Search Results (383)

Background: Turner syndrome is a genotypic disorder in females characterized by the total or partial absence of an X chromosome. While cardiovascular issues and sensorineural hearing loss are well-documented, vestibular system involvement remains understudied. This study aims to examine vestibular system involvement in patients with Turner syndrome and assess if they exhibit a higher prevalence of peripheral vestibular pathology compared to the general population. Methods: A retrospective longitudinal study was conducted with 21 Turner syndrome patients and 21 age-matched controls. Evaluations included clinical history, otoscopy, pure tone audiometry, the Video Head Impulse Test (vHIT) to measure vestibulo-ocular reflex gain, and computerized dynamic posturography, specifically the Sensory Organization Test (SOT) and Stability Limits Analysis. Results: Turner syndrome patients showed significantly higher hearing thresholds across all frequencies compared to controls (p < 0.001). In the vHIT, 30% of the Turner group presented pathological results, with significant gain reductions in the right horizontal and left posterior semicircular canals. Posturography revealed a significant reduction in overall stability (p = 0.006) and a significantly lower vestibular index (p = 0.011) in the Turner group. Additionally, patients with Turner syndrome demonstrated significant impairments in directional control, reaction time, and excursion points during Stability Limits Analysis. Conclusions: Patients with Turner syndrome are more likely to experience vestibular disorders, a finding likely associated with estrogen deficiency and the loss of its protective effect on the inner ear. These results highlight the necessity of including vestibular and posturographic assessments in the routine clinical follow-up of these patients to facilitate early detection and rehabilitation, even in the absence of overt symptoms like vertigo. Full article

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for antivirals that are resilient to resistance. Current Food and Drug Administration (FDA)-approved therapies primarily target single viral mechanisms, leaving gaps in efficacy. Here, we developed a Deep Learning-based Activity Screening Model (DLASM), which integrates graph convolutional network with machine learning to identify SARS-CoV-2 inhibitors, using experimental 3-chymotrypsin-like (3CL) main protease assay data. The optimized DLASMs virtually screened ~170,000 compounds from diverse in-house collections and yielded novel hits, several of which not only inhibited the 3CL protease but also blocked viral entry by interfering with heparan sulfate-mediated host interactions. These activities were validated through multiple assays, including 3CL enzymatic inhibition, SARS-CoV-2 pseudotyped particle entry, α-synuclein fibril uptake as a proxy for endocytosis, live virus cytopathic effect, heparan sulfate-dependent entry assay, and a 3D human lung mucociliary tissue model. Molecular docking studies elucidated binding modes at the 3CL protease active site, while molecular dynamics simulations provided insights into compound–heparan sulfate interactions. The identified compounds represent early-stage hits with moderate potency that demonstrate dual-mechanism antiviral activity. Together, these findings establish dual-target inhibition as a promising antiviral strategy, offering not only enhanced potency but also reduced risk of resistance. Moreover, our DLASM framework provides a generalizable pipeline for identifying chemically diverse scaffolds and for broader applications beyond SARS-CoV-2. Full article

Metallic contaminants in powdered foods represent a serious safety concern. Therefore, effective detection is crucial for food safety. This study aimed to develop an electric-field-based detection system and quantitatively evaluate its performance. An alternating (+/−) electrode array (gap 1–2 mm) was designed, and resonance analysis identified 15 kHz with a 2 mm gap as the optimal operating condition. Using an IGBT-based high-voltage source, 1.35 kV was selected to ensure stable operation without partial discharge. A real-time algorithm based on a minimum current-change threshold was implemented, and detection responses to stainless steel (SUS), aluminum (Al), and copper (Cu) particles in three size classes (<0.5, 0.5–1.0, and 1.0–2.0 mm) were evaluated using hit/miss modeling and logistic regression to obtain probability-of-detection (POD) curves and limits of detection (LOD). The system achieved POD ≥ 0.9 for 1.0–2.0 mm particles; in the 0.5–1.0 mm range, observed POD values were 84%, 90%, and 68% for SUS, Al, and Cu, respectively. Safety was assessed by COMSOL-based localized heating simulation validated by infrared thermography and by ozone monitoring for real-time operation. Compared with conventional inspection approaches, the proposed system provides a compact, cost-effective architecture while reporting inspection-oriented reliability metrics (POD/LOD) for process-line deployment. Full article

Epstein–Barr virus (EBV) is a human pathogenic and oncogenic herpesvirus, with worldwide importance, at times associated with serious to life-threatening symptoms, especially in immunocompromised hosts. The available preventive options against EBV disease are limited to medically elaborate and cost-intensive measures of cell-based immunotherapy. The development of novel options of anti-EBV drug targeting is currently a matter of intense international efforts. A putative target of the antiviral therapy approach is the EBV-encoded protein kinase BGLF4, which fulfills a multifaceted role in productive viral replication. So far, viral BGLF4 interactor proteins and phosphorylated substrates have occasionally been reported, but in particular cellular interactors await further characterization concerning both, their relevance for BGLF4 functionality and their accessibility to antiviral drugs. In this study, we have analyzed host cell–BGLF4 interaction, BGLF4 kinase properties, and BGLF4-directed small molecules. The main results are as follows: (i) a mass spectrometry-based interactomic study was performed with EBV-producing Akata-BX1 cells, thereby identifying the human pyruvate dehydrogenase (PDH) as a relevant BGLF4 interactor; (ii) BGLF4–PDH interaction was confirmed by protein coimmunoprecipitation, subcellular cofractionation, and confocal imaging; (iii) the BGLF4-mediated phosphorylation of PDH was demonstrated by an in vitro kinase assay (IVKA); (iv) a reduction in PDH phosphorylation was shown for selected kinase inhibitors, which also exerted BGLF4-directed inhibitory potential in a quantitative qSox-IVKA, and (v) these hit compounds showed anti-EBV activity in lytically induced P3HR-1 cells using qPCR measurement, as well as PDH-inhibitory activity using standardized PDH assays. These data lead to an improved understanding of EBV–host interaction that may open novel anti-EBV preventive opportunities. Combined, the findings point to PDH as a new cellular interactor of the EBV kinase BGLF4. Also, notably, the data on pharmacological intervention with kinase activity or substrate phosphorylation may possibly provide as yet untapped options of antiviral drug targeting. Full article

Background: Differentiating Ménière’s disease (MD) from vestibular migraine (VM) remains difficult because current diagnostic frameworks are predominantly clinical and incorporate pure-tone thresholds, risking incorporation bias. We asked whether speech discrimination scores (SDS) alone can separate MD from VM at the patient level and whether adding a prespecified vestibular marker, the caloric–vHIT dissociation, pattern A (abnormal calorics with normal horizontal vHIT), improves performance. Methods: In a retrospective cohort (2015–2018) including definite MD (n = 60) and definite VM (n = 40) by Bárány/ICHD criteria, we trained patient-level logistic regression models with 5-fold out-of-fold validation and in-fold preprocessing. To avoid incorporation bias, PTA was excluded from all models. Predefined feature sets were as follows: (1) SDS-only (bilateral SDS), (2) CalHiT-A-only (Yes/No; canal paresis ≥22% with horizontal-canal vHIT gain ≥0.80 in either ear), and (3) SDS+CalHiT-A. Discrimination was assessed by ROC–AUC with bootstrap 95% CIs; calibration and decision-curve analysis (DCA) are reported. An exploratory model encoded SDS as “affected/healthy.” Results: The SDS-only model achieved AUC 0.866 (95% CI 0.787–0.937). CalHiT-A-only yielded AUC 0.674 (0.561–0.778). Adding CalHiT-A to SDS did not improve discrimination (SDS+CalHiT-A AUC 0.844 [0.760–0.913]). The exploratory “affected/healthy” SDS encoding underperformed (AUC 0.801 [0.706–0.882]). CalHiT-A was significantly more prevalent in MD than in VM (56.7% [34/60] vs. 17.5% [7/40]; Fisher’s exact p = 1.49 × 10⁻⁴). Calibration favored SDS-only, and DCA showed the highest net benefit for SDS-only across thresholds p = 0.05–0.40. Conclusions: Bilateral SDS alone provides robust, well-calibrated discrimination between MD and VM and outperforms CalHiT-A and the affected/healthy SDS encoding. In this cohort, vestibular test dissociation did not add diagnostic value beyond SDS at the patient level, supporting SDS-centered diagnostic workflows while reserving CalHiT-A for adjudication and phenotyping rather than primary classification. Full article

Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic–antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward. Full article

The rapid development of the Internet of Vehicles (IoV) has significantly increased data transmission demands, frequently causing backhaul congestion and service delays in traditional static cellular networks. To address these challenges, this paper proposes a joint position deployment and hierarchical caching optimization solution for unmanned aerial vehicle (UAV)-assisted vehicle-to-vehicle (V2V) caching networks towards dynamic vehicle distribution. Firstly, a hierarchical caching architecture is proposed, where the file library is classified into core, supplementary, and infrequent layers based on file popularity, applying deterministic caching, probabilistic caching, and no-caching strategies, respectively, to achieve efficient utilization of caching resources. Secondly, the mathematical expressions for the caching hit rate and service delay are derived, and a joint optimization problem is formulated to minimize service delay, addressing the dual challenges of hierarchical caching and UAV deployment. To address this problem, a decoupled iterative method is designed, decomposing the original problem into hierarchical caching and UAV deployment subproblems. Based on this, a grid search–tail distribution function fitting-based approach and a K-means clustering-based approach are proposed to optimize these subproblems, respectively. Finally, simulation results demonstrate that, compared to existing strategies, the proposed strategy effectively reduces service latency under multi-vehicle distribution while maintaining high cache file coverage. Under typical conditions, the proposed strategy reduced average service latency by 10% to 20%, thereby validating its effectiveness and superiority. Full article

Background: Age-related vestibular decline frequently accompanies presbycusis, and older adults undergoing cochlear implantation (CI) may be particularly vulnerable to postoperative dizziness due to a reduced compensatory capacity and a higher burden of comorbidities. Although CI is an effective treatment for severe-to-profound sensorineural hearing loss in the elderly, its impact on vestibular function remains a critical concern. This study aimed to compare pre and postoperative vestibular performance in older patients (≥65 years) versus younger adults undergoing CI in order to identify the risk factors for postoperative vestibular deterioration and critical issues that characterize this category and carry out personalized preoperative counseling. Methods: In this monocentric observational study, adults undergoing CI were divided into two groups: older patients (OPS, ≥65 years) and younger patients (YPS, <65 years). Vestibular function was assessed preoperatively and one month postoperatively through a Dizziness Handicap Inventory (DHI), history of recurrent falls, clinical examination, video head impulse test (VHIT), bithermal caloric testing, and computerized dynamic posturography (Sensory Organization Test, SOT). Risk factors for postoperative vestibular worsening were analyzed using ANOVA test and chi-square statistics, with significance set at p < 0.05. Results: A total of 63 patients were included, with 18 surgeries involving OPS and 45 involving YPS. Preoperatively, OPS showed significantly higher rates of vestibular abnormalities on caloric testing (55.5% vs. 17.7% bilateral hyporeflexia, p < 0.05) and a higher prevalence of recurrent falls (33.3% vs. 4.4%, p < 0.05). Early postoperative dizziness (DHI¹) increased significantly in both groups, but age ≥ 65 was a risk factor for ≥10% worsening (OR 2.2, p < 0.05). At one month, YPS returned to baseline DHI values, whereas OPS showed persistent dizziness with significantly higher DHI² scores (29.2 vs. 12.9, p < 0.05). Vestibular worsening was identified in 33.3% of VHIT assessments and 44.4% of caloric tests in OPS, with caloric testing proving more sensitive than VHIT. Implantation on the better-functioning vestibular side and the presence of ≥3 comorbidities increased the likelihood of persistent postoperative dizziness. Conclusions: Older age is a significant risk factor for persistent dizziness and vestibular impairment one month after CI. Given the reduced compensatory capacity typical of older adults, vestibular assessment should play a central role in preoperative decision-making, particularly for side selection. Bithermal caloric stimulation is recommended as the most sensitive tool for detecting clinically relevant vestibular changes. Preoperative counseling for older CI candidates should include a detailed discussion of vestibular risks and the possible need for postoperative rehabilitation. Full article

Background/Objectives: This study compared vestibular evoked myogenic potentials (VEMP) and video head impulse test (vHIT) findings between long-term hearing aid users and non-users with moderately severe to profound sensorineural hearing loss (SNHL) to investigate whether prolonged use of high-power hearing aids has any effect on the functioning of peripheral vestibular organs. Methods: A cross-sectional study was conducted in the audiology clinic of a tertiary care hospital. Using convenience sampling, 67 adults aged 20–64 years who visited for hearing evaluation or hearing aid services were recruited and allocated into hearing aid user and non-user groups. VEMP latency and amplitude and vHIT vestibulo-ocular reflex (VOR) gain values were compared between groups. Multiple linear regression was performed to examine the association between the duration of hearing aid use and vestibular function. Results: No significant group differences were observed for any VEMP or vHIT parameter, except for the latency of P1 of the cVEMP in the left ear. Regression analyses indicated that the duration of hearing aid use was not significantly associated with any vestibular test measure. Conclusions: Long-term use of high-power hearing aids does not appear to be associated with measurable alterations in vestibular function. Nonetheless, longitudinal studies with improved control of confounding variables are recommended to validate these preliminary findings. Full article

Background/Objectives: Patients with Idiopathic sudden sensorineural hearing loss (ISSNHL) are often devastated by the unknown etiology coupled with the unknown pathway to recovery. The aim of this study was to evaluate whether abnormalities on the video Head Impulse Test (vHIT) performed early in the course of ISSNHL are associated with poorer hearing recovery. Methods: Forty-four patients with ISSNHL were prospectively enrolled between 2019 and 2022 following exclusion of differential diagnoses on clinical and MRI evaluation. vHIT was performed within 1–14 days of symptom onset and within 48 h of hospitalization. Recovery at six months was assessed both as a dichotomous outcome and by change in pure tone average (PTA). Group differences were analyzed using Fisher’s exact and Mann–Whitney U tests. A two-predictor logistic regression model examined the association between vHIT results, dizziness, and recovery. Results: Twelve patients exhibited abnormal vHIT findings. Abnormal vHIT was strongly associated with the presence of dizziness and with markedly poorer hearing recovery at six months. Patients with normal vHIT demonstrated substantially greater improvement in PTA thresholds compared with those showing abnormal results. Logistic regression further confirmed that abnormal vHIT was an independent predictor of reduced likelihood of hearing recovery, whereas dizziness alone did not independently influence outcomes. Conclusions: Our findings suggest that abnormal vHIT results in ISSNHL patients are linked to poor hearing recovery, which can enhance patient counseling regarding expectations. Although promising as a prognostic tool, we acknowledge our limited sample size and recommend validation in larger prospective cohorts. Full article

Background/Objectives: The diagnosis of vestibular migraine (VM) and Meniere’s disease (MD) is based mainly on clinical criteria. The aim of this study is to systematically review and investigate the potential role of the video Head Impulse Test (vHIT) in the differential diagnosis between VM and MD. Methods: A systematic review of the English-language literature was conducted, including studies from database inception to November 2023, in accordance with PRISMA guidelines. Medline (via PubMed), Cochrane Database and Scopus were reviewed. The review included studies involving adult patients diagnosed with VM, MD, or healthy control individuals who underwent vHIT and reported data on vHIT abnormalities, gain, and refixation saccades. The AXIS tool was applied for risk of bias assessment in all cross-sectional studies. A random-effects meta-analysis was performed to compare vHIT gains between individuals with VM and those with MD. Results: Eleven cross-sectional observational studies with a case–control comparison design were included, comprising a total of 362 patients with VM, 307 patients with MD, and 135 healthy control subjects. All studies applied the same diagnostic criteria for VM; however, varying criteria were used for the diagnosis of MD. Four studies evaluated the duration of vestibular symptoms, two assessed migraine duration, and six provided a rationale for excluding individuals with overlapping VM and MD diagnoses. Criteria for defining an abnormal vHIT result were specified in six studies. Seven studies reported vHIT gain values for the lateral semicircular canal, while eight presented data on saccade incidence and characteristics. Additionally, four studies were included in the meta-analysis, which yielded a mean difference in the vHIT gain of −0.0203 (95% CI: −0.0789 to 0.0383; p = 0.4968), indicating no statistically significant difference between patients with VM and those with MD. Conclusions: In this review, vHIT gain did not differ significantly between VM and MD groups, suggesting that vHIT gain alone has limited utility in their differential diagnosis. Combined saccade patterns may still prove clinically useful as more robust and consistent data become available. Full article

Background/Objectives: Children with hearing loss (HL) could experience significant fatigue which compromises their performance. The effort related to the combination of HL and visual impairment in children affected by Usher syndrome (USH) could compromise mental health, socio-emotional behavior and academic achievement. The aim of the present study was to analyse the listening effort in USH cases types 1 and 2 and its relation to age, molecular diagnosis, visual field, visual acuity, degree of HL, vestibular impairment and spatial orientation. Methods: This was a retrospective monocentric study. Twenty children with genetically confirmed USH (USH2 in 15/20–75% and USH1 in 5/20–25%), age range 3–17 years (mean 9.6 ± 4.7), underwent: the Vanderbilt fatigue scale questionnaire (VFS), audiological and vestibular assessment including the Oldenburg Matrix test in Italian and video head impulse test (VHIT), sound localization test and ophthalmologic examination. Results: We observed a more pronounced HL and deteriorated vestibular function in those with USH1. They also employed significantly more time and head movements to localize sounds compared to USH2 and had the worst visual field on eye examination. The VFS did not show significant differences between the two groups, with the exception of the physical fatigue reported by parents. Mean VFS was linearly related to age, the hearing threshold of the worse ear, data logging hours of hearing device, time and head movements of the localization test, VHIT asymmetry and balance problems referred by parents and the visual field. USH type 1 had no greater risk of fatigue than USH2. Profound hearing loss, data logging of hearing device < 8 h a day, difficult localization test, balance problems and low retinal sensitivity represented risk factors for listening effort measured with VFS. Conclusions: Listening effort in difficult environments such as school rooms in USH patients is not only associated to hearing function but also to the spatial awareness determined in part by vestibular and visual function. Teachers should be informed and made aware of multiple comorbidities in order to facilitate learning. Full article

Background and Clinical Significance: Vestibular disorders include a wide range of conditions with overlapping symptoms such as dizziness, vertigo and imbalance, often offering diagnostic challenges when distinguishing between peripheral and central etiology. Accurate differentiation is essential for establishing effective treatment plans. In rare or atypical cases with subtle findings, comprehensive diagnostic tools—such as extended vestibular tests and structured questionnaires like the Dizziness Handicap Inventory (DHI)—are critical for diagnosis and monitoring patient recovery. Case Presentation: A 35-year-old female presented with chronic imbalance and motion-induced dizziness persisting for four years. The patient had a surgical history of right-sided functional neck dissection for a parotid tumor. A comprehensive audiovestibular evaluation was performed, including pure tone audiometry (PTA), tympanometry, videonystagmography (VNG), cervical vestibular evoked myogenic potentials (cVEMP), ocular vestibular evoked myogenic potentials (oVEMP), video head impulse testing (vHIT), computerized dynamic posturography (CDP), and magnetic resonance imaging (MRI). The Dizziness Handicap Index (DHI) was administered at baseline and post-treatment to monitor subjective symptom changes. Objective testing revealed marked right–left amplitude asymmetry on cVEMP, which were recorded from the trapezius muscle due to prior neck dissection surgery, indicating isolated right-sided saccular hypofunction. Following targeted vestibular rehabilitation and pharmacologic treatment, the 3-month reassessment demonstrated resolution of symptoms and a reduction in DHI scores from 24 to 6. Conclusions: Comprehensive vestibular testing, performed in a single diagnostic session, enabled the accurate identification of isolated right-sided saccular hypofunction in this complex post-surgical case. Combining cVEMP, CDP, and DHI assessment provided a complete functional profile, guided targeted rehabilitation, and allowed objective monitoring of recovery. Full article

Background: Superior semicircular canal dehiscence (SSCD) is characterized by a bony defect of the superior semicircular canal (SSC), leading to vestibular and auditory symptoms. A process of spontaneous “auto-plugging,” in which the overlying dura mater progressively occludes the SSC, may replicate the effects of surgical canal plugging but remains under-recognized. The present study reports diverse clinical, instrumental, and 3d High Resolution MRI findings in patients with SSCD and subsequently confirmed to present with spontaneous complete or partial auto-plugging. Methods: We retrospectively reviewed 11 patients with SSCD diagnosed on high-resolution CT and suspected auto-plugging based on clinical atypia and large dehiscence (>4 mm). Patients underwent comprehensive neurotological assessment, including pure-tone audiometry, vestibular testing, and HR MRI with 3D labyrinthine reconstructions to identify partial or complete auto-plugging. Auto-plugging was classified as partial (Canalis semicircularis superior depressus) or complete (absence of endolymph fluid signal; Canalis semicircularis superior obturatus). Results: Among 13 ears with auto-plugging, 6 were partial and 7 complete. The mean SSCD size in auto-plugged ears was 5.5 mm. Most ears had normal or near-normal vestibular function on VHIT, with minimal air-bone gaps and preserved VEMP responses. Imaging demonstrated varying degrees of dural contact with the SSC, confirming partial or complete canal occlusion. Conclusions: Spontaneous auto-plugging of the SSC is a plausible, under-recognized phenomenon that may reproduce functional effects of surgical plugging. Dedicated 3D labyrinthine MRI enhances detection and characterization. Prospective multimodal studies are needed to clarify the pathophysiology, progression, and clinical implications, optimizing patient selection for surgical versus conservative management. Full article

Background/Objective: The Suppression Head Impulse Paradigm (SHIMP) is a specialized variant of the Head Impulse Test (HIT), designed to evaluate the suppression of the angular Vestibulo-Ocular Reflex (aVOR) by central mechanisms. These mechanisms are primarily mediated by brainstem structures, including the vestibular nuclei, their projections to ocular motor nuclei, and modulatory inputs from the cerebellum. Damage to these areas can impair the generation of anti-compensatory saccades (ACs), even when the peripheral vestibular apparatus remains intact. The present study explores this phenomenon in a cohort of patients with neurological disorders known to potentially involve the brainstem, including multiple sclerosis, severe traumatic brain injury, stroke, and Parkinson’s disease. Methods: This cross-sectional study included 119 patients with multiple sclerosis (PwMS), severe traumatic brain injury (PwTBI), stroke (PwS), and Parkinson’s disease (PwPD). The video Head Impulse Test was performed to assess the aVOR gain across all semicircular canals using both the HIMP and SHIMP. The presence, absence, or delay of ACs was systematically recorded. Results: Among the 119 patients evaluated (238 semicircular canals), 24 (20%) demonstrated normal aVOR gain but failed to generate ACs during SHIMP. The absence of ACs was observed in seven PwMS, five with PwTBI, six with PwS, and six with PwPD. Conclusions: The absence of ACs despite normal aVOR gain suggests a potential impairment in the central pathways controlling saccadic responses, independently of peripheral vestibular function. These findings underscore the clinical relevance of integrating the SHIMP into vestibular assessments to improve the identification of central vestibular dysfunction in neurological disorders. Full article