Detection of SARS-CoV-2 virus in middle ear effusions and its association with otitis media with effusion.

A large-scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS-CoV-2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS-CoV-2 virus was detected by RT-PCR targeting. The SARS-CoV-2 virus, angiotensin-converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID-19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS-CoV-2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID-19 infection. The SARS-CoV-2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019-2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS-CoV-2 virus and the TMPRSS2 cofactors required for virus entry.

Microscopic Versus Endoscopic Ear Surgery for Early-Stage Glomus Tympanicum Tumors.

Purpose: Glomus tympanicum tumors are benign primary tumors of the middle ear that can be completely removed using modern surgery. We compared endoscopic ear surgery (EES) to traditional microscopic ear surgery (MES) in terms of the removal of early-stage glomus tympanicum tumors. Methods: We retrospectively reviewed 25 cases treated from 2003 to 2021 that were of Grade I or II based on the Glasscock-Jackson classification system. Overall, 18 cases underwent MES: 8 via trans-tympanic bone and 10 via canal-wall-down or canal-wall-up tympanomastoidectomy (CWDT or CWUT) and 7 underwent EES. We compared surgery durations, the lengths and costs of hospitalization, postoperative complications, and relapse rates between the two groups and among the three specific operation ways. Results: The postoperative follow-up period ranged from 1 to 19 years. There was no between-group difference in operative time or the length or cost of hospitalization. Operative time and cost of hospitalization did not show a statistically significant correlation to the three surgical procedures, whereas it was found that the group of MES via the trans-tympanic bone had shorter length of hospitalization when compared with CWUT or CWDT group. All tumors were completely resected; pulsatile tinnitus improved in all patients, and there was no major complication. Two patients who underwent CWUT or CWDT (one each) relapsed; no patient relapsed in the EES group. Conclusion: MES via the trans-tympanic bone and EES via the ear canal safely and reliably remove early-stage tumors without excessive patient discomfort.

A New Floating Piezoelectric Microphone for Fully Implantable Cochlear Implants in Middle Ear.

OBJECTIVE: Our team designed a long-lasting, well-sealed microphone, which uses laser welding and vacuum packaging technology. This study examined the sensitivity and effectiveness of this new floating piezoelectric microphone (NFPM) designed for totally implantable cochlear implants (TICIs) in animal experiments and intraoperative testing. METHODS: Different NFPM frequency responses from 0.25 to 10 kHz at 90 dB SPL were analyzed using in vivo testing of cats and human patients. The NFPM was tested in different positions that were clamped to the ossicular chains or placed in the tympanic cavity of cats and human patients. Two volunteers' long incus foot and four cats' malleus neck of the ossicular chain were clamped with the NSFM. The output electrical signals from different locations were recorded, analyzed, and compared. The NFPM was removed after the test without causing any damage to the middle-ear structure of the cats. Intraoperative tests of the NFPM were performed during the cochlear implant surgery and the cochlear implant surgery was completed after all tests. RESULTS: Compared with the results in the tympanic cavity, the NFPM could detect the vibration from the ossicular chain more sensitively in cat experiments and intraoperative testing. We also found that the signal output level of the NFPM decreased as the acoustic stimulation strength decreased in the intraoperative testing. CONCLUSION: The NFPM is effective in the intraoperative testing, making it feasible as an implantable middle-ear microphone for TICIs. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:937-944, 2024.

Involvement of Dmp1 in the Precise Regulation of Hair Bundle Formation in the Developing Cochlea.

Dentin matrix protein 1 (Dmp1) is a highly phosphorylated, extracellular matrix protein that is extensively expressed in bone and teeth but also found in soft tissues, including brain and muscle. However, the functions of Dmp1 in the mice cochlea are unknown. Our study showed that Dmp1 was expressed in auditory hair cells (HCs), with the role of Dmp1 in those cells identified using Dmp1 cKD mice. Immunostaining and scanning electron microscopy of the cochlea at P1 revealed that Dmp1 deficiency in mice resulted in an abnormal stereociliary bundle morphology and the mispositioning of the kinocilium. The following experiments further demonstrated that the cell-intrinsic polarity of HCs was affected without apparent effect on the tissue planer polarity, based on the observation that the asymmetric distribution of Vangl2 was unchanged whereas the Gαi3 expression domain was enlarged and Par6b expression was slightly altered. Then, the possible molecular mechanisms of Dmp1 involvement in inner ear development were explored via RNA-seq analysis. The study suggested that the Fgf23-Klotho endocrine axis may play a novel role in the inner ear and Dmp1 may regulate the kinocilium-stereocilia interaction via Fgf23-Klotho signaling. Together, our results proved the critical role of Dmp1 in the precise regulation of hair bundle morphogenesis in the early development of HCs.

Evaluation of the hearing preservation and tissue response of dexamethasone and hyaluronic acid delivery during cochlear implantation on cats in a three-month period study.

OBJECTIVE: To evaluate the effects of DX and HA on hearing preservation and tissue response with cochlear implantation in a cat mode. METHODS: 11 cats were bilaterally implanted with Nurotron electrode. According to the different treatment, 22 ears were subdivided into four following groups: Electrode (E) only, Electrode +HA (E+H), Electrode + DX (E+DX), and Electrode +HA +DX (E+H+DX). Auditory brainstem responses (ABR) thresholds were recorded before and 3 months after surgery. After 3 months of cochlear implantation histopathological assessment of all cochleae were performed . RESULTS: At low frequencies, the mean ABR thresholds shift in animals treated with E+H+DX demonstrated a statistically significant difference. The proportion of cochleae showing fibrous tissue and new bone formation was 50% in E+H+DX group, 66.7% in E+DX group, 83.3% in E+H group and 100% in E group. CONCLUSION: United HA and DX local delivery could provide better protection against hearing loss at low-frequency threshold and could more effectively reduce the trauma related to electrode insertion and the fibrous tissue formation around the electrode.

Melatonin Alleviates the Oxygen-Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway.

Substantial evidence suggests that pyroptosis is involved in renal, cerebral, and myocardial ischemia-reperfusion injury. However, whether pyroptosis is involved in ischemia-reperfusion injury of cochlear hair cells has not been explored. In this study, we examined the effects of melatonin on the oxygen-glucose deprivation/reperfusion (OGD/R) of hair cell-like House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear hair cells in vitro to mimic cochlear ischemia-reperfusion injury in vivo. We found that melatonin treatment protected the HEI-OC1 and cochlear hair cells against OGD/R-induced cell pyroptosis and reduced the expression level of ROS in these cells. However, these effects were completely abolished by the application of luzindole (a non-selective melatonin receptor blocker) and largely offset by the use of ML385 (an nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor). These findings suggest that melatonin alleviates OGD/R-induced pyroptosis of the hair cell-like HEI-OC1 cells and cochlear hair cells via the melatonin receptor 1A (MT-1) and melatonin receptor 1B (MT-2)/Nrf2 (NFE2L2)/ROS/NLRP3 pathway, which may provide credible evidence for melatonin being used as a potential drug for the treatment of idiopathic sudden sensorineural hearing loss in the future.

Pyroptosis: A Newly Discovered Therapeutic Target for Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury, uncommon among patients suffering from myocardial infarction, stroke, or acute kidney injury, can result in cell death and organ dysfunction. Previous studies have shown that different types of cell death, including apoptosis, necrosis, and autophagy, can occur during I/R injury. Pyroptosis, which is characterized by cell membrane pore formation, pro-inflammatory cytokine release, and cell burst, and which differentiates itself from apoptosis and necroptosis, has been found to be closely related to I/R injury. Therefore, targeting the signaling pathways and key regulators of pyroptosis may be favorable for the treatment of I/R injury, which is far from adequate at present. This review summarizes the current status of pyroptosis and its connection to I/R in different organs, as well as potential treatment strategies targeting it to combat I/R injury.

High frequency hearing loss may act as a screening index evaluating otolith function in vertigo patients with normal semi-circular canal function.

Objective: To investigate whether otolith dysfunction is related to hearing impairment in vertigo patients with normal semicircular canal function, and to clarify the types of hearing impairment that may be related to otolith organ damage. Methods: The demographic data, pure tone threshold audiometry (PTA) results (air-conduction), data of bithermal and video-head impulse test (vHIT), and vestibular evoked myogenic potential (VEMP) results (reaction threshold, P1-N1 amplitude) of patients with vertigo in outpatient clinic from April 2017 to January 2020 were collected. The clinical records of 51 vertigo patients with normal semicircular canal function were included in this study. Low-frequency, speech-frequency, high-frequency, full-frequency PTA were defined as the average of PTA in different frequency bands, respectively (low: 0.125, 0.25, 0.5 kHz; speech: 0.5, 1, 2 kHz, high: 4, 8 kHz, full 0.125-8 kHz). The correlations between hearing impairment in different frequency bands and otolith function impairment were analyzed. Results: The mean thresholds of 51 patients (102 ears) in low-PTA, speech-PTA, high-PTA, full-PTA were 20.95 ± 6.01, 21.92 ± 6.90, 40.12 ± 17.47, 26.97 ± 8.53 dB nHL, respectively. Among 102 ears, 87 ears (85.3%) could elicit c-VEMP waveforms and 65 ears (63.7%) had o-VEMP waveforms. The mean threshold and P1-N1 amplitude of c-VEMP were 83.10 ± 6.96 dB nHL and 176.79 ± 103.10 uV, while those of o-VEMP were 87.92 ± 5.99 dB nHL and 21.45 ± 32.22 uV. The mean threshold in high-PTA was significantly linearly correlated with c-VEMP threshold (P = 0.01) and P1-N1 amplitude (P = 0.028). There were not significant linear correlations between the mean threshold in each frequency band of PTA and o-VEMP threshold (low-PTA: P = 0.266, speech-PTA: P = 0.33, high-PTA: P = 0.311) or P1-N1 amplitude (low-PTA: P = 0.414, speech-PTA: P = 0.069, high-PTA: P = 0.08). Conclusions: There is a positive linear correlation between saccule dysfunction and high-frequency hearing impairment in vertigo patients with normal semi-circular canal function. High frequency hearing loss can be expected in patients who have saccular damage. It suggests that high frequency hearing loss in PTA may act as a screening index that otolith organ function should be comprehensively evaluated.

Atypical manifestations of acute coronary syndrome - throat discomfort: a multi-center observational study.

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.

Chinese Version of the Vestibular Disorders Activities of Daily Living Scale.

OBJECTIVES/HYPOTHESIS: To translate and cross-culturally adapt vestibular disorders activities of daily living (VADL) scale to Chinese population, and verify its psychometric characteristics. STUDY DESIGN: A methodology study to translate, validate, and verify the reliability of the VADL scale. METHODS: The translation of the VADL from English to Chinese was carried out in accordance with the recommendations proposed by the Process of Cross-Cultural Adaptation guideline. All 185 Subjects with chief complaints of dizziness or vertigo were continuously invited to the study from January 2021 to June 2021. Investigation using the Chinese version of VADL (VADL-C) was completed by all the participants. Complete data from all 124 participants were used for reliability and internal consistency analysis by using SPSS 22.0. RESULTS: Through careful and complete translation and adaptation, the VADL-C was successfully created. The content validity of the VADL-C was 0.887, the internal consistency was 0.951, and the test-retest reliability was 0.989. CONCLUSIONS: The VADL-C has an excellent internal consistency, test-retest reliability, and content validity. It will be a new tool to be used in China and for overseas Chinese speakers to explore the functional capacity of individuals with vestibular diseases and guide therapy planning, particularly in vestibular rehabilitation training program. Laryngoscope, 132:1446-1451, 2022.

Rab11a Regulates the Development of Cilia and Establishment of Planar Cell Polarity in Mammalian Vestibular Hair Cells.

Vestibular organs have unique planar cell polarity (Figure 1A), and their normal development and function are dependent on the regular polarity of cilia (Figure 1B) requires. Rab11a is a small G protein that participates in the transportation of intracellular and extracellular materials required for polarity formation; however, our understanding of the mechanisms of the actions of Rab11a in vestibular organs is limited. Here, we showed that the general shape of the utricle was abnormal in Rab11a CKO/CKO mice. These mice also showed abnormal morphology of the stereocilia bundles, which were reduced in both length and number, as well as disturbed tissue-level polarity. Rab11a affected the distribution of polarity proteins in the vestibular organs, indicating that the normal development of cilia requires Rab11a and intraflagellar transportation. Furthermore, small G protein migration works together with intraflagellar transportation in the normal development of cilia. FIGURE 1Morphological changes of stereocilia in the extrastriolar hair cells from Rab11a single or Rab11a/IFT88 double-mutant utricles. (A) Medial view of a mouse left inner ear with its five vestibular sensory organs (gray). Enlarged are the utricle showing their subdivisions, LPR (yellow line), and striola (blue). LES, lateral extrastriola; MES, medial extrastriola; LPR, line of polarity reversal. (B) Schematic view of vestibular hair cell. Kinocilium is marked with ace-tubulin. Basal body is marked with γ-tubulin. (C,C1,D,D1) Normal appearance of the stereocilia of extrastriolar hair cells of wild-type controls. (E,E1,F,F1) Altered morphology in Rab11a CKO/CKO animals. (G,G1,H,H1) The changes in the stereocilia morphology were more severe in Rab11a CKO/CKO /IFT 88 CKO/+ mice. (I-L) Higher magnification of confocal images of hair cells. (M-P) Scanning electron microscopy images of hair cells from wild-type controls and Rab11a mutants. (I,M) Morphology of normal. hair cells of wild-type controls. (J,N) The number of stereocilia on a single hair cell was deceased in the Rab11a mutant. (K,O) Stereocilia were shorter in mutants compared to the wild-type controls. (L,P) The staircase-like hair bundle architecture of hair cells was lost in Rab11a mutant mice. (Q) The percentage of hair cells with abnormal development of static cilia bundles in the extrastriola region was counted as a percentage of the total (n = 5). The percentage of abnormal hair cells was higher in Rab11a CKO/CKO , IFT88 CKO/+ mice compared to Rab11a CKO/CKO . The abnormal ratios of single and double knockout hair cells were 42.1 ± 5.7 and 71.5 ± 10.4, respectively. In (A-J), for all primary panels, hair cell stereociliary bundles were marked with phalloidin (green), the actin-rich cuticular plate of hair cells was labeled with ß-spectrin (red), while the basal body of the hair cell was labeled with γ-tubulin (blue). Scale bars: 10 µm (C-H1), 5 µm (J-N). *P < 0.05.

A Predictive Model Development of Hospital Admission during Triage in a Chinese Ear, Nose, and Throat Emergency Department.

INTRODUCTION: Triaging patients into correct severity categories in an emergency department is an advanced skill that depends on a quick assessment after obtaining very little information. The purpose of this study was to assess specific risk factors associated with hospital admissions in the emergency department environment of the specialized Eye, Ear, Nose, and Throat hospital located in Shanghai, China. METHODS: This study was a retrospective cohort study. Patients visiting the emergency department in a tertiary hospital in eastern China from February 2008 to August 2015 were included. Univariate and multivariate analyses were used to identify the risk factors related to hospital admissions. Combining variables calculated from the regression equation of multivariate analysis (binary logistic regression analysis) enabled the risk factors quantification. The receiver operating characteristic analysis was used to identify the most informative cutoff point of the combining predictors. RESULTS: A total of 188715 patients were enrolled in the study. Of them, 8395 patients (4.4%) required hospital admission. Hour of visit, season, age, sex, chief complaint, anatomical location, and locale of patients were independent risk factors of hospital admission by univariate and multivariate analysis. Combining predictors were calculated from the equation of the multivariate logistic model. The area under the curve of the combining predictors was 0.949, and the 95% confidence interval was 0.947 to 0.951 (P <.001), with a sensitivity of 95.2% and a specificity of 85.6%. A cutoff score of less than -35.1975 was associated with hospital admission. DISCUSSION: This study provided a method to build a feasible predictive model of hospital admission during triage. Understanding risk factors is an important part of the triage process in order to correctly assign priorities to the patients served. The outcomes of this study would add additional information for the triage nurse to consider in assessing the patient and assigning acuity ratings. The model developed here requires validation in future research.

Characteristic manifestation of ocular and cervical vestibular evoked myogenic potentials findings in severe obstructive sleep apnea patients.

BACKGROUND: Studies of saccular and utricular function in patients with obstructive sleep apnea (OSA) are rare. We noticed that some OSA patients also had positive results in vestibular function tests, and this inspired our interest in exploring the vestibular function patterns of OSA patients. OBJECTIVES: To investigate otolithic organ function in severe OSA patients who lack vestibular symptoms and systemic disease. MATERIAL AND METHODS: 32 patients (64 ears) with severe OSA and 22 healthy controls (44 ears) were enrolled. The ocular and cervical vestibular-evoked myogenic potentials (oVEMP and cVEMP) and the caloric test were recorded and analyzed. RESULTS: The response rates of oVEMP (73.4%) and cVEMP (82.8%) in patients with severe OSA were significantly lower than those in controls. In oVEMP, elevated thresholds (p = .002), decreased n1-p1 amplitudes (p < .001), prolonged n1 latencies (p < .001) were observed. In cVEMP, the elevation of thresholds (p < .001), decrease in p1-n1 amplitudes (p < .001), and n1-p2 amplitudes (p < .001), prolongation of p1 latencies (p = .003) were observed. No significant difference in the caloric test was found between the two groups. CONCLUSIONS AND SIGNIFICANCE: Disappearance or impairment of VEMPs could be observed in patients with severe OSA, and reflects different degrees of impairment in the utricle and saccule.

Canonical Wnt Signaling Pathway on Polarity Formation of Utricle Hair Cells.

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out ß-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

Conductive hearing loss in large vestibular aqueduct syndrome -clinical observations and proof-of-concept predictive modeling by a biomechanical approach.

OBJECTIVE: The purpose of this study was to investigate the effect of a dilated vestibular aqueduct on conductive hearing loss (CHL). A biomechanical method was proposed for modeling the patterns of CHL in patients with large vestibular aqueduct syndrome (LVAS). STUDY DESIGN: High resolution computed tomography (CT) scans and pure tone audiometry (PTA) were retrospectively collected from 16 patients who were diagnosed with LVAS. Seventeen ears with measurable air-bone gaps (ABGs) on PTA were applied for model development. The sizes of midpoint, operculum and distal segment were measured from CT to calculate the biomechanical parameters of each vestibular aqueduct. The mechanical effect of the dilated vestibular aqueduct on sound conduction was simulated using a lumped-parameter model. The CHL levels predicted by the model were compared with the observed ABGs at 250, 500 and 1000 Hz respectively. RESULTS: The model was able to predict the trend that greater ABGs occurred at lower frequencies, which were consistent with clinical observations. However, deviations between the predicted and the observed ABGs became larger as the frequency increased. None of the correlation coefficients between the radiologic measures and the observed ABG levels were significant. CONCLUSION: These findings lend support to the feasibility of this approach in modeling CHL in LVAS. The presence of a dilated vestibular aqueduct leads to altered impedance and sound pressure, suggesting the impact of a pathological third window. High individual variability of the observed ABGs implies additional factors may also be involved, especially at 500 Hz and 1000 Hz.

Evaluations on the stability and bio-compatibility of a new piezoelectric microphone for the implantable middle ear microphone.

BACKGROUND: A new floating piezoelectric microphone (NFPM), driven by the acoustic vibration of the ossicles, has been manufactured in the lab. OBJECTIVES: This study aimed at exploring the stability and bio-compatibility of this NFPM. MATERIALS AND METHODS: The NFPM was implanted into the cat tympanic cavity by clamping it to the handle of the malleus, and then a temporal bone computed tomography (CT) plain scan and three dimensional reconstruction were performed to observe its coupling with the handle of the malleus. After six months of implantation, cats' blood samples were taken for pro-inflammatory factor analysis. Then, the operative cavity was opened to check the NFPM, the auditory ossicular chain and some granulation tissue surrounding the NFPM. RESULTS: The NFPM was firmly clamped to the handle of the malleus of the cats during the six months of implantation. Besides, there was no obvious systemic inflammatory response in the experimental animals. In addition, local proliferation of granulation tissue occurred in the tympanic cavity without hampering the movement of the auditory ossicle,or causing ischemia of the auditory ossicle. CONCLUSION: The NFPM could be implanted in our experimental cats for a long period of time and had good bio-compatibility.

The transcriptome characteristics of vestibular organs from delayed endolymphatic hydrops patients (Meniere's disease).

OBJECTIVES: To identify genes that are related to delayed endolymphatic hydrops (DEH) in patients by RNA-Seq analysis. DESIGN: Observational study. SETTING: Eye & ENT Hospital, Fudan University (Shanghai, China). PARTICIPANTS: We collected the entire vestibular system from four patients with DEH who underwent labyrinthectomy. Three control samples were collected from patients with acoustic neuroma or facial neuroma treated via the translabyrinthine approach. High-throughput RNA-Seq analysis was performed to investigate gene expression in the pathological vestibular system. MAIN OUTCOME MEASURES: Our bioinformatic analysis identified 17 genes that were upregulated and eight genes that were downregulated in patients with DEH compared with the controls. RESULTS: The altered gene expression profile suggested that DEH is closely related to neuropathy and autoimmune disease. In addition, many of the differentially regulated genes were involved in cell adhesion, suggesting a role of cell adhesion in DEH. Immunofluorescence analysis confirmed the expression of PMP2 and CLDN19 in the cytoplasm of hair cells and scattered expression of MPZ at cell junctions. The protein expression levels were higher in specimens from patients with Ménière's disease and DEH compared with controls. CONCLUSIONS: The protein expression profile of vestibular organs in patients with endolymphatic hydrops exhibited a degree of similarity to that of Ménière's disease. Endolymphatic hydrops is characterised by autoimmune abnormalities. DEH and Ménière's disease are likely to be different manifestations of the same disease, with disparate clinical symptoms. RNA-Seq is a useful analytical tool to characterise the vestibular pathology based on its transcriptome.

Sound localization, speech and tone recognition for stimuli presented from the rear in bilateral cochlear implant users.

OBJECTIVE: To assess any differences in spatial listening ability of cochlear implant recipients when using both or only one of two bilateral cochlear implants (BCIs) for stimuli originating from behind the subject. DESIGN: Twelve loudspeakers were placed in the rear horizontal plane of the subjects to test the sound localisation performance of BCI users and normal-hearing listeners (NHLs) with or without interfering noise. Stimuli were presented via two rear loudspeakers simultaneously during the speech recognition test. In the tone recognition test, another anechoic chamber was used with stimuli presenting from a loudspeaker behind the participants. STUDY SAMPLE: Twenty-seven NHLs and eleven BCI users. RESULTS: Average root-mean-square (RMS) error for the bilateral condition was significantly lower than that for the right and left cochlear implant (CI) conditions with or without interfering noises (p < 0.05). Average speech or tone recognition scores for the bilateral condition and the right and left CI conditions were not statistically significant (p > 0.05). CONCLUSION: Sound localisation with BCIs was significantly more accurate than with either implant alone. Speech and tone recognition scores were not better with two compared to those of one activated implant. Given the small number of subjects, the results should be considered as preliminary.

Hair cell uptake of gentamicin in the developing mouse utricle.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs. In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

Planar cell polarity governs the alignment of the nasopharyngeal epithelium in mammals.

Planar cell polarity (PCP) signalling specifies the orientation of epithelial cells and regulates directional beating of motile cilia of multiciliated epithelial cells. Clinically, defects in cilia function are associated with nasopharyngeal symptoms. The polarity of the nasopharyngeal epithelium is poorly understood. Here, we demonstrated PCP in the nasopharyngeal epithelium. Multiciliated cells (MCCs) were uniformly aligned with their long axis parallel to the tissue axis of the nasopharynx (NP). In addition, PCP proteins exhibited an asymmetrical localisation between adjacent cells. Motile cilia were uniformly aligned in the same direction within both individual cells and neighbouring cells, which manifested as cilial polarity in MCCs. Mutation of Vangl2, a mammalian homologue of the Drosophila PCP gene, resulted in significant disruption of the orientation of epithelial cells. Finally, keratin-5-positive basal cells constantly replenished the luminal ciliated cells; the new dynamic ciliated cells were also oriented parallel to the tissue axis. These results indicate a role for the PCP pathway in the uniform orientation of dynamically replenished epithelial cells in the NP.