Τρίτη 3 Ιανουαρίου 2017

Contralateral electrically-evoked suppression of transient evoked otoacoustic emissions in single-sided deaf patients

Publication date: Available online 3 January 2017
Source:Hearing Research
Author(s): Oliver Christian Dziemba, Daniel Grafmans, Stephan Merz, Thomas Hocke




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Contralateral electrically-evoked suppression of transient evoked otoacoustic emissions in single-sided deaf patients

Publication date: Available online 3 January 2017
Source:Hearing Research
Author(s): Oliver Christian Dziemba, Daniel Grafmans, Stephan Merz, Thomas Hocke




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Contralateral electrically-evoked suppression of transient evoked otoacoustic emissions in single-sided deaf patients

Publication date: Available online 3 January 2017
Source:Hearing Research
Author(s): Oliver Christian Dziemba, Daniel Grafmans, Stephan Merz, Thomas Hocke




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Gentamicin Applied to the Oval Window Suppresses Vestibular Function in Guinea Pigs

Abstract

Intratympanic gentamicin therapy is widely used clinically to treat the debilitating symptoms of Ménière’s disease. Cochleotoxicity is an undesirable potential side effect of the treatment and the risk of hearing loss increases proportionately with gentamicin concentration in the cochlea. It has recently been shown that gentamicin is readily absorbed through the oval window in guinea pigs. The present study uses quantitative functional measures of vestibular and cochlea function to investigate the efficacy of treating the vestibule by applying a small volume of gentamicin onto the stapes footplate in guinea pigs. Vestibular and cochlea function were assessed by recording short latency vestibular evoked potentials in response to linear head acceleration and changes in hearing threshold, respectively, 1 and 2 weeks following treatment. Histopathology was analyzed in the crista ampullaris of the posterior semi-circular canal and utricular macula in the vestibule, and in the basal and second turns of the cochlea. In animals receiving gentamicin on the stapes footplate, vestibular responses were significantly suppressed by 72.7 % 2 weeks after treatment with no significant loss of hearing. This suggests that the vestibule can be treated directly by applying gentamicin onto the stapes footplate.



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Deleting the HCN1 Subunit of Hyperpolarization-Activated Ion Channels in Mice Impairs Acoustic Startle Reflexes, Gap Detection, and Spatial Localization

Abstract

It has been proposed that the high temporal and spatial acuities of human listeners and animals tested in the hearing laboratory depend in part on the short time constants of auditory neurons that are able to preserve or sharpen the information conveyed in the timing of firing of auditory nerve fibers. We tested this hypothesis in a series of in vivo experiments, based on previous in vitro experiments showing that neuronal time constants are raised in brainstem slices when HCN1 channels are blocked or in slices obtained from Hcn1 −/− null mutant mice. We compared Hcn1 −/− and Hcn1 +/+ mice on auditory brainstem responses (ABRs) and behavioral measures. Those measures included temporal integration for acoustic startle responses (ASRs), ASR depression by noise offset, and ASR inhibition by gaps in noise and by shifts of a noise source along the azimuth as measures of temporal and spatial acuity. Hcn1 −/− mice had less sensitive ABR thresholds at 32 and 48 kHz. Their wavelet P1b was delayed, and wave 2 was absent in the 16 kHz/90 SPL waveform, indicating that groups of neurons early in the auditory pathways were delayed and fired asynchronously. Baseline ASR levels were lower in Hcn1 −/− mice, temporal integration was delayed, time constants for ASR depression by noise offset were higher, and their sensitivity to brief gaps and spatial acuity was diminished. HCN1 channels are also present in vestibular, cutaneous, digestive, and cardiac neurons that variously may contribute to the deficits in spatial acuity and possibly in ASR levels.



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Academy Collaborates with Audiology Project: Hearing Loss Link to Diabetes and Other Comorbidities

In an initiative to raise awareness within the Centers for Disease Control and other national organizations on the link between hearing loss and diabetes mellitus, the Academy has engaged in a memorandum of understanding with the Audiology Project.



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The Cocktail Party Effect

2016 is over, and many of us attended celebrations of remembrance of the year's transpiration and resolutions for the year to come. Civilizations around the world have been celebrating the New Year for at least four millennia, but not always in December. Learn more about the history of New Year’s Eve (NYE).



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Alterations in Evoked Otoacoustic Emissions by the Use of Meglumine Antimoniate in American Tegumentary Leishmaniasis Patients

by Débora Cristina de Oliveira Bezerra, Renata Oliveira de Barcelos, Ellen Carvalho de Castro, Claudia Cristina Jardim Duarte, Raquel de Vasconcellos Carvalhaes Oliveira, Tania Salgado de Sousa Torraca, Maria Helena de Araújo-Melo, Frederico Pereira Bom Braga, Benivaldo Ramos Ferreira Terceiro, Lúcia Regina do Nascimento Brahim Paes, Armando de Oliveira Schubach, Cláudia Maria Valete-Rosalino

Introduction

Tegumentary Leishmaniasis (TL) is a neglected, non-contagious, infectious disease, caused by different protozoa species of the Leishmania genus that affects skin and mucous membranes. Meglumine Antimoniate (MA), the first drug of choice for TL treatment in Brazil, has already been associated with cochlear toxicity, which is defined as damages of the cochlea caused by exposure to chemical substances, resulting in reversible or irreversible hearing loss. Auditory monitoring for cochlear toxicity aims at the early detection of auditory disorders, enabling, when possible, hearing to be preserved or an early auditory rehabilitation. Although otoacoustic emissions (OAEs) are used in this monitoring, there is no consensus on the criteria that define cochlear toxicity by this examination. The objective of this study was to describe the characteristics of the OAEs in cochlear toxicity monitoring in TL patients using MA.

Methods

Prospective and longitudinal study of auditory monitoring of 35 patients with parasitological diagnosis of TL, with liminal tonal audiometry, high frequency audiometry, immitanciometry, distortion product evoked otoacoustic emissions (DPEOAEs) and transient evoked otoacoustic emissions (TEOAEs) before treatment, at the end of treatment, one month after the end of treatment and two months after the end of treatment.

Results

80% male, with median age of 44 years (IIQ: 22–59). In the pre-treatment evaluation: 11.4% complained of hearing loss and 20% of tinnitus, 48.6% presented auditory alterations in liminal tonal audiometry (LTA, 65.2% in high frequency audiometry (HFA), 26.6% in DPEOAE and 51.4% in TEOAE. No association was verified between genre and alterations in the EOAE examinations. We observed that patients that presented disorders in DPEOAE examinations were 17 years older than those without alterations and that patients that showed disorders in TEOAEO examinations were 34 years older than those without disorders. The presence of alterations in DPEOAE and TEOAE before beginning treatment was associated with each other and with the presence of alterations in LTA and HFA, and only DPEOAE was associated with hearing loss. We observed a significantly higher number of alterations of DPEOAE at the end of treatment than during pre-treatment and values of the ratio signal/noise significantly smaller at the end of treatment than during pre-treatment in the frequencies of 2 kHz (difference of 1.7dB; p = 0.016) and 4 kHz (difference of 2.45dB; p = 0.016) in DPEOAE and in the range 1.75/2.5 kHz in TEOAE (difference of 2.9dB; p = 0.039).

Conclusion

The ototoxic signals observed in our study using EOAE indicated that both, DPEOAE and TEOAE are adequate and sensitive techniques for clinical monitoring of ototoxicity by MA. Their application is very simple, and their results help the physician to take the most adequate steps for each patient, thus avoiding permanent hearing damage.



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Variants in WFS1 and other Mendelian deafness genes are associated with cisplatin-associated ototoxicity.

Related Articles

Variants in WFS1 and other Mendelian deafness genes are associated with cisplatin-associated ototoxicity.

Clin Cancer Res. 2016 Dec 30;:

Authors: Wheeler HE, Gamazon ER, Frisina R, Perez-Cervantes C, El Charif O, Mapes B, Fossa SD, Feldman D, Hamilton R, Vaughn DJ, Beard C, Fung C, Kollmannsberger C, Kim J, Mushiroda T, Kubo M, Ardeshir-Rouhani-Fard S, Einhorn LH, Cox N, Dolan ME, Travis L

Abstract
PURPOSE: Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO).
EXPERIMENTAL DESIGN: We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4-12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding.
RESULTS: One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression quantitative trait locus (eQTL) for WFS1 met genome-wide significance for association with CAO (P=1.4x10(-8)). A significant interaction between cumulative cisplatin dose and rs62283056 genotype was evident, indicating that higher cisplatin doses exacerbate hearing loss in patients with the minor allele (P=0.035). The association between decreased WFS1 expression and hearing loss was replicated in an independent BioVU cohort (n=18,620 patients, Bonferroni adjusted P<0.05). Beyond this top signal, we show CAO is a polygenic trait and that SNPs in and near 84 known Mendelian deafness genes are significantly enriched for low P-values in the GWAS (P=0.048).
CONCLUSIONS: We show for the first time the role of WFS1 in CAO and document a statistically significant interaction between increasing cumulative cisplatin dose and rs62283056 genotype. Our clinical translational results demonstrate that pre-therapy patient genotyping to minimize ototoxicity could be useful when deciding between cisplatin-based chemotherapy regimens of comparable efficacy with different cumulative doses.

PMID: 28039263 [PubMed - as supplied by publisher]



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Global Analysis of Protein Expression of Inner Ear Hair Cells.

Related Articles

Global Analysis of Protein Expression of Inner Ear Hair Cells.

J Neurosci. 2016 Dec 30;:

Authors: Hickox AE, Wong AC, Pak K, Strojny C, Ramirez M, Yates JR, Ryan AF, Savas JN

Abstract
The mammalian inner ear subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by employing a host of known and yet unknown protein machinery. To understand the protein composition of these unique post-mitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed inner ear samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP transgenic mice, in which HCs express GFP driven by Pou4f3, we FACS-purified a population of HCs to analyze and compare the HC proteome with other inner ear sub-proteomes from sensory epithelia and whole inner ear. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal inner ear function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes.
SIGNIFICANCE STATEMENT: Hearing and balance rely on specialized sensory hair cells (HCs) in the inner ear to convey information about sound, acceleration and orientation to the brain. Genetically and environmentally induced perturbations to HC proteins can result in deafness and severe imbalance. We used transgenic mice with GFP-expressing HCs, coupled with FACS-sorting and tandem mass spectrometry, to define the most complete HC-, and inner ear-, proteome to-date. We show that hundreds of proteins are uniquely identified or enriched in HCs, extending previous gene expression analyses to reveal novel HC proteins and isoforms. Importantly, deafness-linked proteins were significantly enriched in HCs, suggesting that this in-depth proteomic analysis of inner ear sensory cells may hold potential for deafness gene discovery.

PMID: 28039372 [PubMed - as supplied by publisher]



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Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Related Articles

Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Neuro Oncol. 2016 Dec 29;:

Authors: King AA, Seidel K, Di C, Leisenring WM, Perkins SM, Krull KR, Sklar CA, Green DM, Armstrong GT, Zeltzer LK, Wells E, Stovall M, Ullrich NJ, Oeffinger KC, Robison LL, Packer RJ

Abstract
BACKGROUND: Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized.
METHODS: The Childhood Cancer Survivor Study (CCSS) includes 380 five-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models.
RESULTS: Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66).
CONCLUSIONS: Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority.

PMID: 28039368 [PubMed - as supplied by publisher]



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Global Analysis of Protein Expression of Inner Ear Hair Cells.

Related Articles

Global Analysis of Protein Expression of Inner Ear Hair Cells.

J Neurosci. 2016 Dec 30;:

Authors: Hickox AE, Wong AC, Pak K, Strojny C, Ramirez M, Yates JR, Ryan AF, Savas JN

Abstract
The mammalian inner ear subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by employing a host of known and yet unknown protein machinery. To understand the protein composition of these unique post-mitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed inner ear samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP transgenic mice, in which HCs express GFP driven by Pou4f3, we FACS-purified a population of HCs to analyze and compare the HC proteome with other inner ear sub-proteomes from sensory epithelia and whole inner ear. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal inner ear function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes.
SIGNIFICANCE STATEMENT: Hearing and balance rely on specialized sensory hair cells (HCs) in the inner ear to convey information about sound, acceleration and orientation to the brain. Genetically and environmentally induced perturbations to HC proteins can result in deafness and severe imbalance. We used transgenic mice with GFP-expressing HCs, coupled with FACS-sorting and tandem mass spectrometry, to define the most complete HC-, and inner ear-, proteome to-date. We show that hundreds of proteins are uniquely identified or enriched in HCs, extending previous gene expression analyses to reveal novel HC proteins and isoforms. Importantly, deafness-linked proteins were significantly enriched in HCs, suggesting that this in-depth proteomic analysis of inner ear sensory cells may hold potential for deafness gene discovery.

PMID: 28039372 [PubMed - as supplied by publisher]



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Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Related Articles

Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Neuro Oncol. 2016 Dec 29;:

Authors: King AA, Seidel K, Di C, Leisenring WM, Perkins SM, Krull KR, Sklar CA, Green DM, Armstrong GT, Zeltzer LK, Wells E, Stovall M, Ullrich NJ, Oeffinger KC, Robison LL, Packer RJ

Abstract
BACKGROUND: Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized.
METHODS: The Childhood Cancer Survivor Study (CCSS) includes 380 five-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models.
RESULTS: Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66).
CONCLUSIONS: Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority.

PMID: 28039368 [PubMed - as supplied by publisher]



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