Search Results (264)

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors. Full article

Spinal cord injury (SCI) remains one of the toughest obstacles in neuroscience and regenerative medicine due to both severe functional loss and limited healing ability. This article aims to provide a key integrative, mechanism-focused review of the molecular landscape of SCI and the new disruptive therapy technologies that are now evolving in the SCI arena. Our goal is to unify a fundamental pathophysiology of neuroinflammation, ferroptosis, glial scarring, and oxidative stress with the translation of precision treatment approaches driven by artificial intelligence (AI), CRISPR-mediated gene editing, and regenerative bioengineering. Drawing upon advances in single-cell omics, systems biology, and smart biomaterials, we will discuss the potential for reprogramming the spinal cord at multiple levels, from transcriptional programming to biomechanical scaffolds, to change the course from an irreversible degeneration toward a directed regenerative pathway. We will place special emphasis on using AI to improve diagnostic/prognostic and inferred responses, gene and cell therapies enabled by genomic editing, and bioelectronics capable of rehabilitating functional connectivity. Although many of the technologies described below are still in development, they are becoming increasingly disruptive capabilities of what it may mean to recover from an SCI. Instead of prescribing a particular therapeutic fix, we provide a future-looking synthesis of interrelated biological, computational, and bioengineering approaches that conjointly chart a course toward adaptive, personalized neuroregeneration. Our intent is to inspire a paradigm shift to resolve paralysis through precision recovery and to be grounded in a spirit of humility, rigor, and an interdisciplinary approach. Full article

Botulism is a severe muscle paralysis disease mediated by the botulinum toxin. Here, we reported a foodborne botulism case caused by Clostridium botulinum subtype A5(b3) from self-packaged vacuum spicy rabbit heads. Treatment for this case was delayed due to misdiagnosis and insufficient diagnostic capacity in three hospitals, which resulted in progressive clinical deterioration, and eventually, the patient was transferred to Shandong Public Health Clinical Center for specialized therapy. The case was suspected as foodborne botulism by the Qilu Medical-Prevention Innovation Integration pathway and multi-disciplinary consultation. An epidemiological investigation and laboratory confirmation revealed that the botulinum neurotoxin originated from vacuum-packaged spicy rabbit heads distributed via interprovincial cold chain logistics. After treatment with botulism antiserum, the patient’s condition significantly improved, and they were discharged after recovery. We revealed that this foodborne botulism outbreak was caused by the Clostridium botulinum A5(b3) subtype from food by whole-genome sequencing and SNP typing. All the strains belonged to Group I carrying the botulinum neurotoxin gene classified as the ha cluster. Toxin A was confirmed by MBA and other methods, while toxin B was non-functional due to the truncated bont/B gene. Other virulence genes and antibiotic resistance genes were also detected. Our findings indicate that self-packaged vacuum meat products represent an emerging risk factor for botulism transmission when stored improperly. Importantly, the recurrent misdiagnosis in this case underscored the urgent need to enhance the training of healthcare professionals in medical institutions to improve the diagnostic accuracy and clinical management of botulism. Full article

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

Unilateral vocal fold paralysis (UVFP) can lead to significant dysphonia. Medialization thyroplasty type 1 (TT1) is a common surgical intervention aiming at improving vocal quality by optimally positioning the paralyzed fold to generate the necessary vibrations for phonation. Implants are generally placed through the thyroid cartilage in a sedated patient and positioned either underneath the level of the vocal folds (infraglottal medialization or IM) or at the level of the vocal folds (glottal medialization or GM). Using high-speed three-dimensional digital image correlation (3D-DIC) in an ex vivo canine hemilarynx model, this study explores the impact of implant location, specifically IM versus GM on the pre-phonatory and dynamic vertical thickness, glottal divergence, flow rate (Q), and cepstral peak prominence (CPP) under varying adduction and subglottal pressure conditions. IM consistently increased glottal divergence and dynamic vertical thickness, particularly in under-adducted states (AL1), despite producing lower static thickness than GM. CPP remained unaffected by the implant condition, but Q decreased significantly with IM under AL1, indicating enhanced glottal resistance and closure. These findings suggest that IM may offer superior functional outcomes by restoring divergent glottal shaping and improving vibratory efficiency. This study also introduces a validated method for dynamically quantifying vocal fold thickness and emphasizes the importance of implant depth in medialization thyroplasty strategies. Full article

With the advancement of urbanization and the proposal of sustainable development goals, the complexity and vulnerability of urban transportation systems have become increasingly prominent, and their reliability is directly related to the sustainable operation of urban transportation. The reliability of urban road networks, characterized by their dynamic nature, multi-scale characteristics, and anti-interference capabilities, directly restricts the functional guarantee of urban traffic and the efficiency of emergency response. To address the limitations of existing road network connectivity reliability assessment methods in representing time dynamics and modeling failure correlation, this study proposes a road network reliability assessment method based on a Dynamic Bayesian Network (DBN) by constructing a probabilistic reasoning model that integrates cascading failure characteristics. First, the connectivity reliability of the road network under random and targeted attack strategies was evaluated using a Monte Carlo simulation, revealing the impact of different attack strategies on network reliability. Subsequently, the congestion delay index is used as the standard of road section failure, considering the failure distribution and mutual dependence of road sections over time, a cascade failure mechanism is introduced, and a time-varying reliability assessment model based on a DBN is constructed. The effectiveness of the proposed method was verified through a case study of a partial road network in Dalian. The results show that ignoring cascading effects can significantly overestimate the reliability of the road network, especially during peak traffic hours, where such deviations may mask the real paralysis risks of the network. In contrast, the method proposed in this study fully considers time dynamics and failure correlation and can better capture the reliability of the road network under various dynamic conditions, providing a scientific basis for the sustainable planning and emergency management of urban traffic systems. Full article

Background/Objectives: Myelomeningocele (MMC) is the most severe form of spina bifida, often accompanied by impaired motor function due to paralysis of the lower limbs, as well as neurogenic bladder (NB). These factors may contribute to nutritional disorders and cardiovascular diseases (CVDs) in the future. High-sensitivity CRP (hsCRP) is a positive marker of unstable atherosclerotic plaques and is commonly used in the diagnosis of CVDs. Adiponectin has an opposite, anti-inflammatory function. The aim of this study was to assess the risk of CVDs in a group of children with NB and a control group, based on serum levels of adiponectin, hsCRP, and lipid profiles. Methods: A prospective clinical estimation based on 87 children (67 NB, 20 control group) was conducted. Data collected from medical histories included the following: sex, age, anthropometric parameters (height, weight, BMI), level of spinal lesion, and activity according to Hoffer’s scale. Lipid profile values (cholesterol, HDL, LDL, triglycerides) were assessed using standard blood sample tests. hsCRP and adiponectin were measured using an ELISA kit. Results: A comparison of adiponectin and hsCRP levels revealed statistically significant differences between the NB group and the control. Additionally, significant correlations were identified between BMI and the biomarkers: hsCRP was positively associated with BMI, whereas adiponectin exhibited a negative association. The highest concentrations of hsCRP were detected in MMC patients with a Th lesion level and in non-walker patients. Conclusions: Elevated hsCRP may reflect increased cardiovascular risk in children with NB. While adiponectin levels were also altered, their association with cardiovascular risk appears more complex and may involve additional metabolic mechanisms. Full article

The P300 event-related potential, evoked by attending to specific sensory stimuli, is utilized in non-invasive brain–computer interface (BCI) systems and is considered the only interface through which individuals with complete paralysis can operate devices based on their intention. Conventionally, visual stimuli used to elicit P300 have been presented using displays; however, placing a display directly in front of the user obstructs the field of view and prevents the user from perceiving their surrounding environment. Moreover, every time the user changes posture, the display must be repositioned accordingly, increasing the burden on caregivers. To address these issues, we propose a novel system that employs wirelessly controllable LED visual stimulus presentation devices distributed throughout the surrounding environment, rather than relying on traditional displays. The primary challenge in the proposed system is the communication delay associated with wireless control, which introduces errors in the timing of stimulus presentation—an essential factor for accurate P300 analysis. Therefore, it is necessary to evaluate how such delays affect P300 detection accuracy. The second challenge lies in the variability of visual stimulus strength due to differences in viewing distance caused by the spatial distribution of stimulus devices. This also requires the validation of its impact on P300 detection. In Experiment 1, we evaluated system performance in terms of wireless communication delay and confirmed an average delay of 352.1 ± 30.9 ms. In Experiment 2, we conducted P300 elicitation experiments using the wireless visual stimulus presentation device under conditions that allowed the precise measurement of stimulus presentation timing. We compared P300 waveforms across three conditions: (1) using the exact measured stimulus timing, (2) using the stimulus timing with a fixed compensation of 350 ms for the wireless delay, and (3) using the stimulus timing with both the 350 ms fixed delay compensation and an additional pseudo-random error value generated based on a normal distribution. The results demonstrated the effectiveness of the proposed delay compensation method in preserving P300 waveform integrity. In Experiment 3, a system performance verification test was conducted on 21 participants using a wireless visual presentation device. As a result, statistically significant differences (p < 0.01) in amplitude between target and non-target stimuli, along with medium or greater effect sizes (Cohen’s d: 0.49–0.61), were observed under all conditions with an averaging count of 10 or more. Notably, the P300 detection accuracy reached 85% with 40 averaging trials and 100% with 100 trials. These findings demonstrate that the system can function as a P300 speller and be utilized as an interface equivalent to conventional display-based methods. Full article

Tetanus, a severe and life-threatening illness caused by Clostridium tetani, produces symptoms such as muscle spasms, muscle stiffness and seizures caused by the production of tetanus neurotoxin (TeNT). TeNT causes spastic paralysis through the inhibition of neurotransmission in spinal inhibitory interneurons. This is achieved, in part, through pH-triggered membrane insertion of the translocation (HCT) domain, which delivers the catalytic light-chain (LC) domain to the cytosol. While the function of HCT is well defined, the mechanism by which it accomplishes this task is largely unknown. Based on the crystal structure of tetanus neurotoxin, we identified potential polar interactions between arginine 711, tryptophan 715 and aspartate 821 that appear to be evolutionarily conserved across the clostridial neurotoxin family. We show that the disruption of the Asp-Arg pair in a beltless HCT variant (bHCT) results in changes in thermal stability without significant alterations to the overall secondary structure. ANS (1-anilino-8-napthalene sulfonate) binding studies, in conjunction with liposome permeabilization assays, demonstrate that mutations at R711 or D821 trigger interactions with the membrane at higher pH values compared to wildtype bHCT. Interestingly, we show that the introduction of the D821N mutation into LH_NT (LC-HCT only), but not the holotoxin, resulted in the increased cleavage of VAMP 2 in cortical neurons relative to the wildtype protein. This suggests that, as observed for botulinum toxin A, the receptor-binding domain is not necessary for LC translocation but rather helps determine the pH threshold of membrane insertion. The mutation of W715 did not result in detectable changes in the activity of either bHCT or the holotoxin, suggesting that it plays only a minor role in stabilizing the structure of the toxin. We conclude that the protonation of D821 at low pH disrupts interactions with R711 and W715, helping to drive the conformational refolding of HCT needed for membrane insertion and the subsequent translocation of the LC. Full article

Sepsis and cancer, though distinct in their clinical manifestations, share profound pathophysiological overlaps that underscore their interconnectedness in disease progression and outcomes. Here we discuss the intricate biological mechanisms linking these two conditions, focusing on the roles of inflammation, immune dysregulation, and metabolic alterations. In sepsis, an uncontrolled immune response to infection leads to a cytokine storm, tissue damage, and immune paralysis, while cancer exploits chronic inflammation and immunosuppressive pathways to promote tumor growth and metastasis. Both conditions exhibit metabolic reprogramming, such as the Warburg effect in cancer and glycolysis-driven immune cell activation in sepsis, which fuels disease progression and complicates treatment. Sepsis can exacerbate cancer progression by inducing genomic instability, epigenetic modifications, and a pro-tumorigenic microenvironment, while cancer increases susceptibility to sepsis through immunosuppression and treatment-related complications. The shared pathways between sepsis and cancer present unique opportunities for therapeutic intervention, including anti-inflammatory agents, immune checkpoint inhibitors, and metabolic modulators. Anti-inflammatory therapies, such as IL-6 and TNF-α inhibitors, show promise in mitigating inflammation, while immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 antibodies are being explored to restore immune function in sepsis and enhance antitumor immunity in cancer. Metabolic modulators, including glycolysis and glutaminolysis inhibitors, target the metabolic reprogramming common to both conditions, though their dual roles in normal and pathological processes necessitate careful consideration. Additionally, antimicrobial peptides (AMPs) represent a versatile therapeutic option with their dual antimicrobial and antitumor properties. In this review, we also highlight the critical need for integrated approaches to understanding and managing the complex interactions between sepsis and cancer. By bridging the gap between sepsis and cancer research, this work aims to inspire interdisciplinary collaboration and advance the development of targeted therapies that address the shared mechanisms driving these devastating diseases. Ultimately, these insights may pave the way for novel diagnostic tools and therapeutic strategies to improve outcomes for patients affected by both conditions. Full article

Background and Objectives: Peripheral facial paralysis (PFP) is a condition with diverse etiologies, requiring multidisciplinary management. This study aimed to describe the sociodemographic, clinical, and functional characteristics of patients with PFP treated at the Rehabilitation Service of the University Hospital of Burgos and to evaluate factors associated with the initial degree of impairment. Materials and Methods: A descriptive, cross-sectional study was conducted on 45 patients referred to the Rehabilitation Service from July 2018 to July 2023. Inclusion criteria included first-time rehabilitation visits for PFP during the study period with signed informed consent. Patients with prior PFP on the affected side or severe comorbidities, such as stroke, were excluded. Data were collected from medical records and initial evaluations. The Sunnybrook Facial Grading System (SFGS) was used to assess impairment. Results: Idiopathic paralysis was the most common etiology, with a predominance in men (60.9%) and middle-aged or older adults. Otorhinolaryngology was the leading referral service, though primary care referrals were underrepresented. Delays in initiating rehabilitation were identified, especially in complex cases like acoustic neurinoma. The ANOVA test revealed no significant differences in functional assessments based on age, sex, or etiology, likely due to the limited sample size. Conclusions: The study highlights the predominance of idiopathic etiology in PFP and the importance of otorhinolaryngology in referrals. Greater awareness in primary care and early identification are crucial. Future studies with larger samples are needed to evaluate predictors of impairment and optimize rehabilitation strategies. Full article

Background: The application of intermittent intraoperative neuromonitoring (I-IONM) and continuous intraoperative neuromonitoring (C-IONM) has been widely accepted to improve surgical outcomes after thyroid surgery. This observational study aimed to evaluate the impact of vocal cord paralysis (VCP) in thyroid surgery conducted with I-IONM and C-IONM. Materials and Methods: From January 2018 to December 2022, 147 patients operated on with I-IONM and C-IONM for thyroid surgery were analyzed. Variations in the rates of the occurrence of temporary and permanent vocal cord paralysis between the two groups were compared. A p-value < 0.05 was considered statistically significant. Results: In total, 147 patients were eligible for inclusion in the study. Of these, 96 (65%) patients underwent thyroid surgery with I-IONM, 52 patients (35%) underwent surgery with C-IONM by a single surgeon. The percentage of temporary VCP was 4.1% (4 patients) in the I-IONM group; no patients had permanent VCP. In the C-IONM group, two patients (3.9%) had permanent vocal cord paralysis, and temporary vocal cord paralysis was observed in other two patients (3.9%), who recovered their nerve function after speech therapy. No statistically significant differences were found in the two groups. Conclusions: In our study, both I-IONM and C-IONM proved effective in predicting VCP, and no significant differences were observed between the two techniques in our series. Full article

Objectives: The present scoping review aims to map the existing evidence on psychological and behavioral interventions targeting patients with narcolepsy type 1 and type 2. Methods: A literature search was performed using the databases Scopus, PubMed, and PsycINFO. Studies were included if they (1) employed randomized controlled trials, non-randomized trials, or quasi-experimental studies; (2) were published in English; (3) were published in peer-reviewed journals; (4) examined the impact of psychological interventions on psychopathological (primary outcomes) and narcolepsy-related symptoms (secondary outcomes); and (5) involved patients with a diagnosis of narcolepsy using recognized diagnostic criteria regardless of whether they were receiving pharmacological treatment or were untreated. No restrictions were imposed on the publication date to comprehensively map the available evidence. Data were extracted to address the review aims and presented as a narrative synthesis. Results: The database search yielded six studies. Treatment options for individuals with narcolepsy encompass psychological and behavioral interventions, such as telehealth interventions, meditation/relaxation therapy, and scheduled napping. The primary outcomes were daytime sleepiness, wakefulness maintenance, sleep attacks, the severity of symptoms of narcolepsy, sleep paralysis episodes, depression, and psychological functioning. The secondary outcomes were sleep-problem-related quality of life, sleep inertia, and sleep quality. The psychological and behavioral interventions exhibited variability in terms of the intervention type, personnel involved, number of sessions, and duration. Most of the contributions also lack details regarding the training of professionals and the specifics of the interventions. Additionally, the evidence quality was deemed low based on the Crowe Critical Appraisal Tool. Conclusions: Although the importance of nonpharmacological approaches is well recognized, there is limited evidence to support the efficacy of psychological and behavioral interventions in narcolepsy. This is further complicated by the wide range of psychological and behavioral interventions available. Full article

Introduction: Sleep is a fundamental biological function critical for physical and mental health. Chronic sleep disturbances can significantly impair cognitive, emotional, and social functioning, leading to deficits in attention, alertness, and executive function, alongside increased irritability, anxiety, and depression. For pediatric patients, such disturbances pose additional concerns, potentially disrupting developmental processes and quality of life for both children and their families. Objectives: Emerging evidence suggests a correlation between neurofibromatosis type 1 (NF1) and an increased prevalence of sleep disorders in children. NF1, a genetic condition affecting multiple body systems, including the nervous system, may predispose children to sleep disturbances due to its neurodevelopmental and behavioral impacts. This observational case–control study aimed to explore the association between NF1 and sleep disorders in pediatric patients, comparing the prevalence and patterns of sleep disturbances between NF1 patients and healthy controls. Patients and Methods: The study included 100 children aged 2–12 years, divided into two groups: 50 with NF1 (case group) and 50 children belonging to the control group. NF1 patients were recruited from the Unit of Rare Diseases of the Nervous System in Childhood at the Policlinico “G. Rodolico—San Marco” University Hospital in Catania. Data were collected using a questionnaire completed by parents, assessing parasomnias, breathing-related sleep disorders, and other behavioral and physiological disturbances; these data were compared to a sleep assessment performed using an Apple Watch Ultra. Results: NF1 patients exhibited a significantly higher prevalence of sleep disorders than controls. Notable differences included increased nocturnal hyperhidrosis (48% vs. 10%), bruxism (48% vs. 28%), restless legs syndrome (22% vs. 4%), frequent nighttime awakenings (22% vs. 8%), and sleep paralysis (12% vs. 0%). A finding of poorer sleep quality also emerged from the results of sleep analysis using an Apple Watch Ultra. Conclusions: These findings confirm an elevated risk of sleep disorders in children with NF1, emphasizing the importance of early identification and management to improve quality of life and mitigate cognitive and behavioral impacts. Further research is essential to understand the mechanisms underlying these associations and develop targeted interventions for this population. Full article