SERCA2 protects against cisplatin-induced damage of auditory cells: Possible relation with alleviation of ER stress.

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.

Selection of a Surgical Approach for Middle Ear Cholesteatoma Based on the Fusion Images of Non-Echo Planar Diffusion-Weighted MRI and CT.

PURPOSE: This study aimed to explore the ability of fusion images of non-echo planar diffusion-weighted magnetic resonance imaging (non-EPI-DWI MRI) and computed tomography (CT) to accurately locate cholesteatoma and plan the surgical approach. METHODS: In the first part, 41 patients were included. Their CT images and non-EPI DWMRI images were fused. The scope of cholesteatoma in the fusion image was compared with that in the surgical video to evaluate the capability to locate cholesteatoma. A total of 229 patients were included in the second part, and they were divided into 2 groups. We chose the surgical approach for the CT group and the fusion group, and compared the accuracy of surgical approaches in the CT group and the fusion group using the surgical records. RESULTS: The location of cholesteatoma shown in the fusion images was almost identical to that observed during the operation (kappa = .862). The overall specificity and sensitivity of the fusion images in locating cholesteatoma were 94.12% and 93.06%, respectively. The accuracy of surgical approach selection based on the fusion images (99.02%) was higher than that of surgical approach selection based on the CT images (85.83%). CONCLUSION: It is recommended that the fusion images be used to locate the range of the cholesteatoma before operation.

AdipoRon reduces cisplatin-induced ototoxicity in hair cells:possible relation to the regulation of mitochondrial biogenesis.

AdipoRon (AR) can exert antidiabetic and anti-inflammatory effects by maintaining mitochondrial structure and function. The present study was designed to explore whether AR protects the auditory cells from cisplatin-induced damage and, if so, to probe the possible mechanisms underlying its action on this type of cells. Cell viability and apoptosis in House Ear Institute-Organization of Corti 1 (HEI-OC1 cells) and mouse cochlea hair cells (HCs) were detected by CCK8 and immunofluorescence. The expressions of apoptosis-related proteins (cleaved caspase-3 and Bcl-2), adiponectin receptor 1 (AdipoR 1) and the key factors relevant to mitochondrial biogenesis（SIRT1 and TFAM）were determined by Western blot and immunofluorescence. Changes in apoptotic rate and expression of SIRT1 and TFAM after silencing of AdipoR 1 (AdipoR 1-siRNA) in HEI-OC1 cells were measured by flow cytometry and Western blot. The levels of reactive oxygen species (ROS) were evaluated by MitoSox red staining. We found that 30 µM cisplatin exposure induced severe cellular damage, which resulted from activation of the mitochondrial apoptotic pathway. Cisplatin decreased the expression of AdipoR 1, SIRT1, and TFAM proteins, leading to impaired mitochondrial biogenesis and increased mitochondrial ROS production. 10 µM AR pre-treatment enhanced mitochondrial biogenesis, decreased mitochondrial ROS levels, alleviated imbalances in the mitochondrial apoptotic pathway, thus reducing cisplatin-induced apoptosis. Taken together, this work reveals that AR exerts anti-apoptotic effects, possibly via regulating mitochondrial biogenesis and function. Interestingly, AR might possess the promising potential to be a novel drug for the prevention and/ or treatment of cisplatin-induced ototoxicity.

Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.

Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.

Notch signaling pathway plays a critical role in chemotherapeutic drug-induced vestibular injury.

The vestibule of the inner ear is susceptible to certain chemotherapeutic agents in clinical practice. Therefore, it is of great significance to discover molecular pathways and targets that can protect the vestibule from chemotherapeutic drugs. The Notch signaling pathway is closely related to hair cell regeneration in the inner ear. However, the role of Notch signaling in chemotherapeutic drug-induced vestibular injury still remains unclear. The aim of this study was first to evaluate the role of Notch signaling in chemotherapy-induced vestibular injury. Cisplatin-induced vestibular injury of mice was evaluated by the swimming test. Changes of vestibular hair cells and the expression levels of Notch1, Jagged1, and Hes1 in Notch signaling were observed by immunofluorescence. The results showed that Notch signaling was found activated in cisplatin-induced injured vestibular cells, while, DAPT (Notch signaling inhibitor) could reversed this effect. In conclusion, the Notch signaling pathway may play a critical role in chemotherapeutic drug-induced vestibular injury and, therefore, serves as a promising therapeutic target for vestibular injury.

Comparison and evaluation of three techniques for treating auricular pseudocyst.

BACKGROUND: Auricular pseudocyst is a benign cystic lesion in cartilages of the auricle. Different methods are currently used to manage this disease. In these methods, simple aspiration combined with pressure dressing, local steroid injection and surgery are the most prevalent therapies. OBJECTIVE: To find the best clinical path for the treatment of auricular pseudocyst. METHODS: Eighty-four subjects were randomly allocated into three equal groups (Group A: simple suction combined with pressure dressing; Group B: suction and local steroid injection; and, Group C: surgery). Two otolaryngologists assessed effective rate, sequelae and degree of satisfaction at three-month follow-up. A visual analog scale was used to determine degree of satisfaction. RESULTS: Group A had the lowest effective rate (54%). Group C was highest in terms of effectiveness (100%) but also in incidence of sequelae (71%). Group B had a slightly lower effective rate (86%) than Group C, but the incidence of sequelae was lowest (42%). Degree of satisfaction was highest (7.0 ± 2.7) for Group B. CONCLUSION: Local steroid injection should be the first choice for the treatment of auricular pseudocyst because of high satisfaction, favorable effectiveness and few sequelae. Where this method is ineffective, surgery should be used.

A New Case of Endoscopic Resection of a Chorda Tympani Schwannoma.

Chorda tympani schwannoma is a very rare tumor, with only 12 reported cases in the English literature. There are few reports on the diagnosis of chorda tympani schwannoma, and it is easily misdiagnosed. At present, surgery is recognized as a treatment for chorda tympani schwannoma. We describe the clinical course of a patient presenting with a chorda tympani schwannoma treated with surgical resection using a transcanal endoscopic approach, and the results after this treatment were satisfactory. Therefore, we accordingly advocate the minimally invasive method of transcanal endoscopic resection to maximize intraoperative visualization and reduce postoperative morbidity for middle ear tumors.

Reliability, internal consistency, and concurrent validity of a modified version of the dynamic gait index in people with vestibular disorders.

BACKGROUND: People with vestibular disorders often have abnormalities in gait and balance. The Dynamic Gait Index (DGI) is a relatively effective clinical gait measure that has been validated for use in patients with vestibular disorders. The modified version of the DGI (M-DGI) is based on the original DGI. RESEARCH QUESTION: The objective of this study was to refine and test the clinical application of the M-DGI, and to investigate whether it is an effective indicator of dynamic gait in patients with vestibular disorders. METHODS: A reliability and validity study. All raters reviewed the instructions and scoring criteria for each M-DGI item prior to the initial test. The raters simultaneously scored two M-DGI tasks for the 75 subjects, and the two tasks were completed with an interval of two hours in-between. Reliability of total M-DGI scores was assessed using intraclass correlation coefficients (2,1). Internal consistency of the M-DGI was evaluated using Cronbach's alpha. Concurrent validity of the M-DGI with Dizziness Handicap Inventory (DHI) and Timed "Up & Go" Test (TUG) was assessed using Spearman's rank order correlation coefficient. RESULTS AND SIGNIFICANCE: Interrater and intrarater reliability of the total M-DGI scores were reflected by ICCs of 0.99 and 0.97. Internal consistency of the M-DGI score was 0.9975. Spearman's rank order correlation coefficient of the M-DGI score with the Dizziness Handicap Inventory (DHI) and the Timed "Up & Go" Test (TUG) was 0.72 and 0.65, respectively.The M-DGI demonstrates acceptable reliability, internal consistency, and concurrent validity for use as a clinical gait measurement for patients with vestibular disorders.

Pseudo-Benign Paroxysmal Positional Vertigo: A Retrospective Study and Case Report.

Pseudo-benign paroxysmal positional vertigo (pseudo-BPPV) is a specific type of vestibular migraine disguised as benign paroxysmal positional vertigo, which is characterized by recurrent different types of positional and atypical positional vertigo with migraine features. It is easy to be misdiagnosed with BPPV at the first visit, which means that the ideal therapeutic effects are not achieved. Twenty-five cases of pseudo-BPPV with frequent changing positional vertigo were retrospected and the following key features help to identify the disease: recurrent positional and atypical positional vertigo, migrainous accompanying symptoms or migraine history, mild or indistinctive headaches, with or without impaired vestibular function, ineffective for simply reposition. And we found that vertigo in pseudo-BPPV can be preferable controlled by valproic acid combined with canalith repositioning procedure.

Impact of hyperlipidemia as a coexisting factor on the prognosis of idiopathic sudden sensorineural hearing loss: A propensity score matching analysis.

OBJECTIVE: To define the impact of hyperlipidemia as a coexisting factor on the prognosis of Idiopathic Sudden Sensorineural Hearing Loss (ISSHL), we prospectively analysed the Lipid-lowering therapy Group (LLTG) data compared with Control Group (CG) data to determine the effects of Lipid intervention on the prognosis of sudden hearing loss. DESIGN: A prospective, non-randomized study. SETTING: Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China. PARTICIPANTS: A total of 653 in-patient SSHL patients were enrolled between January 2014 to August 2018. MAIN OUTCOME MEASURES: From January 2014 to August 2018, 653 patients with ISSHL who also had hyperlipidemia as coexisting factor were identified. Patients enrolled in LLTG (n = 200) or CG (n = 453) were compared by a propensity score matching analysis (PSM, caliper = 0.01, n = 2) to balance pre-existing clinical characteristics. After matching, the effective rate of different hyperlipidemia types and different types of audiogram in both groups were performed by Cochran-Mantel-Haenszel test (CMH). RESULTS: After PSM, 440 patients were studied (146 in LLTG, 294 in CG), and the influence of interference factors was balanced, meanwhile, the final hearing level was better in LLTG than CG (P = .043), and hearing gain was higher in LLTG than CG (P = .006). Cure rate (32.9%), significant improvement rate (22.6%) and the total effective rate (76.0%) in LLTG were better than that in CG group (26.5%, 15.6% and 63.6%) after the Pearson chi-square test (P < .05). Analysis with the Cochran-Mantel-Haenszel test showed that the total effective rate was better in LLTG than CG respectively (P = .009) in each different hyperlipidemia types, and there were statistically significant differences in TG higher group (TG Group; P = .018). Moreover, the total effective rate was better in LLTG than CG (P = .006) for all patterns of audiogram, and there were statistically significant differences in flat audiogram (P = .043). CONCLUSIONS: Lipid-lowering therapy can improve the curative effect of sudden hearing loss patients combined with hyperlipidemia. There was a significant difference in the total effective rate of TG Group after lipid intervention, suggesting that there might be causal relationship between TG and sudden hearing loss. There was a significant difference in the total effective rate between flat audiogram, which may suggest flat hearing loss was more likely caused by vascular dysfunction.

Characteristics and prognosis of idiopathic sudden sensorineural hearing loss in aged people: a retrospective study.

Background: Few studies focused on the prognosis of sudden sensorineural hearing loss (ISSHL) of aged people. Objectives: The aim of this study is to analyze the characteristics, treatment, and prognostic factors of ISSHL in aged people. Material and methods: A total of 278 patients diagnosed of ISSHL in aged people from 2014 to 2019 were retrospectively analyzed. Univariates were analyzed by univariate and multivariate logistic analysis. Results: Among the 13 univariates, the patients' age was younger in the overall recovery group ORG (p = .018), while onset days was shorter in ORG (p = .000). The percentage of DM and HTN comorbidities were higher in ORG (p = .026 and .038). Meanwhile differences were significant in audiogram configurations (p = .037), the degree of hearing loss (p = .033), and types of lipid treatment (p = .020). Then these seven independent risk factors were included in the multivariate analysis, final results indicated that hypertension (p = .028), lipid control groups (p = .009), age (p = .000), and onset days (p = .001) were related to the treatment outcome of ISSHL. Conclusions: The prognosis of ISSHL in aged patients was closely related to age, the onset days of treatment, and good control of complications such as hypertension and hyperlipidemia, so vascular factors were considered as the main causes of morbidity.

Gαi Proteins are Indispensable for Hearing.

BACKGROUND/AIMS: From invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ("hair") bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. METHODS: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. RESULTS: Here we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing. CONCLUSION: We propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.

[Correlations between the pathogenesis and prognosis of sudden sensorineural hearing loss and blood lipid].

OBJECTIVE: We aimed to determine whether blood lipid parameters were related to the severity and the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) patients. METHODS: A retrospective cohort study of 258 patients with ISSNHL from December 2013 to February 2015. The distribution characteristics of lipids [total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Non-high-density lipoprotein cholesterol (Non-HDL-C), et al] in different degree of deafness (mild, moderate, severe, and profound), hearing curve types (low frequency, high frequency, full range frequency, and completely deafness type) and prognosis of recovery (complete, partial, slight, and no recovery) were analyzed by IBM SPSS 22.0 ANOVA analysis, chi square test and multiple regression analysis. RESULTS: TG level in mild hearing loss group was significantly lower than that in severe and profound hearing loss group (P = 0.017 and P = 0.007). There were no correlation between curve types and lipid indexes (P > 0.05). Non-HDL-C level was elevated in no recovery and slight recovery groups (P = 0.026 and 0.021). TC levels in partial recovery group and no recovery group were significantly higher than that in the complete recovery group (P = 0.049 and 0.042), TG was higher in slight recovery group (P = 0.014). CONCLUSIONS: TG has significant correlation with the severity of hearing loss. There are negative correlations between hearing recovery and Non-HDL-C, TC and TG levels. Non-HDL-C, TC and TG might be a prognostic factor for treatment outcome in ISSNHL patients.

Temporospatial expression and cellular localization of VGLUT3 in the rat cochlea.

Vesicular glutamate transporter 3 (VGLUT3) plays an important role in hearing, and VGLUT3 knockout mice are deaf. However, the mechanisms whereby VGLUT3 exerts its effects in the cochlea are not well established. Elucidating the developmental and aging dynamics of VGLUT3 localization and expression in the cochlea would aid a functional understanding of auditory glutamatergic transmission. In this study, we characterized the expression of VGLUT3 in rat auditory epithelium and spiral ganglion cells (SGCs) during postnatal development and with age using immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). We observed VGLUT3 expression in cochlea inner hair cells (IHCs) and SGCs as early as postnatally, and its expression increased gradually with maturity. However, the expression of VGLUT3 in the IHCs decreased in the aging rats compared to postnatal day 60 (P60), and VGLUT3 was still expressed in the remaining SGCs in the aging rats. VGLUT3-immunopositive punctate structures were only found in the cytoplasm of SGCs, not IHCs, at P7, or later. Variation in VGLUT3 mRNA expression evaluated by quantitative real time RT-PCR was consistent with the immunohistochemical data except for no statistical difference between P60 and aging rats in the whole cochlea level. Our data suggest that VGLUT3 likely has developmental and physiological roles in the rat cochlea during postnatal development as well as later in life. VGLUT3 may have additional unknown roles in SGCs besides glutamate transport.

Sigmoid sinus diverticulum and pulsatile tinnitus: analysis of CT scans from 15 cases.

BACKGROUND: Although the imaging features of sigmoid sinus diverticulum induced pulsatile tinnitus (PT) have been presented in some extent, detailed imaging findings still have not been systematically evaluated and precise diagnostic radiographic criteria has not been established. PURPOSE: To examine the computed tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with PT. MATERIAL AND METHODS: Fifteen PT patients with sigmoid sinus diverticula proven by surgery were recruited after consenting. CT images of 15 patients were obtained and analyzed, including features of diverticula, brain venous systems, integrity of the sigmoid plate, and the degree of temporal bone pneumatization. RESULTS: Sigmoid sinus diverticulum was located on the same side of PT in 15 patients. Diverticula originated at the superior curve of the sigmoid sinus in 11 patients and the descending segment of the sigmoid sinus in four patients. Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in 12 patients and mastoid cortex in three patients. Among eight patients with unilateral dominant brain venous systems, the diverticula were seen on the dominant side in seven patients and non-dominant side in one patient. In contrast, the other seven patients showed co-dominant brain venous systems, with three presenting diverticula on the right side and four on the left. More notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients. In addition, temporal bone hyper-pneumatization was found in nine patients, good and moderate pneumatization in three patients, respectively. CONCLUSION: Dehiscent sigmoid plate and extensive temporal bone pneumatization are two important imaging characteristics of the PT induced by sigmoid sinus diverticulum.

Petrosquamosal sinus in the temporal bone as a cause of pulsatile tinnitus: a radiological detection.

We report a newly evidenced cause of venous pulsatile tinnitus--the petrosquamosal sinus in the temporal bone. We also present the case of a 45-year-old woman who presented with an incapacitating objective pulsatile tinnitus in the left ear for 10 years. The radiology evidenced a petrosquamosal sinus in the air cells of the left temporal bone. The symptoms of pulsatile tinnitus disappeared completely after surgical treatment.

Cochlear implant challenges encountered in tuberculous otitis media.

Tuberculous otitis media (TOM) is rare in ENT department, and is frequently misdiagnosed as otitis media. Thus early systemic treatment is very important for TOM. We reported a case report with TOM to highlight development of the disease and difficulties in clinical treatment in late stage of TOM. Implantation of ossified and eroded cochlea poses many unique challenges to both the surgeon and programming team. With thorough preparation and complete knowledge about characters of specific issues, implantation would be performed successfully, and patients with ossified cochlear could benefit from cochlear implantation.