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High-fidelity premolded earplugs (HiFi HPDs) are designed to provide relatively uniform attenuation across frequencies. The primary goal of this study was to verify the amount and flatness of individual user attenuation. HiFi HPD attenuation was measured using real-ear attenuation at threshold (REAT) measurements under circumaural earphones. Participants were 16 adults tested using commercial HiFi HPDs marketed for use at recreational music events and/or for use by musicians. There was significant individual variation in attenuation both within and across HiFi HPD brands. In addition to significant differences in achieved attenuation, there were significant differences in the uniformity of the attenuation. These data suggest verification of attenuation is important in musicians who are at risk for music-induced hearing disorders even when using "over-the-counter" uniform-fit HPDs., (Copyright© 2022 by the author(s). Open Access: Licensed under CC-BY-ND-SA 4.0 Int.)

Significance: Noise-induced hearing loss (NIHL) is an important public health issue resulting in decreased quality of life for affected individuals, and significant costs to employers and governmental agencies. Recent Advances: Advances in the mechanistic understanding of NIHL have prompted a growing number of proposed, in-progress, and completed clinical trials for possible protections against NIHL via antioxidants and other drug agents. Thirty-one clinical trials evaluating prevention of either temporary or permanent NIHL were identified and are reviewed. Critical Issues: This review revealed little consistency in the noise-exposed populations in which drugs are evaluated or the primary outcomes used to measure NIHL prevention. Changes in pure-tone thresholds were the most common primary outcomes; specific threshold metrics included both average hearing loss and incidence of significant hearing loss. Changes in otoacoustic emission (OAE) amplitude were relatively common secondary outcomes. Extended high-frequency (EHF) hearing and speech-in-noise perception are commonly adversely affected by noise exposure but are not consistently included in clinical trials assessing prevention of NIHL. Future Directions: Multiple criteria are available for monitoring NIHL, but the specific criterion to be used to define clinically significant otoprotection remains a topic of discussion. Audiogram-based primary outcome measures can be combined with secondary outcomes, including OAE amplitude, EHF hearing, speech-in-noise testing, tinnitus surveys, and patient-reported outcomes. Standardization of test protocols for the above primary and secondary outcomes, and associated reporting criterion for each, would facilitate clinical trial design and comparison of results across investigational drug agents. Antioxid. Redox Signal . 36, 1171-1202.

Firearms produce peak sound pressure levels (peak SPL) between ∼130 and 175 dB peak SPL, creating significant risk of noise-induced hearing loss (NIHL) in those exposed to firearm noise during occupational, recreational, and/or military operations. Noise-induced tinnitus and hearing loss are common in military service members, public safety officers, and hunters/shooters. Given the significant risk of NIHL due to firearm and other noise sources, there is an interest in, and demand for, interventions to prevent and/or treat NIHL in high-risk populations. However, research and clinical trial designs assessing NIHL prevention have varied due to inconsistent data from the literature, specifically with end point definitions, study protocols, and assessment methodologies. This article presents a scoping review of the literature pertaining to auditory changes following firearm noise exposure. Meta-analysis was not possible due to heterogeneity of the study designs. Recommendations regarding audiologic test approach and monitoring of populations at risk for NIHL are presented based on critical review of the existing literature.

Background: The previous 30 years have provided information on the mechanisms of cell death in the inner ear after noise exposure, ototoxic drug injury, and during aging, and clinical trials have emerged for all of these acquired forms of hearing loss. Sudden hearing loss is less well understood, but restoration of hearing after sudden hearing loss is also a long-standing drug target, typically using steroids as an intervention but with other agents of interest as well., Purpose: The purpose of this review was to describe the state of the science regarding clinical testing of investigational medicinal products for the inner ear with respect to treatment or prevention of acquired hearing loss., Data Collection and Analysis: Comprehensive search and summary of clinical trials listed in the National Library of Medicine (www., Clinicaltrials: gov) database identified 61 clinical trials., Results: Study phase, status, intervention, and primary, secondary, and other outcomes are summarized for studies assessing prevention of noise-induced hearing loss, prevention of drug-induced hearing loss, treatment of stable sensorineural hearing loss, and treatment of sudden sensorineural hearing loss., Conclusion: This review provides a comprehensive summary of the state of the science with respect to investigational medicinal products for the inner ear evaluated in human clinical trials, and the current challenges for the field., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Significant variability in noise-induced hearing loss (NIHL) susceptibility suggests there are factors beyond sound level and duration of exposure that contribute to individual susceptibility. External-ear amplification (EEA) from external-ear structures varies significantly due to ear size and shape, potentially influencing NIHL susceptibility. This study tested the hypothesis that EEA can be predicted using non-technical proxy measurements including pinna height (cm), body height (m), and earcanal volume (cm 3 ). 158 participants (4-78 years) completed otoscopy, tympanometry, pinna measurements, body height measurements, and two EEA measurements: (1) total real-ear unaided gain (REUG) of the open ear and (2) real-ear to coupler difference (RECD), representing unaided gain from the earcanal. Participants' individual noise doses were compared in hypothetical exposures. REUG ranged from 5 to 19 dBA and was correlated with pinna height. High-REUG participants were estimated to accrue noise doses at least 5 times higher than low-REUG participants. RECD ranged from 7 to 24 dBA and was correlated with earcanal volume and body height. The results support the hypothesis that EEA measurement could significantly improve estimation of an individual's position along the NIHL risk spectrum. Non-technical proxy measurements of EEA (pinna height, body height, earcanal volume) were statistically significant but yielded high variability in individual EEA prediction.

Animal models have been used to gain insight into the risk of noise-induced hearing loss (NIHL) and its potential prevention using investigational new drug agents. A number of compounds have yielded benefit in pre-clinical (animal) models. However, the acute traumatic injury models commonly used in pre-clinical testing are fundamentally different from the chronic and repeated exposures experienced by many human populations. Diverse populations that are potentially at risk and could be considered for enrollment in clinical studies include service members, workers exposed to occupational noise, musicians and other performing artists, and children and young adults exposed to non-occupational (including recreational) noise. Both animal models and clinical populations were discussed in this special issue, followed by discussion of individual variation in vulnerability to NIHL. In this final contribution, study design considerations for NIHL otoprotection in pre-clinical and clinical testing are integrated and broadly discussed with evidence-based guidance offered where possible, drawing on the contributions to this special issue as well as other existing literature. The overarching goals of this final paper are to (1) review and summarize key information across contributions and (2) synthesize information to facilitate successful translation of otoprotective drugs from animal models into human application.

Guinea pigs have been used in diverse studies to better understand acquired hearing loss induced by noise and ototoxic drugs. The guinea pig has its best hearing at slightly higher frequencies relative to humans, but its hearing is more similar to humans than the rat or mouse. Like other rodents, it is more vulnerable to noise injury than the human or nonhuman primate models. There is a wealth of information on auditory function and vulnerability of the inner ear to diverse insults in the guinea pig. With respect to the assessment of potential otoprotective agents, guinea pigs are also docile animals that are relatively easy to dose via systemic injections or gavage. Of interest, the cochlea and the round window are easily accessible, notably for direct cochlear therapy, as in the chinchilla, making the guinea pig a most relevant and suitable model for hearing. This article reviews the use of the guinea pig in basic auditory research, provides detailed discussion of its use in studies on noise injury and other injuries leading to acquired sensorineural hearing loss, and lists some therapeutics assessed in these laboratory animal models to prevent acquired sensorineural hearing loss.

Noise-induced hearing loss (NIHL) is a common injury for service members and civilians. Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL. There are a host of challenges in translation of investigational new drug agents from animals into human clinical testing, however. Initial articles in this special issue describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective drug agents and design-related factors that impact translation of promising agents into human clinical trials. Additional articles describe populations in which NIHL has a high incidence and factors that affect individual vulnerability. While otoprotective drugs will ultimately be developed for use by specific noise-exposed populations, there has been little effort to develop pre-clinical (animal) models that accurately model exposure hazards across diverse human populations. To facilitate advances in the translational framework for NIHL otoprotection in pre-clinical and clinical testing, the overarching goals of the current series are to (1) review the animal models that have been used, highlighting the relevance to the human populations of interest, (2) provide insight into the populations for whom pharmaceutical interventions might, or might not, be appropriate, and (3) highlight the factors that drive the significant individual variability observed in humans.

The influence of dietary nutrient intake on the onset and trajectory of hearing loss during aging and in mediating protection from challenges such as noise is an important relationship yet to be fully appreciated. Dietary intake provides essential nutrients that support basic cellular processes related to influencing cellular stress response, immune response, cardiometabolic status, neural status, and psychological well-being. Dietary quality has been shown to alter risk for essentially all chronic health conditions including hearing loss and tinnitus. Evidence of nutrients with antioxidant, anti-inflammatory, and anti-ischemic properties, and overall healthy diet quality as otoprotective strategies are slowly accumulating, but many questions remain unanswered. In this article, the authors will discuss (1) animal models in nutritional research, (2) evidence of dietary nutrient-based otoprotection, and (3) consideration of confounds and limitations to nutrient and dietary study in hearing sciences. Given that there are some 60 physiologically essential nutrients, unraveling the intricate biochemistry and multitude of interactions among nutrients may ultimately prove infeasible; however, the wealth of available data suggesting healthy nutrient intake to be associated with improved hearing outcomes suggests the development of evidence-based guidance regarding diets that support healthy hearing may not require precise understanding of all possible interactions among variables. Clinical trials evaluating otoprotective benefits of nutrients should account for dietary quality, noise exposure history, and exercise habits as potential covariates that may influence the efficacy and effectiveness of test agents; pharmacokinetic measures are also encouraged.

With advances in the understanding of mechanisms of noise injury, the past 30 years have brought numerous efforts to identify drugs that prevent noise-induced hearing loss (NIHL). The diverse protocols used across investigations have made comparisons across drugs difficult. A systematic review of the literature by Hammill [(2017). Doctoral thesis, The University of Texas at Austin] identified original reports of chemical interventions to prevent or treat hearing loss caused by noise exposure. An initial search returned 3492 articles. After excluding duplicate articles and articles that did not meet the systematic review inclusion criteria, a total of 213 studies published between 1977 and 2016 remained. Reference information, noise exposure parameters, species, sex, method of NIHL assessment, and pharmaceutical intervention details for these 213 studies were entered into a database. Frequency-specific threshold shifts in control animals (i.e., in the absence of pharmaceutical intervention) are reported here. Specific patterns of hearing loss as a function of species and noise exposure parameters are provided to facilitate the selection of appropriate pre-clinical models. The emphasis of this report is octave band noise exposure, as this is one of the most common exposure protocols across pharmacological otoprotection studies.

Objective: Short-term noise exposure that induces transient changes in thresholds has induced permanent cochlear synaptopathy in multiple species. Here, the literature was reviewed to gain translational insight into the relationships between noise exposure, ABR metrics, speech-in-noise performance and TTS in humans., Design: PubMed-based literature search, retrieval and review of full-text articles., Study Sample: Peer-reviewed literature identified using PubMed search., Results: Permanent occupational noise-induced hearing loss (NIHL) is frequently accompanied by abnormal ABR amplitude and latency. In the absence of NIHL, there are mixed results for relationships between noise exposure and ABR metrics. Interpretation of speech-in-noise deficits is difficult as both cochlear synaptopathy and outer hair cell (OHC) loss can drive deficits. Reductions in Wave I amplitude during TTS may reflect temporary OHC pathology rather than cochlear synaptopathy. Use of diverse protocols across studies reduces the ability to compare outcomes across studies., Conclusions: Longitudinal ABR and speech-in-noise data collected using consistent protocols are needed. Although speech-in-noise testing may not reflect cochlear synaptopathy, speech-in-noise testing should be completed as part of a comprehensive test battery to provide the objective measurement of patient difficulty.

Objectives: The purpose of this study was to examine the relationship between noise exposure history, type 1 diabetes mellitus (DM), and suprathreshold measures of auditory function., Design: A cross-sectional study was conducted; 20 normal-hearing participants without type 1 DM were matched on age and sex to 20 normal-hearing participants with type 1 DM (n=40). Participants, all having normal audiometric thresholds, completed noise history questionnaires and a battery of auditory physiological tests including transient evoked otoacoustic emissions, distortion product otoacoustic emissions, and auditory brainstem responses (ABR) at 80 dB nHL and at 2 different stimulus rates in both ears. Amplitude and latency for waves I and V are presented. Statistical analysis included analysis of variance and multivariate linear regression., Results: No statistically significant difference for noise exposure history, otoacoustic emissions (OAE), or ABR findings were found between type 1 DM and matched controls. Males and females showed statistically significant differences for OAE amplitudes and ABR amplitude and latencies. However, no statistically significant relationship was found between noise outcomes and OAE or ABR findings., Conclusions: No statistically significant relationship between noise history and our suprathreshold ABR or OAE findings was indicated for individuals with type 1 DM or matched controls. The lack of evidence of noise related neuropathology might be due to inadequate noise exposure or lack of comorbidities in our DM group. Implications of these findings are discussed.

Background: Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial., Methods: In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846., Findings: Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference -2·75 dB, 95% CI -4·54 to -0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference -0·84 dB, 95% CI -2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference -0·27, 95% CI -2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group., Interpretation: Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss., Funding: Sound Pharmaceuticals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

For decades, we have presumed the death of hair cells and spiral ganglion neurons are the main cause of hearing loss and difficulties understanding speech in noise, but new findings suggest synapse loss may be the key contributor. Specifically, recent preclinical studies suggest that the synapses between inner hair cells and spiral ganglion neurons with low spontaneous rates and high thresholds are the most vulnerable subcellular structures, with respect to insults during aging and noise exposure. This cochlear synaptopathy can be "hidden" because this synaptic loss can occur without permanent hearing threshold shifts. This new discovery of synaptic loss opens doors to new research directions. Here, we review a number of recent studies and make suggestions in two critical future research directions. First, based on solid evidence of cochlear synaptopathy in animal models, it is time to apply molecular approaches to identify the underlying molecular mechanisms; improved understanding is necessary for developing rational, effective therapies against this cochlear synaptopathy. Second, in human studies, the data supporting cochlear synaptopathy are indirect although rapid progress has been made. To fully identify changes in function that are directly related this hidden synaptic damage, we argue that a battery of tests including both electrophysiological and behavior tests should be combined for diagnosis of "hidden hearing loss" in clinical studies. This new approach may provide a direct link between cochlear synaptopathy and perceptual difficulties., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In animals, noise exposures that produce robust temporary threshold shifts (TTS) can produce immediate damage to afferent synapses and long-term degeneration of low spontaneous rate auditory nerve fibers. This synaptopathic damage has been shown to correlate with reduced auditory brainstem response (ABR) wave-I amplitudes at suprathreshold levels. The perceptual consequences of this "synaptopathy" remain unknown but have been suggested to include compromised hearing performance in competing background noise. Here, we used a modified startle inhibition paradigm to evaluate whether noise exposures that produce robust TTS and ABR wave-I reduction but not permanent threshold shift (PTS) reduced hearing-in-noise performance. Animals exposed to 109 dB SPL octave band noise showed TTS >30 dB 24-h post noise and modest but persistent ABR wave-I reduction 2 weeks post noise despite full recovery of ABR thresholds. Hearing-in-noise performance was negatively affected by the noise exposure. However, the effect was observed only at the poorest signal to noise ratio and was frequency specific. Although TTS >30 dB 24-h post noise was a predictor of functional deficits, there was no relationship between the degree of ABR wave-I reduction and degree of functional impairment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: There has been significant discussion in the literature regarding music player use by adolescents and young adults, including whether device use is driving an increase in hearing loss in these populations. While many studies report relatively safe preferred listening levels, some studies with college student participants have reported listening habits that may put individuals at risk for noise-induced hearing loss (NIHL) if those listening habits continue over the long term., Purpose: The goal of the current investigation was to extend listening level data collection sites from urban city settings studied by others to a more rural campus setting., Research Design: This was a prospective study., Study Sample: Participants were 138 students on the University of Florida campus (94 males, 44 females), 18 years or older (mean = 21 years; range: 18-33 years)., Data Collection and Analysis: In this investigation, the current output level (listening level) was measured from personal listening devices used by students as they passed by a recruiting table located in one of three areas of the University of Florida campus. One location was in an open-air campus square; the other two locations were outside the campus recreation building ("gym") and outside the undergraduate library, with participants recruited as they exited the gym or library buildings. After providing written informed consent, participants completed a survey that included questions about demographics and typical listening habits (hours per day, days per week). The output level on their device was then measured using a "Jolene" mannequin., Results: Average listening levels for participants at the three locations were as follows: gym: 85.9 ± 1.4 dBA; campus square: 83.3 ± 2.0 dBA; library: 76.9 ± 1.3 dBA. After adjusting to free-field equivalent level, average listening levels were gym: 79.7 ± 1.4 dBA; campus square: 76.9 ± 2.1 dBA; library: 70.4 ± 1.4 dBA. There were no statistically significant differences between male and female listeners, and there were no reliable differences as a function of race. After accounting for daily and weekly use patterns, 5% were deemed at risk based on the criteria put forward by the Occupational Safety and Health Administration, and 9% were deemed at risk based on the guidance provided by the National Institute for Occupational Safety and Health., Conclusions: Some 5-10% of the participants were deemed at risk; this finding is consistent with other studies using similar methods. It is possible that the same listeners would have selected different listening levels in other noise backgrounds, however. This unknown variable makes it difficult to estimate risk with a single listening level measurement., (American Academy of Audiology)

Objective: In humans, the accepted clinical standards for detecting hearing loss are the behavioral audiogram, based on the absolute detection threshold of pure-tones, and the threshold auditory brainstem response (ABR). The audiogram and the threshold ABR are reliable and sensitive measures of hearing thresholds in human listeners. However, recent results from noise-exposed animals demonstrate that noise exposure can cause substantial neurodegeneration in the peripheral auditory system without degrading pure-tone audiometric thresholds. It has been suggested that clinical measures of auditory performance conducted with stimuli presented above the detection threshold may be more sensitive than the behavioral audiogram in detecting early-stage noise-induced hearing loss in listeners with audiometric thresholds within normal limits., Methods: Supra-threshold speech-in-noise testing and supra-threshold ABR responses are reviewed here, given that they may be useful supplements to the behavioral audiogram for assessment of possible neurodegeneration in noise-exposed listeners., Conclusion: Supra-threshold tests may be useful for assessing the effects of noise on the human inner ear, and the effectiveness of interventions designed to prevent noise trauma. The current state of the science does not necessarily allow us to define a single set of best practice protocols. Nonetheless, we encourage investigators to incorporate these metrics into test batteries when feasible, with an effort to standardize procedures to the greatest extent possible as new reports emerge.

Objective: Firearm discharges produce hazardous levels of impulse noise that can lead to permanent hearing loss. In the present study, we evaluated the effects of suppression, ammunition, and barrel length on AR-15 rifles., Design: Sound levels were measured left/right of a user's head, and 1-m left of the muzzle, per MIL-STD-1474-D, under both unsuppressed and suppressed conditions., Study Sample: Nine commercially available AR-15 rifles and 14 suppressors were used., Results: Suppressors significantly decreased peak dB SPL at the 1-m location and the left ear location. However, under most rifle/ammunition conditions, levels remained above 140 dB peak SPL near a user's right ear. In a subset of conditions, subsonic ammunition produced values near or below 140 dB peak SPL. Overall suppression ranged from 7-32 dB across conditions., Conclusions: These data indicate that (1) suppressors reduce discharge levels to 140 dB peak SPL or below in only a subset of AR-15 conditions, (2) shorter barrel length and use of muzzle brake devices can substantially increase exposure level for the user, and (3) there are significant left/right ear sound pressure differences under suppressed conditions as a function of the AR-15 direct impingement design that must be considered during sound measurements to fully evaluate overall efficacy.

Purpose: Hearing loss prevention has always been an important issue for audiologists. The importance of hearing loss prevention education for young musicians is now recognized by the National Association for Music Education as well as the National Association of Schools of Music. Adopt-a-Band is a commercial program designed to foster hearing loss prevention behavior in young musicians., Method: This study assessed changes in earplug use, measured using self-report surveys, after Adopt-a-Band training. Participants were members of 2 high school marching bands who viewed an informational DVD and reviewed fact sheets. Flat-attenuation earplugs were distributed, and training was provided. In addition, study participants engaged in discussion of hearing loss with a doctor of audiology student., Results: Before training, 23% of participants reported they had previously used hearing protection. Immediately after training, 94% of participants reported they planned to use hearing protection at least occasionally. In a final end-of-season survey, earplug use had reliably increased; 62% of participants reported they used earplugs at least occasionally., Conclusions: Earplug use increased, but self-reported behavioral change was not as robust as predicted from self-reported participant intentions. Participant comments regarding factors that influenced their earplug use decisions suggest opportunities to improve training.

Background: Human hearing is sensitive to sounds from as low as 20 Hz to as high as 20,000 Hz in normal ears. However, clinical tests of human hearing rarely include extended high-frequency (EHF) threshold assessments, at frequencies extending beyond 8000 Hz. EHF thresholds have been suggested for use monitoring the earliest effects of noise on the inner ear, although the clinical usefulness of EHF threshold testing is not well established for this purpose., Purpose: The primary objective of this study was to determine if EHF thresholds in healthy, young adult college students vary as a function of recreational noise exposure., Research Design: A retrospective analysis of a laboratory database was conducted; all participants with both EHF threshold testing and noise history data were included. The potential for "preclinical" EHF deficits was assessed based on the measured thresholds, with the noise surveys used to estimate recreational noise exposure., Study Sample: EHF thresholds measured during participation in other ongoing studies were available from 87 participants (34 male and 53 female); all participants had hearing within normal clinical limits (≤25 HL) at conventional frequencies (0.25-8 kHz)., Results: EHF thresholds closely matched standard reference thresholds [ANSI S3.6 (1996) Annex C]. There were statistically reliable threshold differences in participants who used music players, with 3-6 dB worse thresholds at the highest test frequencies (10-16 kHz) in participants who reported long-term use of music player devices (>5 yr), or higher listening levels during music player use., Conclusions: It should be possible to detect small changes in high-frequency hearing for patients or participants who undergo repeated testing at periodic intervals. However, the increased population-level variability in thresholds at the highest frequencies will make it difficult to identify the presence of small but potentially important deficits in otherwise normal-hearing individuals who do not have previously established baseline data., (American Academy of Audiology.)

Oxidative stress has been implicated broadly as a cause of cell death and neural degeneration in multiple disease conditions; however, the evidence for successful intervention with dietary antioxidant manipulations has been mixed. In this study, we investigated the potential for protection of cells in the inner ear using a dietary supplement with multiple antioxidant components, which were selected for their potential interactive effectiveness. Protection against permanent threshold shift (PTS) was observed in CBA/J mice maintained on a diet supplemented with a combination of β-carotene, vitamins C and E, and magnesium when compared with PTS in control mice maintained on a nutritionally complete control diet. Although hair cell survival was not enhanced, noise-induced loss of type II fibrocytes in the lateral wall was significantly reduced (P < 0.05), and there was a trend toward less noise-induced loss in strial cell density in animals maintained on the supplemented diet. Taken together, our data suggest that prenoise oral treatment with the high-nutrient diet can protect cells in the inner ear and reduce PTS in mice. The demonstration of functional and morphologic preservation of cells in the inner ear with oral administration of this antioxidant supplemented diet supports the possibility of translation to human patients and suggests an opportunity to evaluate antioxidant protection in mouse models of oxidative stress-related disease and pathology., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Hearing loss encompasses both temporary and permanent deficits. If temporary threshold shift (TTS) and permanent threshold shift (PTS) share common pathological mechanisms, then agents that reduce PTS also should reduce TTS. Several antioxidant agents have reduced PTS in rodent models; however, reductions in TTS have been inconsistent. This study first determined whether dietary antioxidants (beta-carotene and vitamins C and E) delivered in combination with magnesium (Mg) reliably increase plasma concentrations of the active agents. Then, additional manipulations tested the hypothesis that these nutrients reduce acute TTS insult in the first 24 h after loud sound as well as longer lasting changes in hearing measured up to 7 days postnoise. Saline or nutrients were administered to guinea pigs prior to and after noise exposure. Sound-evoked electrophysiological responses were measured before noise, with tests repeated 1-h postnoise, as well as 1-day, 3-days, 5-days, and 7-days postnoise. All subjects showed significant functional recovery; subjects treated with nutrients recovered more rapidly and had better hearing outcomes at early postnoise times as well as the final test time. Thus, this combination of nutrients, which produced significant increases in plasma concentrations of vitamins C and E and Mg, effectively reduced hearing loss at multiple postnoise times. These data suggest that free radical formation contributes to TTS as well as PTS insults and suggest a potential opportunity to prevent TTS in human populations., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7-10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss.