Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca2+) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular level. Computational molecular dynamics show that loss of the disulfide bridge in hNppitch causes structural destabilization of immunoglobulin-like domain (Ig) III and that the novel asparagine in hNpaudio-1 results in steric constraints and an additional N-glycosylation site in IgII. Additional N-glycosylation of hNpaudio-1 was confirmed by PNGaseF treatment. In comparison to hNpWT, transfection of hNppitch and hNpaudio-1 into HEK293T cells resulted in normal mRNA levels but reduced the Np protein levels and their cell surface expression due to proteasomal/lysosomal degradation. Furthermore, hNppitch and hNpaudio-1 failed to promote exogenous PMCA levels in HEK293T cells. In hippocampal neurons, expression of additional hNppitch or hNpaudio-1 was less efficient than hNpWT to elevate endogenous PMCA levels and to accelerate the restoration of basal Ca2+ levels after electrically-evoked Ca2+ transients. We propose that mutations leading to pathological Np variants, as exemplified here by the deafness causing Np mutants, can affect Np-dependent Ca2+ regulatory mechanisms and may potentially cause intellectual and cognitive deficits in humans.

Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs express Tmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, Pclo and Slc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. Tmc2 and Cib3 were not detected in adult mouse HCs but tmc2a and b and cib3 were highly expressed in zHCs. Mouse HCs express Kcna10, Kcnj13, Kcnj16, and Kcnq4, which were not detected in zHCs. Chrna9 and Chrna10 were expressed in mouse HCs. In contrast, chrna10 was not detected in zHCs. OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.

The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear\' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.

BACKGROUND: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking.
METHODS: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps.
RESULTS: Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a.
CONCLUSIONS: Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates.
BACKGROUND: See the Acknowledgements section.

Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.

UNASSIGNED: Meniere\'s disease (MD) is characterized by idiopathic endolymphatic hydrops (ELH). Frequent vertigo attacks is the most disabling symptom of MD.
UNASSIGNED: This study evaluated the efficacy of triple semicircular canal occlusion combined with endolymphatic sac decompression in the treatment of frequent vertigo in patients with MD.
UNASSIGNED: Eleven patients with complete medical records were included in this study conducted from May 2021 to April 2022. All patients were enrolled to undergo triple semicircular canal occlusion (TSCO) with endolymphatic sac decompression (ESD). Various tests including pure tone audiometry (PTA), vestibular evoked myogenic potentials (VEMPs), the video head impulse test (v-HIT), caloric test data, the Dizziness Handicap Inventory (DHI), the Berg Balance Scale (BBS), and the Tinnitus Handicap Inventory (THI) were performed both before and after the surgery.
UNASSIGNED: The successful control rate of vertigo was 100% (9/9) in the average 23-month postoperative follow-up period, with complete control rate of 88.89% (8/9) and substantial control rate of 11.11% (1/9).
UNASSIGNED: Triple semicircular canal occlusion combined with ESD may be an effective treatment option for managing frequent vertigo attacks in patients with MD. This combination therapy has the potential to become a significant addition to the treatment framework for MD.

UNASSIGNED: Artificial intelligence (AI) chatbots, such as ChatGPT-4, have shown immense potential for application across various aspects of medicine, including medical education, clinical practice, and research.
UNASSIGNED: This study aimed to evaluate the performance of ChatGPT-4 in the 2023 Taiwan Audiologist Qualification Examination, thereby preliminarily exploring the potential utility of AI chatbots in the fields of audiology and hearing care services.
UNASSIGNED: ChatGPT-4 was tasked to provide answers and reasoning for the 2023 Taiwan Audiologist Qualification Examination. The examination encompassed six subjects: (1) basic auditory science, (2) behavioral audiology, (3) electrophysiological audiology, (4) principles and practice of hearing devices, (5) health and rehabilitation of the auditory and balance systems, and (6) auditory and speech communication disorders (including professional ethics). Each subject included 50 multiple-choice questions, with the exception of behavioral audiology, which had 49 questions, amounting to a total of 299 questions.
UNASSIGNED: The correct answer rates across the 6 subjects were as follows: 88% for basic auditory science, 63% for behavioral audiology, 58% for electrophysiological audiology, 72% for principles and practice of hearing devices, 80% for health and rehabilitation of the auditory and balance systems, and 86% for auditory and speech communication disorders (including professional ethics). The overall accuracy rate for the 299 questions was 75%, which surpasses the examination\'s passing criteria of an average 60% accuracy rate across all subjects. A comprehensive review of ChatGPT-4\'s responses indicated that incorrect answers were predominantly due to information errors.
UNASSIGNED: ChatGPT-4 demonstrated a robust performance in the Taiwan Audiologist Qualification Examination, showcasing effective logical reasoning skills. Our results suggest that with enhanced information accuracy, ChatGPT-4\'s performance could be further improved. This study indicates significant potential for the application of AI chatbots in audiology and hearing care services.

UNASSIGNED: Recycling of synaptic vesicles plays an important role in vesicle pool replenishment, neurotransmitter release and synaptic plasticity. Clathrin-mediated endocytosis (CME) is considered to be the main mechanism for synaptic vesicle replenishment. AP-2 (adaptor-related protein complex 2) and myosin Ⅵ are known as key proteins that regulate the structure and dynamics of CME.
UNASSIGNED: This study aims to reveal the spatiotemporal expression of AP-2/myosin Ⅵ in inner hair cells (IHCs) of the mouse cochlea and its correlation with auditory function.
UNASSIGNED: Immunofluorescence was used to detect the localization and expression of AP-2 and myosin Ⅵ in cochlear hair cells (HCs) of CBA/CaJ mice of various ages. qRT-PCR was used to verify the differential expression of AP-2 and myosin Ⅵ mRNA in the mouse cochlea, and ABR tests were administered to mice of various ages. A preliminary analysis of the correlation between AP-2/myosin Ⅵ levels and auditory function was conducted.
UNASSIGNED: AP-2 was located in the cytoplasmic region of IHCs and was mainly expressed in the basal region of IHCs and the area near ribbon synapses, while myosin Ⅵ was expressed in the cytoplasmic region of IHCs and OHCs. Furthermore, AP-2 and myosin Ⅵ were not significant detected in the cochleae of P7 mice; the expression level reached a peak at P35 and then decreased significantly with age. The expression patterns and expression levels of AP-2 and myosin Ⅵ in the cochleae of the mice were consistent with the development of the auditory system.
UNASSIGNED: AP-2 and myosin Ⅵ protein expression may differ in mice of different ages, and this variation probably leads to a difference in the efficiency in CME; it may also cause a defect in IHC function.

OBJECTIVE: Trimming of perforation margins and external auditory canal (EAC) packing are basic procedures in underlay myringoplasty for repairing chronic perforations. The objective of this study was to compare the operation time, graft outcome, hearing improvement, and complications of endoscopic cartilage underlay myringoplasty with and without trimming of perforation margins and EAC packing in children.
METHODS: Prospective, randomized study.
METHODS: Tertiary referral center.
METHODS: Pediatric patients older than 12 years with chronic perforations were randomly divided into two groups: myringoplasty with trimming of perforation margin and EAC packing (TPME) group or no trimming of perforation margin and EAC packing (NTPME) group. The operation time, graft success rate, hearing improvement, and complications were compared between the two groups.
RESULTS: Fifty-two patients were ultimately included in the study. The mean operation time was 31.4 ± 4.2 min in the TPME group and 23.6 ± 1.7 min in the NTPME group; the difference was significant (P < 0.01). The rate of aural fullness significantly differed between the TPME and NTPME groups (P = 0.000). All participants were followed up for 12 months; the graft success rate did not significantly differ between the groups (88.5% vs. 96.2%; P = 0.603). No patients developed adhesive otitis media. Between the preoperative and postoperative measurements, the mean air-bone gap improved by 10.2 ± 2.8 dB in the TPME group and 11.6 ± 0.7 dB in the NTPME group; this was significant (P < 0.001) in both groups.
CONCLUSIONS: Endoscopic cartilage underlay myringoplasty NTPME shorted the operation time and avoided aural fullness and EAC discomfort compared with the TPME technique; however, graft success and hearing improvement were comparable between the two techniques for repairing large perforations in children.

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.