Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss.

Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural hearing loss caused by the degeneration or malfunction of cochlear hair cells or spiral ganglion nerves in the inner ear. There is currently no cure for hearing loss. However, emerging frontier technologies such as gene, drug or cell-based therapies offer hope for an effective cure. In this review, we discuss the current therapeutic progress for the treatment of hearing loss. We describe and evaluate the major therapeutic approaches being applied to hearing loss and summarize the key trials and studies.

Overcoming barriers: a review on innovations in drug delivery to the middle and inner ear.

Despite significant advances in the development of therapeutics for hearing loss, drug delivery to the middle and inner ear remains a challenge. As conventional oral or intravascular administration are ineffective due to poor bioavailability and impermeability of the blood-labyrinth-barrier, localized delivery is becoming a preferable approach for certain drugs. Even then, localized delivery to the ear precludes continual drug delivery due to the invasive and potentially traumatic procedures required to access the middle and inner ear. To address this, the preclinical development of controlled release therapeutics and drug delivery devices have greatly advanced, with some now showing promise clinically. This review will discuss the existing challenges in drug development for treating the most prevalent and damaging hearing disorders, in particular otitis media, perforation of the tympanic membrane, cholesteatoma and sensorineural hearing loss. We will then address novel developments in drug delivery that address these including novel controlled release therapeutics such as hydrogel and nanotechnology and finally, novel device delivery approaches such as microfluidic systems and cochlear prosthesis-mediated delivery. The aim of this review is to investigate how drugs can reach the middle and inner ear more efficiently and how recent innovations could be applied in aiding drug delivery in certain pathologic contexts.

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model.

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (µCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using µCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by µCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that µCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using µCT. Overall, µCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Models of service delivery in adult cochlear implantation and evaluation of outcomes: A scoping review of delivery arrangements.

BACKGROUND: This study aimed to describe available evidence of cochlear implantation delivery arrangements in adults and the outcomes by which these service models are measured. METHODS: Scoping review of English language, primary studies conducted on adults (≥18 years) with ten or more subjects, published between January 2000 and June 2022, which assessed the effects of delivery arrangements of cochlear implantation were included. MEDLINE, EMBASE, CINAHL Plus, AMED, PsycINFO, LILACS, KoreaMed, IndMed, Cochrane CRCT, ISRCTN registry, WHO ICTRP and Web of Science were systematically searched. Included studies had to have a method section explicitly measure at least one of the Cochrane Effective Practice and Organization of Care (EPOC) outcome category. Criteria for systematic reviews and delivery arrangement category based on EPOC taxonomy was included in data extraction. Data was narratively synthesized based on EPOC categories. RESULTS: A total of 8135 abstracts were screened after exclusion of duplicates, of these 357 studies fulfilled the inclusion criteria. Around 40% of the studies investigated how care is delivered, focusing on quality and safety systems. New care pathways to coordinate care and the use of information and communication technology were emerging areas. There was little evidence on continuity, coordination and integration of care, how the workforce is managed, where care is provided and changes in the healthcare environment. The main outcome measure for various delivery arrangements were the health status and performance in a test. CONCLUSION: A substantial body of evidence exists about safety and efficacy of cochlear implantation in adults, predominantly focused on surgical aspects and this area is rapidly growing. There is a lack of evidence on aspects of care delivery that may have more impact on patients' experience such as continuity, coordination and integration of care and should be a focus of future research. This would lead to a better understanding of how patient's view CI experience, associated costs and the value of different care models.

Factors Influencing Postoperative Experiences in Adult Cochlear Implant Recipients: A Multistakeholder Perspective.

OBJECTIVE: To explore factors influencing postoperative experiences of adult cochlear implant (CI) recipients, determine the impact of each factor, and conceptualize recipients' postoperative journey. STUDY DESIGN: Participatory mixed methods; concept mapping. SETTING: Tertiary care (private and public). PATIENTS: Ninety-three participated in the brainstorming activity. Eighty-nine completed the sorting tasks (96% retention rate): CI recipients (n = 44), significant others (n = 13), CI audiologists (n = 14) and surgeons (n = 5), CI clinics' administration staff (n = 5) and managers (n = 3), and CI manufactures' clinical support staff (n = 5). INTERVENTIONS: Rehabilitative (CIs). MAIN OUTCOME MEASURES: Statements were generated and rated by participants. Similarity of grouping of the statements informed the matrices used for cluster analysis to form concepts. RESULTS: Eighty-seven unique statements described the factors influencing adapting to, use, and maintenance of CIs after implantation. These were grouped, and five concepts were identified: financial considerations, complications, device usability and durability, device programming and adaptation, and patient motivation and supports. Although statements within the concepts financial considerations and complications were negatively rated, statements within the concepts device programming and adaptation, and patient motivation and supports were mostly rated as having positive influence in patients' postoperative journey. The concept device usability and durability contained both negatively and positively rated statements. CONCLUSIONS: Postoperative experience of adult CI recipients is a multifaceted journey with several challenges to address to improve services. Although support from and connection with family and clinicians, and simplicity of using a CI device facilitated the experience, medical and surgical complications, durability, and cost of maintaining the device challenged the postoperative experience.

Pharmacological Dose-Effect Profiles of Various Concentrations of Humanised Primary Bile Acid in Encapsulated Cells.

Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic ß-cells, allowing assessment of CDCA's impacts when encapsulated. Four different concentrations of the BA were prepared, and viable cells were encapsulated and incubated for 2 days. Multiple analyses were carried out including confocal imaging, glucose-induced cellular mitochondrial viability indices, insulin production, inflammatory biomarker analyses and cellular bioenergetics measurements. There was a significant dose-effect with different concentrations of the BA, affecting cellular viability and antioxidant activities, cell functions and insulin release, inflammatory biomarkers, and cellular-bioenergetics at different oxidative stress levels. The results demonstrate that, when encapsulated, the BA CDCA exerts positive pharmacological effects at the cellular level, and such effects are concentration dependent.

Single-Cellular Biological Effects of Cholesterol-Catabolic Bile Acid-Based Nano/Micro Capsules as Anti-Inflammatory Cell Protective Systems.

Recent studies in our laboratories have shown promising effects of bile acids in ➀ drug encapsulation for oral targeted delivery (via capsule stabilization) particularly when encapsulated with Eudragit NM30D® and ➁ viable-cell encapsulation and delivery (via supporting cell viability and biological activities, postencapsulation). Accordingly, this study aimed to investigate applications of bile acid-Eudragit NM30D® capsules in viable-cell encapsulation ready for delivery. Mouse-cloned pancreatic ß-cell line was cultured and cells encapsulated using bile acid-Eudragit NM30D® capsules, and capsules' images, viability, inflammation, and bioenergetics of encapsulated cells assessed. The capsules' thermal and chemical stability assays were also assessed to ascertain an association between capsules' stability and cellular biological activities. Bile acid-Eudragit NM30D® capsules showed improved cell viability (e.g., F1 < F2 & F8; p < 0.05), insulin, inflammatory profile, and bioenergetics as well as thermal and chemical stability, compared with control. These effects were formulation-dependent and suggest, overall, that changes in ratios of bile acids to Eudragit NM30D® can change the microenvironment of the capsules and subsequent cellular biological activities.

Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.

The Effects of Primary Unconjugated Bile Acids on Nanoencapsulated Pharmaceutical Formulation of Hydrophilic Drugs: Pharmacological Implications.

INTRODUCTION: In a recent study, in our laboratory, primary unconjugated bile acids, commonly found in humans, chenodeoxycholic acid (CDCA), have been shown to improve stability of nanoencapsulated lipophilic drugs and improve their release profile after oral administration likely via electrokinetic stabilisation. Hence, this study aimed to examine the effects of CDCA on exerting similar effects on hydrophilic drugs. METHODS: Various CDCA-based formulations were produced for the orally administered hydrophilic drug, metformin. Analyses of these formulations included electrokinetic potentials, topography, drug and CDCA formulation contents, nano size distribution, heat-induced deformation and outer-core expansion indices, release profiles, shell-resistance ratio, and thermal and chemical indices. With the drug's main target being pancreatic beta-cells, the formulations' effects on cell viability, functions and inflammatory profiles were also investigated. RESULTS AND CONCLUSIONS: CDCA-based metformin formulations exhibited improved stability and release profiles via thermal, chemical and electrokinetic effects, which were formulation-dependent suggesting potential applications of CDCA in the oral targeted delivery of hydrophilic drugs.

Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways.

INTRODUCTION: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable ß-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated ß-cells. METHODS: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA ß-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. RESULTS AND CONCLUSION: Capsules' morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

Probucol Pharmacological and Bio-Nanotechnological Effects on Surgically Transplanted Graft Due to Powerful Anti-Inflammatory, Anti-Fibrotic and Potential Bile Acid Modulatory Actions.

INTRODUCTION: A major obstacle in islet transplantation and graft survival pre and post transplantation is islet apoptosis due to mainly inflammatory bio molecules released during islet harvesting and post graft transplantation and hence, subsequent graft fibrosis and failure. This study aimed to investigate if incorporation of the anti-inflammatory anti-hyperlipidaemic drug probucol (PB) would improve islet-graft survival and function, post transplantation in Type 1 diabetes (T1D). METHODS: T1D was induced in mice, and biological profiles of the diabetic mice transplanted PB-microencapsulated islets harvested from healthy syngeneic mice were measured. RESULTS AND CONCLUSION: Compared with sham (no PB), the treated group showed significant reduction in serum levels of interleukin-1ß, interleukin-6, interleukin-12, interleukin-17, and tumour necrosis factor-α, accompanied by a 3-fold increase in survival duration, which suggests PB islet-protective effects, post transplantation.

Prevalence of Hyperacusis and Its Relation to Health: The Busselton Healthy Ageing Study.

IMPORTANCE: The prevalence of hyperacusis and its relationship with mental and general health is unknown in a nonclinical sample. Therefore, we aimed to determine the prevalence of hyperacusis and its relation with hearing, general and mental health in a population-based study. STUDY DESIGN: Prospective population-based study. MATERIAL AND METHODS: This study uses data from the Busselton Healthy Ageing Study (BHAS). A sample of 5,107 eligible inhabitants aged 45 to 70 years completed a detailed questionnaire and a clinical assessment. A positive answer to "Do you consider yourself sensitive or intolerant to everyday sounds" was used to indicate hyperacusis. Logistic regression was used to examine the association between hearing, mental and general health factors, and hyperacusis. RESULTS: Of 5,107 participants, 775 (15.2%) reported hyperacusis. The majority of participants with hyperacusis reported an occasional effect on daily life (72.0%). Being female, older in age, having a lower income, physical or mental health difficulties, more severe hearing loss, and tinnitus were all associated with the presence of hyperacusis. Individuals who experience hearing impairment, poorer general or mental health have a higher possibility of hyperacusis having an effect on their daily life. CONCLUSIONS: In this community population-based cohort study, we found a prevalence of hyperacusis of 15.2%. Individuals with hearing loss, mental health problems, and lower physical health have a higher possibility of experiencing effects on their daily life associated with their hyperacusis. Unravelling the relationship between hyperacusis hearing, general and mental health can be of major importance for a better understanding of the condition and its consequences. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E2887-E2896, 2021.

Tinnitus and its associations with general health, mental health and hearing loss.

BACKGROUND: A deeper knowledge of tinnitus is essential in order to better manage and treat tinnitus and its effects. Most studies to date are based on small samples and/or conducted in clinical settings. In this study we assessed the associations between tinnitus, general and mental health, hearing status and demographics in a large population cohort study. MATERIALS AND METHODS: The Busselton Healthy Aging Study recruited people born between 1946 and 1964. Data were collected between 2010 and 2015. Logistic regression was used to examine the associations between tinnitus and its effect on daily life, age, gender, hearing, self-reported mental and general health, and doctor diagnosed health conditions. RESULTS: Of 5107 participants, 1154 (22.6%) reported experiencing tinnitus. Of those, 32.4% reported that their tinnitus had an occasional effect on their daily lives, while for a further 8.9% the effect on their daily life was frequent or constant. The odds ratio for having a SF12-PCS was (OR 1.02 (95%CI 1.01-1.03). Furthermore, individuals who experience their tinnitus as having an effect on their daily life, have an increased risk of having a lower general health (OR 1.04 (95%CI 1.02-1.03)) than those without tinnitus. Higher levels of depression, anxiety and stress, as well as doctor diagnosed depression, were all significant risk factors for tinnitus. There were statistically significant worse hearing thresholds related to the presence of tinnitus. CONCLUSION: The outcomes raise the question for clinicians and researchers whether addressing the mental and general health of individuals will influence the presence or burden of tinnitus.

Spontaneous Tegmen Tympani Dehiscence: Causes and Treatment of Conductive Hearing Loss.

OBJECTIVE: Conductive hearing loss (CHL) commonly arises in patients with spontaneous dehiscence of the tegmen of the temporal bone with meningoencephalocele (SME). The aim of this study was to further investigate 1) the potential mechanisms for CHL in this setting; 2) hearing outcomes following surgery to address SME, and 3) the possible causes of persistent CHL following surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS AND INTERVENTION: Seven patients (six female; nine ears) who underwent middle cranial fossa repair of SME and were found to have a tegmen tympani dehiscence from October 2010 to September 2014 were included in the study. MAIN OUTCOME MEASURES: Pre- and postoperative pure-tone audiometry. RESULTS: Eight of nine ears (89%) had audiometric hearing loss at presentation. Seven ears (78%) had an air bone gap of ≥15 dB; all of these had an encephalocele traversing the tegmen tympani defect, four had a middle ear effusion, and three had a simultaneous superior semicircular canal dehiscence (SSCCD). The CHL resolved postoperatively in four of seven ears. Two of the three ears with persistent CHL had SSCCD. Attic ossicular fixation was identified in the other patient and the CHL resolved after ossiculoplasty. CONCLUSIONS: CHL associated with SME can be attributed preoperatively to ossicular chain fixation and synchronous SSCCD as well as the more commonly cited cerebrospinal fluid effusion and prolapse of meningoencephalocele onto the ossicular chain. Persistent postoperative CHL can also occur due to SSCCD and ossicular fixation by adhesions.

Generation of three induced pluripotent stem cell lines from a patient with Usher syndrome caused by biallelic c.949C > A and c.1256G > T mutations in the USH2A gene.

Mutations in the USH2A gene are the most common cause of Usher syndrome and autosomal recessive non-syndromic retinitis pigmentosa. Here, we describe the generation of three induced pluripotent stem cell lines from dermal fibroblasts derived from a patient carrying biallelic c.949C > A and c.1256G > T variants in the USH2A gene, using episomal reprogramming plasmids expressing OCT4, SOX2, KLF4, MYCL, LIN28, mir302/367 and shRNA targeting TP53. All three lines expressed pluripotency markers, displayed unaltered karyotypes as well as trilineage differentiation potential, and were negative for reprogramming episomes and mycoplasma.

Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy.

Usher syndrome (USH) is an autosomal recessive (AR) disorder that permanently and severely affects the senses of hearing, vision, and balance. Three clinically distinct types of USH have been identified, decreasing in severity from Type 1 to 3, with symptoms of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP), and vestibular dysfunction. There are currently nine confirmed and two suspected USH-causative genes, and a further three candidate loci have been mapped. The proteins encoded by these genes form complexes that play critical roles in the development and maintenance of cellular structures within the inner ear and retina, which have minimal capacity for repair or regeneration. In the cochlea, stereocilia are located on the apical surface of inner ear hair cells (HC) and are responsible for transducing mechanical stimuli from sound pressure waves into chemical signals. These signals are then detected by the auditory nerve fibers, transmitted to the brain and interpreted as sound. Disease-causing mutations in USH genes can destabilize the tip links that bind the stereocilia to each other, and cause defects in protein trafficking and stereocilia bundle morphology, thereby inhibiting mechanosensory transduction. This review summarizes the current knowledge on Usher syndrome with a particular emphasis on mutations in USH genes, USH protein structures, and functional analyses in animal models. Currently, there is no cure for USH. However, the genetic therapies that are rapidly developing will benefit from this compilation of detailed genetic information to identify the most effective strategies for restoring functional USH proteins.

Hearing aids to support cognitive functions of older adults at risk of dementia: the HearCog trial- clinical protocols.

BACKGROUND: Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available. METHODS: The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months. DISCUSSION: The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ANZCTR: 12618001278224 ), registered on 30.07.2018.

What Influences Decision-Making for Cochlear Implantation in Adults? Exploring Barriers and Drivers From a Multistakeholder Perspective.

OBJECTIVES: To explore the factors influencing the uptake of cochlear implants in adults, determine the impact of each factor, and to conceptualize the journey to implantation from a multistakeholder perspective. DESIGN: Concept mapping was used to integrate input from multiple stakeholders, each with their own experience and expertise. This mixed participatory method collects qualitative and quantitative data collection and enables further quantitative analysis. There were two participant cohorts: clients (cochlear implant recipients, candidates, and family members) and professionals (cochlear implant audiologists, ear, nose, and throat surgeons, administration staff, managers. and manufacturer representatives). A total of 93 people participated in the study: client cohort (n = 60, M age = 66.60 years) and professional cohort (n = 33, M age = 45.24 years). Participants brainstormed statements in response to the question "What influences people's decision to get/not get a cochlear implant?" They subsequently grouped the statements and named each group. They rated each statement as to its impact on the decision and prioritized the need for each to be changed/improved using a five-point Likert scale. Multidimensional scaling was used to produce a visual representation of the ideas and their relationship in the form of concepts. Further analysis was conducted to determine the differences between the cohorts, subcohorts, and concepts. RESULTS: One hundred ten unique statements were generated and grouped into six concepts which either directly affected the client or their environment. These concepts were: external influences (awareness and attitude of non-implant professionals about uptake, cost, logistics, the referral pathway, public awareness); uncertainties, beliefs, and fears (fears, negative effect of word of mouth, unsuccessful previous ear surgery, cosmetics of the device, misunderstanding of how a cochlear implant functions, eligibility for an implant and outcomes after implantation); health problems (mental and physical health); hearing difficulties (social, emotional, and communication impacts of hearing loss, severity of hearing loss, benefit from and experience with hearing aids); implant professionals (implant team's attitude, knowledge and relationship with clients, quality of overall service); and goals and support (clients 'hearing desires and goals, motivation, positive impact of word of mouth, family support, having a cochlear implant mentor. The six concepts fell into two overarching domains: the client-driven domain with four concepts and the external domain with two concepts. The mean rating of concepts in terms of impact on a client's decision to get an implant ranged from 2.24 (external influences, the main barrier) to 4.45 (goals and support, the main driver). Ratings significantly differed between the client and professional cohorts. CONCLUSIONS: This study increases our understanding of the factors, which influence a client's decision choose a cochlear implant as a hearing treatment. It also provides new information on the influence of the other stakeholders on the client journey. The magnitude of the generated statements in the client-driven domain highlights the pivotal role of individualized care in clinical settings in influencing a client's decision and the need for the professionals to understand a client's needs and expectations. A client's persistent hearing difficulties, goals, and support network were identified as drivers to the uptake of cochlear implants. However, the barriers identified highlight the need for a collaborative multi- and interdisciplinary approach to raise awareness in and educate non-implant hearing professionals about the cochlear implant process, as well as providing information to empower clients to make educated decisions and consider a cochlear implant as a hearing management option.

The effect of hearing loss configuration on cochlear implantation uptake rates: an Australian experience.

Objective: Recent changes to cochlear implant (CI) candidacy criteria have led to the inclusion of candidates with greater levels of hearing in the contralateral and/or implanted ear. This study assessed the impact of various hearing loss configurations on CI uptake rates (those assessed as eligible for CI, who proceed to CI).Design: Retrospective cohort study.Study sample: Post-lingually deaf adult CI candidates (n = 619) seen at a Western Australian cochlear implant clinic.Results: An overall CI uptake rate of 44% was observed. Hearing loss configuration significantly impacted uptake rates. Uptake rates of 62% for symmetrical hearing loss, 48% for asymmetrical hearing loss (four-frequency average hearing loss (4FAHL) asymmetry ≤60 dB), 25% for highly asymmetrical hearing loss (4FAHL asymmetry >60 dB), 38% for hearing losses eligible for electric-acoustic stimulation, and 22% for individuals with single-sided hearing loss were observed. Hearing loss configuration and age were both significant factors in relation to CI uptake although the impact of age was limited.Conclusion: CI clinics who apply or are considering applying expanded CI candidacy criteria within their practice should be aware that candidates with greater levels of residual hearing in at least the contralateral ear are less likely to proceed to CI.

Enhancing Resistance of Silk Fibroin Material to Enzymatic Degradation by Cross-Linking Both Crystalline and Amorphous Domains.

Silk fibroin (SF) membranes are finding widespread use as biomaterial scaffolds in a range of tissue engineering applications. The control over SF scaffold degradation kinetics is usually driven by the proportion of SF crystalline domains in the formulation, but membranes with a high ß-sheet content are brittle and still contain amorphous domains, which are highly susceptible to enzymatic degradation. In this work, photo-cross-linking of SF using a ruthenium-based method, and with the addition of glycerol, was used to generate robust and flexible SF membranes for long-term tissue engineering applications requiring slow degradation of the scaffolds. The resulting mechanical properties, protein secondary structure, and degradation rate were investigated. In addition, the cytocompatibility and versatility of porous micropatterning of SF films were assessed. The photo-cross-linking reduced the enzymatic degradation of SF in vitro without interfering with the ß-sheet content of the SF material, while adding glycerol to the composition grants flexibility to the membranes. By combining these methods, the membrane resistance to protease degradation was significantly enhanced compared to either method alone, and the SF mechanical properties were not impaired. We hypothesize that photo-cross-linking protects the SF amorphous regions from enzymatic degradation and complements the natural protection offered by ß-sheets in the crystalline region. Overall, this approach presents broad utility in tissue engineering applications that require a long-term degradation profile and mechanical support.