Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

In-vitro Modell zur Quantifizierung des Cisplatin-induzierten Haarzellverlustes

Einleitung: Kinder im Alter bis zu 5 Jahren zeigen eine besondere Empfindlichkeit für Cisplatin induzierte Ototoxizität mit einer Inzidenz von bis zu 40% bei einer kumulativen Dosis von 400 mg/m2 . Zur Untersuchung der Cisplatin-induzierten Ototoxizität stehen aufgrund der Nephrotoxizität keine geeigneten in-vivo Modelle zur Verfügung, da diese häufig letal sind. Methoden: In einem organotypischen Kulturmodell des Innenohres wurde durch Applikation von Cisplatin ein Haarzellverlust induziert. Dieser wurde durch Zytocochleogramme quantifiziert. Es wurden Dosis-Wirkungskurven erstellt und mittlere effektive Konzentrationen errechnet (EC50). Ergebnisse: Im in-vitro Modell konnte durch Cisplatinapplikation ein Haarzellverlust mit einem basoapikalen Gradienten erzielt werden. Der Haarzellverlust war linear zur Expositionszeit. Die EC50 für 48h betrug 1,75 µg/ml. Diskussion: Für die Cisplatin-induzierte Ototoxizität wurde ein reproduzierbares und quantifizierbares in-vitro Modell etabliert. Die Ototoxizität alternativer platin-basierter Chemotherapeutika kann an diesem Modell mit der Ototoxizität von Cisplatin verglichen werden. Ebenso kann man die Wirkung otoprotektiver Substanzen prüfen