Tests of human auditory temporal resolution: Simulations of Bayesian threshold estimation for auditory gap detection.

In an attempt to develop tests of auditory temporal resolution using gap detection, we conducted computer simulations of Zippy Estimation by Sequential Testing (ZEST), an adaptive Bayesian threshold estimation procedure, for measuring gap detection thresholds. The results showed that the measures of efficiency and precision of ZEST changed with the mean and standard deviation (SD) of the initial probability density function implemented in ZEST. Appropriate combinations of mean and SD values led to efficient ZEST performance; i.

Tests of human auditory temporal resolution: preliminary investigation of ZEST parameters for amplitude modulation detection.

Auditory temporal resolution plays a critical role in the everyday experience of listening to complex acoustic patterns. Amplitude modulation detection thresholds are widely used to measure auditory temporal resolution. In an attempt to develop a standardized clinical test of auditory temporal resolution, we used ZEST (Zippy Estimation by Sequential Testing, a Bayesian threshold estimation procedure, to measure amplitude modulation detection thresholds.

Phenotype-genotype correlation in patients with typical and atypical branchio-oto-renal syndrome.

Some patients have an atypical form of branchio-oto-renal (BOR) syndrome, which does not satisfy the diagnostic criteria, despite carrying a pathogenic variant (P variant) or a likely pathogenic variant (LP variant) of a causative gene. P/LP variants phenotypic indices have yet to be determined in patients with typical and atypical BOR syndrome. We hypothesized that determining phenotypic and genetic differences between patients with typical and atypical BOR syndrome could inform such indices.

[A Case of Advanced Esophageal Cancer Discovered Due to Suffocation, Which Was Invasive to the Trachea and Internal Carotid Artery and Treated by Chemotherapy].

A 51-year-old male presented with dyspnea due to upper airway obstruction. We decided to perform a cricothyroidotomy due to difficulty in performing orotracheal intubation. A CT scan revealed a massive tumor infiltrating into the right side of the neck, which penetrated the internal carotid artery.

Anticipating real-ear insertion response using an external auditory canal model.

Objectives: This study aimed to determine the acoustic characteristics of the external auditory canal (EAC) and predict the real-ear aided response (REAR) using an EAC model that includes the standing wave effect.

Methods: The EAC transfer function equations were derived by summing the incoming and outgoing waves. First, we investigated the real-ear unaided gain (REUG).

Rising-frequency chirp stimulus to effectively enhance wave-I amplitude of auditory brainstem response.

This study aims to find an effective chirp signal that enhances the amplitude of wave-I of auditory brainstem response (ABR) to diagnose "cochlear synaptopathy." Although several chirp signals have been proposed to enhance the amplitude of wave-V, the effect on wave-I has not been clarified yet. Ten chirp signals, which have shorter group delays than the commonly used "CE-chirp," were produced to measure the amplitudes of wave-I and wave-V of the ABRs.

Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

Objectives: Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions.

Two-Point Method for Measuring the Temporal Modulation Transfer Function.

Objective: The temporal modulation transfer function (TMTF) has been proposed to estimate the temporal resolution abilities of listeners with normal hearing and listeners with hearing loss. The TMTF data of patients would be useful for clinical diagnosis and for adjusting the hearing instruments at clinical and fitting sites. However, practical application is precluded by the long measurement time of the conventional method, which requires several measurement points.

Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall: a potential therapeutic target for sensorineural hearing loss.

Cochlear lateral wall has recently been reported as a common site of inflammation, yet precise molecular mechanisms of the inflammatory responses remain elucidated. The present study examined the inflammatory responses in the lateral wall following acute mitochondrial dysfunction induced by a mitochondrial toxin, 3-nitropropionic acid (3-NP). Reverse-transcription (RT)-PCR revealed increases in the expression of the proinflammatory cytokines interleukin (IL)-1β and IL-6.

Subgroups of enlarged vestibular aqueduct in relation to SLC26A4 mutations and hearing loss.

Objectives/hypothesis: To investigate possible association of hearing loss and SLC26A4 mutations with the subgroups of enlarged vestibular aqueduct (EVA) morphology in Japanese subjects with hearing loss.

Study Design: Retrospective multicenter study.

Methods: Forty-seven subjects who had vestibular aqueduct with midpoint diameter >1 mm by computed tomography of the temporal bone were enrolled at multiple sites across Japan, and DNA samples and clinical data were collected.

Age-related hearing loss and the factors determining continued usage of hearing aids among elderly community-dwelling residents.

While hearing aids are recommended for people with age-related hearing loss, many with impaired hearing do not use them. In this study, we investigated how many elderly people in the study area needed hearing aids, and the factors that determined continued wearing of the devices. The study area was Kurabuchi Town, Japan, where 1,437 residents (those aged 65 years or over) were eligible for participation in the study; 1,414 participated, of whom, 103 (7.

Disease modifying therapies for Alzheimer's disease targeting Aβ oligomers: implications for therapeutic mechanisms.

Several lines of evidence indicate that amyloid β (Aβ), particularly Aβ oligomers (AβOs), plays a causative role in Alzheimer's disease. However, the mechanisms underlying the action of an anti-AβO antibody to clarify the toxic action of AβOs remain elusive. Here, we showed that the anti-AβO antibody (monoclonal 72D9) can modify the Aβ aggregation pathway.

Sortilin is required for toxic action of Aβ oligomers (AβOs): extracellular AβOs trigger apoptosis, and intraneuronal AβOs impair degradation pathways.

Aims: We investigated the pathological relevance of the "Aβ oligomer (AβO) cascade hypothesis" in 3xTg-AD mice. This study was also designed to elucidate the molecular mechanism underlying the toxic action of AβOs.

Main Methods: To target the extracellular AβOs in vivo, a monoclonal antibody specific for AβOs was developed using a novel method.

Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse.

Background: Several lines of evidence indicate that memory loss represents a synaptic failure caused by soluble amyloid β (Aβ) oligomers. However, the pathological relevance of Aβ oligomers (AβOs) as the trigger of synaptic or neuronal degeneration, and the possible mechanism underlying the neurotoxic action of endogenous AβOs remain to be determined.

Results: To specifically target toxic AβOs in vivo, monoclonal antibodies (1A9 and 2C3) specific to them were generated using a novel design method.

Repetitive transcranial magnetic stimulation (rTMS) for treatment of chronic tinnitus.

Objective: There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modifying neural activity at the stimulated area and at a distance along the functional anatomical connections. Depending on the stimulation parameters, cortical networks can be functionally disturbed or modulated in their activities.

Mesenchymal stem cell transplantation accelerates hearing recovery through the repair of injured cochlear fibrocytes.

Cochlear fibrocytes play important roles in normal hearing as well as in several types of sensorineural hearing loss attributable to inner ear homeostasis disorders. Recently, we developed a novel rat model of acute sensorineural hearing loss attributable to fibrocyte dysfunction induced by a mitochondrial toxin. In this model, we demonstrate active regeneration of the cochlear fibrocytes after severe focal apoptosis without any changes in the organ of Corti.

A minimal CENP-A core is required for nucleation and maintenance of a functional human centromere.

Chromatin clusters containing CENP-A, a histone H3 variant, are found in centromeres of multicellular eukaryotes. This study examines the ability of alpha-satellite (alphoid) DNA arrays in different lengths to nucleate CENP-A chromatin and form functional kinetochores de novo. Kinetochore assembly was followed by measuring human artificial chromosome formation in cultured human cells and by chromatin immunoprecipitation analysis.

An artificially constructed de novo human chromosome behaves almost identically to its natural counterpart during metaphase and anaphase in living cells.

Human artificial chromosomes (HACs) are promising reagents for the analysis of chromosome function. While HACs are maintained stably, the segregation mechanisms of HACs have not been investigated in detail. To analyze HACs in living cells, we integrated 256 copies of the Lac operator into a precursor yeast artificial chromosome (YAC) containing alpha-satellite DNA and generated green fluorescent protein (GFP)-tagged HACs in HT1080 cells expressing a GFP-Lac repressor fusion protein.

Cholesterol granuloma surrounding the endolymphatic sac.

We report a unique case of cholesterol granuloma (CG) surrounding the endolymphatic sac (ES). A 49-year-old man presented with the left side of sensorineural hearing loss, tinnitus, and vertigo. Magnetic resonance and computed tomography imaging revealed a CG surrounding the left ES.

[Evaluation of the quality of life in sudden deafness patients by HHIA (hearing Hatidicap Inventory) and questionnaire].

After treatments, several patients with sudden deafness (SD) continued to have symptoms, including hearing loss, tinnitus and dizziness. These unresolved symptoms and their effect on the quality of life (QOL) in SD patients have not been studied. We evaluated QOL using the Hearing handicap inventory (HHIA) and an original questionnaire in SD patients who had been treated more than 6 months prior to the study.

Rapid generation of long synthetic tandem repeats and its application for analysis in human artificial chromosome formation.

Human artificial chromosomes (HACs) provide a unique opportunity to study kinetochore formation and to develop a new generation of vectors with potential in gene therapy. An investigation into the structural and the functional relationship in centromeric tandem repeats in HACs requires the ability to manipulate repeat substructure efficiently. We describe here a new method to rapidly amplify human alphoid tandem repeats of a few hundred base pairs into long DNA arrays up to 120 kb.

Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea.

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment.

A novel animal model of acute cochlear mitochondrial dysfunction.

Acute mitochondrial dysfunction in the cochlea is likely to result in hearing loss as a consequence of local energy shortage, similar to ischemia- or noise-induced hearing loss. To establish an animal model of acute cochlear mitochondrial dysfunction, we applied a mitochondrial toxin, 3-nitropropionic acid (3-NP) in the rat cochlea. Rats treated with 500mM 3-NP exhibited permanent threshold shifts in acoustic brainstem response while the same volume of 300mM 3-NP caused temporary threshold shifts.