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Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skipping events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose: to analyze the impact of a Hearing Conservation Program on occupational noise-induced hearing loss in a metallurgical plant. Methods: a longitudinal case study (2003-2018) was carried out and a Hearing Conservation Program assessed with interviews and document verification. The assessment also included 2,350 audiometric examinations and occupational noise exposure of 152 Hearing Conservation Program - participating employees, collecting the data from the company’s database. Results: high compliance indices regarding occupational noise -induced hearing loss - prevention Hearing Conservation Program practices were found between 2003 and 2018. The comparison between 2018 and 2003 showed a reduced number of workers exposed to noise at 85 dB(A) or above. The final prevalence of audiometric changes suggestive of occupational noise-induced hearing loss that remained in degree I differed from the initial one in the period. The high Hearing Conservation Program percentages and low occupational noise-induced hearing loss indicators point to an inverse relationship between them. Conclusion: the results suggest a positive impact of a Hearing Conservation Program on occupational noise-induced hearing loss in this metallurgical plant, in the period studied.

Glenis Long championed the application of quantitative psychophysical methods to understand comparative hearing abilities across species. She contributed the first psychophysical studies of absolute and masked hearing sensitivities in an auditory specialist, the echolocating horseshoe bat. Her data demonstrated that this bat has hyperacute frequency discrimination in the 83-kHz range of its echolocation broadcast. This specialization facilitates the bat's use of Doppler shift compensation to separate echoes of fluttering insects from concurrent echoes of non-moving objects. In this review, we discuss another specialization for hearing in a species of echolocating bat that contributes to perception of echoes within a complex auditory scene. Psychophysical and behavioral studies with big brown bats show that exposures to long duration, intense wideband or narrowband ultrasonic noise do not induce significant increases in their thresholds to echoes and do not impair their ability to orient through a naturalistic sonar scene containing multiple distracting echoes. Thresholds of auditory brainstem responses also remain low after intense noise exposures. These data indicate that big brown bats are not susceptible to temporary threshold shifts as measured in comparable paradigms used with other mammals, at least within the range of stimulus parameters that have been tested so far. We hypothesize that echolocating bats have evolved a decreased susceptibility to noise-induced hearing losses as a specialization for echolocation in noisy environments., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Purpose: This study aimed to investigate dynamic change of permeability of blood-labyrinth barrier (BLB) after noise exposure and its effect on the drug delivery efficiency of systemic administration., Methods: Gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (DEX) were used as tracers, and magnetic resonance imaging (MRI) and immunofluorescence were used to observe the change of the BLB after strong noise exposure in guinea pigs. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to observe the effect of the breakdown of BLB after noise exposure on the drug delivery efficiency of intravenous DEX. The guinea pigs were divided into 6 groups: normal group (N), 1, 3, 5, 8, and 12 days after noise exposure groups (P1, P3, P5, P8, P12), with 5 animals in each group., Results: The BLB changes dynamically after noise exposure. Increased permeability of the blood-endolymph barrier, the endolymph-perilymph barrier, and the blood-nerve barrier was observed at days 1-3, 1-5, and 1-8, respectively, after noise exposure in guinea pigs. Higher drug concentration in the cochlear tissue was obtained by intravenous administration of DEX in guinea pigs during the time window of increased permeability of the BLB., Conclusion: After noise exposure, the increased BLB permeability makes it easier for drugs to enter the inner ear from blood. In guinea pigs, 1-8 days after strong noise exposure, the drug delivery efficiency of systemic administration increased. After 8 days, the efficiency gradually returned to normal level. 1-8 days after noise exposure may be the best intervention time for systemic administration., Level of Evidence: NA Laryngoscope, 134:2377-2386, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Current approaches for evaluating noise-induced hearing loss (NIHL), such as the International Standards Organization 1999 (ISO) 1999 prediction model, rely mainly on noise energy and exposure time, thus ignoring the intricate time-frequency characteristics of noise, which also play an important role in NIHL evaluation. In this study, an innovative NIHL prediction model based on temporal and spectral feature extraction using an asymmetric convolution algorithm is proposed., Design: Personal data and individual occupational noise records from 2214 workers across 23 factories in Zhejiang Province, China, were used in this study. In addition to traditional metrics like noise energy and exposure duration, the importance of time-frequency features in NIHL assessment was also emphasized. To capture these features, operations such as random sampling, windowing, short-time Fourier transform, and splicing were performed to create time-frequency spectrograms from noise recordings. Two asymmetric convolution kernels then were used to extract these critical features. These features, combined with personal information (e.g., age, length of service) in various configurations, were used as model inputs. The optimal network structure was selected based on the area under the curve (AUC) from 10-fold cross-validation, alongside the Wilcoxon signed ranks test. The proposed model was compared with the support vector machine (SVM) and ISO 1999 models, and the superiority of the new approach was verified by ablation experiments., Results: The proposed model had an AUC of 0.7768 ± 0.0223 (mean ± SD), outperforming both the SVM model (AUC: 0.7504 ± 0.0273) and the ISO 1999 model (AUC: 0.5094 ± 0.0071). Wilcoxon signed ranks tests confirmed the significant improvement of the proposed model ( p = 0.0025 compared with ISO 1999, and p = 0.00142 compared with SVM)., Conclusions: This study introduced a new NIHL prediction method that provides deeper insights into industrial noise exposure data. The results demonstrated the superior performance of the new model over ISO 1999 and SVM models. By combining time-frequency features and personal information, the proposed approach bridged the gap between conventional noise assessment and machine learning-based methods, effectively improving the ability to protect workers' hearing., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models., Competing Interests: Competing interests statement:H.R., S.B., B.B., R.W., M.K., B.Ü., N.E., and R.S. are current employees and T.Z. and F.T. are former employees of AudioCure Pharma GmbH, which is developing treatments for sudden sensorineural hearing loss. H.R. and R.S. own shares of AudioCure Pharma GmbH. H.R., T.Z., and R.S. are named on patents from AudioCure Pharma GmbH, covering AC102 for use in otic diseases. J.H.-R. has an ongoing paid collaboration with AudioCure Pharma GmbH. C.A. is currently holding a grant from the Christian Doppler Research Association (CD Laboratory for Inner Ear Research) and is receiving funding from MED-EL Corporation, Innsbruck, Austria. S.K.P. is a scientific board member and was previously a paid consultant of AudioCure Pharma GmbH. M.N. and C.A. are and were (Principal) Investigators in previous and ongoing clinical studies of AudioCure Pharma GmbH. S.K.P. is a coordinating investigator of one of their ongoing clinical studies.

Objectives. To investigate how mouse cochleae are affected by the striking noise of titanium head golf driver. Methods. Thirty-two BALB/c mice (20–22 g) with normal hearing were used. The impact acoustic stimulus generated by the striking of titanium golf driver head was centered around 4.5 kHz with 120.5 dB sound pressure level. The recorded impact noise was provided to mice in two ways with the same exposure time of 288 seconds: 1,440 repetitions and an impact duration of 0.2 seconds for 2 hours (repetitive noise) or serially connected impact noise for 288 seconds (continuous noise). Auditory brainstem responses were measured at baseline, day 7, and day 14 after exposure. The mice were then sacrificed for histology. Results. Both groups showed statistically significant threshold shifts immediately after noise exposure. Mice in the continuous exposure group, except for those exposed to 32 kHz noise, recovered from threshold shifts 1–2 weeks after noise exposure. However, in the repetitive exposure group, threshold shifts remained for 2 weeks after exposure. The repetitive exposure group had greater hair cell damage than did the continuous exposure group. Structural changes in the stria vascularis were observed in the repetitive exposure group. Conclusion. Overexposure to impact noise caused by hitting of titanium head golf driver may be hazardous to the cochlea, and repetitive exposure may induce greater damage than continuous exposure.

Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to develop a time-efficient music exposure and testing paradigm that safely creates temporary cochlear dysfunction that could be used in future temporary threshold shift (TTS) studies., Method: A 30-min audio compilation of pop rock music tracks was created. Adult volunteers with normal hearing were then exposed to this music material monaurally through headphones for 30 min at 97 dBA or 15 min at 100 dBA. Levels were measured from the ear of a manikin and are considered to provide an equivalent daily noise dose based on a 3-dB exchange. We assessed the changes in their hearing, by means of distortion product otoacoustic emission (DPOAE) testing, and standard and extended high-frequency pure-tone audiometry before and after exposure. There were 17 volunteers in total. In the first trial, eight volunteers (four females; Mdn age = 31 years [interquartile range, IQR = 4.25]) were included. Although TTS was observed in all eight participants for at least one frequency, a large variation in affected frequencies was observed. To address this issue, the audio material was further remastered to adjust levels across the different frequency bands. Fourteen adults (nine newly recruited and five from the first trial; seven females; Mdn age = 31 years [IQR = 5]) were exposed to the new material., Results: All but two of 17 participants presented clinically significant TTS or decrease in DPOAE amplitude in at least one frequency. Statistically significant average TTS of 7.43 dB was observed at 6 kHz. There were statistically significant average DPOAE amplitude shifts of -2.55 dB at 4 kHz, -4.97 dB at 6 kHz, and -3.14 dB at 8 kHz. No participant presented permanent threshold shift., Conclusions: A monaural music paradigm was developed and shown to induce statistically significant TTS and DPOAE amplitude shifts, without evidence of permanent loss. This realistic and time-efficient paradigm may be considered a viable option for experimental studies of temporary music-induced hearing loss., Supplemental Material: https://doi.org/10.23641/asha.25016471.

Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have a central origin. The effects of noise-induced hearing loss on the auditory cortex have been documented in many studies. One limitation of these studies, however, is that the effects of noise trauma have been mostly studied at the granular layer (i.e, the main cortical recipient of thalamic input), while the cortex is a very complex structure, with six different layers each having its own pattern of connectivity and role in sensory processing. The present study aims to investigate the effects of acute and chronic noise trauma on the laminar pattern of stimulus-evoked activity in the primary auditory cortex of the anesthetized guinea pig. We show that acute and chronic noise trauma are both followed by an increase in stimulus-evoked cortical responses, mostly in the granular and supragranular layers. The cortical responses are more monotonic as a function of the intensity level after noise trauma. There was minimal change, if any, in local field potential (LFP) amplitude after acute noise trauma, while LFP amplitude was enhanced after chronic noise trauma. Finally, LFP and the current source density analysis suggest that acute but more specifically chronic noise trauma is associated with the emergence of a new sink in the supragranular layer. This result suggests that supragranular layers become a major input recipient. We discuss the possible mechanisms and functional implications of these changes. NEW & NOTEWORTHY Our study shows that cortical activity is enhanced after trauma and that the sequence of cortical column activation during stimulus-evoked response is altered, i.e. the supragranular layer becomes a major input recipient. We speculate that these large cortical changes may play a key role in the auditory hypersensitivity (hyperacusis) that can be triggered after noise trauma in human subjects.

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: This paper discusses the concept of acoustic shock based on a literature review and the results of our own research into cases seen in both clinical and medicolegal practice. With the demise of traditional 'metal bashing' and 'smoke stack' heavy industries, there has been a decline in the incidence of noise-induced hearing loss and tinnitus in this form of employment. However, with the increasing establishment of call centre work, the emergence of acoustic shock has been noted. Acoustic shock is recognised as a clinical entity distinct from noise-induced hearing loss and acoustic trauma. Objective: This article discusses clinical implications, medicolegal considerations in light of a recent high-profile court case and proposed criteria for diagnosis. [ABSTRACT FROM AUTHOR]