and empowerment of migraine patients is enhanced. BT may not cure migraine, but it could help to reduce pain severity perception, disability, and migraine impact, adding an emotive and cognitive approach to the perceptive role of pharmacopeia. Thus, a better approach in migraine, implementing specific therapeutic management, can improve migraine control. [ABSTRACT FROM AUTHOR]

Objective: The present study investigated the impact of two different light intensities on the pain-modulated pupillary light response (PLR). Additionally, it aimed to demonstrate parasympathetic and sympathetic influences on PLR parameters in response to pain, as predicted by functional models. Method: A total of 24 participants were included in a randomized, repeated-measures design. The PLR wasmeasured in response to both dark and bright light stimuli within two test cycles. Pain was induced using the cold pressor test (CPT), which involved immersing participants' feet in ice water. PLR measurements were taken during baseline and ice-water immersion within each test cycle. The assessed PLR parameters included initial diameter (INIT), latency (LAT), amplitude (AMP), and re-dilation time (ReDIL25). Along with these parameters, heart rate (HR) and pain ratings were also computed and analyzed. Main results: The CPT caused moderate pain in participants, and the resulting PLR parameters were found to be congruent with the expected parasympathetic and sympathetic nervous system activities. Although the luminance of the stimulus did influence PLR parameters, no interaction with pain exposure was found. Significance: The results showed that different aspects of pain experienced by an individual, as modulated through the sympathetic and parasympathetic nervous systems, are visible in their pupillary reactions to light. Notably, within the range used in the current study, light intensity did not significantly affect the pain-related PLR effects. [ABSTRACT FROM AUTHOR]

Background: The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported. Case presentation: This work describes the case of a 42‐year‐old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner's syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren's syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren's syndrome. Conclusions: This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches. [ABSTRACT FROM AUTHOR]

Electrodermal Activity (EDA), which primarily indicates arousal through sympathetic nervous system activity, serves as a tool to measure constructs like engagement, cognitive load, performance, and stress. Despite its potential, empirical studies have often yielded mixed results and found it of limited use. To better understand EDA, we conducted a mixed-methods study in which quantitative EDA profiles and survey data were investigated using qualitative interviews. This study furnishes an EDA dataset measuring the engagement levels of seven participants who watched three videos for 4–10 min. The subsequent interviews revealed five EDA morphologies with varying short-term signatures and long-term trends. We used this dataset to demonstrate the moving average crossover, a novel metric for EDA analysis, in predicting engagement–disengagement dynamics in such data. Our contributions include the creation of the detailed dataset, comprising EDA profiles annotated with qualitative data, the identification of five distinct EDA morphologies, and the proposition of the moving average crossover as an indicator of the beginning of engagement or disengagement in an individual. [ABSTRACT FROM AUTHOR]

NaV1.7 plays a crucial role in inducing and conducting action potentials in pain‐transducing sensory nociceptor fibres, suggesting that NaV1.7 blockers could be effective non‐opioid analgesics. While SCN9A is expressed in both sensory and autonomic neurons, its functional role in the autonomic system remains less established. Our single neuron rt‐PCR analysis revealed that 82% of sympathetic neurons isolated from guinea‐pig stellate ganglia expressed NaV1.7 mRNA, with NaV1.3 being the only other tetrodotoxin‐sensitive channel expressed in approximately 50% of neurons. We investigated the role of NaV1.7 in conducting action potentials in postganglionic sympathetic nerves and in the sympathetic adrenergic contractions of blood vessels using selective NaV1.7 inhibitors. Two highly selective NaV1.7 blockers, GNE8493 and PF 05089771, significantly inhibited postganglionic compound action potentials by approximately 70% (P < 0.01), with residual activity being blocked by the NaV1.3 inhibitor, ICA 121431. Electrical field stimulation (EFS) induced rapid contractions in guinea‐pig isolated aorta, pulmonary arteries, and human isolated pulmonary arteries via stimulation of intrinsic nerves, which were inhibited by prazosin or the NaV1 blocker tetrodotoxin. Our results demonstrated that blocking NaV1.7 with GNE8493, PF 05089771, or ST2262 abolished or strongly inhibited sympathetic adrenergic responses in guinea‐pigs and human vascular smooth muscle. These findings support the hypothesis that pharmacologically inhibiting NaV1.7 could potentially reduce sympathetic and parasympathetic function in specific vascular beds and airways. Key points: 82% of sympathetic neurons isolated from the stellate ganglion predominantly express NaV1.7 mRNA.NaV1.7 blockers inhibit action potential conduction in postganglionic sympathetic nerves.NaV1.7 blockade substantially inhibits sympathetic nerve‐mediated adrenergic contractions in human and guinea‐pig blood vessels.Pharmacologically blocking NaV1.7 profoundly affects sympathetic and parasympathetic responses in addition to sensory fibres, prompting exploration into the broader physiological consequences of NaV1.7 mutations on autonomic nerve activity. [ABSTRACT FROM AUTHOR]

There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow-these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta-hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to the bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei, and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to the bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Dopamine beta‐hydroxylase (DβH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS).A single‐centre, prospective, double‐blind, randomized, placebo‐controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days −1 and 10. Plasma and 24 h‐urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DβH activity, were measured.Compared to placebo, zamicastat showed a − 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (−2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24‐h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter‐individual variability (CV: 32.6%–36.6%). Steady state was already achieved on Day 6.Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator. [ABSTRACT FROM AUTHOR]

Understanding a person's perceived quality of sleep is an important problem, but hard due to its poor definition and high intra- as well as inter-individual variation. In the short term, sleep quality has an established impact on cognitive function during the following day as well as on fatigue. In the long term, good quality sleep is essential for mental and physical health and contributes to quality of life. Despite the need to better understand sleep quality as an early indicator for sleep disorders, perceived sleep quality has been rarely modeled for multiple consecutive days using biosignals. In this paper, we present novel insights on the association of cardiac activity and perceived sleep quality using an interpretable modeling approach utilizing the publicly available intensive-longitudinal study M2Sleep. Our method takes as input signals from commodity wearable devices, including motion and blood volume pulses. Despite processing only simple and clearly interpretable features, we achieve an accuracy of up to 70% with an AUC of 0.76 and reduce the error by up to 36% compared to related work. We further argue that collected biosignals and sleep quality labels should be normalized per-participant to enable a medically insightful analysis. Coupled with explainable models, this allows for the interpretations of effects on perceived sleep quality. Analysis revealed that besides higher skin temperature and sufficient sleep duration, especially higher average heart rate while awake and lower minimal activity of the parasympathetic and sympathetic nervous system while asleep increased the chances of higher sleep quality. [ABSTRACT FROM AUTHOR]

Fluid restriction has long been believed to benefit patients with heart failure by counteracting the activated renin–angiotensin aldosterone system and sympathetic nervous activity. However, its effectiveness remains controversial. In this paper, we summarized the current recommendations and reviewed the scientific evidence on fluid restriction in the setting of both acute decompensated heart failure and compensated heart failure. While a recent meta-analysis demonstrated the beneficial effects of fluid restriction on both all-cause mortality and hospitalization compared to usual care, several weaknesses were identified in the assessment of the methodological quality of the meta-analysis using AMSTAR 2. Further randomized controlled trials with larger sample sizes are needed to elucidate the benefits of fluid restriction for both clinical outcomes and patient-reported outcomes in patients with heart failure. [ABSTRACT FROM AUTHOR]

Introduction: The sympathetic nervous system and the renin-angiotensin system (RAS) are the most pivotal vasoactive systems in regulating renal hemodynamics. The main objective of this study was to determine the role of the angiotensin II (Ang II) type 1 receptor (AT1R) antagonist on renal hemodynamic responses to Ang 1-7 infusion in innervated and denervated male and female rats. Methods: Male and female Wistar rats underwent unilateral nephrectomy. Four weeks later, they were divided into two groups: innervated and acutely denervated groups. Subsequently, the anesthetized and catheterized rats in both groups were treated with saline as a vehicle and losartan infusion. Mean arterial pressure (MAP), renal blood flow (RBF), renal perfusion pressure (RPP), and renal vascular resistance (RVR) responses to Ang 1-7 (100, 300, and 1000 ng kg−1 min−1 ) were then measured at controlled RPP. Results: Basal MAP, RPP, RBF, and RVR did not show significant differences between the intact and denervated groups. Losartan significantly decreased MAP, RPP, and RVR in both innervated and denervated male and female rats (P<0.001), while RBF increased only in innervated and denervated female rats (P<0.004). However, following Ang 1-7 administration, the RBF response to Ang 1-7 infusion differed significantly between intact and denervated male rats treated with losartan (P<0.04). This response was not observed in female rats. Conclusion: These data suggest a synergistic effect of losartan and Ang 1-7 on increased RBF in the presence of renal sympathetic nerves in male rats. [ABSTRACT FROM AUTHOR]

The article provides information on a study about an accredited American Nurses Credentialing Center (ANCC) transition to practice (TTP) residency program developed by an academic teaching medical center in southern California. Topics discussed include participant demographic characteristics, resilience and well-being outcomes among new nurses, and implications for nurse leaders.

Aims Physical symptoms impact patients with heart failure (HF) despite treatment advancements; however, our understanding of the pathogenic mechanisms underlying HF symptoms remains limited, including sex differences therein. The objective of this study was to quantify associations between sympathetic markers [norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DHPG)] and physical symptoms in patients with HF and to explore sex differences in these associations. Methods and results We performed a secondary analysis of combined data from two studies: outpatients with HF (n = 111), and patients prior to left ventricular assist device implantation (n = 38). Physical symptoms were measured with the Heart Failure Somatic Perception Scale (HFSPS) dyspnoea and early/subtle symptom subscales and the Functional Assessment in Chronic Illness Therapy Fatigue Scale (FACIT-F) to capture dyspnoea, early symptoms of decompensation, and fatigue. Norepinephrine and DHPG were measured with high-performance liquid chromatography with electrochemical detection. Multivariate linear regression was used to quantify associations between symptoms and sympathetic markers. The sample (n = 149) was 60.8 ± 15.7 years, 41% women, and 71% non-ischaemic aetiology. Increased plasma NE and NE:DHPG ratio were associated with worse FACIT-F scores (P = 0.043 and P = 0.013, respectively). Increased plasma NE:DHPG ratio was associated with worse HFSPS early/subtle symptoms (P = 0.025). In sex-stratified analyses, increased NE:DHPG ratio was associated with worse FACIT-F scores (P = 0.011) and HFSPS early/subtle scores (P = 0.022) among women but not men. Conclusion In patients with HF, sympathetic dysfunction is associated with worse fatigue and early/subtle physical symptoms with associations stronger in women than men. [ABSTRACT FROM AUTHOR]

Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently associated with chronic inflammatory dermatoses and systemic disorders. Psychogenic pruritus and neurological disorders are other less common etiologies, while, in some patients, it is idiopathic. CP appears to be processed by non-histaminergic pathway, contributing to its complexity and therapeutic challenge. Moreover, regardless of the etiology, it is multidimensional, including cognitive, motivational and affective components. There is a close link between psychological distress and pruritus, with particular clinical expression in chronic inflammatory dermatoses, involving the activation of the hypothalamic-pituitary-adrenal axis (and its cutaneous equivalent), the sympathetic nervous system, the release of hormones and peptides, the role of immune cells (T and B cells, macrophages) and immune-related cells in the skin (mast cells, dendritic cells and keratinocytes). Moreover, there is strong evidence that psychological factors influence the experience of pruritus. CP can also cause psychiatric disorders, including but not limited to anxiety and depression, and also lead to significant quality of life (QoL) impairment. Thereby, although a psychodermatological assessment should ideally be carried out in the context of a specific psychodermatology consultation, a brief mental health assessment could be part of the general dermatological approach to these patients. Considering that mental health, QoL and pruritus are closely linked, psychotherapeutic interventions and/or psychotropic drugs should thus be considered in some patients as an adjunct to the pharmacological treatment of CP. [ABSTRACT FROM AUTHOR]

Emotion regulation (ER) is a multifaceted construct, involving behavioral, cognitive, and physiological processes. Although autonomic coordination is theorized to play a crucial role in adaptive functioning, few studies have examined how different individual and contextual factors together may contribute to such coordination. This study examined the joint influences of narrative processing and emotional negativity/lability (N/L) traits on the coordination of the sympathetic and parasympathetic nervous systems in a sample of 112 children, ages 8–12 years (Mage = 10.15 years, SD = 1.33). Children completed a stress‐induction task followed by an interview about the task. Children's trait‐level N/L was assessed via parent‐report on the Emotion Regulation Checklist. Narrative processing was assessed and coded based on children's narrative accounts of the event (i.e., causal coherence, overall emotional tone). Indexes of sympathetic (skin conductance response, SCR) and parasympathetic (respiratory sinus arrhythmia, RSA) functioning were derived from physiological data obtained during the interview. Results revealed that children's trait‐level N/L and narrative processing of the stressful event interacted to predict the RSA–SCR correlation. Specifically, children who were high on either N/L or narrative causal coherence, but not both, demonstrated significant RSA–SCR correlation. Similarly, children with high N/L and negative‐to‐neutral narratives, as well as those with low N/L and neutral‐to‐positive narratives, exhibited significant RSA–SCR correlation. This work provides empirical evidence that narrative processing and trait N/L, together with RSA–SCR correlation, work in tandem to regulate emotional arousal. This study examined the interactive roles of individual and contextual factors in association with autonomic coordination in ER. Children's trait‐level negativity/lability and narrative processing (i.e., causal coherence, the overall emotional tone) interacted to predict sympathetic and parasympathetic coordination. Findings empirically support that narrative processing and trait N/L, together with RSA–SCR correlation, work in tandem to regulate emotional arousals. [ABSTRACT FROM AUTHOR]

During times of stress, we look to close others for support. Social support conversations are critical for relationship maintenance and well‐being. Yet, certain ways of talking about problems—such as co‐ruminating—can exacerbate stress. Since social support and co‐rumination are both dyadic processes, it is important to examine physiological responses during these conversations in a dyadic manner. Little research has examined physiological synchrony of the sympathetic nervous system (SNS) during social support conversations or co‐ruminative conversations. The current research capitalizes on an experimental manipulation of co‐rumination using a sample of close friends (147 dyads) and romantic partners (113 dyads) to examine physiological covariation in the context of support. Across both samples, dyads exhibited significant physiological covariation in pre‐ejection period reactivity (PEP). Contrary to our hypothesis, dyads in the co‐rumination condition did not show more covariation. Close friend dyads did, however, exhibit more covariation as compared to romantic dyads. We also found significant variability in physiological covariation across dyads, with a minority of dyads exhibiting negative covariation of PEP reactivity. The homogeneity of the samples limits the generalizability of the findings and highlights the need for more diverse samples in future work. These findings underline the need for further exploration into the mechanisms that contribute to distinct patterns of physiological synchrony, the conditions in which negative synchrony occurs, and what predicts especially strong positive synchrony. This work extends our understanding of physiological synchrony of the sympathetic nervous system during support conversations and emphasizes the importance of considering heterogeneity in physiological processes. Impact statement: This research capitalizes on two dyadic experiments to examine physiological covariation during supportive conversations, examining whether certain ways of providing support affects synchrony. The findings show that not only does physiological covariation of the sympathetic nervous system occur, but it is variable across dyads and stronger for close friends as compared to romantic partners. [ABSTRACT FROM AUTHOR]

Introduction: Stress response to surgery is characterized by increase in secretion of endocrinal system and activation of immunological and sympathetic nervous system. Alpha 2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anaesthesia and surgery; reduce anaesthetic and opioid requirements; and cause sedation and analgesia. Aims and objectives; The objective of this study is to evaluate the intra-operative, and postoperative haemodynamic stress responses in patients, when Dexmedetomidine is used as an anaesthetic adjunct. Materials and Method: After the approval from Ethical Committee of Guntur medical college, Guntur, A.P, 100 patients scheduled for elective surgery planned to be done under general anaesthesia were included in the study.Patients were randomly divided into two equal groups, according to the study drug administered, each group include 50 patients in number (n=50), group I (the control or placebo group) and group II (Dexmedetomidine group). Patients received either Dexmedetomidine hydrochloride (available as 100 μg/ml ) in group II or saline solution in group I in equal amount. Data were collected and entered into the software STATA (version 11.0). P<0.05 was considered significant and P>0.05 was considered insignificant. Results: There was no significant difference in the base line parameters among the groups. Dexmedetomidine decreased heart rate significantly compared to control group. Dexmedetomidine reduced the intraoperative use of Propofol and Fentanyl significantly compared to control group. Conclusion: The perioperative infusion of Dexmedetomidine appears to be effective to attenuate stress induced haemodynamic fluctuation, reduced Propofol requirements, decreased the intra and post-operative narcotic analgesic administration, produced perioperative sedation in patients who underwent elective surgeries when compared with placebo. [ABSTRACT FROM AUTHOR]