Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr ^–/– mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.

Objective: To determine if changes in cervical vestibular‐evoked myogenic potential (cVEMP) testing reflect the different stages of cochlea‐saccular hydrops in Meniere's disease (MD).Methods: This is a case‐control retrospective series. Forty‐seven patients with unilateral MD by American Academy of Otolaryngology–Head and Neck Surgery diagnostic and staging criteria, and 30 with non‐MD vertigo as control. Meniere patients were further classified based on symptoms at the time of testing as active or stable. Subsequently, patients underwent cVEMP testing by tone‐burst stimuli at 500 and 1,000 Hz. The main outcome measure was to compare the cVEMP 1,000 and 500 Hz amplitude ratio in ears with MD and non‐MD vertigo, and in active versus stable MD.Results: The cVEMP 1,000/500 Hz amplitude ratio was higher in Meniere's ears (mean = 1.14 μV, SD = 0.25) than in non‐Meniere's ears (mean = 0.96 μV, SD = 0.2) (Student's t test, P = .001), and higher in active (mean = 1.22 μV, SD = 0.25) than in stable MD (mean = 1.00 μV, SD = 0.18) (P = .0035). The diagnostic value of cVEMP 1,000/500 Hz amplitude ratio to differentiate MD versus non‐MD vertigo was evaluated with a receiver‐operating characteristics (ROC) curve and the area under the curve (AUC) was 0.716 (95% confidence interval [CI] [0.591, 0.829]). The ideal cutoff point was 0.9435 with sensitivity and specificity values of 83% and 53%, respectively. The sensitivity and specificity values for this test to differentiate active versus stable MD were 68% and 81%, respectively, with AUC 0.746 (95% CI [0.607, 0.885]) and cutoff value of 1.048. In all ears, the 1,000/500 Hz amplitude ratio increased by a decrease of the 500 Hz amplitude with increasing age.Conclusion: The cVEMP 1,000/500 Hz amplitude ratio is elevated in ears with MD but not in those with non‐MD vertigo. After corrected by age, this ratio is higher in active but not in stable MD, probably reflecting dynamic changes in saccular membrane motion mechanics in hydrops, and may be a useful marker of disease progression and the effect of therapy.Level of Evidence: IV

Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8–10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance.

Objective: To compare the safety and efficacy of manual and powered irrigation of the middle ear using saline or 1% baby shampoo to treat biofilm‐forming bacterial middle ear infections.Background: Biofilms play a major role in recalcitrant otitis media and are challenging to treat. Many therapeutic strategies have been attempted and the role of topical therapies is still being investigated. Topical irrigation using saline or 1% baby shampoo and the use of a hydrodebrider have been investigated in biofilms involved in chronic rhinosinusitis and their role within the middle ear is yet to be determined.Methods: Twenty‐two adult chinchillas underwent bilateral trans‐bullar inoculation of non‐typable biofilm forming Haemophilus influenza followed by unilateral middle ear irrigation 5 days later using saline administered via a powered hydrodebrider or manual irrigation of saline or 1% baby shampoo. Contralateral inoculated ears served as control and were not irrigated. Two days following irrigation, the bullae were harvested and processed for scanning electron microscopy to assess biofilm surface area. Auditory brainstem responses were performed before bacterial inoculation and prior to euthanasia.Results: Manual and powered irrigation were effective in reducing the surface area of biofilm when compared to the control group. The hydrodebrider demonstrated to be more effective at eradicating biofilm than manual irrigation, especially in areas of difficult access, such as the ventral portion of the chinchillas' bullae. There was no difference in manual irrigation of saline when compared to 1% baby shampoo. Irrigations either manually or using the hydrodebrider did not affect hearing, the vestibular system or facial function.Conclusion: Middle ear biofilms can be treated safely and effectively with rinses using either normal saline or 1% baby shampoo administered manually or with a powered hydrodebrider.Level of Evidence: NA.