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1.  Improving optical contact for functional near‑infrared brain spectroscopy and imaging with brush optodes 
Biomedical Optics Express  2012;3(5):878-898.
A novel brush optode was designed and demonstrated to overcome poor optical contact with the scalp that can occur during functional near infrared spectroscopy (fNIRS) and imaging due to light obstruction by hair. The brush optodes were implemented as an attachment to existing commercial flat-faced (conventional) fiber bundle optodes. The goal was that the brush optodes would thread through hair and improve optical contact on subjects with dense hair. Simulations and experiments were performed to assess the magnitude of these improvements. FNIRS measurements on 17 subjects with varying hair colors (blonde, brown, and black) and hair densities (0–2.96 hairs/mm2) were performed during a finger tapping protocol for both flat and brush optodes. In addition to reaching a study success rate of almost 100% when using the brush optode extensions, the measurement setup times were reduced by a factor of three. Furthermore, the brush optodes enabled improvements in the activation signal-to-noise ratio (SNR) by up to a factor of ten as well as significant (p < 0.05) increases in the detected area of activation (dAoA). The measured improvements in SNR were matched by Monte Carlo (MC) simulations of photon propagation through scalp and hair. In addition, an analytical model was derived to mathematically estimate the observed light power losses due to different hair colors and hair densities. Interestingly, the derived analytical formula produced excellent estimates of the experimental data and MC simulation results despite several simplifying assumptions. The analytical model enables researchers to readily estimate the light power losses due to obstruction by hair for both flat-faced fiber bundles and individual fibers for a given subject.
doi:10.1364/BOE.3.000878
PMCID: PMC3342194  PMID: 22567582
(170.2655) Functional monitoring and imaging; (170.3880) Medical and biological imaging; (300.6340) Spectroscopy, infrared
2.  Heritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample 
Genes  2015;6(3):559-576.
Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on hair color within a large cohort of twins, their parents and siblings from the Netherlands Twin Register (NTR). Self-reported hair color was analyzed as five binary phenotypes, namely “blond versus non-blond”, “red versus non-red”, “brown versus non-brown”, “black versus non-black”, and “light versus dark”. The broad-sense heritability of hair color was estimated between 73% and 99% and the genetic component included non-additive genetic variance. Assortative mating for hair color was significant, except for red and black hair color. From GCTA analyses, at most 24.6% of the additive genetic variance in hair color was explained by 1000G well-imputed SNPs. Genome-wide association analysis for each hair color showed that SNPs in the MC1R region were significantly associated with red, brown and black hair, and also with light versus dark hair color. Five other known genes (HERC2, TPCN2, SLC24A4, IRF4, and KITLG) gave genome-wide significant hits for blond, brown and light versus dark hair color. We did not find and replicate any new loci for hair color.
doi:10.3390/genes6030559
PMCID: PMC4584317  PMID: 26184321
hair color; twin-family based heritability; GRM based heritability; Genome Wide Association Study
3.  Combined effects of salicylic acid and furosemide and noise on hearing 
Background
A major cause of the hearing loss following exposure to intense noise involves release of free radicals resulting from the elevated metabolism. The free radicals induce damage to several of the components of the cochlear amplifier including the outer hair cells and indirectly to the transduction currents. Salicylic acid induces a reversible hearing loss since it binds to the motor protein prestin in the outer hair cells, reducing electromotility. Furosemide also induces a reversible hearing loss since it reduces the endocochlear potential which is a major component of the cochlear transduction currents. On the other hand, each of these drugs also provides protection from a noise induced hearing loss if they are injected just before a noise exposure, probably as a result of the decreased metabolism induced in their presence, with release of lower levels of free radicals. In this study, both drugs were administered in order to assess whether their protective effects would be additive.
Methods
The study was conducted on normal hearing albino mice of the Sabra strain. They were injected with either salicylic acid alone (N = 11), or furosemide alone (N = 14), or both together (N = 14), or with saline control (N = 11) and exposed to broad band noise for 3.5 hours. An additional group of 9 mice was injected with both salicylic acid and furosemide, but not exposed to noise. The degree of the resulting hearing loss was assessed by recording thresholds of the auditory nerve brainstem evoked responses to broad band clicks before the injections and noise, and 7, 14 and 21 days after.
Results
The noise induced hearing loss in the mice injected with salicylic acid alone or furosemide alone was smaller than in those injected with saline, i.e. these drugs provided protection, as in previous studies in this laboratory. There was no threshold elevation after two weeks in the mice injected with both drugs without noise exposure, i.e. the effects of the two drugs given together was reversible. On the other hand, there was a significant hearing loss (i.e. threshold elevation) in the group which received both drugs and was also exposed to noise, with mean threshold elevations of 38.8 ± 19.0 dB and 28.3 ± 11.7 dB 7 days after noise exposure.
Conclusions
This result is very surprising, if not paradoxical. Drugs which provide protection from a noise induced hearing loss when administered alone, not only do not provide protection when given together, but also induce a greater hearing loss when accompanied by noise. This observation may be related to the finding that the depression of the endocochlear potential normally caused by furosemide is reduced in the presence of salicylic acid, so that the protection usually provided by furosemide is not present when it is administered together with salicylic acid. Thus it seems that each drug may interfere with the protective action of the other when coupled with noise.
doi:10.1186/1745-6673-7-1
PMCID: PMC3293015  PMID: 22264295
noise induced hearing loss; salicylic acid; furosemide; cochlear amplifier; ABR; free radicals; prestin; endocochlear potential
4.  Morphological Correlates of Hearing Loss after Cochlear Implantation and Electro-Acoustic Stimulation in a Hearing-Impaired Guinea Pig Model 
Hearing research  2015;327:163-174.
Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss.
Guinea pigs were exposed to 24 hours of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n=6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n=6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm.
Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not correlated with threshold shifts at any frequency.
As in the previous study in a normal-hearing model, stria vascularis capillary changes were associated with immediate hearing loss after implantation, while little to no hair cell loss was observed even in cochlear regions with threshold shifts as large as 40-50 dB. These findings again support a role of lateral wall blood flow changes, rather than hair cell loss, in hearing loss after surgical trauma, and implicate the endocochlear potential as a factor in implantation-induced hearing loss. Further, the analysis of the hair cell ribbons and post-synaptic receptors suggest that delayed hearing loss may be linked to synapse or peripheral nerve loss due to stimulation excitotoxicity or inflammation. Further research is needed to separate these potential mechanisms of delayed hearing loss.
doi:10.1016/j.heares.2015.06.007
PMCID: PMC4905574  PMID: 26087114
Hybrid; cochlear implant; electro-acoustic stimulation; stria vascularis; synapse; hearing loss
5.  The Use of the Kurtosis-adjusted Cumulative Noise Exposure Metric in Evaluating the Hearing Loss Risk for Complex Noise 
Ear and hearing  2016;37(3):312-323.
Objective
To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically: to evaluate if the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss; (2) provides a single metric applicable to both complex (non-Gaussian) and continuous or steady-state (Gaussian) noise exposures for predicting noise induced hearing loss (dose-response curves).
Design
Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province, and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N=178) were exposed to complex noise while the subjects from textile manufacturing plant (N=163) were exposed to a Gaussian (G) continuous noise. Each subject was given an otologic examination to determine their pure tone hearing threshold levels (HTL); and had their personal 8-hour equivalent A-weighted noise exposure (LAeq) and full shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject an unadjusted and kurtosis-adjusted cumulative noise exposure (CNE) index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis-adjusted) and the mean HTL at 3, 4 and 6 kHz (HTL346) among the complex noise exposed group.
In addition, each subjects' HTLs from 0.5 - 8.0 kHz were age and gender adjusted using ANNEX A (ISO-1999) to determine whether they had adjusted high frequency noise induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0 or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric.
Results
Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared to the unadjusted CNE (R2=0.386 vs. 0.350), and that noise accounted for a greater proportion of hearing loss. In addition, while dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE.
Conclusions
For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than for workers exposed to a continuous noise. Kurtosis adjustment of CNE both improved the correlation with NIHL and provides a single metric for dose response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments.
doi:10.1097/AUD.0000000000000251
PMCID: PMC4844558  PMID: 26671317
6.  Sunlight Exposure, Pigmentation, and Incident Age-Related Macular Degeneration 
Purpose.
Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD.
Methods.
Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color.
Results.
Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD.
Conclusions.
Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype.
Hair color and eye color were associated with increased risk of early age-related macular degeneration lesions in the context of relatively higher sunlight exposure.
doi:10.1167/iovs.14-14602
PMCID: PMC4165367  PMID: 25125603
sunlight exposure; hair color; eye color; age-related macular degeneration; pigmentation
7.  Effects of unilateral input and mode of hearing in the better ear: Self-reported performance using the Speech, Spatial and Qualities of Hearing Scale 
Ear and hearing  2014;35(1):10.1097/AUD.0b013e3182a3648b.
Objective
To evaluate effects of hearing mode (normal hearing, cochlear implant or hearing aid) on everyday communication among adult unilateral listeners using the Speech, Spatial and Qualities of Hearing scale (SSQ). Individuals with one good, naturally hearing ear were expected to have higher overall ratings than unilateral listeners dependent on a cochlear implant or hearing aid. We anticipated that listening environments reliant on binaural processing for successful communication would be rated most disabling by all unilateral listeners. Regardless of hearing mode, all hearing-impaired participants were expected to have lower ratings than individuals with normal hearing bilaterally. A secondary objective was to compare post-treatment SSQ results of participants who subsequently obtained a cochlear implant for the poorer hearing ear to those of participants with a single normal hearing ear.
Design
Participants were 87 adults recruited as part of ongoing research investigating asymmetric hearing effects. Sixty-six participants were unilateral listeners who had one unaided/non-implanted severe to profound hearing loss ear and were grouped based on hearing mode of the better ear: 30 had one normal hearing ear (i.e., unilateral hearing loss participants); 20 had a unilateral cochlear implant; and 16 had a unilateral hearing aid. Data were also collected from 21 normal-hearing individuals, as well as a subset of participants who subsequently received a cochlear implant in the poorer ear and thus became bilateral listeners. Data analysis was completed at the domain and subscale levels.
Results
A significant mode-of-hearing group effect for the hearing-impaired participants (i.e. with unilateral hearing loss, unilateral cochlear implant or unilateral hearing aid) was identified for two domains (Speech and Qualities) and six subscales (Speech in Quiet, Speech in Noise, Speech in Speech Contexts, Multiple Speech Stream Processing and Switching, Identification of Sound and Objects, and Sound Quality and Naturalness). There was no significant mode-of-hearing group effect for the Spatial domain or the other four subscales (Localization, Distance and Movement, Segregation of Sounds, and Listening Effort). Follow-up analysis indicated the unilateral normal hearing ear group had significantly higher ratings than the unilateral cochlear implant and/or hearing aid groups for the Speech domain and four of the ten subscales; neither the cochlear implant nor hearing aid group had subscale ratings significantly higher than each other or the unilateral hearing loss group. Audibility and sound quality imparted by hearing mode were identified as factors related to subjective listening experience. After cochlear implantation to restore bilateral hearing, SSQ ratings for bilateral cochlear implant and/or cochlear implant plus hearing aid participants were significantly higher than those of the unilateral hearing loss group for Speech in Quiet, Speech in Noise, Localization, Distance and Movement, Listening Effort, and the Spatial domain. Hearing-impaired individuals had significantly poorer ratings in all areas compared to those with bilateral normal hearing.
Conclusions
Adults reliant on a single ear, irrespective of better ear hearing mode, including those with one normal hearing ear, are at a disadvantage in all aspects of everyday listening and communication. Audibility and hearing mode were shown to differentially contribute to listening experience.
doi:10.1097/AUD.0b013e3182a3648b
PMCID: PMC3872501  PMID: 24084062
Unilateral hearing loss; Hearing disability; Cochlear implant; Hearing aid
8.  Protective Effect of Silymarin on Noise-Induced Hearing Loss in Guinea Pigs 
Background
Hearing capability plays a principal role on human's communication. Noise-induced hearing loss (NIHL) caused by exposure to high noise levels is a serious socio-economic problem in modern societies. NIHL can either be reversible, resulting in a temporary threshold shifts (TTS) or irreversible, resulting in a permanent threshold shifts (PTS). PTS is often confirmed in the time span of between 2 - 6 weeks. NIHL may be prevented by avoidance of excessive amounts of noise or reducing the sound energy entering the inner ear using hearing protective devices. However, there are some conditions that such prevention is not possible such as noise exceeding the protective capabilities of the hearing protection device, working in military or the person does not tolerate the protection device. Thus the protective agent for preventing NIHL would be useful.
Objective
Free radical molecules and consequence oxidative stress have been shown to play a significant role in noise-induced hearing loss. Silymarin is an antioxidant flavonoid complex derived from the herb milk thistle has ability to mitigating the oxidative stress, scavenge free radicals. In the current study, we aimed to evaluate the protective effect of silymarin on noise induced hearing loss in guinea pig by auditory brain stem response.
Materials and Methods
Twenty guinea pigs randomly divided into 2 groups. The animals in the experimental group were intraperitoneally injected with 100 mg/kg/day silymarin dissolved in propylene glycol for 6 consecutive days. The control subjects were intraperitoneally injected with propylene glycol for 6 consecutive days. All animals were exposed to 4 kHz octave band noise at 120 dB SPL for 6 hours. Auditory brainstem responses (ABRs) at frequencies of 2, 4, 6, 8, 12, 16 and 20 kHz were precisely recorded before intervention and then on intervals of 0, 3, 10 and 15 days after noise exposure. Data were analyzed using repeated measures ANOVA.
Results
Threshold shifts for the experimental group at all frequencies immediately, 3, 10 and 15 days after noise exposure were significantly reduced compared to the control group (P < 0.01).
Conclusions
The findings indicate a protective effect of silymarin on temporary and permanent noise-induced hearing loss.
doi:10.5812/ircmj.8890
PMCID: PMC3971782  PMID: 24719690
Hearing Loss, Noise-Induced; Silymarin; Auditory Brain Stem Implantation
9.  Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma 
eLife  2014;3:e03564.
Neurotrophin-3 (Ntf3) and brain derived neurotrophic factor (Bdnf) are critical for sensory neuron survival and establishment of neuronal projections to sensory epithelia in the embryonic inner ear, but their postnatal functions remain poorly understood. Using cell-specific inducible gene recombination in mice we found that, in the postnatal inner ear, Bbnf and Ntf3 are required for the formation and maintenance of hair cell ribbon synapses in the vestibular and cochlear epithelia, respectively. We also show that supporting cells in these epithelia are the key endogenous source of the neurotrophins. Using a new hair cell CreERT line with mosaic expression, we also found that Ntf3's effect on cochlear synaptogenesis is highly localized. Moreover, supporting cell-derived Ntf3, but not Bbnf, promoted recovery of cochlear function and ribbon synapse regeneration after acoustic trauma. These results indicate that glial-derived neurotrophins play critical roles in inner ear synapse density and synaptic regeneration after injury.
DOI: http://dx.doi.org/10.7554/eLife.03564.001
eLife digest
Noise-induced hearing loss is common, and can result from prolonged exposure to moderate levels of noise that are not perceived as painful or even unpleasant. Some hearing loss can be attributed to the death of hair cells in a part of the inner ear called the cochlea. When sound waves hit the cochlea, they cause the fluid inside it to vibrate: the hair cells detect these vibrations and convert them into electrical signals that are sent along neurons to the brain. However, vibrations that are too strong can destroy hair cells.
Increasing evidence suggests that hearing loss also results from damage to the synapses that connect the hair cells and the neurons in the cochlea. During development of the inner ear, molecules called growth factors are needed to ensure the survival of these neurons. Wan et al. predicted that these growth factors might also have a role in adult animals, and that producing more of them might help to safeguard hearing from the damaging effects of noise.
Consistent with this, mice that were genetically modified to lack a growth factor called neurotrophin-3 had cochleae that did not work properly and had fewer synapses between hair cells and neurons compared to control mice. Conversely, mice that produced too much neurotrophin-3 had more synapses than controls and also recovered more quickly from the effects of 2 hr exposure to 100 dB noise (roughly the volume of a pneumatic drill). Studies of the cochlea revealed that the extra neurotrophin-3 had boosted the regeneration of synapses damaged by the noise.
The beneficial effects of neurotrophin-3 were still seen when overproduction was started shortly after noise exposure, suggesting that it could have therapeutic potential. This is particularly significant in the light of recent evidence that the loss of synapses often comes before the death of hair cells in both age-related hearing loss and noise-induced hearing loss.
DOI: http://dx.doi.org/10.7554/eLife.03564.002
doi:10.7554/eLife.03564
PMCID: PMC4227045  PMID: 25329343
deafness; synaptogenesis; hearing loss; neuron–glia interactions; glial cell; mouse
10.  Association of Skin Color, Race/Ethnicity, and Hearing Loss Among Adults in the USA 
Epidemiologic studies of hearing loss in adults have demonstrated that the odds of hearing loss are substantially lower in black than in white individuals. The basis of this association is unknown. We hypothesized that skin pigmentation as a marker of melanocytic functioning mediates this observed association and that skin pigmentation is associated with hearing loss independent of race/ethnicity. We analyzed cross-sectional data from 1,258 adults (20–59 years) in the 2003–2004 cycle of the National Health and Nutritional Examination Survey who had assessment of Fitzpatrick skin type and pure-tone audiometric testing. Audiometric thresholds in the worse hearing ear were used to calculate speech- (0.5–4 kHz) and high-frequency (3–8 kHz) pure-tone averages (PTA). Regression models were stratified by Fitzpatrick skin type or race/ethnicity to examine the association of each factor with hearing loss independent of the other. Models were adjusted for potential confounders (demographic, medical, and noise exposure covariates). Among all participants, race/ethnicity was associated with hearing thresholds (black participants with the best hearing followed by Hispanics and then white individuals), but these associations were not significant in analyses stratified by skin color. In contrast, in race-stratified analyses, darker-skinned Hispanics had better hearing than lighter-skinned Hispanics by an average of −2.5 dB hearing level (HL; 95% CI, −4.8 to −0.2) and −3.1 dB HL (95% CI, −5.3 to −0.8) for speech and high-frequency PTA, respectively. Associations between skin color and hearing loss were not significant in white and black participants. Our results demonstrate that skin pigmentation is independently associated with hearing loss in Hispanics and suggest that skin pigmentation as a marker of melanocytic functioning may mediate the strong association observed between race/ethnicity and hearing loss.
doi:10.1007/s10162-011-0298-8
PMCID: PMC3254716  PMID: 22124888
hearing loss; race; melanocytes; epidemiology
11.  Model-based prediction of human hair color using DNA variants 
Human Genetics  2011;129(4):443-454.
Predicting complex human phenotypes from genotypes is the central concept of widely advocated personalized medicine, but so far has rarely led to high accuracies limiting practical applications. One notable exception, although less relevant for medical but important for forensic purposes, is human eye color, for which it has been recently demonstrated that highly accurate prediction is feasible from a small number of DNA variants. Here, we demonstrate that human hair color is predictable from DNA variants with similarly high accuracies. We analyzed in Polish Europeans with single-observer hair color grading 45 single nucleotide polymorphisms (SNPs) from 12 genes previously associated with human hair color variation. We found that a model based on a subset of 13 single or compound genetic markers from 11 genes predicted red hair color with over 0.9, black hair color with almost 0.9, as well as blond, and brown hair color with over 0.8 prevalence-adjusted accuracy expressed by the area under the receiver characteristic operating curves (AUC). The identified genetic predictors also differentiate reasonably well between similar hair colors, such as between red and blond-red, as well as between blond and dark-blond, highlighting the value of the identified DNA variants for accurate hair color prediction.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-010-0939-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s00439-010-0939-8
PMCID: PMC3057002  PMID: 21197618
12.  Auditory function in normal-hearing, noise-exposed human ears 
Ear and hearing  2015;36(2):172-184.
Objectives
To determine if supra-threshold measures of auditory function, such as distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), are correlated with noise exposure history in normal-hearing human ears. Recent data from animal studies have revealed significant deafferentation of auditory nerve fibers following full recovery from temporary noise-induced hearing loss (NIHL). Furthermore, these data report smaller ABR wave I amplitudes in noise-exposed animal ears when compared to non-noise exposed control animals or pre-noise exposure amplitudes in the same animal. It is unknown if a similar phenomenon exists in the normal-hearing, noise-exposed human ear.
Design
Thirty normal-hearing human subjects with a range of noise exposure backgrounds (NEBs) participated in this study. NEB was quantified by the use of a noise exposure questionnaire that extensively queried loud sound exposure over the previous 12 months. DPOAEs were collected at three f2’s (1, 2, and 4 kHz) over a range of L2’s. DPOAE stimulus level began at 80 dB FPL (forward-pressure level) and decreased in 10 dB steps. Two-channel ABRs were collected in response to click stimuli and 4 kHz tone bursts; one channel utilized an ipsilateral mastoid electrode and the other an ipsilateral tympanic membrane (TM) electrode. ABR stimulus level began at 90 dB nHL and was decreased in 10 dB steps. Amplitudes of waves I and V of the ABR were analyzed.
Results
A statistically significant relationship between ABR wave I amplitude and NEB was found for clicked-evoked ABRs recorded at a stimulus level of 90 dB nHL using a mastoid recording electrode. For this condition, ABR wave I amplitudes decreased as a function of NEB. Similar systematic trends were present for ABRs collected in response to clicks and 4 kHz tone bursts at additional supra-threshold stimulation levels (≥ 70 dB nHL). The relationship weakened and disappeared with decreases in stimulation level (≤ 60 dB nHL). Similar patterns were present for ABRs collected using a TM electrode. However, these relationships were not statistically significant and were weaker and more variable than those collected using a mastoid electrode. In contrast to the findings for ABR wave I, wave V amplitude was not significantly related to NEB. Furthermore, there was no evidence of a systematic relationship between supra-threshold DPOAEs and NEB.
Conclusions
A systematic trend of smaller ABR wave I amplitudes was found in normal-hearing human ears with greater amounts of voluntary NEB in response to supra-threshold clicks and 4 kHz tone bursts. These findings are consistent with data from previous work completed in animals, where the reduction in supra-threshold responses was a result of deafferentation of high-threshold/low-spontaneous rate auditory nerve fibers. These data suggest a similar mechanism might be operating in human ears following exposure to high sound levels. However, evidence of this damage is only apparent when examining supra-threshold wave I amplitude of the ABR. In contrast, supra-threshold DPOAE level was not significantly related to NEB. This was expected, given noise-induced auditory damage findings in animal ears did not extend to the outer hair cells, the generator for the DPOAE response.
doi:10.1097/AUD.0000000000000107
PMCID: PMC4374361  PMID: 25350405
noise exposure; auditory brainstem response; distortion-product otoacoustic emissions
13.  Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats 
Nutrients  2016;8(8):456.
We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.
doi:10.3390/nu8080456
PMCID: PMC4997371  PMID: 27483303
iron deficiency without anemia; ribbon synapse; spiral ganglion cell
14.  Factors associated with Hearing Loss in a Normal-Hearing Guinea Pig Model of Hybrid Cochlear Implants 
Hearing research  2014;316:82-93.
The Hybrid cochlear implant (CI), also known as Electro- Acoustic Stimulation (EAS), is a new type of CI that preserves residual acoustic hearing and enables combined cochlear implant and hearing aid use in the same ear. However, 30-55% of patients experience acoustic hearing loss within days to months after activation, suggesting that both surgical trauma and electrical stimulation may cause hearing loss.
The goals of this study were to: 1) determine the contributions of both implantation surgery and EAS to hearing loss in a normal-hearing guinea pig model; 2) determine which cochlear structural changes are associated with hearing loss after surgery and EAS. Two groups of animals were implanted (n=6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no direct acoustic or electric stimulation during this time frame. A third group (n=6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem response thresholds were followed over time at 1, 2, 6, and 16 kHz. At the end of the study, the following cochlear measures were quantified: hair cells, spiral ganglion neuron density, fibrous tissue density, and stria vascularis blood vessel density; the presence or absence of ossification around the electrode entry was also noted.
After surgery, implanted animals experienced a range of 0-55 dB of threshold shifts in the vicinity of the electrode at 6 and 16 kHz. The degree of hearing loss was significantly correlated with reduced stria vascularis vessel density and with the presence of ossification, but not with hair cell counts, spiral ganglion neuron density, or fibrosis area. After 10 weeks of stimulation, 67% of implanted, stimulated animals had more than 10 dB of additional threshold shift at 1 kHz, compared to 17% of implanted, non-stimulated animals and 0% of non-implanted animals. This 1-kHz hearing loss was not associated with changes in any of the cochlear measures quantified in this study. The variation in hearing loss after surgery and electrical stimulation in this animal model is consistent with the variation in human patients. Further, these findings illustrate an advantage of a normal-hearing animal model for quantification of hearing loss and damage to cochlear structures without the confounding effects of chemical- or noise-induced hearing loss. Finally, this study is the first to suggest a role of the stria vascularis and damage to the lateral wall in implantation-induced hearing loss. Further work is needed to determine the mechanisms of implantation- and electrical-stimulation-induced hearing loss.
doi:10.1016/j.heares.2014.07.011
PMCID: PMC4236540  PMID: 25128626
Cochlear implant; Hybrid; EAS; hearing loss; guinea pig; stria vascularis
15.  Noise exposure during prehospital emergency physicians work on Mobile Emergency Care Units and Helicopter Emergency Medical Services 
Background
Prehospital personnel are at risk of occupational hearing loss due to high noise exposure. The aim of the study was to establish an overview of noise exposure during emergency responses in Mobile Emergency Care Units (MECU), ambulances and Helicopter Emergency Medical Services (HEMS). A second objective was to identify any occupational hearing loss amongst prehospital personnel.
Methods
Noise exposure during work in the MECU and HEMS was measured using miniature microphones worn laterally to the auditory canals or within the earmuffs of the helmet. All recorded sounds were analysed in proportion to a known tone of 94 dB. Before and after episodes of noise exposure, the physicians underwent a hearing test indicating whether the noise had had any impact on the function of the outer sensory hair cells. This was accomplished by measuring the amplitude level shifts of the Distortion Product Otoacoustic Emissions. Furthermore, the prehospital personnels’ hearing was investigated using pure-tone audiometry to reveal any occupational hearing loss. All prehospital personnel were compared to ten in-hospital controls.
Results
Our results indicate high-noise exposure levels of ≥80 dB(A) during use of sirens on the MECU and during HEMS operations compared to in-hospital controls (70 dB(A)). We measured an exposure up to ≥90 dB(A) under the helmet for HEMS crew. No occupational hearing loss was identified with audiometry. A significant level shift of the Distortion Product Otoacoustic Emissions at 4 kHz for HEMS crew compared to MECU physicians was found indicating that noise affected the outer hair cell function of the inner ear, thus potentially reducing the hearing ability of the HEMS crew.
Discussion
Further initiatives to prevent noise exposure should be taken, such as active noise reduction or custom-made in-ear protection with communication system for HEMS personnel. Furthermore, better insulation of MECU and ambulances is warranted.
Conclusion
We found that the exposure levels exceeded the recommendations described in the European Regulative for Noise, which requires further protective initiatives. Although no hearing loss was demonstrated in the personnel of the ground-based units, a reduced function of the outer sensory hair cells was found in the HEMS group following missions.
doi:10.1186/s13049-017-0459-9
PMCID: PMC5717803  PMID: 29208018
Noise exposure; Pre-hospital; Ambulance; Helicopter; HEMS; Occupational guidelines; Mobile Emergency Care Unit
16.  Effect of daily noise exposure monitoring on annual rates of hearing loss in industrial workers 
Objectives
Occupational noise-induced hearing loss (NIHL) is prevalent, yet evidence on the effectiveness of preventive interventions is lacking. The effectiveness of a new technology allowing workers to monitor daily at-ear noise exposure was analysed.
Methods
Workers in the hearing conservation program of an aluminium smelter were recruited because of accelerated rates of hearing loss. The intervention consisted of daily monitoring of at-ear noise exposure and regular feedback on exposures from supervisors. The annual rate of change in high frequency hearing average at 2, 3 and 4 KHz before intervention (2000–2004) and 4 years after intervention (2006–2009) was determined. Annual rates of loss were compared between 78 intervention subjects and 234 controls in other company smelters matched for age, gender and high frequency hearing threshold level in 2005.
Results
Individuals monitoring daily noise exposure experienced on average no further worsening of high frequency hearing (average rate of hearing change at 2, 3 and 4 KHz=–0.5 dB/year). Matched controls also showed decelerating hearing loss, the difference in rates between the two groups being significant (p<0.0001). Analysis of a subset of intervention subjects matched to controls for initial rate of hearing loss showed a similar trend but the difference was not statistically significant (p=0.06).
Conclusion
Monitoring daily occupational noise exposure inside hearing protection with ongoing administrative feedback apparently reduces the risk of occupational NIHL in industrial workers. Longer follow-up of these workers will help determine the significance of the intervention effect. Intervention studies for the prevention of NIHL need to include appropriate control groups.
doi:10.1136/oem.2010.055905
PMCID: PMC3738059  PMID: 21193566
17.  Temporary and Permanent Noise-Induced Threshold Shifts: A Review of Basic and Clinical Observations 
Objective
To review basic and clinical findings relevant to defining temporary (TTS) and permanent (PTS) threshold shifts and their sequelae.
Data Sources
Relevant scientific literature and government definitions were broadly reviewed.
Data Synthesis
The definitions and characteristics of TTS and PTS were assessed and recent advances that expand our knowledge of the extent, nature and consequences of noise-induced hearing loss were reviewed.
Conclusions
Exposure to intense sound can produce TTS, acute changes in hearing sensitivity that recover over time, or PTS, a loss that does not recover to pre-exposure levels. In general, a threshold shift ≥10 dB at 2, 3 and 4 kHz is required for reporting purposes in human studies. The high-frequency regions of the cochlea are most sensitive to noise damage. Resonance of the ear canal also results in a frequency region of high noise sensitivity at 4–6 kHz. A primary noise target is the cochlear hair cell. While the mechanisms that underlie such hair cell damage remain unclear, there is evidence to support a role for reactive oxygen species, stress pathway signaling and apoptosis. Another target is the synapse between the hair cell and the primary afferent neurons. Large numbers of these synapses and their neurons can be lost after noise, even though hearing thresholds may return to normal. This affects auditory processing and detection of signals in noise. The consequences of TTS and PTS include significant deficits in communication that can impact performance of military duties or obtaining/retaining civilian employment. Tinnitus and exacerbation of post-traumatic stress disorder are also potential sequelae.
doi:10.1097/MAO.0000000000001071
PMCID: PMC4988324  PMID: 27518135
Auditory; Significant Threshold Shift; STS; Temporary Threshold Shift; TTS; Measurement
18.  Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK 
The Journal of Neuroscience  2016;36(28):7497-7510.
Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL.
SIGNIFICANCE STATEMENT Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy.
doi:10.1523/JNEUROSCI.0782-16.2016
PMCID: PMC4945669  PMID: 27413159
activation of AMPK; cochlear synaptopathy; noise-induced hearing loss; protection of noise-induced hearing loss; sensory hair cells
19.  Spatial Benefit of Bilateral Hearing Aids 
Ear and hearing  2009;30(2):203-218.
Objectives
To assess the extent to which hearing aids improve spatial benefit by restoring the availability of interaural difference cues, the benefit attributable to spatial separation of speech and babble with and without bilateral hearing aids was measured as a function of low-pass cutoff frequency.
Design
Twenty-one older adults with sloping high-frequency hearing loss were provided commercially available bilateral hearing aids. After a 3 to 6 month acclimatization period, speech levels corresponding to 50% correct recognition of sentences from the Hearing in Noise Test (HINT) were measured in a 65-dB SPL babble, with speech and babble low-pass filtered at 1.8, 3.6, and 5.6 kHz. Sentences were always at 0° azimuth, and babble was at either 0° or 90°. Speech and babble spectra for all conditions were digitally recorded using a probe microphone placed in each ear canal of each subject. Spectra and levels of speech and babble and unaided thresholds for narrowband noises were used to calculate the aided audibility index and provide predictions of unaided and aided thresholds for HINT sentences, hearing aid benefit, and spatial benefit for each cutoff frequency. In addition, subjects’ willingness to tolerate background noise with and without amplification was measured in the spatially coincident and spatially separated conditions using the Acceptable Noise Level (ANL) procedure.
Results
Thresholds for HINT sentences in babble and ANL improved significantly when aided and when speech and babble were spatially separated. Specifically, hearing aid benefit improved significantly as cutoff frequency increased from 1.8 to 3.6 kHz but only when speech and babble were spatially separated; likewise, spatial benefit improved significantly from 1.8 to 3.6 kHz but only in the aided condition. No further improvement in hearing aid or spatial benefit was observed when cutoff frequency was increased from 3.6 to 5.6 kHz, although improvement in hearing aid benefit was predicted.
Conclusions
Hearing aid benefit, although significant, was poorer than predicted, suggesting that these older adults with high-frequency hearing loss did not take full advantage of the increase in audible speech information provided by amplification. Hearing aid benefit was also limited because hearing aids for some subjects did not restore speech audibility across the full bandwidth of speech. Unaided and aided spatial benefit was significantly greater than predicted, and aided spatial benefit was greater than unaided. This suggests that these older adults were able to take advantage of interaural level and time difference cues to improve speech recognition in babble and that they benefited from these cues to a greater extent with than without bilateral hearing aids. Finally, in contrast to results of previous studies, ANL may vary for an individual depending on the listening condition.
doi:10.1097/AUD.0b013e31819769c1
PMCID: PMC3693091  PMID: 19194292
20.  Auditory Function and Hearing Loss in Children and Adults with Williams Syndrome: Cochlear Impairment in Individuals with Otherwise Normal Hearing 
Hearing loss is common in school-age individuals with Williams syndrome (WS) and extensive in adults. Prior studies with relatively small sample sizes suggest that hearing loss in WS has an early onset and may be progressive, yet the auditory phenotype and the scope of the hearing loss have not been adequately characterized. We used standard audiometric tools: Otoscopy, tympanometry, air-conduction (bone conduction when available) behavioral testing, and distortion product otoacoustic emissions (DPOAEs) to measure hearing sensitivity and outer hair cell function. We tested 81 individuals with WS aged 5.33 to 59.50 years. 63% of the school-age and 92% of the adult participants had mild to moderately-severe hearing loss. The hearing loss in at least 50% was sensorineural. DPOAE testing corroborated behavioral results. Strikingly, 12 of 14 participants with hearing within normal limits bilaterally had 4000-Hz DPOAE input/output (DPOAE IO) functions indicative of outer hair cell damage and impaired cochlear compression. Our results indicate that hearing loss is very common in WS. Furthermore, individuals with WS who have “normal” hearing as defined by behavioral thresholds may actually have sub-clinical impairments or undetected cochlear pathology. Our findings suggest outer hair cell dysfunction in otherwise normal hearing individuals. The DPOAE IO in this same group revealed growth functions typically seen in groups with noise-induced damage. Given this pattern of findings, individuals with WS may be at increased risk of noise-induced hearing loss. Recommendations regarding audiological testing for individuals with WS and accommodations for these individuals in both academic and nonacademic settings are provided.
doi:10.1002/ajmg.c.30262
PMCID: PMC2913545  PMID: 20425785
Williams syndrome; genetic hearing loss; noise-induced hearing loss; sensorineural hearing loss; distortion product otoacoustic emissions
21.  Automated Screening for High-Frequency Hearing Loss 
Ear and Hearing  2014;35(6):667-679.
Objective:
Hearing loss at high frequencies produces perceptual difficulties and is often an early sign of a more general hearing loss. This study reports the development and validation of two new speech-based hearing screening tests in English that focus on detecting hearing loss at frequencies above 2000 Hz.
Design:
The Internet-delivered, speech-in noise tests used closed target-word sets of digit triplets or consonant–vowel–consonant (CVC) words presented against a speech-shaped noise masker. The digit triplet test uses the digits 0 to 9 (excluding the disyllabic 7), grouped in quasi-random triplets. The CVC test uses simple words (e.g., “cat”) selected for the high-frequency spectral content of the consonants. During testing, triplets or CVC words were identified in an adaptive procedure to obtain the speech reception threshold (SRT) in noise. For these new, high-frequency (HF) tests, the noise was low-pass filtered to produce greater masking of the low-frequency speech components, increasing the sensitivity of the test for HF hearing loss. Individual test tokens (digits, CVCs) were first homogenized using a group of 10 normal-hearing (NH) listeners by equalizing intelligibility across tokens at several speech-in-noise levels. Both tests were then validated and standardized using groups of 24 NH listeners and 50 listeners with hearing impairment. Performance on the new high frequency digit triplet (HF-triplet) and CVC (HF-CVC) tests was compared with audiometric hearing loss, and with that on the unfiltered, broadband digit triplet test (BB-triplet) test, and the ASL (Adaptive Sentence Lists) speech-in-noise test.
Results:
The HF-triplet and HF-CVC test results (SRT) both correlated positively and highly with high-frequency audiometric hearing loss and with the ASL test. SRT for both tests as a function of high-frequency hearing loss increased at nearly three times the rate as that of the BB-triplet test. The intraindividual variability (SD) on the tests was about 2.1 (HF-triplet) and 1.7 (HF-CVC) times less than that for the BB-triplet test. The effect on the HF-triplet test of varying presentation method (professional or cheap headphones and loudspeakers) was small for the NH group and somewhat larger, but nonsignificant for the hearing-impaired group. Test repetition produced a moderate, significant learning effect for the first and second retests, but was small and nonsignificant for further retesting. The learning effect was about two times larger for the HF-CVC test than for the HF-triplet test. The sensitivity of both new tests for high-frequency hearing loss was similar, with an 87% true-positive and 7% false-positive ratio for detecting an average high-frequency hearing loss of 20 dB or more.
Conclusions:
The new HF-triplet and HF-CVC tests provide a sensitive and accurate method for detecting high-frequency hearing loss. The tests may signal developing hearing impairment at an early stage. The HF-triplet is preferred over the HF-CVC test because of its smaller learning effect, smaller error rate, greater simplicity, and lower cultural dependency.
We have developed 2 new simple, internet-delivered, speech-innoise tests for high-frequency (HF) hearing loss. They may be used at home or in the clinic/lab as screening tests or as outcome measures for hearing rehabilitation. The new tests, HF-triplet and HFCVC (Consonant-Vowel-Consonant), both showed better sensitivity for detecting HF hearing loss (HL) than the standard broadband BBtriplet test. The accuracy of the HF-triplet was 2.5 times that of the BB-triplet test. A small training effect for the HF-triplet was about half that of the HF-CVC. The HF-triplet out performed the HF-CVC test in both accuracy and test repeatability and is recommended for screening HFHL.
doi:10.1097/AUD.0000000000000073
PMCID: PMC4212007  PMID: 25127323
Hearing impairment; Hearing rehabilitation; Hearing screening; High-frequency hearing loss; Speech intelligibility
22.  Occupational noise exposure and hearing: a systematic review 
Purpose
To give a systematic review of the development of noise-induced hearing loss (NIHL) in working life.
Methods
A literature search in MEDLINE, Embase, Web of Science, Scopus, and Health and Safety Abstracts, with appropriate keywords on noise in the workplace and health, revealed 22,413 articles which were screened by six researchers. A total of 698 articles were reviewed in full text and scored with a checklist, and 187 articles were found to be relevant and of sufficient quality for further analysis.
Results
Occupational noise exposure causes between 7 and 21 % of the hearing loss among workers, lowest in the industrialized countries, where the incidence is going down, and highest in the developing countries. It is difficult to distinguish between NIHL and age-related hearing loss at an individual level. Most of the hearing loss is age related. Men lose hearing more than women do. Heredity also plays a part. Socioeconomic position, ethnicity and other factors, such as smoking, high blood pressure, diabetes, vibration and chemical substances, may also affect hearing. The use of firearms may be harmful to hearing, whereas most other sources of leisure-time noise seem to be less important. Impulse noise seems to be more deleterious to hearing than continuous noise. Occupational groups at high risk of NIHL are the military, construction workers, agriculture and others with high noise exposure.
Conclusion
The prevalence of NIHL is declining in most industrialized countries, probably due to preventive measures. Hearing loss is mainly related to increasing age.
Electronic supplementary material
The online version of this article (doi:10.1007/s00420-015-1083-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s00420-015-1083-5
PMCID: PMC4786595  PMID: 26249711
NIHL; ISO; Population studies; Vibration; Cardiovascular risk factors; Chemicals; Leisure-time noise; Mechanisms
23.  Pitch and Loudness from Tinnitus in Individuals with Noise-induced Hearing Loss 
Introduction
 Tinnitus is one of the symptoms that affects individuals suffering from noise induced hearing loss. This condition can be disabling, leading the affected individual to turn away from work.
Objective
 This literature review aims to analyze the possible association between gender and tinnitus pitch and loudness, the degree of hearing loss and the frequencies affected in subjects with noise-induced hearing loss.
Methods
 This contemporary cohort study was conducted through a cross-sectional analysis. The study sample consisted of adults with unilateral or bilateral tinnitus, who had been diagnosed with noise-induced hearing loss. The patients under analysis underwent an otorhinolaryngological evaluation, pure tone audiometry, and acuphenometry.
Results
 The study included 33 subjects with noise-induced hearing loss diagnoses, of which 22 (66.7%) were men. Authors observed no statistical difference between gender and loudness/pitch tinnitus and loudness/pitch in subjects with bilateral tinnitus. Authors found an inverse relation between tinnitus loudness with intensity greater hearing threshold and the average of the thresholds and the grade of hearing loss. The tinnitus pitch showed no association with higher frequency of hearing threshold.
Conclusion
 Data analysis shows that, among the individuals evaluated, the greater the hearing loss, the lower the loudness of tinnitus. We did not observe an association between hearing loss and tinnitus pitch.
doi:10.1055/s-0035-1562935
PMCID: PMC4942292  PMID: 27413408
hearing loss; noise-induced; tinnitus
24.  Tone perception in Mandarin-speaking school age children with otitis media with effusion 
PLoS ONE  2017;12(8):e0183394.
Objectives
The present study explored tone perception ability in school age Mandarin-speaking children with otitis media with effusion (OME) in noisy listening environments. The study investigated the interaction effects of noise, tone type, age, and hearing status on monaural tone perception, and assessed the application of a hierarchical clustering algorithm for profiling hearing impairment in children with OME.
Methods
Forty-one children with normal hearing and normal middle ear status and 84 children with OME with or without hearing loss participated in this study. The children with OME were further divided into two subgroups based on their severity and pattern of hearing loss using a hierarchical clustering algorithm. Monaural tone recognition was measured using a picture-identification test format incorporating six sets of monosyllabic words conveying four lexical tones under speech spectrum noise, with the signal-to-noise ratio (SNR) conditions ranging from -9 to -21 dB.
Results
Linear correlation indicated tone recognition thresholds of children with OME were significantly correlated with age and pure tone hearing thresholds at every frequency tested. Children with hearing thresholds less affected by OME performed similarly to their peers with normal hearing. Tone recognition thresholds of children with auditory status more affected by OME were significantly inferior to those of children with normal hearing or with minor hearing loss. Younger children demonstrated poorer tone recognition performance than older children with OME. A mixed design repeated-measure ANCOVA showed significant main effects of listening condition, hearing status, and tone type on tone recognition. Contrast comparisons revealed that tone recognition scores were significantly better under -12 dB SNR than under -15 dB SNR conditions and tone recognition scores were significantly worse under -18 dB SNR than those obtained under -15 dB SNR conditions. Tone 1 was the easiest tone to identify and Tone 3 was the most difficult tone to identify for all participants, when considering -12, -15, and -18 dB SNR as within-subject variables. The interaction effect between hearing status and tone type indicated that children with greater levels of OME-related hearing loss had more impaired tone perception of Tone 1 and Tone 2 compared to their peers with lesser levels of OME-related hearing loss. However, tone perception of Tone 3 and Tone 4 remained similar among all three groups. Tone 2 and Tone 3 were the most perceptually difficult tones for children with or without OME-related hearing loss in all listening conditions.
Conclusions
The hierarchical clustering algorithm demonstrated usefulness in risk stratification for tone perception deficiency in children with OME-related hearing loss. There was marked impairment in tone perception in noise for children with greater levels of OME-related hearing loss. Monaural lexical tone perception in younger children was more vulnerable to noise and OME-related hearing loss than that in older children.
doi:10.1371/journal.pone.0183394
PMCID: PMC5568745  PMID: 28829840
25.  Auditory-Filter Characteristics for Listeners With Real and Simulated Hearing Impairment 
Trends in Amplification  2012;16(1):19-39.
Functional simulation of sensorineural hearing impairment is an important research tool that can elucidate the nature of hearing impairments and suggest or eliminate compensatory signal-processing schemes. The objective of the current study was to evaluate the capability of an audibility-based functional simulation of hearing loss to reproduce the auditory-filter characteristics of listeners with sensorineural hearing loss. The hearing-loss simulation used either threshold-elevating noise alone or a combination of threshold-elevating noise and multiband expansion to reproduce the audibility-based characteristics of the loss (including detection thresholds, dynamic range, and loudness recruitment). The hearing losses of 10 listeners with bilateral, mild-to-severe hearing loss were simulated in 10 corresponding groups of 3 age-matched normal-hearing listeners. Frequency selectivity was measured using a notched-noise masking paradigm at five probe frequencies in the range of 250 to 4000 Hz with a fixed probe level of either 70 dB SPL or 8 dB SL (whichever was greater) and probe duration of 200 ms. The hearing-loss simulation reproduced the absolute thresholds of individual hearing-impaired listeners with an average root-mean-squared (RMS) difference of 2.2 dB and the notched-noise masked thresholds with an RMS difference of 5.6 dB. A rounded-exponential model of the notched-noise data was used to estimate equivalent rectangular bandwidths and slopes of the auditory filters. For some subjects and probe frequencies, the simulations were accurate in reproducing the auditory-filter characteristics of the hearing-impaired listeners. In other cases, however, the simulations underestimated the magnitude of the auditory bandwidths for the hearing-impaired listeners, which suggests the possibility of suprathreshold deficits.
doi:10.1177/1084713812445510
PMCID: PMC4040846  PMID: 22593204
hearing loss; hearing-loss simulation; notched-noise masking; auditory filter shape

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