Hearing Impairment in a Mouse Model of Diabetes Is Associated with Mitochondrial Dysfunction, Synaptopathy, and Activation of the Intrinsic Apoptosis Pathway.

Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Leprdb/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria.

Analysis of Risk Factors for Myringosclerosis Formation after Ventilation Tube Insertion.

BACKGROUND: This study examined possible risk factors for myringosclerosis formation after ventilation tube insertion (VTI). METHODS: A retrospective study was performed in a single tertiary referral center. A total of 582 patients who underwent VTI were enrolled in this study. Patients were divided into two groups based on the presence or absence of myringosclerosis: MS+ and MS-. Characteristics of patients were collected through medical chart review; these included age, gender, nature and duration of effusion, type of ventilation tube (VT), duration and frequency of VTI, incidence of post-VTI infection, incidence of intraoperative bleeding, and presence of postoperative perforation. Incidences of risk factors for myringosclerosis and the severity of myringosclerosis in association with possible risk factors were analyzed. RESULTS: Myringosclerosis developed in 168 of 582 patients (28.9%) after VTI. Patients in the MS+ group had an older mean age than those in the MS- group. The rates of myringosclerosis were higher in patients with older age, serous otitis media, type 2 VT, post-VTI perforation, and frequent VTI. However, there were no differences in occurrence of myringosclerosis based on gender, duration of effusion, duration of VT placement, incidence of post-VTI infection, or incidence of intraoperative bleeding. The severity of myringosclerosis was associated with the duration of effusion and frequency of VTI. CONCLUSION: Older age, serous effusion, type 2 VT, presence of post-VTI perforation, and frequent VTI may be risk factors for myringosclerosis after VTI; the severity of myringosclerosis may vary based on the duration of effusion and frequency of VTI.

Susceptibility of Diabetic Mice to Noise Trauma.

Diabetes can lead to many end-organ complications. However, the association between diabetes and hearing loss is not well understood. Here, we investigated the effect of noise exposure on diabetic mice compared with wild-type mice. Hearing threshold shifts, histopathologic changes in the cochlea, and inflammatory responses were evaluated over time. After noise exposure, more severe hearing threshold shifts, auditory hair cell loss, and synaptopathies were notable in diabetic mice compared with wild-type mice. Moreover, increased inflammatory responses and reactive oxygen species production were observed in the ears of diabetic mice. The results demonstrated that diabetic mice are more susceptible to noise trauma.

Is there any synergic effect for coadministration of mitomycin C and halofuginone on the skin wound healing?

OBJECTIVE: This study compared the potencies of the antifibrotic agents mitomycin C (MMC) and halofuginone (HFN) and investigated whether coadministration of these agents produces synergic effects in an animal skin wound model. SUBJECTS AND METHODS: Twenty male Sprague-Dawley rats were used for this study. After a full-thickness excisional wound was made on the dorsum of each rat, each rat was treated with topical mitomycin, intraperitoneal HFN, or both. Wound surface areas were measured over time, and histologic analysis was performed after wounds healed completely. RESULTS: The groups treated with MMC alone, HFN alone, and a combination of the two all exhibited delayed wound healing compared with the untreated group. Histologically, fibrosis and matrix metalloproteinase-2 expression were significantly inhibited in the treated groups. However, there were no gross or histologic differences between the MMC-treated group, the HFN-treated group, and the combination-treatment group. CONCLUSIONS: Both MMC and HFN inhibited excessive fibrosis. However, there was no significant difference in the antifibrotic effects of MMC and HFN on surgically induced skin wounds. Moreover, combination treatment with both MMC and HFN failed to confer an additional antifibrotic effect on skin wounds when compared with treatment with MMC or HFN alone.

Occult contralateral central lymph node metastases in papillary thyroid carcinoma with unilateral lymph node metastasis in the lateral neck.

BACKGROUND: The frequencies, pattern, and predictive factors for occult contralateral central lymph node (LN) metastases in papillary thyroid carcinoma (PTC) patients with unilateral lateral neck metastases are still unsettled. STUDY DESIGN: We reviewed the medical records of 70 consecutive PTC patients with unilateral positive lateral neck who have initially received total thyroidectomy and comprehensive neck dissection including bilateral central LN dissection. The relationships between occult LN metastases to the contralateral central neck compartment and preoperative image findings and clinicopathologic factors were analyzed. RESULTS: Central neck LN metastases were present in 82.9%, in which 34.3% had bilateral central neck involvement and 48.6% had unilateral ipsilateral central neck involvement. Isolated contralateral central LN metastases without ipsilateral central LN metastases were not found. Multivariate analysis showed that the multifocality of primary thyroid tumor (p = 0.010, odds ratio = 5.120) and the presence of metastases in all lateral neck levels (p = 0.017, odds ratio = 5.130) were independent risk factors for the presence of contralateral central LN metastases. CONCLUSIONS: The rate of occult contralateral central LN metastases was relatively high (34.3%) in PTC with ipsilaterally positive lateral neck, and multifocal primary tumor and positive LN involvement in all lateral neck levels are associated with contralateral central LN metastases.

Predictive factors for ipsilateral or contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma.

OBJECTIVES: To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck. SUMMARY BACKGROUND DATA: Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes. METHODS: We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed. RESULTS: Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis. CONCLUSIONS: Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.

Clinical characteristics of external auditory canal cholesteatoma in children.

OBJECTIVE: The purpose of this study was to investigate the characteristics of pediatric external auditory canal cholesteatoma (EACC). METHODS: Chart review of nine children with EACC between January 1, 2000 and December 31, 2007 was performed with subsequent analysis of etiologic factors, associated symptoms, otoscopic findings, imaging features, and treatment outcomes. RESULTS: The average age of patients was 10.3 years (range 6-15 years). Five patients were girls and four were boys. There was greater incidence of EACC on the right side (eight of nine patients). Otorrhea and hearing impairment were the most common presenting symptoms. The inferior wall of the external auditory canal was most commonly involved. Five patients underwent cholesteatoma removal under general anesthesia. Surgical procedures were performed in four patients. No recurrence except in one patient was found during the follow-up period. CONCLUSIONS: Pediatric EACC is reported as a rare condition, but its low occurrence may be due to underreporting. Early diagnosis and treatment is essential in the management of pediatric EACC.