Search Results (791)

Background/Objectives: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by excessive tachycardia during orthostatic stress. It is frequently observed in patients with syncope, Chronic Fatigue Syndrome (CFS), and post-COVID-19 syndrome (PCS), yet the underlying mechanisms may differ across these conditions. This study aimed to assess autonomic nervous system (ANS) function in patients with syncope, CFS of insidious onset, and CFS post-COVID-19 who presented with POTS, and to compare them with age- and sex-matched patients without POTS. Methods: In this retrospective cross-sectional study, 138 patients over 18 years of age were included following head-up tilt testing (HUTT). Patients were divided into six groups: syncope with and without POTS, CFS with insidious onset with and without POTS, and CFS post-COVID-19 with and without POTS. All participants underwent HUTT, cardiovascular reflex testing (CART) by Ewing, five-minute resting ECG with short-term Heart Rate Variability (HRV) analysis, and 24 h Holter ECG monitoring. Results: The prevalence of POTS across groups ranged from 5% to 7%. Female predominance was consistent across all subgroups. In syncope with POTS, hypertensive responses during HUTT, lower rates of normal Valsalva maneuver results, and reduced HF values in short-term HRV suggested baroreceptor dysfunction with sympathetic overdrive. In both CFS subgroups with POTS, CART revealed higher rates of definite parasympathetic dysfunction, along with more frequent extreme blood pressure variation during HUTT and reduced vagally mediated HRV parameters (rMSSD, pNN50). Across groups, no significant differences were observed with regard to long-term HRV across groups. Conclusions: Distinct autonomic profiles were identified in POTS patients depending on the underlying condition. Syncope-related POTS was associated with baroreceptor dysfunction and sympathetic predominance, whereas CFS-related POTS was characterized by parasympathetic impairment and impaired short-term baroreflex regulation. Evaluating dysautonomia patterns across disease contexts may inform tailored therapeutic strategies and improve management of patients with POTS. Full article

Major depressive disorder (MDD) is a multifaceted psychiatric disorder that has been a longstanding focus of research. However, its underlying mechanisms remain underexplored. Recently, the inflammatory hypothesis has gained attention, highlighting inflammation’s role in MDD progression. Potential contributors to increased systemic inflammation in MDD include hyperactivation of the hypothalamic–pituitary–adrenal axis, dysregulation of the sympathetic nervous system, gut microbiota imbalances, the “pathogen host defense” hypothesis, and damage-associated molecular patterns. Traditional pathways explaining how systemic inflammation affects the central nervous system (CNS) do not fully account for the observed desynchrony between systemic and neuroinflammation in most depressed individuals. Alternative models suggest mechanisms such as reduced blood–brain barrier permeability and the involvement of immune cells from the skull. This review examines the link between inflammation and MDD, focusing on systemic and neuroinflammation interactions, with special emphasis on the heterogeneity of MDD symptoms and the potential impact of dysfunction in the brain’s lymphatic system. Gaining insight into the origins of inflammation in both the central nervous system and the peripheral body, along with their interactions, offers an important understanding of the inflammatory mechanisms associated with MDD for future treatment. Full article

Background/Objectives: Heart rate variability (HRV) reflects autonomic nervous system modulation and may be altered in both unexplained syncope and obstructive sleep apnea (OSA). However, the nocturnal autonomic patterns underlying these conditions and their coexistence remain poorly understood. This study aimed to characterize nocturnal autonomic modulation in patients with unexplained syncope, OSA, or both, compared with individuals without these conditions. Methods: In this multicenter, cross-sectional, comparative study, 304 adults were assigned to four groups: controls (no syncope or OSA), OSA without syncope, syncope without OSA, and syncope with OSA. Time- and frequency-domain HRV parameters were derived from overnight respiratory polygraphy and compared across groups. Results: OSA was associated with increased root mean square of successive differences (RMSSD) and reduced low-frequency (LF) power, indicating enhanced vagal activity and lower nocturnal sympathetic tone. Syncope was characterized by further reductions in sympathetic indices (LF and very low frequency, VLF) with increased RMSSD, suggesting blunted sympathetic reserve. Patients with both conditions exhibited a mixed autonomic profile—elevated overall HRV with concurrent reductions in both sympathetic and parasympathetic components—indicating more profound dysautonomia despite milder OSA severity. Conclusions: OSA and syncope show distinct nocturnal autonomic patterns, and their coexistence leads to deeper autonomic imbalance. Incorporating nocturnal HRV analysis into routine polygraphy may improve pathophysiological stratification of unexplained syncope and identify clinically significant OSA. Full article

Background: Eye and visual symptoms are becoming increasingly common in young people, along with the emerging conditions text neck and computer vision syndrome, though underlying mechanisms are not fully elucidated. The link between cervical spine structure and the eye remains relatively unexplored. Methods: This paper employs a hypothesis-driven, literature-based evidence approach, aiming to explore the hypothesis that cervical spine structural issues may be an underlying mechanism for visual symptoms and eye diseases. The purpose of exploring this hypothesis is to lay the groundwork for future research, and advance diagnostics and treatment options. No new analysis was performed. Results: This article lays the groundwork for the hypothesis that cervical spine structural dysfunctions, including a forward-displaced atlas (C1), can cause dynamic carotid sheath compression, contributing to neurological and neurovascular mechanisms that affect the eye, primarily by (1) impaired venolymphatic drainage of the eye and brain due to compression of the internal jugular veins, and (2) ocular dysautonomia from a disruption of the parasympathetic/sympathetic system balance, partly due to vagus nerve degeneration. Conclusions: Potential mechanisms, diagnostics, and treatment options for visual disorders initiated by cervical structural dysfunction are discussed, providing a foundation for future research aimed at improving clinical outcomes for some eye conditions which have an otherwise unknown etiology. Full article

Early-life feeding strategies are known to affect growth, behavior, and stress physiology in dairy calves. This study examined the effects of different milk feeding regimes on heart rate (HR) and heart rate variability (HRV) during feeding and rehousing as indicators of autonomic activity. Dairy calves were fed either a restrictive milk allowance twice per day (6 L/d; RES; n = 21) or an unlimited amount of milk (ad libitum; ADL; n = 24) during the first three weeks of life. All calves were housed in individual straw bedded hutches from d 1 to 23 of life and were moved to a group pen on d 23 ± 2 of life. Starting at least one day before rehousing until one hour after the rehousing process HR, HRV, and variables in the time and frequency domain were measured continuously using a portable recording system. To study the cardiac response to the feeding process, six time windows of 5 min each were chosen as follows: resting time at 5.00 a.m., start of personnel activity in the barn, 15 min before feeding, during feeding, 15 min after feeding, and 1 h after feeding. For the evaluation of cardiac response to an unknown stressor such as rehousing, four time windows of 5 min each were selected as follows: resting time at 5.00 a.m., during rehousing, 30 min after rehousing, and 1 h after rehousing. During resting as well as before feeding and rehousing, HR was higher in ADL calves compared with RES calves. During feeding and rehousing, HR reached peak values which were comparable in both groups. HRV variables of the time and frequency domain indicated a shift towards a sympathetic dominance in the balance of the autonomic nervous system during feeding time, particularly in RES calves. Differences between resting and feeding values were demonstrated in RES calves at low-frequency and high-frequency power, whereas no differences were observed in ADL calves which did not react to the feeding process. The cardiac response of calves to rehousing was inconsistent in both groups. An increase in RMSSD and SD1 in ADL calves indicated that the vagal component in the vegetative neurological control was increased in these calves during rehousing. In conclusion, our findings indicate that restrictive milk feeding alters autonomic regulation and may increase physiological stress responses in calves. Full article

The autonomic nervous system (ANS) regulates internal organ function to maintain homeostasis. Dysautonomias are ANS disorders involving reduced or excessive sympathetic or parasympathetic activity and can be associated with metabolic syndrome and eating disorders such as binge eating disorder (BED). The ANS exhibits synaptic plasticity phenomena, including long-term potentiation (LTP) and neurotransmitter expression changes, which may influence autonomic function. BED is defined as recurrent, compulsive intake of large amounts of high-calorie food in a short time. Here, we examined dysautonomia in a rat BED model induced by cycles of food restriction and access to highly caloric food, and assessed whether exercise prevents these alterations. After confirming BED induction, we characterized LTP in the superior cervical ganglion (SCG) and analyzed acetylcholine (ACh) and GABA expression and their co-localization/segregation. BED rats exhibited impaired LTP and increased GABA expression. Voluntary aerobic exercise prevented BED onset and the associated changes in LTP and GABA. We propose that BED-associated dysautonomia proceeds at least in the ganglionic sympathetic cholinergic transmission, with reduced sympathetic activity. These results may contribute to a better understanding of the autonomic disorder associated with BED and support exercise as a protective intervention. Full article

The blood–brain barrier (BBB) restricts the entry of therapeutic agents into the brain cardiovascular regulatory region, potentially contributing to drug-resistant hypertension. Objective: The objective of this study was to overcome this limitation by modifying PEGylated liposomes with transferrin (Tf) to facilitate Tf receptor binding at the BBB and penetratin (Pen), a cell-penetrating peptide, to enhance neuronal uptake. Methods: This study evaluated the efficacy of Tf-Pen-liposomes in delivering angiotensin-converting enzyme 2 (ACE2) or EGFP (control) genes across the BBB in rats. In addition, the therapeutic effect of intravenous administration of Tf-Pen-Lip carrying plasmid DNA encoding ACE2 (Tf-Pen-Lip-pACE2) was tested in a neurogenic hypertension model induced by intracerebroventricular (ICV) infusion of angiotensin II (Ang II) via osmotic pump implantation and brain cannulation. Results: Conjugation with Tf and Pen significantly enhanced liposome-mediated gene transfection in cultured cells and increased transport across an in vitro BBB model. In vivo, intravenous administration of Tf-Pen-Lip-pACE2 or Tf-Pen-Lip-pGFP successfully elevated ACE2 or EGFP expression, respectively, in the hypothalamic paraventricular nucleus (PVN). Chronic ICV infusion of Ang II produced a sustained increase in blood pressure and heart rate, accompanied by sympathetic overactivation and elevated arginine vasopressin (AVP) secretion, hallmarks of neurogenic hypertension. Notably, intravenous Tf-Pen-Lip-pACE2 treatment dramatically attenuated Ang II–induced neurogenic hypertension, whereas Tf-Pen-Lip-pGFP had no effect on pressor responses, sympathetic activity, or AVP secretion. Conclusions: This dual-functionalized liposomal delivery system effectively transported the ACE2 gene across the BBB into the brain, increased ACE2 expression, and markedly attenuated neurogenic hypertension following systemic administration. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Heart failure (HF) is a growing public health concern, driven by the increasing prevalence of obesity, diabetes, and aging. Despite therapeutic advances, HF continues to be associated with high morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for glycemic control in type 2 diabetes, have demonstrated cardiovascular benefits in clinical trials. Recent studies, including STEP-HFpEF and SUMMIT, have shown improvement in symptoms and weight loss in patients with HF with preserved ejection fraction (HFpEF). GLP-1 RAs are involved in multiple biological pathways relevant to heart failure pathophysiology. These include pathways related to sympathetic nervous system activity, inflammatory cytokine signaling, oxidative stress, calcium handling, natriuretic peptide signaling, and cardiac metabolism. GLP-1 receptor agonists modulate vascular pathways involving nitric oxide signaling, endothelial function, and renal sodium handling, contributing to improved hemodynamics and neurohormonal balance. Together, these actions intersect with key neurohormonal and cellular processes contributing to chronic heart failure progression. This review explores the mechanistic overlap between GLP-1 receptor signaling and heart failure pathophysiology. This mechanistic overlap suggests a plausible role for these agents as adjunctive treatments in heart failure, especially in metabolically driven phenotypes. While direct cardiac effects remain incompletely defined, systemic metabolic and anti-inflammatory actions provide a mechanistic basis for observed clinical benefits. Full article

Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. Although grape seed extract (GSE) supplementation has been shown to increase nitric oxide production and modify sympathetic output, there is limited evidence on its potential beneficial effects on PHRR. We investigated the effect of GSE supplementation on PHRR during sympathetic overactivation induced by muscle metaboreflex activation (MMA) in young individuals. Participants were randomly assigned, via a double-blind, cross-over design, to either receive GSE (300 mg, two capsules) or PL (300 mg, two capsules), with a washout period of at least 72 h. between trials. A submaximal exercise test was performed using a cycle ergometer combined with an isometric handgrip exercise using a handgrip dynamometer and blood flow occlusion by placing a cuff over the brachial artery of the dominant arm. PHRR was measured at 5 s. intervals throughout the experiment. The PHRR was evaluated between GSE and PL at every min. for 300 s. PHRR kinetics significantly improved following GSE supplementation (74.3 ± 7.5 s) compared with the PL condition (86.2 ± 10.4 s). Our results suggest that GSE is effective in improving HRR kinetics during heightened sympathetic activity induced by MMA in young individuals (p = 0.034; ES = 0.4). Thus, regular treatment with GSE may provide a nonpharmacological intervention to reduce sympathetic hyperactivity in conditions where excessive sympathetic activity is consistently present. Full article

Chronic stress disrupts neuroimmune homeostasis and initiates CNS inflammation. This paper examines the molecular and cellular mechanisms that connect stress to the interplay among the nervous, endocrine, and immune systems, with a focus on the role of the NLRP3 inflammasome in neuroinflammatory processes. It discusses the dynamics of HPA axis, stress-induced changes in glucocorticoid and mineralocorticoid signaling, sympathetic nervous system activation, and the contribution of pro-inflammatory cytokines in brain immune activation. The NLRP3 inflammasome is described in terms of its structure, activation via a two-signal model, and its role in IL-1β and IL-18 maturation in neurons, microglia, and astrocytes. Preclinical evidence highlights the therapeutic potential of targeting NLRP3 in stress-related disorders, underscoring its key role in their pathophysiology. Full article

Background/Objectives: Pain-induced vasoconstriction and thrombosis cause vascular insufficiency, a major etiology of early necrosis in replanted digits. While systemic intravenous analgesia (SIVA) carries significant side effects, continuous brachial plexus block (CBPB) provides analgesia with vasodilation. Amidst uncertainties regarding distal vascular recanalization and sympathetic denervation, whether CBPB’s hemodynamic effects translate into improved perfusion and outcomes in replanted digits remains unknown. This randomized controlled trial compared the effects of CBPB versus SIVA on digit perfusion, vascular insufficiency, and survival rates post-replantation. Methods: After screening 113 patients, 55 patients (71 digits) were ultimately randomized and analyzed: the CBPB group (n = 27, 36 digits) received 0.2% ropivacaine infusion at 5 mL/h; the SIVA group (n = 28, 35 digits) received intravenous parecoxib 20 mg twice daily with supplemental tramadol for visual analog scale (VAS) scores > 3. The primary outcome was digital skin temperature trajectory measured at 0, 12, 24, 36, and 48 h postoperatively. Secondary outcomes included Doppler-quantified combined volumetric flow rate of the radial and ulnar arteries (RA-UA VFR) at identical timepoints, VAS scores, vascular insufficiency incidence, and 7-day digit survival. Results: CBPB significantly enhanced perfusion in replanted digits at all postoperative timepoints, with digital skin temperature peaking at 48 h (32 ± 1.6 °C vs. 31 ± 1.1 °C; p < 0.001) and RA-UA VFR peaking at 24 h (4.0 ± 0.83 vs. 1.8 ± 0.51 mL/s; p < 0.001) versus SIVA. Concurrently, CBPB provided superior analgesia (VAS 0.52 ± 0.51 vs. 1.9 ± 1.0; p < 0.001) and significantly reduced 48-h vascular insufficiency incidence (8.3% vs. 29%; p = 0.028). No significant difference was observed in seven-day survival rates between groups (97% vs. 91%; p = 0.329). Conclusions: CBPB significantly enhanced perfusion in replanted digits and reduced the incidence of vascular insufficiency, despite not conferring additional survival benefits. Full article

Brown adipose tissue (BAT) has shifted from being considered a transient thermogenic organ of infancy to a metabolically dynamic and multifunctional tissue throughout life. Histologically and developmentally distinct from white and beige adipocytes, BAT originates from a myogenic lineage and is characterised by a high mitochondrial density, multilocular lipid droplets, and abundant sympathetic innervation. Its defining function, non-shivering thermogenesis, is mediated by uncoupling protein 1 (UCP1) and complemented by alternative mechanisms such as futile creatine and calcium cycling. Beyond heat production, thermogenic fat is crucial in regulating whole-body metabolism. It contributes to glucose, lipid, and branched-chain amino acid homeostasis, and engages in endocrine and paracrine signalling through a rich secretome of batokines, lipid mediators, and extracellular vesicle-bound microRNAs. These signals orchestrate crosstalk with the liver, skeletal muscle, pancreas, and immune system, enhancing insulin sensitivity, vascularisation, and anti-inflammatory responses. Brown/Beige fat also exhibits notable anti-fibrotic properties and supports adipose tissue remodelling, maintaining structural and functional plasticity under metabolic stress. This review offers a comprehensive synthesis of thermogenic adipose tissue biology, integrating its structural, developmental, and molecular features with its expanding physiological functions, highlighting its pivotal role in energy balance as well as its emerging therapeutic potential in obesity, type 2 diabetes, and related metabolic disorders. Full article

The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone–brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone–brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders. Full article

Background/Objectives: High thoracic erector spinae plane block (ESPB) is a novel technique for managing chronic radicular and sympathetically mediated pain. Although physiological changes, such as increased skin temperature, perfusion index (PI), and optic nerve sheath diameter (ONSD), are known to reflect ESPB-induced sympatholysis, their predictive value for analgesic success remains unclear. In this context, the objective of this study is to investigate whether these objective indicators of sympathetic blockade are associated with the clinical success of high thoracic ESPB. Methods: The sample of this prospective, observational study consisted of 35 adult patients with chronic radicular pain undergoing a high thoracic ESPB procedure. Pre- and post-procedure assessments included bilateral skin temperature, PI, ONSD measurements, and administration of a visual analog scale (VAS). Patients with a greater than 50% decrease in VAS score were deemed responders to the procedure. Results: Of the 35 patients, 29 (82.9%) were responders. The patients’ post-procedure ipsilateral skin temperature (p < 0.001), PI (p = 0.002), and ONSD (p < 0.001) values were significantly higher than their pre-procedure values. However, none of these parameters differed significantly between responders and non-responders (p > 0.05). There was also no significant correlation between VAS score and changes in PI, ONSD, or skin temperature (p > 0.05). Conclusions: In conclusion, although high thoracic ESPB resulted in measurable physiological changes suggestive of sympathetic blockade, these changes did not predict clinical analgesic success. Full article