Mun Young Chang

Protective effect of a purified polyphenolic extract from Ecklonia cava against noise-induced hearing loss: Prevention of temporary threshold shift

OBJECTIVEnNoise is one of the most common causes of hearing loss. Approximately 16% of American teenagers (12-19 years) have hearing loss caused by loud noise. The implication of noise-induced hearing loss (NIHL) in teenagers has received increasing attention. Although temporary threshold shift (TTS), a type of NIHL, is a transient hearing loss, it can accelerate age-related hearing loss. Reactive oxygen species are a primary cause of TTS. As the polyphenols from Ecklonia cava are known to have potent antioxidant effects, we investigated the protective effects of a purified polyphenolic extract of Ecklonia cava (PPEE) against TTS in mice.nnnMETHODSnThe radical-scavenging activity of PPEE was evaluated using the 1,1-diphenyl-2-picrylhydrazyl assay. The PPEExa0+xa0Noise and Salinexa0+xa0Noise groups were administered intraperitoneal PPEE (100xa0mg/kg) and saline, respectively, for 5 days before exposure to noise at 100xa0dB SPL for 60xa0min. Hearing ability was assessed following noise exposure using auditory brainstem responses and distortion product otoacoustic emissions.nnnRESULTSnPPEE exhibited significant radical scavenging activity. The ABR threshold shifts 1 day after exposure to noise at 16xa0kHz and 1, 7, and 14 days after exposure to noise at 32xa0kHz, were significantly less in the PPEExa0+xa0Noise than in the Salinexa0+xa0Noise group. One day after noise exposure, mice in the PPEExa0+xa0Noise group showed a significant degree of protection in relation to their DPOAE level at f2, 17, and 28xa0kHz.nnnCONCLUSIONSnThese findings suggest that PPEE may be a potential preventive agent against TTS. In addition, as a food ingredient approved by the United States Food and Drug Administration, PPEE may be administered to those who are exposed to noise inevitably with little likelihood of adverse effects, thereby contributing to the prevention of TTS.

The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model

Abstract The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin‐Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode‐dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode‐dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode‐dummy insertion. The threshold shift was defined as the difference between the pre‐operative threshold and each of the post‐operative thresholds. The cochleae were examined histologically 4 weeks after electrode‐dummy insertion. Threshold shifts changed with frequency but not time. At 2 kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32 kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode‐dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis.

Protective effects of the seaweed phlorotannin polyphenolic compound dieckol on gentamicin-induced damage in auditory hair cells

OBJECTIVESnDrug-induced ototoxicity from compounds such as aminoglycosides and platinum can damage the inner ear resulting in hearing loss, tinnitus or balance problems and may be caused by the formation of reactive oxygen species (ROS). Dieckol is a phlorotannin polyphenolic compound with strong antioxidant effects found in edible brown algae. This study investigated the protective effects of dieckol on drug-induced ototoxicity in cochlear cultures obtained from neonatal mice.nnnMETHODSnCochlear explants were pretreated with dieckol and exposed to gentamicin for 48h. The explants were then fixed and stained with fluorescein isothiocyanate-phalloidin and the intact hair cells counted. The free radical scavenging activity of dieckol was assessed using a 1,1-diphenyl-2-picrylhydrazyl assay. E. coli (Escherichia coli) cultures were used to evaluate the effect of dieckol on the antibiotic activity of gentamicin.nnnRESULTSnGentamicin treatment resulted in dose-dependent hair cell loss that was partially protected by dieckol. Moreover, at concentrations >67μM dieckol had significant radical scavenging activity. Dieckol did not compromise the antibiotic effect of gentamicin.nnnCONCLUSIONSnThese findings suggest that dieckol can be used as a therapeutic agent that reduces the damage caused by drug-induced ototoxicity.

Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness

BackgroundMYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.MethodsTwo multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.ResultsIn the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504Gu2009>u2009A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790Cu2009>u2009T (p.Q3264X) and c.10263Cu2009>u2009G (p.I3421M) in the FERM domain were detected as candidate variants.ConclusionsSome recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.

MicroRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation

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.

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

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

One-step noninvasive prenatal testing (NIPT) for autosomal recessive homozygous point mutations using digital PCR

Previously, we introduced a noninvasive prenatal testing (NIPT) protocol for diagnosing compound heterozygous autosomal recessive point mutations via maternal plasma DNA and simulated control genomic DNA sampling based on fetal DNA fraction. In our present study, we have improved our NIPT protocol to make it possible to diagnose homozygous autosomal recessive point mutations without the need to acquire fetal DNA fraction. Moreover, chi-squared test and empirical statistical range based on the proportion of mutant allele reads among the total reads served as the gatekeeping method. If this method yielded inconclusive results, then the Bayesian method was performed; final conclusion was drawn from the results of both methods. This protocol was applied to three families co-segregating congenital sensorineural hearing loss with monogenic homozygous mutations in prevalent deafness genes. This protocol successfully predicted the fetal genotypes from all families without the information about fetal DNA fraction using one-step dPCR reactions at least for these three families. Furthermore, we suspect that confirmatory diagnosis under this protocol is possible, not only by using picodroplet dPCR, but also by using the more readily available chip-based dPCR, making our NIPT protocol more useful in the diagnosis of autosomal recessive point mutations in the future.

Characterization of Detailed Audiological Features of Cytomegalovirus Infection: A Composite Cohort Study from Groups with Distinct Demographics

Congenital cytomegalovirus (cCMV) infection is a common congenital infection that causes sensorineural hearing loss (SNHL). Despite its substantial impact on public health and cost burden, epidemiology and clinical features of CMV-related SNHL have never been reported in the Korean populations. This study investigated the detailed audiologic phenotypes of cCMV infection to see if a specific SNHL pattern is associated with a particular clinical setting. A total of 38 patients with cCMV infection were studied retrospectively. Patients were classified into three groups with distinct demographics: clinically driven diagnosis (n=17), routine newborn CMV screening according to the NICU protocols (n=10), or referral to ENT for cochlear implant (CI) (n=11). The incidence of cCMV infection was 3.6%, showing 33.3% of SNHL among cCMV patients, 38% of asymmetric hearing loss, 29% of late-onset hearing loss, and diverse severity spectrum in patients with CMV-related SNHL. CI recipients with CMV-related SNHL showed a significantly improved speech perception. Surprisingly, in 36.4 % of CI implantees, initial audiological manifestation was significant asymmetry of hearing thresholds between both ears, with better ear retaining significant residual hearing up to 50dB. CMV turns out to be a significant etiology of SNHL, first to date reported in the Korean pediatric population. Analysis of audiologic phenotypes showed a very wide spectrum of SNHL and favorable CI outcomes in case of profound deafness. Especially for the patients with asymmetric hearing loss, close surveillance of hearing should be warranted and CI could be considered on the worse side first, based on the observation of rapid progression to profound deafness of better side.

Using temporal bone computed tomography to predict sensorineural hearing loss in otic capsule-sparing temporal bone fracture

OBJECTIVESnThe purpose of this study was to investigate the efficacy of otic capsule-sparing (OCS) length for the prediction of sensorineural hearing loss (SNHL) in patients with OCS temporal bone fracture.nnnMETHODSnThirty-four patients with OCS temporal bone fracture were enrolled, and their temporal bone computed tomography (TBCT), audiogram, and medical records were reviewed. The TBCT measured the shortest length between the otic capsule and fracture line. This length was referred to as the OCS length and was used to predict SNHL. Ossicular dislocation and fracture were also evaluated. Patients were divided into two groups according to the presence of SNHL. Univariate and multivariate analyses were performed for age, gender, brain hemorrhage, mean bone conduction threshold on the contralesional side, OCS length, and ossicular dislocation and fracture on TBCT. A receiver operating characteristic (ROC) curve was produced to evaluate the efficacy of OCS length for the prediction of SNHL. To determine an association between degree of SNHL and OCS length, regression analysis was conducted in the SNHL group.nnnRESULTSnThe mean OCS lengths of the SNHL and non-SNHL groups were 4.42±1.67mm and 8.00±5.71mm, respectively. In the univariate analysis, a relatively significant association (P <0.20) was found between SNHL and age, brain hemorrhage, mean bone conduction threshold on the contralesional side, OCS length, and incus dislocation. Multivariate analysis was performed using these factors. On multivariate analysis, OCS length (P=0.030, odds ratio=0.598; 95% confidence interval 0.375-0.952) was the only independent factor associated with SNHL. The area under the curve (AUC) was 0.747. When the cut-off value of OCS length was 5.27mm, the sensitivity and specificity for the prediction of SNHL were 71.4% and 69.2%, respectively. In the regression analysis, OCS length showed a significant association with degree of SNHL in the SNHL group (P=0.025, β=-12.822, SE=5.282).nnnCONCLUSIONSnThe major finding of our study was that OCS length was significantly associated with SNHL in patients with OCS temporal bone fracture. Such patients with a short OCS length had a higher likelihood of SNHL.

Clinical implication of cervical vestibular evoked myogenic potentials in benign paroxysmal positional vertigo.

OBJECTIVESnTo evaluate the value of cervical vestibular evoked myogenic potential (cVEMP) as a prognostic factor for benign paroxysmal positional vertigo (BPPV).nnnMETHODSnWe reviewed 65 patients with BPPV who underwent cVEMP. Patients were divided into two groups according to resistance to the repositioning maneuver. Univariable and multivariable analyses were performed with age, gender, affected semicircular canal, affected side and cVEMP parameters to find the associated factors for resistance to the repositioning maneuver.nnnRESULTSnFrom univariable analysis, cVEMP interaural amplitude difference (IAD) ratio, the affected semicircular canal and the affected side showed a better association (p<0.10) with resistance to the repositioning maneuver. With multivariable analysis, decreased cVEMP IAD ratio at the affected side (⩽-25%) (p=0.043, OR=4.934) and the posterior semicircular canal (p=0.049, OR=3.780) remained as associated factors.nnnCONCLUSIONSnDecreased cVEMP IAD ratio at the affected side is associated with resistance to the repositioning maneuver. BPPV patients with decreased cVEMP IAD ratio at the affected side have a higher likelihood of their BPPV persisting after a single repositioning maneuver.nnnSIGNIFICANCEncVEMP test may provide a prognosis of BPPV. A decreased cVEMP IAD ratio at the affected side may be prognostic of BPPV not resolving after a single repositioning maneuver.