Hearing Dysfunction Research Articles

Frequency and Patterns of Hearing Dysfunction in Patients Treated with Teprotumumab

To better characterize the frequency and patterns of hearing dysfunction in patients who have received teprotumumab to treat thyroid eye disease. Noncomparative case series. Patients who underwent audiology testing before and after completion of teprotumumab infusions. A review of patients who underwent audiology testing before and after completion of teprotumumab infusions was carried out. Additional audiogram testing during treatment was included when available. Hearing function was analyzed using audiogram data measuring threshold hearing levels at specific frequencies. Basic demographic data as well as information regarding otologic symptoms also were obtained and analyzed. Hearing loss demonstrated by a significant change in decibel hearing thresholds or that meets criteria for ototoxicity. Twenty-two patients (44 ears) were included in the study, with baseline and most recent audiology testing after treatment ranging from 84 days before to 496 days after treatment. Fifteen patients (30 ears) also underwent testing during treatment starting after the second infusion up until the day of, but before, the eighth infusion. Hearing loss after treatment met criteria for ototoxicity in 17 of the 44 ears (38.6%), with 11 of the 22 patients (50.0%) meeting criteria in at least 1 ear. The pure-tone average decibel hearing levels (HLs) across all 44 ears demonstrated hearing loss after treatment (P= 0.0029), specifically at high (P= 0.0008) and middle frequencies (P= 0.0042), but not at low frequencies (P= 0.8344). Patients who were older also were more likely to experience hearing loss after treatment (P= 0.0048). Audiometric data demonstrate that teprotumumab influences hearing function, most significantly at higher frequencies and in older patients. Audiometric testing is critical for counseling patients regarding teprotumumab treatment. A protocol for monitoring hearing during treatment is needed to detect and manage hearing changes associated with teprotumumab use. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Facilitating or disturbing? An investigation about the effects of auditory frequencies on prefrontal cortex activation and postural sway.

Auditory stimulation activates brain areas associated with higher cognitive processes, like the prefrontal cortex (PFC), and plays a role in postural control regulation. However, the effects of specific frequency stimuli on upright posture maintenance and PFC activation patterns remain unknown. Therefore, the study aims at filling this gap. Twenty healthy adults performed static double- and single-leg stance tasks of 60s each under four auditory conditions: 500, 1000, 1500, and 2000 Hz, binaurally delivered through headphones, and in quiet condition. Functional near-infrared spectroscopy was used to measure PFC activation through changes in oxygenated hemoglobin concentration, while an inertial sensor (sealed at the L5 vertebra level) quantified postural sway parameters. Perceived discomfort and pleasantness were rated through a 0-100 visual analogue scale (VAS). Results showed that in both motor tasks, different PFC activation patterns were displayed at the different auditory frequencies and the postural performance worsened with auditory stimuli, compared to quiet conditions. VAS results showed that higher frequencies were considered more discomfortable than lower ones. Present data prove that specific sound frequencies play a significant role in cognitive resources recruitment and in the regulation of postural control. Furthermore, it supports the importance of exploring the relationship among tones, cortical activity, and posture, also considering possible applications with neurological populations and people with hearing dysfunctions.

RADIOLOGICAL EVALUATION OF PEDIATRIC SENSORINEURAL HEARING LOSS AT A TERTIARY CARE CENTER IN CENTRAL INDIA

Objective: Hearing dysfunction is the most common sensory deficit in children. If hearing is lost, especially in children's, it may have a huge impact on life, interfering with the acquisition of spoken language and social development. It is therefore important to detect any abnormalities at an early age. Patients with complaint of inability to hear since birth attending ENT OPD, M.Y.H Hospital, Indore and patients referred to M.Y.H hospital from district hospitals with inability to hear since birth were evaluated clinically and audiometry was done. Patients with SNHL fulfilling the inclusion criteria were considered and their radiological evaluation was done. High resolution computed tomography scan (HRCT) of temporal bone were used in radiological evaluation of patients with congenital sensorineural. SUBJECTS AND METHODS: The study was conducted at a tertiary care centre Maharaja Yashwantrao Holkar (MYH) hospital and Mahatma Gandhi Memorial Medical College (MGMMC), Indore in the Department of otorhinolaryngology and head & neck surgery. Cases with hearing loss from 1 to 16 years of age were selected. A detailed medical history with primary focus on inability to hear was obtained with emphasis on previous hospital stays, developmental delay, maternal history, family history. Complete ENT examination was done. Our study included a total 30 children. All chil Results: dren were between 1-16 years of age with sensorineural hearing loss. Majority 11(36.67%) of the participated in the study were between 5-8 years of age. Cochlear anomaly was found in 03(10%) patients. Cochlea was found normal in 27(90%) on both the ears, 03(10%) child had hypoplastic cochlea bilaterally, none were with aplastic cochlea. Vestibular anomaly was seen normal in 28(93.33%) patients on bilateral side. 02(6.67%) patients were present with dysplastic vestibule. SSC was found dysplastic/malformed in 04(13.33%) patients who had dysplastic/malformed semicircular canal. Conclusion: The selection of candidates for hearing aid trials and cochlear implantation requires consideration of a variety of clinical, audiological and radiological factors. Imaging is a fundamental part of the preoperative workup, it provides the surgeon with details which will lead him to a successful cochlear implantation with no or minimal complications. HRCT temporal bone provided us the information about the presence of various inner ear malformations including cochlea, vestibule, SCC, IAC. Mastoid, pneumatization, variations in vascular anatomy which included forward lying sigmoid sinus and high riding jugular bulb. All these findings are important for a detection of cause of SNHL in patients.

Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.

The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5-/- and Pax2-Pex5-/- ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5-/- mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2+ -activated K+ (BK) channels is less in Atoh1-Pex5-/- mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.

Association between hearing sensitivity and dopamine transporter availability in Parkinson's disease.

In a previous study, we observed: (i) significant hearing function impairment, assessed with pure tone audiometry and distortion product otoacoustic emissions, in patients with Parkinson's disease, compared with a matched control group, and (ii) lateralization of the hearing dysfunction, worse on the side affected by more pronounced Parkinson's disease motor symptoms. This study investigates the association between the basal ganglia dopamine transporter availability and the hearing function in Parkinson's disease patients, focusing also on the lateralization of both dysfunctions, with respect to that of the motor symptoms, and introducing a further distinction between patients with left-sided and right-sided predominant motor symptoms. Patients with right-handed Parkinson's disease with a recent estimation of 123I-FP-CIT striatal uptake were audiologically tested with pure tone audiometry and distortion product otoacoustic emissions. Thirty-nine patients were included in the study. A statistically significant association was found, in the left-side predominant group only, between the distortion product otoacoustic emission levels and the contralateral dopamine transporter availability, and between the hearing threshold and the dopamine transporter availability difference between the ipsi- and the contralateral sides. The hearing impairment lateralization correlated to the motor symptom asymmetry was found significant only in the left-side predominant patients. The association between hearing function and basal ganglia dopamine transporter availability supports the hypothesis that the peripheral hearing function decline associated with dopamine depletion is involved in Parkinson's disease development, with a significant difference between patients with left- and right-sided predominant motor symptoms. These findings also suggest that peripheral hearing function evaluation and its lateralization could be key elements for subtyping the disease.

Redox Imbalance as a Common Pathogenic Factor Linking Hearing Loss and Cognitive Decline

Experimental and clinical data suggest a tight link between hearing and cognitive functions under both physiological and pathological conditions. Indeed, hearing perception requires high-level cognitive processes, and its alterations have been considered a risk factor for cognitive decline. Thus, identifying common pathogenic determinants of hearing loss and neurodegenerative disease is challenging. Here, we focused on redox status imbalance as a possible common pathological mechanism linking hearing and cognitive dysfunctions. Oxidative stress plays a critical role in cochlear damage occurring during aging, as well as in that induced by exogenous factors, including noise. At the same time, increased oxidative stress in medio-temporal brain regions, including the hippocampus, is a hallmark of neurodegenerative disorders like Alzheimer's disease. As such, antioxidant therapy seems to be a promising approach to prevent and/or counteract both sensory and cognitive neurodegeneration. Here, we review experimental evidence suggesting that redox imbalance is a key pathogenetic factor underlying the association between sensorineural hearing loss and neurodegenerative diseases. A greater understanding of the pathophysiological mechanisms shared by these two diseased conditions will hopefully provide relevant information to develop innovative and effective therapeutic strategies.

Development and validation of risk prediction model for identifying 30-day frailty in older inpatients with undernutrition: A multicenter cohort study.

To develop and externally validate a frailty prediction model integrating physical factors, psychological variables and routine laboratory test parameters to predict the 30-day frailty risk in older adults with undernutrition. Based on an ongoing survey of geriatrics syndrome in elder adults across China (SGSE), this prognostic study identified the putative prognostic indicators for predicting the 30-day frailty risk of older adults with undernutrition. Using multivariable logistic regression analysis with backward elimination, the predictive model was subjected to internal (bootstrap) and external validation, and its calibration was evaluated by the calibration slope and its C statistic discriminative ability. The model derivation and model validation cohorts were collected between October 2018 and February 2019 from a prospective, large-scale cohort study of hospitalized older adults in tertiary hospitals in China. The modeling derivation cohort data (n = 2,194) were based on the SGSE data comprising southwest Sichuan Province, northern Beijing municipality, northwest Qinghai Province, northeast Heilongjiang Province, and eastern Zhejiang Province, with SGSE data from Hubei Province used to externally validate the model (validation cohort, n = 648). The incidence of frailty in the older undernutrition derivation cohort was 13.54% and 13.43% in the validation cohort. The final model developed to estimate the individual predicted risk of 30-day frailty was presented as a regression formula: predicted risk of 30-day frailty = [1/(1+e-riskscore )], where riskscore = -0.106 + 0.034 × age + 0.796 × sex -0.361 × vision dysfunction + 0.373 × hearing dysfunction + 0.408 × urination dysfunction - 0.012 × ADL + 0.064 × depression - 0.139 × nutritional status - 0.007 × hemoglobin - 0.034 × serum albumin - 0.012 × (male: ADL). Area under the curve (AUC) of 0.71 in the derivation cohort, and discrimination of the model were similar in both cohorts, with a C statistic of nearly 0.7, with excellent calibration of observed and predicted risks. A new prediction model that quantifies the absolute risk of frailty of older patients suffering from undernutrition was developed and externally validated. Based on physical, psychological, and biological variables, the model provides an important assessment tool to provide different healthcare needs at different times for undernutrition frailty patients. Chinese Clinical Trial Registry [ChiCTR1800017682].

Assessment of Hearing and Vestibular Functions in a Post-COVID-19 Patient: A Clinical Case Study

SARS-CoV-2 infection may cause such complications as post-COVID-19 syndrome, which includes chronic fatigue, myalgia, arthralgia, as well as a variety of neurological manifestations, e.g., neuropathy of small fibers, hearing and vestibular dysfunction, and cognitive impairment. This clinical case describes a 41-year-old patient suffering from post-COVID-19 syndrome and chronic fatigue syndrome. A detailed examination was performed, including an in-depth study of peripheral and central hearing and vestibular functions, as well as small nerve fibers length and density in the skin and cornea of the eye. Contrary to expectations, no peripheral nervous system dysfunction was detected, despite the presence of dizziness and gait instability in the patient. Hearing tests (gap detection test and dichotic test) showed central auditory processing disorders. The evaluated lesion in the processing of temporal and verbal auditory information can be a significant factor contributing to additional overload of the neural activity and leading to chronic fatigue when performing daily activities in patients with CFS and post-COVID-19 complications.

Dysfunkcja słuchu nie jest przeszkodą w uczeniu się języka obcego

A human being communicates with the help of all his/her senses (especially hearing, sight, touch) and language. Hearing dysfunction makes it difficult to perceive reality, prevents, or at least seriously hinders, communication. Learning your first (native) language is not easy, but possible; with the help of inclusive learning it is also possible to learn a foreign language.

Correlation between serum IgM antibody and viral load with clinical symptoms in neonates infected with cytomegalovirus

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.

Cellular autophagy, the compelling roles in hearing function and dysfunction.

Sensorineural hearing loss (SNHL) is currently a major health issue. As one of the most common neurodegenerative diseases, SNHL is associated with the degradation of hair cells (HCs), spiral ganglion neurons (SGNs), the stria vascularis, supporting cells and central auditory system cells. Autophagy is a highly integrated cellular system that eliminates impaired components and replenishes energy to benefit cellular homeostasis. Etiological links between autophagy alterations and neurodegenerative diseases, such as SNHL, have been established. The hearing pathway is complex and depends on the comprehensive functions of many types of tissues and cells in auditory system. In this review, we discuss the roles of autophagy in promoting and inhibiting hearing, paying particular attention to specific cells in the auditory system, as discerned through research. Hence, our review provides enlightening ideas for the role of autophagy in hearing development and impairment.

MicroRNA expression is associated with auditory dysfunction in workers exposed to ototoxic solvents and noise.

This study is part of a project on early hearing dysfunction induced by combined exposure to volatile organic compounds (VOCs) and noise in occupational settings. In a previous study, 56 microRNAs were found differentially expressed in exposed workers compared to controls. Here, we analyze the statistical association of microRNA expression with audiometric hearing level (HL) and distortion product otoacoustic emission (DPOAE) level in that subset of differentially expressed microRNAs. The highest negative correlations were found; for HL, with miR-195-5p and miR-122-5p, and, for DPOAEs, with miR-92b-5p and miR-206. The homozygous (mut) and heterozygous (het) variants of the gene hOGG1 were found disadvantaged with respect to the wild-type (wt), as regards the risk of hearing impairment due to exposure to VOCs. An unsupervised artificial neural network (auto contractive map) was also used to detect and show, using graph analysis, the hidden connections between the explored variables. These findings may contribute to the formulation of mechanistic hypotheses about hearing damage due to co-exposure to noise and ototoxic solvents.

Hearing disorder following COVID-19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System.

What is known and objectiveEvidence on whether the coronavirus disease 2019 (COVID‐19) vaccination could cause hearing‐related adverse events is still conflicting. This study aims to access the association between COVID‐19 vaccine and hearing disorder.MethodsThe Vaccine Adverse Event Reporting System (VAERS) was queried between January 2020 to November 2021. The disproportionality pattern for hearing impairment of COVID‐19 vaccine was accessed by calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR). A further subgroup analysis based on the type of COVID‐19 vaccine and the doses administered was performed. In addition, the disproportionalities for hearing dysfunction between COVID‐19 and influenza vaccines were compared.Results and discussionA total of 14,956 reports of hearing‐related adverse events were identified with COVID‐19 vaccination and 151 with influenza vaccine during the analytic period in VAERS. The incidence of hearing disorder following COVID‐19 vaccination was 6.66 per 100,000. The results of disproportionality analysis revealed that the adverse events of hearing impairment, after administration of COVID‐19 vaccine, was significantly highly reported (ROR 2.38, 95% confidence interval [CI] 2.20–2.56; PRR: 2.35, χ 2 537.58), for both mRNA (ROR 2.37, 95% CI 2.20–2.55; PRR 2.34, χ2 529.75) and virus vector vaccines (ROR 2.50, 95% CI 2.28–2.73; PRR 2.56, χ 2 418.57). While the disproportional level for hearing dysfunction was quite lower in influenza vaccine (ROR 0.36, 95% CI 0.30–0.42; PRR 0.36, χ 2 172.24).What is new and conclusionThis study identified increased risk for hearing disorder following administration of both mRNA and virus vector COVID‐19 vaccines compared to influenza vaccination in real‐world settings.

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

Abstract: Efficient delivery of therapeutic material to target site of the inner ear is considered as the most challenging process due to their poor blood flow and inaccessibility sensitivity towards chemical stimuli, inability of drug to be delivered as well. Novel nanoparticlebased drug transport approaches have emerged for overcoming the restriction associated with inner ear therapeutic material delivery. The main focus of this article is to highlight the potential benefits, pre-clinical level otoprotective effect of different types of NPs based payload delivery strategies in mitigating sensorineural hearing impairment resulting from medication (cisplatin and antibiotic treatment) and noise exposure. This review converses about advantage of nanocarrier assisted targeted cell specific inner ear drug delivery approach and demonstrates that targeted NPs delivery systems have the capability to be utilized as vehicle to transport therapeutic materials into the OHCs within the cochlea in controlled and sustained way and maximize following therapeutic effects. Efficacy of systemic and minimally invasive intratympanic and RWM approach for delivering steroids/ genetic material to the inner ear has also been compared in this article. Understanding the importance (design, formulation, cochlear biocompatibility and cell specific binding efficiency of NPs, mechanistic pathways, route of delivery, positive therapeutic outcomes) and hitches (adverse effects after treatment, negative therapeutic outcome) of currently available NPs based drug delivery systems offer new opportunity to develop best treatment methods for sensorineural hearing dysfunction. Keywords: Nanocarriers, Otoprotective agents, Sensorineural heating loss, Ototoxicity, Noise trauma, Ototoxin.

Risk factors for frailty in older adults.

Aims:To clarify the risk factors for frailty to help doctors prevent diseases that cause weakness, through early interventions.Methods:We searched the PubMed, EMBASE, and Cochrane Library databases to identify all relevant studies using the items “frailty,” “weak,” “risk factors,” and “predictive factors” and compared their results. The aging population (≥65 years old) was divided into 2 groups, a “frailty group” and a “robust control group,” and then the characteristics, lifestyles, and comorbidities were compared.Results:We compared the influence of baseline and concomitant diseases on frailty in the elderly respectively, and the analysis of the influence of baseline on frailty found that increasing age, lower weight, female sex, living alone, low levels of exercise, polypharmacy, higher education level, smoking, drinking, malnutrition, and lower vitamin D levels were associated with aging individuals being more likely to experience frailty. The data about concomitant diseases had shown that diabetes, hearing dysfunction, cognitive impairment, poor sleep, a history of falls, pain, and depression can increase the risk of frailty among the elderly population.Conclusion:Characteristics, comorbidities, and lifestyle factors can impact the occurrence of frailty, and relevant influencing factors should be considered.

The Association between Prenatal Nicotine Exposure and Offspring's Hearing Impairment.

The objective of this study is to evaluate whether there is an association between in-utero exposure to nicotine and subsequent hearing dysfunction. Secondary analysis of a multicenter randomized trial to prevent congenital cytomegalovirus (CMV) infection among gravidas with primary CMV infection was conducted. Monthly intravenous immunoglobulin hyperimmune globulin therapy did not influence the rate of congenital CMV. Dyads with missing urine, fetal or neonatal demise, infants diagnosed with a major congenital anomaly, congenital CMV infection, or with evidence of middle ear dysfunction were excluded. The primary outcome was neonatal hearing impairment in one or more ears defined as abnormal distortion product otoacoustic emissions (DPOAEs; 1 to 8 kHz) that were measured within 42 days of birth. DPOAEs were interpreted using optimized frequency-specific level criteria. Cotinine was measured via enzyme-linked immunosorbent assay kits in maternal urine collected at enrollment and in the third trimester (mean gestational age 16.0 and 36.7 weeks, respectively). Blinded personnel ran samples in duplicates. Maternal urine cotinine >5 ng/mL at either time point was defined as in-utero exposure to nicotine. Multivariable logistic regression included variables associated with the primary outcome and with the exposure (p < 0.05) in univariate analysis. Of 399 enrolled patients in the original trial, 150 were included in this analysis, of whom 46 (31%) were exposed to nicotine. The primary outcome occurred in 18 (12%) newborns and was higher in nicotine-exposed infants compared with those nonexposed (15.2 vs. 10.6%, odds ratio [OR] 1.52, 95% confidence interval [CI] 0.55-4.20), but the difference was not significantly different (adjusted odds ratio [aOR] = 1.0, 95% CI 0.30-3.31). This association was similar when exposure was stratified as heavy (>100 ng/mL, aOR 0.72, 95% CI 0.15-3.51) or mild (5-100 ng/mL, aOR 1.28, 95% CI 0.33-4.95). There was no association between nicotine exposure and frequency-specific DPOAE amplitude. In a cohort of parturients with primary CMV infection, nicotine exposure was not associated with offspring hearing dysfunction assessed with DPOAEs. · Nicotine exposure was quantified from maternal urine.. · Nicotine exposure was identified in 30% of the cohort.. · Exposure was not associated with offspring hearing dysfunction..

FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses.

Ribbon synapses are important structures in transmitting auditory signals from the inner hair cells (IHCs) to their corresponding spiral ganglion neurons (SGNs). Over the last few decades, deafness has been primarily attributed to the deterioration of cochlear hair cells rather than ribbon synapses. Hearing dysfunction that cannot be detected by the hearing threshold is defined as hidden hearing loss (HHL). The relationship between ribbon synapses and FGF22 deletion remains unknown. In this study, we used a 6-week-old FGF22 knockout mice model (Fgf22–/–) and mainly focused on alteration in ribbon synapses by applying the auditory brainstem response (ABR) test, the immunofluorescence staining, the patch-clamp recording, and quantitative real-time PCR. In Fgf22–/– mice, we found the decreased amplitude of ABR wave I, the reduced vesicles of ribbon synapses, and the decreased efficiency of exocytosis, which was suggested by a decrease in the capacitance change. Quantitative real-time PCR revealed that Fgf22–/– led to dysfunction in ribbon synapses by downregulating SNAP-25 and Gipc3 and upregulating MEF2D expression, which was important for the maintenance of ribbon synapses’ function. Our research concluded that FGF22 deletion caused HHL by affecting the function of IHC ribbon synapses and may offer a novel therapeutic target to meet an ever-growing demand for deafness treatment.

Combined effects of the exposure to silver nanoparticles and noise on hearing function and cochlea structure of the male rats

AimsThis study intended to investigate whether exposure to the combination of noise and Ag-NPs in rats induces cochlear damage and hearing dysfunction. Main methodsA total of 24Wistar rats were divided into four treatment groups and received/exposed to saline (IP), Ag-NPs (100 mg/kg, 5d/w for 4 weeks), 8 kHz narrowband noise (104 dB SPL, 6 h/day, 5d/w for 4 weeks) and Ag-NPs plus noise. The DPOAE, serum levels of MDA and SOD and changes in body weight were assessed. The rat cochlea was further stained for investigating the mRNA expression (TL-6, NOX3, and TNF-), IHC (TUJ-1 and MHC7), and histological alterations. The Ag-NPs characteristics were also analysed by SEM and XRD. Key findingsDPOAE values were remarkably reduced (p < 0.05) among the exposed groups. Furthermore, exposure to noise and Ag-NPs significantly increased MDA levels and decreased the SOD activity in the serum. In comparison to the control group, the expression of IL-6, TNF-, and NOX3 was shown to be elevated in the Ag-NPs plus noise group. The body weight also increased significantly in all groups with the exception of the Ag-NPs plus noise group. IHC tests showed remarkable down-regulation of TUJ1 and MYO7A. Morphological changes confirmed our findings as well. SEM and XRD data validated the production of Ag-NPs. SignificanceAccording to the findings of this study, sub-acute exposure to noise and Ag-NPs causes permanent damage to the hair cells that are in charge of high-frequency perception.

Association of hearing loss and tinnitus symptoms with health-related quality of life among long-term oropharyngeal cancer survivors.

This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors. This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory Head & Neck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference. Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48-22.88; p=0.012) and moderate (OR, 30.01; 95% CI; 7.96-113.10; p < 0.001) hearing loss and tinnitus were associated with higher odds of reporting moderate to severe symptom interference scores in comparison to no hearing loss and tinnitus. This association of hearing dysfunction was consistent with all domains of HRQoL. Our findings provide preliminary evidence to support the need for continued audiological evaluations and surveillance to detect hearing dysfunction, to allow for early management and to alleviate the long-term impact on QoL.

Hearing loss: The final frontier of pharmacology.

Despite a prevalence greater than cancer or diabetes, there are no currently approved drugs for the treatment of hearing loss. Research over the past two decades has led to a vastly improved understanding of the cellular and molecular mechanisms in the cochlea that lead to hearing deficits and the advent of novel strategies to combat them. Combined with innovative methods that enable local drug delivery to the inner ear, these insights have paved the way for promising therapies that are now under clinical investigation. In this review, we will outline this renaissance of cochlear biology and drug development, focusing on noise, age‐related, and chemotherapy‐induced hearing dysfunction.