Search Results (513)

Background/Objectives: Hypertension is associated with abnormal bone metabolism and enhanced bone resorption, and altered sympathetic/adrenergic signaling has been proposed as one contributing mechanism. Orthodontically induced inflammatory root resorption (OIRR) involves periodontal ligament inflammation, odontoclast induction, and the resorption of cementum and dentin. This study investigated whether the SHR phenotype is associated with greater OIRR and whether the pharmacological blockade of β2-adrenergic receptor (β2-AR) signaling with butoxamine (BTX) modulates these changes. Methods: A 50 gf Ni-Ti closed-coil spring was placed between the maxillary incisors and left first molar in SHRs and Wistar–Kyoto (WKY) rats for 21 days, beginning 7 days after BTX administration. Animals were assigned to WKY(control), WKY(BTX), SHR(control), and SHR(BTX) groups. The tooth-movement distance, root length, and root volume were assessed via micro-computed tomography. The odontoclast number and surface, TNF-α, IL-1β, and β2-AR immunoreactivity, cementocyte density, empty lacunae ratio, and TUNEL-positive cells within cementocyte lacunae were evaluated histologically. Results: Compared with WKY(control), SHR(control) showed greater tooth movement, a reduced root length and volume, an increased odontoclast number and surface, greater TNF-α- and IL-1β-positive areas, a lower cementocyte density, a higher empty lacunae ratio, and more TUNEL-positive cells within cementocyte lacunae. These root resorption- and inflammation-related changes were significantly attenuated in SHR(BTX) compared with SHR(control). Conclusions: The SHR phenotype was associated with increased OIRR, and the attenuation observed following β2-AR blockade supports a potential contribution of adrenergic signaling to this response. Full article

Hypertension remains the leading modifiable cause of cardiovascular death, yet fewer than one in four treated adults achieves guideline-recommended blood pressure targets. Catheter-based renal denervation interrupts efferent and afferent renal sympathetic signalling and lowers blood pressure continuously and independently of medication adherence. After a decade of controversy following the neutral SYMPLICITY HTN-3 trial, a coherent body of second-generation sham-controlled randomised evidence, generated with radiofrequency, endovascular ultrasound, and perivascular alcohol platforms, has established a reproducible, modest, and durable antihypertensive effect with a favourable safety profile. Between 2024 and 2026, the field crossed three thresholds simultaneously: guideline endorsement on both sides of the Atlantic, including the first United States recommendation in the 2025 AHA/ACC guideline; a national coverage determination with coverage with evidence development; and the maturation of randomised and real-world follow-up to three years in cohorts exceeding 3000 patients. This state-of-the-art review synthesises the contemporary evidence base; quantifies the expected treatment effect and its heterogeneity; appraises safety across renal and vascular domains; examines emerging data in chronic kidney disease, diabetes, heart failure, and atrial fibrillation; and details the practical requirements for delivering renal denervation responsibly. We conclude by defining the research agenda that must now be addressed: the identification of responders, the development of an intraprocedural endpoint, a direct comparison with newly approved pharmacotherapy, and evidence of cardiovascular event reduction. Full article

Alzheimer’s disease (AD), the leading cause of dementia, lacks an inexpensive and non-invasive method for early detection. Here, we investigate whether electrodermal activity (EDA), a measure of changes in electrical conductance at the skin’s surface, can offer a convenient avenue for AD screening by capturing the autonomic dysfunction associated with the disease’s pathology. As few studies have comprehensively examined EDA’s utility as a standalone biomarker for AD, we conducted a pilot study with 10 cognitively healthy controls and 20 patients with AD, evaluating EDA recordings collected during an orthostatic test and a Montreal Cognitive Assessment (MoCA). The AD group included both carriers from Colombian kindreds affected by autosomal-dominant AD and patients with sporadic late-onset AD. We compared EDA features between groups using statistical analysis and tested whether machine learning models could separate the two groups using these features. During the MoCA, phasic EDA measures, specifically the number of skin conductance responses (NSSCR) and mean time-variant sympathetic tone (TVSymp), were significantly lower in the AD group than in controls (NSSCR: $p=0.0083$, Cohen’s $d=-1.07$; mean TVSymp: $p=0.0166$, $d=-0.96$), suggesting a blunted sympathetic response to cognitive stress in AD. No significant between-group differences were observed during the orthostatic test (all $p\ge 0.60$). A random forest classifier trained on MoCA-derived EDA features achieved a balanced accuracy of 78% (95% CI 60 to 93%; 75% sensitivity, 80% specificity, AUROC 0.75), with phasic features contributing most to performance. Performance did not differ significantly from that of the support vector machine or logistic regression models. These results provide preliminary, hypothesis-generating evidence for the utility of EDA in screening for AD. The small sample size, unequal group allocation, sex imbalance, and substantial mean age disparity between groups (≈23.5 years) limit the strength of these conclusions and necessitate replication in larger, age- and sex-matched cohorts that include prodromal stages. Full article

Vagal afferent stimulation exerts potent anti-inflammatory effects through neuroimmune pathways involving the sympathetic nervous system and spleen. However, how vagal afferent stimulation affects splenic responses and CellTrace-positive signals in inflamed tissues remains unclear. In this study, we investigated the effects of vagal afferent electrical stimulation (aVNS) on splenic responses and acute lung inflammation induced by intratracheal lipopolysaccharide (LPS) in mice. As a preconditioning intervention, aVNS was applied to the right cervical vagus nerve 24 h before LPS administration. Pulmonary inflammation was evaluated by measuring tumor necrosis factor-α (TNF-α) levels in bronchoalveolar lavage fluid. Splenic responses were assessed by measuring spleen weight, and CellTrace-positive signals were evaluated following direct intrasplenic injection of CellTrace™ Far Red. aVNS significantly reduced BALF TNF-α levels (sham: 5443 ± 404 pg/mL, n = 5; aVNS: 2891 ± 756 pg/mL, n = 5) following LPS administration. In addition, aVNS reduced spleen weight 24 h after stimulation. Furthermore, the ratio of CellTrace Far Red-positive cells was significantly higher in the aVNS + LPS group than in the sham + LPS group (0.00504 ± 0.00056 vs. 0.00151 ± 0.00017, n = 4 per group). These findings indicate that vagal afferent stimulation reduces the BALF TNF-α response to LPS and is associated with reduced spleen weight and increased CellTrace-positive objects detected in lung sections. These observations suggest that changes in splenic and immune-cell dynamics may accompany the anti-inflammatory effects of vagal afferent stimulation. Full article

Background and Objectives: Postoperative pain after major cancer surgery contributes to pulmonary, cardiovascular, metabolic, and functional complications. Thoracic epidural analgesia [TEA] has traditionally been considered the standard analgesic technique for open thoracic and upper abdominal oncologic surgery, although minimally invasive techniques and ERAS pathways have prompted a re-evaluation of its role. Methods: This narrative review summarizes evidence from PubMed and MEDLINE published between 1995 and June 2026, emphasizing randomized trials, systematic reviews, meta-analyses, large observational studies, and selected work by the authors. Results: TEA provides superior dynamic analgesia and reduces opioid consumption, facilitating early mobilization, respiratory recovery, and gastrointestinal function. By attenuating sympathetic and neuroendocrine stress responses, it may contribute to reductions in pulmonary complications, ileus, insulin resistance, and delirium, particularly in elderly, frail, sarcopenic, and high-risk patients. Limitations include hypotension, urinary retention, technical failure, and rare but potentially serious complications such as epidural hematoma. In minimally invasive surgery, alternative regional techniques and multimodal opioid-sparing analgesia often achieve comparable postoperative outcomes with fewer hemodynamic effects, supporting selective rather than routine TEA use. Although neuraxial techniques may have immunomodulatory effects and potentially preserve immune function, randomized studies have not demonstrated a reduction in cancer recurrence or an improvement in long-term survival. Conclusions: TEA remains an effective analgesic strategy for selected patients undergoing major open thoracic and upper abdominal cancer surgery. In contemporary perioperative practice, its use should be individualized according to surgical invasiveness, patient characteristics and expected postoperative pain. Current evidence supports TEA primarily as a perioperative analgesic and recovery strategy, with no established oncologic benefit. Full article

Chronic heart failure (CHF) is a growing global health concern characterized, in part, by progressive sympathetic overactivation, which exacerbates this condition. Accumulating evidence identifies oxidative stress as a key driver of sympatho-excitation, mediated by excess reactive oxygen species (ROS) and impaired antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) is a central regulator of antioxidant gene expression, but its role in the peripheral sympathetic nervous system, particularly in the stellate ganglia, remains unclear. We hypothesized that Nrf2 signaling is disrupted in the stellate ganglia in CHF and that modulation of Nrf2 alters ROS levels and sympathetic responses. In rats, six weeks post myocardial infarction (MI), the stellate ganglia exhibited increased ROS levels in tyrosine hydroxylase-positive neurons along with reduced Nrf2 protein and mRNA expression; both changes were inversely associated with ejection fraction (EF). To determine the functional role of Nrf2, lentiviral vectors encoding GFP or GFP-Nrf2 were delivered to the stellate ganglia three weeks after MI. Nrf2 upregulation attenuated heart rate responses to stellate stimulation in sham rats but augmented responses in CHF rats. The increase in plasma norepinephrine levels was reduced following stellate stimulation in CHF rats that overexpressed Nrf2, while β1-adrenergic responsiveness to dobutamine was unchanged. This study demonstrates that CHF is associated with increased oxidative stress and reduced Nrf2 expression in the stellate ganglion. Nrf2 overexpression significantly modulated sympathetic regulation, altering heart rate responses and reducing plasma norepinephrine in CHF rats. These findings support the concept that impaired Nrf2 signaling contributes to ganglionic redox imbalance and dysregulated sympathetic nerve activity in CHF. Full article

Purpose: Acute exercise elicits coordinated neuroendocrine and autonomic responses that are strongly influenced by exercise modality and intensity. While cortisol and salivary alpha-amylase are widely used as peripheral indicators of hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system activation, respectively, salivary orexin remains an exploratory biomarker whose relationship with central orexinergic activity is not yet fully established, particularly in response to different exercise conditions. This study aimed to compare the acute salivary responses of orexin, alpha-amylase, and cortisol following distinct exercise modalities characterized by different physiological loads. Methods: A repeated-measures design was employed in a sample of physically active young women. Each participant completed four experimental sessions: high-intensity interval training (HIIT), combined exercise (CE), moderate-intensity continuous training (MICT), and yoga. Saliva samples were collected at baseline (T0), immediately post-exercise (T1), and during early recovery (T2 and T3). Biomarker concentrations were analyzed to assess temporal dynamics and modality-dependent differences. Results: All biomarkers showed modality-dependent responses. HIIT elicited the most pronounced increases in alpha-amylase and cortisol, reflecting robust sympathetic and HPA axis activation, whereas CE and MICT induced more moderate responses. Yoga was associated with minimal changes across all biomarkers. Orexin displayed a graded response across the exercise modalities, with higher post-exercise levels observed following HIIT compared to lower-intensity conditions. Temporal analyses revealed distinct kinetic profiles, with alpha-amylase peaking rapidly in the early post-exercise phase, whereas cortisol exhibited a more delayed response. Conclusions: These findings demonstrate that acute salivary responses of orexin, alpha-amylase, and cortisol are strongly modulated by exercise modality, supporting the importance of an integrated, multi-biomarker approach to characterize the physiological response to exercise. The inclusion of salivary orexin provides exploratory information on a potentially relevant arousal- and energy-regulation-related pathway, complementing established peripheral markers of autonomic and endocrine activation. This integrated perspective may contribute to a more comprehensive understanding of exercise-induced stress responses in young women. Full article

Background/Objectives: Paragangliomas (PGLs) are rare neuroendocrine tumors, and data describing them from a medical oncology perspective are limited. We characterized clinicopathological features, tumor localization, and treatment outcomes. Methods: We retrospectively analyzed 43 patients with PGL at a single medical oncology department. The primary endpoint was recurrence-free survival (RFS), defined as time to first recurrence or death from any cause; overall survival (OS), objective response rate (ORR), disease control rate (DCR), and prognostic associations were secondary. Results: Median age was 44 years, 60.5% were female, and tumors were sympathetic (extra-adrenal) in 55.8% and parasympathetic (head and neck) in 39.5%. After a median follow-up of 116.8 months, 40 patients (93.0%) underwent resection, among whom 14 RFS events occurred (13 recurrences, 1 unrelated death). Median RFS and OS were not reached (60-month RFS, 67.1%; 120-month OS, 83.3%). Among nine patients receiving first-line systemic therapy (eight response-evaluable), ORR was 12.5% and DCR 37.5%. In exploratory univariable analysis, a Ki-67 index ≥ 3% correlated with recurrence (time-averaged hazard ratio, 4.53; 95% CI, 1.55–13.19; p = 0.006), alongside an R1 resection margin (not significant after Bonferroni correction). Conclusions: These findings may support further evaluation of Ki-67 within risk-adapted surveillance but do not replace germline testing. Full article

Background: The autonomic nervous system (ANS) in individuals with obsessive–compulsive disorder (OCD) is often characterized by heightened sympathetic tone and reduced parasympathetic flexibility. This exploratory pilot study aimed to provide a detailed, dynamic portrait of autonomic dysregulation. Methods: Heart rate variability (HRV), galvanic skin response (GSR), and oculomotor measures (pupil size, fixations, saccade velocity) were recorded in 31 participants with OCD (obsessive–compulsive disorder) and 46 healthy controls while viewing 18 videos, half of them designed to trigger specific OCD dimensions and half neutral or positive. Results: The OCD group exhibited a state of sympathetic hyperactivation, evidenced by significantly lower mean NN intervals (average interval between normal heartbeats) and a distinct GSR (galvanic skin response) pattern marked by a rising tonic component across the experiment. Healthy controls exhibited increases in SDNN (standard deviation of NN intervals) and RMSSD (root mean square of successive differences) following pleasant videos, whereas this response was less pronounced and emerged later in the OCD group, suggesting reduced autonomic flexibility. Oculomotor data revealed faster saccade velocities during video viewing in the OCD group; however, unlike controls, their eye movements did not correlate with the pleasantness of the content. Conclusions: These results support the theory that individuals with OCD may exhibit greater sympathetic activation and delayed parasympathetic engagement. The findings suggest that autonomic inflexibility may be a core, measurable feature of OCD. Full article

Electrodermal activity (EDA) has emerged as a promising physiological measure for objectively assessing neurodevelopmental disorders (NDDs) and related disorders, yet its effectiveness across conditions remains unclear. Following PRISMA guidelines, this review analyzed 23 studies (ASD: 11 studies, 410 participants; ADHD: 7 studies, 900 participants; OCD: 5 studies, 154 participants) published between 2010 and 2024 with a focus on methodology, including measurement protocols, signal processing, and analytical approaches. EDA demonstrated utility for diagnostic differentiation, predictive modeling, and physiological evaluation across conditions, with consistent patterns of heightened social arousal in ASD, medication-responsive sympathetic differences in ADHD, and impaired fear extinction in OCD. Machine learning approaches improved performance when combining EDA with multimodal physiological measures. However, substantial methodological heterogeneity existed across devices, recording sites, sampling frequencies, and signal processing, with 11 studies lacking signal processing details and 10 omitting sampling frequencies. The absence of standardized cross-disorder comparisons limited identification of disorder-specific versus shared autonomic signatures. While wearable technologies can enable continuous real-world monitoring, motion artifacts and signal quality remain challenges. Overall, standardized protocols and larger multimodal longitudinal studies are needed to establish EDA as a clinically useful biomarker for disorder assessment and personalized interventions. Full article

Background/Objectives: Guillain–Barré syndrome (GBS) is an acute immune-mediated disorder of the peripheral nervous system. Autonomic involvement in GBS occurs during the acute phase and may persist into the recovery phase. This study aimed to investigate the autonomic nervous system’s function in GBS sufferers. Methods: A cross-sectional exploratory study was conducted at the Clinical Neurophysiology Laboratory, Medical School, University of Cyprus. Eligible patients were previously hospitalized with GBS. Autonomic nervous system assessment included the Ewing battery using the Finapres Nova system as well as sudomotor assessment. Results: Seventeen patients were recruited (53% female; mean age 58.7 ± 14.1 years). The mean follow-up time since diagnosis was 15.5 ± 13.2 months (range 1–45 months). At follow-up, 4/17 patients (24%) demonstrated an abnormal heart rate (HR) response to standing, 3/17 patients (18%) exhibited an abnormal systolic blood pressure (BP) response to standing, and 4/17 patients (24%) exhibited an abnormal diastolic BP response to standing. One patient (6%) demonstrated an abnormal HR response during deep breathing, while another showed an abnormal diastolic BP response during the handgrip test. Overall, 6/17 patients (35%) showed abnormal findings in at least one component of the Ewing battery, and 3/17 (18%) fulfilled the criteria for definite generalised dysautonomia. Two patients (12%) demonstrated abnormal sympathetic skin response (SSR) results; both fulfilling the criteria for dysautonomia based on the Ewing battery. Conclusions: Autonomic dysfunction may be present in GBS patients beyond the acute phase, even in the absence of overt autonomic symptoms. Larger prospective studies with serial autonomic assessments are required to better characterise the long-term course and clinical significance of dysautonomia in GBS. Full article

Psychological stress arises when individuals perceive demands as exceeding their capacity to cope. Social stress can be acute, such as giving a presentation, producing transient increases in heart rate, blood pressure, and neuroendocrine activation, or chronic, in which stressors persist over extended periods. Chronic psychosocial stress disrupts immune homeostasis and contributes to anxiety, depression, and post-traumatic stress, while also increasing risk for infections, inflammatory and autoimmune diseases, cardiovascular disease, metabolic dysfunction, and cancer. Persistent stress engages interconnected neuroendocrine–immune networks, including the hypothalamic–pituitary–adrenal axis, the sympathetic–adrenomedullary system, and the gut microbiota–brain–immune axis, leading to sustained glucocorticoid and catecholamine signaling, gut dysbiosis, impaired barrier integrity, and altered microbial metabolite profiles. In this review, we summarize the molecular and cellular mechanisms by which these axes remodel innate and adaptive immunity and shape disease susceptibility. Using social defeat and social isolation in mice as model systems, we highlight how chronic social stress reprograms immune responses in key tissues, including the lung, brain, and gut. Full article

Background: This study investigates the psychophysiological stress profiles of professional basketball players by simultaneously analyzing two distinct neuroendocrine pathways: the sympathetic–adrenal–medullary (SAM) system, via salivary alpha-amylase (AA), and the hypothalamic–pituitary–adrenal (HPA) axis, via salivary cortisol (C). While competitive environments are known to elicit significant stress, the interaction between game-specific variables—such as playing time (PT) and tactical position—and those biomarkers remains insufficiently explored in real-time, official match settings. Methods: Twelve professional male basketball players were monitored across four official matches. Salivary samples were collected, and stress biomarkers (AA and C) were analyzed at three timepoints: pre-match, half-time, and post-match. Results: Results indicate that stress responses are non-uniform and highly context-dependent. A significant spike in AA was observed during the first match (p < 0.001; ES = 0.82; 95% CI −0.01–1.66), where concentrations rose from a pre-match mean of 247.9 ± 232.59 U/mL to a post-match peak of 674.39 ± 693.33 U/mL. Cortisol responses did not vary significantly across matches but exhibited a strong positive correlation with PT (p = 0.01; R = 0.76), identifying that C may serve as a primary marker of individual physical workload. Positional analysis revealed significant divergence in HPA activation; guards (0.55 ± 0.31 µg/dL) and centers (0.51 ± 0.22 µg/dL) exhibited higher cortisol levels compared to forwards (0.24 ± 0.18 µg/dL), reflecting the high cognitive/decision-making load of guards and the mechanical/physical contact load of centers. Conclusions: The observed differences in AA and C liberation suggest that stress responses during matches are influenced by a complex interaction of physiological and psychological stimuli characteristic of competitive basketball. Consequently, these findings indicate the importance and value of a dual-biomarker approach which might provide a framework for optimized training load management and recovery protocols in elite basketball. Full article

Internalized weight stigma is related to psychological and physiological consequences independent of actual weight status. However, as peers assume an increasingly important role in early adolescence, peer support may protect adolescents from the related costs of weight stigma. The current study examines concurrent associations between internalized weight stigma and heart rate variability in response to an acute stressor in a non-clinical early adolescent sample using a novel peer-to-peer discussion task. We hypothesized that peer acceptance will moderate the effect of internalized weight stigma on changes in sympathetic and parasympathetic indices of HRV. The study included 31 adolescents (58.1% boys; M_age = 12.82, SD_age = 1.00) from a charter middle school who completed self-report questionnaires to assess internalized weight stigma and perceived peer acceptance. Participants also completed a novel peer-to-peer discussion task to induce stress responses. Heart rate variability (HRV) was recorded during the baseline and the discussion task, and baseline-to-task change scores were used as an index of sympathetic and parasympathetic responses. Peer acceptance significantly moderated the association between internalized weight stigma and sympathetic reactivity (∆r² = 0.07, B = −0.97 *, p < 0.05). Specifically, only for adolescents with low peer acceptance, increased internalized weight stigma predicted heightened sympathetic reactivity (B = 0.84, p = 0.03). The findings of this study support the development of a novel peer-to-peer discussion task as an acute stressor and suggest that peer acceptance may alter the association between internalized weight stigma and physiological stress reactivity. Full article

European wild ungulates are captured for different purposes, requiring the assessment of animal welfare and health. Specific guidelines to assess stress and pathophysiological compromise in captured wild ungulates are lacking. This review aims to set the bases for establishing standardised protocols allowing the evaluation of capture and handling stress in wild European ungulates. Physical and chemical capture and handling elicit stress, a physiological response activating sympathetic–adrenal medulla and hypothalamic–pituitary–adrenal cortex axes, releasing catecholamines and corticosteroids, respectively. While being an adaptive response, if prolonged over time, the effects become harmful and life-threatening, increasing body temperature and heart rate, and provoking muscular and renal ischemia. This clinical outcome is known as capture myopathy, which encompasses four sequential syndromes: Hyper acute or capture shock, Acute or ataxic-myoglobinuric, Sub-acute or ruptured muscle, and Chronic debility or delayed per-acute. Monitoring temperature, heart rate, serum muscular enzyme (CK, AST, ALT, and LDH) activities and lactate, creatinine, urea, and potassium concentrations characterises pathophysiological compromise. Wild ungulate capture and handling protocols should include not only methodology but also monitoring, data recording, sample collection, and analyses. This information should serve to improve protocols and eventually develop specific guidelines for stress and welfare assessment when capturing and handling wild ungulates. Full article