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Background: Occupational hearing loss of workers exposed to impulse noise and workers exposed to steady noise for a long time may have different clinical characteristics. Methods: As of May 2019, all 92 servicemen working in a weapon experimental field exposed to impulse noise for over 1 year were collected as the impulse noise group. As of Dec 2019, all 78 servicemen working in an engine working experimental field exposed to steady noise for over 1 year were collected as the steady noise group. The propensity score matching (PSM) model was used to eliminate the imbalance of age and working time between the two groups of subjects. After propensity score matching, 51 subjects in each group were finally included in the study. The machine learning model is constructed according to pure tone auditory threshold, and the performance of the machine learning model is evaluated by accuracy, sensitivity, specificity, and AUC. Results: Subjects in the impulse noise group and the steady noise group had significant hearing loss at high frequencies. The hearing of the steady noise group was worse than that of the impulse noise group at speech frequency especially at the frequency of 1 kHz. Among machine learning models, XGBoost has the best prediction and classification performance. Conclusion: The pure tone auditory threshold of subjects in both groups decreased and at high frequency. The hearing of the steady noise group at 1 kHz was significantly worse than that of the impulse noise group. XGBoost is the best model to predict the classification of our two groups. Our research can guide the prevention of damage caused by different types of noises.
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Introduction: Emerging evidence suggests changes in several cognitive control processes in individuals with age-related hearing loss (ARHL). However, value-directed strategic processing, which involves selectively processing salient information based on high value, has been relatively unexplored in ARHL. Our previous work has shown behavioral changes in strategic processing in individuals with ARHL. The current study examined event-related alpha and theta oscillations linked to a visual, value-directed strategic processing task in 19 individuals with mild untreated ARHL and 17 normal hearing controls of comparable age and education. Methods: Five unique word lists were presented where words were assigned high- or low-value based on the letter case, and electroencephalography (EEG) data was recorded during task performance. Results: The main effect of the group was observed in early time periods. Specifically, greater theta synchronization was seen in the ARHL group relative to the control group. Interaction between group and value was observed at later time points, with greater theta synchronization for high- versus low-value information in those with ARHL. Discussion: Our findings provide evidence for oscillatory changes tied to a visual task of value-directed strategic processing in individuals with mild untreated ARHL. This points towards modality-independent neurophysiological changes in cognitive control in individuals with mild degrees of ARHL and adds to the rapidly growing literature on the cognitive consequences of ARHL.
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BACKGROUND: Hearing loss (HL) is prevalent in older individuals. It is suggested that there is an association between age-related HL, walking and balance, leading to poorer function and increased risk of falls in older individuals. RESEARCH QUESTION: Is HL associated with physical performance, gait variability, and postural sway in older adults, and will additional dizziness moderate the effect of HL on balance? METHODS: In this cross-sectional study we examined 100 older individuals (age ≥70 years, 60â¯% females), divided in two groups, with or without age-related HL. Physical function and balance were evaluated by the Short Physical Performance Battery (SPPB), postural sway measured on a force platform (posturography), and balance in walking (gait variability) measured with a body-worn sensor. Multiple linear regression was used to examine the relationships between the variables, with physical function and balance as outcomes and HL as a dichotomous exposure (>30â¯dB). For all analyses, we further tested if associations were modified by self-reported dizziness. RESULTS: Multiple regression analysis with HL, age, sex, education, diabetes, and cardiovascular disease revealed a significant association between reduced SPPB and HL. Multiple linear regression analysis also showed that HL was associated with increased postural sway on firm surface with eyes open and closed after adjusting for age, sex, education, diabetes, and cardiovascular disease. There was significant association between HL and increased gait variability during dual task walking in all directions after adjusting for age, sex, education, diabetes, and cardiovascular disease. Further, we found that the association between HL and SPPB was significantly stronger in those with dizziness compared with those without dizziness. Dizziness also modified the association of HL with the other SPPB sub-scores but not for the other outcomes of postural sway or gait variability. SIGNIFICANCE: In this study, age-related HL was associated with worse physical performance as measured by SPPB, postural sway, and gait variability. This relationship illustrates the importance of assessing physical performance in people with HL to prevent risk of falls and disability.
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OBJECTIVE: This cross-sectional website analysis aimed to determine the readability and quality of English and Spanish websites pertaining to the prevention of noise-induced hearing loss. STUDY DESIGN: Cross-sectional website analysis. SETTING: Various online search engines. METHODS: We queried four popular search engines using the term "noise-induced hearing loss prevention" to reveal the top 50 English and top 50 Spanish websites for data collection. Websites meeting inclusion criteria were stratified based on the presence of a Health on the Net Code certificate (independent assessment of honesty, reliability, and quality). Websites were then independently reviewed by experts using the DISCERN criteria in order to assess information quality. Readability was calculated using the Flesch reading ease score for English and the Fernandez-Huerta formula for Spanish websites. RESULTS: Thirty-six English websites and 32 Spanish websites met the inclusion criteria. English websites had significantly lower readability (average = 56.34, SD = 11.17) compared to Spanish websites (average = 61.88, SD = 5.33) (P < .05). Spanish websites (average = 37, SD = 8.47) were also of significantly higher quality than English websites (average = 25.13, SD = 10.11). CONCLUSION: This study emphasizes the importance of providing quality and readable materials to patients seeking information about noise-induced hearing loss prevention. All of the English and Spanish websites reviewed were written at a level higher than the American Medical Association-recommended sixth-grade reading level. The study also highlights the need for evidence-based information online provided by experts in our field.
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The primary etiology of congenital hearing loss is attributed to genetic factors, with GJB2 identified as a pivotal gene across diverse ethnic groups. Additionally, nonsyndromic hearing loss is predominantly inherited in an autosomal recessive manner. We used Sanger sequencing to analyze GJB2 in 17 deaf children from 13 unrelated Ivory Coast families. One family had two children born with severe congenital deafness and exhibited pathogenic compound heterozygous variants. These variants included a nonsense substitution (c.132G > A or p.Trp44Ter) and a newly discovered duplication of 7 base pairs (c.205_211dupTTCCCCA or p.Ser72ProfsTer32). Segregation testing confirmed these variants, marking the first identification of GJB2 in an Ivorian family with congenital hearing loss.
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BACKGROUND: Biallelic pathogenic variants in CDH23 can cause Usher syndrome type I (USH1), typically characterized by sensorineural hearing loss, variable vestibular areflexia, and a progressive form of rod-cone dystrophy. While missense variants in CDH23 can cause DFNB12 deafness, other variants can affect the cadherin 23 function, more severely causing Usher syndrome type I D. The main purpose of our study is to describe the genotypes and phenotypes of patients with mild retinitis pigmentosa (RP), including sector RP with two pathogenic variants in CDH23. MATERIALS AND METHODS: Clinical examination included medical history, comprehensive ophthalmologic examination, and multimodal retinal imaging, and in case 1 and 2, full-field electroretinography (ERG). Genetic analysis was performed in all cases, and segregation testing of proband relatives was performed in case 1 and 3. RESULTS: Three unrelated cases presented with variable clinical phenotype for USH1 and were found to have two pathogenic variants in CDH23, with missense variant, c.5237 G > A: p.Arg1746Gln being common to all. All probands had mild to profound hearing loss. Case 1 and 3 had mild RP with mid peripheral and posterior pole sparing, while case 2 had sector RP. ERG results were consistent with the marked loss of retinal function in both eyes at the level of photoreceptor in case 1 and case 2, with normal peak time in the former. CONCLUSION: Patients harbouring c.5237 G > A: p.Arg1746Gln variants in CDH23 can present with a mild phenotype including sector RP. This can aid in better genetic counselling and in prognostication.
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OBJECTIVES: The objective of this systematic review was to assess the evidence about the prevalence of permanent hearing loss for children not identified from newborn hearing screening (NHS). DESIGN: Articles were grouped into three categories based on the methodological approach: (1) all participants received diagnostic testing, (2) otoacoustic emission (OAE) or pure tone screening was completed and those not passing were referred for a diagnostic test, and (3) data were retrieved from archival records. Study characteristics, prevalence, and contextual factors were synthesised and narratively described. STUDY SAMPLE: 30 peer-reviewed articles. RESULTS: Prevalence of permanent hearing loss per 1,000 children ranged from 0.32 to 77.87 (M = 7.30; SD = 16.87). Variations in the criteria for inclusion contributed to prevalence differences. Prevalence was higher when unilateral and milder degrees of hearing loss were included, and older children had higher prevalence (M = 13.71; SD = 23.21) than younger children (M = 1.57; SD = 0.86). CONCLUSION: There is scant research on prevalence of childhood hearing loss after NHS that utilised methods to accurately differentiate between permanent and temporary hearing loss. Rigorous research is needed on the prevalence of permanent childhood hearing loss to inform strategies for monitoring, identification, intervention, and management.
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Background Hearing-impaired children may face challenges in communication, social interaction, academic performance, and emotional well-being, which can have a notable impact on their overall quality of life. Beyond these challenges, oral health can also be significantly impacted. The relationship between hearing impairment and dental diseases is an intriguing and interconnected aspect of overall well-being that merits attention and exploration. This study aimed to assess the relationship between various oral health factors and hearing impairments. Methodology This cross-sectional study involved 90 hearing-impaired children aged 6-12 years. To evaluate the children's hearing abilities, diagnostic tools such as pure-tone audiometry were employed. To measure dental health, the decayed, missing, and filled teeth (DMFT) and decayed, missing, and filled primary teeth (dmft) indices, as well as plaque index (PI) and gingival index (GI) were calculated. The chisquare test was used to identify significant differences between genders. Spearman's test was used to determine the correlation between variables. Results The severity of hearing impairment varied, with 5.6% having severe hearing loss, 8.9% having profound hearing loss, and 85.6% having complete hearing loss. The mean DMFT score was 2.5 ± 1.86, with no significant difference observed between males and females. The mean dmft score was 4.2 ± 3.12, with no significant difference between genders. However, there was a difference in the PI scores between males and females. Males presented a higher PI score of 2.6 ± 0.09 compared to 1.8 ± 0.08 for females. The overall mean PI was 2.1 ± 0.80. The mean GI was 1.5 ± 0.90, and no significant difference was observed between males and females. Spearman's test identified a significant positive correlation between the severity of hearing impairment and both PI scores (p = 0.000) and GI scores (p = 0.000). Conversely, the severity of hearing impairment showed a weak positive correlation with both DMFT scores (p = 0.487) and dmft scores (p = 0.229), but these correlations were not statistically significant. Conclusions The connection between oral health and severe hearing impairment in children is significant and has potential implications. Pediatric healthcare providers, including dentists and audiologists, need to work collaboratively to monitor the oral and aural health of young patients.
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BACKGROUND: Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the ACHIEVE study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss. METHODS: Participants aged 70-84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, NC; Jackson, MS; Minneapolis, MN; Washington County, MD) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle. RESULTS: Participants (n=977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (ß= -0.12 [95% CI -0.22, -0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS fatigue score (ß= -0.32 [95% CI -1.15, 0.51]). CONCLUSIONS: Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.
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BACKGROUND: In aging populations, understanding predictors of cognitive decline is essential. We aimed to investigate the risk of cognitive decline and dementia by sensory impairments across sex, age, and European regions, and examined the mediating role of activities of daily living (ADL), physical activity, and depressive symptoms. METHODS: A cohort study of 72,287 Europeans aged 50+ participating in at least two waves of the Survey of Health, Ageing and Retirement in Europe. We employed mixed-effects and time-to-event models, incorporating sex interactions, and adjusting for socio-demographic factors and medical history. RESULTS: Compared to individuals with good vision and hearing, lower cognitive function was found for people with vision impairment (VI) (males: coef. -0.70, 95 % CI -0.95; -0.46; females: coef. -1.12, 95 % CI -1.33; -0.92), hearing impairment (HI) (males: coef. -0.64, 95 % CI -0.93; -0.35; females: coef. -0.96, 95 % CI -1.27; -0.65) and dual sensory impairment (DSI, i.e. VI and HI) (males: coef. -1.81, 95 % CI -2.16; -1.46; females: coef. -2.71, 95 % CI -3.05; -2.38), particularly among females. Moreover, higher dementia risk was observed among participants with VI (hazard ratio (HR) 1.29, 95 % CI 1.17; 1.43), HI (HR 1.18, 95 % CI 1.05; 1.34), and DSI (HR 1.62, 95 % CI 1.45; 1.81) with no sex-interactions. Findings were overall consistent across age and European regions. CONCLUSION: The results suggest the necessity of preventing sensory impairments to maintain good cognitive function. Mitigating depressive symptoms, ADL limitations, and physical inactivity could potentially reduce a significant portion of the total effect of sensory impairments on cognitive decline.
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Participation in complex listening situations such as group conversations in noisy environments sets high demands on the auditory system and on cognitive processing. Reports of hearing-impaired people indicate that strenuous listening situations occurring throughout the day lead to feelings of fatigue at the end of the day. The aim of the present study was to develop a suitable test sequence to evoke and measure listening effort (LE) and listening-related fatigue (LRF), and, to evaluate the influence of hearing aid use on both dimensions in mild to moderately hearing-impaired participants. The chosen approach aims to reconstruct a representative acoustic day (Time Compressed Acoustic Day [TCAD]) by means of an eight-part hearing-test sequence with a total duration of approximately 2½ h. For this purpose, the hearing test sequence combined four different listening tasks with five different acoustic scenarios and was presented to the 20 test subjects using virtual acoustics in an open field measurement in aided and unaided conditions. Besides subjective ratings of LE and LRF, behavioral measures (response accuracy, reaction times), and an attention test (d2-R) were performed prior to and after the TCAD. Furthermore, stress hormones were evaluated by taking salivary samples. Subjective ratings of LRF increased throughout the test sequence. This effect was observed to be higher when testing unaided. In three of the eight listening tests, the aided condition led to significantly faster reaction times/response accuracies than in the unaided condition. In the d2-R test, an interaction in processing speed between time (pre- vs. post-TCAD) and provision (unaided vs. aided) was found suggesting an influence of hearing aid provision on LRF. A comparison of the averaged subjective ratings at the beginning and end of the TCAD shows a significant increase in LRF for both conditions. At the end of the TCAD, subjective fatigue was significantly lower when wearing hearing aids. The analysis of stress hormones did not reveal significant effects.
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Estimulación Acústica , Audífonos , Ruido , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ruido/efectos adversos , Corrección de Deficiencia Auditiva/instrumentación , Corrección de Deficiencia Auditiva/métodos , Atención , Personas con Deficiencia Auditiva/psicología , Personas con Deficiencia Auditiva/rehabilitación , Adulto , Fatiga Auditiva , Factores de Tiempo , Tiempo de Reacción , Realidad Virtual , Percepción Auditiva/fisiología , Fatiga , Pérdida Auditiva/psicología , Pérdida Auditiva/rehabilitación , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/diagnóstico , Percepción del Habla/fisiología , Saliva/metabolismo , Saliva/química , Audición , Umbral AuditivoRESUMEN
INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin-based chemoradiotherapy (CRT) frequently experience irreversible sensorineural hearing loss (SNHL). Patients with low lumbar skeletal muscle index (LSMI) may experience higher serum peak dosages of cisplatin. This study investigated whether pre-treatment low LSMI is associated with increased SNHL upon cisplatin-based CRT. MATERIALS AND METHODS: LSMI was assessed using routine pre-treatment CT scans. Pure tone audiometry was performed at baseline and at follow-up to assess treatment-related SNHL. Linear mixed models were used to reveal a potential association between the continuous variable LSMI and SNHL. RESULTS: This retrospective cohort study included 81 patients and found a significant association between low LSMI and increased treatment-related SNHL at pure tone frequencies vital for the perception of speech (averaged of 1, 2, and 4 kHz) (p = 0.048). CONCLUSIONS: HNSCC patients with low LSMI suffer increased treatment-related SNHL upon cisplatin-based CRT.
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INTRODUCTION: Patients with fibromyalgia (FM) have innumerable complaints due to the central amplification of somatic stimuli. The aim of this paper was to review the ear complaints in patients with FM. METHODS: A review of articles published in PubMed/MEDLINE, Embase, Web of Science, and Scopus from 1966 to June 2023 was performed. RESULTS: Seventeen papers were included in the review. They showed that patients with FM have a higher hearing loss rate, mostly at high frequencies, and hyperacusis. The prevalence of vestibular symptoms (tinnitus, dizziness) and hyperacusis was higher than in the general population, reaching 87.0% of the sample. Subjective findings did not always correspond to objective results. In some studies, the degree of FM severity was associated with ear symptoms; in others, it was not. CONCLUSIONS: Ear complaints in patients with FM are linked to subjacent disease and may be related to stimuli central amplification.
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BACKGROUND: Hearing loss is a prevalent issue resulting from loud noise exposure, aging, diseases, and genetic differences. As individuals age, the likelihood of experiencing hearing loss and depression escalates; yet, the link between hearing loss and the risk of depression remains ambiguous. This study explores the relationship between hearing and depression risk, taking into account sociodemographic and health-related factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a cross-sectional analysis was conducted, focusing on adult participants. It evaluated their hearing status and depression levels using the Patient Health Questionnaire-9 (PHQ-9). The study examined a range of variables, such as age, gender, socioeconomic status, lifestyle choices, and comorbidities, to understand their influence on the link between hearing loss and depression. RESULTS: Analysis indicated a significant association between moderate to severe hearing loss and an increased risk of depression, notably in older adults. This relationship remained significant even after adjusting for a variety of sociodemographic and health factors. LIMITATIONS: This is a study using the NHANES database using self-reported surveys. CONCLUSION: The findings of this study emphasize the need to integrate hearing health in the holistic assessment and treatment of depression, particularly advocating for combined care strategies for the elderly.
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Introduction: Hearing health is a public health concern that affects the quality of life and can be disturbed by noise exposure, generating auditory and extra-auditory symptoms. Objective. To identify the hearing health status in adults living in Bogotá and its association with environmental noise exposure and individual and otological factors. Objective: To identify the hearing health status in adults living in Bogotá and its association with environmental noise exposure and individual and otological factors. Materials and methods: We conducted a cross-sectional study using a database with 10,311 records from 2014 to 2018, consigned in a structured survey of noise perception and hearing screening. We performed a descriptive, bivariate, and binary logistic regression analysis. Results: Of the included participants, 35.4% presented hearing impairment. In the perception component, 13.0 % reported not hearing well; 28.8 % had extra-auditory symptoms, 53.3 % informed otological antecedents and 69.0 % presented discomfort due to extramural noise. In the logistic regression, the variables with the highest association for hearing impairment were living in noisy areas (OR = 1.50) (95% CI: 1.34-1.69), being male (OR = 1.85) (95% CI: 1.64-2.09), increasing age (for each year of life, the risk of hearing impairment increased 6%), and having history of extra-auditory symptoms (OR = 1.86) (95% CI: 1.66-2.08). Conclusions: Hearing impairment is multi-causal in the studied population. The factors that promote its prevalence are increasing age, being male, smoking, ototoxic medications, living in areas with high noise exposure, and extra-auditory symptoms.
Introducción. La salud auditiva es un tema de interés en salud pública que afecta la calidad de vida y que puede afectarse por la exposición continua al ruido, un factor de riesgo que genera síntomas auditivos y extraauditivos. Objetivo. Identificar el estado de salud auditiva de adultos que viven en Bogotá, y su asociación con factores de exposición a ruido ambiental, individuales y otológicos. Materiales y métodos. Se realizó un estudio transversal mediante el análisis de una base de datos con 10.311 registros, obtenidos entre los años 2014 y 2018, producto de una encuesta estructurada de percepción de ruido y tamizaje auditivo. Se hizo un análisis descriptivo bivariado y una regresión logística binaria. Resultados. El 35,4 % de los participantes presentó disminución auditiva. En el componente de percepción: 13,0 % refirió no escuchar bien, 28,8 % informó síntomas extraauditivos, 53,3 % tenía antecedentes otológicos, y 69,0 % manifestó molestia por ruido extramural. En la regresión logística, las variables más asociadas con disminución auditiva fueron: de las ambientales, vivir en zonas de mayor ruido (OR = 1,50) (IC95%: 1,34-1,69); de las individuales, ser hombre (OR = 1,85) (IC95%: 1,64-2,09) y la edad (por cada año de vida, el riesgo de disminución auditiva aumentó 6 %); y de las otológicas, tener antecedente de síntomas otológicos (OR = 1,86) (IC95%: 1,66-2,08). Conclusiones. La disminución auditiva es multicausal en la población evaluada. Los factores que aumentan su prevalencia son incremento de la edad, ser hombre, tabaquismo, medicamentos ototóxicos, vivir en zonas de mayor exposición a ruido y presentar síntomas extraauditivos.
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Exposición a Riesgos Ambientales , Pérdida Auditiva Provocada por Ruido , Ruido , Humanos , Colombia/epidemiología , Adulto , Estudios Transversales , Persona de Mediana Edad , Masculino , Adolescente , Femenino , Ruido/efectos adversos , Adulto Joven , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Exposición a Riesgos Ambientales/efectos adversos , Factores de RiesgoRESUMEN
OBJECTIVE: This study aimed to highlight the differences in the clinical management and treatment of sudden sensorineural hearing loss (SSNHL) due to the impact of the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: This study compared patients diagnosed with SSNHL between March 2020 and March 2022, following the first reported case of COVID-19 in our country, with patients diagnosed between March 2018 and March 2020. The evaluation encompassed demographic characteristics, comorbidities, other ear-related complaints, hearing loss thresholds at each frequency, medical treatment administered, treatment duration, and post-treatment follow-up audiograms. RESULTS: The demographic characteristics and comorbidities of patients before and during the pandemic showed similar distribution. There was no significant difference in the duration from the onset of symptoms to hospital admission during the pandemic compared to the previous period. When evaluating the treatment responses of hospitalized and treated patients according to Siegel's criteria during the pandemic, a similar trend to the pre-pandemic period was observed. It was noted that the use of systemic steroids and hyperbaric oxygen therapy decreased during the pandemic period, while the use of antivirals increased. CONCLUSIONS: In our study conducted as a reference center, we want to emphasize that no clear data indicating a relationship between COVID-19 infection and NHL. Also, we believe that COVID-19 infection does not affect the course and prognosis of SSNHL.
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Mangiferin(MGF) exhibits crucial biological roles, including antioxidant and anti-inflammatory functions. However, how to clearly elucidate the functioning mechanism of MGF for inhibiting cisplatin-induced hearing loss requires in-depth investigation. In this work, we aimed at gaining insight into how MGF functions as the protective agent against cisplatin-triggered ototoxicity using various assays. The variation for reactive oxygen species (ROS) concentrations was determined with MitoSOX-Red and 2',7'-Dichlorodihydrofluorescein diacetate staining (DCFH-DA). The protective function and corresponding mechanism of MGF in hair cell survival in the House Ear Institute-Organ of Corti (HEI-OC1) cell line were assessed using RNA sequencing (RNA-Seq). Our findings demonstrated that MGF significantly alleviated cisplatin-induced injury to hair cells in vitro, encompassing cell lines and cochlear explants, as well as in vivo models, including C57BL/6â¯J mice and zebrafish larvae. Mechanistic studies revealed that MGF reversed the increased accumulation of ROS and inhibited cell apoptosis through mitochondrial-mediated intrinsic pathway. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting data indicated MGF protected against cisplatin-mediated ototoxicity via the mitogen-activated protein kinase pathway (MAPK). These findings demonstrated MGF has significant potential promise in combating cisplatin-induced ototoxicity, offering a foundation for expanded investigation into therapeutic approaches for auditory protection.
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Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGN causes autosomal dominant nonsyndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.
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Introduction: Listeners can rapidly adapt to English speech produced by non-native speakers of English with unfamiliar accents. Prior work has shown that the type and number of talkers contained within a stimulus set may impact rate and magnitude of learning, as well as any generalization of learning. However, findings across the literature have been inconsistent, with relatively little study of these effects in populations of older listeners. Methods: In this study, adaptation and generalization to unfamiliar talkers with familiar and unfamiliar accents are studied in younger normal-hearing adults and older adults with and without hearing loss. Rate and magnitude of adaptation are modelled using both generalized linear mixed effects regression and generalized additive mixed effects modelling. Results: Rate and magnitude of adaptation were not impacted by increasing the number of talkers and/or varying the consistency of non-native English accents across talkers. Increasing the number of talkers did strengthen generalization of learning for a talker with a familiar non-native accent, but not for an unfamiliar accent. Aging alone did not diminish adaptation or generalization. Discussion: These findings support prior evidence of a limited benefit for talker variability in facilitating generalization of learning for non-native accented speech, and extend the findings to older adults.
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BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is characterized by rapid, unexplained loss of hearing within a 72-hour period and exhibits a high incidence globally. Despite this, the outcomes of therapeutic interventions remain largely unpredictable, especially for those with profound hearing loss. Extracellular vesicles (EVs), nano-sized entities containing biological materials, are implicated in the development of numerous diseases. The specific relationship between EVs and both the severity and treatment effectiveness of SSNHL, however, is not well understood. METHODS: This study involved the analysis of medical records from the Department of Otolaryngology (September 1, 2020 - December 31, 2022) of patients diagnosed with SSNHL according to the 2015 Guidelines for Diagnosis and Treatment of Sudden Deafness in China. Peripheral blood samples from patients with various types of SSNHL before and after treatment were collected, alongside samples from healthy volunteers serving as controls. Plasma EVs were isolated using gel rejection chromatography and analyzed for concentration, marker presence, and morphology using Nanosight, Western blot, and transmission electron microscopy (TEM), respectively. Proteomics and miRNA assessments were conducted to identify differentially expressed proteins and miRNAs in the plasma EVs of SSNHL patients and healthy volunteers. Key proteins were further validated through Western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the levels of complement C3 in plasma EVs, and correlation analyses were performed with audiological data pre- and post-treatment. RESULTS: Plasma from SSNHL patients of varying types was collected and their EVs were successfully isolated and characterized. Proteomic analysis revealed that complement C3 levels in the plasma EVs of patients with profound SSNHL were significantly higher compared to healthy controls. Differential expression of miRNAs in plasma EVs and their related functions were also identified. The study found that the level of complement C3 in plasma EVs, but not the total plasma complement C3, positively correlated with the severity of SSNHL in patients exhibiting positive therapeutic responses, particularly in those with initially lower levels of EV-associated complement C3. After treatment, complement C3 level was decreased in patients with initially higher levels of EV-associated complement C3. No significant correlation was observed between changes in plasma EV-derived complement C3 levels and the degree of hearing loss in either responders or non-responders among patients with profound SSNHL. CONCLUSION: Differential profiles of proteins and miRNAs were identified in patients with profound SSNHL. Notably, plasma EV-derived complement C3 was linked to both the severity and early treatment effectiveness of patients with profound SSNHL.