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Journal of the Chinese Medical... Dec 2023Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitin-proteasome system has been reported to be associated with...
BACKGROUND
Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitin-proteasome system has been reported to be associated with cochlear development and hearing loss. The gene related to anergy in lymphocytes ( GRAIL ), as an E3 ubiquitin ligase, has not, as yet, been examined in aging-related and noise-induced hearing loss mice models.
METHODS
This study used wild-type (WT) and GRAIL knockout (KO) mice to examine cochlear hair cells and synaptic ribbons using immunofluorescence staining. The hearing in WT and KO mice was detected using auditory brainstem response. Gene expression patterns were compared using RNA-sequencing to identify potential targets during the pathogenesis of noise-induced hearing loss in WT and KO mice.
RESULTS
At the 12-month follow-up, GRAIL KO mice had significantly less elevation in threshold level and immunofluorescence staining showed less loss of outer hair cells and synaptic ribbons in the hook region compared with GRAIL WT mice. At days 1, 14, and 28 after noise exposure, GRAIL KO mice had significantly less elevation in threshold level than WT mice. After noise exposure, GRAIL KO mice showed less loss of outer hair cells in the cochlear hook and basal regions compared with WT mice. Moreover, immunofluorescence staining showed less loss of synaptic ribbons in the hook regions of GRAIL KO mice than of WT mice. RNA-seq analysis results showed significant differences in C-C motif chemokine ligand 19 ( CCL19 ), C-C motif chemokine ligand 21 ( CCL21 ), interleukin 25 ( IL25 ), glutathione peroxidase 6 ( GPX6 ), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 ( NOX1 ) genes after noise exposure.
CONCLUSION
The present data demonstrated that GRAIL deficiency protects against aging-related and noise-induced hearing loss. The mechanism involved needs to be further clarified from the potential association with synaptic modulation, inflammation, and oxidative stress.
Topics: Animals; Mice; Aging; Auditory Threshold; Chemokines; Evoked Potentials, Auditory, Brain Stem; Gene Knockout Techniques; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; Ligands; Noise
PubMed: 37820291
DOI: 10.1097/JCMA.0000000000001005 -
Frontiers in Integrative Neuroscience 2023Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system....
INTRODUCTION
Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP).
METHODS
A cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold.
RESULTS
cVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway.
DISCUSSION
In the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.
PubMed: 37849955
DOI: 10.3389/fnint.2023.1236661 -
European Journal of Public Health Aug 2023Environmental noise is becoming increasingly recognized as an urgent public health problem, but the quality of current studies needs to be assessed. To evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Environmental noise is becoming increasingly recognized as an urgent public health problem, but the quality of current studies needs to be assessed. To evaluate the significance, validity and potential biases of the associations between environmental noise exposure and health outcomes.
METHODS
We conducted an umbrella review of the evidence across meta-analyses of environmental noise exposure and any health outcomes. A systematic search was done until November 2021. PubMed, Cochrane, Scopus, Web of Science, Embase and references of eligible studies were searched. Quality was assessed by AMSTAR and Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
RESULTS
Of the 31 unique health outcomes identified in 23 systematic reviews and meta-analyses, environmental noise exposure was more likely to result in a series of adverse outcomes. Five percent were moderate in methodology quality, the rest were low to very low and the majority of GRADE evidence was graded as low or even lower. The group with occupational noise exposure had the largest risk increment of speech frequency [relative risk (RR): 6.68; 95% confidence interval (CI): 3.41-13.07] and high-frequency (RR: 4.46; 95% CI: 2.80-7.11) noise-induced hearing loss. High noise exposure from different sources was associated with an increased risk of cardiovascular disease (34%) and its mortality (12%), elevated blood pressure (58-72%), diabetes (23%) and adverse reproductive outcomes (22-43%). In addition, the dose-response relationship revealed that the risk of diabetes, ischemic heart disease (IHD), cardiovascular (CV) mortality, stroke, anxiety and depression increases with increasing noise exposure.
CONCLUSIONS
Adverse associations were found for CV disease and mortality, diabetes, hearing impairment, neurological disorders and adverse reproductive outcomes with environmental noise exposure in humans, especially occupational noise. The studies mostly showed low quality and more high-quality longitudinal study designs are needed for further validation in the future.
Topics: Humans; Longitudinal Studies; Systematic Reviews as Topic; Environmental Exposure; Noise; Occupational Exposure; Cardiovascular Diseases
PubMed: 37030015
DOI: 10.1093/eurpub/ckad044 -
Otology & Neurotology : Official... Oct 2023Metformin treatment will protect mice from noise-induced hearing loss (NIHL).
HYPOTHESIS
Metformin treatment will protect mice from noise-induced hearing loss (NIHL).
BACKGROUND
We recently identified metformin as the top-ranking, Food and Drug Administration-approved drug to counter inner ear molecular changes induced by permanent threshold shift-inducing noise. This study is designed to functionally test metformin as a potential otoprotective drug against NIHL.
METHODS
Male and female B6CBAF1/J mice were obtained at 7 to 8 weeks of age. A cohort of the females underwent ovariectomy to simulate menopause and eliminate the effect of ovarian-derived estrogens. At 10 weeks of age, mice underwent a permanent threshold shift-inducing noise exposure (102.5 or 105 dB SPL, 8-16 kHz, 2 h). Auditory brainstem response (ABR) thresholds were obtained at baseline, 24 h after noise exposure, and 1 week after noise exposure. Mice were administered metformin (200 mg/kg/d) or a saline control in their drinking water after the baseline ABR and for the remainder of the study. After the 1-week ABR, mice were euthanized and cochlear tissue was analyzed.
RESULTS
Metformin treatment reduced the 1-week ABR threshold shift at 16 kHz ( p < 0.01; d = 1.20) and 24 kHz ( p < 0.01; d = 1.15) as well as outer hair cell loss in the 32-45.5 kHz range ( p < 0.0001; d = 2.37) in male mice. In contrast, metformin treatment did not prevent hearing loss or outer hair cell loss in the intact or ovariectomized female mice.
CONCLUSIONS
Metformin exhibits sex-dependent efficacy as a therapeutic for NIHL. These data compel continued investigation into metformin's protective effects and demonstrate the importance of evaluating the therapeutic efficacy of drugs in subjects of both sexes.
Topics: Female; Male; United States; Animals; Mice; Hearing Loss, Noise-Induced; Deafness; Cochlea; Ear, Inner; Metformin
PubMed: 37641232
DOI: 10.1097/MAO.0000000000004002 -
Scientific Reports Oct 2023Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration...
Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration of the spiral ganglion neurons (SGNs). Although macrophages play an essential role after cochlear injury, its role in the SGNs is limitedly understood. We analyzed the status of macrophage activation and neuronal damage in the spiral ganglion after kanamycin-induced unilateral hearing loss in mice. The number of ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages increased 3 days after unilateral kanamycin injection. Macrophages showed larger cell bodies, suggesting activation status. Interestingly, the number of activating transcription factor 3 (ATF3)-positive-neurons, an indicator of early neuronal damage, also increased at the same timing. In the later stages, the number of macrophages decreased, and the cell bodies became smaller, although the number of neuronal deaths increased. To understand their role in neuronal damage, macrophages were depleted via intraperitoneal injection of clodronate liposome 24 h after kanamycin injection. Macrophage depletion decreased the number of ATF3-positive neurons at day 3 and neuronal death at day 28 in the spiral ganglion following kanamycin injection. Our results suggest that suppression of inflammation by clodronate at early timing can protect spiral ganglion damage following cochlear insult.
Topics: Mice; Animals; Spiral Ganglion; Kanamycin; Hearing Loss, Unilateral; Clodronic Acid; Hair Cells, Auditory; Cochlea; Neurons; Macrophages
PubMed: 37798459
DOI: 10.1038/s41598-023-43927-9 -
International Journal of Molecular... Apr 2024Hearing is essential for communication, and its loss can cause a serious disruption to one's social life. Hearing loss is also recognized as a major risk factor for... (Review)
Review
Hearing is essential for communication, and its loss can cause a serious disruption to one's social life. Hearing loss is also recognized as a major risk factor for dementia; therefore, addressing hearing loss is a pressing global issue. Sensorineural hearing loss, the predominant type of hearing loss, is mainly due to damage to the inner ear along with a variety of pathologies including ischemia, noise, trauma, aging, and ototoxic drugs. In addition to genetic factors, oxidative stress has been identified as a common mechanism underlying several cochlear pathologies. The cochlea, which plays a major role in auditory function, requires high-energy metabolism and is, therefore, highly susceptible to oxidative stress, particularly in the mitochondria. Based on these pathological findings, the potential of antioxidants for the treatment of hearing loss has been demonstrated in several animal studies. However, results from human studies are insufficient, and future clinical trials are required. This review discusses the relationship between sensorineural hearing loss and reactive oxidative species (ROS), with particular emphasis on age-related hearing loss, noise-induced hearing loss, and ischemia-reperfusion injury. Based on these mechanisms, the current status and future perspectives of ROS-targeted therapy for sensorineural hearing loss are described.
Topics: Humans; Oxidative Stress; Hearing Loss, Sensorineural; Animals; Reactive Oxygen Species; Antioxidants; Cochlea; Hearing Loss, Noise-Induced; Reperfusion Injury; Mitochondria
PubMed: 38673731
DOI: 10.3390/ijms25084146 -
Progress in Neurobiology Dec 2023Tinnitus induced by hearing loss is caused primarily by irreversible damage to the peripheral auditory system, which results in abnormal neural responses and frequency...
Tinnitus induced by hearing loss is caused primarily by irreversible damage to the peripheral auditory system, which results in abnormal neural responses and frequency map disruption in the central auditory system. It remains unclear whether and how electrical rehabilitation of the auditory cortex can alleviate tinnitus. We hypothesize that stimulation of the cortical surface can alleviate tinnitus by enhancing neural responses and promoting frequency map reorganization. To test this hypothesis, we assessed and activated cortical maps using our newly designed graphene-based electrode array with a noise-induced tinnitus animal model. We found that cortical surface stimulation increased cortical activity, reshaped sensory maps, and alleviated hearing loss-induced tinnitus behavior in adult mice. These effects were likely due to retained long-term synaptic potentiation capabilities, as shown in cortical slices from the mice model. These findings suggest that cortical surface activation can be used to facilitate practical functional recovery from phantom percepts induced by sensory deprivation. They also provide a working principle for various treatment methods that involve electrical rehabilitation of the cortex.
Topics: Mice; Animals; Tinnitus; Auditory Cortex; Hearing Loss; Disease Models, Animal; Brain Mapping; Neuronal Plasticity
PubMed: 37924858
DOI: 10.1016/j.pneurobio.2023.102543 -
Seminars in Hearing Nov 2023The National Institute for Occupational Safety and Health (NIOSH) evaluated continuous and impact noise exposures and hearing loss among workers at a hammer forge... (Review)
Review
The National Institute for Occupational Safety and Health (NIOSH) evaluated continuous and impact noise exposures and hearing loss among workers at a hammer forge company. Full-shift personal noise exposure measurements were collected on forge workers across 15 different job titles; impact noise characteristics and one-third octave band noise levels were assessed at the forge hammers; and 4,750 historic audiometric test records for 483 workers were evaluated for hearing loss trends. Nearly all workers' noise exposures exceeded regulatory and/or recommended exposure limits. Workers working in jobs at or near the hammers had full-shift time-weighted average noise exposures above 100 decibels, A-weighted. Impact noise at the hammers reached up to 148 decibels. Analysis of audiometric test records showed that 82% of workers had experienced a significant threshold shift, as defined by NIOSH, and 63% had experienced a standard threshold shift, as defined by the Occupational Safety and Health Administration (OSHA). All workers with an OSHA standard threshold shift had a preceding NIOSH significant threshold shift which occurred, on average, about 7 years prior. This evaluation highlights forge workers' exposures to high levels of noise, including impact noise, and how their hearing worsened with age and length of employment.
PubMed: 37818145
DOI: 10.1055/s-0043-1769498 -
Ear and HearingThe aim of this study is to present an explanatory model of hearing loss in the Bering Strait region of Alaska in order to contextualize the results of a cluster... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The aim of this study is to present an explanatory model of hearing loss in the Bering Strait region of Alaska in order to contextualize the results of a cluster randomized trial and propose implications for regional hearing-related health care.
DESIGN
To promote ecological validity, or the generalizability of trial findings to real world experiences, qualitative methods (focus groups and interviews) were used within a mixed methods cluster randomized trial evaluating school hearing screening and follow-up processes in 15 communities in the Bering Strait region of Alaska. Focus groups were held between April and August 2017, and semistructured interviews were conducted between December 2018 and August 2019. Convenience sampling was used for six of the 11 focus groups to capture broad community feedback. Purposive sampling was used for the remaining five focus groups and for all interviews to capture a variety of experiences with hearing loss. Audio recordings of focus groups and interviews were transcribed, and both notes and transcripts were deidentified. All notes and transcripts were included in the analysis. The constant comparative method was used to develop a codebook by iteratively moving between transcripts and preliminary themes. Researchers then used this codebook to code data from all focus groups and interviews using qualitative analysis software (NVIVO 12, QSR International) and conducted thematic analyses to distill the findings presented in this article.
RESULTS
Participants in focus groups (n = 116) and interviews (n = 101) shared perspectives in three domains: etiology, impact, and treatment of hearing loss. Regarding etiology, participants emphasized noise-induced hearing loss but also discussed infection-related hearing loss and various causes of ear infections. Participants described the impact of hearing loss on subsistence activities, while also detailing social, academic, and economic consequences. Participants described burdensome treatment pathways that are repetitive and often travel and time intensive. Communication breakdowns within these pathways were also described. Some participants spoke positively of increased access via onsite hearing health care services in "field clinics" as well as via telemedicine services. Others described weaknesses in these processes (infrequent field clinics and communication delays in telemedicine care pathways). Participants also described home remedies and stigma surrounding the treatment for hearing loss.
CONCLUSIONS
Patient-centered health care requires an understanding of context. Explanatory models of illness are context-specific ways in which patients and their networks perceive and describe the experience of an illness or disability. In this study, we documented explanatory models of hearing loss to foster ecological validity and better understand the relevance of research findings to real-life hearing-related experiences. These findings suggest several areas that should be addressed in future implementation of hearing health care interventions elsewhere in rural Alaska, including management of repetitious treatments, awareness of infection-mediated hearing loss, mistrust, and communication breakdowns. For hearing-related health care in this region, these findings suggest localized recommendations for approaches for prevention and treatment. For community-based hearing research, this study offers an example of how qualitative methods can be used to generate ecologically valid (i.e., contextually grounded) findings.
Topics: Humans; Alaska; Deafness; Delivery of Health Care; Telemedicine; Hearing Loss, Noise-Induced; Qualitative Research
PubMed: 36939709
DOI: 10.1097/AUD.0000000000001348