No abstract

The genes responsible for the formation of various sensory organs in the inner ear are not known. There are eight sensory organs in the chick inner ear, and our previous study showed that all presumptive sensory organs initially express bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF)-beta gene family. To address the potential role of BMPs in the patterning of different sensory organ structures, we investigated the expression of BMP4, BMP5, and BMP7 during sensory organ differentiation in the chick inner ear. The gene expression pattern of BMP5, although similar to that of BMP4, was transient and disappeared by embryonic day 3.5 (E3.5). In contrast, BMP7 gene expression was quite extensive, starting in the otic placode. By E5, gene expression patterns of BMP4 and BMP7 differed among vestibular and auditory sensory organs. In the vestibular sensory organs, BMP7 gene expression segregated from the main sensory tissue areas at the onset of differentiation, whereas BMP4 expression concentrated in supporting cells. In the cochlea, however, BMP7 gene expression became restricted to sensory tissue over time and eventually concentrated in supporting cells, whereas BMP4 gene expression was localized to hair cells. The different BMP expression patterns in developing auditory and vestibular sensory organs may help to shape each respective sensory structure. Furthermore, the expression of BMP4 in the cochlea also revealed an interesting pattern of sensory cell differentiation: the distal portion of the cochlea differentiates first, and the tall hair cells develop before the short hair cells.

Mice present an ideal model for inner ear gene therapy because their genome is being rapidly sequenced, their generation time is relatively short, and they serve as a valuable model for human hereditary inner ear disease. However, the small size of the mouse inner ear poses a particular challenge for surgical procedures. We have developed a new approach for viral inoculation into the mature mouse inner ear, using a replication-deficient adenovirus expressing the bacterial gene lacZ. We administered the virus through the posterior semicircular canal (canalostomy) and into the cochlea (cochleostomy). Both approaches caused lacZ to be expressed in cells lining the perilymphatic space. One canalostomy case showed gene expression in sensory cells of the crista ampullaris, whereas the cochleostomy group showed gene expression in the sensory cells in the organ of Corti and saccule. Functional tests after the surgery showed that the canalostomy preserved hearing, whereas the cochleostomy did not. Any vestibular function transiently lost after the canalostomy was recovered. Our findings indicate that inoculation of adenovirus vectors into the mouse inner ear through the semicircular canal has the potential to efficiently introduce transgenes to the vestibular system and the cochlea without compromising hearing.

A branchial remnant originating in the pyriform sinus causes a recurrent fistula or abscess in the neck. In spite of excision, recurrence may result from inadequate removal of the fistula tract. We attempted chemocauterization of the internal opening of the fistula tract with trichloroacetic acid (TCA) on direct endoscopy. This is a 6-year review of 18 patients with pyriform sinus fistula. Medical history, barium esophagography, computed tomography scans, operative findings, and treatment results were analyzed. By direct endoscopy, all patients were found to have a fistula opening in the pyriform sinus, exclusively on the left side. In only 9 patients, the fistula tract was identified by barium esophagography before operation. Computed tomography revealed a suspicious fistula tract originating from the pyriform sinus in 8 of 10 patients. Sixteen patients were initially managed by TCA chemocauterization. There were no serious intraoperative or postoperative complications. Four patients had recurrent masses, which were managed by simple excision in 2 patients and repeated TCA cauterization in the other 2 patients with unobliterated internal openings. We recommend barium swallow study and direct endoscopy for all patients presenting with a recurrent lateral neck abscess, especially on the left side. Our results suggest that initial chemocauterization of the internal opening can be a reasonable alternative procedure for the management of pyriform sinus fistula.

Sodium-dependent vitamin C transporters (SVCTs) is known to transport the reduced form of ascorbic acid into the cell, whereas the oxidized form of vitamin C (VC) is moved through a facilitative sugar transporter, such as glucose transporter (GLUT). With regard to the distribution of SVCT1 and -2 within the various organs, they were reported to be expressed in different types of cells. Especially in the central nervous system, only SVCT2 mRNA was expressed mainly in neurons and some types of neuroglial cells. However, data on the expression of SVCT proteins in the brain are scant. Therefore, we tried to develop comprehensive data on the distribution of SVCT proteins in adult rat brain by using immunohistochemical techniques for the first time. In our study, SVCT2 immunoreactivities (IRs) were intensely localized in the neurons of cerebral cortex, hippocampus, and Purkinje cells of cerebellum, and much weaker SVCT2 IRs were found in the other brain regions. Judging from double-immunohistochemical data, most of the cells expressing SVCT2 IRs were likely to be neurons or microglia, even though the cells in choroids plexus or ependymal cells around the ventricles also exhibited SVCT2 IRs. Complete mapping of the distribution of SVCT2 IRs was available by using a semiquantitative method. The subcellular localization of SVCT proteins is necessary for understanding the exact role of the protein, so the current overall mapping of SVCT IRs in the rat brain could be the basis for further studies on related subjects.

The extent of hypometabolism as assessed by FDG-PET seemed to be one of the major factors predicting the outcome of cochlear implantation.

Given our aging society and the prevalence of age-related hearing loss that often develops during adulthood, hearing loss is a common public health issue affecting almost all older adults. Moderate-to-moderately severe hearing loss can usually be corrected with hearing aids; however, severe-to-profound hearing loss often requires a cochlear implant (CI). However, post-operative CI results vary, and the performance of the previous prediction models is limited, indicating that a new approach is needed. For postlingually deaf adults (n de120) who received CI with full insertion, we predicted CI outcomes using a Random-Forest Regression (RFR) model and investigated the effect of preoperative factors on CI outcomes. Postoperative word recognition scores (WRS) served as the dependent variable to predict. Predictors included duration of deafness (DoD), age at CI operation (ageCI), duration of hearing-aid use (DoHA), preoperative hearing threshold and sentence recognition score. Prediction accuracy was evaluated using mean absolute error (MAE) and Pearson’s correlation coefficient r between the true WRS and predicted WRS. The fitting using a linear model resulted in prediction of WRS with r = 0.7 and MAE = 15.6 ± 9. RFR outperformed the linear model (r = 0.96, MAE = 6.1 ± 4.7, p < 0.00001). Cross-hospital data validation showed reliable performance using RFR (r = 0.91, MAE = 9.6 ± 5.2). The contribution of DoD to prediction was the highest (MAE increase when omitted: 14.8), followed by ageCI (8.9) and DoHA (7.5). After CI, patients with DoD < 10 years presented better WRSs and smaller variations (p < 0.01) than those with longer DoD. Better WRS was also explained by younger age at CI and longer-term DoHA. Machine learning demonstrated a robust prediction performance for CI outcomes in postlingually deaf adults across different institutes, providing a reference value for counseling patients considering CI. Health care providers should be aware that the patients with severe-to-profound hearing loss who cannot have benefit from hearing aids need to proceed with CI as soon as possible and should continue using hearing aids until after CI operation.

The tracheal luminal contour and functional epithelial regeneration without graft rejection and inflammation were observed after repair of a tracheal resection using allogeneic implants with chondrocytes cultured with fibrin/HA.