Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes.

This study aimed to examine the effects of Lactobacillus plantarum, a lactic acid bacteria strain isolated from kimchi, on the development of low-grade inflammation and type 2 diabetes mellitus (T2DM) exacerbated by chronic stress. C57BL/6 mice were fed either a high-fat diet (HFD) and randomized into an HFD group or a group that was fed an HFD and subjected to chronic cold exposure-related stress (HFDS), or mice were fed a normal diet (ND) and randomized into an ND group or a group that was fed an ND and subjected to chronic cold exposure-related stress (NDS). Lactobacillus plantarum LRCC5310 (108, 1010 CFU) and LRCC5314 (108, 1010 CFU) as well as L. gasseri BNR17 (108 CFU), as a positive control, were administered orally twice every day to all the mice for 12 weeks. The expression of Glut4 and adiponectin, main glucose transporter-related genes, was upregulated in the LRCC5310- and LRCC5314-treated groups. Levels of serum proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) and of mRNAs of proinflammatory genes (Tnf-α, Il-6, Ccl2, leptin) were elevated in HFDS mice. The expression of proinflammatory genes was downregulated in LRCC5310- and LRCC5314-treated groups; this was not the case for Tnf-α expression in HFDS mice. Levels of serum corticosterone and mRNA levels of stress-related genes (Npy, Y2r) were decreased in lactic acid bacteria (LAB)-fed groups, with only LRCC5314 downregulating Npy expression in HFDS mice. These results suggest that the LAB strains can normalize the expression of metabolic genes, inhibit inflammatory responses, and suppress stress in HFDS mice.

Potential benefits of salvage intratympanic dexamethasone injection in profound idiopathic sudden sensorineural hearing loss.

PURPOSES: To compare hearing recovery levels after initial treatment or salvage intratympanic dexamethasone injection (ITDI), and to find the prognostic factor on salvage ITDI therapy in profound ISSNHL. METHODS: We retrospectively reviewed 115 patients with profound ISSNHL. All patients were treated with combination or systemic steroid therapy as the initial treatment. Next, we used salvage ITDI therapy on patients who showed slight or no improvement according to Siegel's criteria. To find the prognostic factors for the effectiveness of salvage ITDI therapy, we analyzed clinical data, such as, age, sex, vertigo, symptom duration, diabetes, hypertension, initial PTA, pre-salvage PTA, and treatment methods, using multiple regression analyses. RESULTS: The rate of serviceable hearing recovery were 10.4% (12/115) in the initial-treatment group and 20.4% (21/103) in the salvage group. The difference was statistically significant (p = 0.041). Pre-salvage PTA, diabetes mellitus, and symptom duration were affective factors for the effectiveness of salvage ITDI therapy in profound ISSNHL refractory to initial treatment, with odds ratios of 1.169 (95% confidence interval, 1.088-1.256), 0.069 (95% confidence interval, 0.005-0.889), and 9.242 (95% confidence interval, 1.079-79.146). CONCLUSIONS: Salvage therapy should be considered for profound ISSNHL, which is expected to result in poor prognosis or hearing recovery: ITSI therapy might be an effective treatment as salvage therapy.

Impaired Glycolysis Promotes AlcoholExposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling.

Glucose metabolism is an important metabolic pathway in the auditory system. Chronic alcohol exposure can cause metabolic dysfunction in auditory cells during hearing loss. While alcohol exposure has been linked to hearing loss, the mechanism by which impaired glycolysis promotes cytotoxicity and cell death in auditory cells remains unclear. Here, we show that the inhibition of epidermal growth factor receptor (EGFR)-induced glycolysis is a critical mechanism for alcohol exposure-induced apoptosis in HEI-OC1 cells. The cytotoxicity via apoptosis was significantly increased by alcohol exposure in HEI-OC1 cells. The glycolytic activity and the levels of hexokinase 1 (HK1) were significantly suppressed by alcohol exposure in HEI-OC1 cells. Mechanistic studies showed that the levels of EGFR and AKT phosphorylation were reduced by alcohol exposure in HEI-OC1 cells. Notably, HK1 expression and glycolytic activity was suppressed by EGFR inhibition in HEI-OC1 cells. These results suggest that impaired glycolysis promotes alcohol exposure-induced apoptosis in HEI-OC1 cells via the inhibition of EGFR signaling.

Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.

Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

Performance Comparison of Convolutional Neural Network-Based Hearing Loss Classification Model Using Auditory Brainstem Response Data.

This study evaluates the efficacy of several Convolutional Neural Network (CNN) models for the classification of hearing loss in patients using preprocessed auditory brainstem response (ABR) image data. Specifically, we employed six CNN architectures-VGG16, VGG19, DenseNet121, DenseNet-201, AlexNet, and InceptionV3-to differentiate between patients with hearing loss and those with normal hearing. A dataset comprising 7990 preprocessed ABR images was utilized to assess the performance and accuracy of these models. Each model was systematically tested to determine its capability to accurately classify hearing loss. A comparative analysis of the models focused on metrics of accuracy and computational efficiency. The results indicated that the AlexNet model exhibited superior performance, achieving an accuracy of 95.93%. The findings from this research suggest that deep learning models, particularly AlexNet in this instance, hold significant potential for automating the diagnosis of hearing loss using ABR graph data. Future work will aim to refine these models to enhance their diagnostic accuracy and efficiency, fostering their practical application in clinical settings.

miR-409-3p Regulates IFNG and p16 Signaling in the Human Blood of Aging-Related Hearing Loss.

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.

Improving Accuracy and Reliability of Hearing Tests: Measurement Standards for Audiometric Devices.

Pure-tone audiometry, using an audiometer, is the fundamental hearing test for diagnosing hearing loss. The requirements of the devices and the detailed process for calibrating the related equipment are described in international standards. However, traceable calibration and uncertainty evaluation processes are not widely accepted or applied to the qualification and maintenance of audiometric equipment. Here, we briefly review standard measurement systems for audiometric devices and introduce their calibration procedures. The uncertainty of each calibration process was investigated, and its impact on hearing test results was considered. Our findings show that the traceability of each procedure can be secured, satisfying the uncertainty requirement and being sufficiently smaller than the permissible deviation from the audiometer requirement. To guarantee the objectivity and reliability of hearing tests and maintain low uncertainty, close cooperation and mutual understanding between the metrology field and the medical community are necessary.

Trends in Distributions of Hearing Threshold Levels by Ages: A Comparison of the ISO 7029 and Newly Available Country-Specific Data.

Hearing thresholds provide essential information and references about the human auditory system. This study aimed to identify changing trends in distributions of hearing threshold levels across ages by comparing the International Organization for Standardization (ISO) 7029 and newly available data after publishing ISO 7029. To compare ISO 7029 and newly available hearing threshold data after publishing ISO 7029, four country-specific datasets that presented average hearing threshold levels under conditions similar to ISO 7029 were utilized. For frequencies between 125 Hz and 8,000 Hz, the deviations of hearing threshold values by ages from the hearing threshold of the youngest age group for each data point were utilized. For frequencies from 9,000 Hz to 12,500 Hz, the median threshold information was utilized. Hearing threshold data reported after publishing ISO 7029 from the four countries were mostly similar to the ISO 7029 data but tended to deviate in some age groups and sexes. As national hearing threshold trends change, the following ISO 7029 revision suggests the need to integrate hearing threshold data from different countries.

Auditory Brainstem Response Data Preprocessing Method for the Automatic Classification of Hearing Loss Patients.

Auditory brainstem response (ABR) is the response of the brain stem through the auditory nerve. The ABR test is a method of testing for loss of hearing through electrical signals. Basically, the test is conducted on patients such as the elderly, the disabled, and infants who have difficulty in communication. This test has the advantage of being able to determine the presence or absence of objective hearing loss by brain stem reactions only, without any communication. This paper proposes the image preprocessing process required to construct an efficient graph image data set for deep learning models using auditory brainstem response data. To improve the performance of the deep learning model, we standardized the ABR image data measured on various devices with different forms. In addition, we applied the VGG16 model, a CNN-based deep learning network model developed by a research team at the University of Oxford, using preprocessed ABR data to classify the presence or absence of hearing loss and analyzed the accuracy of the proposed method. This experimental test was performed using 10,000 preprocessed data, and the model was tested with various weights to verify classification learning. Based on the learning results, we believe it is possible to help set the criteria for preprocessing and the learning process in medical graph data, including ABR graph data.

Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards.

This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.

Performance of evacuated calcium phosphate microcarriers loaded with mesenchymal stem cells within a rat calvarium defect.

Tissue engineering of stem cells in concert with 3-dimensional (3D) scaffolds is a promising approach for regeneration of bone tissues. Bioactive ceramic microspheres are considered effective 3D stem cell carriers for bone tissue engineering. Here we used evacuated calcium phosphate (CaP) microspheres as the carrier of mesenchymal stem cells (MSCs) derived from rat bone marrow. The performance of the CaP-MSCs construct in bone formation within a rat calvarium defect was evaluated. MSCs were first cultured in combination with the evacuated microcarriers for 7 days in an osteogenic medium, which was then implanted in the 6 mm-diameter calvarium defect for 12 weeks. For comparison purposes, a control defect and cell-free CaP microspheres were also evaluated. The osteogenic differentiation of MSCs cultivated in the evacuated CaP microcarriers was confirmed by alkaline phosphatase staining and real time polymerase chain reaction. The in vivo results confirmed the highest bone formation was attained in the CaP microcarriers combined with MSCs, based on microcomputed tomography and histological assays. The results suggest that evacuated CaP microspheres have the potential to be useful as stem cell carriers for bone tissue engineering.

In vitro development of nuclear transfer embryos derived from porcine embryonic germ cells and their descendent neural precursor cells.

Undifferentiated stem cells may support a greater development of cloned embryos compared with differentiated cell types due to their ease of reprogramming during the nuclear transfer (NT) process. Hence, stem cells may be more suitable as nuclear donor cells for NT procedures than are somatic cells. Embryonic germ (EG) cells are undifferentiated stem cells that are isolated from cultured primordial germ cells (PGC) and can differentiate into several cell types. In this study, the in vitro development of NT embryos using porcine EG cells and their derivative neural precursor (NP) cells was investigated, thus eliminating any variation in genetic differences. The rates of fusion did not differ between NT embryos from EG and NP cells; however, the rate of cleavage in NT embryos derived from EG cells was significantly higher (p < 0.05) than that from NP cells (141/247 [57.1%] vs. 105/228 [46.1%]). Similarly, the rate of blastocyst development was significantly higher (P < 0.05) in NT using EG cells than the rate using NP cells (43/247 [17.4%] vs. 18/228 [7.9%]). The results obtained from the present study in pigs demonstrate a reduced capability for nuclear donor cells to be reprogrammed following the differentiation of porcine EG cells. Undifferentiated EG cells may be more amenable to reprogramming after reconstruction compared with differentiated somatic cells.

The hsa-miR-5739 modulates the endoglin network in endothelial cells derived from human embryonic stem cells.

MicroRNAs are small, noncoding RNAs that bind to seed sequences on the 3' untranslated regions of their target genes and then negatively regulate gene expressions via the RISC complex. The novel miRNA, hsa-miR-5739, was cloned and characterized its function and cellular expression in current study. The hsa-miR-5739 downregulated endothelial cells that were derived from human ES cells significantly suppressed the translational level of endoglin. This study showed that characterized hsa-miR-5739 expression by performing expression during endothelial differentiation and demonstrate potential roles of hsa-miR-5739 in human endothelial cell differentiation.

Clinical effect of reduced-intensity conditioning regimen containing antithymocyte globulin for hematopoietic cell transplantation from unrelated-donors.

The impact of reduced-intensity conditioning (RIC) on the outcomes of hematopoietic cell transplantation (HCT) from unrelated -donors (UD) remains to be determined. We therefore assessed 128 patients, aged 16 to 66 years, with acute leukemia (n = 105) or myelodysplastic syndrome (n = 23) in a UD-HCT trial using RIC with busulfan, fludarabine, and antithymocyte globulin. Patients were transplanted with unmanipulated bone marrow (BM, n = 41) or mobilized peripheral blood mononuclear cells (M-PB, n = 87) and received cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. After a median follow-up of 26.7 months (range, 5.9-70.7 months) in surviving patients, 19 patients had died without progression/recurrence of underlying disease, giving a cumulative incidence of transplantation-related mortality (TRM) of 17% (95% confidence interval, 11%-27%; 1-year TRM, 14%). Graft failure (n = 7) and infections (n = 5) were the most common causes of TRM. Only three patients died due to GVHD (acute, one; chronic, two). Graft failure, which occurred in eight patients, showed a significant correlation with graft source (BM, 6/41 vs. M-PB, 2/87; P = 0.009). Donor-patient HLA-disparity did not correlate with GVHD, 1-year TRM, and graft failure. RIC containing antithymocyte globulin led to decreased GVHD-associated, as well as overall, TRM after UD-HCT.

Green tea prevents down-regulation of gap junction intercellular communication in human keratinocytes treated with PMA.

It has been suggested that connexin (Cx) gap junction proteins act as tumor suppressors and green tea has a potential to prevent tumor development, however, the studies on their association with human keratinocytes were rare. We evaluated the effects of a tumor promoter, phorbol-12-myristate-13-acetate (PMA), on the expression of Cxs and gap junction intercellular communication (GJIC) in human keratinocytes (HaCaT cells) and explored the preventive effects of green tea extracts-epicatechin (EC) and epigallocatechin-3-gallate (EGCG). We performed neutral red dye uptake assay to determine the optimal concentrations of PMA, EC, and EGCG for this study and confirmed the expression of Cx mRNAs using RT-PCR. We evaluated GJIC quantitatively using the 'scrape-loading dye transfer (SLDT)' technique after 24-h culture of HaCaT cells treated with agents. To analyze the expression change of Cxs, we also performed Western blot and immunocytochemistry. HaCaT cells were found to express Cx26, Cx30, Cx31, and Cx43, but not Cx29. In 'scrape-loading dye transfer' for functional study for GJIC, EC and EGCG significantly prevented PMA-induced down-regulation of GJIC. Western blot analyses revealed that EC and EGCG prevented down-regulation of Cx26 and Cx43 proteins in HaCaT cells treated with PMA. Immunocytochemistry showed decreased expression and abnormal location of Cx26 and Cx43 in HaCaT cells when treated with PMA, and EC and EGCG inhibited its effect. These results suggest an important role of GJIC played in carcinogenesis involving human keratinocytes and green tea as a useful anticancer diet.

The efficiency of intratympanic dexamethasone injection as a sequential treatment after initial systemic steroid therapy for sudden sensorineural hearing loss.

The effect of intratympanic steroid injection is controversial as salvage or initial treatment option for sudden sensorineural hearing loss (SSNHL) and almost unknown if it is consecutively to use after initial systemic steroids. This study aimed to analyze the efficiency of intratympanic dexamethasone injection (ITDI) as a sequential treatment in the patients who failed initial systemic steroid treatments for SSNHL. Forty-six patients with SSNHL who did not respond to initial systemic steroids were prospectively included in the study. The patients were randomly classified into two groups; the ITDI group (21 patients) did not take four sequential ITDI within 2 weeks after systemic steroids, and the control group (25 patients) took any more medications. Hearing improvement was defined as a 10 dB or more decrease in the pure tone average (PTA) of the four-frequencies (0.5, 1, 2, and 3 kHz). Hearing improvement was observed in 10 (47.6%) of 21 ITDI patients and in 4 (16.0%) of 25 control patients (P = 0.027). An improvement of the mean PTA was 11.4 dB in the ITDI group and 1.7 dB in the control group (P = 0.004). The ITDI group showed significant hearing improvement at low frequency (500 Hz) than the control group. The patients with 70 or more dB in PTA before ITDI showed significant hearing improvement than the other patients with better PTAs (P = 0.038). The sequential ITDI, which is performed immediately after initial systemic steroid therapy, may be a simple, effective second-line treatment of choice for the patients who show poor response to initial treatments for SSNHL.

Re-analysis of the outcomes of post-remission therapy for acute myeloid leukemia with core binding factor according to years of patient enrollment.

OBJECTIVE: The purpose of this study was to re-evaluate post-remission therapy outcomes after first remission according to years of patient enrollment in patients with core binding factor acute myeloid leukaemia. METHODS: We conducted a retrospective study on 138 patients aged less than 60 years diagnosed with core binding factor acute myeloid leukaemia between 1994 and 2006, comparing allogeneic stem cell transplantation and high-dose cytarabine chemotherapy as post-remission treatment options after the first remission. RESULTS: The 5-year probabilities of disease-free survival and overall survival were not different between allogeneic stem cell transplantation and high-dose cytarabine groups. However, 3-year probabilities of disease-free survival (86.7% vs. 67.0%) and overall survival (90.0% vs. 67.3%) showed a trend towards improvement in the allogeneic stem cell transplantation group compared with the high-dose cytarabine group in cohort after 2003 (2003-2006), whereas outcomes were not different in cohort before 2003 (1994-2002). Especially, 3-year probabilities of disease-free survival (95.2% vs. 59.3%, P = 0.008) and overall survival (95.2% vs. 59.6%, P = 0.032) of allogeneic stem cell transplantation group were significantly better than high-dose cytarabine group in cohort after 2003 of acute myeloid leukaemia patients with t(8;21). The relative risk of overall survival with allogeneic stem cell transplantation, compared with high-dose cytarabine chemotherapy, was significantly improved in the cohort after 2003 (0.33; 95% CI, 0.07-1.48) when compared with that before 2003 (1.92; 95% CI, 0.77-4.82). In multivariate analysis in cohort after 2003, allogeneic stem cell transplantation as post-remission therapy was associated with better disease-free survival. CONCLUSIONS: Allogeneic stem cell transplantation is currently the more effective post-remission therapy than it was prior to 2003 for core binding factor acute myeloid leukaemia achieving first remission. On the contrary to previous findings, allogeneic stem cell transplantation provides significantly improved outcomes than high-dose cytarabine chemotherapy in acute myeloid leukaemia with t(8;21).

Nimodipine and Steroid Combination Therapy for Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To evaluate the treatment outcomes of nimodipine and steroid combination therapy for idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seventy-eight patients who were diagnosed with ISSNHL were divided into two group based on the treatment strategies used: steroid+nimodipine (SN, n = 36) and steroid only (SO, n = 42) groups. Based on the level of hearing loss before treatment, subgroup analysis (<90 dB HL, SN-S versus SO-S groups; ≥90 dB HL, SN-P versus SO-P groups) was performed. INTERVENTIONS: Nimodipine+dexamethasone versus dexamethasone alone. MAIN OUTCOME MEASURES: Hearing thresholds and complete/partial recovery rate after treatment. RESULTS: Hearing thresholds after treatment were not significantly different between the SN and SO groups (46.8 ±â€Š29.4 versus 54.8 ±â€Š27.6 dB HL, p = 0.218). However, the complete recovery rate was significantly higher in the SN group than in the SO group (41.7% versus 16.8%, p = 0.014). In subgroup analysis, the complete recovery rate was significantly higher in the SN-S group than in the SO-S group (60.9% versus 19.2%, p = 0.003), whereas the difference between the SN-P and SO-P groups was not significant (7.7% versus 12.5%, p = 0.672). The cumulative incidence of complete recovery was significantly higher in SN-S group than in the SO-S group (p = 0.005); the mean recovery time was 4.4 weeks (95% confidence interval [CI], 2.8-6.1) in the SN-S group and 8.8 weeks (95% CI, 7.0-10.5) in the SO-S group. CONCLUSIONS: The results of this study suggest that nimodipine and steroid combination therapy for ISSNHL results in a higher complete recovery rate than steroid alone in patients with moderate to severe hearing loss.

Expression profiles of SV40-immortalization-associated genes upregulated in various human cancers.

Immortalization is an early and essential step of human carcinogenesis which is associated with alterations in gene expression and regulation. Suppression subtractive hybridization (SSH) was successfully performed to identify immortalization-associated genes upregulated in SV40-immortalized lung fibroblasts. We identified 116 known genes which were related to diverse functions, with 32.8% relevant for cell cycle or proliferation indicating the potential involvement of these genes in immortalization. We chose eight known genes located on the overrepresented chromosomes of non-small-cell lung cancers (NSCLCs). ASPM, RFC4, C3orf26, BXDC2, C15orf44, AURKA, C20orf77, and RBMX were upregulated in immortalized cells, cancer cells, and non-small-cell lung cancer (NSCLC) tissues. We additionally cloned two novel genes (CHA-V-97 and CHA-V-165) which showed similar upregulated expression patterns in cells and tissues examined. Identification and further characterization of these genes may provide insights of novel players for immortalization and human carcinogenesis.

Intralabyrinthine schwannoma involving the cochlea, vestibule, and internal auditory canal: 'canalolabyrinthine schwannoma'.

Intralabyrinthine schwannomas (ILSs) are very rare and most of them involve cochlea-vestibule, internal auditory canal (IAC)-cochlea, or IAC-vestibule areas. However, there is no study reporting on schwannomas involving simultaneously the vestibule, cochlea, and IAC. We report a case of schwannoma involving simultaneously the vestibule, cochlea, and IAC, with the discussion of its possible origin and propose one more new classification, the 'canalolabyrinthine schwannoma', among the ILSs.