Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Effects of Drilling in Mastoid Cavity over Hearing in the Contralateral Ear

In advanced otological surgeries, powered instruments form an indispensable part. The risk of deterioration to hearing in the operated ear is a commonly discussed issue, however, there remains a possibility of affecting the hearing in the contralateral ear due to transcranial vibration. So in this study we aimed to assess the possibility of the non-operated ear being affected by the noise generated during ear surgeries and whether it is temporary or permanent in nature. Methodology: This study included 63 patients diagnosed with unilateral disease who underwent mastoid surgery. Preoperatively all the patients were subjected to Pure tone audiometry (PTA), Transient evoked otoacoustic emission (TEOAE) and Distortion product otoacoustic emission (DPOAE). Patients were operated using both cutting and diamond burrs of ranging from sizes 1 - 6 mm. Total drilling time was recorded. Results: Post-operative hearing evaluation was done at 1 week, 4 weeks and 12 weeks. The sound emitted by various burrs was recorded by Sound Level Meter. Out of the total 58 patients that followed up, 46 showed change in at least one of the hearing parameters. Patients showing changes had a higher drilling time as compared to those with no changes. Of these, the changes associated with the total drilling time and with cutting burr time were found to be significant. The hearing changes seen on PTA, TEOAE and DPOAE were transient in nature with only one patient having a persistent decreased high frequency threshold at the end of 12 weeks. It was also found that cutting burrs produce more sound as compared to diamond burrs and a larger size burr of a type produces more sound than a smaller one of its type. Conclusion: The drilling of mastoid bone during ear surgeries can transiently impair the hearing in the contralateral ear which is of great significance in patients with only one hearing ear.

The potential of miR-183 family expression in inner ear for regeneration,treatment,diagnosis and prognosis of hearing loss

miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory development, maintenance, survival and function. In addition, it has potential neuroprotective effects in response to neurosensory destructive stimulations. miRNA-96 mutation causes hereditary deafness in humans and mice, and therefore affects the inner ear activity and its maintenance. Certain roles have been identified for mi R-96 in the maintenance and function of the inner ear. The comparison of the target genes of family-183 in transcriptomes of newborn and adult hair cells shows that hundreds of target genes in this family may affect development and maintenance of the ears. Identifying the genes that are regulated by miRNA-183 family provides researchers with important information about the complex development and environmental regulation of the inner ear, and can offer new approaches to the maintenance and regeneration of hair cells and auditory nerve.

Design of Floating Mass Type Piezoelectric Actuator for Implantable Middle Ear Hearing Devices

To overcome some of the problems inherent in conventional heating aids such as low gain at high fi＇equencies due to acoustic feedback, discomfort in occlusion of the extemal ear canal and so on, implantable middle ear hearing devices （IMEHDs） have been developed over the past two decades. For such kinds of IMEHDs, this paper presents the design of a floating mass piezoelectric actuator using a PMN-30%PT stack as a new type of vibrator. The proposed piezoelectric actuator consists of only three components of a piezoelectric stack, a metal case and a clamp. For the purpose of aiding the design of this actuator, a coupling biomechanics model of human middle ear and the piezoelectric actuator was constructed. This model was built based on a complete set of computerized tomography section images of a healthy volunteer＇s left ear by reverse engineering technology. The validity of this model was confirmed by comparing the motion of the tympanic membrane and stapes footplate obtained by this model with published experimental measurements on human temporal bones. It is shown that the designed actuator can be implanted on the incus long process by a simple surgical operation, and the stapes footplate displacement by its excitation at 10.5 V root-mean-square（RMS） voltage was equivalent to that from acoustic stimulation at 100 dB sound pressure level（SPL）, which is adequate stimulation to the ossicular chain. The corresponding power consumption is 0.04 mW per volt of excitation at 1 kHz, which is low enough for the transducer to be used in an implantable middle ear device.

Crystallographic texture and earing behavior analysis for different second cold reductions of double-reduction tinplate

Since the production of tinplate with non-earing properties is difficult, especially when it is produced via the double-reduction process, the optimal degree of second cold reduction is particularly important for achieving desirable drawing properties. The evolution of texture and the earing propensity of double-reduction tinplate with different extents of second reduction were investigated in this study. Optical microscopy and scanning electron microscopy were used to observe the changes in the microstructure at various extents of reduction. Two common testing methods, X-ray diffraction（XRD） and electron backscatter diffraction, were used to investigate the texture of the specimens, which revealed the effects of deformation percentage on the final texture development and the change in the grain boundary. The earing rate was determined via earing tests involving measurement of the height of any ear. The results obtained from both XRD analyses and earing tests revealed the same ideal value for the second cold reduction on the basis of the relationship between crystallographic texture and the degree of earing.

Hearing analysis in heterozygous and homozygous klotho gene deficient mice

Objective: To understand the crucial role of the klotho gene in hearing development in mouse models.Methods: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous(klotho +/-)or homozygous(klotho-/-). Mice phenotype and weight were recorded postnatal 25 days(P-25) and auditory brainstem responses(ABR) were used to determine auditory function at P-60.Results: klotho-/-mice tended to have smaller size, lighter weight and higher ABR thresholds at P-60,showing early onset age-related hearing loss(ARHL).Conclusion: Heterozygous and homozygous klotho deficient mice exhibit different degrees of hearing loss at young age, with homozygous mice(klotho-/-) showing more severe hearing loss. Our results indicate that persisted expression of klotho protein in the inner ear may potentially delay the onset of ARHL and play an important role in the protection of auditory function.

A child with severe inner ear malformations with favorable hearing utilization and balance functions after wearing hearing aids

Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recovering hearing, necessitating cochlear implants. We report a case of a 6-year-old boy with congenital deafness and bilateral inner ear malformations(right side, incomplete partition type I [IP-I]; left side, common cavity deformity). Hearing aids had a remarkable effect in this patient, enabling sufficient and favorable hearing recovery such as to allow the patient to engage in daily conversations. Per-rotatory nystagmus was recorded on an electronystagmogram for both right and left rotations in a damped rotational chair test. It is rare for deaf children with severe bilateral inner ear malformation to demonstrate favorable development in hearing and good equilibrium function. Our findings suggest that auditoryevestibular hair cells in this patient may have been partially preserved despite IP-I in the right ear and common cavity deformity of the left ear.

EFFECTS OF DIABETES ON HEARING AND COCHLEAR STRUCTURES

Diabetes mellitus (DM) is a chronic systemic disease characterized by hyperglycemia, with various patho-genic mechanisms. From absolute or relative insulin deficiency, patients with DM often demonstrate vari-ous levels of metabolic disorders. Major clinical manifestations of DM include metabolic disorders, vascu-lar lesions, circulatory disturbances and neurologic complications. Along with advances in DM research, re-ports of DM related tinnitus and hearing impairment have increased continuously. Research on DM related auditory system dysfunction has focused on cochlear microcirculation, cellular homeostasis, genetics and ag-ing. Cochlear microcirculation plays an important role in cochlear physiology and its disorders are associat-ed with many inner ear diseases. Ischemia and subsequent reperfusion seen in cochlear microcirculation dis-orders are important factors in hearing damage. Understanding cochlear microcirculation and structural as well as functional changes in DM patients with hearing loss and their causal factors will help reveal patho-genic mechanisms in diabetic hearing loss and provide new ideas in developing interventions and preventing damages caused by diabetes.

Intra-operative hearing monitoring methods in middle ear surgeries

Hearing loss is a condition affecting millions of people worldwide. Conductive hearing loss(CHL) is mainly caused by middle ear diseases.The low frequency area is the pivotal part of speech frequencies and most frequently impaired in patients with CHL. Among various treatments of CHL, middle ear surgery is efficient to improve hearing. However, variable success rates and possible needs for prolonged revision surgery still frustrate both surgeons and patients. Nowadays, increasing numbers of researchers explore various methods to monitor the efficacy of ossicular reconstruction intraoperatively, including electrocochleography(ECoch G), auditory brainstem response(ABR), auditory steady state response(ASSR), distortion product otoacoustic emissions(DPOAE), subjective whisper test, and optical coherence tomography(OCT). Here,we illustrate several methods used clinically by reviewing the literature.

Expression ofα2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss

K^(+)cycling in the cochlea is critical to maintain hearing.Many sodium-potassium pumps are proved to participate in K^(+)cycling,such as Na/K-ATPase.Theα2-Na/K-ATPase is an important isoform of Na/K-ATPase.The expression ofα2-Na/K-ATPase in the cochlea is not clear.In this study,we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR,and theα2-Na/K-ATPase expression pattern was confirmed in the inner ear.It was foundα2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging(4-,14-,26-and 48-weeks old mice).We suspected that,the down-regulation ofα2-Na/K-ATPase expression might be associated with the remodeling of K^(+)cycling,degeneration of morphological structure and decrease of hearing function in aging C57 mice.In conclusion,we speculated that the reduction ofα2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

Impact of noise on hearing in the military

Hearing plays a vital role in the performance of a soldier and is important for speech processing. Noise-induced hearing loss is a significant impairment in the military and can affect combat performance. Military personnel are constantly exposed to high levels of noise and it is not surprising that noise induced hearing loss and tinnitus remain the second most prevalent service-connected disabilities. Unfortunately, unlike civilian personnel, military personnel have little option but to remain in noisy environments in order to complete specific tasks and missions. Use of hearing protection devices and follow-up audiological tests have become the mainstay of prevention of noise-induced hearing loss. This review focuses on sources of noise within the military, pathophysiology and management of patients with noise induced hearing loss.

Comparative Study of Earing Behavior in Cold Rolled-batch Annealed and Cold Rolled-Continuous Annealed of DoubleReduced (DR) Tinplate Steels

Two double cold reduction-drawn and redrawn(DRD) tinplate steels of the same chemistries that have been processed by continuous and batch annealing line have been researched. The composition of fibers were studied through X-ray diffraction. The results indicate that a strong intensity of {114}<110> was formed in the continuous annealing steel and a strong intensity of {111}<112> was formed in the batch annealing steel; not only that but the γ fiber slowly rotated to the low angel α fiber with the angel being about 30° nearly {112}<110>texture owing to the higher second reduction.

The anatomic determinants of conductive hearing loss secondary to tympanic membrane perforation

Objectives: Recent studies have introduced middle ear volume(MEV) as a novel determinant of perforation-induced conductive hearing loss(CHL) in a mechanism driven by trans-tympanic membrane pressure differences. The primary aims of this preliminary report are to: 1) correlate CHL with perforation size; 2) describe the relationship between CHL and MEV; and 3) compare CHL across a range of cholesteatoma involvement.Design: A retrospective pilot study was performed in 31 subjects with audiometry indicative of conductive hearing loss, temporal bone CT scans,and no prior middle ear surgery. Perforation size and MEV were analyzed with respect to CHL in a cohort of 10 perforated ears with no cholesteatoma. CHLs were compared in 3 groups defined by extent of cholesteatoma involvement.Results: Ears with large and small perforations showed mean ABG values of 32.0 ± 15.7 dB and 16.0 ± 16.4 dB, respectively. A direct relationship was observed between MEV and CHL for ears with large perforations across all frequencies, whereas this relationship for small perforations was frequency-dependent. Finally, a statistically significant increase in CHL was found across ears with increasing cholesteatoma involvement at 1000 Hz(X^2(2) = 9.786, p = 0.008),2000 Hz(x^2(2) = 8.455, p = 0.015),and 4000 Hz(x^2(2)= 8.253, p = 0.016).Conclusions: These pilot data suggest that greater perforation-induced conductive hearing losses may be associated with larger perforation sizes and cholesteatoma. The correlation between MEV and CHL may require additional study.

Histone deacetylases in hearing loss: Current perspectives for therapy

Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes in many physiological processes, including chromatin remodeling,regulation of transcription, DNA repair, metabolism, genome stability and protein secretion. Recent studies indicated that HDACs are associated with the development and progression of hearing loss. Dysfunction of HDACs could promote the oxidative stress and aging in the inner ear. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of hearing loss has never been so pressing. In this review, we will summarize the reported literatures for HDACs in hearing loss and discuss how HDAC family members show different performances for the possibility of process of diseases development. The possibility of pharmacological intervention on hearing loss opens a novel path in the treatment of hearing loss.

INFLUENCE OF STRESS STATE IN EARING PREDICTION (Ⅱ) CRYSTALLOGRAPHIC ANALYSIS OF BCC METALS

The influence of stress state on earing behavior in cup drawing of BCC metals is analyzed by use of the modified Tucker method. The results show that, this influence varies with orientations, and that the earing behavior can be well predicted by the total slip model.

FLANGE EARING AND ITS CONTROL ON DEEP-DRAWING OF ANISOTROPY CIRCULAR SHEETS

The Hill's quadric anisotropy yield function and the Barlat-Lian anisotropy yield func- tion describing well anisotropy sheet metal with stronger texture are introduced into a quadric-flow cor- ner constitutive theory of elastic-plastic finite deformation suitable for deformation localization analy- sis.And then,the elastic-plastic large deformation finite element formulation based on the virtual power principle and the discrete Kirchhoff shell element model including the yield functions and the constitutive theory are established.The focus of the present research is on the numerical simulation of the flange earing of the deep-drawing of anisotropy circular sheets,based on the investigated results, the.schemes for controlling the flange earing are proposed.

Hearing loss due to urate deposition in the middle ear:A case report and literature review

Gout is the most common cause of monoarthritis in men occurring classically in the great toe and the knee.Extra-articular gout manifestations are rare.Only a few cases of head and neck urate crystals deposits have been described in the literature.Precipitations in the middle ear cause conductive hearing loss with common otoscopic anomalies and difficult imaging diagnosis.We report a case of a healthy 58-years-old man with a middle ear urate deposit causing a progressive hearing loss as the very first symptom of gout.The nature of the deposit was unsure on computer tomography(CT)due to atypical density.The final diagnosis was revealed after surgical procedure and histologic examination.A review of the literature is also presented.Seven cases of middle ear urate deposit as the first symptom of gout were found and compared.Progressive conductive hearing loss in middle-aged patients with abnormal otoscopy and middle ear atypical density mass on CT scan must lead to a minimal surgical procedure with a histologic examination to exclude urate crystals deposits.

PREDICTION OF EARING IN TEXTURED ALUMINIUM SHEETS BASED ON CRYSTAL PLASTICITY

The phenomenon of earing is investigated in the present studybased on the theory of crystal plasticity with the dynamic explicityfinite element program developed. Firstly texture analysis is carriedout of rolled aluminum alloy A15052 by means of X-ray technique. Thenfrom the texture coefficients an analytical expression for theorientation distribution function (ODF) is derived making use of thecomputer algebraic language Mathematica4.0, which makes it easier todiscretize the ODF into a series of Eulerian angles repre- sentingthe distribution of lattices and further the preferred orientation(texture) of crystals of the original she- ets.

A Case-control Study on High-risk Factors for Newborn Hearing Loss in Seven Cities of Shandong Province

To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening （UNHS） were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn＇t pass the heating screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit （NICU）, neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity （OR=16.285, 95% CI 3.379--78,481）, neonatal disease （OR=34;968, 95% CI 2.720 449.534）, family history of congenital hearing loss （OR=69.488, 95% CI 4.417--1093.300） and birth weight （OR=0.241, 95% CI 0.090--0.648）. It is concluded that parity, neonatal disease and family history of heating loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.

Complete restoration of congenital conductive hearing loss by staged surgery: A case report

BACKGROUND Stapedial tendon ossification is a rare disease,with only a few reports.The stapedial tendon originates from the apex of the pyramidal eminence and is attached to the neck of the stapes.In stapedial tendon ossification,the stapes is fixed,causing conductive hearing loss.In most cases,complete hearing restoration is achieved by dividing the stapedial tendon after exploratory tympanotomy.CASE SUMMARY A 28-year-old woman presented to our hospital with the major complaint of bilateral hearing loss that started during childhood.Exploratory tympanotomy was performed due to suspicion of otosclerosis or middle ear anomalies.We found bilateral conductive hearing loss due to stapedial tendon ossification with a middle ear anomaly during surgery.There have been several reports of complete recovery of hearing after resection of the stapedial tendon.However,in this case,recovery of hearing was insufficient,even with the division of the stapedial tendon.In the second surgery,the stapes anomaly and footplate fixation were confirmed,and hearing was completely recovered after stapedotomy.Therefore,we report this case with a review of the relevant literature.CONCLUSION This is the first case of stapedial tendon ossification and fixation of the footplate surgically diagnosed on both sides.With surgical treatment,successful results are expected.