Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2−/− Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS

Association between vestibular schwannomas and mobile phone use

Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case–control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case–case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case–control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case–case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2) = 0.144, p = 0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p < 0.001). When the analysis was limited to regular users who had serviceable hearing, laterality showed a strong correlation with tumor side (OR = 4.5). We found that tumors may coincide with the more frequently used ear of mobile phones and tumor volume that showed strong correlation with amount of mobile phone use, thus there is a possibility that mobile phone use may affect tumor growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13277-013-1081-8) contains supplementary material, which is available to authorized users

Reliability modeling of digital component in plant protection system with various fault-tolerant techniques

With the improvement of digital technologies, digital protection system (DPS) has more multiple sophisticated fault-tolerant techniques (FTTs), in order to increase fault detection and to help the system safely perform the required functions in spite of the possible presence of faults. Fault detection coverage is vital factor of FTT in reliability. However, the fault detection coverage is insufficient to reflect the effects of various FTTs in reliability model. To reflect characteristics of FTTs in the reliability model, integrated fault coverage is introduced. The integrated fault coverage considers the process of FTT from detection to fail-safe generation process. A model has been developed to estimate the unavailability of repairable component of DPS using the integrated fault coverage. The new developed model can quantify unavailability according to a diversity of conditions. Sensitivity studies are performed to ascertain important variables which affect the integrated fault coverage and unavailability

Developmental changes of ENaC expression and function in the inner ear of pendrin knock-out mice as a perspective on the development of endolymphatic hydrops.

Pendrin mutations cause enlarged vestibular aqueducts and various degrees of sensorineural hearing loss. The selective abolition of pendrin causes dilation of the membranous labyrinth known as endolymphatic hydrops, loss of the endocochlear potential, and consequently loss of hearing function. Because Na+ transport is one of the most important driving forces for fluid transport, the epithelial Na+ channel (ENaC) is believed to play an important role in fluid volume regulation in the inner ear. Therefore, the dysfunction of Na+ transport through ENaC by the acidification of endolymph in Pendred syndrome is one of the potential causes of endolymphatic hydrops. We investigated the changes of ENaC expression and function during the development of the pendrin knock-out mouse. In the cochlea, the expression of β and γENaC was significantly increased at P56 in Pds-/- mice compared with Pds+/+ mice. In the vestibule, the expression of βENaC was significantly increased at P56, and γENaC expression significantly increased from P6 to P56 in Pds-/- mice. The ENaC-dependent trans-epithelial current was not significantly different between Pds+/+ and Pds-/- mice in Reissner's membrane or the saccular extramacular roof epithelium at P0, but the current was significantly increased in Pds-/- mice at P56 compared with Pds+/+ mice. These findings indicate that the expression and function of ENaC were enhanced in Pds-/- mice after the development of endolymphatic hydrops as a compensatory mechanism. This result provides insight into the role of Na+ transport in the development and regulation of endolymphatic hydrops due to pendrin mutations

National representative analysis of unilateral hearing loss and hearing aid usage in South Korea.

A definitive study on the prevalence of adult unilateral hearing loss and hearing aid rehabilitation is lacking in Korea. The purpose of our study was to investigate the prevalence of adult unilateral hearing loss and the factors associated with hearing aid use in patients with unilateral hearing loss in South Korea. We obtained data from 2009 to 2012 from the Korea National Health and Nutrition Examination Surveys (KNHANES), a cross-sectional, nationwide and population-based survey in the Republic of Korea. We analyzed the prevalence and associated factors of unilateral hearing loss and hearing aid adoption by univariable and multivariable analysis. Unilateral hearing loss was defined as pure tone average ≥ 41 dB in the worse hearing ear, and < 41 dB in the other ear assessed at 0.5, 1.0, 2.0, and 3.0 kHz. From 2009 to 2012, 33,252 individuals participated in the KNHANES. Among them, the number of patients with unilateral hearing loss was 1632 (5.55%) and the prevalence of hearing aid adoption in unilateral hearing loss was 1.56%. We also compared the factors between hearing aid users and non-users. Occupational status (OR 3.759, 95% CI 1.443-9.804), the hearing threshold in the better ear (OR 1.088, 95% CI 1.029-1.151), and hearing threshold in the worse ear (OR 1.031, 1.005-1.058) were found to affect the adoption of hearing aids. The prevalence of noise exposure at work in hearing aid users was significantly lower than the prevalence of noise exposure at work in those with no hearing aid. The prevalence of hearing aid use in patients with unilateral hearing loss in Korea is very low compared to other countries. Public health education is needed to increase public awareness of unilateral hearing loss, hearing aid adoption and its continued usage. Auditory rehabilitation should be actively recommended to patients with unilateral hearing loss

A software tool for integrated risk assessment of spent fuel transportation and storage

When temporary spent fuel storage pools at nuclear power plants reach their capacity limit, the spent fuel must be moved to an alternative storage facility. However, radioactive materials must be handled and stored carefully to avoid severe consequences to the environment. In this study, the risks of three potential accident scenarios (i.e., maritime transportation, an aircraft crashing into an interim storage facility, and on-site transportation) associated with the spent fuel transportation process were analyzed using a probabilistic approach. For each scenario, the probabilities and the consequences were calculated separately to assess the risks: the probabilities were calculated using existing data and statistical models, and the consequences were calculated using computation models. Risk assessment software was developed to conveniently integrate the three scenarios. The risks were analyzed using the developed software according to the shipment route, building characteristics, and spent fuel handling environment. As a result of the risk analysis with varying accident conditions, transportation and storage strategies with relatively low risk were developed for regulators and licensees. The focus of this study was the risk assessment methodology; however, the applied model and input data have some uncertainties. Further research to reduce these uncertainties will improve the accuracy of this model

Autoimmunity as a Candidate for the Etiopathogenesis of Meniere's Disease: Detection of Autoimmune Reactions and Diagnostic Biomarker Candidate

<div><p>Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23–48 kDa and 63–75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease.</p></div