'The burden is very much on yourself': A qualitative study to understand the illness and treatment burden of hearing loss across the life course.

INTRODUCTION: Hearing loss is a chronic health condition that rises sharply with age. The way people respond to and cope with health conditions is influenced by their capacity to perform illness and treatment-related work. The aim was to explore the cumulative burdens of living with hearing loss and the resources mobilised to ease the burdens. METHODS: A qualitative design was used with semi-structured interviews (online or in-person) with participants recruited through audiology services and nonclinical services, such as lip-reading classes. Forty-six participants with hearing loss aged between 16 and 96 years were interviewed. An abductive approach, informed by May et al.'s burden of treatment theory, was used to analyse the data. RESULTS: The illness burden involved participants working to make sense of their hearing loss, engaging in emotional work in response to changes in sound, social interactions and identity and coping with the daily frustrations required to communicate with others. Abandonment and uncertainty characterised the treatment burden; participants engaged in emotional work to adjust to hearing technology and deal with the uncertainty of how their hearing might progress. To ameliorate the burdens, participants drew on internal resources (psychological, health literacy, cognitive) and external resources (social support, financial, information, technology). CONCLUSIONS: The workload of hearing loss appears largely devolved to the patient and is not always visible. Our work indicates the need to widen approaches in audiological care through the implementation of lifeworld-led care, family-centred care and peer support to build support for those with hearing loss. PATIENT OR PUBLIC CONTRIBUTION: We developed the project in consultation with members of the public who have lived experience of hearing loss recruited through Aston University and volunteer links to audiology services. We also consulted people more likely to be affected by hearing loss adults including adults with learning disabilities, older adults in residential care and people from South Asia (Bangladeshi, Indian and Pakistani communities). These individuals commented on the study aims, interview schedule and participant recruitment practices. One of our co-authors (expert by experience) contributed to the development and interpretation of themes and preparation of the final manuscript.

Investigation of the effectiveness of sound enrichment in the treatment of tinnitus due to hearing loss.

OBJECTIVE: In previous animal studies, sound enhancement reduced tinnitus perception in cases associated with hearing loss. The aim of this study was to investigate the efficacy of sound enrichment therapy in tinnitus treatment by developing a protocol that includes criteria for psychoacoustic characteristics of tinnitus to determine whether the etiology is related to hearing loss. METHODS: A total of 96 patients with chronic tinnitus were included in the study. Fifty-two patients in the study group and 44 patients in the placebo group considered residual inhibition (RI) outcomes and tinnitus pitches. Both groups received sound enrichment treatment with different spectrum contents. The tinnitus handicap inventory (THI), visual analog scale (VAS), minimum masking level (MML), and tinnitus loudness level (TLL) results were compared before and at 1, 3, and 6 months after treatment. RESULTS: There was a statistically significant difference between the groups in THI, VAS, MML, and TLL scores from the first month to all months after treatment (p < .01). For the study group, there was a statistically significant decrease in THI, VAS, MML, and TLL scores in the first month (p < .01). This decrease continued at a statistically significant level in the third month of posttreatment for THI (p < .05) and at all months for VAS-1 (tinnitus severity) (p < .05) and VAS-2 (tinnitus discomfort) (p < .05). CONCLUSION: In clinical practice, after excluding other factors related to the tinnitus etiology, sound enrichment treatment can be effective in tinnitus cases where RI is positive and the tinnitus pitch is matched with a hearing loss between 45 and 55 dB HL in a relatively short period of 1 month.

Reported Unmet Hearing Aid Need in Older People With Dementia: The US National Core Indicators Survey.

OBJECTIVES: Hearing aids have important health benefits for older adults with Alzheimer disease and related dementias (ADRD); however, hearing aid adoption in this group is low. This study aimed to determine where to target hearing aid interventions for American long-term care recipients with ADRD by examining the association of ADRD and residence type with respondent-reported unmet hearing aid need. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the United States National Core Indicators-Aging and Disabilities survey (2015-2019) for long-term care recipients aged ≥65 years. METHODS: We used multivariable logistic regression to model the likelihood of reporting unmet hearing aid need conditional on ADRD status and residence type (own/family house or apartment, residential care, or nursing facility/home), adjusting for sociodemographic factors and response type (self vs proxy). RESULTS: Of the 25,492 respondents [median (IQR) age, 77 (71, 84) years; 7074 (27.8%) male], 5442 (21.4%) had ADRD and 3659 (14.4%) owned hearing aids. Residence types were 17,004 (66.8%) own/family house or apartment, 4966 (19.5%) residential care, and 3522 (13.8%) nursing home. Among non-hearing aid owners, ADRD [adjusted odds ratio (AOR) 0.90, 95% CI 0.80-1.0] and residence type were associated with respondent-reported unmet hearing aid need. Compared to the nursing home reference group, respondents in their own/family home (AOR 1.85, 95% CI 1.61-2.13) and residential care (AOR 1.30, 95% CI 1.10-1.53) were more likely to report unmet hearing aid need. This pattern was significantly more pronounced in people with ADRD than in those without, stemming from an interaction between ADRD and residence type. CONCLUSIONS AND IMPLICATIONS: American long-term care recipients with ADRD living in their own/family home are more likely to report unmet hearing aid need than those with ADRD in institutional and congregate settings. This information can inform the design and delivery of hearing interventions for older adults with ADRD.

Optogenetics: Illuminating the Future of Hearing Restoration and Understanding Auditory Perception.

Hearing loss is a prevalent sensory impairment significantly affecting communication and quality of life. Traditional approaches for hearing restoration, such as cochlear implants, have limitations in frequency resolution and spatial selectivity. Optogenetics, an emerging field utilizing light-sensitive proteins, offers a promising avenue for addressing these limitations and revolutionizing hearing rehabilitation. This review explores the methods of introducing Channelrhodopsin- 2 (ChR2), a key light-sensitive protein, into cochlear cells to enable optogenetic stimulation. Viral- mediated gene delivery is a widely employed technique in optogenetics. Selecting a suitable viral vector, such as adeno-associated viruses (AAV), is crucial in efficient gene delivery to cochlear cells. The ChR2 gene is inserted into the viral vector through molecular cloning techniques, and the resulting viral vector is introduced into cochlear cells via direct injection or round window membrane delivery. This allows for the expression of ChR2 and subsequent light sensitivity in targeted cells. Alternatively, direct cell transfection offers a non-viral approach for ChR2 delivery. The ChR2 gene is cloned into a plasmid vector, which is then combined with transfection agents like liposomes or nanoparticles. This mixture is applied to cochlear cells, facilitating the entry of the plasmid DNA into the target cells and enabling ChR2 expression. Optogenetic stimulation using ChR2 allows for precise and selective activation of specific neurons in response to light, potentially overcoming the limitations of current auditory prostheses. Moreover, optogenetics has broader implications in understanding the neural circuits involved in auditory processing and behavior. The combination of optogenetics and gene delivery techniques provides a promising avenue for improving hearing restoration strategies, offering the potential for enhanced frequency resolution, spatial selectivity, and improved auditory perception.

Availability of resources for paediatric hearing care in a South African province.

BACKGROUND:  Unavailability of healthcare resources can lead to poor patient outcomes. The latter is true for infants with hearing loss and require early hearing detection and intervention (EHDI). AIM:  To determine the availability and distribution of resources for EHDI in state hospitals in the Eastern Cape (EC) province, South Africa. SETTING:  Sixteen state hospitals (nine district, four regional and three tertiary hospitals). METHODS:  Descriptive cross-sectional survey completed between July 2022 and October 2022. RESULTS:  Thirteen hospitals had audiologists (n = 4) or speech therapists and audiologists (n = 9). Specific to equipment, 10 hospitals had a screening otoacoustic emissions or automated auditory brainstem response, 8 hospitals had diagnostic middle ear analysers and only 3 hospitals had diagnostic auditory brainstem response and/or auditory steady state response. Twelve hospitals did not have visual response audiometry (VRA) and 94% had no hearing aid verification systems. Budget allocations were uneven, with only 10 hospitals, i.e., 4 districts, all regional and 2 tertiary hospitals being allocated varying amounts. Subsequently, only 50% provided newborn hearing screening, 56% provided diagnostic evaluations and 14 hospitals fitted hearing aids. CONCLUSION:  Results revealed a limited and uneven distribution of resources, which negatively impacted the provision of EHDI. Even distribution of healthcare resources and further research aimed at strengthening hearing health services is recommended as these could potentially improve equitable access to EHDI and the overall quality of healthcare provided.Contribution: This study highlights the need for even distribution of resources and strengthening of health systems, especially in the dawn of the National Health Insurance.

Help-seeking journey to accessing audiology services in a peri-urban community in South Africa.

BACKGROUND:  Hearing impairment is an invisible disability affecting one in five people globally. Its ability to affect participation in activities of daily living means that it requires prompt identification and intervention. OBJECTIVE:  This article aims to define the process of accessing audiologists from the onset of symptoms for adults with hearing impairment in a peri-urban community in South Africa. METHOD:  Twenty-three participants were recruited through purposive sampling from an audiology department of a public hospital. Semi-structured interviews were conducted using an interview guide, and data were mapped according to the participants' responses from the onset of ear and hearing symptoms to the point of audiologist consultation for analysis. RESULTS:  Seventeen (74%) participants had long journeys to accessing the audiologist after seeking help from multiple providers, with those with short journeys (26%) being referred mostly by public healthcare providers. Despite participants being from one peri-urban community, their journeys were influenced by socio-economics, health illiteracy and other structural factors. Finally, Ear-Nose-Throat specialists linked participants with audiology services. CONCLUSION:  Accessing audiology services is a complex process in some contexts. The disparities in the social environment, lifestyle factors and pluralistic healthcare models influence access to audiologists. Healthcare providers must take cognisance of the journeys of adults with hearing impairment in their clinical interventions. Universal health coverage, in the form of the planned National Health Insurance (NHI) for all South African citizens, will play an important role in addressing the societal inequalities in accessing healthcare. Factors leading to long journeys should be addressed to facilitate early intervention.Contribution: The study raises implications for the planned NHI in South Africa, suggesting that universal health coverage could play a vital role in addressing societal inequalities in accessing healthcare, including audiology services.

Clinical Practice Guideline: Age-Related Hearing Loss.

OBJECTIVE: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life (QOL). (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related QOL at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing.

Education Intervention on 'Hearing Impairment - Its Assessment and Management' among Medical Practitioners in Sikkim, India.

BACKGROUND: Health care providers must be aware of the choices in aural rehabilitation methods and assessment procedures available presently to those with hearing impairment in order to facilitate early identification and intervention and ensure quality of care to those hearing impaired individuals. The referrals from the medical fraternities for the audiological services are not uniform across India. Part of reason may be that awareness about the roles of and responsibilities of audiologist's is poor among medical practitioners. In some regions of India medical practitioners may be only grossly be aware of audiologists per se. They may not know enough to refer all individuals with hearing or balance disorders for the required audiological services. AIM: To evaluate changes in pre survey and post survey after education intervention specifically planned for medical practitioners in the state of Sikkim, India. Education intervention included awareness about hearing impairment and its assessment and management by audiologists. METHOD: A pre and post survey comparison research design with purposive convenient sampling technique was applied. Participants were medical practitioners working in geographical area of Sikkim at the time of the study. Inspection of demographic data of respondents showed that they were in their age range of 24 and 60 years and with work experience ranging 1-40 years. Participants were invited for an awareness talk which included, information about hearing loss, early identification and early intervention, tests and management of hearing loss in different age groups, need for hearing aids/cochlear implants, auditory training, and the role of an audiologist in the management of hearing loss and ways to prevent hearing loss. A pre and post awareness program responses were collected from all the participants using a customized questionnaire tool. RESULTS: Respondents exhibited, in the pre-survey questionnaire, lack of awareness in many aspects of audiology, including assessing hearing impairment, diagnosing hearing loss, and the role of an audiologist. There was an overall, statistically significant difference in the level of performance on the pre-awareness and post-awareness responses. CONCLUSION: Following an awareness campaign among the medical professionals in Sikkim, there was a considerable change in their level of awareness of hearing impairment, its assessment, and management by audiologists. The reach of the awareness campaign was significant as around 70% of subjects showed significant change in their knowledge and attitude towards hearing impairment, its management.

Towards universal access: A review of global efforts in ear and hearing care.

Hearing loss affects 1.6 billion people worldwide and disproportionately affects those in low- and middle-income countries. Despite being largely preventable or treatable, ear and hearing conditions result in significant and lifelong morbidity such as delayed language development, reduced educational attainment, and diminished social well-being. There is a need to augment prevention, early identification, treatment, and rehabilitation for these conditions. Expanded access to hearing screening, growth of the hearing health workforce, and innovations in ear and hearing care delivery systems are among the changes that are needed. To that end, the World Health Organization has prioritized ear and hearing care as a component of Universal Health Coverage, and recent publications have advanced the priority for ear and hearing care. Efforts are underway at the national levels around the world, as evidenced by countries like Zambia and Nigeria that have integrated ear and hearing care within national health strategies. While significant strides have been made in improving access, a critical need remains for additional research, advocacy, and intervention to ensure that no one is left behind in the goal to achieve universal access to ear and hearing care.

Genetically modified pigs: Emerging animal models for hereditary hearing loss.

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.

How have services for diabetes, eye, hearing and foot health been integrated for adults? Protocol for a scoping review.

INTRODUCTION: The global population is ageing, and by 2050, there will be almost 2.1 billion people over the age of 60 years. This ageing population means conditions such as diabetes are on the increase, as well as other conditions associated with ageing (and/or diabetes), including those that cause vision impairment, hearing impairment or foot problems. The aim of this scoping review is to identify the extent of the literature describing integration of services for adults of two or more of diabetes, eye, hearing or foot services. METHODS AND ANALYSIS: The main database searches are of Medline and Embase, conducted by an information specialist, without language restrictions, for studies published from 1 January 2000 describing the integration of services for two or more of diabetes, eye, hearing and foot health in the private or public sector and at the primary or secondary level of care, primarily targeted to adults aged ≥40 years. A grey literature search will focus on websites of key organisations. Reference lists of all included articles will be reviewed to identify further studies. Screening and data extraction will be undertaken by two reviewers independently and any discrepancies will be resolved by discussion. We will use tables, maps and text to summarise the included studies and findings, including where studies were undertaken, which services tended to be integrated, in which sector and level of the health system, targeting which population groups and whether they were considered effective. ETHICS AND DISSEMINATION: As our review will be based on published data, ethical approval will not be sought. This review is part of a project in Aotearoa New Zealand that aims to improve access to services for adults with diabetes or eye, hearing or foot conditions. The findings will be published in a peer-reviewed journal and presented at relevant conferences.

Outcomes and device use in children with bone-conduction hearing devices in South Africa.

BACKGROUND:  Bone-conduction hearing devices (BCHD) can provide hearing solutions in settings where middle ear pathology is rife. OBJECTIVES:  Describe functional hearing outcomes and device use of children fitted with BCHD. METHOD:  Retrospective review of 79 children fitted with BCHD between January 2017 and May 2022. Outcomes included device use and subjective reports measured with the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) and the Teachers' Evaluation of Aural/Oral Performance of Children (TEACH). Analysis of variance established association between mean data logging and type and degree of hearing loss. Thematic analyses were done for qualitative outcomes. RESULTS:  Average usage was 7.0 h/day (5.4 SD; range 0.1-24). PEACH ratings indicated 93.3% of children wore their BCHD 'always' or 'often', with 80% displaying Typical auditory performance at 1-month follow-up. TEACH ratings indicated 84.2% of children wore their BCHD 'always' or 'often', with 78.9% showing typical auditory behaviour. Increased usage was noted for conductive, mixed, moderate and severe hearing losses. There was a mean delay of 17.2 months (23.4 SD; range 0-90) between age of diagnosis and fitting. Thematic analyses identified two main themes: advantages and barriers to BCDH use. CONCLUSION:  Average device use fell short of the internationally recommended 10 h/day. Higher BCHD use was associated with higher functional listening performance scores. Long waiting times for medical or surgical intervention for conductive hearing losses can delay BCHD fitting.Contribution: Limited information is available to examine outcomes in children fitted with BCHD.

Hearing Loss Detection and Early Intervention Strategies in Kenya.

Background: Thirty-four million children globally have disabling hearing loss, with the highest prevalence in low- and middle-income countries (LMICs). Early identification and management is crucial, yet barriers to screening and treatment of hearing loss are extensive in LMICs. Unaddressed hearing loss negatively impacts individuals and communities. The WHO's 2021 World Report on Hearing urges the development of Ear and Hearing Care (EHC) programs to improve access to all aspects of care, including screening, diagnostics, management, and developmental support. A joint Nairobi- and Seattle-based group convened in 2021 to discuss strategies for program development in Kenya, as presented in this paper. Findings: Developing a national EHC program must include the necessary support services for a child with a diagnosed hearing loss, while simultaneously promoting engagement of family, community, and healthcare workers. Existing government and healthcare system policies and priorities can be leveraged for EHC programming. Strategies for success include strengthening connections between policymakers at national, county, and municipal levels and local champions for the EHC agenda, with a concurrent focus on policy, early detection and intervention, habilitation, and family-centered care. Updates to health policy and funding to support the accessibility of services and equipment should focus on leveraging national healthcare coverage for hearing technologies and services, strengthening referral pathways, training to bolster the workforce, and metrics for monitoring and evaluation. Additional strategies to support forward progress include strategic engagement of partners and leveraging local partners for phased scale-up. Conclusions and Recommendations: Recommendations to strengthen EHC within the Kenyan health system include concurrent leverage of existing health policies and priorities, partner engagement, and strengthening referral pathways, monitoring and evaluation, and training. These strategies may be generalized to other countries too.

Prevalence and predictors of self-reported hearing aid use and benefit in Norway: the HUNT study.

BACKGROUND: Knowledge on hearing aid use and benefit is important to ensure appropriate and effective treatment. We aimed to assess prevalence and predictors of hearing aid use and benefit in Norway, as well as possible birth cohort changes. METHODS: We analyzed two large cross-sectional, population-based hearing surveys of 63,182 adults in 1996-1998 and 2017-2019 (the HUNT study). We used multivariable regression models to examine independent predictors of hearing aid use and benefit, including demography, hearing-related variables, known risk factors for hearing loss and birth cohort. RESULTS: The nationally weighted hearing aid use in the adult population increased from 4.2% in 1997 to 5.8% in 2018. The use among individuals with disabling hearing loss (≥ 35 dB HL) increased from 46.3% to 64.4%. Most users reported some (47%) or great (48%) help from their hearing aids. In addition to the level of hearing loss and birth cohort, factors associated with hearing aid use included lower age, tinnitus, childhood-onset hearing loss, higher education, marriage, having children, being exposed to occupational noise or impulse noise, recurrent ear infections, and head injury. In addition to the level of hearing loss, factors related to hearing aid benefit included younger age, female gender, and higher income. Being bothered by tinnitus reduced the benefit. CONCLUSION: Our study shows an increase in self-reported hearing aid usage over time in Norway, with lower adoption rates and perceived benefits observed among the elderly. The results suggest that having a spouse and children positively influences the adoption of hearing aids. These findings emphasize the necessity of customized strategies to address demographic disparities and the need for innovative enhancements in hearing rehabilitation programs.

[Genetic counseling for hearing loss today].

Genetic counseling for hearing loss today originated from decoding the genetic code of hereditary hearing loss, which serves as an effective strategy for preventing hearing loss and constitutes a crucial component of the diagnostic and therapeutic framework. This paper described the main principles and contents of genetic counseling for hearing loss, the key points of counseling across various genetic models and its application in tertiary prevention strategies targeting hearing impairment. The prospects of an AI-assisted genetic counseling decision system and the envisions of genetic counseling in preventing hereditary hearing loss were introduced. Genetic counseling for hearing loss today embodies the hallmark of a new era, which is inseparable from the advancements in science and technology, and will undoubtedly contribute to precise gene intervention!

[Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice].

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Extracellular vesicles for developing targeted hearing loss therapy.

Substantial efforts have been made for local administration of small molecules or biologics in treating hearing loss diseases caused by either trauma, genetic mutations, or drug ototoxicity. Recently, extracellular vesicles (EVs) naturally secreted from cells have drawn increasing attention on attenuating hearing impairment from both preclinical studies and clinical studies. Highly emerging field utilizing diverse bioengineering technologies for developing EVs as the bioderived therapeutic materials, along with artificial intelligence (AI)-based targeting toolkits, shed the light on the unique properties of EVs specific to inner ear delivery. This review will illuminate such exciting research field from fundamentals of hearing protective functions of EVs to biotechnology advancement and potential clinical translation of functionalized EVs. Specifically, the advancements in assessing targeting ligands using AI algorithms are systematically discussed. The overall translational potential of EVs is reviewed in the context of auditory sensing system for developing next generation gene therapy.

Clarin-2 gene supplementation durably preserves hearing in a model of progressive hearing loss.

Hearing loss is a major health concern affecting millions of people worldwide with currently limited treatment options. In clarin-2-deficient Clrn2-/- mice, used here as a model of progressive hearing loss, we report synaptic auditory abnormalities in addition to the previously demonstrated defects of hair bundle structure and mechanoelectrical transduction. We sought an in-depth evaluation of viral-mediated gene delivery as a therapy for these hearing-impaired mice. Supplementation with either the murine Clrn2 or human CLRN2 genes preserved normal hearing in treated Clrn2-/- mice. Conversely, mutated forms of CLRN2, identified in patients with post-lingual moderate to severe hearing loss, failed to prevent hearing loss. The ectopic expression of clarin-2 successfully prevented the loss of stereocilia, maintained normal mechanoelectrical transduction, preserved inner hair cell synaptic function, and ensured near-normal hearing thresholds over time. Maximal hearing preservation was observed when Clrn2 was delivered prior to the loss of transducing stereocilia. Our findings demonstrate that gene therapy is effective for the treatment of post-lingual hearing impairment and age-related deafness associated with CLRN2 patient mutations.

Improving quality of life in the elderly: hearing loss treatment with cochlear implants.

BACKGROUND: Hearing loss impacts health-related quality of life and general well-being and was identified in a Lancet report as one of the largest potentially modifiable factors for the prevention of age-related dementia. There is a lack of robust data on how cochlear implant treatment in the elderly impacts quality of life. The primary objective was to measure the change in health utility following cochlear implantation in individuals aged ≥ 60 years. METHODS: This study uniquely prospectively recruited a large multinational sample of 100 older adults (mean age 71.7 (SD7.6) range 60-91 years) with severe to profound hearing loss. In a repeated-measures design, pre and post implant outcome measures were analysed using mixed-effect models. Health utility was assessed with the Health Utilities Index Mark III (HUI3). Subjects were divided into groups of 60-64, 65-74 and 75 + years. RESULTS: At 18 months post implant, the mean HUI3 score improved by 0.13 (95%CI: 0.07-0.18 p < 0.001). There was no statistically significant difference in the HUI3 between age groups (F[2,9228] = 0.53, p = 0.59). The De Jong Loneliness scale reduced by an average of 0.61 (95%CI: 0.25-0.97 p < 0.014) and the Lawton Instrumental Activities of Daily Living Scale improved on average (1.25, 95%CI: 0.85-1.65 p < 0.001). Hearing Handicap Inventory for the Elderly Screening reduced by an average of 8.7 (95%CI: 6.7-10.8, p < 0.001) from a significant to mild-moderate hearing handicap. Age was not a statistically significant factor for any of the other measures (p > 0.20). At baseline 90% of participants had no or mild depression and there was no change in mean depression scores after implant. Categories of Auditory perception scale showed that all subjects achieved a level of speech sound discrimination without lip reading post implantation (level 4) and at least 50% could use the telephone with a known speaker. CONCLUSIONS: Better hearing improved individuals' quality of life, ability to communicate verbally and their ability to function independently. They felt less lonely and less handicapped by their hearing loss. Benefits were independent of age group. Cochlear implants should be considered as a routine treatment option for those over 60 years with bilateral severe to profound hearing loss. TRIAL REGISTRATION: ClinicalTrials.gov ( http://www. CLINICALTRIALS: gov/ ), 7 March 2017, NCT03072862.

Critical role of TPRN rings in the stereocilia for hearing.

Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region of the stereocilia, and mutations in TPRN cause hereditary hearing loss through an unknown mechanism. Here, using biochemistry and dual stimulated emission depletion microscopy imaging, we show that the TPRN, together with its binding proteins CLIC5 and PTPRQ, forms concentric rings in the taper region of stereocilia. The disruption of TPRN rings, triggered by the competitive inhibition of the interaction of TPRN and CLIC5 or exogenous TPRN overexpression, leads to stereocilia degeneration and severe hearing loss. Most importantly, restoration of the TPRN rings can rescue the damaged auditory function of Tprn knockout mice by exogenously expressing TPRN at an appropriate level in HCs via promoter recombinant adeno-associated virus (AAV). In summary, our results reveal highly structured TPRN rings near the taper region of stereocilia that are crucial for stereocilia function and hearing. Also, TPRN ring restoration in stereocilia by AAV-Tprn effectively repairs damaged hearing, which lays the foundation for the clinical application of AAV-mediated gene therapy in patients with TPRN mutation.