Search Results (1,269)

The treatment of central nervous system (CNS) autoimmune diseases has evolved from broad immunosuppression toward targeted disease-modifying therapies (DMTs). While current DMTs effectively control inflammatory activity in many patients, unmet needs remain, including persistent compartmentalised CNS pathology, limited tissue penetration, and the cumulative burden of chronic therapy. Chimeric antigen receptor (CAR) T-cell therapy represents a novel “living” immunotherapy capable of antigen-specific cellular depletion. Although currently approved only for B-cell malignancies, CAR T-cells are increasingly being explored in CNS autoimmunity leveraging their capacity for autonomous cytotoxicity and expected access to immune cells within protected CNS niches following a potentially single intervention. In this review, we examine CAR T-cells in the context of CNS-autoimmunity, we outline principles derived from oncologic applications, assess current DMTs, their limitations and side effects, and define parameters where CAR T-cells may offer added value. We discuss biological and practical requirements for broader clinical application, as currently they are investigated only for the very severe and refractory cases where all alternative treatments have failed. We further review the plasticity of CAR constructs, distinguishing clinically advanced platforms from early proof-of-concept approaches. Finally, we summarise clinical experience from 15 patients with CNS autoimmunity treated with CAR T-cells and review ongoing or planned trials that include such patients. We conclude that CAR T-cell therapy remains investigational for severe, treatment-refractory disease, with future applicability dependent on demonstrable efficacy, safety, cost, and feasibility beyond existing DMTs. Full article

Heart rate (HR), a non-invasive indicator of physiological arousal and autonomic nervous system engagement, is widely used in cognitive and affective sciences to monitor individual responses and interpersonal synchrony in dynamic emotional and social contexts. Recent advances in wearable sensors have enabled researchers to assess HR synchrony in ecologically valid settings. In this study, we replicate prior validations of the Polar H10 chest strap for individual HR measurement and extend these findings by evaluating its validity for measuring HR synchrony between individuals. Dyads completed a previously validated experimental task designed to elicit HR fluctuations while jointly attending to emotionally evocative, 5-min audiovisual stimuli. First, we observed high correspondence (Pearson’s r > 0.99) between the Polar H10 and a gold-standard ECG system in measuring individuals’ HR, both at the aggregate and moment-to-moment levels, thus confirming and extending prior findings. Second, we found high correspondence (Pearson’s r > 0.95) between the two systems in quantifying dyadic HR synchrony using multiple analytical approaches. These results support the use of the Polar H10 as a low-cost, easy-to-use, and reliable tool for both individual and dyadic HR measurement. This represents an important step toward establishing its applicability in real-world settings where traditional ECG systems are impractical. Full article

Aim: This study compared the effects of standard evening smartphone restriction with an adapted intervention combining progressive restriction, psychoeducational guidance, and pre-sleep relaxation on sleep, psychological state, cognitive performance, and physical performance in physically active physical education students with moderate-to-high nomophobia. Methods: Thirty participants (age 21.9 ± 1.2 years; intermediate chronotype) completed a randomized controlled trial consisting of a 7-day baseline period, a 14-day intervention phase, and post-intervention assessments. The standard group (n = 15) implemented a 2-h pre-bedtime smartphone restriction combined with general sleep hygiene guidance. The adapted group (n = 15) followed a progressive restriction protocol (30→60→120 min) supplemented with psychoeducational guidance targeting smartphone-related anxiety and a nightly slow-paced breathing routine. Objective sleep parameters were quantified using wrist-worn actigraphy. Subjective sleep quality, pre-sleep anxiety, and stress were assessed using visual analog scales. Cognitive performance (psychomotor vigilance task and choice reaction time) and physical performance (vertical jumps and agility) were evaluated at both morning and afternoon time points. Results: The adapted intervention produced significantly greater improvements in sleep efficiency (time × group: F(1,28) = 6.84, p = 0.014, ηp² = 0.20; d = 0.78) and sleep onset latency (F(1,28) = 5.97, p = 0.021, ηp² = 0.18; d = 0.72) compared with standard restriction. Significant reductions were also observed in pre-sleep anxiety (F(1,28) = 7.12, p = 0.012, ηp² = 0.20; d = 0.81) and stress (F(1,28) = 6.45, p = 0.017, ηp² = 0.19; d = 0.74). Cognitive performance showed significant time × group × time-of-day interactions, with improvements during afternoon assessments in psychomotor vigilance (F(1,28) = 7.48, p = 0.011; d = 0.83) and choice reaction time (F(1,28) = 6.89, p = 0.014; d = 0.79) exclusively in the adapted group. Physical performance outcomes remained stable across interventions. Conclusions: Progressive smartphone restriction combined with psychoeducational strategies and pre-sleep relaxation yields clinically meaningful improvements in sleep continuity, psychological arousal, and afternoon cognitive performance, exceeding the benefits achieved through behavioral restriction alone. Full article

Sympathetic nervous system (SNS) imbalance is a common pathological basis for cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. This review focuses on these diseases, analyzing two core mechanisms: excessive sympathetic excitation induced by endoplasmic reticulum stress (ERS) or autophagy dysfunction in key central nuclei (e.g., hypothalamus, rostral ventrolateral medulla); and ERS/autophagy abnormalities in peripheral target organs caused by chronic SNS overactivation. Existing studies confirm that chronic SNS overactivation promotes peripheral metabolic overload via sustained catecholamine release, inducing persistent ERS and disrupting the protective unfolded protein response (UPR)–autophagy network, ultimately leading to cell apoptosis, inflammation, and fibrosis. Notably, central ERS or autophagy dysfunction further perturbs autonomic homeostasis, exacerbating sympathetic overexcitation. This review systematically elaborates on SNS overactivation as a critical bridge mediating UPR–autophagy network dysregulation in central and peripheral tissues, and explores therapeutic prospects of targeting key nodes (e.g., chemical chaperones, specific UPR modulators, nanomedicine), providing a theoretical basis for basic research and clinical translation. Full article

Background/Objectives: Falls are a major global issue for older adults, and emotional stress may increase the risk due to its effects on postural control and balance. However, the immediate effects of a stressful stimulus on objective measures of balance and fall risk are unknown. The study aims to explore differences in older adults’ performance on the Timed Up and Go (TUG) test before and after such exposure. Methods: In this cross-sectional study, 31 older adults (71.6 ± 4.98 years) were exposed to an emotionally stressful stimulus using high-arousal images from the International Affective Picture System. Participants performed the TUG before (t1) and after (t2) exposure as the primary outcome measure. To assess the physiological and psychological impact of the stressful stimulus, heart rate variability (HRV) was recorded before and during image viewing. A visual analogue scale (VAS) of unease was completed both before and after the stimulus. Results: During the stressful stimulus, the HRV high-frequency (HF) band decreased significantly (p = 0.001), while the low-frequency (LF) band (p = 0.002) and the LF/HF ratio (p = 0.004) showed a significant increase. Similarly, after stressful stimulus, VAS scores demonstrated a statistically significant increase (p < 0.001). The time to complete the TUG showed a statistically significant increase at t2 (p < 0.001). Conclusions: The stressful stimulus triggered both physiological and subjective stress responses. Subsequently, TUG test performance declined (increased duration), suggesting that emotionally stressful stimuli could deteriorate functional balance performance in older adults, potentially increasing fall risk. Full article

Plasticity is fundamental to the development, strengthening, and maintenance of healthy synaptic connections and recovery from injury in both the central and peripheral nervous systems. Yet, the processes involved are poorly understood. Herein, using a combination of patch-clamp electrophysiology and immuno-fluorescence confocal microscopy in adult mice, it is shown that blockade of synaptic transmission at submandibular ganglion junctions exposed to botulinum neurotoxin type A was accompanied by a rapid and striking decline in the abundance of synaptic vesicle markers—SV2, vesicle-associated membrane protein 2, and vesicular acetylcholine transporter—plus SNAP-25 (cleaved and intact) and postsynaptic α7 nicotinic acetylcholine receptors. Such alterations by the neurotoxin of parasympathetic synapses contrast starkly with the stability of postsynaptic proteins at nearby skeletal neuromuscular junctions. Both neurotransmission and the expression of SV2 and α7 nicotinic acetylcholine receptors remained depressed for 4 weeks, with full recovery of synaptic function delayed for more than 8 weeks. These novel findings may explain the relatively slow recovery of autonomic function after botulism or following therapeutic injections to alleviate hypersecretory disorders. Full article

Traumatic brain injury (TBI) and malignancies, despite their distinct nature, are characterized by similar immune responses, including the development of local and systemic inflammation and T-cell exhaustion. This article compares the role of immune checkpoints in the development of immune dysfunction in cancer and TBI, examines the contribution of the sympathetic nervous system to these changes, and discusses the relationship between local and systemic inflammation in these two conditions. Particular attention is paid to approaches to pharmacological modulation of inflammation and the impact on exhausted T-cells in these conditions. Comparison of inflammation and T-cell exhaustion in cancer and TBI highlights existing gaps in our understanding of immune regulation in TBI and points to areas requiring further investigation. Clarification of the immune mechanisms underlying the pathogenesis of TBI may facilitate the search for new diagnostic markers and lay the groundwork for the development of new therapeutic approaches for TBI treatment. Full article

Hereditary polyneuropathies represent a genetically and clinically heterogeneous group of disorders affecting the peripheral nervous system, characterized by progressive motor, sensory, and autonomic impairment. Advances in molecular genetics have identified key causative genes, including PMP22, MPZ, MFN2, TTR, EGR2, and CX32 (GJB1), which are implicated in Charcot–Marie–Tooth disease, Dejerine–Sottas syndrome, and related neuropathies. These conditions display substantial allelic and locus heterogeneity. Pathogenetically, mechanisms involve impaired myelin maintenance, disrupted axonal transport, mitochondrial dysfunction, and aberrant Schwann cell biology. Despite these insights, therapeutic options remain limited, and there is a pressing need to translate genetic findings into effective interventions. This review aims to provide a comprehensive synthesis of current knowledge compiling all known mutations resulting in hereditary polyneuropathies. In addition, it underscores the molecular pathomechanisms of hereditary polyneuropathies and evaluates emerging therapeutic strategies, including adeno-associated virus mediated RNA interference, CRISPR-based gene editing, antisense oligonucleotide therapy, and small-molecule modulators of axonal degeneration. Furthermore, the integration of precision diagnostics, such as next-generation sequencing and functional genomic approaches, is discussed in the context of personalized disease management. Collectively, this review underscores the need for patient-centered approaches in advancing care for individuals with hereditary polyneuropathies. Full article

Background and Objectives: Diabetes mellitus (DM) is a major risk factor for cardiovascular diseases (CVD), including acute myocardial infarction (MI), and is frequently associated with cardiac autonomic neuropathy (CAN). Post-MI autonomic dysfunction contributes to adverse outcomes, but data on prognostic markers in diabetic patients remain limited. This study aimed to (1) compare autonomic nervous system (ANS) function between patients with MI and DM (MI/DM), MI without DM, and DM without MI; (2) assess differences in MI/DM patients based on survival status; and (3) identify prognostic factors for all-cause mortality in diabetic patients following MI. Materials and Methods: This retrospective–prospective study included 375 patients: 93 MI/DM, 229 MI, and 53 DM. MI patients were treated with fibrinolytic or conservative therapy. All participants underwent cardiovascular reflex tests (CARTs) and 24 h Holter ECG with heart rate variability (HRV) analysis; DM patients without MI were tested in an outpatient setting. The primary endpoint was all-cause mortality during a median follow-up of 38 months. Univariable and multivariable Cox regression analyses were performed to determine mortality predictors. Results: Autonomic dysfunction was prevalent in all groups, with MI/DM patients showing the most pronounced impairment, particularly in parasympathetic function. MI/DM patients had significantly lower SDNN values and higher prevalence of definite parasympathetic dysfunction than other groups. In the MI/DM group, abnormal Valsalva maneuver (VM) was more frequent among non-survivors. Multivariable analysis identified abnormal VM and NSTEMI as predictors of overall mortality. Conclusions: Diabetic patients after MI exhibit the most severe autonomic impairment, predominantly parasympathetic, which may contribute to their increased cardiovascular risk. In this high-risk group, abnormal VM and NSTEMI presentations independently predict long-term mortality. Assessment of autonomic function, particularly VM, may provide valuable prognostic information and aid in risk stratification. Full article

Prader–Willi syndrome (PWS) is a rare, multisymptomatic genetic disorder caused by the absence or dysfunction of specific genes on chromosome 15. The genetic abnormality is anticipated to cause a dysfunction of the hypothalamus, which is also central in the regulation of the autonomic nervous system (ANS). Typical symptoms of PWS indicating a hypothalamic dysfunction include muscular hypotonia, poor growth, short stature, and feeding difficulties in infancy, which in early childhood are replaced by hyperphagia, leading to a high risk of obesity. Other characteristics, such as sleep difficulties, altered pain perception, delayed gastric emptying and constipation, blood pressure irregularities and dysregulated stress response, altered temperature regulation, delayed pupillary reaction, and urine retention and incontinence, all indicate a dysfunction of ANS. The ANS is usually divided into three parts: the sympathetic nervous system (SNS), which activates the fight-or-flight response during stress; the parasympathetic nervous system (PNS), which promotes calm and digestion; and the independent enteric nervous system (ENS), which regulates the gastrointestinal tract. Noradrenaline is the main neurotransmitter for the SNS, and acetylcholine for the PNS, while the ENS is regulated mainly by acetylcholine and serotonin. However, the ENS is modulated by both the SNS and the PNS, as well as many neuropeptides. Peptides regulating behavior, metabolism, appetite, and satiety have been extensively studied in PWS. However, studies of the role of neuropeptides in regulating other autonomic functions are limited and remain poorly understood. This review aims to synthesize current evidence from both animal models and human studies to explore potential mechanisms by which neuropeptides may contribute to autonomic dysfunction in individuals with PWS. Full article

Objective: The aim of this study was to analyse the evolution of heart rate variability (HRV) during official competition in high-level amateur padel players according to match outcome. Methods: HRV was measured in 44 individual recordings obtained across 11 matches involving 12 padel players. Measurements were taken before the match (PRE), during three sets (S1, S2 and S3) and during the two rest periods between sets (R1 and R2). Time-domain variables analysed included mean R–R interval (Mean RR), standard deviation of normalised R–R intervals (SDNN), root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and standard deviation of heart rate (STD HR), while nonlinear variables included the transverse (SD1) and longitudinal (SD2) axes of the Poincare plot, stress score (SS) and the sympathetic–parasympathetic ratio (SNS/PNS ratio). Results: Significant fluctuations in HRV were observed throughout the match. Players who won exhibited significantly higher values of Mean RR, SDNN, RMSSD, LnRMSSD, SD1 and SD2 during S1 (p < 0.05), and higher Mean RR, RMSSD, LnRMSSD and SD1 during R1 (p < 0.01). These differences diminished as the match progressed, disappearing in the later phases (S3, R2). Temporal analysis revealed that both groups showed parasympathetic recovery during the rest periods. Conclusions: This study provides novel evidence on the temporal dynamics of autonomic regulation in padel, showing that match outcome is associated with differences in cardiovascular regulation during the initial phases of competition. These findings support the usefulness of HRV monitoring for performance management in real competition settings. Full article

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia globally, linked to significant cardiovascular morbidity and mortality. Catheter ablation has emerged as a primary therapeutic approach, yet substantial recurrence rates limit its long-term efficacy. This review critically examines the molecular mechanisms underlying AF recurrence post-ablation, synthesizing recent findings from current literature. Key molecular pathways identified include structural remodeling mediated by fibrosis involving transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinases (MMPs), ion-channel dysregulation, inflammatory pathways, autonomic nervous system imbalance, and genetic and epigenetic alterations. Despite considerable advances, critical gaps persist due to small, heterogeneous studies and insufficient long-term follow-up. Comprehensive mechanistic research integrating genomics, proteomics, and advanced imaging is urgently needed to better characterize these pathways. Future studies must validate biomarkers such as TGF-β1, MMPs, connexins, and novel markers like GDF-15 and relaxin. Clinical translation of these molecular insights through precision diagnostics and personalized interventions holds great promise to enhance patient selection, optimize ablation strategies, reduce recurrence, and ultimately improve clinical outcomes in AF management. Full article

The gut microbiota is crucial for metabolic homeostasis and cardiovascular health. Dysbiosis triggers a gut–brain–heart axis dysfunction: vagal signaling promotes neuroinflammation and cerebral damage, which in turn impairs cardiac function. This bidirectional cycle is further exacerbated by reduced cerebral perfusion. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline and L-carnitine, acts as a primary mediator in this network. Elevated TMAO levels—resulting from bacterial conversion and hepatic oxidation—are linked to atherosclerosis and heart failure. Mechanistically, TMAO activates the NLRP3 inflammasome, inhibits the SIRT3-SOD2 pathway, and promotes platelet hyperreactivity. Furthermore, it modulates the autonomic nervous system, enhancing sympathetic activity and cardiac arrhythmias. Clinical evidence suggests TMAO is a potent predictor of mortality in HF. While current HF therapies focus on end-organ response (beta-blockers) or humoral pathways (ACE inhibitors), directly targeting the microbiota and TMAO offers a novel therapeutic frontier. Integrating TMAO assessment into risk models and utilizing advanced in vitro gut–brain models will be essential for developing personalized, groundbreaking cardiovascular interventions. Within this framework, the main aim of the present review is to describe how cardiac autonomic control can be directly modulated by the microbiota and its byproducts like TMAO. This latter is a leading target candidate for novel HF prevention and therapy interventions. Full article

Purpose: This preliminary study examined the associations between a 6-week sprint interval training (SIT) program and mental-fatigue (MF) related neurophysiological and subjective indicators in elite skateboarders. Methods: In this preliminary study, a single-group, repeated-measures design was employed. Twelve elite skateboarders completed a 6-week sprint interval training (SIT) program. Mental fatigue was assessed at three time points—pre-intervention (Week 0), mid-intervention (Week 3), and post-intervention (Week 6)—using a standardized 60 min Stroop task, with post-task EEG, HRV, and VAS measures collected to characterize neurophysiological and subjective responses. Results: Across the intervention, EEG indices indicated higher central nervous system activation and more stable post-task neural profiles. HRV indices suggested more flexible autonomic regulation, with favorable changes in low- and high-frequency components, sympathovagal balance, and recovery-related scores, whereas baseline-related indices such as RMSSD and SDNN showed no clear change. VAS ratings showed stable MF, accompanied by increased mental exertion and motivation and reduced physical fatigue over time. Conclusions: These preliminary findings suggest that a 6-week SIT program may be associated with enhanced resistance to Stroop-related MF in elite skateboarders, potentially through coordinated adaptations in neural activation, autonomic regulation, and psychological factors. Future randomized studies incorporating behavioral performance and sport-specific cognitive tasks are warranted to confirm and extend these observations. Full article

Emergency Departments (EDs) are high-pressure environments that place significant psychological and physiological stress on both patients and healthcare staff. Despite increasing awareness of stress-related impacts, proactive stress management interventions have limited uptake in healthcare. This proof-of-concept study will evaluate WeCare: a 6-week, wearable-integrated, self-guided program grounded in a “Learn–Track–Act” framework to support stress regulation, resilience, and wellbeing. The study will examine four key aspects of implementing the program: (1) feasibility, (2) acceptability and usability, (3) preliminary clinical effectiveness (self-report and physiological outcomes), and (4) preliminary economic impacts. Using a mixed-methods, multiple-baseline N-of-1 design, the program will be trialled with up to 32 participants across four ED-exposed groups: patients with non-severe or severe injuries, patients with acute medical presentations, and ED staff. The intervention includes digital psychoeducation, continuous biofeedback via a smart ring, personalised guidance, and evidence-based self-regulation strategies. Assessments will include standardised questionnaires combined with continuous physiological monitoring via a smartwatch, and interviews. Quantitative outcomes include heart rate variability, sleep patterns, perceived stress, wellbeing, healthcare use, and time off work. Qualitative interviews will explore user experience, usability, and perceived barriers. The findings will inform the refinement of the intervention and co-design of a larger-scale trial, contributing valuable evidence to support low-cost, wearable-enabled proactive mental healthcare in high-stress healthcare environments. Full article