{"title":"A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2<sup>+</sup> Progenitors in the Neonatal Mouse Inner Ear Organoids.","authors":"Wenjin Wu, Penghui Chen, Jun Yang, Yupeng Liu","doi":"10.1007/s10162-024-00938-1","DOIUrl":"10.1007/s10162-024-00938-1","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the impact of rapamycin on the differentiation of hair cells.</p><p><strong>Methods: </strong>Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages.</p><p><strong>Results: </strong>Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2<sup>+</sup> progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects.</p><p><strong>Conclusion: </strong>Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2<sup>+</sup> progenitors in an in vitro setting.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"149-165"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Demoen, Emilie Cardon, Laure Jacquemin, Annick Timmermans, Vincent Van Rompaey, Annick Gilles, Sarah Michiels
{"title":"Health-Related Quality of Life in Subjective, Chronic Tinnitus Patients: A Scoping Review.","authors":"Sara Demoen, Emilie Cardon, Laure Jacquemin, Annick Timmermans, Vincent Van Rompaey, Annick Gilles, Sarah Michiels","doi":"10.1007/s10162-024-00926-5","DOIUrl":"10.1007/s10162-024-00926-5","url":null,"abstract":"<p><strong>Purpose: </strong>This scoping review aims to assess whether the severity or distress of subjective tinnitus is negatively associated or correlated with the level of health-related quality of life (HRQoL). A second objective is to examine whether tinnitus patients score differently on HRQoL questionnaires in comparison to subjects without tinnitus and whether HRQoL differs between specific subgroups of tinnitus.</p><p><strong>Methods: </strong>This scoping review adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA guidelines): the statement and extension for scoping reviews (PRISMA-ScR). The following databases were consulted (on the 20th of October 2023): PubMed, Cochrane Library, Web of Science, and Scopus. The search string was composed of the terms tinnitus, HRQoL, and synonyms. A double-blinded screening for eligibility was performed, first on the title and abstract and subsequently on the full-text articles. Studies were considered eligible if they looked at HRQoL questionnaire results for adult patients (> 18 years) reporting chronic (> 3 months), subjective tinnitus as a primary complaint.</p><p><strong>Results: </strong>In total, 37 studies with a total sample size of 33,900 participants were included in this scoping review, with some studies answering multiple study objectives. Seventeen studies demonstrated the presence of a significant negative correlation between tinnitus-related distress and HRQoL. Two studies indicated that HRQoL is mediated by tinnitus-related distress. Eighteen studies found that, in general, patients with tinnitus scored significantly lower on HRQoL questionnaires in comparison to subjects without tinnitus. Nineteen studies demonstrated that subgroups of patients with more severe tinnitus complaints or specific additional complaints scored worse on HRQoL questionnaires.</p><p><strong>Conclusion: </strong>Based on the current literature, chronic subjective tinnitus-related distress has a significant impact on health-related quality of life. In addition, subjects without tinnitus generally score significantly higher on HRQoL questionnaires than patients with tinnitus. The heterogeneity in outcome measures between studies precludes meta-analysis. Increased homogeneity in the choice of HRQoL questionnaires would make a comparison between studies possible, which would give valuable information on both a clinical and an economic level, guiding future tinnitus treatment.</p><p><strong>Registration: </strong>The protocol for the scoping review is registered at Open Science Framework: https://doi.org/10.17605/OSF.IO/F5S9C .</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"103-129"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Swept Along: Measuring Otoacoustic Emissions Using Continuously Varying Stimuli.","authors":"Christopher A Shera","doi":"10.1007/s10162-024-00934-5","DOIUrl":"10.1007/s10162-024-00934-5","url":null,"abstract":"<p><p>At the 2004 Midwinter Meeting of the Association for Research in Otolaryngology, Glenis Long and her colleagues introduced a method for measuring distortion-product otoacoustic emissions (DPOAEs) using primary-tone stimuli whose instantaneous frequencies vary continuously with time. In contrast to standard OAE measurement methods, in which emissions are measured in the sinusoidal steady state using discrete tones of well-defined frequency, the swept-tone method sweeps across frequency, often at rates exceeding 1 oct/s. The resulting response waveforms are then analyzed using an appropriate filter (e.g., by least-squares fitting). Although introduced as a convenient way of studying DPOAE fine structure by separating the total OAE into distortion and reflection components, the swept-tone method has since been extended to stimulus-frequency emissions and has proved an efficient and valuable tool for probing cochlear mechanics. One day-a long time coming-swept tones may even find their way into the audiology clinic.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"91-102"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patricia Perez-Carpena, Jose A Lopez-Escamez, Álvaro Gallego-Martinez
{"title":"A Systematic Review on the Genetic Contribution to Tinnitus.","authors":"Patricia Perez-Carpena, Jose A Lopez-Escamez, Álvaro Gallego-Martinez","doi":"10.1007/s10162-024-00925-6","DOIUrl":"10.1007/s10162-024-00925-6","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.</p><p><strong>Methods: </strong>After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.</p><p><strong>Results: </strong>The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.</p><p><strong>Conclusions: </strong>The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"13-33"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insights Into Electrophysiological Metrics of Cochlear Health in Cochlear Implant Users Using a Computational Model.","authors":"Marko Takanen, Stefan Strahl, Konrad Schwarz","doi":"10.1007/s10162-023-00924-z","DOIUrl":"10.1007/s10162-023-00924-z","url":null,"abstract":"<p><strong>Purpose: </strong>The hearing outcomes of cochlear implant users depend on the functional status of the electrode-neuron interface inside the cochlea. This can be assessed by measuring electrically evoked compound action potentials (eCAPs). Variations in cochlear neural health and survival are reflected in eCAP-based metrics. The difficulty in translating promising results from animal studies into clinical use has raised questions about to what degree eCAP-based metrics are influenced by non-neural factors. Here, we addressed these questions using a computational model.</p><p><strong>Methods: </strong>A 2-D computational model was designed to simulate how electrical signals from the stimulating electrode reach the auditory nerve fibers distributed along the cochlea, evoking action potentials that can be recorded as compound responses at the recording electrodes. Effects of physiologically relevant variations in neural survival and in electrode-neuron and stimulating-recording electrode distances on eCAP amplitude growth functions (AGFs) were investigated.</p><p><strong>Results: </strong>In line with existing literature, the predicted eCAP AGF slopes and the inter-phase gap (IPG) effects depended on the neural survival, but only when the IPG effect was calculated as the difference between the slopes of the two AGFs expressed in linear input-output scale. As expected, shallower eCAP AGF slopes were obtained for increased stimulating-recording electrode distance and larger eCAP thresholds for greater electrode-neuron distance. These non-neural factors had also minor interference on the predicted IPG effect.</p><p><strong>Conclusions: </strong>The model predictions demonstrate previously found dependencies of eCAP metrics on neural survival and non-neural aspects. The present findings confirm data from animal studies and provide insights into applying described metrics in clinical practice.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"63-78"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ARO's 47th Annual MidWinter Meeting in Anaheim 2024: podium and poster titles.","authors":"","doi":"10.1007/s10162-024-00930-9","DOIUrl":"10.1007/s10162-024-00930-9","url":null,"abstract":"","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"1-74"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Z Zhang, Lukas Graf, Annesya Banerjee, Aaron Yeiser, Christopher I McHugh, Ioannis Kymissis, Jeffrey H Lang, Elizabeth S Olson, Hideko Heidi Nakajima
{"title":"Correction: An Implantable Piezofilm Middle Ear Microphone: Performance in Human Cadaveric Temporal Bones.","authors":"John Z Zhang, Lukas Graf, Annesya Banerjee, Aaron Yeiser, Christopher I McHugh, Ioannis Kymissis, Jeffrey H Lang, Elizabeth S Olson, Hideko Heidi Nakajima","doi":"10.1007/s10162-024-00933-6","DOIUrl":"10.1007/s10162-024-00933-6","url":null,"abstract":"","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"89"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inner Ear Organoids: Strengths and Limitations.","authors":"Giulia Pianigiani, Marta Roccio","doi":"10.1007/s10162-024-00929-2","DOIUrl":"10.1007/s10162-024-00929-2","url":null,"abstract":"<p><p>Inner ear organoids derived from differentiation of human pluripotent stem cells have recently gained momentum as tools to study inner ear development and developmental defects. An additional exciting aspect about this technology is represented by its translational potential, specifically, the use of organoids to validate therapeutics for hearing and balance restoration on human/patient-specific cells. This latter aspect will be briefly discussed here including opportunities and current limitations.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"5-11"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Z Zhang, Lukas Graf, Annesya Banerjee, Aaron Yeiser, Christopher I McHugh, Ioannis Kymissis, Jeffrey H Lang, Elizabeth S Olson, Hideko Heidi Nakajima
{"title":"An Implantable Piezofilm Middle Ear Microphone: Performance in Human Cadaveric Temporal Bones.","authors":"John Z Zhang, Lukas Graf, Annesya Banerjee, Aaron Yeiser, Christopher I McHugh, Ioannis Kymissis, Jeffrey H Lang, Elizabeth S Olson, Hideko Heidi Nakajima","doi":"10.1007/s10162-024-00927-4","DOIUrl":"10.1007/s10162-024-00927-4","url":null,"abstract":"<p><strong>Purpose: </strong>One of the major reasons that totally implantable cochlear microphones are not readily available is the lack of good implantable microphones. An implantable microphone has the potential to provide a range of benefits over external microphones for cochlear implant users including the filtering ability of the outer ear, cosmetics, and usability in all situations. This paper presents results from experiments in human cadaveric ears of a piezofilm microphone concept under development as a possible component of a future implantable microphone system for use with cochlear implants. This microphone is referred to here as a drum microphone (DrumMic) that senses the robust and predictable motion of the umbo, the tip of the malleus.</p><p><strong>Methods: </strong>The performance was measured by five DrumMics inserted in four different human cadaveric temporal bones. Sensitivity, linearity, bandwidth, and equivalent input noise were measured during these experiments using a sound stimulus and measurement setup.</p><p><strong>Results: </strong>The sensitivity of the DrumMics was found to be tightly clustered across different microphones and ears despite differences in umbo and middle ear anatomy. The DrumMics were shown to behave linearly across a large dynamic range (46 dB SPL to 100 dB SPL) across a wide bandwidth (100 Hz to 8 kHz). The equivalent input noise (over a bandwidth of 0.1-10 kHz) of the DrumMic and amplifier referenced to the ear canal was measured to be about 54 dB SPL in the temporal bone experiment and estimated to be 46 dB SPL after accounting for the pressure gain of the outer ear.</p><p><strong>Conclusion: </strong>The results demonstrate that the DrumMic behaves robustly across ears and fabrication. The equivalent input noise performance (related to the lowest level of sound measurable) was shown to approach that of commercial hearing aid microphones. To advance this demonstration of the DrumMic concept to a future prototype implantable in humans, work on encapsulation, biocompatibility, and connectorization will be required.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"53-61"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
François Deloche, Satyabrata Parida, Andrew Sivaprakasam, Michael G Heinz
{"title":"Estimation of Cochlear Frequency Selectivity Using a Convolution Model of Forward-Masked Compound Action Potentials.","authors":"François Deloche, Satyabrata Parida, Andrew Sivaprakasam, Michael G Heinz","doi":"10.1007/s10162-023-00922-1","DOIUrl":"10.1007/s10162-023-00922-1","url":null,"abstract":"<p><strong>Purpose: </strong>Frequency selectivity is a fundamental property of the peripheral auditory system; however, the invasiveness of auditory nerve (AN) experiments limits its study in the human ear. Compound action potentials (CAPs) associated with forward masking have been suggested as an alternative to assess cochlear frequency selectivity. Previous methods relied on an empirical comparison of AN and CAP tuning curves in animal models, arguably not taking full advantage of the information contained in forward-masked CAP waveforms.</p><p><strong>Methods: </strong>To improve the estimation of cochlear frequency selectivity based on the CAP, we introduce a convolution model to fit forward-masked CAP waveforms. The model generates masking patterns that, when convolved with a unitary response, can predict the masking of the CAP waveform induced by Gaussian noise maskers. Model parameters, including those characterizing frequency selectivity, are fine-tuned by minimizing waveform prediction errors across numerous masking conditions, yielding robust estimates.</p><p><strong>Results: </strong>The method was applied to click-evoked CAPs at the round window of anesthetized chinchillas using notched-noise maskers with various notch widths and attenuations. The estimated quality factor Q10 as a function of center frequency is shown to closely match the average quality factor obtained from AN fiber tuning curves, without the need for an empirical correction factor.</p><p><strong>Conclusion: </strong>This study establishes a moderately invasive method for estimating cochlear frequency selectivity with potential applicability to other animal species or humans. Beyond the estimation of frequency selectivity, the proposed model proved to be remarkably accurate in fitting forward-masked CAP responses and could be extended to study more complex aspects of cochlear signal processing (e.g., compressive nonlinearities).</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"35-51"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}