Auditory Damage Research Articles

High-Speed Three-Dimensional-Digital Image Correlation and Schlieren Imaging Integrated With Shock Tube Loading for Investigating Dynamic Response of Human Tympanic Membrane Exposed to Blasts.

Investigating the dynamic response of human tympanic membranes (TMs) exposed to blasts requires full-field-of-view and three-dimensional (3D) methodologies. Our paper introduces a system that combines high-speed 3D digital image correlation (HS 3D-DIC) and Schlieren imaging (HS-SI) with a custom-designed shock tube for generating blast waves. This integrated system allows us to measure TM surface motions under intense transient loading, capturing full-field-of-view shape deformations exceeding 100 μm with a temporal resolution of 10 μs. System characterization encompasses (i) measuring the shock tube's output levels and repeatability, (ii) assessment of the spatial and temporal resolutions of the imaging techniques, and (iii) identification of overall system limitations. Optimizing these factors is crucial for improving the reliability of our system to ensure the accurate measurement of deformations. To assess our shock tube's reliability in generating repeated blast waves, we instrumented it with high-pressure (HP) and high-frequency (HF) pressure sensors along the blast wave pathway to record overpressure waveforms and compared them with Schlieren imaging visualized blast waves. We validate our HS 3D-DIC measured deformations by comparing them with deformations measured using single-point laser Doppler vibrometry (LDV), establishing a comprehensive assessment of the TM's dynamic response and potential fracture mechanics under blast. Finally, we test our approach with 3D-printed TM-like samples and a real cadaveric human TM. This methodology lays the groundwork for further investigations of blast-related auditory damage and the invention of more effective protective and medical solutions.

The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.Graphical HHL mice had a transient threshold shift, reduced ABR wave I amplitude, and decreased number of ribbon synapses.HHL mice's cochlear hair cells exhibited increased oxidative stress and elevated GDF15 expression.Upregulation of GDF15 attenuated oxidative stress and auditory damage in the cochlea of HHL mice, implying that GDF15-targeted treatment techniques may be useful for HHL.

353 Eph/Ephrin Signaling Influences Innervation of Outer Hair Cells in Cochlea

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.

Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

Tinnitus-related increases in single-unit activity in awake rat auditory cortex correlate with tinnitus behavior

Tinnitus is known to affect 10–15 % of the population, severely impacting 1–2 % of those afflicted. Canonically, tinnitus is generally a consequence of peripheral auditory damage resulting in maladaptive plastic changes in excitatory/inhibitory homeostasis at multiple levels of the central auditory pathway as well as changes in diverse nonauditory structures. Animal studies of primary auditory cortex (A1) generally find tinnitus-related changes in excitability across A1 layers and differences between inhibitory neuronal subtypes. Changes due to sound-exposure include changes in spontaneous activity, cross-columnar synchrony, bursting and tonotopic organization. Few studies in A1 directly correlate tinnitus-related changes in neural activity to an individual animal's behavioral evidence of tinnitus. The present study used an established condition-suppression sound-exposure model of chronic tinnitus and recorded spontaneous and driven single-unit responses from A1 layers 5 and 6 of awake Long-Evans rats. A1 units recorded from animals with behavioral evidence of tinnitus showed significant increases in spontaneous and sound-evoked activity which directly correlated to the animal's tinnitus score. Significant increases in the number of bursting units, the number of bursts/minute and burst duration were seen for A1 units recorded from animals with behavioral evidence of tinnitus. The present A1 findings support prior unit recording studies in auditory thalamus and recent in vitro findings in this same animal model. The present findings are consistent with sensory cortical studies showing tinnitus- and neuropathic pain-related down-regulation of inhibition and increased excitation based on plastic neurotransmitter and potassium channel changes. Reducing A1 deep-layer tinnitus-related hyperactivity is a potential target for tinnitus pharmacotherapy.

Revised comprehensive new definition of noise

A revised comprehensive new definition of noise is proposed. Noise: a) For living things, noise is unwanted and/orharmfulnd. b) In engineering and electronics, noise is any unwanted disturbance within a useful frequency band, such as undesired lectric waves in a transmission channel or device. c) In scientific measurements, noise is erraic, intermittent, or statistically random oscillation. The revised comphrehensive new definition builds on the Acoustical Society of America/American National Standards institute definition to include technical considerations, and acknowledges the harmful effect of noise on plants. It updates the noise definition presented at the 2019 Acoustical Society of America winter meeting, noise is unwanted and/or harmful sound. Unlike the standard definition, noise is unwanted sound, that new definition emphasized that unwanted sound is harmful, able to cause adverse auditory and non-auditory health effects, and that wanted sound can also caus auditory damage. The Proceedings of Meetings on Acoustics article based on that presentation has been cited 37 times. The prevvious new definition opens the 2021 American Public Health Association policy statement, Noise as a Public Health Hazard, was adopted for use by the International Commission on Biological Effects of Noise (ICBEN) in 2023, and added to the ICBEN Constitution.

Oxidative stress and inflammation cause auditory system damage via glial cell activation and dysregulated expression of gap junction proteins in an experimental model of styrene-induced oto/neurotoxicity

BackgroundRedox imbalance and inflammation have been proposed as the principal mechanisms of damage in the auditory system, resulting in functional alterations and hearing loss. Microglia and astrocytes play a crucial role in mediating oxidative/inflammatory injury in the central nervous system; however, the role of glial cells in the auditory damage is still elusive.ObjectivesHere we investigated glial-mediated responses to toxic injury in peripheral and central structures of the auditory pathway, i.e., the cochlea and the auditory cortex (ACx), in rats exposed to styrene, a volatile compound with well-known oto/neurotoxic properties.MethodsMale adult Wistar rats were treated with styrene (400 mg/kg daily for 3 weeks, 5/days a week). Electrophysiological, morphological, immunofluorescence and molecular analyses were performed in both the cochlea and the ACx to evaluate the mechanisms underlying styrene-induced oto/neurotoxicity in the auditory system.ResultsWe showed that the oto/neurotoxic insult induced by styrene increases oxidative stress in both cochlea and ACx. This was associated with macrophages and glial cell activation, increased expression of inflammatory markers (i.e., pro-inflammatory cytokines and chemokine receptors) and alterations in connexin (Cxs) and pannexin (Panx) expression, likely responsible for dysregulation of the microglia/astrocyte network. Specifically, we found downregulation of Cx26 and Cx30 in the cochlea, and high level of Cx43 and Panx1 in the ACx.ConclusionsCollectively, our results provide novel evidence on the role of immune and glial cell activation in the oxidative/inflammatory damage induced by styrene in the auditory system at both peripheral and central levels, also involving alterations of gap junction networks. Our data suggest that targeting glial cells and connexin/pannexin expression might be useful to attenuate oxidative/inflammatory damage in the auditory system.

Investigation of METTL3 as an inhibitor of kanamycin-induced ototoxicity via stress granule formation.

Methyltransferase-like 3 (METTL3), a component of the N6-methyladenosine (m6A) methyltransferase family, exhibits significant expression in HEI-OC1 cells and cochlear explants. Aminoglycoside antibiotics, known for their ototoxic potential, frequently induce irreversible auditory damage in hair cells, predominantly through oxidative stress mechanisms. However, the specific role of METTL3 in kanamycin-induced hair cell loss remains unclear. This study aims to elucidate the mechanisms by which METTL3 contributes to kanamycin-induced ototoxicity. In vivo experiments demonstrated a notable reduction in METTL3 expression within cochlear explants following kanamycin administration, concomitant with the formation of stress granules (SGs). Similarly, a 24-hour kanamycin treatment led to decreased METTL3 expression and induced SG formation both in HEI-OC1 cells and neonatal cochlear explants, corroborating the in vivo observations. Lentivirus-mediated transfection was employed to overexpress and knockdown METTL3 in HEI-OC1 cells. Knockdown of METTL3 resulted in increased reactive oxygen species (ROS) levels and apoptosis induced by kanamycin, while concurrently reducing SG formation. Conversely, overexpression of METTL3 attenuated ROS generation, decreased apoptosis rates, and promoted SG formation induced by kanamycin. Therefore, METTL3-mediated SG formation presents a promising target for mitigating kanamycin-induced ROS generation and the rate of apoptosis. This finding indicates that METTL3-mediated SG formation holds potential in mitigating kanamycin-induced impairments in cochlear hair cells by reducing ROS formation and apoptosis rates.

Fluctuating hearing loss secondary to spontaneous intracranial hypotension: A case report and review of the literature.

Fluctuating sensorineural hearing loss (SNHL) has multiple etiologies, most commonly Ménière's disease (MD), recurrent sudden SNHL, and autoimmune inner ear disorders. Fluctuating SNHL has rarely been described as a symptom of spontaneous intracranial hypotension (SIH). A 39-year-old previously healthy female presented with "Ménière's like" symptoms responsive to steroid treatment, which worsened during the day and improved in the supine position. Conservative treatment for MD consisting of low salt and caffeine diet and betahistine medication yielded no improvement. Secondary revision of brain imaging scans showed signs indicative of SIH, and a spinal cerebrospinal fluid leak was ultimately found and treated by a novel technique of transvenous fistula embolization by means of Onyx® glue, leading to gradual clinical improvement and near-complete resolution of symptoms. SIH should be considered as part of the differential diagnosis of fluctuating SNHL. Clinical and radiological features should be known and sought. We suspect that early diagnosis and treatment can lead to cure and prevent permanent auditory damage.

Luteolin inhibits the JAK/STAT pathway to alleviate auditory cell apoptosis of acquired sensorineural hearing loss based on network pharmacology, molecular docking, molecular dynamics simulation, and experiments in vitro

PurposeThe study aimed to explore the mechanisms of luteolin in acquired sensorineural hearing loss (SNHL) through network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. MethodsFirst, the practices of network pharmacology were used to obtain the intersecting targets of luteolin and acquired SNHL, construct the PPI (Protein-Protein Interaction) network, conduct GO and KEGG enrichments, and establish luteolin-acquired SNHL-target-pathway network, aiming to gain the core targets and pathways. Then, the affinity between the core targets and luteolin was verified by molecular docking. Moreover, molecular dynamics (MD) simulation was applied to simulate the binding between targets and luteolin. Finally, with the HEI-OC1 cell line, some molecular biology techniques were adopted to verify the pharmacological actions of luteolin and the significance of the pathway from KEGG enrichment in luteolin-protecting auditory cell damage related to acquired SNHL. Results14 intersecting targets were obtained, and the 10 core targets were further verified through molecular docking and MD simulation to get 5 core targets. The JAK/STAT was selected as the critical pathway through KEGG enrichment. Luteolin could dose-dependently alleviate auditory cell apoptosis by inhibiting the JAK/STAT pathway, confirmed by a series of experiments in vitro. ConclusionThis study manifested that luteolin could reduce acquired SNHL-related auditory cell apoptosis through the JAK/STAT pathway, which provided a new idea for acquired SNHL pharmacological treatment.

Electrophysiological Changes Associated with the Progression of Noise-Induced Hearing Loss.

The aim of this study is to evaluate the clinical characteristics and electrophysiological changes in patients with different degrees of noise-induced hearing loss compared with those of normal controls to elucidate the progression of auditory neural damage attributed to noise exposure. A retrospective cohort study was conducted through a review of the medical records for the patients who presented to a tertiary referral center. Sixty-nine participants were included in the study: 29 had noise-induced hearing loss, and 40 were healthy controls. All the participants underwent electrophysiological tests and pure-tone audiometry. Nine patients showed mild hearing loss (mild hearing loss group), while the others showed worse than moderate hearing loss on puretone audiometry (severe hearing loss group). Significantly reduced wave I and V amplitudes of auditory brainstem response were present in both mild and severe hearing loss groups compared to the control group (P -lt; .001 and P=.002, respectively), without significant differences between the mild and severe hearing loss groups. In the multivariate analysis, auditory brainstem response wave V amplitude was negatively associated with auditory brainstem response wave I-V inter-peak latency delay (B=-0.48, P=.02). The results of the present study confirm the similarity in the electrophysiological characteristics between the mild and severe hearing loss groups. Thus, widespread disruption in the auditory neural conduction could have been established in the early period when the patient developed mild hearing loss following noise exposure.

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1–4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1’s peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1’s Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I–III, and I–V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group. Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia. Trial registration: ClinicalTrials.gov, Identifier: NCT06018012.What is Known:• MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemiaWhat is New:• ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.

Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus).

Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified. The budgerigar, a parakeet species, has recently emerged as an animal model for synaptopathy studies based on its capacity for vocal learning and ability to behaviorally discriminate simple and complex sounds with acuity similar to humans. Kainic acid infusions in the budgerigar produce a profound reduction of compound auditory nerve responses, including wave I of the auditory brainstem response, without impacting physiological hair cell measures. These results suggest selective auditory nerve damage. However, histological correlates of neural injury from kainic acid are still lacking. We quantified the histological effects caused by intracochlear infusion of kainic acid (1mM; 2.5 µL), and evaluated correlations between the histological and physiological assessments of auditory nerve status. Kainic acid infusion in budgerigars produced pronounced loss of neural auditory nervesoma (60% on average) in the cochlearganglion, and of peripheral axons, at time points 2 or more months following injury. The hair cell epithelium was unaffected by kainic acid. Neural loss was significantly correlated with reduction of compound auditory nerve responses and auditory brainstem response wave I. Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.

Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

Background and Objectives: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. Materials and Methods: After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. Results: We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. Conclusions: In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.

A Review of Environmental Noise Pollution and Impacts on Human Health in Rajshahi City, Bangladesh

Noise pollution refers to excessive, unwanted, or disruptive sound in the environment. It can originate from various sources, such as road traffic, air traffic, railways, construction, using loudspeakers, industrial operations, and even household appliances. The purpose of the study was to review noise pollution and its effects on human health in Rajshahi City, Bangladesh. Most of the studies identified that the main source of noise pollution in the city is road traffic noise. The city is at a crossroads with prominent national as well as educational institutions like Rajshahi University, Rajshahi College, Varendra Museum, Bank of Padma River, Rajshahi University of Engineering and Technology, Hospital and Diagnostic Centre, BSCIC Industry, and numerous other educational institutions. All studies showed that noise pollution levels higher than the recommended acceptable limits were detected in various areas. Exposure to high levels of noise causes stress on human health, such as auditory, hearing, and nervous system damage, reducing productivity, insomnia, sexual impotency, respiratory, cardio-vascular, neurological, and outing damages, and limiting human life. It is recommended that affected sites develop a practical management approach for reducing noise pollution.

Experimental and finite element analysis of the generation mechanism of high impulse noise overpressure (caused by a recoilless weapon) at the bottom of the ear

The intense impulse noise may damage the soldiers’ hearing organs during a weapon's firing. It is essential to find out the generation mechanism of the overpressure at the bottom of the ear. The experiments of measuring the overpressure at the bottom of the ear were conducted through a rotating human head model at a recoilless weapon firing platform. The results showed that the overpressure peak at the bottom of the ear decreases with the increasing incident angle. A simulation of the test condition was developed based on the plane shock wave method. The finite element model was verified reasonably compared to the test results. The Friedlander wave propagating to the ear canal was implemented at different incident angles. The generation of the overpressure at the bottom of the ear was analyzed. According to the pressure nephograms, the impulse noise stagnated at the bottom of the ear, so the overpressure was the total pressure of impulse noise. Two parts of impulse noise entered the canal successively due to the influence of the pinna. The overpressure and Mach number at the entrance of the ear canal both decreased with increasing incident angles, resulting in impulse noise superimposed at the bottom of the ear. Investigating the generation of overpressure at the bottom of the ear under varying incident angles may have important reference value for analyzing and preventing auditory organ damage caused by impulse noise.

The Development of Speaking and Singing in Infants May Play a Role in Genomics and Dementia in Humans.

The development of the central auditory system, including the auditory cortex and other areas involved in processing sound, is shaped by genetic and environmental factors, enabling infants to learn how to speak. Before explaining hearing in humans, a short overview of auditory dysfunction is provided. Environmental factors such as exposure to sound and language can impact the development and function of the auditory system sound processing, including discerning in speech perception, singing, and language processing. Infants can hear before birth, and sound exposure sculpts their developing auditory system structure and functions. Exposing infants to singing and speaking can support their auditory and language development. In aging humans, the hippocampus and auditory nuclear centers are affected by neurodegenerative diseases such as Alzheimer's, resulting in memory and auditory processing difficulties. As the disease progresses, overt auditory nuclear center damage occurs, leading to problems in processing auditory information. In conclusion, combined memory and auditory processing difficulties significantly impact people's ability to communicate and engage with their societal essence.

The pyroptosis mechanism of ototoxicity caused by unconjugated bilirubin in neonatal hyperbilirubinemia

When activated by unconjugated bilirubin (UCB), inflammatory mediators such as IL − 18 and TNF contribute to the neurotoxicity and ototoxicity observed in severe neonatal hyperbilirubinemia. However, in cell and molecular level, the regulation and mechanism of UCB-induced ototoxicity are remained unclear. In this study, 7-day-old mammary rats were exposed to various concentrations of UCB to imitate the infant auditory damage. The auditory brainstem response result (ABR) indicated severe hearing loss, which occurred with increasing concentration. Morphological analysis of organotypic cochlear cultures treated with different concentrations of UCB indicated that auditory nerve fibers (ANF) were demyelinated and the density of spiral ganglion neurons (SGN) were decreased. In addition, HEI-OC1 cells treated with different concentrations of UCB showed severe necrosis by Flow Cytometry. The morphologic feature of pyroptosis has been observed by scanning electronic microscope. Cleaved Caspase-1, GSDMD and NLRP3 expression were significantly increased in cochlear explants with UCB-induced. To further clarify the molecular mechanism of UCB-induced inner ear cell pyroptosis, specific inhibitors of pyroptosis were applied, the protein associated with pyrotosis such as Cleaved Caspase-1, GSDMD, ASC, IL-18 and NLRP3 were significantly lower than the group with UCB alone. All the data above indicated that ERK /NLRP3/GSDMD signaling pathway involved in UCB-induced ototoxicity.

486 Molecular Mechanisms of Type II Spiral Ganglion Neuron Development

OBJECTIVES/GOALS: 30,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Understanding auditory axon guidance for spiral ganglia neurons (SGNs) will aid development of new therapies. I study role of Eph/Ephrin signaling in mediating type II SGN turning events, and how planar cell polarity (PCP) signaling modulates this process. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin 1 CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomato in a restricted number of SGNs, including type IIs. Together these lines permit SGN sparse labeling. Bulk-labeling was used for Efna3;Vangl2 double knockout (DKO) mutants. Immunostaining and confocal imaging was used to analyze dsRed in Efna3; Vangl2 and NF-200 in DKOs to quantify type II SGN turning. In combination, 3D rendering in Imaris software was used to quantify type II SGN turning, branching and other growth and navigation characteristics. 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype controls. RESULTS/ANTICIPATED RESULTS: EPHRIN-A3 is expressed on the membranes of outer pillar and Deiters’cells of the cochlear epithelium. Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error frequency of 16.9% compared to controls (n=6; p=0.05). Efna3 nulls had reduced branch number/fiber compared to controls, 4.14 and 7.22, respectively (n=129; p DISCUSSION/SIGNIFICANCE: Our results suggest that Eph/Ephrin signaling acts parallel of PCP signaling to mediate type II SGN guidance during development. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in this pathway could stimulate new outer hair cell innervation by type II SGNs following auditory damage.