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.

Effect of foot reflexology on an infant with sensorineural hearing loss:A case report

BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.

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Universal newborn hearing screening program in Saudi Arabia: Current insight

Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Ionically Imprinting-Based Copper(Ⅱ)Label-Free Detection for Preventing Hearing Loss

Copper is a microelement with important physiological functions in the body.However,the excess copper ion(Cu^(2+))may cause severe health problems,such as hair cell apoptosis and the resultant hearing loss.Therefore,the assay of Cu^(2+)is important.We integrate ionic imprinting technology(IIT)and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads(IIHBs)as a low-cost and high-specificity platform for Cu^(2+)detection.The IIHBs have a macroporous microstructure,uniform size,vivid structural color,and magnetic responsiveness.When incubated in solution,IIHBs recognize Cu^(2+)and exhibit a reflective peak change,thereby achieving label-free detection.In addition,benefiting from the IIT,the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100μmol·L^(-1).These features indicated that the developed IIHBs are promising candidates for Cu^(2+)detection,particularly for the prevention of hearing loss.

Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

Additional comments on foot reflexology treatment for sensorineural hearing loss in infant

Currently,treatment options for infant sensorineural hearing loss(SNHL)are limited.This article describes a novel case of SNHL in an infant successfully treated with foot reflexology,along with observed brain activity changes before and after treatment,as indicated by functional magnetic resonance imaging.Hence,this commentary discusses the case and our viewpoints regarding foot reflexology for treating SNHL.

Impact of auditory stimulation nursing protocol on auditory response in cerebrovascular stroke patients

Objectives:The objective of the study was to explore the impact of auditory stimulation protocol on auditory response in cerebrovascular stroke(CVS)patients.Materials and Methods:A pre-posttest nonequivalent control group quasi-experimental study was conducted at Al Mainal Hospital at Al Kars Einy Hospital,Cairo University,among 60 CVS patients,and the sample was randomly assigned through a coin to allocate subjects to study or control group(30 for each group).Auditory stimulation techniques were applied three times per week for the study group for two consecutive weeks.Patients in the control group received only routine hospital care during the study period.The Glasgow Coma Scale(GCS)score for assessing the neurological function and level of arousal and the auditory subscale score of Western Neuro Sensory Stimulation Profile(WNSSP)for assessing auditory response were recorded and compared between the two groups before and after the intervention.Results:There were statistically significant differences between the study group and the control group regarding third reading of GCS score(11.5±0.3 vs.10.6±0.9,t=4.676,P=0.000).The scores of all auditory subscales of WNSSP in the study groups increased after implementing the auditory stimulation protocol(P<0.05).Conclusion:Utilizing the auditory stimulation protocol by nurse proves to be an effective method for enhancing hearing responses in individuals with CVS.

Brain networks in newborns and infants with and without sensorineural hearing loss:A functional near-infrared spectroscopy study

BACKGROUND Understanding the impact of early sensory deficits on brain development is essential for understanding developmental processes and developing potential interventions.While previous studies have looked into the impact of prenatal experiences on language development,there is a lack of research on how these experiences affect early language and brain function development in individuals with sensorineural hearing loss(SNHL).AIM To investigate SNHL effects on early brain development and connectivity in 4-month-olds vs healthy newborns and controls.METHODS The research involved analyzing the functional brain networks of 65 infants,categorized into three groups:28 healthy newborns,224-month-old participants with SNHL,and 15 age-matched healthy participants.The resting-state functional connectivity was measured and compared between the groups using functional near-infrared spectroscopy and graph theory to assess the brain network properties.RESULTS Significant differences were found in resting-state functional connectivity between participants with SNHL and age-matched controls,indicating a developmental lag in brain connectivity for those with SNHL.Surprisingly,SNHL participants showed better connectivity development compared to healthy newborns,with connectivity strengths of 0.13±0.04 for SNHL,0.16±0.08 for controls,and 0.098±0.04 for newborns.Graph theory analysis revealed enhanced global brain network properties for the SNHL group,suggesting higher communication efficiency at 4 months.No significant differences were noted in network properties between 4-month-old SNHL participants and neonates.A unique pattern of central hubs was observed in the SNHL group,with 2 hubs in the left hemisphere compared to 6 in controls.CONCLUSION 4-month-old infants with SNHL have a distinct brain network pattern with efficient long-distance information transmission but less effective local communication compared to age-matched controls.

Clinical characteristics and analysis of vestibular-evoked myogenic potentials in patients with sudden sensorineural hearing loss in different ages

BACKGROUND Numerous studies have found that patients experiencing sudden sensorineural hearing loss(SSHL),with or without accompanying vertigo,often show impaired vestibular function.However,there is a dearth of studies analyzing vestibularevoked myogenic potentials(VEMPs)in SSHL patients across various age groups.AIM To investigate vestibular condition in SSHL patients across various age demographics.METHODS Clinical data of 84 SSHL patients were investigated retrospectively.Audiometry,cervical vestibular evoked myogenic potentials(c-VEMPs),and ocular vestibular evoked myogenic potentials(o-VEMPs)were conducted on these patients.Parameters assessed included the latencies of P1 and N1 waves,as well as the amplitudes of P1–N1 waves.Moreover,the study evaluated the influence of factors such as sex,affected side,configuration of hearing loss,and presence of accompanying vertigo.RESULTS Among the 84 SSHL patients,no significant differences were observed among the three groups in terms of gender,affected side,and the presence or absence of vertigo.Group II(aged 41–60 years)had the highest number of SSHL cases.The rates of absent o-VEMPs in the affected ears were 20.83%,31.58%,and 22.72%for the three age groups,respectively,with no statistically significant difference among them.The rates of absent c-VEMPs in the affected ears were 8.3%,34.21%,and 18.18%for the three age groups,respectively,with significant differences.In the unaffected ears,there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups.In the three age groups,no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1–P1 waves for c-VEMPs and o-VEMPs,either on the affected side or on the unaffected side,across the three age groups.CONCLUSION The extraction rate of VEMPs is more valuable than parameters.Regardless of the presence of vertigo,vestibular organs are involved in SSHL.Notably,SSHL patients aged 41–60 appear more susceptible to damage to the inferior vestibular nerve and saccule.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid-to high-frequency sudden sensorineural hearing loss

BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.

Navigating Silence: A Comprehensive Review of Parental Roles in the Rehabilitation of Children with Hearing Loss

This narrative literature review delves into the multifaceted realm of parental involvement in the rehabilitation of children with permanent hearing loss. While existing research has made strides in elucidating parental roles in this context, critical gaps persist, necessitating a comprehensive exploration to inform future endeavors. Our review synthesizes a wide array of studies, identifying these gaps and emphasizing the significance of addressing them. Themes emerging from the literature include the varying degrees of parental engagement, the impact of cultural and socio-economic factors, and the challenges faced by families navigating rehabilitation processes. The synthesis of this literature not only highlights the current state of knowledge but also provides a roadmap for future research efforts. By addressing these gaps, we aim to contribute to a more nuanced understanding of parental involvement in the rehabilitation of children with permanent hearing loss, ultimately fostering improved support systems and holistic care for affected families.

Endoscopic push through tragal cartilage tympanoplasty: A 10-year retrospective review of our technique and outcomes

BACKGROUND Endoscopic ear surgery(EES)provides a magnified,high-definition view of the otological surgical field.EES allows otologists to avoid surgical incisions and associated postoperative complications.It is an ideal technique for the perfor-mance and teaching of tympanoplasty.AIM To examine the efficacy of total Endoscopic Push Through Tragal Cartilage Tympanoplasty(EPTTCT),at our institution over a 10-year period.METHODS A retrospective analysis of 168 cases of EPTTCT for closure of small to medium tympanic membrane perforations from 2013-2023 was conducted.Patient sex,age range(pediatric vs adult),etiology of injury,success rate,complications,and postoperative hearing status were collected.RESULTS Graft uptake results indicated success in 94%of patients,with less than a 2%complication rate.Postoperative pure tone audiometry demonstrated hearing status improvement in 69%of patients.CONCLUSION EPTTCT has been shown to be effective in tympanic membrane perforation closures with minimal complications.This study further demonstrates the efficacy and safety of these procedures in a single-center review.

Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

耳内窥镜下鼓膜置管联合腺样体切除术与鼓膜穿刺治疗分泌性中耳炎患儿的临床疗效比较

目的探讨耳内窥镜下鼓膜置管联合腺样体切除术治疗分泌性中耳炎(OME)患儿的临床疗效。方法选取2021年1月~2022年3月SOM患儿120例,按术式分为穿刺组(n=60)和置管组(n=60),穿刺组给予耳内窥镜下鼓膜穿刺联合腺样体切除术,置管组给予耳内窥镜下鼓膜置管联合腺样体切除术,比较两组积液消退时间、听觉脑干诱发电位(ABR)阈值、ABRⅠ波潜伏期、干扰素γ(IFN-γ)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、治疗效果以及并发症。结果置管组积液消退时间显著低于穿刺组,差异有统计学意义(P<0.05);穿刺组和置管组术后ABR、ABRⅠ波潜伏期、IFN-γ、IL-6和TNF-α均显著低于术前(P均<0.05);置管组术后ABR、ABRⅠ波潜伏期、IFN-γ、IL-6和TNF-α均显著低于穿刺组,差异有统计学意义(P均<0.05);置管组治疗有效率显著高于穿刺组,差异有统计学意义(P<0.05);置管组并发症发生率显著低于穿刺组,差异有统计学意义(P<0.05)。结论耳内窥镜下鼓膜置管联合腺样体切除术可有效改善SOM患儿听力及炎症,有利于提高疗效,且可减少并发症,值得临床推广。

Social Effects of Hearing Loss on Patients in Jos, North Central Nigeria

Hearing loss has caused serious social effects among people living with it. Those who relate to patients with hearing loss (PHL) also share some part of the negative effects. Some specifics are communication disability, which impacts speech and language development, academic performance, and social or work life. In previous years, the problem was predicted to be aggravated as the expected life span of the population increased. The study was conducted among PHL and their family members in JUTH and Kazahyet Audiology Service in Jos. 150 PHL were purposively sampled. The study was guided by a Cross-sectional Survey Research Design, and the specific objectives were to (1) identify the social effects of hearing loss on the PHL, (2) determine the implication of social effects on PHL, and (3) determine the extent at which these social effects affect PHL. The outcome of the study shows that the social effects faced by PHL are poor relationships, no secrets, dependence on sign language, frustration, depression, and dependence on lip reading. Some stop schooling, and others feel laughed at and therefore choose the path of isolation. The implication is that hearing loss is expensive to manage. PHL always feel they are not contributing their quarter in life as usual;they feel stigmatized and are not easy to relate with. The study recommends that the government should come up with policies that will check man-made behaviors that exert negative social effects on PHL in our society, subsidize the cost of hearing aids and cochlear implants to be affordable for PHL, formulate a policy on mandatory newborn hearing screening before the infant is discharged from the hospital to help in the early identification of hearing loss. Finally, the early creation of awareness of the dangers or consequences of hearing loss will go a long way in preventing our society from involvement in high-risk behaviors that will cause hearing loss.