Sensorineural hearing loss (SNHL), caused by pathology in the cochlea, is the most common type of hearing loss in humans. It is generally irreversible with very few effective pharmacological treatments available to prevent the degenerative changes or minimise the impact. Part of this has been attributed to difficulty of translating "proof-of-concept" for novel treatments established in small animal models to human therapies. There is an increasing interest in the use of sheep as a large animal model. In this article, we review the small and large animal models used in pre-clinical hearing research such as mice, rats, chinchilla, guinea pig, rabbit, cat, monkey, dog, pig, and sheep to humans, and compare the physiology, inner ear anatomy, and some of their use as model systems for SNHL, including cochlear implantation surgeries. Sheep have similar cochlear anatomy, auditory threshold, neonatal auditory system development, adult and infant body size, and number of birth as humans. Based on these comparisons, we suggest that sheep are well-suited as a potential translational animal model that bridges the gap between rodent model research to the clinical use in humans. This is especially in areas looking at changes across the life-course or in specific areas of experimental investigation such as cochlear implantation and other surgical procedures, biomedical device development and age-related sensorineural hearing loss research. Combined use of small animals for research that require higher throughput and genetic modification and large animals for medical translation could greatly accelerate the overall translation of basic research in the field of auditory neuroscience from bench to clinic.

Objectives Hearing loss is one of the most prevalent conditions affecting older people. In addition, there is little known about the factors influencing the uptake of hearing services among underserved communities. Our objective was to identify the barriers to accessing hearing care services among older Pacific Island people in New Zealand. Settings Eligible participants from Auckland City, New Zealand. Participants Individual face-to-face in-depth interviews were conducted with 36 older Pacific Island people who were experienced hearing difficulties. Methods A Pacific Island research methodology (Talanoa) and the 'Health Care Access Barriers' (HCAB) model, which identifies modifiable barriers to healthcare, was used as a theoretical framework for this research. The interviews were transcribed and analysed using a deductive approach to identify HCAB themes and subthemes experienced by older Pacific Island people. Results Identified themes aligned with HCAB's themes of financial, structural and cognitive barriers and subthemes described Pacific Island perspectives related to hearing care access in New Zealand. The financial barriers related to the high cost of hearing care and the structural barriers included transportation difficulties, limited family support, preference for community-based services and the absence of hearing care delivered by family doctors. Community norms and attitudes, communication limitations and limited awareness of hearing care services formed cognitive barriers among older Pasifika people in this study. Conclusion We identified financial, structural and cognitive barriers that dissuaded older Pasifika people from accessing hearing care services. These modifiable barriers need to be eliminated or minimised to enable people to readily receive the hearing care assistance they need. It is essential to improve and develop culturally responsive models of hearing service delivery to ensure equitable access to hearing care, especially for underserved groups such as Pacific Island communities.

The World Health Organization (WHO) estimates that 466 million people globally have significant hearing loss, a figure set to double by 2050. 1 Ear disease, such as otitis media, and hearing loss can have significant consequences on individuals, affecting communication, language development, educational opportunities and employment choices, and may also contribute to social isolation, cognitive decline and depression. 1,2The 2017 World Health Assembly resolution Prevention of deafness and hearing loss recognizes that ear disease and hearing loss are important public health issues. 3revalence of these conditions in low-and middle-income countries is higher than in high-income countries. 4,5HO estimates that 75% of hearing loss in children in low-and middle-income countries is preventable through relatively low-cost and timely public health strategies 1 such as immunization, good ear-care practices, strengthening maternal and child health programmes and screening children for otitis media.However, providing accessible hearing and ear health services to all the population remains a challenge in many of these countries because of resource constraints and competing health priorities. 6The 22 countries and territories

Objective: To examine cortical auditory evoked potentials (CAEPs) and behavioural measures of spatial speech in noise recognition, sound localization and self-reported perception of hearing performance before and after surgical removal of an acoustic neuroma, and to monitor changes over time after surgery.Methods: CAEPs in noise were recorded and auditory skills were assessed using tests of sound localization, spatial speech perception in noise and self-ratings of auditory abilities (Speech, Spatial and Qualities of Hearing questionnaire, SSQ) in a male adult with single-sided deafness due to acoustic neuroma removal. Measurements took place at 2, 6 and 12 months after surgery.Results: The pattern of CAEP responses, behavioural measurements and self-reported perception after surgery differed from the pre-surgery baseline and changed over time after surgery.Conclusions: The participant experienced considerable listening fatigue and deficits in auditory skills after losing hearing in one ear. Different patterns of change in CAEPs and other measures over time suggest multiple physiological mechanisms for auditory plasticity after acute onset of single sided deafness.

Abstract Objective: To develop and assess use, acceptability and feasibility of an ecological hearing conservation programme for workplaces. Design: A school-based public health hearing preservation education programme (Dangerous Decibels®) was adapted for workplaces using the Multi-level Approach to Community Health (MATCH) Model. The programme was delivered in small manufacturing companies and evaluated using a questionnaire before the training and at one week and two-months after training. Study sample: Workers (n = 56) from five small manufacturing companies were recruited. Results: There was a significant improvement in knowledge, attitudes and behaviour of workers at the intrapersonal level; in behaviour motivation and safety culture at the interpersonal and organisational levels; and an overall improvement in hearing-health behaviour after two months post-intervention. Conclusions: The developed programme offers a simple, interactive and theory-based intervention that is well accepted and effective in promoting positive hearing-health behaviour in workplaces.

INTRODUCTION Hearing impairment (HI) affects an estimated 538 million people worldwide, with 80% of these living in developing countries. Untreated HI in childhood may lead to developmental delay and in adults results in social isolation, inability to find or maintain employment, and dependency. Early intervention and support programmes can significantly reduce the negative effects of HI. AIM To estimate HI prevalence and identify available hearing services in some Pacific countries - Cook Islands, Fiji, Niue, Samoa, Tokelau, Tonga. METHODS Data were collected through literature review and correspondence with service providers. Prevalence estimates were based on census data and previously published regional estimates. RESULTS Estimates indicate 20-23% of the population may have at least a mild HI, with up to 11% having a moderate impairment or worse. Estimated incidence of chronic otitis media in Pacific Island nations is 3-5 times greater than other Australasian countries in children under 10 years old. Permanent HI from otitis media is substantially more likely in children and adults in Pacific Island nations. Several organisations and individuals provide some limited hearing services in a few Pacific Island nations, but the majority of people with HI are largely underserved. DISCUSSION Although accurate information on HI prevalence is lacking, prevalence estimates of HI and ear disease suggest they are significant health conditions in Pacific Island nations. There is relatively little support for people with HI or ear disease in the Pacific region. An investment in initiatives to both identify and support people with hearing loss in the Pacific is necessary.

BACKGROUND Noise-induced hearing loss (NIHL) remains an important occupational health issue as the second most commonly self-reported occupational injury or illness. The incorrect and inconsistent use of hearing protection devices (HPDs) compromises their effectiveness in preventing NIHL. AIMS To describe the development of an easily administered yet robust questionnaire to investigate factors that influence HPD use. METHODS A hearing protection assessment (HPA-2) questionnaire was developed using items based on themes identified in our previous research. These fell into two classes: supports and barriers to wearing HPD, which formed two scales within the questionnaire. The questionnaire, which also included demographic items, was administered to workers from 34 manufacturing companies. The internal consistency of the scales was tested, and factor analysis was conducted to investigate the underlying structure of the scales. RESULTS Of the 1053 questionnaires distributed, 555 completed questionnaires were received giving a response rate of 53%. The Cronbach's alpha for the barriers scale (α = 0.740) and supports scale (α = 0.771) indicated strong internal reliability of the questionnaire. The supports and barriers were further described as five key factors (risk justification, HPD constraints, hazard recognition, behaviour motivation and safety culture) that influence hearing protection behaviour. Workers who reported always using HPDs had more supports across these factors, while those who did not always wear HPDs reported more barriers. CONCLUSIONS The HPA-2 questionnaire may be useful in both research and interventions to understand and motivate hearing protection behaviour by identifying and targeting supports and barriers to HPD use at different levels of the ecological model.

AIM:This study was undertaken to determine if young Maori have more permanent bilateral hearing loss, or less severe and profound hearing loss than New Zealand (NZ) Europeans. METHODS:Data include hearing-impaired children from birth to 19 years of age from the New Zealand Deafness Notification Database (DND) and covering the periods 1982-2005 and 2009-2013. These were retrospectively analysed, as was information on children and young people with cochlear implants. RESULTS:Young Maori are more likely to be diagnosed with permanent hearing loss greater than 26 dB HL, averaged across speech frequencies, with 39-43% of hearing loss notifications listed as Maori. Maori have a lower prevalence of severe/profound losses (n=1571, chi squared=22.08, p=0.01) but significantly more bilateral losses than their NZ European peers (n=595, Chi-squared=9.05, p=0.01). The difference in severity profile is supported by cochlear implant data showing Maori are less likely to receive a cochlear implant. CONCLUSIONS:There are significant differences in the proportion of bilateral (compared to unilateral) losses and in the rates and severity profile of hearing loss among young Maori when compared with their NZ European peers. This has implications for screening and other hearing services in NZ.

The sense of hearing is remarkable for its auditory dynamic range, which spans more than 10 12 in acoustic intensity. The mechanisms that enable the cochlea to transduce high sound levels without damage are of key interest, particularly with regard to the broad impact of industrial, military, and recreational auditory overstimulation on hearing disability. We show that ATP-gated ion channels assembled from P2X 2 receptor subunits in the cochlea are necessary for the development of temporary threshold shift (TTS), evident in auditory brainstem response recordings as sound levels rise. In mice null for the P2RX2 gene (encoding the P2X 2 receptor subunit), sustained 85-dB noise failed to elicit the TTS that wild-type (WT) mice developed. ATP released from the tissues of the cochlear partition with elevation of sound levels likely activates the broadly distributed P2X 2 receptors on epithelial cells lining the endolymphatic compartment. This purinergic signaling is supported by significantly greater noise-induced suppression of distortion product otoacoustic emissions derived from outer hair cell transduction and decreased suprathreshold auditory brainstem response input/output gain in WT mice compared with P2RX2- null mice. At higher sound levels (≥95 dB), additional processes dominated TTS, and P2RX2- null mice were more vulnerable than WT mice to permanent hearing loss due to hair cell synapse disruption. P2RX2- null mice lacked ATP-gated conductance across the cochlear partition, including loss of ATP-gated inward current in hair cells. These data indicate that a significant component of TTS represents P2X 2 receptor-dependent purinergic hearing adaptation that underpins the upper physiological range of hearing.

NADPH oxidases are enzymes that transport electrons across the plasma membrane and generate superoxide radical from molecular oxygen. The current study investigated the expression and distribution of NOX/DUOX members of the NADPH oxidase family (NOX1-5 and DUOX1-2) in the rat cochlea and their regulation in response to noise. Wistar rats (8-10 weeks) were exposed for 24 h to band noise (8-12 kHz) at moderate (100 dB) or traumatic (110 dB) sound pressure levels (SPL). Animals exposed to ambient noise (45-55 dB SPL) served as controls. Immunohistochemistly demonstrated predominant expression of all NOX/DUOX isoforms in the sensory and supporting cells of the organ of Corti, with very limited immunoexpression in the lateral wall tissues and spiral ganglion neurons. Noise exposure induced up-regulation of NOX1 and DUOX2 in the cochlea, whereas NOX3 was down-regulated. A significant reduction in the intensity of NOX3 immunolabeling was observed in the inner sulcus region of the cochlea after exposure to noise. Post-exposure inhibition of NADPH oxidases by Diphenyleneiodonium (DPI), a broadly selective NADPH oxidase inhibitor, mitigated noise-induced hearing loss. Conclusion: Noise-induced up-regulation of NOX1 and DUOX2 could be linked to cochlear injury. In contrast, down-regulation of NOX3 may represent an endogenous protective mechanism to reduce oxidative stress in the noise-exposed cochlea. Inhibition of NADPH oxidases is potentially a novel pathway for therapeutic management of noise-induced hearing loss. (C) 2013 Elsevier B.V. All rights reserved.

PurposeTo quantify spatial and temporal inflammation‐induced changes in vascular permeability and macrophage infiltration in guinea‐pig (GP) cochlea using MRI.Materials and MethodsGPs were injected with lipopolysaccharide (LPS) to induce cochlear inflammation. One group was injected with a gadolinium based contrast agent (GBCA) and dynamic contrast enhanced (DCE)‐MRI was performed at 4, 7, and 10 days after LPS treatment. A two‐compartment pharmacokinetic model was used to determine the apparent rate constant of GBCA extravasation (Ktrans). A second group was injected with ultrasmall superparamagnetic iron oxide particles (USPIOs) and studied at 2, 3, and 7 days after LPS treatment to detect tissue USPIO uptake and correlate with histology. For both groups, control GPs were scanned similarly.ResultsThe signal enhancement increased substantially and more rapidly at day 4 in LPS‐treated than in control cochlea shortly following GBCA injection. Ktrans of LPS‐treated cochlea was maximum on day 4 at 0.0218 ± 0.0032 min−1 and then decreased to control level at 0.0036 ± 0.0004 min−1 by day 10. In the second group, the relative signal intensity and T2 in cochlear perilymphatic spaces on day 2 decreased, on average, by 54% and 45%, respectively, compared with baseline and then remained under control levels by day 7. This suggests the infiltration of inflammatory cells, although unconfirmed by histology.ConclusionThis provides the first measurement of cochlear vascular permeability using MRI and a quantitative evaluation of the development of cochlear inflammation. MRI holds considerable potential for the assessment of disease processes such as clinical diagnosis of conditions such as labyrinthitis. J. Magn. Reson. Imaging 2014;39:150–161. © 2013 Wiley Periodicals, Inc.

A complex extracellular nucleotide signalling system acting on P2 receptors is involved in regulation of cochlear function in the mammalian inner ear. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are ectonucleotidases that regulate P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from the CD39/ENTPD family (NTPDase1-8) are expressed in the adult rat cochlea, but their expression and distribution in the vestibular end organ is unknown. This report demonstrates selective expression of NTPDase6 by rat vestibular hair cells. Hair cells transducing both angular acceleration (crista ampullaris) and static head position (maculae of the utricle and saccule) exhibited strong immunolabelling with a bias towards the sensory pole and in particular, the hair cell bundle. NTPDase6 is an intracellular enzyme that can be released in a soluble form from cell cultures and shows an enzymatic preference for nucleoside 5'-diphosphates, such as guanosine 5'-diphosphate (GDP) and uridine 5'-diphosphate (UDP). The main function of NTPDase6 may be the regulation of nucleotide levels in cellular organelles by regulating the conversion of nucleotides to nucleosides. NTPDase6 immunolocalisation in the vestibular end organ could be linked to the regulation of P2 receptor signalling and sensory transduction, including maintenance of vestibular hair bundles.

This study was undertaken to determine the role of adenosine signalling in the development of age-related hearing loss (ARHL). We and others have shown previously that adenosine signalling via A(1) receptors is involved in cochlear protection from noise-induced cochlear injury. Here we demonstrate that enhanced adenosine signalling in the cochlea provides partial protection from ARHL in C57BL/6J mice. We targeted adenosine kinase (ADK), the key enzyme in adenosine metabolism, using a treatment regime with the selective ADK inhibitor ABT-702 (1.5mg/kg intraperitoneally twice a week) commencing at the age of three months or six months. This treatment, intended to increase free adenosine levels in the cochlea, was maintained until the age of nine months and hearing thresholds were evaluated monthly using auditory brainstem responses (ABR). At nine months, when C57BL/6J mice normally exhibit significant ARHL, both groups treated with ABT-702 showed lower ABR threshold shifts at 10 and 16kHz compared to control animals receiving the vehicle solution. The better thresholds of the ABT-702-treated mice at these frequencies were supported by increased survival of hair cells in the apical region of the cochlea. This study provides the first evidence that ARHL can be mitigated by enhancing adenosine signalling in the cochlea.

INTRODUCTION Hearing loss is a major cause of disability in the world. Occupational noise exposure is likely to contribute to a very high proportion of the cases of hearing loss in adults. Concern has been raised by the Accident Compensation Corporation (ACC) in New Zealand about the fact that the number of new cases of noise-induced hearing loss (NIHL) is not declining, despite the health and safety legislation and establishment of hearing conservation programmes in industry. To inform strategies for prevention, a review of the burden of NIHL in New Zealand was undertaken, particularly focusing on the trends in compensation claims and costs, and the associated sociodemographic patterns. METHODS A review of the peer-reviewed published literature was conducted to identify national and international estimates of NIHL prevalence. The ACC claims dataset (July 1995 to June 2006) was analysed to describe annual trends in new NIHL claims, cost to ACC, and claimants' age, gender and occupational group. RESULTS There is currently no reliable information regarding the overall incidence and prevalence of NIHL in New Zealand. ACC data reveals a substantial increase in the number of new NIHL claims annually, rising from 2823 in July 1995-June 1996, to 5580 in July 2005-June 2006. Together with ongoing claims the overall costs of NIHL claims increased by an average of 20% each year (a six-fold increase over the decade) resulting in a total cost to ACC of $193.82M over the review period. Collectively, agriculture and fisheries workers, trades workers, machine operators, and assemblers accounted for 53% of new claims. Most claims were lodged in middle age or later, with the vast majority of claimants (95%) being men. The relationship of age with the probability of making a claim changed significantly over the study period with rates in older age groups increasing faster than in younger. CONCLUSIONS The substantial and increasing societal costs despite decades of NIHL control legislation suggests that current strategies addressing this problem are not effective, inadequately implemented, or both.

Even though extracellular adenosine plays multiple roles in the cochlea, the mechanisms that control extracellular adenosine concentrations in this organ are unclear. This study investigated the expression of nucleoside transporters and adenosine uptake in the rat cochlea. Reverse transcription-polymerase chain reaction revealed the expression of mRNA transcripts for two equilibrative (ENT1 and ENT2) and two concentrative (CNT1 and CNT2) nucleoside transporters. Exogenous adenosine perfused through the cochlear perilymphatic compartment was taken up by cells lining the compartment. Adenosine uptake was sensitive to changes in extracellular Na+ concentrations and inhibited by nitrobenzylthioinosine (an adenosine uptake blocker). The study suggests that the bi-directional nucleoside transport supports the uptake and recycling of purines and regulates the activation of adenosine receptors by altering adenosine concentrations in cochlear fluid spaces.

Type I and type II spiral ganglion neurons (SGN) innervate the inner and outer hair cells of the cochlea, respectively. This neural system is established by reorganization of promiscuous innervation of the hair cells, immediately before hearing is established. The mechanism for this synaptic reorganization is unresolved but probably includes regulation of trophic support between the hair cells and the neurons. We provide evidence that P2X receptors (ATP-gated ion channels) contribute such a mechanism in the neonatal rat cochlea. Single-cell quantitative RT-PCR identified the differential expression of two P2X receptor subunits, splice variant P2X2-3 and P2X3, in a 1:2 transcript ratio. Downregulation of this P2X2-3/3 receptor coincided with maturation of the SGN innervation of the hair cells. When the P2X2-3 and P2X3 subunits were co-expressed in Xenopus oocytes, the resultant P2X receptor properties corresponded to the SGN phenotype. This included enhanced sensitivity to ATP and extended agonist action. In P4 spiral ganglion explants, activation of the P2X receptor signaling pathway by ATPγS or α,βMeATP inhibited BDNF-induced neurite outgrowth and branching. These findings indicate that P2X receptor signaling provides a mechanism for inhibiting neurotrophin support of SGN neurites when synaptic reorganization is occurring in the cochlea.

Stimuli such as noise or hypoxia can induce a release of ATP into the cochlear fluid spaces. At nanomolar concentrations, ATP affects neurotransmission and electrochemical regulation of sound transduction. At higher concentrations, ATP may exert cytotoxicity acting on specific P2X(7) receptor subunits, thus contributing to the pathophysiology of noise-induced cochlear injury. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are pivotal to regulation of extracellular nucleotide concentrations and therefore P2 receptor signaling in the cochlea. Here, we characterize the distribution of NTPDase3 ectonucleotidase (preferentially hydrolyzes ATP over ADP) in cochlear tissues and investigate the effect of noise exposure on NTPDase3 expression. Marked NTPDase3 immunoreactivity in the primary afferent neurones of the spiral ganglion, extending in the distal neurite processes to the synapses beneath the inner and outer hair cells, suggests involvement in auditory neurotransmission. Immunolabeling in the lateral wall and epithelial cells lining the cochlear partition was also evident. Semi-quantitative immunohistochemistry revealed increased NTPDase3 immunolabeling in the synaptic regions of the inner and outer hair cells at sound intensities that induce temporary threshold shift. The results suggest a role for NTPDase3 in regulating ATP signaling associated primarily with auditory neurotransmission, and the potential neuroprotective nature of noise-induced up-regulation of this ectonucleotidase in the cochlea.