Effects of Protective Measures against COVID-19 on Auditory Communication for People with Hearing Loss

WHO has recommended various measures to combat the COVID-19 pandemic, including mask-wearing and physical distancing. However, these changes impair communication for individuals with hearing loss. We investigated the changes in auditory communication associated with COVID-19 measures in 269 patients (male: 45.7%, female: 54.3%, median age: 54 y.o.). Most patients with hearing loss had difficulty engaging in auditory communication with people wearing masks, especially in noisy surroundings or with physical distanc-ing. These difficulties were noticeable in patients with severe hearing loss. Developing communication support strategies for people with hearing loss is an urgent need while COVID-19 measures are in place

Hair cell transduction efficiency of single- and dual-AAV serotypes in adult murine cochleae

Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells

Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice

Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and −0.33, 95% confidence intervals [11.75-37.45] and [−0.58 to −0.09], respectively), but the CI surgery side did not (−6.76, [−14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing

Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss

Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-kappa B subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-kappa B would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-kappa B-interacting inflammatory molecules, TNF alpha and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL

Time course of shifts in the auditory brainstem response (ABR) threshold following exposure to 120-dB octave band noise (8.0–16.0kHz) for 2 h.

<p>Significant elevation of the ABR threshold at 0 h (immediately after the noise exposure; 58.1±12.5 dB sound pressure level (SPL)), 12 h (73.6±14.4), and 24 h (48.6±15.7) exhibited a component of temporary threshold shift (TTS) during 0–24 h. The TTS was more severe at 12 h than at 0 h, and partial recovery was observed at 24 h. A significant permanent threshold shift was confirmed at 14 days (40.0±13.8), compared with the control level before the noise exposure (20.6±5.6 dB SPL).</p

Time course of phospho-JNK expression in the cochlear lysate following exposure to the intense noise.

<p>The levels of phospho-JNK in the cochlear lysate at 0 h (immediately after the noise exposure; 104.7±7.6), 3 h (167.2±18.1; <i>p</i><0.01), 6 h (146.4±13.3; <i>p</i><0.01), 12 h (129.2±10.8; <i>p<</i>0.01), 24 h (127.1±11.8; <i>p<</i>0.01), and 48 h (185.4±13.8; <i>p<</i>0.01) after the noise exposure significantly increased from the control level (100.0±11.8), with the early and late peaks at 3 h and 48 h. (*<i>p</i><0.01, Kruskal-Wallis test and Mann-Whitney <i>U</i>-test; <i>n</i> = 8 for each time point).</p