BACKGROUND:Noise exposure at work can damage hearing at speech-frequency essential for speech perception, leading to communication difficulties, life quality decline, and adverse mental and cognitive outcomes. Early identification of individuals at high risk is crucial for occupational health management. This study aims to develop prediction models to estimate the risk of speech-frequency hearing loss among noise-exposed workers. METHODS:We developed and validated multimodal prediction models using epidemiological, hearing assessment, and genetic information from shipyard workers. The training cohort included 5053 workers and the testing cohort included 2086 workers recruited between 2012 and 2024. Noise exposure was estimated using detailed work durations and workplace measurements. Participants completed questionnaires, underwent standardized hearing examinations, and provided blood samples for genetic analysis. Sex-specific models were constructed based on two commonly used definitions of speech-frequency hearing loss. Longitudinal risk was evaluated using repeated-measures statistical approaches. RESULTS:Here we show that binaural hearing thresholds at 3 and 6 kHz are the strongest predictors of subsequent speech-frequency hearing loss, together with age and noise exposure (P < 0.001). Longitudinal prediction models demonstrate good discrimination and calibration, with AUCs exceeding 0.80 and C-indices above 0.78 in both training and testing cohorts. Incorporation of genetic variants further improves predictive performance, increasing discrimination by approximately 2% in males and 3% in females. CONCLUSIONS:These findings provide evidence-based prediction tools that enable individualized risk assessment. Practically, identifying workers at high risk would benefit the hearing preservation in the frequencies more relevant to speech sounds and maintain good communication.

BACKGROUND:Substantial variability in susceptibility to noise-induced hearing loss (NIHL) with comparable noise exposures suggests a genetic contribution, but population-based evidence remains limited. This study evaluated whether a polygenic risk score (PRS), summarizing the effect of genetic variants, was associated with NIHL susceptibility. METHODS:Participants were recruited from an ongoing Occupational Noise Exposure and Health Study (ONEHS), including 3836 NIHL cases and 2028 normal hearing (NH) controls. A weighted PRS, calculated from seven genetic variants, stratified participants into low (0-20%), moderate (20-80%), and high (80-100%) PRS groups. Cross-sectional associations with prevalence of NIHL were assessed using logistic regression, while longitudinal associations with incident NIHL and hearing deterioration were evaluated using Cox proportional hazards models and generalized estimating equations. RESULTS:For cross-sectional analyses, participants with high PRS had an increased NIHL risk relative to low PRS participants (odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.13-1.63, P = 0.001). PRS exhibited an interaction with cumulative noise exposure (CNE). For the longitudinal study (907 with NH and 897 with mild hearing loss at baseline), approximately one-third of participants experienced hearing deterioration. High PRS participants showed increased risk of developing NIHL (hazard ratio [HR] = 1.57, 95% CI: 1.13-2.18, P = 0.008) and further hearing deterioration (HR = 1.49, 95% CI: 1.08-2.07, P = 0.017). Joint associations were observed for high PRS with CNE and age. CONCLUSIONS:Common genetic variation, captured by PRS, contributes to NIHL susceptibility and modifies the relationship between noise exposure and hearing outcomes.

Traumatic tympanic membrane perforation (TTMP) is common worldwide, with a reported incidence as high as 6.1

INTRODUCTION:Central auditory processing (CAP) is crucial for speech perception and is also fundamental for cognitive function. This study investigated whether gap detection threshold (GDT) could serve as an early marker for identifying individuals with cognitive impairment (CI) at high risk of dementia. METHODS:Sixty-four older adults underwent peripheral auditory, cognitive, and CAP assessments. Machine learning and resting state electroencephalography (EEG)/event-related potential (ERP) analyses explored predictors and neural correlates of CI. RESULTS:GDT was significantly higher in those with CI (mean ± standard deviation: 8.25 ± 6.14 versus 5.98 ± 3.44 ms, respectively, p = 0.034), and negatively correlated with cognitive test scores (e.g., Addenbrooke's Cognitive Examination III: r = -0.40, p = 0.001). GDT emerged as a key predictor. EEG showed altered auditory connectivity and ERP revealed reduced N1/N2 amplitudes in high-GDT individuals (false discovery rate corrected p < 0.05). DISCUSSION:GDT may reflect early neurophysiological changes in individuals with CI and has potential as a non-invasive biomarker. Highlights:Central auditory processing (CAP) test scores were found to be significantly correlated with cognitive tests.By machine learning, the best variable gap detection threshold (GDT) for predicting cognitive impairment was screened out.GDT subgroup analysis was performed within the normal control (NC) group. Compared to the low GDT subgroup, the high GDT subgroup had lower amplitudes of the cognitive components of the event-related potential and many differences in functional connectivity, indicating that GDT has predictive value for changes in cognitive function.

Noise-induced hearing loss (NIHL), a common sensory disorder, is traditionally thought to stem primarily from direct damage to sound-sensing hair cells (HCs). Here, we demonstrate that supporting cells (SCs), neighboring cells not previously implicated in NIHL pathogenesis, orchestrate hearing loss and HC degeneration through Gasdermin D (GSDMD) activation. Mechanistically, noise-induced oxidative stress in HCs triggers activation of epidermal growth factor receptor in SCs, leading to extracellular-regulated kinase phosphorylation and caspase-11-dependent cleavage of GSDMD, thereby establishing an HC-to-SC signaling cascade. Furthermore, GSDMD activation in SCs reciprocally exacerbates oxidative injury in HCs, creating a pathogenic positive feedback loop between the two cell types. Our findings uncover a central role for SCs in noise-induced hearing loss and identify GSDMD-mediated intercellular communication as a potential therapeutic target.

PurposeTo evaluate the efficacy, safety, and outcomes of a blade- and cautery-free surgical protocol for pterygium removal.MethodsPterygium removal surgery was done in 69 eyes (67 patients; 24 males and 43 females) who were followed up for at least 6 months. The surgery was characterized by blunt separation of the pterygium from the head to the limbal arc using the tip of Vannas scissors and modified procedures, such as transpositional flapping and suture closure. Neither a blade nor a cautery was used.ResultsThe reported subjects were 60.7 years old on average, and most of them had primary pterygium (66 out of 69). The proposed surgical protocol was simple to perform, requiring an average operation time of 18.7 min which was shorter than that of the suture and fibrin glue groups mentioned in relevant reports. Post-anesthesia pain was relieved quickly 1 day after surgery without the use of pain killers. During the follow-up period of 11.3 ± 3.1 months, recurrence of pterygium requiring additional surgery was seen in only three eyes (4.3%).ConclusionThe potential of the examined protocol as an easy, efficient, and reliable approach was demonstrated.

Noise-induced synaptopathy and relevant hidden hearing loss (NIS and NIHHL) have been a hot topic in hearing research for almost 15 years. The progress is summarized in this review to address the reversibility of the synaptic damage after the initial loss, and the role of functional deficit in the repaired synapses as the reason for hearing impairment in addition to the deafferentiation caused by the synaptic loss, per se. The evidence supporting the synaptic repair is summarized. It is pointed out that coding-in-noise deficit (CIND) may not be the major problem of NIS and NIHHL, since solid evidence supporting the existence of this deficit is not available even in animal studies, as well as in in human reports. Rather, temporal processing deficits are clearly demonstrated in subjects with NIS and potentially NIHHL. The idea of CIND as the major concern in NIHHL is proposed based upon the functional categorization of the auditory nerve (ANF) by spontaneous rate and the biased loss of the ribbon synapses innervation the low-SR ANF. The limitation of this hypothesis is discussed in detail. The review also addresses the difficulty of translating animal data to humans and the need for new research in the future.

HYPOTHESIS:The current study employed a skull-simulator verification method to assess whether the output of softband bone conduction hearing devices (BCHDs) at the manufacturer's default settings deviated widely from the target determined by the fitting formula. BACKGROUND:Real ear analysis is utilized for the verification of the fitting of air conduction hearing devices (ACHDs) in a variety of institutions. This procedure, however, has not been used in the fitting of BCHDs, largely due to the difficulty of testing the output of these devices to temporal bones. Despite the availability of skull simulators, they have not been utilized clinically to measure BCHD output. MATERIALS AND METHODS:This prospective, single-center study enrolled 42 subjects, aged 3 months to 10 years, with microtia-atresia-associated mild-to-severe bilateral conductive hearing loss. Hearing sensitivity was evaluated behaviorally by pure tone audiometry (PTA) in 22 subjects 4 years or older (the PTA group), and by auditory brainstem response (ABR) in 20 subjects younger than 4 years (the ABR group). Following 6 months of subjects wearing the prescribed softband BCHDs, their dial level (DL) thresholds were reassessed while using their own BCHDs, configured with zero gain across all frequencies, functioning solely as a bone vibrator. These DL thresholds were inputted into the fitting formula, desired sensation level-bone conduction devices (DSL-BCD) for children, to obtain the target values of BCHD output. The simulator output of the BCHD programmed at the manufacturer's default setting was measured in response to speech presented at 55, 65, and 80 dB SPL, followed by gain adjustment based on the differences between the simulator output and the target. Aided speech intelligibility index (SII) was measured before and after the gain adjustment. RESULTS:The softband BCHDs at the manufacturer's settings generally had lower output than the prescribed target values. This difference was larger at low frequencies and low levels. Across the 12 points tested (four frequencies from 500 to 4000 Hz multiplied by three levels), 22 (52.3%) and 42 (100%) BCHDs had deviations of +7 and +5 dB, respectively, at one point or more. The gain adjustments reduced the deviation and improved the SII values at the two lower levels of speech presented. CONCLUSION:The simulator output of softband bone conduction hearing devices (BCHDs) with the manufacturer's settings may exhibit significant deviations from the formula. Objective output verification should be considered a beneficial step in BCHD fitting and is recommended when applicable.

Tympanojugular paragangliomas (TJP) originate from the parasympathetic ganglia in the lateral base of the skull. Although the cellular composition and oncogenic mechanisms of paragangliomas have been evaluated, a comprehensive transcriptomic atlas specific to TJP remains to be established to facilitate further investigations. In this study, single-cell RNA sequencing and whole-exome sequencing were conducted on six surgically excised TJP samples to determine their cellular composition and intratumoral heterogeneity. Fibroblasts were sub-classified into two distinct groups: myofibroblasts and fibroblasts associated with bone remodeling. Additionally, an elaborate regulatory and cell-cell communication network was determined, highlighting the multifaceted role of fibroblasts, which varies depending on expression transitions. The Kit receptor (KIT) signaling pathway mediated interactions between fibroblasts and mast cells, whereas robust connections with endothelial and Schwann cell-like cells were facilitated through the platelet-derived growth factor signaling pathway. These findings establish a foundation for studying the mechanisms underlying protumor angiogenesis and the specific contributions of fibroblasts within the TJP microenvironment. IL6 signaling pathway of fibroblasts interacting with macrophages and endothelial cells may be involved in tumor regrowth. These results enhance our understanding of fibroblast functionality and provide a resource for future therapeutic targeting of TJP.

Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to the pathogenesis of HFM is largely unknown. Here, we sought to elucidate the effects of the VWA1 mutation at the molecular level by generating a vwa1-knockout zebrafish line using CRISPR/Cas9. Mutants and crispants showed cartilage dysmorphologies, including hypoplastic Meckel's cartilage and palatoquadrate cartilage, malformed ceratohyal with widened angle, and deformed or absent ceratobranchial cartilages. Chondrocytes exhibited a smaller size and aspect ratio and were aligned irregularly. In situ hybridization and RT-qPCR showed a decrease in barx1 and col2a1a expression, indicating abnormal cranial neural crest cell (CNCC) condensation and differentiation. CNCC proliferation and survival were also impaired in the mutants. Expression of FGF pathway components, including fgf8a, fgfr1, fgfr2, fgfr3, fgfr4, and runx2a, was decreased, implying a role for VWA1 in regulating FGF signaling. Our results demonstrate that VWA1 is essential for zebrafish chondrogenesis through effects on condensation, differentiation, proliferation, and apoptosis of CNCCs, and likely impacts chondrogenesis through regulation of the FGF pathway.

This study aimed to investigate the alterations of cognition and functional connectivity post noise, and find the progress and neural substrates of noise induced hearing loss (NIHL)-associated cognitive impairment. We exposed rats to 122 dB broad-band noise for 2 h to induce hearing loss and the auditory function was assessed by measuring auditory brainstem response thresholds. Morris water maze test and resting state MRI were computed at 0 day, 1, 3, 6 months post noise to reveal cognitive ability and neural substrate. The interregional connections in the auditory network and default mode network, as well as the connections using the auditory cortex and cingulate cortex as seeds were also examined addtionally. The deficit in spatial learning/memory was only observed at 6 months after noise exposure. The internal connections in the auditory network and default mode network were enhanced at 0 day and decreased at 6 months post noise. The connectivity using the auditory cortex and cingulate cortex as seeds generally followed the rule of “enhancement-normal-decrease-widely decrease”. A new model accounting for arousal, dementia, motor control of NIHL in is proposed. Our study highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Noise-induced hearing loss (NIHL), caused by direct damage to the cochlea, reduces the flow of auditory information to the central nervous system, depriving higher order structures, such as the hippocampus with vital sensory information needed to carry out complex, higher order functions. Although the hippocampus lies outside the classical auditory pathway, it nevertheless receives acoustic information that influence its activity. Here we review recent results that illustrate how NIHL and other types of cochlear hearing loss disrupt hippocampal function. The hippocampus, which continues to generate new neurons (neurogenesis) in adulthood, plays an important role in spatial navigation, memory, and emotion. The hippocampus, which contains place cells that respond when a subject enters a specific location in the environment, integrates information from multiple sensory systems, including the auditory system, to develop cognitive spatial maps to aid in navigation. Acute exposure to intense noise disrupts the place-specific firing patterns of hippocampal neurons, "spatially disorienting" the cells for days. More traumatic sound exposures that result in permanent NIHL chronically suppresses cell proliferation and neurogenesis in the hippocampus; these structural changes are associated with long-term spatial memory deficits. Hippocampal neurons, which contain numerous glucocorticoid hormone receptors, are part of a complex feedback network connected to the hypothalamic-pituitary (HPA) axis. Chronic exposure to intense intermittent noise results in prolonged stress which can cause a persistent increase in corticosterone, a rodent stress hormone known to suppress neurogenesis. In contrast, a single intense noise exposure sufficient to cause permanent hearing loss produces only a transient increase in corticosterone hormone. Although basal corticosterone levels return to normal after the noise exposure, glucocorticoid receptors (GRs) in the hippocampus remain chronically elevated. Thus, NIHL disrupts negative feedback from the hippocampus to the HPA axis which regulates the release of corticosterone. Preclinical studies suggest that the noise-induced changes in hippocampal place cells, neurogenesis, spatial memory, and glucocorticoid receptors may be ameliorated by therapeutic interventions that reduce oxidative stress and inflammation. These experimental results may provide new insights on why hearing loss is a risk factor for cognitive decline and suggest methods for preventing this decline.

AIMS:This study aimed to explore the neural substrate of hearing loss-related central nervous system in rats and its correlation with cognition.METHODS:We identified the neural mechanism for these debilitating abnormalities by inducing a bilateral hearing loss animal model using intense broadband noise (122 dB of broadband noise for 2 h) and used the Morris water maze test to characterize the behavioral changes at 6 months post-noise exposure. Functional magnetic resonance imaging (fMRI) was conducted to clarify disrupted functional network using bilateral auditory cortex (ACx) as a seed. Structural diffusion tensor imaging (DTI) was applied to illustrate characteristics of fibers in ACx and hippocampus. Pearson correlation was computed behavioral tests and other features.RESULTS:A deficit in spatial learning/memory, body weight, and negative correlation between them was observed. Functional connectivity revealed weakened coupling within the ACx and inferior colliculus, lateral lemniscus, the primary motor cortex, the olfactory tubercle, hippocampus, and the paraflocculus lobe of the cerebellum. The fiber number and mean length of ACx and different hippocampal subregions were also damaged in hearing loss rats.CONCLUSION:A new model of auditory-limbic-cerebellum interactions accounting for noise-induced hearing loss and cognitive impairments is proposed.

Eardrum perforation and associated hearing loss is a global health problem. Grafting perforated eardrum with autologous tissues in clinic can restore low‐frequency hearing but often leaves poor recovery of high‐frequency hearing. In this study, the potential of incorporating a thin multilayered graphene membrane (MGM) into the eardrum for broadband hearing recovery in rats is examined. The MGM shows good biocompatibility and biostability to promote the growth of eardrum cells in a regulated manner with little sign of tissue rejection and inflammatory response. After three weeks of implantation, the MGM is found to be encapsulated by a thin layer of newly grown tissue on both sides without a significant folded overgrowth that is often seen in natural healing. The perforation is well sealed, and broadband hearing recovery (1–32 kHz) is enabled and maintained for at least 2 months. Mechanical simulations show that the high elastic modulus of MGM and thin thickness of the reconstructed eardrum play a critical role in the recovery of high‐frequency hearing. This work demonstrates the promise of the use of MGM as a functional graft for perforated eardrum to recover hearing in the broadband frequency region and suggests a new acoustics‐related medical application for graphene‐related 2D materials.

AIMS:We aimed to find where and how noise-induced cochlear hearing loss affects the central nervous system during the early state and identify the neural substrate for aberrant patterns that mediating noise-related anxiety-/depression- like behaviors.METHODS:Broad band noise with 122 dB for 2 hours was conducted to induce hearing loss. We defined 0 day (N0D) and 10 days (N10D) post noise as the acute and sub-acute period. Behavioral tests (Open field test and light/dark test) and resting-state fMRI were computed to evaluate emotional conditions and aberrant neural activity. Functional connectivity analysis using the anterior cingulate cortex as a seed was computed to reveal the spatial distribution beyond auditory network during both periods.RESULTS:Anxiety-/depression-like behaviors were found in rats with noise exposure. Between-group analysis revealed that N0D rats displayed widespread reductions in functional connectivity, spanning primary somatosensory cortex, medial geniculate body, inferior colliculus, cingulate cortex, cerebellar lobule comparing with N10D rats and a similar pattern was also occurred in comparison with the control group.CONCLUSION:Taken together, an "acoustic-causing" network accounting for distress and gating of noise exposure related anxiety/depression was proposed.

Noise induced synaptopathy (NIS) and hidden hearing loss (NIHHL) have been hot topic in hearing research since a massive synaptic loss was identified in CBA mice after a brief noise exposure that did not cause permanent threshold shift (PTS) in 2009. Based upon the amount of synaptic loss and the bias of it to synapses with a group of auditory nerve fibers (ANFs) with low spontaneous rate (LSR), coding-in-noise deficit (CIND) has been speculated as the major difficult of hearing in subjects with NIS and NIHHL. This speculation is based upon the idea that the coding of sound at high level against background noise relies mainly on the LSR ANFs. However, the translation from animal data to humans for NIS remains to be justified due to the difference in noise exposure between laboratory animals and human subjects in real life, the lack of morphological data and reliable functional methods to quantify or estimate the loss of the afferent synapses by noise. Moreover, there is no clear, robust data revealing the CIND even in animals with the synaptic loss but no PTS. In humans, both positive and negative reports are available. The difficulty in verifying CINDs has led a re-examination of the hypothesis that CIND is the major deficit associated with NIS and NIHHL, and the theoretical basis of this idea on the role of LSR ANFs. This review summarized the current status of research in NIS and NIHHL, with focus on the translational difficulty from animal data to human clinicals, the technical difficulties in quantifying NIS in humans, and the problems with the SR theory on signal coding. Temporal fluctuation profile model was discussed as a potential alternative for signal coding at high sound level against background noise, in association with the mechanisms of efferent control on the cochlea gain.

Noise induced synaptopathy (NIS) has been researched extensively since a large amount of synaptic loss without permanent threshold shift (PTS) was found in CBA mice after a brief noise exposure. However, efforts to translate these results to humans have met with little success-and might not be possible since noise exposure used in laboratory animals is generally different from what is experienced by human subjects in real life. An additional problem is a lack of morphological data and reliable functional methods to quantify loss of afferent synapses in humans. Based on evidence for disproportionate synaptic loss for auditory nerve fibers (ANFs) with low spontaneous rates (LSR), coding-in-noise deficits (CIND) have been speculated to be the major difficulty associated with NIS without PTS. However, no robust evidence for this is available in humans or animals. This has led to a re-examination of the role of LSR ANFs in signal coding in high-level noise. The fluctuation profile model has been proposed to support a role for high-SR ANFs in the coding of high-level noise in combination with efferent control of cochlear gain. This study aimed to induce NIS by a low-level, intermittent noise exposure mimicking what is experienced in human life and examined the impact of the NIS on temporal processing under masking. It also evaluated the role of temporal fluctuation in evoking efferent feedback and the effects of NIS on this feedback.

To investigate if the anxiety associated with coronavirus disease 2019 (COVID-19) is a promoting factor to tinnitus. A retrospective research design collected from 188 tinnitus patients, was used to compare the clinical characteristics of tinnitus between the patients in 2020 under pandemic pressure and those from the matching period in 2019. While anxiety was quantified using the Zung's Self-rating Anxiety Scale (SAS), tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) questionnaire and the test of tinnitus loudness (TL). The assessments were repeated after the sound therapy plus educational counselling (STEC) for 38 patients in 2020 and 58 patients in 2019 and compared with EC alone therapy for 42 patients in 2020 and 17 patients in 2019. A large increase in anxiety was evident in 2020 in both case rate and SAS. The treatment of both methods was less effective in 2020. SAS, THI and TL were all deteriorated after the EC alone treatment in 2020, while an improvement was seen in 2019. This suggests that EC alone could not counteract the stress by COVID-19 at all, and the stress, if not managed well, can significantly increase the severity of tinnitus and associated anxiety. By using the EC subgroup in virtual control, we conclude that anxiety can serve as a promoting factor to tinnitus. We believe that this is the first study report that confirm the causative/promotive role of anxiety on tinnitus during COVID-19 pandemic.