Joong-Wook Shin

Genetic Screening of GJB2 and SLC26A4 in Korean Cochlear Implantees: Experience of Soree Ear Clinic.

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.

Evaluation of stress reactivity and recovery using biosignals and fuzzy theory

This paper is about the evaluation of stress reactivity and recovery using biosignals and fuzzy theory. We induced mental stress by means of a coin-stacking task. During the experiment, 4 kinds of biosignals, which are frontalis EMG, ECG, peripheral skin temperature and skin conductance level, were acquired. Then, the degree of stress was assessed by synthetically analyzing those signals using fuzzy inference. From the fuzzy inference result, the parameters (Amount of Physiological Change/Amount of Imposed Stress) and (Time to 25% Recovery), which represent reactivity and recovery respectively, were derived. We made a graph using the reactivity parameter as an abscissa and the recovery parameter as an ordinate for each subject. From the graph, the distance from the origin to the coordinate ((Amount of Physiological Change/Amount of Imposed Stress), (Time to 25% Recovery)) was introduced as a stress index. An insensitive reactivity and a fast recovery is an effective coping with stress. Therefore, the small value of the stress index proposed in this research will indicate being in good health.

Identification of CDH23 mutations in Korean families with hearing loss by whole-exome sequencing

BackgroundPatient genetic heterogeneity renders it difficult to discover disease-cause genes. Whole-exome sequencing is a powerful new strategy that can be used to this end. The purpose of the present study was to identify a hitherto unknown mutation causing autosomal recessive nonsyndromic hearing loss (ARNSHL) in Korean families.MethodsWe performed whole-exome sequencing in 16 individuals from 13 unrelated small families with ARNSHL. After filtering out population-specific polymorphisms, we focused on known deafness genes. Pathogenic effects of the detected mutations on protein structure or function were predicted via in silico analysis.ResultsWe identified compound heterozygous CDH23 mutations in hearing-loss genes of two families. These include two previously reported pathological mutations, p.Pro240Leu and p.Glu1595Lys, as well as one novel mutation, p.Asn342Ser. The p.Pro240Leu mutation was found in both families. We also identified 26 non-synonymous variants in CDH23 coding exons from 16 hearing-loss patients and 30 Korean exomes.ConclusionThe present study is the first to show that CDH23 mutations cause hearing loss in Koreans. Although the precise contribution made by such mutations needs to be determined using a larger patient cohort, our data indicate that mutations in the CDH23 gene are one of the most important causes of non-syndromic hearing loss in East Asians. Further exome sequencing will identify common mutations or polymorphisms and contribute to the molecular diagnosis of, and development of new therapies for, hereditary hearing loss.

The Web-based fuzzy patient monitor system

We tried to develop a patient monitoring system using fuzzy information. According to a trend from a client-server system to a Web-based system, this fuzzy patient monitoring system was advanced by adding a Web-based monitoring system which was offered with real-time per about 10 seconds. This system is operated in the Microsoft Internet Explorer 5.0 because of a FTP ActiveX control which transfers the updated-file of a patient monitoring information and alarms by pre-setting values on a server. This system offers not only the real-time monitoring information but also the references of a patients ECG waveform and a past recorded data.

Intrafamilial phenotypic variability in families with biallelic SLC26A4 mutations

Enlarged vestibular aqueduct (EVA) and hearing loss are known to be caused by SLC26A4 mutations, but large phenotypic variability exists among patients with biallelic SLC26A4 mutations. Intrafamilial phenotypic variability was analyzed in multiplex EVA families carrying biallelic SLC26A4 mutations to identify the contribution of SLC26A4 mutations and other genetic or environmental factors influencing the clinical manifestations.

Surgical and Audiologic Comparison Between Sophono and Bone-Anchored Hearing Aids Implantation

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.

Evaluation of body movement during sleep by thermopile using wavelet and neuro-fuzzy

Body movement is one of the important factors in sleep analysis. Instant body movement signals were evaluated for the upper, lower, and entire part of the body from a combination of the eighth scale detail signals using the Haar wavelet. These signals show the points of time when the upper-body or lower-body movement occurred and the level of body movement. Additionally, partial body movement was decomposed to three parts of body movement comprising head-only, whole body, and leg-only movement using the ANFIS. After training data for 30 epochs, the three parts of the body movement data were acquired with minimized RMSE, 23.4, 12.1, and 20.8 respectively. Finally, three subjects data were evaluated for 60 minutes, and the detection rates of instant and partial body movement, on average, were 96.3% and 89.2%, respectively.

Chronic stress evaluation using neuro-fuzzy

The purpose of this research was to evaluate chronic stress using physiological parameters. Wistar rats were exposed to sound stress for 14 days. Biosignals were acquired hourly. To develop a fuzzy inference system that can integrate physiological parameters, the parameters of the system were adjusted by the adaptive neuro-fuzzy inference system. Of the training dataset, the input dataset was the physiological parameters from the biosignals and the output dataset was the target values from the cortisol production. Physiological parameters were integrated using the fuzzy inference system, then 24-hour results were analyzed by the Cosinor method. Chronic stress was evaluated from the degree of circadian rhythm disturbance. Suppose that the degree of stress for initial rest period was 1. Then, the degree of stress after 14-day sound stress increased to 131, and increased to 1.47 after the 7-day recovery period. That is, the rat was exposed to 37%increased amount of stress by the 14-day sound and did not recover after the 7-day recovery period.

Similarity classification for bio-signals using fuzzy table look-up by distance and eigenvector

In this paper, two kinds of features, the distance and the angle difference of eigenvectors between two signals, were selected to input a fuzzy similarity inference system. Twelve visual evoked potential (VEP) signals were experimented on to test the fuzzy classification of similarity, and they were compared to each other in similarity. The similarity was taken by the regular section, so the the partial similarity analysis was available, and the total degree of similarity was calculated by averaging to similarity of each section.

Viability of bone cement augmented compression hip screw system for the treatment of intertrochanteric fracture: a biomechanical analysis

Screw cut-out and non-union have been cited as major complications with hip screw systems for the treatment of intertrochanteric femoral fractures. Recently, cement augmentation of hip screw system has been introduced to provide better purchase of the screw. This study investigates the biomechanical efficacy of cement augmentation technique by assessing the changes in stress distributions within the femur and the surgical construct. Finite element models of the operated femur with sliding hip screw assemblies were constructed with and without bone cement augmentation. To simulate the fracture plane and other interfacial regions, 3-D contact elements were used with appropriate friction coefficients. Our results demonstrated the efficacy of the cement augmentation: 80% reduction in stresses was found in the cancellous bone due to cement augmentation, suggesting that the fractures of the cancellous bone and the cut-out of the screw are far less likely to take place. The peak von Mises stress within the cement mantle was about 1/3 of its fatigue strength. The likelihood of cement failure that might lead to osteolysis due to cement debris was not apparent. The micromotion at the hip screw interface was reduced from 0.275 mm to 0.008 mm, an indication for strong fixation after surgery.