Allele-specific effects of distinct SLC26A4 variants on cochlear function and transcriptomic programs in compound heterozygous models.

This study examined the relationship between behavioural thresholds as measured by pure tone audiometry and electrophysiological thresholds measured by the Auditory Steady-State Response (ASSR) in children with normal hearing and sensorineural hearing loss. After being assessed, 45 children of both sexes, ranging in age from 5 to 15, were split into four groups: 10 with moderate to moderately severe sensorineural hearing loss (G2M); 10 with steeply sloping sensorineural hearing loss (G2D); 10 with profound and severe sensorineural hearing loss (G2S); and 15 with normal hearing (G1). ASSR, tympanometry, acoustic reflex testing, pure tone audiometry, and speech audiometry (SRT and SDT) were performed. The electrophysiological maximum in the group with normal hearing thresholds varied from 19 to 27 dB NA. The correlation in the group with moderate to moderately severe hearing loss was 0.42-0.74. The correlation in the steeply sloping hearing loss group was 0.68-0.94. The correlation in the group of people with profound and severe hearing loss was 0.59-0.86. The normal hearing group's mean differences in ASSR threshold and audiometric threshold ranged from -0.3 to 12 dB, in the moderate and moderately severe hearing loss group from -9 to 2 dB, in the steeply sloping hearing loss group from 1.4 to 7.5 dB, and in the severe and profound hearing loss group from -0.40 to 8.5 dB. As expected, there was no strong relationship between behavioural and electrophysiological thresholds in the group with normal hearing. But in children with hearing loss, there was a strong correlation between electrophysiological and behavioural thresholds; this relationship was especially evident in children with severe and profound hearing loss and those with steeply sloping hearing loss.

To evaluate the associations between hearing status and hearing aid use and performance on the Montreal Cognitive Assessment (MoCA) in older adults in a cross-sectional study in Norway. This study utilized data from the fourth wave of the Trøndelag Health Study (HUNT4, 2017-2019). Hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz (or PTA4) in the better hearing ear were used to determine participants' hearing status [normal hearing (PTA4 hearing threshold, ≤ 15 dB), or slight (PTA4, 16-25 dB), mild (PTA4, 26-40 dB), moderate (PTA4, 41-55 dB), or severe (PTA4, ≥ 56 dB) hearing loss]. Both standard scoring and alternate MoCA scoring for people with hearing loss (deleting MoCA items that rely on auditory function) were used in data analysis. The analysis was adjusted for the confounders age, sex, education, and health covariates. The pattern of results for the alternate scoring was similar to that for standard scoring. Compared with the normal-hearing group, only individuals with moderate or severe hearing loss performed worse in the MoCA. In addition, people with slight hearing loss performed better in the MoCA than those with moderate or severe hearing loss. Within the hearing loss group, hearing aid use was associated with better performance in the MoCA. No interaction was observed between hearing aid use and participants' hearing status with performance on the MoCA test. While hearing loss was associated with poorer performance in the MoCA, hearing aid use was found to be associated with better performance in the MoCA. Future randomized control trials are needed to further examine the efficacy of hearing aid use on the MoCA performance. When compared with standard scoring, the alternate MoCA scoring had no effect on the pattern of results.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease of unknown origin with a prevalence rate about 1% in the population. Audiovestibular dysfunction is encountered in AS and sensorineural hearing loss is the most common form. The present study aimed to evaluate auditory and cochlear function in AS patients according to the site of involvement. A total of 47 patients followed for AS in the rheumatology outpatient clinic and 30 healthy controls were enrolled in the study. Subgroups of AS were identified according to the site of involvement. The participants underwent complete otolaryngological examination together with audiometry, otoacoustic emission and tympanometry tests. Disease Activity Index (BASDAI) was determined in the AS group. Hearing loss was detected in seven patients (15%) in the AS group and in four subjects (8%) in the control group. There was statistically significant difference between the patient and control groups in terms of mean bone conduction hearing level at 4000 hertz (Hz) in the right and left ears (p=0.028, p=0.049). There was no significant difference between the subgroups of AS in terms of overall auditory and cochlear functions. No correlation was determined between auditory values and Disease Activity Index and CRP (p>0.05 for all). Our results reveal that AS has minimal effect on auditory and cochlear functions. The effects of subgroups of AS on auditory functions were comparable. The authors concluded that BASDAI and CRP are not convenient in monitoring auditory functions of AS patients.

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function.

Physical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-β (TGFβ)-responsive pathway that controls osteoblast differentiation. Deregulated TGFβ or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2+/⁻ mice, inhibition of TGFβ signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue function.

Introduction: Hearing impairments are often associated with communication difficulties, which can hinder effective health education and the implementation of programs for proper oral hygiene and dental disease prevention. Aim: To assess the impact of oral hygiene, dietary patterns, and socioeconomic factors on dental caries prevalence in children with varying grades of hearing impairment Materials and methods: The objects of the study were 58 children (7 to 10 years) – 21 healthy children without hearing impairment,19 with mild and moderate hearing loss (they can't hear sounds below 20- 65 dB), 18 with severe and profound hearing loss (65 + dB). A comprehensive dental examination and professional oral hygiene were carried out on each child, during which the social status and eating habits were assessed through responses to a structured questionnaire administered in simple language and suitable formats. Data were collected and analyzed to identify the main factors influencing the prevalence of oral diseases in this special care need group. Results: In the control group, 52.4% had a high socioeconomic status. In the mild to moderate hearing loss group, 84% had a medium status, and in the severe hearing loss group, 44.4% had a low status. Children with hearing impairments, particularly those with severe hearing loss, exhibit significantly higher DMF scores, with the severe hearing loss group and poor oral hygiene having a DMF of 8.31 ± 2.93, compared to 5.29 ± 0.49 in the control group with poor hygiene. Children with frequent carbohydrate intake, reported by 67.7% of children with severe hearing loss, exhibit the highest mean DMF score (8.1), while those with limited intake, mostly from the control group (52.4%), show the lowest DMF score (2.4). Conclusion: The results of this study emphasize the heightened oral health risks in children with hearing impairments, particularly those with severe hearing loss. Addressing socioeconomic, hygiene, and dietary factors through targeted interventions is essential for improving oral health outcomes in this vulnerable group.

A Genome‐First Approach to Rare Variants in Dominant Postlingual Hearing Loss Genes in a Large Adult Population

The study aimed to assess the incidence of hearing loss (HL) in children with human immunodeficiency virus (HIV) using pure-tone audiometry and to find the association of HL with the duration of the disease and severity of HIV infection. A cross-sectional study was done on 60 children in the age group of five to 18 years who presented to the anti-retroviral therapy (ART) clinic for follow-up. All children were confirmed cases of HIV by reverse transcription polymerase chain reaction (RT-PCR). For the study, all HIV-positive children were screened for any HL. Pure-tone audiometry was used for determining the hearing test. The degree and type of HL were assessed. The laterality of HL was assessed. The association of HL with the CD4 count and viral load was assessed. Mann-Whitney test, Fisher's exact test, and independent t-test were used for statistical analysis with a p-value < 0.05 being considered statistically significant. HL was present in 10 (16.67%) cases, and all of them had conductive HL. Six cases had unilateral HL, while four cases had bilateral HL. In the majority (seven (70.00%)) of patients, the degree of HL was mild, followed by moderate HL (two (20.00%)) and minimal in only one (10.00%) patient. Compared to the HL- group, the HL+ group had significantly lower mean CD4 counts (483 ± 247.17 vs. 690.32 ± 301.09, p-value = 0.046) and significantly higher median viral load (2036.5 vs. 0, p < 0.0001). A significantly strong positive correlation was seen between the severity of HL with the viral load (r = 0.749, p = 0.018), and a significantly very strong negative correlation was seen between the severity of HL with CD4 counts (r = -0.809, p = 0.008). An incidence rate of 16.67% HL was found among children with HIV. HL was predominantly mild in nature, and all cases had conductive HL. HL holds a direct correlation with increasing severity of HIV disease and subsequent falling of CD4 counts.Based on the results, it is recommended that all HIV-positive children must undergo routine audiology screening to determine the HL and provide them with audiological aid.

Hearing loss is associated with higher hospitalization risk among older adults. However, evidence on whether hearing aid use is associated with fewer hospitalizations among individuals with hearing loss remains limited. To assess the association between audiometric hearing loss severity and hearing aid use and hospitalization. This population-based cross-sectional study used audiometric and health care utilization data for respondents aged 65 years or older from 4 cycles of the National Health and Nutrition Examination Survey from 2005 to 2016. Data were analyzed from February 23, 2021, to March 22, 2022. Audiometric hearing loss severity and participant-reported hearing aid use. The main outcome was respondent-reported hospitalization in the past 12 months. Multivariable logistic regression was performed to assess the association of hearing loss severity with hospitalization. To assess the association of hearing aid use with hospitalization, propensity score matching was performed with 2:1 nearest neighbor matching without replacement. Of 2060 respondents (mean [SD] age, 73.9 [5.9] years; 1045 [50.7%] male), 875 (42.5%) had normal hearing, 653 (31.7%) had mild hearing loss, 435 (21.1%) had moderate hearing loss, and 97 (4.7%) had severe to profound hearing loss. On multivariable analysis, moderate and severe hearing loss were associated with hospitalization (moderate hearing loss: odds ratio [OR], 1.50; 95% CI, 1.01-2.24; severe hearing loss: OR, 1.71; 95% CI, 1.03-2.84). Of 1185 respondents with at least mild hearing loss, 200 (16.9%) reported using a hearing aid. Propensity score-matched analysis showed that hearing aid use was not associated with hospitalization (OR, 1.17; 95% CI, 0.74-1.84), including among respondents with moderate or severe hearing loss (OR, 1.17; 95% CI, 0.71-1.92). In this cross-sectional study, hearing loss was associated with higher risk of hospitalization, but hearing aid use was not associated with a reduction in hospitalization risk in the population with hearing loss. The association of hearing aid use with hospitalization should be evaluated in larger prospective studies with reliable data on the frequency of hearing aid use.

Cerebrospinal fluid shunting has previously been associated with hearing loss. Although the mechanism for this is unclear, it is thought that changes in CSF pressure can affect cochlear physiology via endolymph expansion in the setting of a patent cochlear aqueduct. Patients undergoing radiation and cisplatin chemotherapy are at risk for hearing loss. The authors hypothesized that the incidence and severity of hearing loss in patients undergoing radiation and chemotherapy for medulloblastoma would be greater in those with shunts than in those without shunts. Baseline and longitudinal audiology data were collected in 33 patients with medulloblastoma who were receiving radiation and cisplatin chemotherapy. Additional data included age, sex, details of shunt placement and revision, and details of chemotherapy and radiation. Hearing sensitivity and peripheral auditory function measures included pure tone audiometry, immittance audiometry, and distortion product evoked otoacoustic emissions. Ototoxicity was determined according to the American Speech-Language-Hearing Association criteria. Severity of hearing loss was determined using the Brock hearing loss grades. Incidence of hearing loss and association with shunting was determined. Thirteen (39.4%) of the 33 patients evaluated had undergone shunt placement. Hearing loss occurred in 14 (70%) of 20 patients without shunts and in 13 (100%) of 13 patients with shunts. The difference between the rates of hearing loss in patients with shunts versus those without the devices was highly significant (p = 0.0008). The odds ratio for hearing loss in patients with a CSF shunt compared with those without a shunt was 23.49 (95% CI 4.21-131.15). Age, side of shunt, evidence of dissemination, diameter of cochlear aqueduct, and treatment protocol did not have a significant effect on shunt-related ototoxicity. This study suggests an independent association between CSF shunting and hearing loss in children undergoing treatment for medulloblastoma, laying the foundation for a prospective study evaluating hearing loss in children with shunts who are not treated with ototoxic therapy.

Mouse Otocyst Transuterine Gene Transfer Restores Hearing in Mice With Connexin 30 Deletion-associated Hearing Loss

Disabling hearing loss affects millions of adults world-wide. Metabolomics investigations are comprehensive assessments of an individual's metabolic processes that could provide insight into biological pathways underlying auditory dysfunction, yet data are limited. We conducted a cross-sectional investigation of the association of plasma metabolite profiles and self-reported adult-onset moderate or severe hearing loss among 3925 women, including 1167 hearing loss cases and 2758 controls in the Nurses' Health Study. Information on hearing status at the time of the blood collection and on relevant risk factors was collected on biennial questionnaires. Metabolic profiling was conducted by liquid chromatography-mass spectrometry. The independent associations of 278 metabolites with hearing loss was assessed in logistic regression models adjusted for age, fasting status, race/ethnicity, co-morbidities, medication use and biobehavioral factors. The false discovery rate was controlled at 5% through the q-value approach. Metabolite Set Enrichment Analysis was conducted to identify metabolite classes that are enriched for concordant associations with hearing loss. We identified 10 metabolites that were significantly associated (q value < 0.05) with moderate or severe hearing loss in multivariable-adjusted models. Steroid esters were enriched for negative associations, while triglycerides were enriched for positive associations. Triglycerides with fewer double bonds were enriched for significant, positive associations with hearing loss (p = 0.04). In this population-based investigation, we identified that triglycerides were enriched for positive associations, while steroid esters were inversely associated with adult-onset moderate or severe hearing loss. This study indicates that metabolic perturbations may contribute to the pathoetiology underlying adult-onset hearing loss.

To assess the results of drug therapy in patients with severe idiopathic sudden sensorineural hearing loss (ISSHL) with total frequency hearing loss. A prospective randomized, single blind, multi-center clinical trial was designed. The untreated patients with ISSHL were included, who had severe hearing loss (pure tone audiometry showed patients had total frequency hearing loss, and their mean auditory threshold of 500, 1000, 2000, 4000 Hz was beyond 81 dB HL), age between 18 to 65 years old, and within 14 days of the onset . The patients were divided into one of the four drug groups [batroxobin, batroxobin + ginkgo biloba leaves extract (EGb), batroxobin + EGb + glucocorticoids, EGb + glucocorticoids] according to the random table, and receive treatment. Totally 276 patients with unilateral severe ISSHL were included from 33 hospitals, from August 2007 to October 2011. Among them, male patients accounted for 135 (48.91%), female 141 (51.09%); the average age was (41.7 ± 13.3)years. Forty cases were recovered (14.49%), 78 cases had marked effective (28.26%), 76 cases were effective (27.54%), 82 cases were in-effective (29.71%), and the total effective rate was 70.29%. Among four drug groups, the separate effective rate were 73.33%, 61.43%, 78.31% and 67.95% respectively, no significant difference was found between groups (χ(2) = 9.97,P = 0.62). Among the four groups, the separate cure rate for hearing loss were 11.11%, 12.86%, 16.87% and 15.38%, the glucocorticoid groups were significantly better than those not used. Among severe sudden deafness patients, 92.39% cases accompanied with tinnitus, 44.93% with dizziness (or vertigo), 50.36% with ear stuffy. There had no significant difference between the four groups with accompanied symptoms (all P > 0.05). It is value to give active treatment to sever sudden deafness patients because of an effective rate of 70%. However, the doctors and patients should be mind of a cure rate of only 14%. Steroids are recommended bacause it may play a role in the improvement rate.

Comparison of ABR and ASSR using NB-chirp-stimuli in children with severe and profound hearing loss

Objectives:Hereditary hearing loss exhibits high degrees of genetic and clinical heterogeneity. To elucidate the population-specific and age-related genetic and clinical spectra of hereditary hearing loss, we investigated the sequencing data of causally associated hearing loss genes in a large cohort of hearing-impaired probands with a balanced age distribution from a single center in Southwest Germany.Design:Genetic testing was applied to 305 hearing-impaired probands/families with a suspected genetic hearing loss etiology and a balanced age distribution over a period of 8 years (2011–2018). These individuals were representative of the regional population according to age and sex distributions. The genetic testing workflow consisted of single-gene screening (n = 21) and custom-designed hearing loss gene panel sequencing (n = 284) targeting known nonsyndromic and syndromic hearing loss genes in a diagnostic setup. Retrospective reanalysis of sequencing data was conducted by applying the current American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines.Results:A genetic diagnosis was established for 75 (25%) of the probands that involved 75 causal variants in 35 genes, including 16 novel causal variants and 9 medically significant variant reclassifications. Nearly half of the solved cases (47%; n = 35) were related to variants in the five most frequently affected genes: GJB2 (25%), MYO15A, WFS1, SLC26A4, and COL11A1 (all 5%). Nearly one-quarter of the cases (23%; n = 17) were associated with variants in seven additional genes (TMPRSS3, COL4A3, LOXHD1, EDNRB, MYO6, TECTA, and USH2A). The remaining one-third of single cases (33%; n = 25) were linked to variants in 25 distinct genes. Diagnostic rates and gene distribution were highly dependent on phenotypic characteristics. A positive family history of autosomal-recessive inheritance in combination with early onset and higher grades of hearing loss significantly increased the solve rate up to 60%, while late onset and lower grades of hearing loss yielded significantly fewer diagnoses. Regarding genetic diagnoses, autosomal-dominant genes accounted for 37%, autosomal-recessive genes for 60%, and X-linked genes for 3% of the solved cases. Syndromic/nonsyndromic hearing loss mimic genes were affected in 27% of the genetic diagnoses.Conclusions:The genetic epidemiology of the largest German cohort subjected to comprehensive targeted sequencing for hereditary hearing loss to date revealed broad causal gene and variant spectra in this population. Targeted hearing loss gene panel analysis proved to be an effective tool for ensuring an appropriate diagnostic yield in a routine clinical setting including the identification of novel variants and medically significant reclassifications. Solve rates were highly sensitive to phenotypic characteristics. The unique population-adapted and balanced age distribution of the cohort favoring late hearing loss onset uncovered a markedly large contribution of autosomal-dominant genes to the diagnoses which may be a representative for other age balanced cohorts in other populations.