Biallelic p.V37I variant in GJB2 is associated with increasing incidence of hearing loss with age.

PURPOSE: This study aimed to quantitatively assess the incidence of hearing loss in relation to age in individuals with biallelic p.V37I variant in GJB2. METHODS: Population screening of the biallelic p.V37I variant was performed in 30,122 individuals aged between 0 and 97 years in Shanghai. Hearing thresholds of the biallelic p.V37I individuals and the controls were determined by click auditory brainstem response or pure tone audiometry. RESULTS: Biallelic p.V37I was detected in 0.528% (159/30,122) of the subjects. Of the biallelic p.V37I newborns, 43.91% (18/41) passed their distortion-product otoacoustic emissions-based newborn hearing screening or had hearing thresholds lower than 20 decible above normal hearing level. The older newborns had elevated hearing thresholds, with increasing incidence of 9.52%, 23.08%, 59.38%, and 80.00% for moderate or higher grade of hearing loss in age groups of 7 to 15 years, 20 to 40 years, 40 to 60 years, and 60 to 85 years, respectively. Their hearing deteriorated at a rate of 0.40 dB hearing level per year on average; males were more susceptible, and deterioration occurred preferentially at higher sound frequencies. CONCLUSION: The biallelic p.V37I variant is associated with steadily progressive hearing loss with increasing incidence over the course of life. Most of the biallelic p.V37I individuals may develop significant hearing loss in adulthood and, can benefit from early diagnosis and intervention through wide-spread genetic screening.

Development and initial validation of the Chinese Version of the Noise Exposure Questionnaire (C-NEQ).

BACKGROUND: With a high prevalence of noise-induced hearing loss (NIHL), the noise survey tools for identifying individuals with high risk of NIHL are still limited. This study was aimed to translate and develop a Chinese version of noise exposure questionnaire (C-NEQ), and validate its reliability and reproducibility. METHODS: This study was conducted from May 2020 to March 2021 in China. The questionnaire was translated from the original NEQ and adapted into Chinese culture using the method according to the International Test Committee. Content validity was evaluated by our expert group. Construct validity and reliability of the C-NEQ was determined through estimating the confirmatory factor analysis and Cronbach's alpha in a cross-sectional analysis among 641 Chinese speaking adults, respectively. The retest reproducibility of the C-NEQ was analyzed by using the intra-group correlation coefficient (ICC) in a follow-up analysis among 151 participants. RESULTS: The C-NEQ comprises ten items covering four domains: occupational, housework, transport and recreational noise exposure. The annual noise exposure (ANE) was calculated as the protocol of original NEQ. A total of 641 adult participants (aged 26.9 ± 10.1 years, 53.4% males) completed the C-NEQ. The average time for completing the C-NEQ was 4.4 ± 3.0 min. Content validity indicated high relevance of the C-NEQ. The confirmatory factor analysis indices illustrated that the items of the C-NEQ were suitable with the data in the study. For the internal reliability, the Cronbach's α coefficients of the total items and four domains (occupational, housework, transport, and recreational noise exposure) were 0.799, 0.959, 0.837, 0.825, and 0.803, respectively. Among them, 151 participants (aged 36.1 ± 11.1 years, 65.6% males) completed the retest of the C-NEQ 1 month after the first test. The ICC value of total ANEs between the first test and the second test was 0.911 (P < 0.001). CONCLUSIONS: In this study, we have validated the C-NEQ with adequate reliability and reproducibility for quantifying an individual's annual daily noise exposure, which provides an effective fast-screen tool for researches and clinics to identify those individuals with high risks of NIHL within the short time duration (no more than five minutes) among Chinese population.

Transcriptome Analyses Reveal the Role of Light in Releasing the Morphological Dormancy of Celery Seed by Integrating Plant Hormones, Sugar Metabolism and Endosperm Weakening.

Celery seed is known to be difficult to germinate due to its morphological dormancy. Light is the key signal to release morphological dormancy and promote seed germination. However, this mechanism has rarely been studied. We performed physiological, transcriptome analyses on celery seed exposed to light and dark to decipher the mechanism by which light promotes germination of celery seed. The results showed that light significantly enhanced the expression of gibberellin synthesis genes and abscisic acid degradation genes and inhibited the expression of abscisic acid synthesis genes and gibberellin degradation genes. Moreover, gibberellin synthesis inhibitor could completely inhibit the germination capacity of celery seed, indicating that gibberellin is indispensable in the process of celery seed germination. Compared with dark, light also increased the activity of α-amylase and ß-amylase and the expression of related coding genes and promoted the degradation of starch and the increase of soluble sugar content, suggesting that light enhanced the sugar metabolism of celery seed. In addition, transcriptome analysis revealed that many genes related to endosperm weakening (cell wall remodeling enzymes, extension proteins) were up-regulated under light. It was also found that light promoted the accumulation of hydrogen peroxide in the radicle, which promoted the endosperm weakening process of celery seed. Our results thus indicated that light signal may promote the release of morphological dormancy through the simultaneous action of multiple factors.

Identification and characterization of amphibian SLC26A5 using RNA-Seq.

BACKGROUND: Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Limited knowledge of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage and the studies of it were quite rare with only one species identified. RESULTS: Here we report a new coding sequence of SLC26A5 for a frog species, Rana catesbeiana (the American bullfrog). In our study, the SLC26A5 gene of Rana has been mapped, sequenced and cloned successively using RNA-Seq. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of Rana's inner ear and HEK293T cells transfected with this new coding gene. HEK293T cells expressing Rana prestin showed electrophysiological features similar to that of hair cells from its inner ear. Comparative studies of zebrafish, chick, Rana and an ancient frog species showed that chick and zebrafish prestin lacked NLC. Ancient frog's prestin was functionally different from Rana. CONCLUSIONS: We mapped and sequenced the SLC26A5 of the Rana catesbeiana from its inner ear cDNA using RNA-Seq. The Rana SLC26A5 cDNA was 2292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. This new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line. While comparing to its orthologs, the amphibian prestin has been evolutionarily changing its function and becomes more advanced than avian and teleost prestin.

Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure.

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

An In Vitro Study on Prestin Analog Gene in the Bullfrog Hearing Organs.

The prestin-based active process in the mammalian outer hair cells (OHCs) is believed to play a crucial role in auditory signal amplification in the cochlea. Prestin belongs to an anion transporter family (SLC26A). It is densely expressed in the OHC lateral plasma membrane and functions as a voltage-dependent motor protein. Analog genes can be found in the genome of nonmammalian species, but their functions in hearing are poorly understood. In the present study, we used the gerbil prestin sequence as a template and identified an analog gene in the bullfrog genome. We expressed the gene in a stable cell line (HEK293T) and performed patch-clamp recording. We found that these cells exhibited prominent nonlinear capacitance (NLC), a widely accepted assay for prestin functioning as a motor protein. Upon close examination, the key parameters of this NLC are comparable to that conferred by the gerbil prestin, and nontransfected cells failed to display NLC. Lastly, we performed patch-clamp recording in HCs of all three hearing organs in bullfrog. HCs in both the sacculus and the amphibian papilla exhibited a capacitance profile that is similar to NLC while HCs in the basilar papilla showed no sign of NLC. Whether or not this NLC-like capacitance change is involved in auditory signal amplification certainly requires further examination; our results represent the first and necessary step in revealing possible roles of prestin in the active hearing processes found in many nonmammalian species.

A dominant variant in DMXL2 is linked to nonsyndromic hearing loss.

PURPOSE: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss. METHODS: Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice. RESULTS: The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21.2 (maximum logarithm of the odds score = 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c.7250G>A (p.Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons. CONCLUSION: Our data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.Genet Med advance online publication 22 September 2016.

Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.

Spontaneous neuronal activity in dorsal cochlear nucleus (DCN) may be involved in the physiological processes underlying salicylate-induced tinnitus. As a neuronal activity marker, immediate-early gene (IEG) expression, especially activity-dependent cytoskeletal protein (Arc/Arg3.1) and the early growth response gene-1 (Egr-1), appears to be highly correlated with sensory-evoked neuronal activity. However, their relationships with tinnitus induced by salicylate have rarely been reported in the DCN. In this study, we assessed the effect of acute and chronic salicylate treatment on the expression of N-methyl D-aspartate receptor subunit 2B (NR2B), Arg3.1, and Egr-1. We also observed ultrastructural alterations in the DCN synapses in an animal model of tinnitus. Levels of mRNA and protein expression of NR2B and Arg3.1 were increased in rats that were chronically administered salicylate (200 mg/kg, twice daily for 3, 7, or 14 days). These levels returned to baseline 14 days after cessation of treatment. However, no significant changes were observed in Egr-1 gene expression in any groups. Furthermore, rats subjected to long-term salicylate administration showed more presynaptic vesicles, thicker and longer postsynaptic densities, and increased synaptic interface curvature. Alterations of Arg3.1 and NR2B may be responsible for the changes in the synaptic ultrastructure. These changes confirm that salicylate can cause neural plasticity changes at the DCN level.

The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.

This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals.

Comparison between hearing screening-detected cases and sporadic cases of delayed-onset hearing loss in preschool-age children.

OBJECTIVE: This study aimed to compare the diagnosis and ages of intervention for cases of delayed-onset hearing loss identified sporadically or via a preschool hearing screening program. DESIGN: Retrospective study with the comparative analysis of two groups of children. STUDY SAMPLE: Cases identified from screening were selected from 34 321 preschool children who underwent screening for delayed-onset hearing loss between October 2009 and May 2011. Sporadic cases of delayed-onset hearing loss were selected from pediatric clinical records. Cases from the first group were excluded from the latter to avoid duplication. Two groups were given the same questionnaire to record risk indicators, diagnosis, and age at intervention. RESULTS: The average age of 26 children at the time of diagnosis in the screening group (52.81 ± 13.23 months) was significantly earlier than in the 33 cases identified in the sporadic group (62.03 ± 12.86 months; p < 0.05). The age at intervention of children with bilateral moderate to severe hearing loss in the screening group (50.40 ± 10.76 months) was also earlier than in the sporadic group (62.73 ± 13.77 months; p < 0.05). CONCLUSIONS: Improved rates of early diagnosis could therefore be achieved with hearing screening for preschool children with no significant symptoms of delayed-onset hearing loss.

Investigating the Impact of Origins on the Quality Characteristics of Celery Seeds Based on Metabolite Analysis through HS-GC-IMS, HS-SPME-GC-MS and UPLC-ESI-MS/MS.

Celery seeds contain various bioactive compounds and are commonly used as a spice and nutritional supplement in people's daily lives. The quality of celery seeds sold on the market varies, and their regions of production are unclear. This study evaluated the metabolites of Chinese celery seeds from three production regions using HS-SPME-GC-MS, HS-GC-IMS, and UPLC-ESI-MS/MS. The results indicate that GC-IMS analysis obtained a metabolic profile different from that detected using GC-MS. Terpenoids, polyphenols, coumarins, and phthalides are the main bioactive compounds in celery seeds. The production region significantly affects the metabolic characteristics of celery seeds. Based on GC-MS data, GC-IMS data, and LC-MS data, the variation analysis screened 6, 12, and 8 metabolites as potential characteristic metabolites in celery seeds related to the production region, respectively. According to the aromatic characteristics of the characteristic metabolites, seeds from the HCQ region and HZC region have a strong herbal, woody, celery, and turpentine aroma. The concentration of secondary metabolites was highest in the seeds from the HCQ region followed by the HZC region, and it was the lowest in the JJC region. Altogether, this study investigates how geographical origins influence the metabolomic profile of celery seeds. The results can be used to guide the planting and harvesting of celery seeds in suitable regions.

Strong, tough, and elastic poly(vinyl alcohol)/polyacrylamide DN hydrogels based on the Hofmeister effect for articular cartilage replacement.

Traditional hydrogels are usually weak and brittle, which limit their application in articular cartilage replacement because cartilage is generally strong, tough, and elastic in nature. Therefore, it is highly desirable to construct hydrogels to mimic the mechanical properties of the native articular cartilage. Herein, in this work, poly(vinyl alcohol)/polyacrylamide (PVA/PAM) DN hydrogels were prepared by in situ polymerization, which were then treated with Hofmeister series ions (Cit3-, SO42-, and Cl-) to achieve H-PVA/PAM DN hydrogels. Among the three Hofmeister ions, the DN hydrogel treated with Cit3- (named PVA/PAM-Cit) showed the densest microstructure and the highest crystallinity degree. In this context, PVA/PAM-Cit exhibited a tensile strength of 18.9 ± 1.6 MPa, a compressive strength of 102.3 ± 7.9 MPa, a tensile modulus of 10.6 ± 2.1 MPa, a compressive modulus of 8.9 ± 0.8 MPa, and a roughness of 66.2 ± 4.2 MJ m-3, respectively, which were the highest strength and modulus, and the second highest toughness when compared with those of the reported PVA and PVA based DN hydrogels so far. It also showed an extreme high elasticity, which could maintain a stress of 99.2% after 500 cycles of fatigue testing. Additionally, PVA/PAM-Cit can promote the adhesion, spreading and proliferation of chondrocytes. These results verify that such a strong, tough, and elastic hydrogel could be a novel candidate material for articular cartilage replacement.

Adaptive Log-Euclidean Metrics for SPD Matrix Learning.

Symmetric Positive Definite (SPD) matrices have received wide attention in machine learning due to their intrinsic capacity to encode underlying structural correlation in data. Many successful Riemannian metrics have been proposed to reflect the non-Euclidean geometry of SPD manifolds. However, most existing metric tensors are fixed, which might lead to sub-optimal performance for SPD matrix learning, especially for deep SPD neural networks. To remedy this limitation, we leverage the commonly encountered pullback techniques and propose Adaptive Log-Euclidean Metrics (ALEMs), which extend the widely used Log-Euclidean Metric (LEM). Compared with the previous Riemannian metrics, our metrics contain learnable parameters, which can better adapt to the complex dynamics of Riemannian neural networks with minor extra computations. We also present a complete theoretical analysis to support our ALEMs, including algebraic and Riemannian properties. The experimental and theoretical results demonstrate the merit of the proposed metrics in improving the performance of SPD neural networks. The efficacy of our metrics is further showcased on a set of recently developed Riemannian building blocks, including Riemannian batch normalization, Riemannian Residual blocks, and Riemannian classifiers.

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation.

Litsea cubeba essential oil (LCEO) has garnered widespread attention due to its robust biological activity. However, challenges such as high volatility, limited water solubility, and low bioavailability impede its application. Nano-emulsion encapsulation technology offers an effective solution to these issues. In this study, we prepared litsea cubeba essential oil nano-emulsion (LCEO-NE) for the first time using whey protein (WP) as the emulsifier through an ultrasonic-assisted method, achieving high efficiency with minimal energy consumption. Transmission electron microscopy and dynamic light scattering analyses revealed that the nanoparticles were uniformly spherical, with a particle size of 183.5 ± 1.19 nm and a zeta potential of -35.5 ± 0.95 mV. Stability studies revealed that LCEO-NE exhibited excellent thermal and salt stability, maintaining its integrity for up to four weeks when stored at 4 °C and 25 °C. In vitro digestion assays confirmed the digestibility of LCEO-NE. Furthermore, evaluation of the DPPH, ABTS, and antimicrobial activities revealed that LCEO-NE displayed superior bacteriostatic and antioxidant properties compared to LCEO. Scanning electron microscopy elucidated that its bacteriostatic effect involved the disruption of bacterial microstructure. Hemocompatibility and cytotoxicity assays demonstrated the safety of LCEO-NE within the effective concentration range. This research supports the utilization of nanoparticles for encapsulating LCEO, thereby enhancing its stability and bioactivity, and consequently expanding its applications in the food and pharmaceutical industries.

Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China.

Recessive mutations in SLC26A4 and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4 lead to hearing impairment associated with enlarged vestibular aqueduct (EVA), the most common inner ear malformation. In our large cohort study, we addressed several important questions to the molecular etiology of this disorder. The overall prevalence of SLC26A4 mutations in nonsyndromic childhood sensorineural hearing loss (11.2%, 37/330) were determined by sequencing of SLC26A4 in 330 hearing impaired children who did not undergo inner ear radiologic imaging prior to their genetic test. The penetrance of EVA in bi-allelic SLC26A4 mutation carriers (100%, 37/37) was determined by follow-up computed tomography scanning. Combined with the study of 140 additional probands diagnosed with nonsyndromic EVA, we characterized the mutation spectrum of SLC26A4 in East China, which consisted of 19 novel SLC26A4 mutations and differed from those reported in other regions of China.

Distributed Group Coordination of Multiagent Systems in Cloud Computing Systems Using a Model-Free Adaptive Predictive Control Strategy.

This article studies the group coordinated control problem for distributed nonlinear multiagent systems (MASs) with unknown dynamics. Cloud computing systems are employed to divide agents into groups and establish networked distributed multigroup-agent systems (ND-MGASs). To achieve the coordination of all agents and actively compensate for communication network delays, a novel networked model-free adaptive predictive control (NMFAPC) strategy combining networked predictive control theory with model-free adaptive control method is proposed. In the NMFAPC strategy, each nonlinear agent is described as a time-varying data model, which only relies on the system measurement data for adaptive learning. To analyze the system performance, a simultaneous analysis method for stability and consensus of ND-MGASs is presented. Finally, the effectiveness and practicability of the proposed NMFAPC strategy are verified by numerical simulations and experimental examples. The achievement also provides a solution for the coordination of large-scale nonlinear MASs.

Comprehensive Quality and Bioactive Constituent Analysis of Celery Juice Made from Different Cultivars.

Celery juice is rich in bioactive constituents, has good health properties, and is becoming much more popular, with its demand continuing to rise. The results of this study show that celery juice from Chinese cultivars contains more bioactive constituents, whereas celery cultivars from the United States and European countries have a higher juice yield. Compared with the other juices, the juices of five cultivars may taste sweeter, and the juices of three cultivars had a higher antioxidant capacity. The juices of six cultivars (three with the highest antioxidant capacity and three with the lowest antioxidant capacity) were selected to analyze bioactive constituents by LC/MS and GC/MS. A total of 71 phenolic acids, 38 flavonoids, 18 coumarins, 41 terpenoids, and 11 phthalides were detected in the juices of the six celery cultivars. The contents of 14 compounds had a more than 10-fold difference among these celery juices. This study first evaluated the comprehensive quality of the juices made from 26 celery cultivars and then analyzed the differences in bioactive constituents in the juices of6 celery cultivars. These findings provide information for the further study on the health functions of celery juice and can also guide celery juice production and celery breeding.

Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III.

BACKGROUND: POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing. METHODS: Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region. RESULTS: In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876-1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342). CONCLUSIONS: Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.

Acute Recreational Noise-Induced Cochlear Synaptic Dysfunction in Humans With Normal Hearing: A Prospective Cohort Study.

OBJECTIVES: The objective of the study was to identify the acute high-intensity recreational noise-induced effects on auditory function, especially the cochlear synaptopathy-related audiological metrics, in humans with normal hearing. METHODS: This prospective cohort study enrolled 32 young adults (14 males and 18 females); the mean age was 24.1 ± 2.4 years (ranging from 20 to 29). All participants with normal hearing (audiometric thresholds ≤25 dB HL at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for both ears) had already decided to participate in the outdoor music festival. Participants were asked to measure the noise exposure dose and complete auditory examinations, including the air-conduction pure-tone audiometry (PTA), distortion product otoacoustic emission (DPOAE), contralateral suppression (CS) on transient evoked otoacoustic emission (TEOAE), auditory brainstem response (ABR) test and Mandarin Hearing in Noise Test (MHINT), at baseline and 1 day and 14 days after music festival noise exposure. RESULTS: The mean time of attending the music festival was 7.34 ± 0.63 h (ranging from 6.4 to 9.5), the mean time-weighted average (TWA) of noise exposure dose was 93.2 ± 2.39 dB(A) (ranging from 87.9 to 97.7). At neither 1 day nor 14 days post exposure, there were no statistically significant effects on PTA thresholds, DPOAE amplitudes, CS on TEOAEs, or MHINT signal-to-noise ratios (SNRs) of acute outdoor music festival noise exposure, regardless of sex. While the ABR wave I amplitudes significantly decreased at 1 day after exposure and recovered at 14 days after exposure, the exposed/unexposed ABR wave I amplitude ratio was significantly correlated with MHINT SNR change at 1 day after exposure, although it was not correlated with the noise exposure dose. CONCLUSION: In young adults with normal hearing, we found the self-compared decrement of ABR wave I amplitudes at 1 day post acute recreational noise exposure at high intensity, which also contributes to the change in speech perceptual ability in noisy backgrounds. This study indicated that auditory electrophysiological metric changes might be a more sensitive and efficient indicator of noise-induced cochlear synaptic dysfunction in humans. More attention should be paid to the recreational noise-induced cochlear synaptopathy and auditory perceptual disorder.

[The efficacy of modified mini-mental state examination in patients with severe to profound hearing loss].

Objective:To evaluate the efficacy of modified mini-mental state examination（MMSE） in elderly patients with severe to profound hearing loss. Methods:A total of 24 elderly patients with severe to profound hearing loss from April to June 2019 were involved. Severe to profound hearing loss was defined by a pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Modified and original MMSE was completed for the patients at first visit. Two weeks later, they all return hospital and MMSE were carried out by the other method. The aggregate score and subitem score of MMSE by modified and original instrument were analyzed. The degree of cognitive impairment evaluated by two methods were compared. Results:Among the 24 patients, the mean MMSE score by routine method and improved method were 10.88±9.70 and 25.29±3.70（P<0.01）. The average score of sub-items of MMSE with routine method and improved method are as follows: orientation 3.21±4.03 vs 8.71±1.92（P<0.01）, registration 1.04±1.33 vs 2.79±0.51（P<0.01）, attention and calculation 1.63±2.02 vs 4.00±1.41（P<0.01）, recall 0.79±1.14 vs 2.50±0.72（P<0.01）, language 4.21±2.11 vs 7.29±1.33（P<0.01）. Compared with the routine method, the degree of cognitive impairment getting better in 83.3% patients with improved method, meanwhile, 16.7% of the patients remain the same and no deterioration. Conclusion:The routine method of MMSE should be improved to seek the real cognitive state of the patients with severe to profound hearing loss.