OBJECTIVES: Genetic hearing loss is highly heterogeneous and more than 100 genes are predicted to cause this disorder in humans. In spite of this large genetic heterogeneity, mutations in SLC26A4 and GJB2 genes are primarily responsible for the major etiologies of genetic hearing loss among Koreans. The purpose of this study is to investigate the genetic cause of deafness in Korean cochlear implantees by performing a genetic screening of the SLC26A4 and GJB2 genes. METHODS: The study cohort included 421 unrelated Korean patients with sensorineural hearing loss (SNHL) and who had received cochlear implants (CI) at Soree Ear Clinic from July 2002 to December 2010. Among 421 CI patients, we studied 230 cases who had received the genetic screening for SLC26A4 or GJB2 genes. Written informed consent was obtained from all participants. All patients had severe to profound, bilateral hearing loss. For 56 patients who showed enlarged vestibular aqueduct on their computed tomography (CT) scan, we analyzed SLC26A4. For 174 CT negative patients, GJB2 gene was sequenced. RESULTS: For the 56 SLC26A4 patients, 32 (57.1%) had two pathogenic recessive mutations in SLC26A4. A single recessive SLC26A4 mutation was identified in 14 patients (25%). H723R and IVS7-2A>G were the most commonly found mutations, accounting for 60.3% (47/78) and 30.8% (24/78) of the mutated alleles, respectively. For the 174 GJB2 patients, 20 patients (11.5%) had two pathogenic recessive mutations in GJB2. 235delC was the most common mutation, accounting for 43.0% (31/72) of mutant alleles. CONCLUSION: The two major genes, SLC26A4 and GJB2, contribute major causes of deafness in CI patients. Continuous studies are needed to identify new genes that can cause hearing loss to Korean CI patients.
Accounting ; Alleles ; Cochlear Implants ; Cohort Studies ; Connexins ; Deafness ; Ear ; Genetic Heterogeneity ; Genetic Testing ; Goiter, Nodular ; Hearing Loss ; Hearing Loss, Bilateral ; Hearing Loss, Sensorineural ; Humans ; Informed Consent ; Vestibular Aqueduct

OBJECTIVE: The aim of the present study was to examine the relative role of anxiety sensitivity and hearing loss on the tinnitus symptoms severity in a large clinical sample of patients with tinnitus. METHODS: A total of 1,705 patients with tinnitus who visited the tinnitus clinic underwent the pure-tone audiometric testing and a battery of self-report questionnaires. Multiple linear regression analyses were performed to identify the relationship of anxiety sensitivity and hearing loss to tinnitus symptoms severity. RESULTS: Both anxiety sensitivity and hearing loss were a significant association with of annoyance (anxiety sensitivity β=0.11, p=0.010; hearing loss β=0.09, p=0.005) and THI score (anxiety sensitivity β=0.21, p < 0.001; hearing loss β=0.10, p < 0.001) after adjusting for confounding factors. Meanwhile, the awareness time (β=0.19, p < 0.001) and loudness (β=0.11, p < 0.001) of tinnitus was associated with only the hearing loss but not with anxiety sensitivity CONCLUSION: Our results indicate that both hearing loss and anxiety sensitivity were associated with increased tinnitus symptom severity. Furthermore, these associations could be different according to the characteristics of tinnitus symptoms.
Anxiety ; Hearing Loss ; Hearing ; Humans ; Linear Models ; Tinnitus

BACKGROUND AND OBJECTIVES: After the bone anchored hearing aid (BAHA) surgery, soft tissue problems have frequently been reported. To solve this problem, a surgical procedure that routinely involves so-called skin thinning using BAHA dermatome has been utilized. But, this procedure includes many peri-implant complications and cosmetic trouble. Recently, a single vertical incision technique that does not involve skin thinning has been reported with favorable results. In this study, we evaluated the benefits of performing this procedure without skin thinning compared with the dermatome technique. SUBJECTS AND METHOD: We evaluated 10 patients who were operated on without skin thinning using longer (8.5 mm) abutments (the test group) and 5 patients with the routine skin thinning and 5.5-mm abutments (the control group). A mean follow-up time was 11.3 months, the mean age was 34.2 years in the test group, the mean follow-up time was 54.5 months and a mean age is 24.5 years in the control group. RESULTS: The mean time required for surgery was 25 minutes and 55 minutes for the test and control groups, respectively. The wound healing time was 28 days and 56 days for the test and control groups, respectively. Fixture extrusion, skin infection and skin overgrowth were not observed in the test group but fixture extrusion case, two skin infection cases and two skin overgrowth cases were observed in the control group. Two cases of abutment loosening were observed in the test group. CONCLUSION: The single vertical incision technique without skin thinning has many benefits when compared with the BAHA dermatome. With this technique, infection and skin overgrowth could be reduced, and a more rapid procedure and a more short healing time could also be possible. Moreover, the aesthetic outcome was far better when no skin thinning was involved.
Bone Conduction ; Cosmetics ; Follow-Up Studies ; Hearing ; Hearing Aids ; Humans ; Osseointegration ; Postoperative Complications ; Skin ; Suture Anchors ; Wound Healing

OBJECTIVES: Bone-anchored hearing aids (BAHA) occasionally cause soft tissue problems due to abutment. Because Sophono does not have abutment penetrating skin, it is thought that Sophono has no soft tissue problem relating to abutment. On the other hand, transcutaneous device's output is reported to be 10 to 15 dB lower than percutaneous device. Therefore, in this study, Sophono and BAHA were compared to each other from surgical and audiological points of view. METHODS: We retrospectively reviewed the medical records of 9 Sophono patients and 10 BAHA patients. In BAHA cases, single vertical incision without skin thinning technique was done. We compared Sophono to BAHA by operation time, wound healing time, postoperative complications, postoperative hearing gain after switch on, and postoperative air-bone gap. RESULTS: The mean operation time was 60 minutes for Sophono and 25 minutes for BAHA. The wound healing time was 14 days for Sophono and 28 days for BAHA. No major intraoperative complication was observed. Skin problem was not observed in the 2 devices for the follow-up period. Postoperative hearing gain of bilateral aural atresia patients was 39.4 dB for BAHA (n=4) and 25.5 dB for Sophono (n=5). However, the difference was not statistically significant. In all patients included in this study, the difference of air-bone gap between two groups was 16.6 dB at 0.5 kHz and 18.2 dB at 4 kHz. BAHA was statistically significantly better than Sophono. CONCLUSION: Considering the audiologic outcome, BAHA users were thought to have more audiologic benefit than Sophono users. However, Sophono had advantages over BAHA with abutment in cosmetic outcome. Sophono needed no daily skin maintenance and soft tissue complication due to abutment would not happen in Sophono. Therefore, a full explanation about each device is necessary before deciding implantation.
Bone Conduction ; Follow-Up Studies ; Hand ; Hearing Aids* ; Hearing Loss ; Hearing Loss, Conductive ; Hearing* ; Humans ; Intraoperative Complications ; Medical Records ; Postoperative Complications ; Retrospective Studies ; Skin ; Wound Healing

Background/Aims: The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. Methods: Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. Results: We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. Conclusions Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

BACKGROUND/AIMS: Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. METHODS: The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. RESULTS: The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. CONCLUSIONS: We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues.
DNA ; Drug Resistance ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Lamivudine ; Mass Screening ; Oligonucleotide Array Sequence Analysis ; Sensitivity and Specificity