Jaro-Journal of the Association for Research in Otolaryngology最新文献

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.

Purpose: This systematic review aims to assess the impact of sensorineural hearing loss (SNHL) on various frequency-following response (FFR) parameters.

Methods: Following PRISMA guidelines, a systematic review was conducted using PubMed, Web of Science, and Scopus databases up to January 2023. Studies evaluating FFRs in patients with SNHL and normal hearing controls were included.

Results: Sixteen case-control studies were included, revealing variability in acquisition parameters. In the time domain, patients with SNHL exhibited prolonged latencies. The specific waves that were prolonged differed across studies. There was no consensus regarding wave amplitude in the time domain. In the frequency domain, focusing on studies that elicited FFRs with stimuli of 170 ms or longer, participants with SNHL displayed a significantly smaller fundamental frequency (F₀). Results regarding changes in the temporal fine structure (TFS) were inconsistent.

Conclusion: Patients with SNHL may require more time for processing (speech) stimuli, reflected in prolonged latencies. However, the exact timing of this delay remains unclear. Additionally, when presenting longer stimuli (≥ 170 ms), patients with SNHL show difficulties tracking the F₀ of (speech) stimuli. No definite conclusions could be drawn on changes in wave amplitude in the time domain and the TFS in the frequency domain. Patient characteristics, acquisition parameters, and FFR outcome parameters differed greatly across studies. Future studies should be performed in larger and carefully matched subject groups, using longer stimuli presented at the same intensity in dB HL for both groups, or at a carefully determined maximum comfortable loudness level.

Purpose: Attempts to use current-focussing strategies with cochlear implants (CI) to reduce neural spread-of-excitation have met with only mixed success in human studies, in contrast to promising results in animal studies. Although this discrepancy could stem from between-species anatomical and aetiological differences, the masking experiments used in human studies may be insufficiently sensitive to differences in excitation-pattern width.

Methods: We used an interleaved-masking method to measure psychophysical excitation patterns in seven participants with four masker stimulation configurations: monopolar (MP), partial tripolar (pTP), a wider partial tripolar (pTP + 2), and, importantly, a condition (RP + 2) designed to produce a broader excitation pattern than MP. The probe was always in partial-tripolar configuration.

Results: We found a significant effect of stimulation configuration on both the amount of on-site masking (mask and probe on same electrode; an indirect indicator of sharpness) and the difference between off-site and on-site masking. Differences were driven solely by RP + 2 producing a broader excitation pattern than the other configurations, whereas monopolar and the two current-focussing configurations did not statistically differ from each other.

Conclusion: A method that is sensitive enough to reveal a modest broadening in RP + 2 showed no evidence for sharpening with focussed stimulation. We also showed that although voltage recordings from the implant accurately predicted a broadening of the psychophysical excitation patterns with RP + 2, they wrongly predicted a strong sharpening with pTP + 2. We additionally argue, based on our recent research, that the interleaved-masking method can usefully be applied to non-human species and objective measures of CI excitation patterns.

Purpose: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice.

Methods: We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 10⁵ colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function.

Results: Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis.

Conclusions: Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is r

Purpose: To investigate the impact of rapamycin on the differentiation of hair cells.

Methods: Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages.

Results: Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2⁺ progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects.

Conclusion: Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2⁺ progenitors in an in vitro setting.

Purpose: This scoping review aims to assess whether the severity or distress of subjective tinnitus is negatively associated or correlated with the level of health-related quality of life (HRQoL). A second objective is to examine whether tinnitus patients score differently on HRQoL questionnaires in comparison to subjects without tinnitus and whether HRQoL differs between specific subgroups of tinnitus.

Methods: This scoping review adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA guidelines): the statement and extension for scoping reviews (PRISMA-ScR). The following databases were consulted (on the 20th of October 2023): PubMed, Cochrane Library, Web of Science, and Scopus. The search string was composed of the terms tinnitus, HRQoL, and synonyms. A double-blinded screening for eligibility was performed, first on the title and abstract and subsequently on the full-text articles. Studies were considered eligible if they looked at HRQoL questionnaire results for adult patients (> 18 years) reporting chronic (> 3 months), subjective tinnitus as a primary complaint.

Results: In total, 37 studies with a total sample size of 33,900 participants were included in this scoping review, with some studies answering multiple study objectives. Seventeen studies demonstrated the presence of a significant negative correlation between tinnitus-related distress and HRQoL. Two studies indicated that HRQoL is mediated by tinnitus-related distress. Eighteen studies found that, in general, patients with tinnitus scored significantly lower on HRQoL questionnaires in comparison to subjects without tinnitus. Nineteen studies demonstrated that subgroups of patients with more severe tinnitus complaints or specific additional complaints scored worse on HRQoL questionnaires.

Conclusion: Based on the current literature, chronic subjective tinnitus-related distress has a significant impact on health-related quality of life. In addition, subjects without tinnitus generally score significantly higher on HRQoL questionnaires than patients with tinnitus. The heterogeneity in outcome measures between studies precludes meta-analysis. Increased homogeneity in the choice of HRQoL questionnaires would make a comparison between studies possible, which would give valuable information on both a clinical and an economic level, guiding future tinnitus treatment.

Registration: The protocol for the scoping review is registered at Open Science Framework: https://doi.org/10.17605/OSF.IO/F5S9C .

At the 2004 Midwinter Meeting of the Association for Research in Otolaryngology, Glenis Long and her colleagues introduced a method for measuring distortion-product otoacoustic emissions (DPOAEs) using primary-tone stimuli whose instantaneous frequencies vary continuously with time. In contrast to standard OAE measurement methods, in which emissions are measured in the sinusoidal steady state using discrete tones of well-defined frequency, the swept-tone method sweeps across frequency, often at rates exceeding 1 oct/s. The resulting response waveforms are then analyzed using an appropriate filter (e.g., by least-squares fitting). Although introduced as a convenient way of studying DPOAE fine structure by separating the total OAE into distortion and reflection components, the swept-tone method has since been extended to stimulus-frequency emissions and has proved an efficient and valuable tool for probing cochlear mechanics. One day-a long time coming-swept tones may even find their way into the audiology clinic.

Purpose: To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.

Methods: After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.

Results: The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.

Conclusions: The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.

Purpose: The hearing outcomes of cochlear implant users depend on the functional status of the electrode-neuron interface inside the cochlea. This can be assessed by measuring electrically evoked compound action potentials (eCAPs). Variations in cochlear neural health and survival are reflected in eCAP-based metrics. The difficulty in translating promising results from animal studies into clinical use has raised questions about to what degree eCAP-based metrics are influenced by non-neural factors. Here, we addressed these questions using a computational model.

Methods: A 2-D computational model was designed to simulate how electrical signals from the stimulating electrode reach the auditory nerve fibers distributed along the cochlea, evoking action potentials that can be recorded as compound responses at the recording electrodes. Effects of physiologically relevant variations in neural survival and in electrode-neuron and stimulating-recording electrode distances on eCAP amplitude growth functions (AGFs) were investigated.

Results: In line with existing literature, the predicted eCAP AGF slopes and the inter-phase gap (IPG) effects depended on the neural survival, but only when the IPG effect was calculated as the difference between the slopes of the two AGFs expressed in linear input-output scale. As expected, shallower eCAP AGF slopes were obtained for increased stimulating-recording electrode distance and larger eCAP thresholds for greater electrode-neuron distance. These non-neural factors had also minor interference on the predicted IPG effect.

Conclusions: The model predictions demonstrate previously found dependencies of eCAP metrics on neural survival and non-neural aspects. The present findings confirm data from animal studies and provide insights into applying described metrics in clinical practice.