Service delivery approaches related to hearing aids in low- and middle-income countries or resource-limited settings: A systematic scoping review.

Hearing loss is an important global public health issue which can be alleviated through treatment with hearing aids. However, most people who would benefit from hearing aids do not receive them, in part due to challenges in accessing hearing aids and related services, which are most salient in low- and middle-income countries (LMIC) and other resource-limited settings. Innovative approaches for hearing aid service delivery can overcome many of the challenges related to access, including that of limited human resources trained to provide ear and hearing care. The purpose of this systematic scoping review is to synthesize evidence on service delivery approaches for hearing aid provision in LMIC and resource-limited settings. We searched 3 databases (PubMed, Scopus, Ovid MEDLINE) for peer-reviewed articles from 2000 to 2022 that focused on service delivery approaches related to hearing aids in LMIC or resource-limited settings. Fifteen peer-reviewed articles were included, which described hospital-based (3 studies), large-scale donation program (1 studies), community-based (7 studies), and remote (telehealth; 4 studies) service delivery approaches. Key findings are that hearing aid services can be successfully delivered in hospital- and community-based settings, and remotely, and that both qualified hearing care providers and trained non-specialists can provide quality hearing aid services. Service delivery approaches focused on community-based and remote care, and task sharing among qualified hearing care providers and trained non-specialists can likely improve access to hearing aids worldwide, thereby reducing the burden of untreated hearing loss.

Sheep as a large animal model for hearing research: comparison to common laboratory animals and humans.

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.

Functional topography of the neocortex predicts covariation in complex cognitive and basic motor abilities.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g. hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year-old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Functional Topography of the Neocortex Predicts Covariation in Complex Cognitive and Basic Motor Abilities.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g., hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Patterns of vestibular dysfunction in chronic traumatic brain injury.

Background: Dizziness and imbalance are common following traumatic brain injury (TBI). While these symptoms are often attributed to vestibular dysfunction, the relative contribution of peripheral vs. central mechanisms is unclear. This study investigated the prevalence of semicircular canal and otolith abnormalities in a cohort of patients with chronic TBI and symptoms of dizziness or imbalance. The relationship between vestibular, oculomotor and posturography results was further explored. Methods: Clinical records of patients attending the New Zealand Dizziness and Balance Centre from January 2015 to December 2019 were reviewed for consideration in the study. Inclusion required: an age of 18-80 years, a diagnosed TBI, and vestibular assessment using three-dimensional video head impulses (vHIT), cervical and ocular vestibular-evoked myogenic potentials (c and o VEMPs, respectively) and caloric testing. Severe TBI, pre-existing vestibular diagnoses, and incomplete test results were excluded. Rates of abnormalities were determined for each test and compared with results of oculomotor function testing and postural control, measured using the sensory organization test (SOT). Results: Of 158 reviewed records, 99 patients aged 49 ± 15 years (59 female) fulfilled criteria for inclusion in the study. The median time between the head injury and the clinical assessment was 12 (IQR 6-21) months. Abnormalities involving one or more components of the vestibular labyrinth and/or nerve divisions were identified in 33 of 99 patients (33.3%). The horizontal semicircular canal was most frequently affected (18.2%), followed by the saccule (14.1%), utricle (8.1%), posterior (7.1%) and anterior (2.0%) semicircular canals. Vestibular test abnormalities were associated with skull-base fractures, superior canal dehiscence, and focal ear trauma. Oculomotor dysfunction and postural instability were recorded in 41.1 and 75.5% of patients, respectively. Postural instability correlated with abnormal oculomotor function (p = 0.008) but not peripheral vestibular hypofunction (p = 0.336). Conclusions: Dizziness and/or imbalance in chronic TBI was associated with impaired postural stability for tasks requiring high levels of use of vestibular and visual input for balance. Vestibular hypofunction identified through vHIT, VEMP and caloric testing was recorded but was less common, except when the injury involved a fractured skull-base. There was no specific pattern of end-organ or nerve involvement which characterized this group of patients.

Purinergic Signalling in the Cochlea.

The mammalian cochlea is the sensory organ of hearing with a delicate, highly organised structure that supports unique operating mechanisms. ATP release from the secretory tissues of the cochlear lateral wall (stria vascularis) triggers numerous physiological responses by activating P2 receptors in sensory, supporting and neural tissues. Two families of P2 receptors, ATP-gated ion channels (P2X receptors) and G protein-coupled P2Y receptors, activate intracellular signalling pathways that regulate cochlear development, homeostasis, sensory transduction, auditory neurotransmission and response to stress. Of particular interest is a purinergic hearing adaptation, which reflects the critical role of the P2X2 receptor in adaptive cochlear response to elevated sound levels. Other P2 receptors are involved in the maturation of neural processes and frequency selectivity refinement in the developing cochlea. Extracellular ATP signalling is regulated by a family of surface-located enzymes collectively known as "ectonucleotidases" that hydrolyse ATP to adenosine. Adenosine is a constitutive cell metabolite with an established role in tissue protection and regeneration. The differential activation of A1 and A2A adenosine receptors defines the cochlear response to injury caused by oxidative stress, inflammation, and activation of apoptotic pathways. A1 receptor agonism, A2A receptor antagonism, and increasing adenosine levels in cochlear fluids all represent promising therapeutic tools for cochlear rescue from injury and prevention of hearing loss.

Life-Course Persistent Antisocial Behavior and Accelerated Biological Aging in a Longitudinal Birth Cohort.

Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (ß, 0.22, 95%CI, 0.14, 0.28, p ≤ 0.001). This amounted to 4.3 extra years of biological aging between ages 25-45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (ß, -0.14, 95%CI, -0.21, -0.08, p ≤ 0.001), balance (ß, -0.13, 95%CI, -0.18, -0.06, p ≤ 0.001), gait speed (ß, -0.18, 95%CI, -0.24, -0.10, p ≤ 0.001), and cognitive functioning (ß, -0.25, 95%CI, -0.31, -0.18, p ≤ 0.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on healthcare systems and improve their wellbeing.

Diagnostic and management plan concordance across advanced audiologists, paediatric audiologists and non-specialist ENT doctors.

OBJECTIVE: To compare the concordance of advanced audiologists (AA), junior doctors (JD) and paediatric audiologists (PA) with an Ear, Nose and Throat (ENT) specialist on the diagnosis and management of children with middle ear or hearing concerns. DESIGN: A clinical equivalence (concordance) study. STUDY SAMPLE: Three AAs, five JDs, three PAs and one ENT specialist asynchronously reported diagnoses and management plans for ten, online paediatric cases consisting of video-otoscopic images and clinical findings. RESULTS: For medical diagnosis, significant agreement with the ENT specialist was observed at moderate and near-perfect levels for two AAs (k = 0.561 and 0.815), moderate levels for four JDs (k = 0.5 to 0.603) and near-perfect level for one PA (k = 0.815). For management decisions, significant agreement with the ENT specialist was observed at substantial (k = 0.636) and near-perfect (k = 0.818) levels for two AAs, and at a moderate level (k = 0.538) for one PA. Within group inter-rater agreement for management plans was substantial for AAs and JDs, and moderate for PAs. CONCLUSIONS: For children with middle ear disease or hearing concerns, AAs, JDs and PAs showed similar levels of agreement with an ENT specialist on diagnosis, but AAs were more likely than JDs or PAs to agree with an ENT specialist on management.

Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

Knowledge of a person's risk for Alzheimer's disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer's Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (ß's from 0.16 to 0.22), white matter hyperintensities volume (ß's from 0.16 to 0.19), hippocampal volume (ß's from -0.08 to -0.11), tested cognitive deficits (ß's from -0.36 to -0.49), everyday cognitive problems (ß's from 0.14 to 0.38), and longitudinal cognitive decline (ß's from -0.18 to -0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

Ear and hearing health in Niue: a qualitative study on the worldviews, knowledge, beliefs and use of health care.

Introduction Hearing is a primary sense that facilitates the development of spoken language, social connection and an appreciation of sounds within the natural world. Hearing loss has multiple adverse effects across the life course. Understanding the worldviews of ear and hearing health in Pacific peoples is crucial to inform responsive and appropriate hearing health and primary healthcare services. Aim To understand the worldviews, knowledge and beliefs held by the Niuean community in Niue towards ear and hearing health, and the use of healthcare methods to contribute to service development. Methods Twenty semi-structured interviews were conducted with Niuean community members. Interviews were audio-recorded, transcribed verbatim, and analysed using thematic analysis methods. Results Niuean people value hearing health as an important way to communicate and connect with each other. They are proactive health seekers, have good knowledge about ear disease and hearing health and use mainstream medicines alongside spiritual practices and traditional remedies to maintain good ear and hearing health. The hospital system is responsive and accessible to the community's needs, contrasting with Pacific people's access to hearing health services in New Zealand. Discussion There is a high level of awareness of the importance of hearing health amongst the Niuean community and good accessibility and utilisation of healthcare services. There is potential to implement locally focused ear and hearing health strategies in Niue and conduct hearing health research among the New Zealand-based Niuean community to improve primary healthcare services delivery.

Effects of aging on neural processing during an active listening task.

Factors affecting successful listening in older adults and the corresponding electrophysiological signatures are not well understood. The present study investigated age-related differences in attention and temporal processing, as well as differences in the neural activity related to signal degradation during a number comparison task. Participants listened to digits presented in background babble and were tested at two levels of signal clarity, clear and degraded. Behavioral and electrophysiological measures were examined in 30 older and 20 younger neurologically-healthy adults. Relationships between performance on the number comparison task, behavioral measures, and neural activity were used to determine correlates of listening deficits associated with aging. While older participants showed poorer performance overall on all behavioral measures, their scores on the number comparison task were largely predicted (based on regression analyses) by their sensitivity to temporal fine structure cues. Compared to younger participants, older participants required higher signal-to-noise ratios (SNRs) to achieve equivalent performance on the number comparison task. With increasing listening demands, age-related changes were observed in neural processing represented by the early-N1 and later-P3 time windows. Source localization analyses revealed age differences in source activity for the degraded listening condition that was located in the left prefrontal cortex. In addition, this source activity negatively correlated with task performance in the older group. Together, these results suggest that older adults exhibit reallocation of processing resources to complete a demanding listening task. However, this effect was evident only for poorer performing older adults who showed greater posterior to anterior shift in P3 response amplitudes than older adults who were good performers and younger adults. These findings might reflect less efficient recruitment of neural resources that is associated with aging during effortful listening performance.

The developmental journey of therapies targeting purine receptors: from basic science to clinical trials.

Since the discovery of ATP as an extracellular signalling molecule in 1972, purinergic signalling, mediated by extracellular purines and pyrimidines has been identified in virtually all mammalian tissues and is implicated in regulating fundamental cellular processes. In recent years, there has been an increasing focus on the pathophysiology and potential therapeutic interventions based on purinergic signalling. A vast range of compounds targeting purine receptors are in clinical development, and many more are in preclinical studies, which highlights the fast growth in this research field. As a tribute to Professor Geoffrey Burnstock's legacy in purinergic signalling, we present here a brief review of compounds targeting purine receptors that are in different stages of clinical trials. The review highlights the 50-year journey from basic research on purinergic receptors to clinical applications of therapies targeting purine receptors.

Auditory processing in rodent models of autism: a systematic review.

Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population. A search was conducted in the PubMed and Web of Science databases to find primary research articles in mouse or rat models of autism which investigate central auditory processing. A total of 88 studies were included. These used non-invasive measures of auditory function, such as auditory brainstem response recordings, cortical event-related potentials, electroencephalography, and behavioural tests, which are translatable to human studies. They also included invasive measures, such as electrophysiology and histology, which shed insight on the origins of the phenotypes found in the non-invasive studies. The most consistent results across these studies were increased latency of the N1 peak of event-related potentials, decreased power and coherence of gamma activity in the auditory cortex, and increased auditory startle responses to high sound levels. Invasive studies indicated loss of subcortical inhibitory neurons, hyperactivity in the lateral superior olive and auditory thalamus, and reduced specificity of responses in the auditory cortex. This review compares the auditory phenotypes across rodent models and highlights those that mimic findings in human studies, providing a framework and avenues for future studies to inform understanding of the auditory system in autism.

Spironolactone Ameliorates Cochlear Implant Induced Endolymphatic Hydrops.

BACKGROUND: Endolymphatic hydrops (EH) has been observed in both animal and human cochleae following cochlear implant (CI) surgery. We tested whether EH could be eliminated by administration of mineralocorticoid steroid antagonist spironolactone and explored the electrophysiological consequences of this. METHODS: Sixty-four adult guinea pigs underwent cochlear implantation with a dummy electrode. Animals then survived either 2, 7, or 28 days. Auditory function was monitored by recording electrocochleography from the round window membrane preimplantation, and on the last day of the experiment. Spironolactone or control solution was added to animals' feed for 7 days (if they survived that long) beginning immediately prior to surgery. The presence of EH was determined using thin-sheet laser imaging microscopy. RESULTS: Treatment with spironolactone resulted in significant reduction in EH in the second cochlear turn 7 days postimplantation. In all animals, the compound action potential (CAP) threshold was elevated 2 days postimplantation, but for most frequencies had recovered substantially by 28 days. There was no treatment effect on CAP thresholds. SP/AP ratios were elevated at day 2. The amplitude growth of the CAP did not differ between test and control groups at any time after implantation. CONCLUSIONS: EH can be suppressed by antagonism of mineralocorticoid receptors in the week after cochlear implantation. Reduction in EH did not lead to any change in hearing, and there was no indication of synaptopathy signalled by reduced CAP amplitude at high sound intensities. We found no electrophysiological evidence that EH early after implantation impacts negatively upon preservation of residual hearing.

The relationship between obstructive sleep apnea with hearing and balance: A scoping review.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to multiple co-morbidities, and some research points to a potential relationship between OSA and hearing and balance dysfunction, and the benefits of continuous positive airway pressure (CPAP) treatment. OBJECTIVE: The present study was undertaken as a scoping review of research on OSA and its impact on hearing and balance function in adults and children and whether the treatment of CPAP would affect hearing and balance function. METHOD: Online databases were used to identify 45 papers published that used hearing and balance assessments concerning OSA and CPAP therapy as a primary outcome. The secondary outcome was the subjective perception through validated questionnaires. RESULTS: Whilst the data on the effect of OSA on middle ear function remains inconclusive, most papers demonstrate an increase in hearing thresholds, an absence of otoacoustic emissions (OAE) and delayed auditory brainstem response (ABR) in adults with OSA. Nystagmus and abnormal vestibular evoked myogenic potentials (VEMPs) were observed in the small number of papers. The positive pressure from CPAP significantly and transiently increases middle ear pressure, however, its effects on other auditory regions and the vestibular system remains inconclusive. Research on hearing and balance function in children with OSA is limited. CONCLUSIONS: Narrow assessments of hearing and balance are not sufficient to understand the nature of hearing and balance function in OSA patients and the effect of CPAP therapy. More comprehensive assessments are necessary to observe peripheral and central changes in the auditory and vestibular pathways.

A High-Fat Diet Induces Low-Grade Cochlear Inflammation in CD-1 Mice.

There is growing evidence for a relationship between gut dysbiosis and hearing loss. Inflammatory bowel disease, diet-induced obesity (DIO), and type 2 diabetes have all been linked to hearing loss. Here, we investigated the effect of a chronic high-fat diet (HFD) on the development of inner ear inflammation using a rodent model. Three-week-old CD-1 (Swiss) mice were fed an HFD or a control diet for ten weeks. After ten weeks, mouse cochleae were harvested, and markers of cochlear inflammation were assessed at the protein level using immunohistochemistry and at the gene expression level using quantitative real-time RT-PCR. We identified increased immunoexpression of pro-inflammatory biomarkers in animals on an HFD, including intracellular adhesion molecule 1 (ICAM1), interleukin 6 receptor α (IL6Rα), and toll-like-receptor 2 (TLR2). In addition, increased numbers of ionized calcium-binding adapter molecule 1 (Iba1) positive macrophages were found in the cochlear lateral wall in mice on an HFD. In contrast, gene expression levels of inflammatory markers were not affected by an HFD. The recruitment of macrophages to the cochlea and increased immunoexpression of inflammatory markers in mice fed an HFD provide direct evidence for the association between HFD and cochlear inflammation.

Parental satisfaction with an advanced audiology-led triage service in paediatric ENT outpatient clinics.

OBJECTIVE: The advanced audiology-led service is designed to triage and manage children who are referred to Ear Nose and Throat (ENT) outpatient services with middle ear or hearing concerns. This service has resulted in shorter waiting times for children to receive ENT treatment, and improved ENT capacity. The aim of this study was to explore parental satisfaction with the advanced audiology-led ENT service and to determine if there were cultural or process factors affecting satisfaction. DESIGN: Prospective cross-sectional study using a modified Visit-Specific Satisfaction Questionnaire (VSQ-9) survey. STUDY SAMPLE: One hundred and thirteen parents of children consecutively attending a first appointment in the advanced audiology-led service recruited between October 2016 and October 2017. RESULTS: There were a total of 100 valid responses (rate of 88.5%). The survey showed high levels of satisfaction. Satisfaction scores were significantly higher for items related to interactions with the audiologist compared to items related to waiting times. There were no differences in satisfaction across cultural groups. Parents were equally satisfied with the service whether their child was managed independently by the audiologist or required another appointment for medical input. CONCLUSIONS: The advanced audiology-led service had high levels of satisfaction from parents attending with their children.

The Link between Gut Dysbiosis Caused by a High-Fat Diet and Hearing Loss.

This review aims to provide a conceptual and theoretical overview of the association between gut dysbiosis and hearing loss. Hearing loss is a global health issue; the World Health Organisation (WHO) estimates that 2.5 billion people will be living with some degree of hearing loss by 2050. The aetiology of sensorineural hearing loss (SNHL) is complex and multifactorial, arising from congenital and acquired causes. Recent evidence suggests that impaired gut health may also be a risk factor for SNHL. Inflammatory bowel disease (IBD), type 2 diabetes, diet-induced obesity (DIO), and high-fat diet (HFD) all show links to hearing loss. Previous studies have shown that a HFD can result in microangiopathy, impaired insulin signalling, and oxidative stress in the inner ear. A HFD can also induce pathological shifts in gut microbiota and affect intestinal barrier (IB) integrity, leading to a leaky gut. A leaky gut can result in chronic systemic inflammation, which may affect extraintestinal organs. Here, we postulate that changes in gut microbiota resulting from a chronic HFD and DIO may cause a systemic inflammatory response that can compromise the permeability of the blood-labyrinth barrier (BLB) in the inner ear, thus inducing cochlear inflammation and hearing deficits.

Istradefylline Mitigates Age-Related Hearing Loss in C57BL/6J Mice.

Age-related hearing loss (ARHL) is the most common sensory disorder among older people, and yet, the treatment options are limited to medical devices such as hearing aids and cochlear implants. The high prevalence of ARHL mandates the development of treatment strategies that can prevent or rescue age-related cochlear degeneration. In this study, we investigated a novel pharmacological strategy based on inhibition of the adenosine A2A receptor (A2AR) in middle aged C57BL/6 mice prone to early onset ARHL. C57BL/6J mice were treated with weekly istradefylline (A2AR antagonist; 1 mg/kg) injections from 6 to 12 months of age. Auditory function was assessed using auditory brainstem responses (ABR) to tone pips (4-32 kHz). ABR thresholds and suprathreshold responses (wave I amplitudes and latencies) were evaluated at 6, 9, and 12 months of age. Functional outcomes were correlated with quantitative histological assessments of sensory hair cells. Cognitive function was assessed using the Morris water maze and the novel object recognition test, and the zero maze test was used to assess anxiety-like behaviour. Weekly injections of istradefylline attenuated ABR threshold shifts by approximately 20 dB at mid to high frequencies (16-32 kHz) but did not improve ABR suprathreshold responses. Istradefylline treatment improved hair cell survival in a turn-dependent manner, whilst the cognitive function was unaffected by istradefylline treatment. This study presents the first evidence for the rescue potential of istradefylline in ARHL and highlights the role of A2AR in development of age-related cochlear degeneration.

Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics.

The sense of hearing enables us to enjoy sounds and music and engage with other people [...].