Transcriptomic analysis reveals prolonged neurodegeneration in the hippocampus of adult C57BL/6N mouse deafened by noise.

Introduction: Several studies have reported a significant correlation between noise-induced hearing loss and cognitive decline. However, comprehensive analyses of this relationship are rare. This study aimed to assess the influence of hearing impairment on cognitive functions by analyzing organ samples in the afferent auditory pathway of deafened mice using mRNA sequencing. Methods: We prepared 10 female 12-week-old C57BL/6N mice as the experimental and control groups in equal numbers. Mice in the experimental group were deafened with 120 dB sound pressure level (SPL) wideband noise for 2 h. Cochlea, auditory cortex, and hippocampus were obtained from all mice. After constructing cDNA libraries for the extracted RNA from the samples, we performed next-generation sequencing. Subsequently, we analyzed the results using gene ontologies (GOs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases for differentially expressed genes (DEGs) of each organ. Results: Our results revealed 102, 89, and 176 DEGs for cochlea, auditory cortex, and hippocampus, respectively. We identified 294, 203, and 211 GOs; 10, 7, and 17 KEGG pathways in the cochlea, auditory cortex, and hippocampus, respectively. In the long term (12 weeks) from noise-induced hearing loss, GOs and KEGG pathways related to apoptosis or inflammation persisted more actively in the order of hippocampus, auditory cortex, and cochlea. Discussion: This implies that the neurodegenerative effects of noise exposure persist more longer time in the central regions.

Comparison of hearing outcomes in patients with congenital aural atresia managed with canaloplasty and bone conduction hearing devices.

BACKGROUND: Treatment options for congenital aural atresia (CAA) include canaloplasty and implantation of an osseointegrated bone conduction device (OBCD). Few studies have compared hearing outcomes in these two treatment methods. OBJECTIVES: Hearing outcomes and revision surgery rates were compared in CAA patients managed by canaloplasty and surgically implanted OBCD. METHODS: This study retrospectively analyzed 36 patients with CAA at a single institution. The same surgeon performed canaloplasty on 23 patients. Hearing outcomes before surgery as well as 3 and 6 months after surgery were compared to those of 13 patients with OBCD implantation. RESULTS: Postoperative hearing outcomes were better in the OBCD group, but the difference was not statistically significant. At 6-month follow-up, the hearing thresholds in the canaloplasty and OBCD group were 38.6 ± 21.4 and 31.9 ± 6.4 dB, respectively. The success rates 6 months after surgery were 75.0% in the canaloplasty group and 100% in the OBCD group. Two out of 23 patients in the canaloplasty group and 7 out of 13 patients in the OBCD group underwent revision surgery. CONCLUSION: In terms of hearing, the outcome was better with the OBCD compared to canaloplasty. Canaloplasty may be an alternative option in patients who refuse OBCD implantation.

Outcome of cochlear implantation in the worse ear of post-lingual asymmetric hearing loss: elucidation of prognostic markers.

BACKGROUND: Specific correlations between the outcomes of cochlear implantation (CI) and hearing thresholds of the both ears in post-lingual asymmetric hearing loss (AHL) patients were not clear. AIMS/OBJECTIVES: To identify the variables influencing the outcome of CI in post-lingual AHL patients. METHOD: We included 18 adult subjects who had CI in the worse ear due to post-lingual AHL with average hearing asymmetry of 36 dB. Speech perception scores were evaluated in the sound field with hearing aid on the better ear before CI, and with the cochlear implant in the worse ear at 3, 6, and 12 months after CI switch-on. RESULTS: Average increases in phonetically balanced word score, spondee word score, and everyday sentence score at 12 months from CI switch-on compared with those before CI were 38.9%p, 46.2%p, and 52.4%p, respectively. Multiple linear regression analysis showed that speech perception scores were negatively influenced by age at implantation and hearing threshold difference of both ears (HTD-Both) itself, rather than the worse or better ear hearing thresholds. CONCLUSIONS AND SIGNIFICANCE: Post-lingual AHL subjects with high average hearing asymmetry can benefit from CI in the worse ear, while CI outcomes can be adversely influenced by HTD-Both and age at implantation both in the short- and long-term follow-up.

Associations between Particulate Matter and Otitis Media in Children: A Meta-Analysis.

Particulate matter (PM), a primary component of air pollution, is a suspected risk factor for the development of otitis media (OM). However, the results of studies on the potential correlation between an increase in the concentration of PM and risk of developing OM are inconsistent. To better characterize this potential association, a meta-analysis of studies indexed in three global databases (PubMed, EMBASE, and The Cochrane Library) was conducted. These databases were systematically screened for observational studies of PM concentration and the development of OM from the time of their inception to 31 March 2020. Following these searches, 12 articles were analyzed using pooled odds ratios generated from random-effects models to test for an association between an increased concentration of PM and the risk of developing OM. The data were analyzed separately according to the size of particulate matter as PM2.5 and PM10. The pooled odds ratios for each 10 µg/m3 increase in PM2.5 and PM10 concentration were 1.032 (95% confidence interval (CI), 1.005-1.060) and 1.010 (95% CI, 1.008-1.012), respectively. Specifically, the pooled odds ratios were significant within the short-term studies (PM measured within 1 week of the development of OM), as 1.024 (95% CI, 1.008-1.040) for PM2.5 concentration and 1.010 (95% CI, 1.008-1.012) for PM10 concentration. They were significant for children under 2 years of age with pooled odds ratios of 1.426 (95% CI, 1.278-1.519) for an increase in the concentration of PM2.5. The incidence of OM was not correlated with the concentration of PM, but was correlated with an increase in the concentration of PM. In conclusion, an increase in the concentration of PM2.5 is more closely associated with the development of OM compared with an increase in the concentration of PM10; this influence is more substantial in shorter-term studies and for younger children.

Clinical Characteristics of Patients with Cochlear Fistulas Caused by Chronic Otitis Media with Cholesteatoma.

OBJECTIVES: To analyze the clinical characteristics of cochlear fistulas (CFs) and propose a new fistula classification system with regard to the cochlea. MATERIALS AND METHODS: A retrospective chart review was conducted between January 2008 and December 2015 to identify patients who had undergone surgery for cholesteatoma with an associated CF. The following data were collected: preoperative symptoms, findings of temporal bone computed tomography (TBCT), fistula stage, cholesteatoma classification, surgical technique, and pre- and postoperative pure-tone audiometry. RESULTS: We analyzed a total of 159 patients, out of which 9 (5.7%) were diagnosed with a CF. The average duration of the chronic otitis media was 19.8 years. Cholesteatomas that induced CF rarely existed in the nonaggressive state; recurrent otorrhea was observed in all but one of our subjects. All the patients with CF had a distinct origin of cholesteatoma that developed from the retraction of posterior pars tensa; further, 88.9% cholesteatomas extended to and filled the sinus tympani. Preoperative audiometry revealed total hearing loss in 4 (44.4%) patients. Further, five patients with residual hearing before surgery had stage I fistulas, and the bone conduction thresholds remained stable after surgery. CONCLUSION: Cochlear fistulas were often detected in patients with (1) a history of chronic otitis media (exceeding 10 years), (2) frequently recurring otorrhea, and (3) pars tensa cholesteatomas that extended to the posterior mesotympanum and filled the sinus tympani. Such patients can suffer from potentially severe and irreparable sensorineural hearing loss.

Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.

Natural Course of Unilateral Vocal Fold Paralysis and Optimal Timing of Permanent Treatment.

Importance: Permanent surgical treatment for unilateral vocal fold paralysis (UVFP) should be performed when further neural recovery is improbable. Conservative delay of the surgical procedure may cause unnecessary deterioration of the patient's quality of life. Knowledge of the natural course of UVFP is important for better management and counseling. Objective: To evaluate the natural course of UVFP, focusing on the recovery time according to the injury level to assess the optimal timing for permanent surgical intervention. Design, Setting, and Participants: This retrospective case series enrolled 1264 patients with UVFP who visited the voice clinic of Seoul National University Hospital, Seoul, Korea, from November 1, 2005, through December 31, 2016. Medical records and stroboscopic video images were reviewed to obtain data on demographic characteristics, vocal fold movement, onset and recovery time, follow-up duration, and cause. Cases of UVFP were classified into 5 groups based on the location of injury: distal to the thyroid level, thyroid level, esophagus and mediastinum level, heart and lung level, and proximal to the thorax level. Data analysis was performed from January 23, 2018, to May 21, 2018. Main Outcomes and Measures: Recovery of vocal fold movement defined as more than vocal fold twitching confirmed by stroboscopy video images, estimated injury level, and start time of recovery. The recovery time was analyzed according to age, sex, paralytic side, and 5 injury levels. Results: Of 1264 eligible patients with UVFP (655 [51.8%] male; median age, 56 years [range, 1-90 years]), 208 had evidence of recovery with the recovery time relatively accurate. The maximum recovery time for the group with distal to the thyroid-level injury was 120 days; the group with thyroid-level injury, 157 days; the group with esophagus and mediastinum-level injury, 244 days; the group with heart and lung-level injury, 328 days; and the group with proximal to the thorax-level injury, 333 days with the exception of 1 outlier value (482 days). Recovery time did not differ according to age, sex, or paralytic side. As distance between the vocal fold and injury level increased, the maximum recovery time increased, plateauing at 1 year. Among the patients who showed recovery of the vocal fold movement, most patients with injuries distal to or at the level of the thyroid recovered within 6 months, whereas those with injury more distant from the vocal fold recovered within approximately 1 year. Conclusions and Relevance: A linear association between injury level and maximum recovery time was observed. The findings suggest that the decision to proceed with permanent phonosurgical treatment should be based on the level of injury associated with UVFP.

Nasopharyngeal Width and Its Association With Sleep-Disordered Breathing Symptoms in Children.

OBJECTIVES: Although adenotonsillar hypertrophy is the main cause of sleep-disordered breathing in children, surrounding anatomic factors, such as the width of the nasopharynx, can affect upper airway patency. However, there have been no reports of the association of nasopharyngeal width with sleep-disordered breathing in children. This study was undertaken to measure nasopharyngeal width in children undergoing adenotonsillectomy for sleep-disordered breathing and to investigate the clinical implications of this factor. METHODS: This was a retrospective study with a follow-up period of 1 year, performed at a tertiary referral center. We reviewed the operative records of children who underwent adenotonsillectomy at our center for symptoms of sleepdisordered breathing, such as snoring, apnea, and mouth breathing. The nasopharyngeal width was measured immediately before adenotonsillectomy, which was performed under general anesthesia with a microscopy-assisted mirror view. Adenotonsillar hypertrophy was graded on a four-point scale, and symptoms of sleep-disordered breathing were evaluated by using the Korean version of the Obstructive Sleep Apnea-18 questionnaire before and after surgery. The relationships between the average nasopharyngeal width and patient age and sex, adenotonsillar hypertrophy, and the Korean version of the Obstructive Sleep Apnea-18 score were analyzed. RESULTS: The study included 549 children (343 boys) with a mean age of 6.0 years (range, 2 to 11 years). The average nasopharyngeal width was 11.9 mm (range, 7.0 to 18.0 mm) and increased with age (range, 11.2 to 13.3; ß=0.264; P< 0.001). At 1 year after surgery, children with a greater nasopharyngeal width at the time of surgery exhibited additional improvements in symptoms of obstruction relative to those at 1 month after surgery. CONCLUSION: The average nasopharyngeal width in children is approximately 11.9 mm and exhibits a slight increase with age. The width of the nasopharynx may be a factor associated with the degree of improvement in symptoms of sleepdisordered breathing after adenotonsillectomy.

Involvement of the Internal Auditory Canal in Subjects With Cochlear Otosclerosis: A Less Acknowledged Third Window That Affects Surgical Outcome.

OBJECTIVE: To investigate the effects of cavitating lesions involving the internal auditory canal (IAC) in subjects with cochlear otosclerosis with regard to poststapedotomy hearing outcome. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A retrospective chart review of 134 subjects with otosclerosis treated from January 2011 to June 2017 at Seoul National University Bundang Hospital was conducted. Sixteen subjects (23 ears) with temporal bone computed tomography (TBCT)-confirmed cochlear otosclerosis who underwent stapedotomy were included in the study. MAIN OUTCOME MEASURES: Pure tone audiometry (PTA) (i.e., air and bone conduction; AC and BC, respectively) thresholds and air-bone gap (ABG), measured at 6 months postoperatively were compared between cochlear otosclerosis with and without IAC involvement (IAC group and non-IAC group, respectively). RESULTS: A total of 14 of 23 ears showed involvement of the IAC. There were no significant differences in age, side of otosclerosis, or preoperative hearing threshold between the two groups. The mean postoperative AC and BC thresholds and ABG of the IAC group were significantly poorer (45.7 dB, 33.8 dB, and 11.8 dB, respectively) than those of the nonIAC group (24.1 dB, 20.0 dB, and 4.1 dB, respectively). CONCLUSIONS: Cochlear otosclerosis with cavitating lesions involving the IAC showed significantly poorer postoperative audiological outcomes than those without any cavitating lesion. Cavitation extending to the IAC may act as a third window providing a route for sound energy shunting, and thus precluding successful hearing outcome in some subjects with cavitating otosclerosis after stapedotomy.

Cochlear Implantation in Postlingually Deaf Adults is Time-sensitive Towards Positive Outcome: Prediction using Advanced Machine Learning Techniques.

Given our aging society and the prevalence of age-related hearing loss that often develops during adulthood, hearing loss is a common public health issue affecting almost all older adults. Moderate-to-moderately severe hearing loss can usually be corrected with hearing aids; however, severe-to-profound hearing loss often requires a cochlear implant (CI). However, post-operative CI results vary, and the performance of the previous prediction models is limited, indicating that a new approach is needed. For postlingually deaf adults (n de120) who received CI with full insertion, we predicted CI outcomes using a Random-Forest Regression (RFR) model and investigated the effect of preoperative factors on CI outcomes. Postoperative word recognition scores (WRS) served as the dependent variable to predict. Predictors included duration of deafness (DoD), age at CI operation (ageCI), duration of hearing-aid use (DoHA), preoperative hearing threshold and sentence recognition score. Prediction accuracy was evaluated using mean absolute error (MAE) and Pearson's correlation coefficient r between the true WRS and predicted WRS. The fitting using a linear model resulted in prediction of WRS with r = 0.7 and MAE = 15.6 ± 9. RFR outperformed the linear model (r = 0.96, MAE = 6.1 ± 4.7, p < 0.00001). Cross-hospital data validation showed reliable performance using RFR (r = 0.91, MAE = 9.6 ± 5.2). The contribution of DoD to prediction was the highest (MAE increase when omitted: 14.8), followed by ageCI (8.9) and DoHA (7.5). After CI, patients with DoD < 10 years presented better WRSs and smaller variations (p < 0.01) than those with longer DoD. Better WRS was also explained by younger age at CI and longer-term DoHA. Machine learning demonstrated a robust prediction performance for CI outcomes in postlingually deaf adults across different institutes, providing a reference value for counseling patients considering CI. Health care providers should be aware that the patients with severe-to-profound hearing loss who cannot have benefit from hearing aids need to proceed with CI as soon as possible and should continue using hearing aids until after CI operation.

Association of Coffee Consumption with Hearing and Tinnitus Based on a National Population-Based Survey.

Coffee is the one of the most common beverages worldwide and has received considerable attention for its beneficial health effects. However, the association of coffee with hearing and tinnitus has not been well studied. The aim of this study was to investigate the association of coffee with hearing and tinnitus based on a national population-based survey. We evaluated hearing and tinnitus data from the 2009⁻2012 Korean National Health and Nutrition Examination Survey and their relationship with a coffee consumption survey. All patients underwent a medical interview, physical examination, hearing test, tinnitus questionnaire and nutrition examination. Multivariable logistic regression models were used to examine the associations between coffee and hearing loss or tinnitus. We evaluated 13,448 participants (≥19 years) participants. The frequency of coffee consumption had a statistically significant inverse correlation with bilateral hearing loss in the 40⁻64 years age group. Daily coffee consumers had 50⁻70% less hearing loss than rare coffee consumers, which tended to be a dose-dependent relationship. In addition, the frequency of coffee consumption had an inverse correlation with tinnitus in the 19⁻64 years age group but its association was related with hearing. Brewed coffee had more of an association than instant or canned coffee in the 40⁻64 years age group. These results suggest a protective effect of coffee on hearing loss and tinnitus.

Corrigendum: A Quantitative Electroencephalography Study on Cochlear Implant-Induced Cortical Changes in Single-Sided Deafness with Tinnitus.

[This corrects the article on p. 210 in vol. 11, PMID: 28572760.].

Comparison of Free-Beam- and Fiber-Type CO2 Laser Delivery Systems in Stapes Surgery.

BACKGROUND AND OBJECTIVES: A free-beam-type CO2 laser, which use a micromanipulator mounted on a microscope as the delivery system, has the merit of not being affected by hand tremor at the time of shooting. However, this delivery system has several disadvantages, including a restricted operation range and a risk of incorrect focusing. A fiber-type CO2 laser uses a hand-held delivery system and has the opposite merits and demerits. We compared the results of stapes surgery with free-beam and fiber type delivery systems. SUBJECTS AND METHODS: The study enrolled 36 patients who underwent stapedotomy with free-beam- (n=26) or fiber- (n=10) type CO2 lasers. The air-bone (AB) gap closure, bone conduction (BC) change, and operating time were evaluated. The AB gap closure was calculated by subtracting the preoperative BC thresholds from the postoperative air conduction thresholds. The BC change was calculated by subtracting the postoperative BC thresholds from the preoperative BC thresholds. RESULTS: The mean operating time was significantly (p=0.035) shorter in the fiber-type group (72.5±8.2 min) than in the free-beam-type group (80.5±11.4 min). The mean AB gap closure did not differ significantly (p=0.297) between the free-beamand fiber-type groups (5.8±10.1 and 1.4±6.8 dB, respectively). The mean BC change did not differ significantly (p=0.873) between the free-beam- and fiber-type groups (2.4±6.9 and 2.8±5.3 dB, respectively). The hearing outcomes did not differ significantly between the two groups. CONCLUSIONS: Operating times were significantly shorter using the fiber-type CO2 laser, while hearing outcomes did not differ significantly between the two groups.

A Quantitative Electroencephalography Study on Cochlear Implant-Induced Cortical Changes in Single-Sided Deafness with Tinnitus.

The mechanism of tinnitus suppression after cochlear implantation (CI) in single-sided deafness (SSD) is not fully understood. In this regard, by comparing pre- and post-CI quantitative electroencephalography (qEEG), we explored cortical changes relevant to tinnitus improvement. In SSD patients who underwent CI, qEEG data were collected: (1) before CI, (2) 6 months post-operatively with CI-on, and (3) 30 min after CI-off and source-localized cortical activity/functional connectivity analyses were performed. Compared to the pre-operative baseline, the CI-on condition demonstrated significantly decreased activity in the right auditory- and orbitofrontal cortices (OFC) for the delta frequency band as well as decreased connectivity between the auditory cortex/posterior cingulate cortex for the delta/beta2 bands. Meanwhile, compared to the CI-off condition, the CI-on condition displayed decreased activity in the right auditory cortices/OFC for the delta band, and in bilateral auditory cortices, left inferior frontal cortex/OFC for the gamma band. However, qEEG analyses showed no significant differences between the CI-off and baseline conditions. CI induced overall decreased cortical activity and functional connectivity. However, judging from no differences between the CI-off and baseline conditions, CI-induced cortical activity and functional connectivity changes are not by cortical plastic changes, but by dynamic peripheral reafferentation.

The mechanism behind the selective metal nanoscale etch method for precise metal nanopatterning.

This paper reports for the first time the exact mechanism of the selective metal nanoscale etch method (SMNEM), which is a simply controllable and cost-effective approach for metal nanoscale etching and size reduction. This method is based on the galvanic displacement, Kirkendall effect, and selective etching. The size reduction is linearly controlled by the galvanic displacement in the early stage (1 min). In the later stage, a Kirkendall void is formed between the Ni and Au layer, which is well understood from Fick's law of diffusion. As matching with the experimental results, Ni nanowires with 30 +/- 4 nm width and 50 +/- 7 nm height were easily fabricated from nanostructures with 150 +/- 3 nm width and 110 +/- 2 nm height. The morphology and position of the Ni nanostructures are all predetermined by their initial conditions. Also achieved was the fabrication of complicated three-dimensional nanostructures such as Au nanowires and nanochannels from reduced Ni nanowires by a full replacement reaction.

Microenvironment-controlled encapsulation (MiCE) process: effects of PLGA concentration, flow rate, and collection method on microcapsule size and morphology.

PURPOSE: To evaluate the real-time effects of formulation and instrumental variables on microcapsule formation via natural jet segmentation, a new microencapsulation system termed the microenvironment-controlled encapsulation (MiCE) process was developed. METHODS: A modified flow cytometer nozzle hydrodynamically focuses an inner drug and outer polymer solution emanating from a coaxial needle assembly into a two-layer compound jet. Poly(lactic-co-glycolic acid) (PLGA) dissolved in a water-miscible organic solvent resulted in formation of reservoir-type microcapsules by interfacial phase separation induced at the boundary between the PLGA solution and aqueous sheath. RESULTS: The MiCE process produced microcapsules with mean diameters ranging from 15-25 microm. The resultant microcapsule size distribution and number of drug cores existing within each microcapsule was largely influenced by the PLGA concentration and microcapsule collection method. Higher PLGA concentrations yielded higher mean diameters of single-core microcapsules. Higher drug solution flow rates increased the core size, while higher PLGA solution flow rates increased the PLGA film thickness. CONCLUSION: The MiCE microencapsulation process allows effective monitoring and control of the instrumental parameters affecting microcapsule production. However, the microcapsule collection method in this process needs to be further optimized to obtain microcapsules with desired morphologies, precise membrane thicknesses, high encapsulation efficiencies, and tight size distributions.