Yumi Ohta

Background/Objectives: Dysregulated gamma oscillations are associated with cognitive dysfunction. Auditory stimulation at 40 Hz enhances neural activity in brain regions associated with learning, attention, and memory. This study assessed the safety and acceptability of 40 Hz amplitude-modulated auditory stimulation in healthy older people. Auditory stimuli were created using popular songs, where vocals and background music were separated and independently amplitude-modulated at 40 Hz with different modulation depths to generate periodic 40 Hz gamma waveforms. Methods: In this open-label, single-arm study, healthy participants aged ≥65 years received 40 Hz amplitude-modulated auditory stimulation daily via a smartphone for 28 days through earphones/headphones. Safety was assessed through adverse event (AE) monitoring and changes in clinical scores for depression, cognitive function, and hearing thresholds. Acceptability was evaluated by adherence rates, listening time, dropout reasons, volume levels, intent for future use, and subjective impressions of the sound source on a 7-point Likert scale. Results: Among 28 participants (mean age 69.1 years, 53.6% female), six reported 12 AEs, with six considered device-related (e.g., ear discomfort, jaw pain, musculoskeletal stiffness). The AEs observed were mild or moderate. Scores for cognitive function, depression, and hearing thresholds did not worsen during the study period. Adherence was observed in 96.4%, with 85.7% expressing interest in continuing. Most participants rated the sounds’ unnaturalness between 2 and 3 and discomfort between 1 and 3 on the 7-point Likert scale. Conclusions: The intervention was well tolerated and acceptable in study participants, with no major safety concerns identified. Auditory stimulation did not cause severe discomfort or reduce acceptability. Further studies should explore the long-term effects and broader clinical applications.

The case is of a 60-year-old woman with a history of radiotherapy for parotid adenoid cystic carcinoma. Twenty years after irradiation, a papilloma developed in the left external auditory canal. Nine years after excision of the papilloma, a squamous cell carcinoma developed in the same region. This is a rare case of squamous cell carcinoma following treatment for a papilloma and is considered radiation-induced cancer. Because re-irradiation is not possible as a treatment for radiation-induced cancer, it is necessary to diagnose the cancer early so that curative resection is possible. Multiple biopsies should be considered when malignancy is suspected because a single biopsy may not be sufficient to diagnose an auditory canal tumor.

Background/Objectives: The OTOG gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative OTOG variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for OTOG-associated hearing loss remain unclear. Methods: In this study, we analyzed 7065 patients with non-syndromic hearing loss (mean age 26.4 ± 22.9 years, 2988 male, 3855 female, and 222 without gender information) using massively parallel DNA sequencing for 158 target deafness genes. We identified the patients with biallelic OTOG variants and summarized the clinical characteristics. Results: Among the 7065 patients, we identified 14 possibly disease-causing OTOG variants in 26 probands, with 13 of the 14 variants regarded as novel. Patients with OTOG-associated hearing loss mostly showed congenital or childhood-onset hearing loss. They were considered to show non-progressive, mild-to-moderate hearing loss. There were no symptoms that accompanied the hearing loss in OTOG-associated hearing loss patients. Conclusions: We confirmed non-progressive, mild-to-moderate hearing loss as the clinical characteristics of OTOG-associated hearing loss. These findings will contribute to a better understanding of the clinical features of OTOG-associated HL and will be useful in clinical practice.

Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in the initiation and progression of this disease. However, whether the cochlear properties can be influenced by pathological signals associated with dementia remains unclear. In this study, using a mouse model of Alzheimer’s disease (AD), we investigated the impacts of the AD-like amyloid β (Aβ) pathology in the brain on the cochlea. Despite little detectable change in the age-related shift of the hearing threshold, we observed quantitative and qualitative alterations in the protein profile in perilymph, an extracellular fluid that fills the path of sound waves in the cochlea. Our findings highlight the potential contribution of Aβ pathology in the brain to the disturbance of cochlear homeostasis.

Eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) are debilitating inflammatory conditions that affect the paranasal sinuses and middle ear, respectively, and are characterized by eosinophilic infiltration. This study describes a rare and intricate case of a 65-year-old male patient concurrently afflicted with ECRS, EOM, and bronchial asthma. Despite the systematic administration of corticosteroids and various antibody drugs, the patient's condition remained unimproved, necessitating a cochlear implant for EOM, which is seldom an aggressive intervention. The patient had a history of symptoms dating back to 2005, with notable exacerbations and treatment resistance over the years. Multiple antibody drugs, including anti-IgE, anti-IL-5, and anti-IL-4α antibodies, failed to ameliorate the patient's condition, presenting a significant clinical challenge. Pathological examination revealed marked eosinophilic infiltration and severe fibrosis, suggesting a possible mechanism underlying the poor response to antibody therapy. Cochlear implantation significantly enhanced the patient's communicative abilities. This case highlights the limitations of the current antibody drugs in managing severely intertwined cases of ECRS, EOM, and bronchial asthma, highlighting the need for novel therapeutic strategies. This case also propounds cochlear implantation as an efficacious intervention for refractory EOM with severe sensorineural hearing impairment, extending the spectrum of treatment modalities for such challenging scenarios. This singular case contributes to the growing body of evidence regarding the management of ECRS and EOM, especially against the backdrop of treatment resistance, and can aid clinicians in identifying and navigating similar complex cases in clinical practice.

Recognition of the anatomical course of the chorda tympani nerve (CTN) is important for preventing iatrogenic injuries during middle-ear surgery. This study aims to compare visualization of the CTN using two computed tomography (CT) methods: conventional high-resolution CT (C-HRCT) and ultra‐high-resolution CT (U-HRCT). We performed a retrospective visual assessment of 59 CTNs in normal temporal bones of 54 consecutive patients who underwent both C-HRCT and U-HRCT. After dividing CTN into three anatomical segments (posterior canaliculus, tympanic segment, and anterior canaliculus), two neuroradiologists scored the visualizations on a four-point scale. On C-HRCT, the visual scores of the posterior canaliculus, tympanic segment, and anterior canaliculus were 3.5 ± 0.7, 1.6 ± 0.6, and 3.1 ± 0.7, respectively. The respective values were significantly higher in all segments on U-HRCT: 3.9 ± 0.2, 2.4 ± 0.6, 3.5 ± 0.6 (p < 0.01). Although the difference in scores between methods was greatest for the tympanic segment, the visual score on U-HRCT was lower for the tympanic segment than for the anterior and posterior segments (p < 0.01). Ultra‐high-resolution CT provides superior visualization of the CTN, especially the tympanic segment.

The organ of Corti is an auditory organ located in the cochlea, comprising hair cells (HCs) and other supporting cells. Cellular shape changes of HCs are important for the development of auditory epithelia and hearing function. It was previously observed that HCs and inner sulcus cells (ISCs) demonstrate cellular shape changes similar to the apical constriction of the neural epithelia. Apical constriction is induced via actomyosin cable contraction in the apical junctional complex and necessary for the physiological function of the epithelium. Actomyosin cable contraction is mainly regulated by myosin regulatory light chain (MRLC) phosphorylation by myosin light chain kinase (MLCK). However, MRLC and MLCK isoforms expressed in HCs and ISCs are unknown. Hence, we investigated the expression patterns and roles of MRLCs and MLCKs in HCs. Droplet digital PCR revealed that HCs expressed MYL12A/B and MYL9, which are non-muscle MRLC and smooth muscle MLCK (smMLCK), respectively. Immunofluorescence staining throughout the organ of Corti demonstrated that only MYL12 was expressed in the apical portion of HCs, whereas MYL12 and MYL9 were expressed on ISCs. In addition, purified MYL12B was phosphorylated by smMLCK in vitro, and the harvested HCs contained phosphorylated MYL12. Furthermore, accompanied by the expansion of the cell area of outer HCs, MYL12 phosphorylation was reduced by ML-7, which is an inhibitor of smMLCK. In conclusion, MYL12 phosphorylation by smMLCK contributed to the apical constriction-like cellular shape change of HCs possibly relating to the development of auditory epithelia and hearing function.

Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1β, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1β was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.