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.

Endolymphatic Hydrops on Magnetic Resonance Imaging May Be an Independent Finding on Aging in Neurotologic Patients.

OBJECTIVE: To clarify whether age impacts the development of endolymphatic hydrops (ELH) in neurotologic patients. Documentation of ELH in living patients on magnetic resonance imaging (MRI) allows analysis of patient age and formation of ELH, which is impossible by means of postmortem temporal bone pathology. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fifty patients (100 ears) with top 3 diagnoses of definite Menière's disease, delayed ELH, or probable Menière's disease. INTERVENTIONS: Endolymph MRI after intravenous gadolinium injection and pure-tone audiometry. MAIN OUTCOME MEASURES: Cochlear and vestibular ELH confirmed by MRI. RESULTS: The prevalences of ears showing both cochlear and vestibular ELH were similar among age groups <30 years (30%), 30-59 years (25.9%), and ≥60 years (34.4%; p > 0.05; χ2 test). Using logistic regression modeling, mean hearing level at the six frequencies was positively associated with a higher risk of cochlear ELH (odds ratio, 1.3; 95% confidence interval, 1.1-1.5 per 10-dB increment). In the same regression model, age did not impact the outcome of cochlear ELH (odds ratio, 1.0; 95%confidence interval, 0.7-1.4 per 10-year increment). Age did not differ among ears with no ELH (mean ± standard deviation age, 48.6 ± 14.4 yr), ears with only cochlear ELH (59.3 ± 10.7 yr), ears with only vestibular ELH (50.4 ± 16.9 yr), or ears with both cochlear and vestibular ELH (51.5 ± 18.4 yr; p > 0.05, analysis of variance). CONCLUSION: Chronological age was not associated with the formation of ELH. Aging per se may not be associated with the development of ELH in neurotologic patients.

15-year follow-up for steroid-responsive, fluctuating hearing loss in the ear with endolymphatic hydrops confirmed by magnetic resonance imaging.

Autoimmune mechanisms may play crucial roles in the etiology of endolymphatic hydrops (ELH), which was previously regarded as a postmortem finding in the temporal bone. Recently, ELH has been visualized using 3-T MR imaging in living patients. A 47-year-old woman with deafness in the left ear since adolescence developed right-sided steroid-responsive sensorineural hearing loss in the low frequencies. During over 15 years of follow-up at our otolaryngology clinic, acute deteriorations of hearing in the only hearing ear repeatedly recovered with administration of intravenous and oral steroids. Hearing in the only hearing ear at 62 years old was preserved and comparable to that at 47 years old. At 61 years old, cochlear ELH was documented bilaterally on MR imaging, appearing more severe in the deafened ear than in the hearing ear. This case provides new evidence of the potential steroid-responsiveness of hearing loss due to contralateral-type delayed ELH distinctly visualized on MR imaging.

Relationship between spontaneous nystagmus and video Head Impulse Test findings among patients with chronic neurotologic conditions.

The vestibulo-ocular reflex (VOR) in neurotologic patients can be evaluated most quickly by spontaneous nystagmus examinations, and the video Head Impulse Test (vHIT) quantitatively evaluates the VOR of the semicircular canals. We aimed to clarify the concordance and discrepancies between spontaneous nystagmus and vHIT findings, to provide guidance on screening vestibular functions by initial spontaneous nystagmus examination then vHIT. We evaluated 169 outpatients by spontaneous nystagmus examination in the dark using a charge-coupled device camera, then by horizontal vHIT the same day. Vestibular loss on vHIT was defined if both reduced VOR gain (<0.8) and corrective saccade were observed. Adjusted logistic regression modelling revealed that differences in right and left VOR gain positively impacted the presence of nystagmus, which suggests lateralised vestibular dysfunction (P<0.05; odds ratio 1.39 [95% confidence interval, 1.1-1.8] per 0.1 increment). When vHIT is regarded as the standard clinical test, the positive predictive value of nystagmus for vestibular loss on vHIT was 44.4%, and the negative predictive value was 93.5%. The adjusted odds ratio of adults ≥65 years old compared to younger patients associated with a discrepancy of nystagmus and vHIT was significant (2.4 [1.1-5.3]). In conclusion, if spontaneous nystagmus is initially observed in patients, further assessment by vHIT could confirm vestibular dysfunction in 40-50% of cases. If no nystagmus is observed, vHIT might also result in a negative finding in >90% of cases. Older adults appear more likely to show discrepancies between nystagmus and vHIT.

Static posturographic balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing process.

BACKGROUND: Understanding how sensorineural hearing loss (SNHL) impacts postural balance in patients is important, as postural balance predicts the risk of falls. AIMS/OBJECTIVES: We aimed to clarify the relationship between characteristics in the configuration of audiograms and static postural balance as measured by posturography. MATERIALS AND METHODS: We evaluated 385 outpatients (mean [± standard deviation] age, 58.4 ± 18.4 years) with SNHL by audiometry and posturography. Data were analysed by multiple regression models with the outcome of postural sway area with eyes closed (PSA) and predictive variables of audiometric data, adjusted for sex, age and the presence of nystagmus. RESULTS: The increased hearing threshold in the better hearing ear was associated with poorer or higher PSA (beta coefficient [ß] = 0.39, 95% confidence interval [CI] = 0.03-0.75, per 10-dB increment). No difference in PSA was detected between patients with asymmetric or symmetric SNHL. None of the frequent diagnoses (presbyacusis, Meniere's disease, and idiopathic sudden SNHL) were associated with poorer PSA. Hearing thresholds at middle (ß = 0.39, 95%CI = 0.10-0.67) and high frequencies (ß = 0.31, 95%CI = 0.07-0.55) were associated with poorer PSA, whereas those at low frequencies was not. CONCLUSIONS AND SIGNIFICANCE: Postural balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

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-κB subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-κB 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-κB-interacting inflammatory molecules, TNFα 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.

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.

Lack of collagen α6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation.

Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen α6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen α6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the α6(IV) chain and/or α5α6α5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.

A Multi-Institutional Study of Older Hearing Aids Beginners-A Prospective Single-Arm Observation on Executive Function and Social Interaction.

OBJECTIVES: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. DESIGN: Multi-institutional prospective single-arm observational study. SETTING AND PARTICIPANTS: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. METHODS: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). RESULTS: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. CONCLUSIONS AND IMPLICATIONS: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family.

Subjective Evaluation of Balance by the Dizziness Handicap Inventory Does Not Predict Fall Risk in Older Adults Visiting Otolaryngology Clinics.

OBJECTIVES: Subjective symptoms of dizziness in older adults are affected not only by objective data such as postural balance, but also by complex psychological factors. Published data analyzing how simultaneous evaluations of both objective and subjective assessments of balance can predict fall risk remain lacking. This study examined how fall risk can be predicted based on both objective data for balance and hearing and subjective symptoms of dizziness among older adults visiting otolaryngology clinics. METHODS: Medical charts of 76 patients ≥65 years old with dizziness/vertigo who visited the otolaryngology clinic were reviewed. Objective data were evaluated by postural balance (posturographic data with eyes open and closed, and one-leg standing test), spontaneous nystagmus, and mean hearing levels. Subjective handicap associated with dizziness/vertigo was assessed using the Dizziness Handicap Inventory (DHI). Subjective mental status of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Information on history (cardiovascular diseases) and fall accidents within the preceding year was collected using an in-house interview sheet. RESULTS: Objective data on postural balance did not correlate with subjective symptoms on DHI or HADS (P > .05, Pearson's correlation coefficient). Adjusted logistic regression modeling with the outcome of incident falls revealed that poor postural balance significantly predicted fall risk (P < .05; 4.9 [1.4-16.8] per 10-cm2 increment). Nystagmus tended to be associated with fall risk. In contrast, DHI score did not predict fall risk (P = .43; 1.0 [0.9-1.03]). Receiver operating characteristic analysis proposed a cut-off for postural sway with eyes closed >6.1 cm2 as optimal to predict falls in patients with nystagmus (AUC, 0.74; 95% confidence interval, 0.48-0.997). CONCLUSION: Poor postural balance is associated with increased fall risk after adjusting for subjective symptoms in older adults at otolaryngology clinics. Conversely, the self-perceived dizziness handicap of DHI score is an insufficient tool to evaluate their fall risk.

Immediate changes in transcription factors and synaptic transmission in the cochlea following acoustic trauma: A gene transcriptome study.

Pathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss.

Prevalence and risk factors for delayed-onset hearing loss in early childhood: A population-based observational study in Okayama Prefecture, Japan.

OBJECTIVES: The aim of this study was to retrospectively document prevalence rates of delayed-onset hearing loss (DOHL) under 7 years old after passing the newborn hearing screening (NHS) program using its database in Okayama Prefecture, as well as records from Okayama Kanariya Gakuen (OKG, Auditory Center for Hearing Impaired Children, Okayama Prefecture, Japan). We explored the percentage of children with DOHL among all children who underwent the NHS and surveyed risk factors abstracted from their clinical records. METHODS: We collected data of 1171 children, who first visited OKG from April 2006 to March 2018. DOHL children were defined as bilaterally hearing-impaired children who were diagnosed under 7 years old after passing the NHS at birth. Based on the medical records, we investigated age at diagnosis, hearing levels, and risk factors. As population-based data of 168,104 children, the percentage of DOHL subjects was retrospectively calculated among the total number of children who underwent the NHS in Okayama Prefecture from April 2005 to March 2017. RESULTS: During the period, we identified 96 children with bilateral DOHL, of which 34 children had failed the NHS unilaterally and 62 had passed the NHS bilaterally. Among all children who underwent the NHS in Okayama Prefecture, the prevalence rate of DOHL in unilaterally referred infants was 5.2%, and 0.037% in bilaterally passed children. The prevalence of bilateral DOHL was 0.057% overall. Unilaterally referred children with DOHL were diagnosed at an average of 13.9 months, while bilaterally passed children with DOHL were diagnosed at an average of 42.3 months. Approximately 59.4% of children with DOHL had risk factors, among which family history of hearing loss was the most frequent. CONCLUSION: We propose the first English report of DOHL prevalence in the prefecture population in Japann, which is among the largest community-based population ever reported. The NHS is not a perfect strategy to detect all early-childhood hearing loss; therefore, careful assessment of hearing throughout childhood is recommended, especially in children with risk factors of hearing loss. Further interventional strategies must be established, such as regular hearing screening in high-risk children and assessments of hearing and speech/language development in public communities and nursery schools.

Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media.

HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1ß and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. BACKGROUND: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. METHODS: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1ß, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. RESULTS: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF mice as compared with the wild-type mice. The concentrations of IL-1ß, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF mice with lipopolysaccharide had decreased levels of IL-1ß, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. CONCLUSION: Macrophage migration inhibitory factor has an important role in the production of IL-1ß and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.

Progression of hearing loss and choice of hearing aids by patients in their 60s, 70s, and 80s and older: experience in the Japanese super-aged era.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (HA) use in patients in their 60s, 70s, and 80s and older during the super-aged era.Material and methods: Medical charts and audiograms of 2064 older patients with SNHL who visited a Japanese University Hospital in 2007-2018 were retrospectively reviewed. Among 270 patients referred to the HA service unit (HASU), the percentage of final decisions to continue using HAs was calculated.Results: The average pure tone thresholds on initial visit to the clinic were 56.9, 60.6, 69.4, and 82.4 dB HL in patients in their 60s, 70s, 80s, and 90s, respectively. The rates of progression were 0.25, 0.87, 1.19, and 1.37 dB/year in patients in their 50s, 60s, 70s, and 80s, respectively. The percentage of patients in HASU who chose to use HAs did not differ among the 60s (59.3%), 70s (51.2%), and 80s and older (58.2%).Conclusions and significance: The clinical picture of patients with SNHL in their 70s and 80s differs because progression accelerates exponentially through these ages. HAs can be recommended to older adult patients in all the age groups.

Impact of reading and writing skills on academic achievement among school-aged hearing-impaired children.

OBJECTIVES: Reading and writing skills are important for hearing-impaired children since these skills help them to develop their language skills, but the prevalence of reading/writing difficulties and its effects on language development aspects among them are unclear. In this study, we identified language development features and demographic factors of Japanese hearing-impaired children diagnosed as having reading/writing difficulties. METHODS: We analyzed data from a total of 546 sever-to-profound pre-school and elementary school hearing-impaired children for this study. Children with reading/writing difficulties (Group A) were defined as children obtaining low scores (-1.5 SD compared to others in the same grade) in the Screening Test of Reading and Writing for Japanese Primary School Children (STRAW), and we compared other language development features (communication ability, vocabulary, syntax and academic achievement) and demographic factors to those of hearing-impaired children with normal reading and writing skills (Group B). We assessed language development domains as outcomes using the Assessment of Language Development for Japanese Children (ALADJIN) package, and analyzed the results stratified by age groups (5-6, 7-8, 9-10, and 11-12 years) using multiple regression analyses. RESULTS: The prevalence of reading/writing difficulties was 20.1% among the participants. Almost all point estimates in each language development domain showed better odds ratios (OR) except Criterion Referenced Test -II (CRT-II) mathematics in 11- to 12-year-olds in fully-adjusted models. Among 9- to 10-year-olds, the ORs (95% confidence interval) for fair academic achievement measured by CRT-II were 2.60 (1.09-6.20) for Japanese and 3.02 (1.29-7.11) for mathematics in Group B, even after adjusting for possible confounding factors. CONCLUSIONS: Reading and writing are important for language development of hearing-impaired children, especially for academic achievement during the middle phase of elementary school. Screening for reading/writing difficulties is important for appropriate intervention and to prevent language and academic delays among hearing-impaired children.

Clinical feasibility of auditory processing tests in Japanese older adults: a pilot study.

Background: Difficulty in listening comprehension is a major audiological complaint of older adults. Behavioural auditory processing tests (APTs) may evaluate it. Aims/Objectives: The aim was to assess the feasibility of administering Japanese APTs to older adults at otolaryngology clinics. Material and Methods: Using computer programs interfaced with an audiometer, APTs (dichotic listening test; fast speech test, FST; gap detection test, GDT; speech in noise test; rapidly alternating speech perception test) were administered to 20 older adults (65-84 years old; mean 75.3 years) and 20 young adults at the 40 dB sensation level. Monosyllable speech perception (MSP) and the Mini-Mental State Examination (MMSE) were evaluated. Results: APT results except for GDT were significantly correlated with MSP. The performance on each APT was worse in older adults than in young adults (p < .01). The older adults with good MSP ≥ 80% (n = 13) or excellent cognitive function (MMSE ≥ 28; n = 11) also did worse on APTs (p < .05). A ceiling effect was noted in the APT data, with FST showing a minimum ceiling effect and reflecting interindividual variations of data. Conclusions and Significance: It is feasible to administer APTs to older adults who visit otolaryngology clinics. Among our Japanese APTs, FST may be suitable for further large-scale clinical studies.

Targeted PCR Array Analysis of Genes in Innate Immunity and Glucocorticoid Signaling Pathways in Mice Cochleae Following Acoustic Trauma.

AIM: To comprehensively analyze cochlear gene expressions related to innate immunity and glucocorticoid signaling at onset of acute noise-induced hearing loss (NIHL). BACKGROUND: Recent studies suggested innate immunity is involved in the cochlear pathology of NIHL. Glucocorticoids may modulate immune actions in cochleae. METHODS: Mice were exposed to 120 dB-octave band noise for 2 hours. Twelve hours later, a targeted PCR array analyzed cochlear expressions of 84 key genes in inflammation and immune pathways and 84 genes in the glucocorticoid signaling pathway. Real-time RT-PCR was used to analyze expression of two immune-related genes, Ccl12 and Glycam1, in noise-exposed cochleae with or without dexamethasone. RESULT: In inflammatory and immune gene pathways, 31.0% (26/84 genes) were significantly upregulated (>2-fold change) or downregulated (<0.5-fold change) (p < 0.05) in noise-exposed cochleae compared with controls. Sixteen of these differentially expressed genes (DEGs) encoded chemokines. DEGs included Ccl12, Ccl2, Ccl4, Ccl7, Cxcl1, Cxcl10, and Ptgs2 (upregulated genes), and Ccr7, Cxcr2, Kng1, Ltb, and Tnfsf14 (downregulated genes). In the glucocorticoid signaling pathway, 92.9% (78/84 genes) were unchanged in noise-exposed cochleae without dexamethasone administration. Cochlear expressions of Ccl12 and Glycam1 were significantly upregulated by noise and downregulated by dexamethasone. CONCLUSION: The targeted PCR array demonstrated that several dozen genes involved in innate immunity are actively regulated in cochleae with NIHL. The glucocorticoid signaling pathway was not endogenously regulated at 12 hours post-noise trauma. Systemic dexamethasone downregulated Ccl12 and Glycam1, which are upregulated in noise-exposed cochleae. These data may provide a basis for genomic medicine treatment of acute sensorineural hearing loss.

The diagnostic performance of a novel ELISA for human CTP (Cochlin-tomoprotein) to detect perilymph leakage.

Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.