Significant Threshold Shift Research Articles

Oral D-methionine protects against cisplatin-induced hearing loss in humans: phase 2 randomized clinical trial in India

Objective: This exploratory Phase 2 clinical trial is the first determining safety and efficacy of oral D-methionine (D-met) in reducing cisplatin-induced ototoxicity. Design: Randomised parallel double-blind placebo-controlled exploratory Phase 2 study. Study samples: Fifty adult cancer patients received oral D-met or placebo before each cisplatin dose. Physical examination, blood collection and audiometry occurred at baseline and subsequent visits plus post-treatment audiometry. After attrition, final analysis included 27 patients. Results: Significant treatment group by ear and time (baseline vs. post-treatment) interactions occurred at 10 kHz and 11.2 kHz. Placebo and D-met groups differed in threshold shift for left ear at 11.2 kHz (mean difference = 22.97 dB [9.59, 36.35]). Averaging across ears, placebo group showed significant threshold shifts from baseline to post-treatment at 10 kHz (mean shift= −13.65 dB [−21.32,−5.98]), 11.2 kHz (−16.15 dB [−25.19,−7.12]), and 12.5 kHz (−11.46 dB [−19.18,−3.74]) but not 8 kHz (−8.65 dB [−17.86, 0.55]). The D-met group showed no significant threshold shifts (8 kHz: −1.25 dB [−7.75, 5.25]; 10 kHz:−3.93 dB [−8.89, 1.03]; 11.2 kHz:−4.82 dB [−11.21, 1.57]; 12.5 kHz:−3.68 dB [−11.57, 4.21]). Side effects did not significantly differ between groups. Conclusion: Oral D-met reduces cisplatin-induced ototoxicity in humans.

The Relationship Between Blast-related Hearing Threshold Shift and Insomnia in U.S. Military Personnel.

Hearing loss and insomnia emerged as preeminent sources of morbidity among military service members and veterans who served in the recent Iraq and Afghanistan conflicts. Significant threshold shift (STS), an early indicator of hearing loss, has not been studied in relation to insomnia. This study's objective was to examine the co-occurrence of STS and insomnia among U.S. military personnel with blast-related injury. A total of 652 service members who were blast-injured during military operations in Iraq or Afghanistan between 2004 and 2012 were identified from the Blast-Related Auditory Injury Database. Pre- and post-injury audiometric data were used to ascertain new-onset STS, defined as 30 dB or greater increase for the sum of thresholds at 2,000, 3,000, and 4,000 Hz for either ear. Insomnia diagnosed within 2 years post-injury was abstracted from electronic medical records. Multivariable logistic regression analysis examined the relationship between STS and insomnia, while adjusting for age, year of injury, occupation, injury severity, tinnitus and concussion diagnosed in-theater, and PTSD. A majority of the study sample was aged 18-25 years (79.9%) and sustained mild-to-moderate injuries (92.2%). STS was present in 21.1% of service members. Cumulative incidence of diagnosed insomnia was 22.3% and 11.1% for those with and without STS, respectively. After adjusting for covariates, those with STS had nearly 2-times higher odds of insomnia (odds ratio (OR) = 1.91, 95% CI = 1.12-3.24) compared with those without STS. In multivariable modeling, the strongest association was between PTSD and insomnia (OR = 5.57, 95% CI = 3.35-9.26). A secondary finding of note was that military personnel with STS had a significantly higher frequency of PTSD compared with those without STS (28.1% vs. 15.2%). Hearing threshold shift was associated with insomnia in military personnel with blast-related injury and could be used to identify service members at risk. Multidisciplinary care is needed to manage the co-occurrence of both conditions during the post-deployment rehabilitation phase. Future research should evaluate the specific mechanisms involved in this relationship and further explore the association between hearing threshold shift and PTSD.

Occupational Noise Exposure and Longitudinal Hearing Changes in Post-9/11 US Military Personnel During an Initial Period of Military Service.

Auditory impairments, particularly those resulting from hazardous occupational noise exposures, are pressing concerns for the US Departments of Defense (DoD) and Veterans Affairs (VA). However, to date, no studies have estimated the rate of hearing threshold change that occurs during service or how changes may vary by military occupation. Hearing threshold changes during military service have historically been reported as the proportion of Service members demonstrating a significant threshold shift. This approach does not capture the rate of the hearing threshold change or the specific audiometric frequencies impacted. Determining the rate of hearing threshold change, and factors that affect the rate of change, is important to elucidate the impact of military service on hearing and to guide prevention strategies and subsequent hearing health care. Our primary objective was to estimate the annual rate of hearing threshold change during military service as a consequence of military occupational noise exposure ranking. We linked audiometric data, collected from military personnel as part of a DoD hearing conservation program, to data describing demographic and military-service characteristics obtained from individuals enrolled in the Noise Outcomes In Service members Epidemiology Study. The analytic cohort included Veterans who enlisted in military service after September 2001 (n = 246). We examined the longitudinal association between military occupations categorized as having a low, moderate, or high noise exposure ranking and pure-tone hearing thresholds (500 to 6000 Hz) using a hierarchical linear model. The average annual rate of hearing threshold change and their 95% confidence intervals were estimated by service branch, military occupational noise exposure ranking, and audiometric test frequency. On average, hearing threshold change ranged between -0.5 and 1.1 dB/year and changes over time varied by service branch, audiometric test frequency, and military occupation noise ranking. Generally, higher test frequencies (3000 to 6000 Hz) and military occupations with moderate or high noise exposure rankings had the greatest average annual rates of hearing threshold change; however, no dose-response relationship was observed. Among Marine Corps personnel, those exposed to occupations with high noise rankings demonstrated the greatest average annual rate of change (1.1 dB/year at 6000 Hz). Army personnel exposed to occupations with moderate noise rankings demonstrated the greatest average annual rate of change (0.6 dB/year at 6000 Hz). This study (1) demonstrates the unique use of DoD hearing conservation program data, (2) is the first analysis of hearing threshold changes over time using such data, and (3) adds to the limited literature on longitudinal changes in hearing. The difference in hearing threshold changes across military branches is likely indicative of their varying noise exposures, hearing protection device use and enforcement, and surveillance practices. Results suggest Marine Corps and Army personnel are at risk for hearing threshold changes and that, among Army personnel, this is most pronounced among those exposed to moderate levels of occupational noise exposure. Estimates of the rate of hearing threshold change by frequency and factors that impact hearing are useful to inform the DoD's efforts to protect the hearing of their Service members and to the Veterans Affairs's efforts to identify and rehabilitate those most likely to experience hearing threshold change.

Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity.

Cisplatin chemotherapy often causes permanent hearing loss, which leads to a multifaceted decrease in quality of life. Identification of early cisplatin-induced cochlear damage would greatly improve clinical diagnosis and provide potential drug targets to prevent cisplatin's ototoxicity. With improved functional and immunocytochemical assays, a recent seminal discovery revealed that synaptic loss between inner hair cells and spiral ganglion neurons is a major form of early cochlear damage induced by noise exposure or aging. This breakthrough discovery prompted the current study to determine early functional, cellular, and molecular changes for cisplatin-induced hearing loss, in part to determine if synapse injury is caused by cisplatin exposure. Cisplatin was delivered in one to three treatment cycles to both male and female mice. After the cisplatin treatment of three cycles, threshold shift was observed across frequencies tested like previous studies. After the treatment of two cycles, beside loss of outer hair cells and an increase in high-frequency hearing thresholds, a significant latency delay of auditory brainstem response wave 1 was observed, including at a frequency region where there were no changes in hearing thresholds. The wave 1 latency delay was detected as early cisplatin-induced ototoxicity after only one cycle of treatment, in which no significant threshold shift was found. In the same mice, mitochondrial loss in the base of the cochlea and declining mitochondrial morphometric health were observed. Thus, we have identified early spiral ganglion-associated functional and cellular changes after cisplatin treatment that precede significant threshold shift.

Are fitness instructors at risk of hearing impairment?

The entertainment industry can pose a risk of hearing impairment to employees. The aim of the study is to assess whether occupational exposure to loud sounds (music) is related to temporary hearing threshold shifts in fitness instructors. The study comprised a total of 29 fitness instructors working in fitness clubs. The noise dosimeters were used to determine individual noise exposure during typical 1-2 hours exercises conducting by the instructors. Pure-tone audiometry and Hearing in Noise Test (HINT) were performed before and just after the session to assess temporary changes in hearing. The A-weighted equivalent-continuous sound pressure level (LAeq,T) during typical exercises session ranged from 76.3 to 96 dB. Referring to the 3-dB equal energy rule, such exposures may exceed the upper exposure action value (85 dB) set for the occupational settings by the Directive 2003/10/EC. A significant temporary threshold shift (at least 6 dB) was observed in 33 audiograms (40 %). No impairment of speech understanding was observed in the HINT. Fitness instructors may constitute a population at increased risk of hearing impairment. Further studies are needed to conclude on hearing protection programs in this group of workers.

Prospective cohort study of ototoxicity in persons with cystic fibrosis following a single course of intravenous tobramycin

IntroductionAminoglycoside (AG) antibiotics, such as tobramycin, are known to be ototoxic but important clinically due to their bactericidal efficacy. Persons with cystic fibrosis (CF) are at risk for AG-induced ototoxicity due to the repeated use of intravenous (IV) tobramycin for the treatment of pulmonary exacerbations. While it is well-established that ototoxic hearing loss is highly prevalent in this clinical population, the progression of hearing loss over time remains unclear. Cumulative IV-AG dosing has been associated with a higher risk of ototoxic hearing loss, yet some individuals lose substantial hearing after a single IV-AG treatment, while others never seem to lose hearing. Methods31 persons with CF (18 on IV tobramycin, 13 controls) were enrolled in an observational study. Pure-tone hearing thresholds (0.25–16 kHz) were measured at baseline (pre-treatment) and at follow-up for each subject. A hearing shift was determined using various metrics, and outcomes were compared to characterize changes in hearing bilaterally for both study groups. ResultsComparison of pure-tone threshold shifts between baseline and follow-up audiograms following either a course of IV tobramycin (n = 18) or no intervening therapy (n = 13) demonstrated significant (p < 0.05) threshold shifts in all continuous metrics tested. ConclusionA single course of IV tobramycin causes ototoxic hearing loss in some people with CF, which supports the need for routine ototoxicity monitoring and management in this clinical population. These findings also suggest that people with CF are a suitable population for clinical trials examining ototherapeutics in single IV-tobramycin treatment episodes.

Fully Integrated Organic Field‐Effect Transistor Platform to Detect and to Quantify NO2 Gas

Herein, the gas sensing characteristics of PDVT‐10 organic field‐effect transistor (OFET) devices are explored and integrated to build a compact analog‐to‐digital converter (ADC) gas detection system. The electrical characteristics of the pristine PDVT‐10 OFET exhibit Ion/Ioff ratio and threshold voltage as 104 and −12 V, respectively. Through the coating of a metal‐organic framework (MOF) on the surface of PDVT‐10, the Ion/Ioff improves by one order of magnitude accompanied by significant positive threshold shift measured around 4 V. MOF is added as a pre‐concentrating material, and the device exhibits excellent selectivity and good sensitivity toward the target NO2 gas. Most of the reports available in the literature generally focus on the gas sensing performance of individual sensors, which does not have the potential to solve real‐time sensing problems. Hence, for the first time, a fully integrated ADC system is designed with just two OFETs. The integrated ADC system not only detects the NO2 gas with high sensitivity and selectivity but also generates a 5 bit digital output corresponding to different NO2 gas concentrations from 25 ppb to 1 ppm.

Ebselen attenuates tobramycin-induced ototoxicity in mice

BackgroundCystic fibrosis patients are often adminstered tobramycin to treat pulmonary infections. Unfortunately, a common side effect is hearing loss, which can fluctuate. Ebselen has known anti-inflammatory properties and could reduce the incidence and severity of tobramycin-induced hearing loss. MethodsIn vitro: neonatal cochlear cultures were treated with tobramycin or cotreated with tobramycin and ebselen for 3 days. In vivo: adult mice were injected with tobramycin or tobramycin and ebselen for 14 days. ABRs were collected in a repeated measures design until 56 days after treatments. ABR threshold shifts were analyzed and a novel cochleotoxic criteria applied to determine the incidence of ototoxicity. Cochlear immunohistology was analyzed for IHC and OHC loss. ResultsTobramycin leads to significant IHC and OHC loss in cochlear explant cultures. Ebselen co-treatment at 1:20 concentrations resulted in significant otoprotection. Tobramycin leads to significant ABR threshold shifts that are ameliorated by ebselen co-treatment. Hearing loss did not correlate with significant IHC or OHC loss. ConclusionsThis mouse model of tobramycin-induced ototoxicity is clinically relevant in that it results in an incidence and severity of hearing loss recently documented in clinic. The in vitro experiments show that tobramycin kills hair cells and that ebselen co-treatment can attenuate this ototoxicity. The in vivo model shows tobramycin-induced hearing loss is ameliorated by ebselen co-treatment, but this is not explained by concomitant hair cell loss. These preclinical data support the testing of ebselen in CF patients receiving tobramycin treatment.

Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.

Lack of Significant Audiometric Changes Under Hypobaric Hypoxia at 15,000 ft.

BACKGROUND: The aim of this study was pure tone audiometry (PTA) evaluation in normal individuals exposed to hypobaric hypoxia, taking into account the influence of air rarefaction on sound transmission via a standard earphone.METHODS: The study was conducted in a hypobaric chamber using a standard audiometer and a TDH-39P earphone whose performance at altitudes was analyzed in a previous research. Eight male volunteers underwent PTA testing at ground level and at 15,000 ft under normoxia (via an oxygen mask) and after 20 min of hypoxia. Auditory threshold at 500, 1000, 2000, and 4000 Hz was recorded from the right ear while monitoring arterial oxygen saturation (Sao₂). The PTA data obtained at high altitude were corrected according to a specific recalibration table.RESULTS: During hypoxia, a significant threshold shift was observed only at 4000 Hz, with respect to ground level recording, for the sole not-corrected data. At the same frequency a significant threshold shift was also observed between the ground level recording and normoxia at 15,000 ft, confirming the presence of a hypobaric effect not related to hypoxia. After the recalibration procedure, this hearing impairment was not significant. No correlation with Sao₂ levels was observed.DISCUSSION: The mild and not significant presence of high altitude-induced PTA derangements in healthy normal individuals was documented, although a stimulus recalibration was needed for a correct interpretation of our data.Lucertini M, Lancia S, Sanjust F, Guadagno AG, Lucertini L, Sisto R. Lack of significant audiometric changes under hypobaric hypoxia at 15,000 ft. Aerosp Med Hum Perform. 2020; 91(1):32-36.

Functional and morphological analysis of different aminoglycoside treatment regimens inducing hearing loss in mice.

Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo. Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea.

Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K\u2013Akt pathway

Gentamicin is a widely used antibiotic for the treatment of gram-negative bacterial infections; however, its use often results in significant and permanent hearing loss. Hearing loss resulting from hair cell (HC) degeneration affects millions of people worldwide, and one major cause is the loss of sensory HCs in the inner ear due to aminoglycoside exposure. Strategies to overcome the apparently irreversible loss of HCs in mammals are crucial for hearing protection. Here, we report that the somatostatin analog pasireotide protects mouse cochlear HCs from gentamicin damage using a well-established in vitro gentamicin-induced HC loss model and that the otoprotective effects of pasireotide are due to Akt up-regulation via the PI3K–Akt signal pathway activation. We demonstrate active caspase signal in organ of Corti (OC) explants exposed to gentamicin and show that pasireotide treatment activates survival genes, reduces caspase signal, and increases HC survival. The neuropeptide somatostatin and its selective analogs have provided neuroprotection by activating five somatostatin receptor (SSTR1–SSTR5) subtypes. Pasireotide has a high affinity for SSTR2 and SSTR5, and the addition of SSTR2- and SSTR5-specific antagonists leads to a loss of protection. The otoprotective effects of pasireotide were also observed in a gentamicin-injured animal model. In vivo studies have shown that 13 days of subcutaneous pasireotide application prevents gentamicin-induced HC death and permanent hearing loss in mice. Auditory brainstem response analysis confirmed the protective effect of pasireotide, and we found a significant threshold shift at all measured frequencies (4, 8, 16, 24, and 32 kHz). Together, these findings indicate that pasireotide is a novel otoprotective peptide acting via the PI3K–Akt pathway and may be of therapeutic value for HC protection from ototoxic insults.

Lower expression of prestin and MYO7A correlates with menopause-associated hearing loss

Objective: This study aimed to test the hearing function and to investigate the effect of estrogen on prestin and MYO7A expression in hair cells of the cochlea in ovariectomized rats.Study design: We compared the hearing function systematically in normal female Sprague–Dawley rats and in ovariectomized rats with or without exogenous β-estradiol administration by auditory brainstem response measurements and distortion product otoacoustic emissions. In addition, a correlation analysis between the functional parameters and cochlear histology was carried out.Results: There was a significant auditory threshold shift in the high-frequency range in the ovariectomized rats. Prestin and MYO7A expression was lowered in the cochlea of ovariectomized rats. These effects could be recovered by subcutaneous administration of β-estradiol.Conclusion: Low estrogen levels may lead to reduced expression of prestin and MYO7A in cochlea, leading to a menopause-related hearing loss.

Noise-Induced Cochlear Synaptopathy and Ribbon Synapse Regeneration: Repair Process and Therapeutic Target.

The synapse between the inner hair cells (IHCs) and the spiral ganglion neurons (SGNs) in mammalian cochleae is characterized as having presynaptic ribbons and therefore is called ribbon synapse. The special molecular organization is reviewed in this chapter in association with the functional feature of this synapse in signal processing. This is followed by the review on noise-induced damage to this synapse with a focus on recent reports in animal models in which the effect of brief noise exposures is observed without causing significant permanent threshold shift (PTS). In this regard, the potential mechanism of the synaptic damage by noise and the impact of this damage on hearing are summarized to clarify the concept of noise-induced hidden hearing loss, which is defined as the functional deficits in hearing without threshold elevation. A controversial issue is addressed in this review as whether the disrupted synapses can be regenerated. Moreover, the review summarizes the work of therapeutic research to protect the synapses or to promote the regeneration of the synapse after initial disruption. Lastly, several unresolved issues are raised for investigation in the future.

Smart automated noise policy monitoring and feedback control system for mining application

Abstract This work develops an integrated smart noise monitoring model that can be used to monitor mine workers on site. The system provides mine administrators with the current state of hearing of the individual employee. The information obtained from the model can be used by the administration, for various purposes including monitoring and provision of early intervention. The main purpose of the model is to protect mining employees from experiencing significant hearing threshold shifts which can result in permanent hearing loss. The novelty of this model is the formulation of noise policy management model using feedback control with policies acting as actuators. Mining noise policies, Code of Practice and milestones are used in the selection of the appropriate controllers to be used in the system. Feedback is used in the system to compare the threshold output to the baseline. The output of the system is further processed using Internet of Things to ensure effective communication between the mine employees and the administrators. The model was validated using open source data from a real deep gold mine in South Africa. The results were generated using Matlab as a platform and were found to be comparable to the existing static model and more accurate. Future improvements to this work is to include artificial intelligence and machine learning concepts to the system to make it more robust.

Noise-Induced Hearing Loss in Mice: Effects of High and Low Levels of Noise Trauma in CBA Mice.

Acoustic trauma can induce temporary or permanent noise-induced hearing loss (NIHL). Noise exposed animal models allow us to study the effects of various noise trauma insults on the cochlea and auditory pathways. Here we studied the short-term and long-term functional changes occurring in the auditory system following exposure to two different noise traumas. Several measures of hearing function known to change following noise exposure were examined: Temporary (TTS) and permanent (PTS) threshold shifts were measured using auditory brainstem responses (ABR), outer hair cell function was examined using distortion product otoacoustic emissions (DPOAEs), and auditory temporal processing was assessed using a gap-in-noise (GIN) ABR paradigm. Physiological measures were made before and after the exposure (24 hours, 2 weeks, 4 weeks, and 1 year). The animals were perfused and their brain, and cochlea were collected for future biomarker studies. Young adult mice were exposed to 110 dB and 116 dB octave-band noise levels for 45 minutes, and both groups demonstrated significant threshold shifts 1 day post-noise exposure across all frequencies. However 2 weeks postexposure, PTS within the 110 dB group was significantly reduced compared to 1 day post trauma, this improvement in thresholds was not as great in the 116 dB exposure group. At 2 weeks post-trauma, differences between the measured PTS in the two groups was significant for 4 of the 7 measured frequencies. At this 1 year time point after exposure, mice in the 110 dB group showed very minor PTS, but the 116 dB group showed a large PTS comparable to their 2 and 4 week PTS. At this time point, PTS variation between the two groups was significant across all frequencies. DPOAE amplitudes measured 2 weeks post exposure showed recovery for all frequencies within 10 dB (average) of the baseline in the 110 dB group, however for the 116 dB exposure DP amplitudes were elevated by about 30 dB. The differences in DPOAE amplitudes between the 110 dB and 116 dB groups were significant at 2 weeks, 4 weeks, and 1 year post-trauma in the mid frequency range. At 2 weeks, 4 weeks, and 1 year, DPOAE thresholds returned to within 10 dB of the baseline for the 110 dB group in the low and mid frequency range, whereas the 116 dB group still showed shifts of 30 dB for all frequency ranges. For Gap ABRs, there was a significant decrease in both noise burst 1 (NB1) and noise burst 2 (NB2) amplitudes for peaks 1 and 4 in the 116 dB group relative to the 110 dB group when measured at 1 year post trauma. These results indicate that a 6 dB increase in noise exposure intensity results in a significant increased ototrauma in both the peripheral and central auditory systems.

Platelet-Derived Growth Factor Subunit B Signaling Promotes Pericyte Migration in Response to Loud Sound in the Cochlear Stria Vascularis.

Normal blood supply to the cochlea is critical for hearing. Noise damages auditory sensory cells and has a marked effect on the microvasculature in the cochlear lateral wall. Pericytes in the stria vascularis (strial pericytes) are particularly vulnerable and sensitive to acoustic trauma. Exposure of NG2DsRedBAC transgenic mice (6-8weeks old) to wide-band noise at a level of 120dB for 3h per day for 2 consecutive days produced a significant hearing threshold shift and caused pericytes to protrude and migrate from their normal endothelial attachment sites. The pericyte migration was associated with increased expression of platelet-derived growth factor beta (PDGF-BB). Blockade of PDGF-BB signaling with either imatinib, a potent PDGF-BB receptor (PDGFR) inhibitor, or APB5, a specific PDGFRβ blocker, significantly attenuated the pericyte migration from strial vessel walls. The PDGF-BB-mediated strial pericyte migration was further confirmed in an in vitro cell migration assay, as well as in an in vivo live animal model used in conjunction with confocal fluorescence microscopy. Pericyte migration took one of two different forms, here denoted protrusion and detachment. The protrusion is characterized by pericytes with a prominent triangular shape, or pericytes extending fine strands to neighboring capillaries. The detachment is characterized by pericyte detachment and movement away from vessels. We also found the sites of pericyte migration highly associated with regions of vascular leakage. In particular, under transmission electron microscopy (TEM), multiple vesicles at the sites of endothelial cells with loosely attached pericytes were observed. These data show that cochlear pericytes are markedly affected by acoustic trauma, causing them to display abnormal morphology. The effect of loud sound on pericytes is mediated by upregulation of PDGF-BB. Normal functioning pericytes are required for vascular stability.

Cochlear Damage Caused by the Striking Noise of Titanium Head Golf Driver.

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.

Protective Effects of Silymarin Against Age-Related Hearing Loss in an Aging Rat Model.

Age-related hearing loss (ARHL) is one of the most common chronic degenerative disorders. Several studies have indicated that supplementation with some antioxidants can slow down the progression of ARHL. Despite several lines of evidence about the potent antioxidant and anti-aging effects of silymarin, its protective effect against ARHL has not evaluated yet. The aim of the current study was to investigate the effects of silymarin in prevention of ARHL in a d-Galactose-induced aging rat model for the first time. 45 male wistar rats aged 3-month old were divided into 5 groups: group 1, 2 and 3 received 500mg/kg/day d-Gal plus 100, 200 and 300mg/kg/day silymarin respectively for 8weeks, placebo group received 500mg/kg/day d-Gal plus propylene glycol as placebo, and control group received normal saline during this period of time. Auditory brainstem responses were measured at several frequencies (4, 6, 8, 12 and 16kHz) before and after the intervention. Placebo group and group 3 showed significant ABR threshold increase across frequencies of 4, 6, 16kHz compared with the other groups (P < 0.05). However, rats treated with silymarin 100 and 200 mg/kg/day plus d-Gal did not show any significant ABR threshold shifts. Similarly, ABR amplitude of P2 at 4, 8kHz and P1, P4 at 4kHz in the placebo group and group 3 were decreased significantly compared with other groups (P < 0.05). However, no significant differences are found in ABR absolute and inter-peak latencies between groups (P > 0.05). The findings indicates that silymarin with doses of 100 and 200mg/kg/day has protective effect against ARHL and it can be supplemented into the diet of older people to slow down the progression of age-related hearing loss.

Risk Factors for Hearing Decrement Among U.S. Air Force Aviation-Related Personnel.

The purpose of this study was to analyze historical hearing sensitivity data to determine factors associated with an occupationally significant change in hearing sensitivity in U.S. Air Force aviation-related personnel. This study was a longitudinal, retrospective cohort analysis of audiogram records for Air Force aviation-related personnel on active duty during calendar year 2013 without a diagnosis of non-noise-related hearing loss. The outcomes of interest were raw change in hearing sensitivity from initial baseline to 2013 audiogram and initial occurrence of a significant threshold shift (STS) and non-H1 audiogram profile. Potential predictor variables included age and elapsed time in cohort for each audiogram, gender, and Air Force Specialty Code. Random forest analyses conducted on a learning sample were used to identify relevant predictor variables. Mixed effects models were fitted to a separate validation sample to make statistical inferences. The final dataset included 167,253 nonbaseline audiograms on 10,567 participants. Only the interaction between time since baseline audiogram and age was significantly associated with raw change in hearing sensitivity by STS metric. None of the potential predictors were associated with the likelihood for an STS. Time since baseline audiogram, age, and their interaction were significantly associated with the likelihood for a non-HI hearing profile. In this study population, age and elapsed time since baseline audiogram were modestly associated with decreased hearing sensitivity and increased likelihood for a non-H1 hearing profile. Aircraft type, as determined from Air Force Specialty Code, was not associated with changes in hearing sensitivity by STS metric.Greenwell BM, Tvaryanas AP, Maupin GM. Risk factors for hearing decrement among U.S. Air Force aviation-related personnel. Aerosp Med Hum Perform. 2018; 89(2):80-86.