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Objectives. Balloon dilation of the Eustachian tube (BDET) is widely recognized as a minimally invasive treatment for obstructive Eustachian tube dysfunction (ETD). We employed a Delphi consensus methodology to develop recommendations for the clinical management of BDET in cases of obstructive ETD. Methods. A Delphi panel consisting of 26 expert physicians specializing in otology participated in two rounds of anonymous, iterative questionnaires. Consensus was defined as agreement from ≥70% of the panelists on a recommendation, while disagreement was defined as

Background: Pain associated with subjective tinnitus is known to be alleviated by treatments using a repetitive transcranial magnetic stimulation (rTMS). However, the mechanisms underneath are still on debate. We investigated the mechanism of tinnitus alleviation using time–frequency analyses. Methods: Twenty-four patients were randomly assigned to the dual-site stimulation group (temporal and frontal stimulation, TF), singlesite stimulation group (temporal stimulation, T), or sham stimulation group. An age-matched control group was also included (n = 12). Electroencephalography (EEG) was recorded and patient data were analyzed before and after treatment. Results: A frontal increase in EEG power was observed in the alpha (8-12 Hz) frequency band domain after treatment; this increase was most pronounced in the TF group, followed by the T group. The TF and T groups showed increased alpha power in the fronto-central channels only in the silent period between paired-pulse tones. The TF and T groups showed decreases in alpha power in the temporal region, particularly in the neural response to the first of the paired-pulse tones. The difference in tinnitus handicap index between pre- and post-treatment was positively correlated with the alpha power of the silent period in the frontal and fronto-central channels. Conclusion: Dual-site stimulation showed the greatest alleviation of tinnitus-related discomfort, followed by single-site stimulation. Additionally, the modulation of alpha power was prominent in the active stimulation groups. Low frequency rTMS can alleviate tinnitus by increasing alpha band power and reducing hyperactivity.

Objectives. Facial nerve sacrifice during radical parotidectomy can impair quality of life. This study assessed the effectiveness of single-stage facial reanimation surgery performed concurrently with radical parotidectomy in restoring facial function. Methods. A retrospective analysis was conducted on patients who underwent single-stage facial reanimation combined with radical parotidectomy. The techniques employed included selective reinnervation and orthodromic temporalis tendon transfer. Outcomes were evaluated using the modified House-Brackmann and Terzis grading systems, Emotrics facial assessment, and the Facial Disability Index (FDI). Results. Among the 13 patients studied (median age, 54 years; 69% male), 10 underwent selective reinnervation. Of these, nine patients demonstrated improvement, achieving House-Brackmann grade III and Terzis grade 4 or 5. The other three patients underwent tendon transfer and achieved moderate functional outcomes. Emotrics analysis revealed balanced facial symmetry in the selective reinnervation group. Furthermore, FDI scores indicated satisfactory physical and social/well-being functions. Conclusion. Single-stage facial reanimation effectively restores facial function in patients undergoing radical parotidectomy. This approach offers meaningful benefits in the early recovery of facial function.

Abstract The relationship between tinnitus and body composition in specific regions has not been extensively investigated. This study aimed to identify associations between tinnitus and body composition. Individuals with data on physical and otological examination findings, and bioelectrical impedance analysis were included from the ninth Korea National Health and Nutritional Examination Survey. They were divided into a tinnitus group and a non-tinnitus group. Participants with tinnitus were further classified into acute or chronic tinnitus group. The tinnitus group showed significantly higher body fat percentages in each region (arms: P = 0.014; legs: P = 0.029; trunk: P = 0.008; whole body: P = 0.010) and waist circumference (P = 0.007) than the non-tinnitus group, and exhibited lower leg muscle percentage (P = 0.038), total body fluid percentage (P = 0.010), and intracellular fluid percentage (P = 0.009) than the non-tinnitus group in men. Furthermore, men with chronic tinnitus showed a significantly higher trunk fat percentage (P = 0.015) and waist circumference (P = 0.043), and lower intracellular fluid percentage (P = 0.042) than their counterparts without tinnitus. No significant differences in body composition were observed among the groups in the female population. In men, body composition may be associated with tinnitus.

Abstract While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-l-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA, P

Abstract Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method.Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations.Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27 days) compared to the saline + D group (1.1 ± 0.3 days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group.Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.

ObjectivesSymptomatic vestibulopathy impairs patients' lives. However, few studies have explored the lives of patients with compensated or asymptomatic vestibulopathy. This study investigated the quality of life (QOL), psychological health, and physical function of patients with vestibulopathy.Materials and methodsUsing the eighth Korea National Health and Nutrition Examination Survey database, we included individuals with data on demographic factors, diabetes, hypertension, dizziness experiences, pure-tone audiometry, video head impulse test (vHIT), Health-related Quality of Life Instrument with 8 Items, General Anxiety Disorder 7-item scale, stress, and walking and sitting times. Participants were classified into the following groups: an uncompensated group with abnormal vHIT result and chronic dizziness, a compensated group with abnormal vHIT result and a history of dizziness, an asymptomatic group with abnormal vHIT result and no history of dizziness, and a normal group without abnormal vHIT result or a history of dizziness.ResultsUncompensated vestibulopathy was more common in older individuals and women. The uncompensated group showed impairments in climbing stairs (P < 0.001), pain (P < 0.001), vitality (P = 0.001), working (P < 0.001), depression (P < 0.001), sleep (P = 0.001), happiness (P = 0.002), anxiety (P = 0.006), and stress (P = 0.003). The compensated group showed deficits in pain (P < 0.001), work (P = 0.006), sleep (P = 0.001), and happiness (P = 0.001). The asymptomatic group had no deficits in QOL, psychological health, or physical function. These tendencies were similar after controlling for age and gender.ConclusionVestibulopathy with a history of dizziness has a long-lasting impact on QOL and emotional status, even after compensation. Uncompensated vestibulopathy has a significant effect on QOL and mental health. Notably, though, the compensated group also showed a reduction in QOL. Appropriate interventions for each category of patients should be provided based on their impaired functions.

BackgroundMany endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls.MethodsGadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age−/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10–15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in μL) of the endolymphatic and perilymphatic spaces.ResultsFor the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls.ConclusionCompared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Abstract Performing an accurate canalith repositioning procedure (CRP) is important for treating benign paroxysmal positional vertigo, because inadequate rotational head angles can result in ineffective otolith mobilization and consequent treatment failure. Specialists-guided Epley maneuver reportedly had mean errors of 13.7°–24.4° while they were significantly larger (40.0°–51.5°) when self-administered. Similar results were obtained for the Barbeque maneuver: mean errors were 9.2°–13.0° by the specialists while they were significantly larger (22.9°–28.6°) when self-administered. Our study aimed to validate the feasibility of an inertial measurement unit sensor-based CRP (IMU-CRP) by analyzing the differences in accuracy in the rotational angles, comparing them with education-based conventional CRP (EDU-CRP). A pilot validation was also performed by analyzing the treatment success rate of IMU-CRP in patients with BPPV. This single-institution prospective, comparative effectiveness study examined 19 participants without active vertigo or prior knowledge of benign paroxysmal positional vertigo and CRP. Participants conducted the Epley and Barbeque roll maneuvers without and with auditory guidance (EDU-CRP vs. IMU-CRP, respectively) twice, and head rotation accuracies were compared. Differences in target angles based on the American Academy of Otolaryngology-Head and Neck Surgery guidelines were considered errors. For BPPV participants, treatment success was assessed based on the presence or absence of nystagmus, vertigo, and dizziness. For all the Epley and Barbeque roll maneuvers steps, the absolute errors were smaller for IMU- than for EDU-CRPs, with significant differences in steps 2–4 and 3–6 of the Epley and Barbeque roll maneuvers, respectively. A learning effect was found in steps 4 and 5 of the Barbeque roll maneuver but not in the Epley maneuver. The treatment success rates after 1 h were 71.4% and 100% for the Epley and Barbeque roll maneuvers, respectively. Real-time feedback on head rotation angles induced more appropriate movements in the Epley and Barbeque roll maneuvers. A guiding device based on head monitoring providing real-time auditory feedback may increase the self-administered CRP success rates in treating benign paroxysmal positional vertigo.

Everyday speech communication often occurs in environments with background noise, and the impact of noise on speech recognition can vary depending on factors such as noise type, noise intensity, and the listener’s hearing ability. However, the extent to which neural mechanisms in speech understanding are influenced by different types and levels of noise remains unknown. This study aims to investigate whether individuals exhibit distinct neural responses and attention strategies depending on noise conditions. We recorded electroencephalography (EEG) data from 20 participants with normal hearing (13 males) and evaluated both neural tracking of speech envelopes and behavioral performance in speech understanding in the presence of varying types of background noise. Participants engaged in an EEG experiment consisting of two separate sessions. The first session involved listening to a 12-min story presented binaurally without any background noise. In the second session, speech understanding scores were measured using matrix sentences presented under speech-shaped noise (SSN) and Story noise background noise conditions at noise levels corresponding to sentence recognitions score (SRS). We observed differences in neural envelope correlation depending on noise type but not on its level. Interestingly, the impact of noise type on the variation in envelope tracking was more significant among participants with higher speech perception scores, while those with lower scores exhibited similarities in envelope correlation regardless of the noise condition. The findings suggest that even individuals with normal hearing could adopt different strategies to understand speech in challenging listening environments, depending on the type of noise.

Abstract To assess the safety and efficacy of navigation-guided balloon Eustachian tuboplasty (BET) compared to medical management (MM) alone in patients with chronic Eustachian tube dilatory dysfunction (ETD). This is a prospective, multicenter, 1:1 parallel-group, randomized controlled trial (RCT). It aims to assess the efficacy of navigation-guided BET compared to MM alone in patients with chronic ETD. The primary outcome measure was an improvement in the Eustachian tube dysfunction questionnaire (ETDQ)-7 score at the 6-week follow-up compared with baseline. Secondary outcome measures included changes in the signs and symptoms during the follow-up, changes in the score for each subcategory of ETDQ-7, type of tympanometry, pure tone audiometry, and the availability of a positive modified Valsalva maneuver. Navigation-guided BET was safely performed in all patients. A total of 38 ears of 31 patients (19 ears of 16 patients in the BET group and 19 ears of 15 patients in the control group) completed the planned treatment and 6 weeks of follow-up. More patients in the BET group (1.99 ± 0.85) had less symptomatic dysfunction than in the control group (3.40 ± 1.29) at 6 weeks post-procedure (P = 0.001). More patients experienced tympanogram improvement in the BET group at 6 weeks compared to the control group (36.5% vs. 15.8%) with a positive modified Valsalva maneuver (36.6% vs. 15.8%, P = 0.014). Additionally, air–bone gap change was significantly decreased in the BET group compared to the control group at the 6-week follow-up visit (P = 0.037). This prospective, multicenter, RCT study suggests that navigation-guided BET is a safe and superior treatment option compared to MM alone in patients with chronic ETD.

Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.

BackgroundTinnitus retraining therapy (TRT) is a standard treatment for tinnitus that consists of directive counseling and sound therapy. However, it is based on face-to-face education and a time-consuming protocol. Smart device–based TRT (smart-TRT) seems to have many advantages, but the efficacy of this new treatment has been questioned. ObjectiveThe aim of this study was to compare the efficacy between smart-TRT and conventional TRT (conv-TRT). MethodsWe recruited 84 patients with tinnitus. Results were compared between 42 patients who received smart-TRT and 42 control participants who received conv-TRT. An interactive smart pad application was used for directive counseling in the smart-TRT group. The smart pad application included detailed education on ear anatomy, the neurophysiological model of tinnitus, concept of habituation, and sound therapy. The smart-TRT was bidirectional: There were 17 multiple choice questions between each lesson as an interim check. The conv-TRT group underwent traditional person-to-person counseling. The primary outcome measure was the Tinnitus Handicap Inventory (THI), and the secondary outcome measure was assessed using a visual analogue scale (VAS). ResultsBoth treatments had a significant treatment effect, which comparably improved during the first 2 months. The best improvements in THI were –23.3 (95% CI –33.1 to –13.4) points at 3 months and –16.8 (95% CI –30.8 to –2.8) points at 2 months in the smart-TRT group and conv-TRT group, respectively. The improvements on the VAS were also comparable: smart-TRT group: –1.2 to –3.3; conv-TRT: –0.7 to –1.7. ConclusionsTRT based on smart devices can be an effective alternative for tinnitus patients. Considering the amount of time needed for person-to-person counseling, smart-TRT can be a cost-effective solution with similar treatment outcomes as conv-TRT.

Abstract Meniere’s disease is thought to be a disorder of the inner ear function, affected by genetic and environmental factors. Several recent studies have shown that air pollution could affect middle and inner ear diseases. The purpose of this study was to investigate the relationship between the Meniere’s disease occurrence and air pollution status in Korea. This study used a time-stratified case-crossover design. Hospital visit data by Meniere’s disease were collected from the Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Daily air pollution data for sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and particulate matter (PM10: ≤ 10 μm in diameter, and PM2.5: ≤ 2.5 μm in diameter) were collected from the National Ambient air quality Monitoring Information System (NAMIS) database. We used two-stage analysis to assess the association between degree of air pollution and the occurrence of Meniere’s disease. In the first stage, region-specific analysis was conducted to estimate the odds ratios (ORs) of Meniere’s disease risk associated with each air pollutant exposure by using conditional logistic regression for matched case–control sets in 16 regions. In the second stage, region-specific ORs from the first stage were combined and the pooled effect estimates were derived through fixed and random effect meta-analysis. Subgroup analysis was conducted for age, sex, seasonality, and urbanization of residence. In total, 29,646 (32.1% males and 67.9% females) Meniere’s disease cases were identified from Korea NHIS-NSC database between 2008 and 2015. Overall, SO2, NO2, CO, and PM10 showed significant correlation with Meniere’s disease risk at immediate lags, and weaker correlation at delayed lags, whereas O3 showed slightly negative correlation at the immediate lag (lag0) and PM2.5 did not show strong correlation (SO2: 1.04 [95% confidence interval: 1.01, 1.06]; NO2: 1.08 [1.06, 1.11]; CO: 1.04 [1.02, 1.06]; O3: 0.96 [0.93, 0.99]: statistically significant ORs at lag0 are listed). These positive and negative associations between Meniere’s disease and each air pollutant were generally stronger in the age of 40–64, female, summer (June–August) season, and urban subgroups. Our results showed that hospital visits for Meniere’s disease were associated with the measured concentrations of ambient air pollutants SO2, NO2, CO, and PM10. Further studies are required to confirm these associations and find their mechanisms.

Lymphangiogenesis and angiogenesis might have significant involvement in the pathogenesis of otitis media with effusion. This study investigated the effect of diesel exhaust particles (DEP) on inflammation and lymphangiogenesis in a mouse model of acute otitis media (AOM). BALB/c mice were injected with LPS and exposed to 100 µg/m3 DEP. The mice were divided into four groups: control (no stimulation), AOM, AOM + DEP, and DEP + AOM.The effects of DEP inhalation pre- and post-DEP induction were estimated based on measurements of the auditory brainstem response, mRNA levels of lymphangiogenesis-related genes and cytokines, and histology of the middle ear. Cell viability of human middle ear epithelial cells decreased in a dose-response manner at 24 and 48 hours post-DEP exposure. DEP alone did not induce AOM. AOM-induced mice with pre- or post-DEP exposure showed thickened middle ear mucosa and increased expression of TNF-α and IL1-β mRNA levels compared to the control group, but increased serum IL-1β levels were not found in the AOM + Post DEP. The mRNA expression of TLR4, VEGFA, VEGFAC, and VEGFR3 was increased by pre-AOM DEP exposure.The expression of VEFGA protein was stronger in the AOM + Post DEP group than in any other group. The expression of CD31 and CD45 markers in the mouse middle ear tissue was higher in the Pre DEP + AOM group than in the AOM group. This result implies that pre-exposure to DEP more strongly increases inflammation and lymphangiogenesis in a mouse model of acute otitis media.

Clinically there is no effective method to prevent drug induced hearing loss in patients undergoing chemotherapy and anti-tuberculosis therapy. In this study, we developed an intratympanic (IT) local drug delivery vehicle featuring hyaluronic acid-based dual viscosity mixture encapsulation of dexamethasone (D), named dual-vehicle + D, and assessed its protective effect in ototoxic hearing loss. We assessed the residence time, biocompatibility, and treatment outcome of the novel vehicle compared with the current standard of care vehicle (saline) and control conditions. The hearing threshold and hair cell count were significantly better in the dual-vehicle + D group compared to the other two groups. The final hearing benefit in the dual-vehicle group was approximately 25–35 dB, which is significant from a clinical point of view. Morphologic evaluation of the cochlear hair cells also supported this finding. Due to the high viscosity and adhesive property of the vehicle, the residence time of the vehicle was 49 days in the dual-vehicle + D group, whereas it was less than 24 h in the saline + D group. There was no sign of inflammation or infection in all the animals. From this study we were able to confirm that dual viscosity mixture vehicle for IT D delivery can effectively block ototoxic hearing loss.

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages.Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods.Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear.Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.

Objective. Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. Materials and methods. Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. Results. The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. Conclusion. Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

Intratympanic (IT) gadolinium (Gd) injection is one method of delivering Gd into the inner ear to evaluate the amount of endolymphatic hydrops (EH) using magnetic resonance imaging (MRI). As Gd is usually prepared in a fluid form mixed with saline, Gd injected into the middle ear drains easily through the Eustachian tube within several hours. High-molecular-weight (hMW) hyaluronic acid (HA) is an ideal vehicle for IT Gd due to its viscous and adhesive properties. The present study was performed to elucidate whether novel hMW HA is superior to conventional HA in delivering Gd into the inner ear in the short term. The second aim was to verify the long-term Gd delivery efficiency of hMW HA compared to the standard-of-care vehicle (saline). IT Gd injection and 3D T1-weighted MRI were performed in 13 rats. For the short-term study (imaging after 1, 2, and 3 h), the left ear was treated with hMW HA+Gd and the right ear with conventional HA+Gd. For the long-term study (imaging after 1, 2, 3, and 4 h, 1 – 3 days, and 7 – 10 days), the left ear was treated with hMW HA+Gd and the right ear with saline+Gd. Signal intensities (SIs) in the scala tympani (ST) and scala vestibuli (SV) were quantified. Compared to conventional HA, signal enhancement was 2.3 – 2.4 times greater in the apical and middle turns after hMW HA+Gd injection (SV at 1 h). In comparison to the standard-of-care procedure, the SI was not only greater in the short term but the higher SI also lasted for a longer duration. On days 7 – 10 after IT Gd delivery, the SI in the basal turn was 1.9 – 2.1 times greater in hMW HA+Gd-treated ears than in saline IT Gd-treated ears. Overall, hMW HA may be a useful vehicle for more efficient IT Gd delivery. Gd enhancement in the cochlea improved approximately two-fold when hMW HA was used. In addition, this greater enhancement lasted for up to 7 – 10 days. Repeated MRI of EH may be possible for several days with a single IT hMW HA+Gd delivery.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Abstract Unilateral vestibular deafferentation (UVD) interrupts afferent signals from one side, resulting in an imbalance of the resting activity between bilateral vestibular nuclei. Vestibular compensation is the process of balancing the resting activity to reestablish homeostasis. Here, we investigated microRNAs (miRNAs) that regulate vestibular compensation using the Sprague–Dawley rat. After determining the progression of vestibular compensation following UVD, microarray analysis was performed and nine miRNAs were selected as candidates. Following validation by quantitative reverse transcription-PCR, three miRNAs remained. We assessed the effect of these miRNAs on vestibular compensation using miRNA oligomers. We compared the results of the rotarod test and 5-bromo-2′-deoxyuridine immunohistochemistry following UVD between the control group and the groups in which the candidate miRNA oligomers were administered. Administration of miR-218a-5p, 219a-5p, and 221-3p oligomers significantly affected vestibular compensation. Target pathway analysis of these miRNAs supported our results. Our findings suggest that the miRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation.

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

Using behavioral evaluation of free recall performance, we investigated whether reverberation and/or noise affected memory performance in normal-hearing adults. Thirty-four participants performed a free-recall task in which they were instructed to repeat the initial word after each sentence and to remember the target words after each list of seven sentences, in a 2 (reverberation) × 2 (noise) factorial design. Pupil dilation responses (baseline and peak pupil dilation) were also recorded sentence-by-sentence while the participants were trying to remember the target words. In noise, speech was presented at an easily audible level using an individualized signal-to-noise ratio (95% speech intelligibility). As expected, recall performance was significantly lower in the noisy environment than in the quiet condition. Regardless of noise interference or reverberation, sentence- baseline values gradually increased with an increase in the number of words to be remembered for a subsequent free-recall task. Long reverberation time had no significant effect on memory retrieval of verbal stimuli or pupillary responses during encoding.

This study was aimed at investigating the effects of placenta-derived mesenchymal stem cells (PL-MSCs) on particulate matter- (PM-) exposed human middle ear epithelial cells (HMEECs). HMEECs were treated with 300 μg/ml PM for 24 hours. The PL-MSCs were cocultured with PM-treated HMEECs. Cells were harvested on days 0, 1, and 4, and the expression of the inflammatory genes TNFα, COX2, IL1β, IL6, and MUC5B in HMEECs and anti-inflammatory genes PTGES, TGFβ, and VEGF in PL-MSCs was examined by qRT-PCR. The culture media were collected to measure the secreted PGE2 level using an enzyme-linked immunosorbent assay. The mRNA expression of TNFα, COX2, IL1β, IL6, and MUC5B in HMEECs increased following PM treatment. PM-treated HMEECs cocultured with PL-MSCs showed alleviated inflammatory reactions represented by lower mRNA expression levels of MUC5B, TNFα, IL1β, and IL6 compared to monocultured PM-treated HMEECs. The mRNA expression levels of PGE2, TGFβ, and VEGF were elevated in cocultured PL-MSCs compared to those of control PL-MSCs. The medium of PM-treated HMEECs cocultured with PL-MSCs exhibited increased PGE2 levels. The increased inflammatory response in PM-treated HMEECs was reversed using PL-MSCs. The PGE2, TGFβ, and VEGF were the mediators of the anti-inflammatory effects of PL-MSCs.

BACKGROUND:Otitis media (OM) is a major reason for children's visits to physicians and a major cause of their being treated with antibiotics. It not only causes economic burdens but also influences hearing, speech, and education. To our knowledge, no nationwide population-based study has assessed the association between air pollution and OM. Therefore, this study evaluated the association between air pollution levels and the incidence of OM. METHODS:We identified cases of OM that occurred in South Korea between January 2011 and December 2012 from the Korea National Health Insurance Service-National Sample Cohort database, and evaluated its relationship with five air pollutants: particulate matter (PM10, particulates ≤10 μm in diameter), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide, and carbon monoxide. Associations between the weekly incidence of OM and the five air pollutants were analyzed using generalized estimating equations. Conditional logistic regression analysis was used to obtain odds ratios (ORs) and their 99.9% Bonferroni-corrected confidence intervals after adjusting for gender, age, season, and region. RESULTS:We based our analysis on 160,875 hospital visits for OM by children aged

ObjectivesThe purpose of this study was to evaluate the therapeutic effect of three different types of sounds on tinnitus patients undergoing tinnitus retraining therapy (TRT).MethodsThis is a single-institution retrospective study, performed in one tertiary otological referral center. Thirty-eight adults with subjective idiopathic tinnitus who were followed for at least 9 weeks were enrolled. Sound therapy was delivered in 3 different ways: narrowband noise TRT (nTRT); mixed band noise TRT (mTRT); broadband noise TRT (bTRT). Treatment response was measured through validated psychometric questionnaires: Tinnitus Handicap Inventory (THI), visual analog scale (VAS) on annoyance, and numerical description of hours of tinnitus perception (awareness hours).ResultsA total of 38 patients were followed for at least 9 weeks. In nTRT group, all outcome measures including THI, VAS, and the awareness hours, decreased over 9 weeks with no statistical significance. In mTRT group, all outcome measures except for awareness hours significantly improved 9 weeks after the beginning of the treatment. In bTRT group, all outcome measures decreased significantly in 9 weeks. When therapeutic success is defined as improvement in THI 7 or more, bTRT group (77.8%) showed a higher success rate than other groups for 38 patients with the minimum follow-up of 9 weeks.ConclusionAll three sounds can provide relief in patients with annoying tinnitus after TRT. However, there is difference in the therapeutic effect according to sound types. Broadband sound seems to be better than narrowband sound or mixed sound in relieving the patients from tinnitus. Therefore, sound therapy with broadband noise may be more appropriate during TRT, but further evidence is needed for precise conclusion.

ObjectivesRectified vestibular evoked myogenic potential (rVEMP) is new method that simultaneously measures the muscle contraction power during VEMP recordings. Although there are a few studies that have evaluated the effect of the rVEMP, there is no study that has evaluated the capacity of rVEMP during asymmetrical muscle contraction.MethodsThirty VEMP measurements were performed among 20 normal subjects (mean age, 28.2±2.1 years; male, 16). VEMP was measured in the supine position. The head was turned to the right side by 0°, 15°, 30°, and 45° and the VEMPs were recorded in each position. The interaural amplitude difference (IAD) ratio was calculated by the conventional non-rectified VEMP (nVEMP) and rVEMP.ResultsThe nVEMP IAD increased significantly according to increasing neck rotation. The IAD in rVEMP was almost similar from 0° to 30°. However, the IAD was significantly larger than the other positions when the neck was rotated 45°. When IAD during 0° was set as a standard, the IAD of the rVEMP was significantly smaller that the nVEMP only during the 30°rotaion.ConclusionRectified VEMP is capable of correcting asymmetrical muscle contraction power. In contrast, it cannot correct the asymmetry if muscle contraction power asymmetry is 44.8% or larger. Also, it is not necessary if muscle contraction power asymmetry is 22.5% or smaller.

[This corrects the article DOI: 10.1371/journal.pone.0166044.].

ObjectivesFrom our previous study about the weak expressions of potassium-chloride (KCC2) and sodium-potassium-2 chloride (NKCC1) co-transporters in the lateral superior olive (LSO) in circling mice, we hypothesized that partially damaged cochlea of circling mice might be a cause of the weak expressions of KCC2 or NKCC1. To test this possibility, we reproduced the altered expressions of KCC2 and NKCC1 in the LSO of rats, whose cochleae were partially destroyed with kanamycin.MethodsRat pups were treated with kanamycin from postnatal (P)3 to P8 (700 mg/kg, subcutaneous injection, twice a day) and sacrificed for immunohistochemical analysis, scanning electron microscope (SEM) and auditory brain stem response.ResultsThe SEM study revealed partially missing hair cells in P9 rats treated with kanamycin, and the hearing threshold was elevated to 63.8±2.5 dB SPL (4 ears) at P16. Both KCC2 and NKCC1 immunoreactivities were more prominent in control rats on P16. On 9 paired slices, the mean densities of NKCC1 immunoreactivities were 118.0±1.0 (control) and 112.2±1.2 (kanamycin treated), whereas those of KCC2 were 115.7±1.5 (control) and 112.0±0.8 (kanamycin treated).ConclusionWe concluded that weak expressions of KCC2 and NKCC1 in circling mice were due to partial destruction of cochleae.

ObjectivesThis study was undertaken to confirm the clinical characteristics of recurrent pleomorphic adenoma (RPA), and to identify those factors that affect the development of malignant transformation (MT) from RPA.MethodsThe medical records of 270 patients, who were operated upon for parotid PA, were retrospectively reviewed. The pathologic specimens of a selected series of 23 patients were reviewed for histologic subtype and microscopic multi-nodularity.ResultsMean age of initial operation in RPA without MT (RPA-MT) group was significantly lower than that of primary PA group. Mean age of the revision operation in RPA with MT (RPA+MT) group was significantly greater than that of RPA-MT group. Mean interval from operation to recurrence shortened after each revision operation. The risk of MT and additional recurrence increased significantly with recurrence. In RPA-MT group tumor recurrence occurred in 21.4% of patients despite a clear resection margin.ConclusionThe risk factors for MT may be an age of over 45 yr and multiple recurrences. However, younger patients are more at risk of recurrence. A clear resection margin cannot guarantee a cure in RPA, and it seems that parotid pleomorphic adenomas slowly gain malignant characteristics after repeated recurrences.

ObjectivesThe objective of this study was to compare the long-term auditory performance and language skill depending on the age of cochlear implantation in the Korean population. We especially tried to separate the effect of maturation/development from that of the age at implantation.MethodsEighty-six pre-lingual children with profound hearing loss who underwent a cochlear implantation before the age of six and had been followed for more than 3 yr were included in this study prospectively. Categories of Auditory Performance (CAP) and Korean Picture Vocabulary Test (K-PVT) were serially followed up. In order to separate the age at implantation effect, K-PVT results were readjusted to the child's chronological age in the normal hearing population.ResultsWhen the CAP and K-PVT scores were directly compared without chronological readjustment, we failed to show a significant difference for improvements according to the age at implantation. Early cochlear implantation was associated with better language development, only when the K-PVT scores were readjusted to percentile scores of their chronological age.ConclusionEarly cochlear implantation was associated with better language development even within the critical period. This advantage may be recognized only when the effect of the age at implantation is separated from the effect of maturation/development.

ObjectivesThe aim of this study was to evaluate the clinical features of cochlear reimplantation due to device failure.MethodsThe medical records of 30 patients who had undergone a revision cochlear implantation were retrospectively reviewed. Causes of revision operations, number of electrode channels inserted, and postoperative speech performances were analyzed.ResultsDevice failure (N=12, 38.7%) and hematoma (N=3, 9.6%) were the two most common reasons for revision surgery. In patients with device failure, the number of electrode channels reinserted was equal to, or more than the number of channels inserted during initial implantation. Speech performance scores remained the same, or improved after reimplantation in patients with device failure.ConclusionDevice failure was the most common cause of revision operation in patients with cochlear implanttion. Contrary to expectation, new electrodes were fully inserted without difficulty in all reimplantation cases. Intracochlear damage due to reimplantation appeared to be clinically insignificant.

Dizziness and vertigo frequently occur after cochlear implantation (CI) surgery, particularly during the early stages. It could recover over time but some of the patients suffered from delayed or sustained vestibular symptoms after CI. This study used rat animal models to investigate the effect of unilateral cochleostomy on the vestibular organs over time. Twenty-seven Sprague Dawley rats underwent cochleostomy to evaluate the postoperative changes in hearing threshold, gain and symmetry of the vestibular ocular response, overall balance function, number of hair cells in the crista, and the c-Fos activity in the brainstem vestibular nucleus. Loss of vestibular function was observed during the early stages, but function recovered partially over time. Histopathological findings demonstrated a mild decrease in vestibular hair cells numbers. Increased c-Fos immunoreactivity in the vestibular nucleus, observed in the early stages after cochleostomy, decreased over time. Cochleostomy is a risk factor for peripheral vestibular organ damage that can cause functional impairment in the peripheral vestibular organs. Altered vestibular nucleus activity may be associated with vestibular compensation and plasticity after unilateral cochleostomy.