Search Results (287)

Background: Hearing loss is increasingly prevalent and poses a significant public health concern. While both aging and occupational noise exposure are recognized contributors, their interactive effects and gender-specific patterns remain underexplored. Methods: This cross-sectional study analyzed data from 135,251 employees in Jiangsu Province, China. Demographic information, noise exposure metrics, and hearing thresholds were obtained through field measurements, questionnaires, and audiometric testing. Multivariate logistic regression, restricted cubic spline modeling, and interaction analyses were conducted. Machine learning models were employed to assess feature importance. Results: A nonlinear relationship between age and high-frequency hearing loss (HFHL) was identified, with a critical inflection point at 37.8 years. Noise exposure significantly amplified HFHL risk, particularly in older adults (OR = 2.564; 95% CI: 2.456–2.677, p < 0.001), with consistent findings across genders. Men exhibited greater susceptibility at high frequencies, even after adjusting for age and co-exposures. Aging and noise exposure have a joint association with hearing loss (OR = 2.564; 95% CI: 2.456–2.677, p < 0.001) and an interactive association (additive interaction: RERI = 2.075, AP = 0.502, SI = 2.967; multiplicative interaction: OR = 1.265; 95% CI: 1.176–1.36, p < 0.001). And machine learning also confirmed age, gender, and noise exposure as key predictors. Conclusions: Aging and occupational noise exert synergistic effects on auditory decline, with distinct gender disparities. These findings highlight the need for integrated, demographically tailored occupational health strategies. Machine learning approaches further validate key risk factors and support targeted screening for hearing loss prevention. Full article

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology—comprising cell-model selection, transcriptomic analysis, and a gentamicin–Texas Red (GTTR) uptake assay—to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines—UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage. In conclusion, our findings showed a complex ototoxic cascade involving OCT2- and TMC1-mediated drug uptake, calcium imbalance, ER stress, and disruption of PI3K-Akt survival signaling. We believe that UB/OC-2 cells serve as a practical in vitro model for mechanistic investigations and screening of otoprotective compounds. Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies. Full article

Implementing neonatal hearing screening has significantly reduced the age at which hearing impairments are detected in children. Nevertheless, objective electrophysiological assessments, such as auditory brainstem response (ABR) or auditory steady-state response (ASSR) testing, are often necessary for children older than six months. These evaluations should be conducted while the child is asleep to obtain accurate and interpretable results, as movement and muscle activity can introduce artifacts that compromise the quality of the recordings. In this narrative review, we evaluate sedation strategies in paediatric procedures, focusing on the efficacy, safety, and practicality of agents/routes for inducing sleep during ABR/ASSR testing. Sedation choices should prioritise patient safety, clinical context, and result reliability and be tailored to the individual’s age, health status, and procedural needs. Full article

Transmembrane channel-like (TMC) proteins are essential for hearing and balance; however, the molecular mechanisms that regulate their proper folding and membrane targeting remain poorly understood. Here, we establish Caenorhabditis elegans as a genetically tractable model to dissect TMC-1 trafficking by combining CRISPR knock-in strains, super-resolution microscopy, and genome-wide forward genetic screening. We show that TMC-1 robustly localizes to the plasma membrane in both neurons and muscle cells and identify a conserved valine (V803) in transmembrane domain 9 (TM9) as critical for its biogenesis and trafficking. Structural analyses guided by AlphaMissense and AlphaFold uncover two evolutionarily conserved functional hotspots, one in the extracellular loop adjacent to TM9 and the other in the TMC signature motif, which are interconnected by an evolutionarily conserved disulfide bond. Disrupting this bond in worm TMC-1 abolishes its cell-surface localization and destabilizes the mechanotransduction channel complex. Together, these findings provide a structural framework for interpreting deafness-causing mutations in human TMC1 and highlight disulfide-bond-linked hotspots as key molecular determinants of TMC protein biogenesis and trafficking. Full article

Objectives: This systematic review aimed to evaluate the diagnostic accuracy of self-administered web- and app-based tools for audiometric testing compared to pure-tone audiometry (PTA), the clinical gold standard. Methods: Studies were eligible if they involved human participants, evaluated self-administered digital tools for audiometric testing, reported diagnostic accuracy metrics (e.g., sensitivity, specificity, and accuracy), were published between 2014 and 2024, and were written in English. Studies were excluded if they did not compare to PTA, were reviews, or did not assess self-administered tools. MEDLINE, Web of Science, Scopus, and EMBASE were systematically searched throughout November 2024. Study quality was assessed using the QUADAS-2 tool, evaluating four domains: patient selection, index test, reference standard, and flow and timing. Most studies showed some concern for a risk of bias. Results: Twelve studies, including a total of 2453 participants and evaluating 15 applications, met the inclusion criteria. The studies reported wide variability in diagnostic accuracy. Sensitivity ranged from 18% to 100%, specificity from 35.5% to 99.1%, and accuracy from 14% to 97.4%. SHOEBOX and Screenout demonstrated high diagnostic accuracy, while other apps showed inconsistent results across studies and settings. Heterogeneity in definitions of hearing loss, test environments, device and headphone types and a lack of standardized reporting limited comparability. Most studies were conducted in non-soundproof environments, and some had unclear or a high risk of bias. Conclusions: Self-administered audiometric apps and web tools show promise for remote hearing screening but require further validation and methodological standardization. Clinicians should interpret the results cautiously given the current variability in performance. Full article

Part of the vision of the ISNS is ‘to enhance the quality of neonatal screening and medical services through dissemination of information, guidelines and best practices.’ Although newborn screening encompasses testing in the newborn period for critical congenital heart disease, hearing impairment, birth defects, and congenital biochemical disorders (usually on bloodspots), this guideline is specifically about bloodspot screening. The ISNS has provided neonatal screening guidelines for many years and here presents the renewed 2025 General Guidelines for Neonatal Bloodspot Screening. They are intended to provide a framework for screening programs to develop specific policies around all aspects of the newborn screening system, offering the basic set of items for consideration. These guidelines provide trusted anchors to build, expand, or maintain robustly organized neonatal or newborn screening (NBS) programs and a checklist to evaluate and improve the essential elements of those programs. For starting or developing programs, it is a set of elements for which provisions need to be in place and a checklist of items that the screening program should at a minimum have provisions for. The publication of these guidelines is meant as a starting point for interactive discussion, to further improve this document and expand where necessary. Full article

Objective: To evaluate the feasibility of vestibular screening in infants and investigate age-related changes in the characteristics of air-conducted sound cervical vestibular evoked myogenic potential (ACS-cVEMP) and bone-conducted vibration cervical vestibular evoked myogenic potential (BCV-cVEMP) in infants and children with normal hearing, aiming to provide new insights into the developmental trajectory of vestibular function during early childhood. Methods: A total of 159 subjects aged 3 months to 17 years old were divided into seven age groups. Additionally, 20 adults aged 18–30 years were included as controls to explore developmental changes in the sacculocollic reflex pathway. Results: The response rates of BCV-cVEMP in 3-month-olds were significantly higher than that of ACS-cVEMP (p = 0.048), while no significant difference was observed in other age groups (p > 0.05). Age-related changes were found in both latencies and amplitudes of ACS-cVEMP and BCV-cVEMP. ACS-cVEMP latencies reached adult levels at 13–17 years, while BCV-cVEMP latencies normalized by 7–12 years. ACS-cVEMP amplitudes increased with age, stabilizing at 4 years, whereas BCV-cVEMP amplitudes peaked at 4–6 years before gradually decreasing. Conclusions: This study demonstrates that cVEMP is not only a viable tool for vestibular screening in infants but also reveals crucial age-related developmental changes in the vestibular system. These findings contribute new insights into the maturation of the vestibular reflex pathways and provide normative data that can be used to guide early vestibular screening practices. Full article

Background: Children with Down syndrome (DS) are at high risk for a broad spectrum of otorhinolaryngologic (ENT) disorders, including hearing impairment, obstructive sleep apnea (OSA), dysphagia, and language delay. These conditions often coexist and interact with the neurodevelopmental and anatomical features of DS, requiring early identification and coordinated management. Despite the clinical burden, ENT involvement in DS remains under-characterized and inconsistently addressed in care pathways. Methods: A narrative review was conducted to provide an integrative overview of ENT manifestations in pediatric patients with DS. A literature search was performed in PubMed, Scopus, and Web of Science, covering studies published between 1979 and 2025. Articles were included if they addressed ENT disorders in children with DS and met clinical relevance criteria. A total of 45 studies were selected and analysed by study design, focus, and contribution to diagnostic or therapeutic frameworks. Results: The majority of included studies were observational in nature, covering key domains such as conductive hearing loss, chronic otitis media with effusion, sleep-disordered breathing, and feeding/swallowing dysfunction. Several articles emphasized the importance of early audiologic and polysomnographic screening. Gaps in standardization and accessibility of multidisciplinary ENT care were consistently reported. A proposed framework for integrated evaluation is discussed. Conclusions: ENT manifestations in pediatric DS are frequent, multifactorial, and clinically impactful. A multidisciplinary, anticipatory model of care is essential for timely diagnosis and targeted intervention. This review highlights the need to formalize ENT pathways within comprehensive care protocols for children with DS. Full article

Globally, many countries have promulgated extensive, contextually relevant disability legislative policies for children with hearing impairment/d/Deafness (HI/d/D). The alignment of policies with their implementation, with robust monitoring, is essential for effective early intervention (EI) and early education (EE) outcomes. The study’s purpose was to review current South African EI and EE regulations, acts, and policies in relation to children with HI/d/D from birth to age six. An adapted Arksey and O’Malley framework with inductive thematic analysis was applied to synthesise and evaluate relevant information. Documentation was sourced between 1993 and 2023 from the official South African government portal and Google online searches using keywords. While 7976 documents were initially identified with the broad search and 1249 with a refined category search, only 17 met the specific inclusion criteria for policies referencing hearing impairment in early intervention and education. Seventeen documents were selected for study inclusion, with sixteen mentioning HI/d/D and multi-disciplinary, multi-sectoral, family-centred, culturally sensitive considerations superficially. One document from the Department of Health (DoH) specifically addressed early hearing detection and intervention (EHDI). Three main themes emerged, including Partnerships, Participation and Integration, Screening, Identification and/or Intervention, and Education/Special Education. Greater engagement with South African EI and education policies is essential to strengthen implementation, especially across sectors and at the community level. Mandating EHDI guidelines is critical to improving service delivery and ensuring smoother transitions between health, education, and social services for children with hearing impairment. Full article

Background/Objectives: Pathogenic recessive GJB2 variants are the main genetic cause of non-syndromic sensorineural hearing loss. However, following GJB2 testing, a significant proportion of deaf patients are only found to be heterozygous carriers of pathogenic GJB2 alleles. Five large deletions not affecting GJB2 but encompassing a minimal common 62 kb region within the neighbouring CRYL1 gene have been described to cause loss of cis GJB2 expression and, as a result, produce hearing loss when in trans with pathogenic GJB2 variants. We describe the identification and characterization of a novel deletion of this type in deaf patients from northwestern Spain. Methods: We used panel NGS sequencing to detect the deletion, MLPA to validate it, whole-genome sequencing to map its breakpoints, PCR + Sanger sequencing to finely characterize it and triple-primer PCR to screen for it. Results: We identified a novel 200 kb deletion spanning the whole CRYL1 gene in two unrelated deaf patients from Asturias (in northwestern Spain) who were heterozygous for the pathogenic GJB2 c.35delG variant. Although the large deletion was absent from gnomAD v4.1.0 and 2052 local control alleles, screening for it in 20 additional deaf carriers of monoallelic pathogenic GJB2 variants detected it in another patient from Galicia (also in northwestern Spain). The novel deletion, termed del(200 kb)insATTATA, explained hearing loss in 3/43 (7%) deaf patients from our cohort that were otherwise heterozygous for pathogenic GJB2 variants. Conclusions: This work highlights the importance of comprehensively testing all genomic regions known to be clinically relevant for a given genetic condition, including thorough CRYL1 CNV screening for DFNB1A diagnostics. Full article

Hearing loss (HL) is a major global health concern, with drug-induced ototoxicity contributing significantly, particularly in patients undergoing treatment for drug-resistant tuberculosis (DR-TB). In South Africa, where both TB and HIV are prevalent, the risk of treatment-related auditory damage is especially high. This study aimed to assess the prevalence and predictors of hearing impairment among DR-TB patients in rural Eastern Cape, South Africa. A retrospective analysis was conducted on 438 DR-TB patients treated between 2018 and 2020, using pure tone audiometry (PTA) to assess hearing status post-treatment. Demographic, clinical, and lifestyle data were extracted from patient records and analyzed using logistic regression. The overall prevalence of hearing loss was 37.2%. Risk was significantly associated with an older age, a male gender, DR-TB classification (MDR, pre-XDR, and XDR), unsuccessful treatment outcomes, and substance use. Prevalence of HL increased notably in patients aged 70 and older. Lifestyle factors, particularly combined use of tobacco, alcohol, and drugs, were linked to higher odds of HL. These findings underscore the need for routine audiometric screening and personalized treatment monitoring in DR-TB care, especially for high-risk populations. Early identification of ototoxicity risk factors can inform safer treatment regimens and improve patient outcomes in resource-limited settings. Full article

Background: Cytomegalovirus (CMV) infection is the most common and serious congenital infection, with universal screening in pregnancy, standardized therapy, and a vaccine still lacking. Study design: In the 1990s, we noted that intravenous ganciclovir did not cure some children with severe sequelae due to congenital cytomegalovirus (CMV) infection. Therefore, we performed an open randomized trial using intravenous foscarnet as an alternative to intravenous ganciclovir in 24 infants (12 in each therapy group), all with severe neurological manifestations due to congenital CMV infection. Nine and five infants, belonging to the foscarnet or ganciclovir group, respectively, had abnormal hearing. One infant in each group also had chorioretinitis. Concomitantly, 12 CMV-infected infants with similar manifestations, who did not receive any therapy, were used as controls. The results of short-term (2 years) and long-term (7–29 years, mean 22.2) follow-up are reported herein. Short-term results: Neurological outcomes were normal in five of the twelve children who were treated with foscarnet, compared to nine of the twelve children given ganciclovir. None of the untreated children were healthy. There was a statistically significant difference (p = 0.023) between the treated and untreated children. Hearing was normal in four of the twelve children treated with foscarnet, seven of the twelve children treated with ganciclovir, and two untreated children. Long-term-results: Two children in both therapy groups died before the age of 17 years, and six untreated children died between 7 and 26 years of age. Neurological outcomes were normal in three of the ten children treated with foscarnet, in two of the ten treated with ganciclovir, and in none of the untreated children. Hearing was normal in two children treated with foscarnet, in six children treated with ganciclovir, and in one untreated child. Conclusions: Intravenous ganciclovir and foscarnet were found to be safe at long-term follow-up and appeared to be capable of mitigating the neurological and auditory consequences of congenital CMV disease at the short-term follow-up. However, there was progressive worsening of the symptomatology in all three groups, with a statistically significant increase in the number of deaths (p = 0.035) among 4 of the 24 children in the therapy groups and 6 of the 12 untreated children. Full article

Background/Objectives: Idiopathic immune-mediated uveitis (IIMU) is an intraocular inflammatory condition affecting the uveal tract and adjacent ocular structures, potentially leading to systemic involvement. Audiovestibular symptoms, such as sensorineural hearing loss (SNHL) and balance disturbances, are often underdiagnosed in these patients. The potential correlation between IIMU and audiovestibular dysfunction remains insufficiently studied. This study aimed to estimate the prevalence and describe the clinical characteristics of audiovestibular manifestations in patients with IIMU. Methods: We conducted a cross-sectional observational study of 34 patients with a confirmed diagnosis of IIMU at a tertiary academic center. All participants underwent a standardized neurootological assessment, including pure-tone audiometry, video head impulse testing (vHIT), and cervical vestibular-evoked myogenic potentials (cVEMP). Demographic and clinical data were also collected. Results: Audiovestibular dysfunction was identified in 41.18% of patients, with bilateral SNHL (B-SNHL) being the most common finding. Patients with B-SNHL had a significantly later age of uveitis onset (52.3 ± 14.4 vs. 35.9 ± 13.9 years, p = 0.003) and a higher incidence of ocular complications (83.3% vs. 59.1%, p = 0.252). Furthermore, worsening ophthalmologic activity was observed in 25% of patients with B-SNHL, compared to 0% in those without B-SNHL (p = 0.037). Vestibular dysfunction was also associated with delayed onset of uveitis (51.0 ± 17.4 vs. 36.0 ± 12.2 years, p = 0.006) and a non-significantly higher complication rate (76.9% vs. 61.9%, p = 0.465). Conclusions: Audiovestibular dysfunction is a frequent finding in patients with IIMU and is associated with delayed uveitis onset and greater ocular morbidity. These results support the inclusion of systematic audiovestibular screening in clinical evaluations of IIMU patients and suggest that earlier detection may inform prognosis and guide multidisciplinary management strategies. Full article

There is significant inter-individual variability in the prevalence and severity of cisplatin-induced ototoxicity, which is greatly influenced by genetic and non-genetic factors that predispose the patient to the development of hearing loss. Currently, the focus should be on identifying patients who are more likely to develop ototoxicity based on genetic and non-genetic factors, as therapies to combat ototoxicity are limited or still under study. The severity of hearing loss and the time of its onset may be influenced by certain genetic polymorphisms or the dose administered, age, sex, diet, the administration of other drugs with ototoxic potential, and association with radiotherapy of the head and neck. Knowing the risk factors allows the doctor to manage each case in a personalized manner, preventing hearing damage, especially in the long term. With the help of PubMed and Scopus, we searched for relevant studies documenting the genetic and non-genetic risk in patients treated with cisplatin. This review article is a synthesis of the literature that points out the importance of these factors, encouraging genetic screening and improving quality of life in patients treated with cisplatin. Full article

Background/Objectives: Previous research has shown that listeners may use acoustic cues for speech processing that are perceived during brief segments in the noise when there is an optimal signal-to-noise ratio (SNR). This “glimpsing” effect requires higher cognitive skills than the speech tasks used in typical audiometric evaluations. Purpose: The aim of this study was to investigate the use of an online test of speech processing in noise in listeners with typical hearing sensitivity (TH, defined as thresholds ≤ 25 dB HL) who were asked to determine the gender of the subject in sentences that were presented in increasing levels of continuous and interrupted noise. Methods: This was a repeated-measures design with three factors (SNR, noise type, and syntactic complexity). Study Sample: Participants with self-reported TH (N = 153, ages 18–39 years, mean age = 20.7 years) who passed an online hearing screening were invited to complete an online questionnaire. Data Collection and Analysis: Participants completed a sentence recognition task under four SNRs (−6, −9, −12, and −15 dB), two syntactic complexity settings (subjective-relative and objective-relative center-embedded), and two noise types (interrupted and continuous). They were asked to listen to 64 sentences through their own headphones/earphones that were presented in an online format at a user-selected comfortable listening level. Their task was to identify the gender of the person performing the action in each sentence. Results: Significant main effects of all three factors as well as the SNR by noise-type two-way interaction were identified (p < 0.05). This interaction indicated that the effect of SNR on sentence comprehension was more pronounced in the continuous noise compared to the interrupted noise condition. Conclusions: Listeners with self-reported TH benefited from the glimpsing effect in the interrupted noise even under low SNRs (i.e., −15 dB). The evaluation of glimpsing may be a sensitive measure of auditory processing beyond the traditional word recognition used in clinical evaluations in persons who report hearing challenges and may hold promise for the development of auditory training programs. Full article