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Abstract In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.

Objectives. When performing middle ear operations, such as ossiculoplasty or stapes surgery, patients and surgeons expect an improvement in air conduction (AC) hearing, but generally not in bone conduction (BC). However, BC improvement has often been observed after surgery, and the present study investigated this phenomenon. Methods. We reviewed the preoperative and postoperative surgical outcomes of 583 patients who underwent middle ear surgery. BC improvement was defined as a BC threshold decrease of >15 dB at two or more frequencies. Subjects in group A underwent staged ossiculoplasty after canal wall up mastoidectomy (CWUM), group B underwent staged ossiculoplasty after canal wall down mastoidectomy (CWDM), group C underwent ossiculoplasty only (thus, they had no prior history of CWUM or CWDM), and group D received stapes surgery. We created a hypothetical circuit model to explain this phenomenon. Results. BC improvement was detected in 12.8% of group A, 9.1% of group B, and 8.5% of group C. The improvement was more pronounced in group D (27.0%). A larger gain in AC hearing was weakly correlated with greater BC improvement (Pearson’s r=0.395 in group A, P

In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae may be a therapeutic target for hearing regeneration. The ubiquitin proteasome system plays an important role in cochlear development and maintenance. In this study, we investigated the role of ubiquitin C-terminal hydrolase L1 (UCHL1) in the process of the transdifferentiation of auditory supporting cells (SCs) into hair cells (HCs). The expression of UCHL1 gradually decreased as HCs developed and was restricted to inner pillar cells and third-row Deiters’ cells between P2 and P7, suggesting that UCHL1-expressing cells are similar to the cells with Lgr5-positive progenitors. UCHL1 expression was decreased even under conditions in which supernumerary HCs were generated with a γ-secretase inhibitor and Wnt agonist. Moreover, the inhibition of UCHL1 by LDN-57444 led to an increase in HC numbers. Mechanistically, LDN-57444 increased mTOR complex 1 activity and allowed SCs to transdifferentiate into HCs. The suppression of UCHL1 induces the transdifferentiation of auditory SCs and progenitors into HCs by regulating the mTOR pathway.

Abstract Objective In this prospective study, each subject experienced three modes electric acoustic stimulation (EAS), full electrical stimulation (FES), and electrical complement (EC), and the performance of each mode and subject preference were evaluated. Methods Eight ears (seven patients) with successfully preserved residual hearing after cochlear implantation (CI) were included. EAS, FES, and EC programs were set up on each patient's device, and each mode was used for at least 1 h per day for a month. The Speech Intelligibility test, the Speech, Spatial and Qualities of Hearing Scale, and the Hearing in Noise test (HINT) results in each stimulation mode. Results The mean monosyllabic word score (EAS: 90.3 ± 4.0; FES: 81.2 ± 16.1) and the mean sentence score (EAS: 98.3 ± 1.7; FES: 95.0 ± 3.0) were significantly higher in the EAS mode than in the FES mode. The mean bisyllabic word score (EAS: 95.6 ± 5.6; EC: 90.1 ± 5.6) was higher in the EAS mode than in the EC mode. In HINT, the signal‐to‐noise ratios under the noise front (EAS: 4.7 ± 2.5; FES: 7.9 ± 4.4) and noise composite conditions (EAS: 4.2 ± 2.7; FES: 6.6 ± 4.0) were significantly smaller in the EAS mode than in the FES mode. After trials of the three modes, five subjects preferred EAS, one preferred EC, and two preferred FES. Conclusion Among the three stimulation modes, EAS produced slightly better results, and subjects generally preferred EAS (five of seven patients, 71.4%). The use of hearing aids before CI was considered an important factor in mode preference. FES may be preferred when CI was performed at a young age and subjects had little experience with hearing aids. However, adults may prefer EC over EAS if there was little or no hearing‐aid use before CI.

The inner ear is responsible for both hearing and balance in the body, and since the initial development of otic (inner ear) organoids from mouse pluripotent stem cells (PSCs) in 2013, significant advances have been made in this field. Bone morphogenetic proteins, fibroblast growth factors, and Wnt agonists, which are signaling molecules in the early development of the inner ear, can induce PSCs into the otic fate. In the inner ear, hair cells and the surrounding supporting cells are essential for proper function and structure. Recent advancements in otic organoid research have enabled the generation of cells that closely resemble these key components. The developed otic organoids contain both hair cell-like cells and supporting cells, which have been confirmed to have the intrinsic function of those cell types. Otic organoids have been used for disease modeling and are expected to be more widely applied in various areas of research on the inner ear. However, the otic organoids developed to date remain immature. Although they mimic hair cells, their properties resemble vestibular (balance) hair cells more closely than cochlear (auditory) hair cells. The ultimate goal of research on the inner ear is hearing restoration and prevention; thus, it is essential to produce otic organoids that contain cochlear hair cells. In addition, the organ of Corti—a cell arrangement unique to the cochlea—has not yet been simulated. Along with a description of the current status of otic organoids, this review article will discuss future directions for otic organoids in inner ear research.

In vitro miniaturized organoids are innovative tools with varying applications in biomedical engineering, such as drug testing, disease modeling, organ development studies, and regenerative medicine. However, conventional organoid development has several hurdles in reproducing and reconstituting organ-level functions in vitro, hampering advanced and impactful studies. In this review, we summarize the emerging microengineering-based organoid development techniques aiming to overcome these hurdles. First, we provide basic information on microengineering techniques, including those for reconstituting organoids with organ-level functions. We then focus on recent advances in microengineered organoids with better morphological, physiological, and functional characteristics than conventionally developed organoids. We believe that microengineered organoids possessing organ-level functions in vitro will enable widespread studies in the field of biological sciences and have clinical applications.

Objectives This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy. Methods The study included 27 patients (mean age, 58.7 years; age range, 28–76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates. Results The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections. Conclusion RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

Hydroxyapatite (HA) is a representative substance that induces bone regeneration. Our research team extracted nanohydroxyapatite (EH) from natural resources, especially equine bones, and developed it as a molecular biological tool. Polyethylenimine (PEI) was used to coat the EH to develop a gene carrier. To verify that PEI is well coated in the EH, we first observed the morphology and dispersity of PEI-coated EH (pEH) by electron microscopy. The pEH particles were well distributed, while only the EH particles were not distributed and aggregated. Then, the existence of nitrogen elements of PEI on the surface of the pEH was confirmed by EDS, calcium concentration measurement and fourier transform infrared spectroscopy (FT-IR). Additionally, the pEH was confirmed to have a more positive charge than the 25 kD PEI by comparing the zeta potentials. As a result of pGL3 transfection, pEH was better able to transport genes to cells than 25 kD PEI. After verification as a gene carrier for pEH, we induced osteogenic differentiation of DPSCs by loading the BMP-2 gene in pEH (BMP-2/pEH) and delivering it to the cells. As a result, it was confirmed that osteogenic differentiation was promoted by showing that the expression of osteopontin (OPN), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) was significantly increased in the group treated with BMP-2/pEH.In conclusion, we have not only developed a novel nonviral gene carrier that is better performing and less toxic than 25 kD PEI by modifying natural HA (the agricultural byproduct) but also proved that bone differentiation can be effectively promoted by delivering BMP-2 with pEH to stem cells.

Objectives The aim of this study was to evaluate vestibular function loss after cochlear implantation (CI) and the relationship between vestibular function and hearing changes. Methods Seventy-five patients with CI were enrolled and divided into those with normal preoperative caloric function (group I) and those with a normal preoperative waveform in cervical vestibular evoked myogenic potential (c-VEMP) testing (group II). The relationship between hearing and changes in the vestibular system was analyzed preoperatively and at 3 and 6 months postoperatively. Results In group I, unilateral weakness on the implanted side was detected in five (7.7%) and eight (12.3%) patients at 3 and 6 months post-CI, respectively. By 3 months post-CI, the total slow-phase velocity (SPV; warm and cold stimulations) was significantly different between the implanted and non-implanted sides (P=0.011), and the shift in total SPV from pre- to post-CI was significantly correlated with the average hearing threshold at 6 months post-CI. In group II, an abnormal c-VEMP was detected on the implanted side in six patients (16.2%) at 3 months post-CI, and in six patients (16.2%) at 6 months post-CI. Significant changes were noticed in the P1 and N1 amplitude at 3 months postCI (P=0.027 and P=0.019, respectively). Conclusion Vestibular function and residual hearing function should be afforded equal and simultaneous consideration in terms of preservation.

Cochlear implants (CIs) have become the standard treatment for severe-to-profound sensorineural hearing loss. Conventional CIs have some challenges, such as the use of extracorporeal devices, and high power consumption for frequency analysis. To overcome these, artificial basilar membranes (ABMs) made of piezoelectric materials have been studied. This study aimed to verify the conceptual idea of a totally implantable ABM system. A prototype of the totally implantable system composed of the ABM developed in previous research, an electronic module (EM) for the amplification of electrical output from the ABM, and electrode was developed. We investigated the feasibility of the ABM system and obtained meaningful auditory brainstem responses of deafened guinea pigs by implanting the electrode of the ABM system. Also, an optimal method of coupling the ABM system to the human ossicle for transducing sound waves into electrical signals using the middle ear vibration was studied and the electrical signal output according to the sound stimuli was measured successfully. Although the overall power output from the ABM system is still less than the conventional CIs and further improvements to the ABM system are needed, we found a possibility of the developed ABM system as a totally implantable CIs in the future.

Diagnostic tests for hearing impairment not only determines the presence (or absence) of hearing loss, but also evaluates its degree and type, and provides physicians with essential data for future treatment and rehabilitation. Therefore, accurately measuring hearing loss conditions is very important for proper patient understanding and treatment. In current-day practice, to quantify the level of hearing loss, physicians exploit specialized test scores such as the pure-tone audiometry (PTA) thresholds and speech discrimination scores (SDS) as quantitative metrics in examining a patient's auditory function. However, given that these metrics can be easily affected by various human factors, which includes intentional (or accidental) patient intervention, there are needs to cross validate the accuracy of each metric. By understanding a "normal" relationship between the SDS and PTA, physicians can reveal the need for re-testing, additional testing in different dimensions, and also potential malingering cases. For this purpose, in this work, we propose a prediction model for estimating the SDS of a patient by using PTA thresholds via a Random Forest-based machine learning approach to overcome the limitations of the conventional statistical (or even manual) methods. For designing and evaluating the Random Forest-based prediction model, we collected a large-scale dataset from 12,697 subjects, and report a SDS level prediction accuracy of 95.05% and 96.64% for the left and right ears, respectively. We also present comparisons with other widely-used machine learning algorithms (e.g., Support Vector Machine, Multi-layer Perceptron) to show the effectiveness of our proposed Random Forest-based approach. Results obtained from this study provides implications and potential feasibility in providing a practically-applicable screening tool for identifying patient-intended malingering in hearing loss-related tests.

Abstract Background While auditory neuropathy spectrum disorder (ANSD) is a heterogeneous disorder and its management quite varies depending upon the etiology, even including self-resolution, OTOF is an important molecular etiology of prelingual ANSD and has emerged as an attractive target for implementation of precision medicine in terms of timing and prognosis prediction of auditory rehabilitation. However, to date, the literature is lacking in the genotype–phenotype relationship of this gene as well as efficient molecular testing strategy in the clinic in many populations and to make things more complicated in Koreans, the most prevalent variant p.Arg1939Gln among Korean ANSD children frequently evaded detection by next generation sequencing (NGS), resulting in delayed genetic diagnosis and late cochlear implantation (CI). The aims of this study are to document the mutational and phenotypic spectrum of OTOF-related ANSD (DFNB9) in the Korean population, further establishing genotype–phenotype correlation and proposing a set of the most commonly found OTOF variants to be screened first. Methods Genetic diagnosis through the NGS-based sequencing was made on patients with ANSD in two tertiary hospitals. Genotype and phenotypes of eleven DFNB9 patients were reviewed. For data analysis, Mann–Whitney test and Fisher’s exact test were applied. Results This study disclosed four prevalent variants in Koreans: p.Arg1939Gln with an allele frequency of 40.9%, p.Glu841Lys (13.6%), p.Leu1011Pro and p.Arg1856Trp (9.1%). Three novel variants (c.4227 + 5G > C, p.Gly1845Glu, and p.Pro1931Thr) were identified. Interestingly, a significant association of p.Arg1939Gln with worse ASSR thresholds was observed despite consistently no ABR response. Ten of 11 DFNB9 patients received CI for auditory rehabilitation, showing favorable outcomes with more rapid improvement on early-CI group (age at CI ≤ 18 mo.) than late-CI group. Conclusions This study included the largest Korean DFNB9 cohort to date and proposed a set of the most frequent four OTOF variants, allowing the potential prioritization of exons during Sanger sequencing. Further, a significant association of p.Arg1939Gln homozygotes with poor residual hearing was observed. We may have to suspect p.Arg1939Gln homozygosity in cases of poor auditory thresholds in ANSD children with putative negative OTOF variants solely screened by NGS. Reciprocal feedback between bench and clinics regarding DFNB9 would complement each other.

Objectives Combined mastoidectomy is generally preferred to tympanoplasty alone when treating patients with chronic otitis media (COM), particularly when temporal bone computed tomography (TBCT) shows that the mastoid cavity contains opacification of soft tissue density. However, in cases with Eustachian tube dysfunction, a mastoid cavity volume may be a burden to its function. We hypothesized that tympanoplasty alone might be better than tympanoplasty combined with mastoidectomy because soft tissue in the mastoid cavity is a sequel to a protective physiological response. Thus, we explored the efficacy of tympanoplasty without mastoidectomy in COM patients exhibiting mastoid air cell opacification on TBCT. Methods Between 2010 and 2014, a total of 33 patients, diagnosed with COM and with evidence of mastoid cavity opacification on TBCT, underwent tympanoplasty without mastoidectomy. All ears had been dry for ≥3 months before surgery. All procedures were performed by the same surgeon. We retrospectively analyzed the preoperative otoscopic findings, pre- and postoperative pure tone averages (PTAs; the mean of the values at 0.5, 1, 2, and 4 kHz), surgical procedures, and complications or recurrence. Results Of the 33 patients, 28 (84.8%) exhibited hearing improvement after surgery. The mean pre- and postoperative PTAs were 46.9±21.2 dB and 29.4±17.0 dB, respectively (P

Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea.

Abstract Background Hearing Aids amplify sounds at certain frequencies to help patients, who have hearing loss, to improve the quality of life. Variables affecting hearing improvement include the characteristics of the patients’ hearing loss, the characteristics of the hearing aids, and the characteristics of the frequencies. Although the two former characteristics have been studied, there are only limited studies predicting hearing gain, after wearing Hearing Aids, with utilizing all three characteristics. Therefore, we propose a new machine learning algorithm that can present the degree of hearing improvement expected from the wearing of hearing aids. Methods The proposed algorithm consists of cascade structure, recurrent structure and deep network structure. For cascade structure, it reflects correlations between frequency bands. For recurrent structure, output variables in one particular network of frequency bands are reused as input variables for other networks. Furthermore, it is of deep network structure with many hidden layers. We denote such networks as cascade recurring deep network where training consists of two phases; cascade phase and tuning phase. Results When applied to medical records of 2,182 patients treated for hearing loss, the proposed algorithm reduced the error rate by 58% from the other neural networks. Conclusions The proposed algorithm is a novel algorithm that can be utilized for signal or sequential data. Clinically, the proposed algorithm can serve as a medical assistance tool that fulfill the patients’ satisfaction.

The relationship between type 1 diabetes and hearing loss is not well known, although based on many pathological studies, type 2 diabetes induced hearing loss is associated with microcirculation problems in the inner ear. The purpose of this study was to investigate the correlation between type 1 diabetes and hearing loss through hearing function and immunohistochemical analyses using type 1 diabetic Akita or wild-type (WT) mice. The Akita mice had a significant increase in hearing thresholds, blood glucose, and insulin tolerance compared to WT mice. Histological analysis showed that the loss of cells and damage to mitochondria in the spiral ganglion neurons of Akita mice were significantly increased compared to WT. Also, the stria vascularis showed decreased thickness, loss of intermediate cells, and disturbance in blood capillary shape in the Akita mice. Moreover, a reduction in type I, II, and IV fibrocytes and Na+/K+-ATPase α1 expression in spiral ligament was also observed. Cleaved caspase-3 expression was highly expressed in spiral ganglion neurons. In conclusion, hearing loss in type 1 diabetes is caused not only by ion imbalance and blood flow disorders of cochlear endolymph, but through the degenerative nervous system via apoptosis-mediated cell death.

Engineering complex extracellular matrix (ECM) is an important challenge for cell and tissue engineering applications as well as for understanding fundamental cell biology. We developed the methodology for fabrication of precisely controllable multiscale hierarchical structures using capillary force lithography in combination with original wrinkling technique for the generation of well-defined native ECM-like platforms by culturing fibroblast cells on the multiscale substrata [1]. This paper provides information on detailed characteristics of polyethylene glycol-diacrylate multiscale substrata. In addition, a possible model for guided extracellular matrix formation from fibroblast cells cultured on bio-inspired configurable multiscale substrata is proposed.

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague−Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H & E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

ObjectivesMastoid obliteration is used to obliterate the mastoid cavity following a mastoidectomy or to prevent the formation of a retraction pocket. This study evaluated the effectiveness of β-tricalcium phosphate and polyphosphate (β-TPP) for mastoid obliteration in middle ear surgeries in prospective human and animal studies.MethodsTwenty patients with chronic otitis media underwent mastoid obliteration using β-TPP after a intact canal wall mastoidectomy or simple mastoidectomy. The clinical data were prospectively evaluated including: the diagnosis, temporal bone computed tomography (TBCT), otoscopic findings, pure tone audiogram, and complications. In the animal experiment, β-TPP was applied into the right bulla in five rats, and the opposite bulla was used as the control in the non-obliterated state. The skulls of five other rats were drilled out and the holes were obliterated with β-TPP. TBCT were obtained at 3, 6, and 9 months after the obliteration and histologic analysis was done at 3 and 9 months after surgery.ResultsIn the human study, fourteen TBCTs were obtained at 12 months after the surgery. All demonstrated no bone resorption in the obliterated mastoids. Among the 15 cases displaying retracted tympanic membranes preoperatively, 11 showed no retraction, 2 showed retraction postoperatively, 1 was lost to follow-up and 1 was a case of postoperative wound infection. Among 20 cases, one case developed a postoperative infection that necessitated a second operation. Sixteen underwent ossiculoplasty; hearing improvements were obtained in 15 cases and 1 case showed decreased hearing. In the animal study, new bone formation without significant bone resorption in the radiologic and histologic findings were noted in both the skull and bulla groups.ConclusionAlthough β-TPP is a foreign material having the possibility of infection, mastoid obliteration with it can be a treatment option in middle ear surgeries to prevent retraction pockets or the recurrence of diseases.

ObjectivesA non-progressive and conductive hearing loss with normal eardrum, but no history of trauma and infection, is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, stapes anomaly is the most common. The purpose of this study is to describe patterns of stapes anomaly and to analyze its surgical outcome with special reference to its patterns.MethodsWe conducted a retrospective case review. The subjects comprised 66 patients (76 ears) who were decisively confirmed by the exploratory tympanotomy as congenital stapes anomalies without any anomalies of the tympanic membrane and external auditory canal. The preoperative and postoperative audiological findings, temporal bone computed tomography scan, and operative findings were analyzed.ResultsThere were 16 anomalous patterns of stapes among which footplate fixation was the most common anomaly. These 16 patterns were classified into 4 types according to the status of stapes footplate. Successful hearing gain was achieved in 51 out of 76 ears (67.1%) after surgical treatment.ConclusionFootplate fixation was usually bilateral, whereas stapes anomalies associated with other ossicular anomaly were usually unilateral. The success of the surgical treatment of stapes anomaly might depend on its developmental status of the footplate. Stapes anomalies were detected without any fixed patterns, therefore, it is quite possible to detect a large variety of patterns in future.

ObjectivesRecently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.MethodsEighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.ResultsThirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).ConclusionIn the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.

ObjectivesExperimental models are of importance to study the pathogenesis of middle ear cholesteatoma, however, they were not established until now. We aimed to develop in vitro model of middle ear cholesteatoma using primary keratinocytes and fibroblasts isolated from cholesteatoma tissue. HaCaT cell line was used as a "skin equivalent" and to compare the grade of homogeneity between cholesteatoma keratinocytes and HaCaT cells.MethodsPrimary keratinocytes were isolated from cholesteatoma tissue, co-cultured with preliminary prepared feeder layer from cholesteatoma fibroblasts and subsequently air-exposed. The protein profile of cholesteatoma keratinocytes and HaCaT cells was evaluated by means of immunoblot using monoclonal antibody against cytokeratin (CK) 13 and 16. Tissue localization of CK 13 and 16 was accomplished with immunohistochemistry.ResultsDifferent protein profile and stronger expression of CK 13 and 16 were demonstrated in cholesteatoma keratinocytes in comparison with HaCaT cells. Bigger stratification was observed in the 3D-in vitro systems when both cholesteatoma keratinocytes and HaCaT cells were respectively co-cultured with fibroblasts in comparison with the corresponding control groups without fibroblasts.Conclusion3D-model demonstrates the significance of intercellular interaction between components of cholesteatoma tissue.

Meningioma's account for around 15% of all primary brain tumors with some 10% of meningiomas arising in the posterior fossa. In rare cases, a meningioma can form around the endolymphatic sac. When formed in the posterior fossa, meningioma tumors can produce vague, non-specific vertiginous symptoms. Research has observed that a subset of these lesions could produce symptoms indistinguishable from those of Meniere's disease. Therefore, we described the clinical features of a case of posterior petrous meningioma with recurrent vertigo as well as the substantial resolution of symptoms after tumor removal via transmastoid approach.

Objective: To assess the usefulness of cone beam computed tomography (CBCT) for characterizing electrode insertion and evaluate the influence of electrode insertion status on post-cochlear implantation (CI) outcomes. Design: Twenty-six ears with post-CI CBCT scans were included. The devices were MED-EL Flex28 (n=21) and Nucleus slim straight (n=5). The parameters including cochlear duct length (CDL), insertion depth angle (IDA), insertion length of electrode (IL), and cochlear coverage (CC) were analyzed and compared with aided pure-tone threshold (PTA) with implant in free field, and open-set sentence score. Results: The mean CDL was 36.8 ± 1.4mm. Electrode array was dislocated into scala tympani in two ears. The mean IL and IDA were 26.5 ± 1.9mm and 541.4 ± 70.2°. The mean linear CC (IL/CDL, 0.73 ± 0.06) was larger than the mean angular CC (IDA/900, 0.60 ± 0.08). The CBCT parameters showed correlation one another. While the aided pure-tone threshold was correlated with IL and IDA, there were no significant correlations in the open-set sentence score. For the postlingually deaf patients with single electrode (Flex 28), the sentence score had no significant correlation and the aided PTA was positively correlated with IL (R=0.517, p=.028). Conclusions: This study validated the CBCT evaluating the electrode array position. The CBCT could be helpful for the preoperative selection of the optimal array and prediction of the CC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the validity of student ratings of instruction by analyzing their relationships with several variables, including gender, academic rank, specialty, teaching time, and teaching method, at a medical school. Methods: This study analyzed the student ratings of 297 courses at Ajou University School of Medicine in 2013. SPSS version 12.0 was used to analyze the data and statistics by t-test, analysis of variance, and Scheffe test. Results: There were no statistically significant differences in student ratings between gender, rank, and specialty. However, student ratings were significantly influenced by teaching times and methods (p<0.05). Student ratings were high for teaching times of 10 hours or more and small-group learning, compared with lectures. There was relatively mean differences in students ratings by teaching times, specialty and rank, although the difference in ratings was not statistically significant. Conclusion: Student ratings can be classified by teaching time and method for summative purposes. To apply student ratings to the evaluation of the performance of faculty, further studies are needed to analyze the variables that influence student ratings. [ABSTRACT FROM AUTHOR]

Inspired by ultrastructural analysis of ex vivo human tissues as well as the physiological importance of structural density, we fabricated nanogrooves with 1:1, 1:3, and 1:5 spacing ratio (width: spacing, width = 550nm). In response to the nanotopographical density, the adhesion, migration, and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled, but the proliferation showed no significant difference. In particular, the osteo- or neurogenesis of hMSCs were enhanced at the 1:3 spacing ratio rather than 1:1 or 1:5 spacing ratio, implying an existence of potentially optimized nanotopographical density for stem cell function. Furthermore, such cellular behaviors were positively correlated with several cell morphological indexes as well as the expression of integrin β1 or N-cadherin. Our findings propose that nanotopographical density may be a key parameter for the design and manipulation of functional scaffolds for stem cell-based tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

It has been suggested that connexin (Cx) gap junction proteins act as tumor suppressors and green tea has a potential to prevent tumor development, however, the studies on their association with human keratinocytes were rare. We evaluated the effects of a tumor promoter, phorbol-12-myristate-13-acetate (PMA), on the expression of Cxs and gap junction intercellular communication (GJIC) in human keratinocytes (HaCaT cells) and explored the preventive effects of green tea extracts-epicatechin (EC) and epigallocatechin-3-gallate (EGCG). We performed neutral red dye uptake assay to determine the optimal concentrations of PMA, EC, and EGCG for this study and confirmed the expression of Cx mRNAs using RT-PCR. We evaluated GJIC quantitatively using the 'scrape-loading dye transfer (SLDT)' technique after 24-h culture of HaCaT cells treated with agents. To analyze the expression change of Cxs, we also performed Western blot and immunocytochemistry. HaCaT cells were found to express Cx26, Cx30, Cx31, and Cx43, but not Cx29. In 'scrape-loading dye transfer' for functional study for GJIC, EC and EGCG significantly prevented PMA-induced down-regulation of GJIC. Western blot analyses revealed that EC and EGCG prevented down-regulation of Cx26 and Cx43 proteins in HaCaT cells treated with PMA. Immunocytochemistry showed decreased expression and abnormal location of Cx26 and Cx43 in HaCaT cells when treated with PMA, and EC and EGCG inhibited its effect. These results suggest an important role of GJIC played in carcinogenesis involving human keratinocytes and green tea as a useful anticancer diet. [ABSTRACT FROM AUTHOR]

The effect of intratympanic steroid injection is controversial as salvage or initial treatment option for sudden sensorineural hearing loss (SSNHL) and almost unknown if it is consecutively to use after initial systemic steroids. This study aimed to analyze the efficiency of intratympanic dexamethasone injection (ITDI) as a sequential treatment in the patients who failed initial systemic steroid treatments for SSNHL. Forty-six patients with SSNHL who did not respond to initial systemic steroids were prospectively included in the study. The patients were randomly classified into two groups; the ITDI group (21 patients) did not take four sequential ITDI within 2 weeks after systemic steroids, and the control group (25 patients) took any more medications. Hearing improvement was defined as a 10 dB or more decrease in the pure tone average (PTA) of the four-frequencies (0.5, 1, 2, and 3 kHz). Hearing improvement was observed in 10 (47.6%) of 21 ITDI patients and in 4 (16.0%) of 25 control patients ( P = 0.027). An improvement of the mean PTA was 11.4 dB in the ITDI group and 1.7 dB in the control group ( P = 0.004). The ITDI group showed significant hearing improvement at low frequency (500 Hz) than the control group. The patients with 70 or more dB in PTA before ITDI showed significant hearing improvement than the other patients with better PTAs ( P = 0.038). The sequential ITDI, which is performed immediately after initial systemic steroid therapy, may be a simple, effective second-line treatment of choice for the patients who show poor response to initial treatments for SSNHL. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the preventive effects of Korean red ginseng (KRG) on gentamicin (GM)-induced ototoxicity and to identify the effective components of KRG. Study Design: In vivo and in vitro studies. Methods: Thirty-five Sprague-Dawley rats were divided into four groups. The GM group (n ¼ 15) received intraperitoneal injections (IPI) of GM (160 mg/kg) for 5 days. The KRG þ GM group (n ¼ 12) was treated with intragastric feeding of KRG (500 mg/kg) for 12 days with 5 days of IPIs of GM. KRG (n ¼ 4) and control (n ¼ 4) groups were treated with KRG and saline, respectively. Auditory brainstem response (16 or 32 kHz) and Rotarod treadmill tests were done before and after treatments. Cochleas were evaluated by a scanning electron microscope (SEM) and phalloidin staining. Ginsenosides Rb1, Rb2, Rg1, and Re were evaluated as the water-soluble terazolium salt assay, annexin V/propidium iodide assay, and Western blots in HEI-OC1 cells. Results: Posttreatment hearing thresholds in GM, KRG þ GM, KRG, and control groups were: 27.7 6 7.2 dB, 23.1 6 4.1dB, 16.9 6 2.6 dB, and 21.3 6 3.5 dB, respectively, for 16 kHz, 30.5 6 6.6 dB, 25.2 6 4.3 dB, 22.5 6 2.7 dB, and 22.5 6 3.8 dB, respectively for 32 kHz. The KRG þ GM group had significantly better hearing than the GM group (P < .05). On SEM and phalloidin staining, the GM group showed severe loss of stereocilia in the basal outer hair cells and a few losses in the middle turns, whereas the KRG þ GM group showed relatively intact hair cells. Balance impairment in treadmill tests was not definite in any group. Rb1 and Rb2 showed more effective protection than other components. Conclusions: KRG protects against GM-induced hearing loss and hair cell death in rats. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Horizontal semicircular canal (HSC) benign paroxysmal positional vertigo (BPPV) has been reported to have a poorer prognosis than posterior semicircular canal BPPV. Incorrect determination of the affected ear appears to be one of the causes of poorer outcome. The aim of this study was to assess the efficacy of the ''bow and lean test'' (BLT) for proper determination of the affected ear followed by preferable treatment outcomes of HSC-BPPV. Study Design: A prospective study. Methods: The 211 patients (225 cases) with HSCBPPV were sequentially classified into two groups by hospital visiting time and diagnostic methods. The head roll test (HRT) group (61 cases) was treated with canalith repositioning procedure (CRP) on the basis of the results of HRT alone between 2001 and 2004. The BLT group (164 cases) was treated based on the results of both BLT and HRT from 2005 to 2008. Results: The remission rates after two sessions of CRPs in the BLT group and the HRT group were 83.1% and 67.4% (P = .041), respectively, for the canalolithiasis type and 74.7% and 61.1% (P = .250), respectively, for the cupulolithiasis type. In the BLT group, 76.8% had bowing and/or leaning nystagmus; 35.7% of them (45 of 126 cases) benefited from BLT with regard to determining the affected ears because HRT was unable to provide the definitive affected ears (17 cases) or showed different localization between two methods (28 cases). Conclusions: BLT is a useful method to improve the remission rates of HSC-BPPV, giving more corrective information regarding affected ears than the HRT alone. [ABSTRACT FROM AUTHOR]

The purposes of this study were to review the clinical characteristics and treatment outcomes of patients with lateral sinus thrombosis (LST) and to discuss the need of internal jugular vein (IJV) ligation or anticoagulants. We retrospectively reviewed the charts of five patients (1 male and 4 female) with LST. The chief complaints were otalgia, fever, mastoid tenderness, and neck pain. All patients were confirmatively diagnosed with MRI-Venography or Angio-CT scans. The patients were treated with appropriate antibiotics and operations including mastoidectomies with/without thrombectomy according to their suspected disease course. The authors did not perform IJV ligation and use anticoagulants in all cases, but there were no mortalities or morbidities. IJV ligation and use of anticoagulants do not seem to be essential procedures for the management of LST, and it should be considered carefully according to the extents of disease and the state of patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: The present study prospectively investigated the frequencies and characteristics of audio-vestibular disturbance and the results of audiologic and vestibular function tests in patients with Behçet’s disease.STUDY DESIGN:: A prospective study.METHODS:: Seventeen patients with Behçet’s disease (mean age 41.2 [30–56] years, 5 males and 12 females), as well as age- and sex-matched healthy controls, were included in this study. All subjects satisfied the diagnostic criteria of the International Study Group for Behçet’s Disease. Information on the subjects was obtained through questionnaires. Tests, including those for hearing impairment, tinnitus, ear fullness, and dizziness, pure-tone audiometry, and vestibular function, were performed.RESULTS:: Auditory symptoms were reported by 7 (41.2%) and dizziness by 14 (82.4%) of the subjects. Sensorineural hearing loss was present in four (23.5%) subjects. One was treated with a cochlear implantation because of bilateral sudden deafness. Spontaneous nystagmus was detected in two (11.8%) subjects. Abnormal findings were noted in 1 (5.9%) in saccadic movement, 5 (29.4%) in the bithermal caloric tests, and 10 (58.9%) in the rotation chair tests. In total, audiologic or vestibular disturbance were noted in 16 (94.1%) of the subjects. However, audio-vestibular abnormalities were not noted in the healthy controls.CONCLUSION:: Audio-vestibular disturbance is not rare in Behçet’s disease patients compared with healthy controls. We believe that audio-vestibular assessment and management may be helpful for the diagnosis and treatment of patients with Behçet’s disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: This case-control study aimed to analyze the effect of intratympanic dexamethasone injection (ITDI) as a treatment option for patients with sudden sensorineural hearing loss (SSNHL) who were refractory to classic oral steroid treatment.METHODS:: Sixty-six patients with SSNHL, who were refractory to a course of oral steroid therapy, were included in this study. We prospectively treated consecutive 33 patients (34 ears) with ITDI from August 2002 to January 2004. We then retrospectively collected data from age- and sex-matched previous patients who did not take any more treatments after the initial regimen between March 2000 and July 2002. ITDI was performed in the supine position on four separate occasions over the course of 2 weeks. Hearing was assessed immediately before every injection and at 1 week after therapy. Hearing improvement was defined as more than 10 dB in pure-tone average (PTA).RESULTS:: Hearing improvement was observed in 13 (39.4%) of 33 patients who underwent ITDI and in two (6.1%) of 33 patients in the control group. Five of 13 represented hearing improvement over than 20 dB in PTA, and 11 of 20 patients, who showed no improvement in PTA by ITDI, showed improvement over 10 dB in some frequencies. There were no definite prognostic factors between the patients who responded to ITDI and those who did not.CONCLUSION:: ITDI may be a simple and effective therapy for patients with refractory SSNHL. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish the eventual presence of progesterone receptor (PGR) and oestrogen receptor (EGR) in human middle-ear cholesteatoma (MECh) tissues and to compare their expression between male and female patients. An immunohistochemical technique was employed for detection of PGR- and EGR-specific immunoreactivity in MECh samples using formalin-fixed paraffin-embedded tissue sections. The positive results were verified with reverse transcriptase polymerase chain reaction (RT-PCR). The morphological study revealed stable expression of PGR in suprabasal layers of all cholesteatoma samples. Weaker immunoreactivity for PGR was demonstrated in external auditory canal skin (EACS) samples in comparison with MECh, while PGR-specific staining was not observed in retroauricular skin (RAS) samples. EGR was detected only at mRNA levels. Stronger expression of EGR PCR products was disclosed in female cholesteatoma samples, while PGR mRNA was predominantly detected in male cholesteatoma specimens. Our preliminary experimental results give us ground to assume that female sex hormones may stimulate proliferation and affect differentiation of MECh keratinocytes. [ABSTRACT FROM AUTHOR]

Conclusion The results of this study encourage our belief that some cholesteatomas can be managed using only conservative treatments. Objective We hypothesized that once cholesteatoma is in a normal environment, its cellular or molecular pathology can revert to those characteristic of normal epidermis. The aim of this study was to determine whether or not common molecular characteristics of cholesteatoma were reversible after removal of inductive factors in experimental cholesteatoma induced in gerbils. Material and methods We induced cholesteatoma using ear canal ligation in Mongolian gerbils. After ligation, the animals in the treated group were managed for 2 weeks. We examined differences between treated and untreated cholesteatomas using terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining and an immunohistochemical technique using the proliferation markers proliferating cell nuclear antigen (PCNA) and cytokeratin (CK). Results With PCNA and CK 13/16, the untreated group showed positive staining in the suprabasal and basal cells, but the treated group showed weakly positive staining only in the basal cell layer. With TUNEL staining, there were more positive cells in the untreated than the treated group. [ABSTRACT FROM AUTHOR]

In order to develop a biomimetic polymer for cell recognition, poly [3-O-(4'-vinylbenzyl)-D-glucose] (PVG) and different types of glucose transport (GLUT)-carrying cells, namely, HepG2 cells (GLUT-1), 3T3-L1 fibroblast cells (GLUT-1 and GLUT-4), and MIN6 cells (GLUT-2), were tested for specific interaction. To clarify the nature of interaction between PVG and the different cell types, rhodamine-B isothiocyanate (RITC)-labeled polymers were used to prove and visualize the interactions. In this study, we found that labeled polymer strongly binds to HepG2 cells. The fluorescence intensity of PVG with in the presence of HepG2 cells was found to be stronger than that of 3T3-L1 fibroblast cells (0.11 ± 0.05) and MIN6 cells, which carry GLUT-2 (0.028 ± 0.01); a confocal laser microscopic study confirmed this interaction. To confirm the specificity of the interaction mediated by GLUT, the cells were pretreated with phloretin, an inhibitor of GLUT-1, before adding RITC-labeled PVG polymer to the cell culture medium. This treatment suppressed the interaction of PVG with HepG2 cells and partially suppressed its interaction with 3T3-L1 fibroblast cells. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1055–1059, 2003 [ABSTRACT FROM AUTHOR]

Objective-To establish the eventual presence of human β-defensins (hBD) in middle ear cholesteatoma and paired retroauricular skin samples obtained during surgical treatment. Material and Methods-hBD were detected using immunohistochemical techniques and reverse transcriptase-polymerase chain reaction (RT-PCR). Results-It is hypothesized that hBD-1 and -2 are upregulated in cholesteatoma in comparison with retroauricular skin. The immunohistochemical study demonstrated stronger hBD-2-positive staining in middle ear cholesteatoma in comparison with retroauricular skin. No significant differences in hBD-1 expression were detected between cholesteatoma and skin samples. RT-PCR established elevated expression of hBD-2 mRNA in middle ear cholesteatomas. HBD-1 mRNA was constitutively expressed in cholesteatoma and retroauricular skin specimens. Conclusion-These preliminary experimental results lead us to believe that hBD may play an important role in the chronic inflammatory state of middle ear cholesteatoma. [ABSTRACT FROM AUTHOR]

Intralabyrinthine schwannomas (ILSs) are very rare and most of them involve cochlea–vestibule, internal auditory canal (IAC)–cochlea, or IAC–vestibule areas. However, there is no study reporting on schwannomas involving simultaneously the vestibule, cochlea, and IAC. We report a case of schwannoma involving simultaneously the vestibule, cochlea, and IAC, with the discussion of its possible origin and propose one more new classification, the ‘canalolabyrinthine schwannoma’, among the ILSs. [ABSTRACT FROM AUTHOR]

This article focuses on cochlear implantation in a case with Waardenburg syndrome. Waardenburg syndrome, an autosomal dominant syndromic deafness, is characterized by pigmentary abnormalities and deafness with or without dystopia canthorum. The prevalence of this syndrome is 1/42000 of the population and 1.43 % of the congenitally deaf. Here the author has presented a Korean family of Waardenburg syndrome type 2 not associated with microphthalmi associated transcription factor gene mutation and the cochlear implantation in one of them.

Objectives The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion. Methods A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged

Objectives The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. Methods Patients