Search Results (1,356)

Anxiety disorders and chronic stress are the most common types of mental disorder. According to the WHO, more than 359 million people worldwide suffered from these conditions in 2021. The function of mastication and the masticatory muscles undergo significant changes under the influence of a disturbed psychoemotional state. This manifests as their parafunctional activity, accompanied by increased tone and damage to elements of the dentofacial system, including increased tooth wear, chipping, cracks, and fractures. Attention to this problem is growing annually among researchers in both dental and neurological fields. This is evidenced by a wide range of therapeutic and preventive interventions aimed at correcting chronic stress, muscle hypertonia, and pathology of the dentofacial system. Despite the aforementioned measures, it is often only possible to slow down the pathological process rather than completely resolve it. This is because knowledge regarding the biology and pathophysiology of how chronic stress affects muscle activity remains limited. Understanding such mechanisms and establishing precise interrelationships could help identify targets for effective therapeutic interventions and eliminate the problem. This review of the literature systematizes information on how chronic stress and various autonomic stimuli affect changes in the functional activity of the masticatory muscles and the pathology of hard dental tissues. Full article

Background: Varicella-zoster virus (VZV) is a neurotropic alphaherpesvirus capable of causing a broad spectrum of neurologic complications beyond classic dermatomal herpes zoster. Although meningitis and encephalitis are well recognized manifestations of neuroinvasive VZV infection, associated autonomic dysfunction remains comparatively underreported, particularly in immunocompetent individuals. Case Presentation: We describe a 66-year-old immunocompetent man who developed VZV meningoencephalitis associated with sacral dermatomal herpes zoster, urinary retention, and bowel dysmotility. Initial symptoms included fever, severe headache, photophobia, and low back pain, with delayed recognition of the characteristic sacral vesicular eruption. The patient subsequently developed encephalopathy and meningeal signs requiring intensive care unit admission. Cerebrospinal fluid analysis demonstrated lymphocytic pleocytosis and markedly elevated protein concentration, and VZV DNA was detected by polymerase chain reaction testing. During hospitalization, the patient developed severe urinary retention and gastrointestinal dysmotility without evidence of mechanical obstruction, raising concern for concurrent autonomic nervous system involvement. Following intravenous acyclovir therapy and supportive management, the patient experienced gradual neurologic and autonomic recovery. Conclusions: This case highlights the potential for multifocal neuroinvasive VZV disease involving both central and autonomic nervous system structures in immunocompetent hosts. Clinicians should maintain awareness that urinary retention and bowel dysmotility may represent clinically significant autonomic manifestations of VZV reactivation, particularly in the setting of sacral dermatomal involvement. Full article

Equine asthma is a chronic inflammatory disease of the lower respiratory tract, primarily associated with inhalation of organic dust, microbial particles and environmental aeroantigens. Although the inflammatory and immunological mechanisms underlying equine asthma have been extensively investigated, the potential contribution of neuroimmune pathways remains poorly understood. In humans and rodent models, asthma is increasingly recognised as a disorder involving complex bidirectional interactions between the nervous and immune systems. Sensory nerve activation, neuropeptide release, autonomic dysregulation and neuronal remodelling contribute to bronchoconstriction, airway hyperresponsiveness, mucus hypersecretion and chronic airway remodelling. This review summarises current knowledge of the neuroimmune mechanisms involved in asthma, with particular emphasis on comparative aspects across humans, rodents and horses. Literature searches were conducted using the PubMed database, focusing on studies investigating neurogenic inflammation, airway innervation, neuropeptides, transient receptor potential channels and neuronal remodelling in asthma and chronic airway disease. Existing equine evidence indicates the presence of substance P- and calcitonin gene-related peptide-immunoreactive nerve fibres in the equine airways, increased neurokinin-mediated bronchoconstriction in severe equine asthma, and enhanced airway innervation in affected horses. However, compared with human and rodent studies, horse-specific data remain extremely limited. Current evidence suggests that neuroimmune pathways are unlikely to be the primary initiating mechanism of equine asthma, but may act as important modulators of chronic airway dysfunction and disease progression. The marked scarcity of equine studies investigating neuroimmune signalling represents a major knowledge gap and highlights an important direction for future research in equine respiratory medicine. Full article

Temporomandibular disorder (TMD) and bruxism affect a significant portion of the adult population, yet why patients with comparable occlusal findings respond so differently to identical interventions remains unexplained by both structural and biopsychosocial frameworks. Traditional occlusal paradigms identified the importance of structural relationships but could not account for clinical variability. Biopsychosocial models advanced understanding of central regulation but lack the physiological specificity needed to connect regulatory state to functional jaw behavior. This paper proposes the Functional Occlusion Regulated Model (FORM), a hierarchical framework integrating central regulatory state, masticatory performance, and structure into a coherent model of jaw function, and identifies its clinical and research implications. Narrative synthesis of the peer-reviewed literature across masticatory physiology, autonomic neuroscience, pain neuroscience, and clinical dentistry was conducted; seventy-two references are cited. Converging evidence supports a three-tier hierarchy in which autonomic and neuromuscular regulatory state is proposed to shape masticatory performance, which influences how structural occlusal conditions are expressed and clinically experienced. FORM generates four testable predictions distinguishing it from existing models, and a preliminary clinical observation documents symptom resolution through regulatory intervention alone without occlusal modification, representing an early published dental observation of this connection. FORM provides a physiologically grounded framework for understanding treatment response variability and proposes central regulatory state as a potentially important upstream influence on functional jaw outcomes. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

Background: Sleep-disordered breathing (SDB) is frequently accompanied by autonomic nervous system (ANS) dysfunction, which is closely associated with an increased incidence of cardiovascular diseases and elevated mortality risk. Heart rate variability (HRV) serves as a classic metric for evaluating sympathovagal balance; however, the specific impacts of four distinct types of respiratory events—obstructive apnea (OA), central apnea (CA), mixed apnea (MA), and hypopnea (HYP)—on HRV remain underinvestigated. Utilizing ultra-short-term HRV analysis, this study aimed to evaluate the immediate effects of different respiratory events on ANS function, while further exploring the modulatory roles of arousal, Apnea–Hypopnea Index (AHI) severity and sleep stages (non-rapid eye movement [NREM] vs. rapid eye movement [REM]). Methods: A total of 108 patients with SDB undergoing overnight polysomnography (PSG) were included. A total of 19,862 respiratory events, including obstructive apnea (OA), central apnea (CA), mixed apnea (MA), and hypopnea (HYP), were analyzed using 15 s ECG segments. Linear mixed-effects models (LMMs) and estimated marginal means (EMMs) with Sidak-adjusted pairwise comparisons were constructed to evaluate differences in ECG-derived features and to analyze differences between event types. Results: Central apnea (CA) was associated with significantly reduced HRV and heart rate indices, including Standard Deviation of Successive Differences (SDSD), Root Mean Square of the Successive (RMSSD), Standard Deviation 1 (SD1), and heart rate (HR), compared with other respiratory event types (all p < 0.05). Across all event types, HRV metrics exhibited consistent dynamic changes before, during, and after respiratory events (all p < 0.001), characterized by a decrease during the event followed by post-event recovery. In the interaction effect of sleep stage, SDSD was significantly lower in CA compared with both OA (estimate = −11.67, 95% CI −18.78 to −4.59, p < 0.001) and HYP (estimate = −11.38, 95% CI −18.55 to −4.20, p < 0.001) during NREM sleep. No significant differences in HRV parameters, heart rate, or QRS duration were observed between OA and HYP (all p > 0.05). Conclusions: This study is the first to elucidate the differential impacts of four distinct types of sleep respiratory events on ultra-short-term HRV, confirming that CA events exert the most profound effects on autonomic function. These findings suggest that the proportion of CA occurrences could serve as a more precise biomarker for identifying individuals at high risk for cardiovascular diseases within the SDB population. Full article

This pilot study aimed to examine autonomic nervous system responses in student-athletes using heart rate variability (HRV) and skin conductance level (SCL) during sequential cognitive stressors, including a modified Stroop test and a mental math task. Fifty-two university athletes (mean age = 21.7 ± 2.8 years) participated in this repeated-measures experimental study. HRV and SCL were recorded at baseline, during each stressor, and throughout the recovery periods following each task. Repeated-measures ANOVA revealed significantly elevated SCL across experimental conditions [F(2.09, 100.53) = 45.69, p < 0.001, η² = 0.488], which remained above baseline during recovery, indicating sustained sympathetic activation. HR also increased significantly during stress exposure, indicating increased autonomic activation during cognitive stress [F(2, 103.11) = 14.30, p < 0.001, η² = 0.230]. Contrary to the initial hypothesis, vagally mediated HRV indices, including RMSSD [F(2.73, 131.11) = 6.88, p < 0.001, η² = 0.125] and HF power [F(2.85, 136.99) = 16.86, p < 0.001, η² = 0.260], increased during cognitive stress, suggesting adaptive parasympathetic modulation rather than vagal withdrawal. These findings indicate that autonomic responses to cognitive stress in athletes may involve simultaneous sympathetic and parasympathetic activation rather than a simple vagal withdrawal response. Overall, the findings only partially supported the initial hypotheses. Despite limitations related to sample size and short recording periods, the present findings highlight the importance of evaluating HRV and SCL together when examining psychophysiological stress responses in athletic populations. Full article

Perioperative anxiety is a common psychophysiological stress response experienced by patients before and after surgery, with a global prevalence of approximately 48%. Its occurrence is influenced by multiple factors including age, sex, type of surgery, and psychosocial determinants. The underlying pathophysiological mechanisms are complex, involving multi-system interactions such as autonomic nervous system imbalance, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, dysfunction of limbic system neural circuits, and neuroinflammation. Current assessment strategies are evolving from sole reliance on psychological scales toward multimodal approaches incorporating objective biomarkers including heart rate variability, cortisol, and electroencephalography. Management paradigms have shifted from traditional pharmacological premedication to integrated systems encompassing structured patient education, digital health tools, neuromodulation techniques, and cognitive behavioral therapy. However, significant gaps persist regarding standardized screening protocols, biomarker validation, and targeted intervention pathways for high-risk populations. Future management is likely to require more individualized risk assessment and intervention selection. Biomarker-based risk prediction, artificial intelligence-assisted intervention decision-making, and the deep integration of digital therapeutics such as virtual reality with existing enhanced recovery pathways will be key directions for improving patient outcomes and recovery quality. This structured narrative review summarizes current evidence on perioperative anxiety in adults, focusing on epidemiology, pathophysiological mechanisms, assessment tools, biomarkers, and multimodal management strategies. Full article

Considerable efforts have been devoted to accurately monitoring the depth of anesthesia to ensure patient safety during surgery. Traditional approaches typically rely on electroencephalogram (EEG)-based indices, such as the Bispectral Index (BIS), which require specialized equipment. In contrast, electrocardiogram (ECG) signals are widely available in clinical settings and can be conveniently acquired via wearable devices, while also exhibiting strong responsiveness to anesthetic agents. Inspired by biomimetic physiological regulation mechanisms, this study proposes a wearable-compatible ECG-based framework for depth-of-anesthesia detection that leverages autonomic nervous system characteristics and a knowledge graph-enhanced graph convolutional network (GCN). ECG recordings from 110 patients were preprocessed, and 20 anesthesia-related features were extracted, spanning morphological, statistical, spectral, heart rate variability (HRV), and entropy-based descriptors; feature selection methods identified 13 discriminative features. A patient-level knowledge graph was first constructed using the 88 training patients (1760 nodes), and test patient nodes were incorporated only after training was complete for inductive inference. Experimental results demonstrate that the proposed deep knowledge GCN achieves a test accuracy of 98.18% in distinguishing between awake and deep sleep anesthesia states, indicating that biomimetic, wearable-compatible ECG analysis combined with knowledge graph learning holds strong potential as a cost-effective alternative to traditional EEG-based anesthesia monitoring systems. Full article

Background: Fatigued driving is a key contributing factor to major traffic accidents. Existing detection technologies suffer from issues such as delayed identification, high error rates, and a lack of quantified causal relationships between physiological and behavioral indicators. This study aims to clarify the intrinsic relationship between electrophysiological and driving behavior data during the progression of driving fatigue. Methods: Four categories of driving behavior data and electrocardiographic (ECG) heart rate variability (HRV) indicators were selected as the study subjects. Based on a four-stage standardized simulated driving experiment ranging from wakefulness to severe fatigue, the correlations between indicators were quantified using Pearson correlation analysis, and a four-layer physiological–behavioral fusion fatigue assessment model was constructed. Results: Autonomic dysregulation is the intrinsic cause of abnormal driving behavior. The two exhibit a highly synchronized, stepwise progressive evolution pattern, with |r| ≥ 0.75 among core indicators. The accuracy of the constructed model exceeded 90% for all fatigue stages, reaching 97.8% for severe fatigue detection, with a response time of ≤0.5 s. Conclusions: This model effectively addresses the limitations of single-monitoring technologies and provides theoretical support and technical guidance for multimodal identification and graded early warning of driving fatigue. Full article

Objectives: Summer heat can impair sleep and contribute to autonomic dysregulation and fatigue-related symptoms. Because heat exposure may induce oxidative stress and gut-related dysfunction, we hypothesized that combined intake of the probiotic Lacticaseibacillus paracasei subsp. paracasei NY1301 and the antioxidant 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) would improve sleep, fatigue, and autonomic recovery during the summer. Methods: In this randomized, double-blind, placebo-controlled, parallel-group trial, 171 healthy adults were administered a beverage containing NY1301 and DDMP or placebo once daily for 8 weeks during the summer. The primary outcome was subjective fatigue assessed by a web-based daily log. Secondary outcomes included visual analog scale (VAS) fatigue scores, weekly questionnaire items, sleep parameters, and heart rate variability before and after mental arithmetic tasks. Results: No statistically significant between-group difference was observed in the primary outcome, subjective fatigue assessed using the web-based daily log. However, among secondary outcomes, sleep onset latency at week 8 was significantly shorter in the NY1301 + DDMP group (mean difference: −2.07 min, 95% CI −3.96 to −0.17; p = 0.033), and pre-task fatigue VAS at week 8 was lower (mean difference: −6.79, 95% CI −13.6 to −0.3; p = 0.047). At week 8, the NY1301 + DDMP group showed a greater increase in LF/HF during the task (mean difference: 1.32, 95% CI 0.06 to 2.58; p = 0.040), greater decrease in LF/HF during recovery (mean difference: −1.34, 95% CI −2.39 to −0.30; p = 0.012), and greater increase in HF during recovery (mean difference: 140, 95% CI 43 to 239; p = 0.005). In an exploratory analysis, the temperature-associated rise in nocturnal respiratory rate was significantly attenuated in the NY1301 + DDMP group (group × temperature interaction, p < 0.05). Conclusions: The primary outcome, subjective fatigue assessed using the web-based daily log, was not significantly different between groups during the summer study period. However, combined intake of NY1301 and DDMP was associated with shorter sleep onset latency, lower pre-task fatigue under standardized conditions, attenuation of the temperature-associated rise in nocturnal respiratory rate, and more pronounced post-stress autonomic recovery during the summer. These findings suggest a potential physiological benefit of this combined nutritional approach under summer conditions and warrant confirmation in independent trials. The study was funded by Nissin York Co., Ltd., and potential conflicts of interest related to sponsor-affiliated authors are disclosed in the manuscript. Full article

Background: The use of wearable sensors to measure and monitor heart rate has exponentially grown in recent years, representing an inexpensive, time-efficient, and non-invasive method to assess the status of cardiovascular fitness and the autonomic nervous system. Validating new devices against a criterion standard, such as electrocardiography (ECG), is essential to ensure their accuracy and reliability. This study examined the accuracy and validity of the Prevayl heart rate monitor against 3-lead ECG. Methods: Twenty-six healthy adults (15 female, mean age 32.0 ± 10.4 years) completed a 16-min, incremental running test on a treadmill. Heart rate data were recorded simultaneously throughout the test via ECG and the Prevayl wearable and compared retrospectively. Beat count error (%), mean heart rate absolute error (beats per minute (bpm)), and percentage error (bpm) were calculated. In addition, a Bland–Altman analysis and Pearson’s correlation coefficient were conducted to assess agreement and correlation, respectively. Results: The Prevayl device demonstrated a median beat count agreement of 100.5% with ECG (range: 98.6–104.4%; N_part = 26). Strong correlations were observed between ECG and Prevayl for both raw beat count (r = 0.94, p < 0.01) and heart rate (beats per minute (bpm)) from ECG and the Prevayl algorithm (r = 0.96, p < 0.01). Across running speeds (0–12 kph), a strong correlation was found between raw beat count from ECG and Prevayl (r = 0.82–0.89, p < 0.01) and between bpm from ECG and Prevayl (r = 0.86–0.93, p < 0.01). Bland–Altman plots demonstrated negligible systematic bias. Conclusions: The Prevayl system provides valid measurements when compared to ECG during incremental running. This is demonstrated through strong correlations to ECG heart rate data at different speeds and with different analysis methods, supporting its use for monitoring cardiovascular responses during exercise. Full article

Medical workers are frequently exposed to high-stress environments, highlighting the need for non-invasive stress monitoring strategies based on autonomic nervous system activity. Ammonia emitted from the human skin surface has been reported to increase under physical and psychological stress; however, its relationship with autonomic nervous system (ANS) dynamics remains unclear. In this study, we performed simultaneous, time-resolved measurements of dermal ammonia emission and heart rate variability (HRV) in 11 medical workers during 3 h of routine work. Dermal ammonia emission flux was continuously monitored using a passive flux sampler (PFS) coupled with ion chromatography, while autonomic nervous system activity was assessed by Holter electrocardiography. The temporal profiles of ammonia emission were analyzed in relation to HRV indices, including high frequency (HF) and the low-frequency-to-high-frequency ratio (LF/HF). Dermal ammonia emission increased under conditions characterized by lower HF and/or higher LF/HF, whereas elevated HF was associated with reduced ammonia emission (r = −0.47, p < 0.001). Furthermore, temporal fluctuations in ammonia emission were associated with sympathetic–parasympathetic switching. These findings suggest that dermal ammonia emission may be associated with HRV-related physiological responses under real-world working conditions and may have potential as a non-invasive indicator for stress-related physiological monitoring. Full article

Acetylcholine (ACh) is an evolutionarily conserved neurotransmitter that is widely distributed in the central and peripheral nervous systems and plays essential roles in multiple physiological processes. This review summarizes the full biological cycle of ACh, including its synthesis, vesicular storage, release, degradation, and reuptake, and discusses the regulatory mechanisms underlying its functions in the nervous system and peripheral organs. Through nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), ACh is involved in central nervous system functions such as cognition, learning and memory, attention, arousal, reward, and decision-making, as well as peripheral processes including motor control, autonomic regulation, and immune modulation. In addition, ACh plays a pivotal role in the brain–body axis. At the central level, the nervous system regulates peripheral organ function through autonomic and neuroendocrine pathways. At the peripheral level, cholinergic signals derived from the enteric nervous system and immune cells convey information about the body’s internal state to the central nervous system through vagal and other afferent pathways, forming an important bottom-up regulatory network. Collectively, these findings indicate that ACh is not only a classical neurotransmitter but also a key molecular mediator of brain–body communication. A more comprehensive understanding of cholinergic signaling may provide new insights into physiological regulation and the pathogenesis of neurological, psychiatric, cardiovascular, and inflammatory diseases. Full article

Background/Objectives: Post-COVID syndrome (PCS) is frequently associated with persistent cognitive complaints such as fatigue and impaired concentration, yet objective markers related to cognitive dysfunction are lacking. Pupillary oscillation metrics have emerged as non-invasive indicators of task-related cognitive load and autonomic regulation. This study investigated the Index of Pupillary Activity (IPA) and the Low/High Index of Pupillary Activity (LHIPA) in a large cohort of patients with PCS compared with healthy controls. Methods: In this cross-sectional study, 526 participants (397 PCS patients, 129 controls) performed a standardized virtual reality-based stereoscopic task at three disparity levels: 275 arcsec (high difficulty), 550 arcsec (medium difficulty), and 1100 arcsec (low difficulty), using a head-mounted display with integrated eye tracking. Continuous pupillometry data were recorded, and IPA and LHIPA were calculated. Linear mixed-effects models with random intercepts for participants were applied, adjusting for age, sex, and task difficulty. Results: Both IPA and LHIPA were significantly lower in PCS patients than in controls at all three task difficulty levels in post hoc model-based contrasts. In adjusted mixed-effects models, PCS was also associated with lower overall IPA ($\beta =-0.111$, 95% CI $-0.160$ to $-0.062$, $p<0.001$) and lower overall LHIPA ($\beta =-0.164$, 95% CI $-0.253$ to $-0.074$, $p<0.001$). Lower task difficulty was associated with higher values of both metrics: for IPA, $\beta =0.164$ at 550 arcsec and $\beta =0.287$ at 1100 arcsec (both $p<0.001$); for LHIPA, $\beta =0.161$ at 550 arcsec and $\beta =0.254$ at 1100 arcsec (both $p<0.001$), relative to 275 arcsec. Thus, both indices showed an inverse association with task difficulty. Age was negatively associated with both metrics, whereas male sex was positively associated with both. No significant interaction between cohort and task difficulty was observed. Conclusions: PCS was associated with reduced IPA and LHIPA during a standardized stereoscopic task. These findings indicate altered task-related pupillary dynamics in PCS and may reflect altered cognitive-load processing and autonomic regulation. LHIPA, and with caution also IPA, may contribute to the objective assessment of task-related pupillary alterations in PCS. Full article