野田 昌生

Hearing impairment, one of the most prevalent sensory disorders, remains a major risk factor for dementia in the aging population. Although interventions such as hearing aids and cochlear implants provide partial benefit, they do not address the underlying pathology of sensorineural hearing loss. Inner ear gene therapy has attracted significant attention as a promising approach; however, its clinical translation requires minimally invasive and controllable methods for gene activation. We previously developed a photoactivatable Cre recombinase (PA-Cre) system for spatiotemporal regulation of gene expression. In this study, we evaluated the feasibility of irradiating the external auditory canal (EAC) and tympanic membrane (TM) as minimally invasive approaches for activating cochlear gene expression. Tyrosine-mutant AAV9/3 vectors (AAV.GTX) encoding PA-Cre and a Cre-dependent reporter (sfGFP-to-tdTomato) were injected via the round window membrane in 9-week-old C57BL/6J mice. Seven days later, light irradiation was applied using three approaches: (1) Direct cochlear irradiation via postauricular access, (2) TM irradiation with a fiber-optic probe, and (3) noninvasive EAC irradiation through the intact TM. Recombination efficiency in inner hair cells (IHCs) was quantified using whole-mount immunohistochemistry. AAV.GTX efficiently transduced IHCs and drove robust sfGFP expression. In the absence of light, tdTomato expression remained minimal (<5%), indicating low basal Cre leak activity. Direct cochlear irradiation produced strong recombination (conversion rate: 88.4 ± 1.5%), confirming the functionality of PA-Cre in the mouse inner ear. TM and EAC irradiation yielded high conversion efficiencies (95.8 ± 1.7% and 97.6 ± 1.2%, respectively), comparable to direct irradiation, while preserving cochlear integrity. These findings indicate that PA-Cre functions effectively in the mouse cochlea with minimal leak activity and that TM and EAC irradiation enable robust, minimally invasive gene activation. This strategy highlights the light-mediated, noninvasive modulation of cochlear gene expression, informing future translational development.

OBJECTIVE: The aim of this study was to investigate the prevalence of frailty and the factors associated with frailty in patients with vestibular hypofunction. DESIGN: This observational study included 185 individuals with dizziness aged 40 and above who suffered from chronic vestibular hypofunction. We defined frailty using the diagnostic algorithm by the revised Japanese version of the Cardiovascular Health Study criteria. Frailty, prefrailty, and robust were defined as including 3 to 5, 1 to 2, and 0 points, respectively. For comparison, we also assessed the prevalence of frailty in community-dwelling adults over 40 years old (control group, n = 203). RESULTS: The average ages for the groups with vestibular hypofunction and the control were 72.0 ± 10.1 and 69.8 ± 8.2 years, respectively. In the vestibular hypofunction group (185 patients), 32 were identified as frail (17.3%) and 103 as prefrail (55.7%). Of the patients with vestibular hypofunction aged 65 years or older (n = 151), 31 (20.5%) were frail and 80 (53.0%) were prefrail. In the control group, consisting of 203 community-dwelling adults, 15 were identified as frail (7.0%) and 108 as prefrail (54.0%). Among patients with vestibular hypofunction, 64 (34.6%) exhibited low gait speed, the most common of the frailty components. Age, female, Hospital Anxiety and Depression Scale-Depression subscale, and Dizziness Handicap Inventory were associated with frailty and prefrailty in patients with vestibular hypofunction, after adjustment for confounding factors. CONCLUSIONS: The present study demonstrates that the prevalence of frailty in patients with vestibular hypofunction is higher than that in community-dwelling adults. Therefore, evaluating frailty in patients with vestibular hypofunction is crucial for identifying those at higher risk and implementing early interventions such as dietary guidance and exercises to strengthen the lower body along with vestibular rehabilitation.

BackgroundSubjective visual vertical (SVV) test is a key functional assessment tool that provides insights into vestibular imbalance. Mobile virtual reality SVV measurement system (MVR-SVV) has the potential to facilitate simple, low-cost, and reliable measurements.ObjectiveThis study aimed to verify the reliability and validity of MVR-SVV by comparing its data with the previously established bucket test (bucket-SVV).MethodsThirty-eight healthy adults completed both bucket-SVV and MVR-SVV tests. The reliability and validity of MVR-SVV were examined using intraclass correlation coefficients (ICCs), Pearson's correlation, Bland-Altman plots (BAP), and minimum detectable change (MDC).ResultsBAP results indicated that the limits of agreement for the SVV angles were 1.61 to -1.24°. No fixed errors were identified (p = 0.13), although a small proportional error was detected (y = -0.59x + 0.157, p < 0.001). Pearson's correlation coefficient between bucket-SVV and MVR-SVV was 0.716 (p < 0.001). Within-day reliability was poor for bucket-SVV, with ICC = 0.33-0.38, but moderate for MVR-SVV, with ICC = 0.70-0.71. Between-day reliability was poor for both methods, with ICC = 0.38 for MVR-SVV and ICC = 0.28 for bucket-SVV. MDC was 1.78° for bucket-SVV and 2.67° for MVR-SVV.ConclusionsOur findings suggest that MVR-SVV can be used for assessing SVV. Its portability, availability, and reliability make it a valuable tool for clinicians in clinical settings.