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The aim of this study was to determine whether autophagy and AMPK contribute to premature senescence in auditory cells. Incubating HEI-OC1 auditory cells with 5 mM H2O2 for 1 h induced senescence, as demonstrated by senescence-associated β-galactosidase (SA-β-gal) staining. H2O2 treatment significantly delayed population-doubling time, leaving cell viability unchanged. Furthermore, the proportion of SA-β-gal-positive cells significantly increased. Autophagy-related protein expression increased, with Atg7 and LC3-II peaking 6 h and Lamp2 peaking 24 h after H2O2 treatment. The expression of these proteins decreased 48 h after treatment. Transmission electron microscopy revealed lipofuscin and aggregates within autolysosomes, which accumulated markedly in the cytoplasm of HEI-OC1 cells 48 h after treatment. Akt and P70S6 phosphorylation markedly decreased after H2O2 treatment, but 4EBP1 phosphorylation significantly increased 48 h after treatment. After RNAi-mediated knockdown (KD) of Atg7 and AMPK, H2O2-treated cells displayed dense SA-β-gal staining. Also, premature senescence was significantly induced. These suggest that a negative feedback loop may exist between autophagy and AMPK signaling pathways in HEI-OC1 cells. In our model, oxidative stress-induced premature senescence occurred due to impaired autophagy function through 4EBP1 phosphorylation. Our results also indicate that AMPK may regulate premature senescence in auditory cells in an autophagy-dependent and independent manner.

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Objectives/Hypothesis The extreme rarity of temporal bone squamous cell carcinoma (TB‐SCC) has delayed the accumulation of high‐quality clinical evidence. For the purposes of retrospective meta‐analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB‐SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors. Study Design Retrospective chart review. Methods The medical records of all TB‐SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment. Results T4 status was associated with lower disease‐specific 5‐year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins. Conclusions Definitive treatments can offer disease‐specific 5‐year survival of over 85% in T1 to T3 cases of TB‐SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB‐SCC. Level of Evidence 4 Laryngoscope, 131:E583–E589, 2021

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More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Rats were given vitamin E (Vit-E), idebenone (ID), or vitamin C (Vit-C) in their food for 2 or 4 weeks. After feeding, the ability of rats to reduce 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) in terms of the half-life of Tempol was examined as a specific marker. Tempol was repeatedly injected intravenously, and its half-life was serially evaluated by an in vivo electron spin resonance (ESR) technique. The radical-reducing ability in rats was enhanced differently by Vit-E, ID, and Vit-C, i.e., slow onset of the ability after Vit-E and ID (lipid-soluble antioxidants) and fast onset after Vit-C (a water-soluble antioxidant).