Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss

Objectives@#. Age-related hearing loss (ARHL), or presbycusis, is caused by disorders of sensory hair cells and auditory neurons. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, noise, inflammation, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Long non-coding RNA (lncRNA) has been reported to play important roles in various diseases. However, the function of lncRNA in ARHL remains unclear. In this study, we analyzed the common expression profiles of messenger RNA (mRNA) and lncRNA through ARHL-related RNA-sequencing datasets. @*Methods@#. We selected and downloaded three different sets of RNA-sequencing data for ARHL. We performed differential expression analysis to find common mRNA and lncRNA profiles in the cochleae of aged mice compared to young mice. Gene Ontology (GO) analysis was used for functional exploration. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate mRNAs and lncRNAs. In addition, we performed trans target prediction analysis with differentially expressed mRNAs and lncRNAs to understand the function of these mRNAs and lncRNAs in ARHL. @*Results@#. We identified 112 common mRNAs and 10 common lncRNAs in the cochleae of aged mice compared to young mice. GO analysis showed that the 112 upregulated mRNAs were enriched in the defense response pathway. When we performed qRT-PCR with 1 mM H2O2-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, the qRT-PCR results were consistent with the RNA-sequencing analysis data. lncRNA-mRNA networks were constructed using the 10 common lncRNAs and 112 common mRNAs in ARHL. @*Conclusion@#. Our study provides a comprehensive understanding of the common mRNA and lncRNA expression profiles in ARHL. Knowledge of ARHL-associated mRNAs and lncRNAs could be useful for better understanding ARHL and these mRNAs and lncRNAs might be a potential therapeutic target for preventing ARHL.

Development of Sound Field Audiometry System for Small Audiometric Booths and Comparison of Its Equivalence With Traditional System

Objectives@#. Sound field (SF) audiometry tests are usually conducted in audiometric booths measuring greater than 2×2 m in size. However, most private ENT clinics carry about 1×1-m-sized audiometric booths, making SF audiometry testing difficult to perform. The aims of this study were to develop an SF audiometry system for use in smaller audiometric booths and compare its performance with traditional system. @*Methods@#. The newly developed SF audiometry system can yield an SF signal at a distance of about 30 cm from the subject’s ears. Its height can be adjusted according to the subject’s head height. We compared SF hearing results between the new SF system and the traditional SF audiometry system in 20 adults with normal hearing (40 ears) and 24 adults with impaired hearing levels (38 ears) who wore hearing aids. Comparative parameters included warble tone audiometry threshold, a speech reception threshold (SRT), and a speech discrimination score (SDS). For statistical analysis, paired t-test was used. The equivalence of both SF systems was tested using two one-sided test (TOST) with a margin of 5 dB (normal hearing participants) and 10 dB (hearing aids wearing participants). @*Results@#. Among participants with normal hearing, warble tone hearing thresholds of 0.5, 1, 2, and 4 kHz, average values of these four frequencies, and SRT were similar between the two systems (all P>0.05). Participants with hearing aids showed similar warble tone threshold and SRT (P>0.05) in both systems except for threshold of 4 kHz (P=0.033). SDS was significantly higher in the newly developed system (P<0.05). TOST results showed equivalent SF audiometry results using either system. @*Conclusion@#. Audiometric results of the newly developed SF audiometry system were equivalent to those of a traditional system. Therefore, the small SF audiometry system can be used at small audiometric booths present in most private ENT clinics.

Transcanal Endoscopic Tympanoplasty for Pediatric Patients Under 15 Years of Age With Chronic Otitis Media

Objectives@#. To evaluate the results of transcanal endoscopic tympanoplasty for pediatric patients with chronic otitis media (COM) and compare them to that of the previously standard microscopic assisted tympanoplasty technique. @*Methods@#. The patients were divided into two groups based on the operative method. Group 1 underwent tympanoplasty with a totally endoscopic assisted technique (n=21, 24 ears), and group 2 underwent tympanoplasty with the conventional microscopic technique (n=14, 15 ears). We used a transcanal approach in group 1 and a postauricular approach in group 2. In group 1, there were 15 cases of simple COM and nine cases of adhesive otitis media. In group 2, only 15 cases of simple COM were present. We analyzed the outcomes in terms of the hearing gain according to the surgical method and COM type, operation time, hospital stay after surgery, and graft success rate. @*Results@#. Postoperative hearing gain results including air conduction (AC) thresholds and air-bone gap (ABG) were not significantly different between the two groups (P>0.05). In both the groups, significant improvement in the postoperative AC and ABG was observed compared to the preoperative hearing. The hospital stay after surgery was significantly shorter in group 1 than the group 2: 2.1±0.4 days and 4.8±0.9 days (P0.05). There was neither intra- nor postoperative complications. @*Conclusion@#. Transcanal endoscopic ear surgery technique is more conservative than microscopic approach and can be performed in pediatric patients under 15 years of age with COM. Moreover, it offers similar surgical results compared to traditional microscopic technique, and a shorter operative time and hospital stay after surgery are the advantages of this technique.

Atoh1 as a Coordinator of Sensory Hair Cell Development and Regeneration in the Cochlea / 전남의대학술지

Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs. We will also discuss the potential applicability of these signals for the induction of HC regeneration.

The Effect of Mastoidectomy Combined with Tympanoplasty Type I on Postoperative Hearing in Chronic Otitis Media Patients Older than 65 Years / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Although canal wall up mastoidectomy (CWUM) has been performed frequently as a treatment for chronic otitis media (COM), the necessity of CWUM for non-cholesteatomatous COM (NCCOM) is still controversial. Since elderly people often have systemic problems, there is a high likelihood of side effects after general anesthesia, so it is important to judge the necessity of mastoidectomy. The purpose of this study was to investigate the effect of CWUM for the treatment of NCCOM in patients over 65 years of age. SUBJECTS AND METHOD: Forty-two cases of CWUM with tympanoplasty type I performed as a treatment for NCCOM from 2007 through 2016 were reviewed retrospectively. Pure tone audiometry was performed preoperatively and postoperatively, and preoperative temporal bone CT was used to evaluate the mastoid status. The valsalva maneuver (VM) was used to evaluate the eustachian tube function. RESULTS: The total number of patients was 42 and the success rate of eardrum repair was 92.8%. Comparison of hearing results taken preoperatively and postoperatively showed significant hearing improvement in both air conduction and air-bone gap. When hearing results were compared according to the mastoid status and the response of VM, there were no significant differences. CONCLUSION: Mastoidectomy combined with tympanoplasty type I showed a high success rate of ear drum repair and good hearing improvement, with no critical side effects. Therefore, mastoidectomy does not need to be limited by one's old age. Adequate mastoidectomy after proper consideration of the mastoid status will be helpful in the treatment of the disease.

Atoh1 as a Coordinator of Sensory Hair Cell Development and Regeneration in the Cochlea / 전남의대학술지

Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs. We will also discuss the potential applicability of these signals for the induction of HC regeneration.

Middle Ear Actinomycosis Involving Facial Nerve and Lateral Semicircular Canal / 대한이비인후과학회지

Actinomycosis is a chronic granulomatous disease caused by the species of Actinomyces. Although it has become a rare disease in the present antibiotics era, it still needs long term antibiotic treatment and often mis- or delayed- diagnosed due to no typical sign and symptoms. Most often, it occurs in the cervicofacial region. Middle ear is not a common site for Actinomycosis, and the inner ear involvement is extremely rare. Here, we report a case of middle ear Actinomycosis involving facial nerve and lateral semicircular canal.

A Case of Cochlear Implantation in Bromate-Induced Bilateral Sudden Deafness

Despite the well-established nature of bromate-induced ototoxicity, cochlear implantation after bromate intoxication has been rarely documented. We hereby present a case of a 51-year-old female deafened completely after bromate ingestion. Her hearing was not restored by systemic steroid treatment and hearing aids were of no use. A cochlear implantation was performed on her right ear 3 months after the bromate ingestion. In bromate intoxication cases, early monitoring of hearing level is necessary and other drugs with potential ototoxicity should be avoided. The outcome of cochlear implantation was excellent in this case of bromate-induced deafness.

Outcomes of Severe to Profound Idiopathic Sudden Sensorineural Hearing Loss

OBJECTIVES: While a severe to profound sudden sensorineural hearing loss (SSNHL) may cause serious disability in verbal communication, there have been little studies focusing on this high degree SSNHL. The present study was aimed to investigate the characteristics of hearing recovery in a high degree SSNHL (>70 dB). METHODS: Three hundred and two SSNHL patients were enrolled. For a long-term follow-up, 46 patients were evaluated. Hearing level was examined by pure tone audiometry on day 1, week 3, month 3, month 6, and year 1 or after. According to the degree of the initial hearing loss, the patients were divided into 4 groups from 70 to > or =100 dB. RESULTS: After 3 weeks, the recovery rate and mean hearing gain was 61%, 23.85 dB in the 70 dB group, whereas 10%, 6.61 dB in the > or =100 dB group. There was a significant correlation between 3-week recovery and final hearing outcome. However, there was almost no recovery after 3 months. CONCLUSION: An early recovery can be a prognostic factor for the final recovery in severe to profound SSNHL. Since recovery after 3 months is rare, an early hearing intervention like hearing aid or cochlear implantation should be considered in the high degree SSNHL to restore the patient's verbal communication.

A Case of Cochlear Implantation Targeting Preserved Cerebral Cortex in Severe Traumatic Brain Injury

Temporal bone fracture and blunt head trauma was once considered as contraindication for the surgery. Increasing numbers of successful cochlear implantation are being reported. However, the outcome of cochlear implantation in severe damaged brain is unclear. A multichannel cochlear implant was successfully implanted in a 33-year-old man who had both sensorineural deafness, left hemiplegia due to bilateral transverse temporal bone fractures and severe right brain damage after a traffic accident.

Blunted Indomethacin-Induced Downregulation of Aquaporins by Nitric Oxide Synthesis Inhibition in Rats

The present study was aimed to determine whether nitric oxide (NO) plays a role in the regulation of aquaporin (AQP) channels in the kidney. Male Brattleboro rats (250~300 g body weight) were used. The experimental group was treated with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 1 week, and cotreated with indomethacin (5 mg/kg, twice a day, i.p.) for the last two days. Control groups were treated with either L-NAME for 1 week, indomethacin for 2 days, or without any drug treatment. The abundance of AQP1, AQP2 and AQP3 proteins in the kidney was determined by Western blot analysis. Indomethacin downregulated AQP channels, whereas L-NAME by itself showed no significant effects on them. The indomethacin-induced downregulation of AQP2 and AQP3 was significantly blunted in L-NAME-treated rats, while that of AQP1 was not affected. These results suggest that endogenous NO, when stimulated, may downregulate AQP channels that are specifically regulated by AVP/cAMP pathway in the kidney.

Altered Regulation of Aquaporin-2 Water Channels in the Kidney Following Acute Blood Volume Depletion in Rats / 대한신장학회잡지

BACKGROUND: The present study was aimed to examine the regulation of aquaporin (AQP)-2 water channels in the kidney following blood volume depletion. METHODS: Male Sprague-Dawley rats were acutely blood volume-depleted by withdrawal of arterial blood up to 2% of body weight. The expression of AQP2 mRNA and protein was determined by reverse transcription - polymerase chain reaction and Western blot analysis, respectively, in the inner medulla of the kidney 1 and 3 hours after the hemorrhage. RESULTS: The mRNA expression of AQP2 was significantly increased 1 hour after the bleeding. However, neither the shuttling nor the total abundance of AQP2 proteins was significantly altered. On the contrary, 3 hours after the bleeding, the expression of AQP2 proteins as well as that of AQP2 mRNA was significantly increased. The shuttling of AQP2 proteins was also increased. CONCLUSION: These results suggest that an increased expression of AQP2 channels in the kidney may confer one of compensatory mechanisms restoring the circulating volume in an acute hypovolemic state.

Enhanced Expression of Aldosterone Synthase and Adrenomedullin in Left and Right Ventricular Hypertrophy in Rats

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.