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COVID-19, caused by a novel coronavirus, is a persistent global pandemic. It is crucial to examine existing reports to effectively summarize and characterize its clinical course. We used a large-scale meta-analysis to establish prevalence rates for loss of olfaction and gustation in COVID-19 positive patients. PubMed/Medline, Embase, and Web of Sciences were searched for articles published until April 30, 2020. Furthermore, to avoid missing papers, more searches were carried out in the reference lists of covered studies. Articles that mentioned olfactory and/or gustatory disorder in patients with COVID-19 were included for further analysis. Articles that did not report the aforementioned information were excluded. Duplicated articles, reviews, and meta-analysis were excluded as well. The quality of the references was assessed according to the checklist provided by JBI (Joanna Briggs Institute). We used independent extraction of data by multiple observers. The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. The main outcome measures reported were the pooled frequency of olfaction and pooled frequency of gustation disorder in patients with COVID-19 calculated using a random effect model weighted by the study population. The 15 included studies had 3,739 participants which all had confirmed COVID-19. Olfactory and gustatory disorders were assessed and a total number of 1,354 and 1,729 were reported to have taste or smell impairment, respectively. The estimated rate of taste disorder in patients with COVID-19 was 49.0% [95% confidence interval (CI) 34.0-64.0, I2: 96%] (Figure 2). The estimated rate of olfactory disorder in patients with COVID-19 was 61.0% (95% CI 44.0%-75.0%). Our meta-analysis demonstrated high rates of taste (49.0%) and smell (61.0%) disorders in patients with confirmed COVID-19. Results increase the power of recent reports-loss of olfactory and loss of gustation should now routinely be considered in the setting of COVID-19 infection., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

The use and utility of cochlear implantation has rapidly increased in recent years as technological advances in the field have expanded both the efficacy and eligible patient population for implantation. This review aims to serve as a general overview of the most common hearing disorders that have favorable auditory outcomes with cochlear implants (CI). Hearing loss in children caused by congenital cytomegalovirus infection, syndromic conditions including Pendred Syndrome, and non-syndromic genetic conditions such as hearing impairment associated with GJB2 mutations have shown to be successfully managed by CI. Furthermore, cochlear implantation provides the auditory rehabilitation for the most common etiology of hearing loss in adults and age-related hearing loss (ARHL) or presbycusis. However, in some cases, cochlear implantation have been associated with some challenges. Regarding implantation in children, studies have shown that sometimes parents seem to have unrealistic expectations regarding the ability of CI to provide auditory rehabilitation and speech improvement. Given the evidence revealing the beneficial effects of early intervention via CI in individuals with hearing disorders especially hearing loss due to genetic etiology, early auditory and genetic screening efforts may yield better clinical outcomes. There is a need to better understand genotype-phenotype correlations and CI outcome, so that effective genetic counseling and successful treatment strategies can be developed at the appropriate time for hearing impaired individuals., (Copyright © 2020 Eshraghi, Polineni, Davies, Shahal, Mittal, Al-Zaghal, Sinha, Jindal and Mittal.)

Cochlear implants (CIs) are widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, insertion of electrode leads to inner trauma and activation of inflammatory and apoptotic signaling cascades resulting in loss of residual hearing in implanted individuals. Pharmaceutical interventions that can target these signaling cascades hold great potential for preserving residual hearing by preventing sensory cell damage. Bile salts have shown efficacy in various regions of the body as powerful antioxidants and anti-inflammatory agents. However, their efficacy against inner ear trauma has never been explored. The objective of this study was to determine whether taurodeoxycholic acid (TDCA), a bile salt derivative, can prevent sensory cell damage employing an in vitro model of electrode insertion trauma (EIT). The organ of Corti (OC) explants were dissected from postnatal day 3 (P-3) rats and placed in serum-free media. Explants were divided into control and experimental groups: (1) untreated controls; (2) EIT; (3) EIT+ TDCA (different concentrations). Hair cell (HC) density, analyses of apoptosis pathway (cleaved caspase 3), levels of reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) activity and Mitochondrial Membrane Potential (MMP) were assayed. Treatment with TDCA provided significant otoprotection against HC loss in a dose-dependent manner. The molecular mechanisms underlying otoprotection involved decreasing oxidative stress, lowering levels of iNOS, and abrogating generation of cleaved caspase 3. The results of the present study suggest that TDCA provides efficient otoprotection against EIT, in vitro and should be explored for developing pharmaceutical interventions to preserve residual hearing post-cochlear implantation., (Copyright © 2020 Shah, Mittal, Shahal, Sinha, Bulut, Mittal and Eshraghi.)

Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder with considerable clinical heterogeneity. With no cure for the disorder, treatments commonly center around speech and behavioral therapies to improve the characteristic social, behavioral, and communicative symptoms of ASD. Gastrointestinal disturbances are commonly encountered comorbidities that are thought to be not only another symptom of ASD but to also play an active role in modulating the expression of social and behavioral symptoms. Therefore, nutritional interventions are used by a majority of those with ASD both with and without clinical supervision to alleviate gastrointestinal and behavioral symptoms. Despite a considerable interest in dietary interventions, no consensus exists regarding optimal nutritional therapy. Thus, patients and physicians are left to choose from a myriad of dietary protocols. This review, summarizes the state of the current clinical and experimental literature on nutritional interventions for ASD, including gluten-free and casein-free, ketogenic, and specific carbohydrate diets, as well as probiotics, polyunsaturated fatty acids, and dietary supplements (vitamins A, C, B6, and B12; magnesium and folate)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

Background: Electrode insertion trauma (EIT) during cochlear implantation (CI) can cause loss of residual hearing. L-N-acetylcysteine (L-NAC) and dexamethasone (Dex) have been individually shown to provide otoprotection albeit at higher concentrations that may be associated with adverse effects. Objective/Aims: The aim of this study is to determine whether L-NAC and Dex could be combined to decrease their effective dosage., Materials and Methods: The organ of Corti (OC) explants were divided into various groups: 1) control; 2) EIT; 3) EIT treated with different concentrations of Dex; 4) EIT treated with different concentrations of L-NAC; 5) EIT treated with L-NAC and Dex in combination. Hair cell (HC) density, levels of oxidative stress, proinflammatory cytokines and nitric oxide (NO) was determined., Results: There was a significant loss of HCs in explants subjected to EIT compared to the control group. L-NAC and Dex in combination was able to provide significant otoprotection at lower concentrations compared to individual drugs., Conclusions and Significance: A combination containing L-NAC and Dex is effective in protecting sensory cells at lower protective doses than each compound separately. These compounds can be combined allowing a decrease of potential side effects of each compound and providing significant otoprotection for EIT.

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti-inflammatory, anti-apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non-surgical administration of rodent bone marrow derived MSCs (BM-MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM-MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM-MSCs administrated rats. The results of this study suggest that transtympanic administration of BM-MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487-493, 2020. © 2019 American Association for Anatomy., (© 2019 Wiley Periodicals, Inc.)

Noise-induced hearing loss (NIHL) poses a significant burden on not only the economics of health care but also the quality of life of an individual, as we approach an unprecedented age of longevity. In this article, we will delineate the current landscape of management of NIHL. We discuss the most recent results from in vitro and in vivo studies that determine the effectiveness of established pharmacotherapy such as corticosteroid and potential emerging therapies like N-acetyl cysteine and neurotrophins (NTs), as well as highlight ongoing clinical trials for these therapeutic agents. We present an overview of how the recent advancements in the field of gene-based and stem cell-based therapies can help in developing effective therapeutic strategies for NIHL. Gene-based therapies have shown exciting results demonstrating cochlear cellular regeneration using Atoh1, NRF2 as well as NT gene therapy employing viral vectors. In addition, we will discuss the recent advancements in genome-editing technologies, such as CRISPR/Cas9, and its potential role in NIHL therapy. We will further discuss the current state of stem cell therapy as it pertains to treating neurodegenerative conditions including NIHL. Embryonic stem cells, adult-derived stem cells, and induced pluripotent stem cells all represent an enticing reservoir of replacing damaged cells as a result of NIHL. Finally, we will discuss the barriers that need to be overcome to translate these promising treatment modalities to the clinical practice in pursuit of improving quality of life of patients having NIHL. Anat Rec, 303:516-526, 2020. © 2019 American Association for Anatomy., (© 2019 Wiley Periodicals, Inc.)

Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focussed on highly specific viral vector designs, plasmid transfection, nanoparticles, polymer-mediated gene delivery, engineered microRNA and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapeutics. These advanced techniques have profound applications in treating highly prevalent neurological diseases and neurodevelopmental disorders including Parkinson's disease, Alzheimer's disease and autism spectrum disorder, as well as rarer diseases such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, lysosomal storage diseases, X-linked adrenoleukodystrophy and oncological diseases. In this article, we present an overview of the latest advances in targeted gene delivery and discuss the challenges and future direction of gene therapy in the treatment of neurological disorders.

Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere's disease, noise-induced hearing loss, autoimmune hearing loss or hearing loss from exposure to ototoxic substances can benefit from delivery of otoprotective drugs to the inner ear. However, systemic drug delivery through oral, intravenous and intramuscular methods leads to undesirable side effects due to the inner ear's limited blood supply and the relatively poor penetration of the blood-inner ear barrier (BLB). Therefore, there has been an increased interest for the targeted drug delivery to the inner ear using nanoparticles. Drug delivery through nanoparticles offers several advantages including drug stabilization for controlled release and surface modification for specific targeting. Understanding the biocompatibility of nanoparticles with cochlea and developing novel non-invasive delivery methods will promote the translation of nanoparticle-mediated drug delivery for auditory disorders from bench to bedside.

Cochlear implantation (CI) is now widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, CI can lead to electrode insertion trauma (EIT) that can cause damage to sensory cells in the inner ear resulting in loss of residual hearing. Even with soft surgical techniques where there is minimal macroscopic damage, we can still observe the generation of molecular events that may initiate programmed cell death via various mechanisms such as oxidative stress, the release of pro-inflammatory cytokines, and activation of the caspase pathway. In addition, individuals with CI may be exposed to noise trauma (NT) due to occupation and leisure activities that may affect their hearing ability. Recently, there has been an increased interest in the auditory community to determine the efficacy of drug-eluting electrodes for the protection of residual hearing. The objective of this study is to determine the effect of NT on implanted cochlea as well as the otoprotective efficacy of dexamethasone eluting electrode to implanted cochlea exposed to NT in a guinea pig model of CI. Animals were divided into five groups: EIT with dexamethasone eluting electrode exposed to NT; EIT exposed to NT; NT only; EIT only and naïve animals (control group). The hearing thresholds were determined by auditory brainstem recordings (ABRs). The cochlea was harvested and analyzed for transcript levels of inflammation, apoptosis and fibrosis genes. We observed that threshold shifts were significantly higher in EIT, NT or EIT + NT groups compared to naive animals at all the tested frequencies. The dexamethasone eluting electrode led to a significant decrease in hearing threshold shifts in implanted animals exposed to NT. Proapoptotic tumor necrosis factor-α [TNF-α, TNF-α receptor 1a (TNFαR1a)] and pro-fibrotic transforming growth factor β1 (TGFβ) genes were more than two-fold up-regulated following EIT and EIT + NT compared to the control group. The use of dexamethasone releasing electrode significantly decreased the transcript levels of pro-apoptotic and pro-fibrotic genes. The dexamethasone releasing electrode has shown promising results for hearing protection in implanted animals exposed to NT. The results of this study suggest that dexamethasone releasing electrode holds great potential in developing effective treatment modalities for NT in the implanted cochlea., (Copyright © 2019 Eshraghi, Wolfovitz, Yilmazer, Garnham, Yilmazer, Bas, Ashman, Roell, Bohorquez, Mittal, Hessler, Sieber and Mittal.)

Objective  In the management of facial nerve schwannoma (FNS), surgical tumor resection is now often being replaced with more conservative approaches, such as observation with serial imaging or stereotactic radiosurgery (SRS). Given the scarcity of these lesions, determining the optimal management of FNS remains challenging and subject of debate with multiple treatment approaches supported in the literature. Methods  A retrospective chart review was performed in two academic centers for patients diagnosed with FNS between 1996 and 2017. The clinical presentation, treatment modalities employed, tumor control rates, and facial nerve function (FNF) outcomes (House-Brackmann system) were assessed and analyzed. Results  The study comprised 50 adult patients. Initial treatment modalities included observation with serial clinicoradiologic review in 27 patients (54%), surgery in 17 patients (34%), and SRS in 6 patients (12%). The FNF were decreased in more than half of the patients who had surgery. Nonetheless, more than 80% of the patients who were initially managed with observation or SRS had stable or improved FNF. Conclusion  A prevailing trend toward more conservative treatment modalities for FNS has evolved over time, providing relatively long-term preservation of FNF. As there are multiple management options available, it is of paramount importance that the treating physician be familiar with all treatment modalities and outcomes and counsel patients appropriately. The surgery should be reserved for large tumors and poor FNF at initial presentation or follow-up while watchful observation with imaging is the treatment of choice for rest of the patients.

Objective: To develop a clinical consensus statement on the use of balloon dilation of the eustachian tube (BDET)., Methods: An expert panel of otolaryngologists was assembled with nominated representatives of general otolaryngology and relevant subspecialty societies. The target population was adults 18 years or older who are candidates for BDET because of obstructive eustachian tube dysfunction (OETD) in 1 or both ears for 3 months or longer that significantly affects quality of life or functional health status. A modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus., Results: After 3 iterative Delphi method surveys, 28 statements met the predefined criteria for consensus, while 28 statements did not. The clinical statements were grouped into 3 categories for the purposes of presentation and discussion: (1) patient criteria, (2) perioperative considerations, and (3) outcomes., Conclusion: This panel reached consensus on several statements that clarify diagnosis and perioperative management of OETD. Lack of consensus on other statements likely reflects knowledge gaps regarding the role of BDET in managing OETD. Expert panel consensus may provide helpful information for the otolaryngologist considering the use of BDET for the management of patients with OETD.

Objective: Tinnitus is the perception of sound in the ears or head without any external or internal acoustic stimulation, and it is usually associated with hearing loss. In addition, it has been reported that there is a relationship between vestibular problems and sensorineural hearing loss. The aim of this study was to evaluate the vestibular function in patients with tinnitus without hearing loss., Methods: A total of 32 patients who complained only of tinnitus without hearing loss and 30 control subjects without tinnitus or hearing loss were included in this study. Oculomotor and caloric tests were performed on all subjects with videonystagmography. The tinnitus handicap inventory questionnaire, side and duration of tinnitus were recorded in all patients., Results: The caloric test was abnormal in 13 of 32 (40.6%) patients in the tinnitus group and was normal in all of the control group. Abnormal caloric responses in patients with severe tinnitus were more frequent than in patients with mild or moderate tinnitus. There was a statistically significant difference in the optokinetic gain values between the tinnitus and control groups., Conclusion: A relationship between tinnitus and abnormal caloric responses was determined. Tinnitus may be the first symptom of vestibular dysfunction.

Background: Precise techniques to find the facial nerve (FN) and recess are lacking., Objectives: We aimed to define incus-spine and incus-FN angles which can be used to localize the FN and recess during mastoidectomy., Material and Methods: Thirty adult cadaveric temporal bones were studied. Canal-wall up mastoidectomy with a facial recess approach was performed. The temporal bones and microscope were positioned differently to change the visual angle. The following distances were measured: (1) Short process of the incus (SPI)-FN; (2) Body of the incus-FN. Photographs were taken. Three lines were drawn on the photographs between the SPI, FN, and the spine of Henle. The angles were created and measured., Results: Three of the temporal bones were excluded due to the absence of the spine of Henle and two of them due to the displacement of the SPI. The mean of the incus-spine angle in 25 temporal bones was 90.12° and the mean of the Incus-FN angle was 135.96°. The mean distances of the SPI-FN and body of incus-FN were 4.85 and 9.26 mm, respectively., Conclusions and Significance: The incus-spine and the incus-FN angles along with the distances can help localize the FN and recess.

There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The etiology and the underlying pathogenetic mechanisms of autism spectrum disorders are still largely unknown. This article provides a comprehensive review of the studies that are relevant to autism spectrum disorders and central auditory processing disorders and also discusses the relationship between autism spectrum disorders and central auditory processing disorders in the light of recent studies on this subject, which may provide new pathways in a therapeutic perspective. Several studies confirm that most of the individuals with an autism spectrum disorder have some degree of sensory dysfunction related to disorders of processing auditory, visual, vestibular, and/or tactile stimuli. Among these studies, some have addressed central auditory processing disorders. There is an increasing amount of effort for studies regarding the link between autism spectrum disorders and central auditory processing disorders. Most of the studies investigating central auditory processing disorders in patients with autism spectrum disorders have used electrophysiological measurements such as mismatch negativity and P300 event-related potentials. In addition to these, several studies have reported deterioration in speech perception and expression in patients with autism spectrum disorders, which may also be related to central auditory processing disorders in this unique group of individuals.

Currently, 1 out of every 59 children in the United States is diagnosed with autism. While initial research to find the possible causes for autism were mostly focused on the genome, more recent studies indicate a significant role for epigenetic regulation of gene expression and the microbiome. In this review article, we examine the connections between early disruption of the developing microbiome and gastrointestinal tract function, with particular regard to susceptibility to autism. The biological mechanisms that accompany individuals with autism are reviewed in this manuscript including immune system dysregulation, inflammation, oxidative stress, metabolic and methylation abnormalities as well as gastrointestinal distress. We propose that these autism-associated biological mechanisms may be caused and/or sustained by dysbiosis, an alteration to the composition of resident commensal communities relative to the community found in healthy individuals and its redox and epigenetic consequences, changes that in part can be due to early use and over-use of antibiotics across generations. Further studies are warranted to clarify the contribution of oxidative stress and gut microbiome in the pathophysiology of autism. A better understanding of the microbiome and gastrointestinal tract in relation to autism will provide promising new opportunities to develop novel treatment modalities.

Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined., Design: Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed., Results: l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001)., Conclusions: l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

The current advancements in otosclerosis therapy cannot be fully appreciated without studying the history, rediscovery, and modification of a once-forgotten procedure. The evolution of stapes surgery can be best summarized into 4 noteworthy eras: the preantibiotic era (which was forgotten and then rediscovered), the fenestration era (mainstreamed by Julius Lempert), the mobilization era (led by Samuel Rosen), and the modern stapedectomy era (revived and revolutionized by John Shea). Each era is unique with its own challenges and ingenious techniques to overcome what used to be among the leading causes of deafness., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Diagnosis and treatment of advanced otosclerosis can be controversial. In 1961, House and Sheehy defined advanced otosclerosis as hearing loss in air conduction threshold by 85 dB with nonmeasurable bone conduction. Recently, the definition of advanced otosclerosis is mostly based on the decrease of speech recognition. There are some treatment modalities: stapes surgery and hearing aids, cochlear implantation, or direct acoustic cochlear implant. The authors propose a new algorithm for treatment. If the patient is treated with cochlear implantation, the surgeon should be cautious for facial nerve stimulation after surgery because it is the most prevalent complication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The use of stem cells in cell-based therapy is an emerging concept for the treatment of ear disorders. Tympanic membrane perforation (TMP) and inner ear disorders are some of the most commonly presented otologic disorders that can benefit from advances in cell-based therapy. Studies have already demonstrated that stem cell-based therapy can potentially be an effective treatment modality for acute and chronic TMP. Recent studies have also shown promise in application of cell-based approach to treat inner ear dysfunction. In this perspective, we will discuss the recent advancements regarding the use of cell-based therapy for ear disorders., (© 2017 Wiley Periodicals, Inc.)

Hearing loss (HL) is a common sensory impairment in humans, with significant economic and social impacts. With nearly 20% of the world's population, China has focused on economic development and health awareness to improve the care for its hearing-impaired population. Recently, the Chinese government has initiated national programs such as the China Disabled Persons Federation to fund prevention, treatment, and rehabilitation of hearing impairment. Newborn hearing screening and auditory rehabilitation programs in China have expanded exponentially with government support. While facing many challenges and overcoming obstacles, cochlear implantation (CI) programs in China have also experienced considerable growth. This review discusses the implementation of CI programs for HL in China and presents current HL data including epidemiology, newborn hearing screening, and determination of genetic etiologies. Sharing the experience in Chinese auditory rehabilitation and CI programs will shine a light on the developmental pathway of healthcare infrastructure to meet emerging needs of the hearing-impaired population in other developing countries.

Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Neurosensory responses of hearing and balance are mediated by receptors in specialized neuroepithelial sensory cells. Any disruption of the biochemical and molecular pathways that facilitate these responses can result in severe deficits, including hearing loss and vestibular dysfunction. Hearing is affected by both environmental and genetic factors, with impairment of auditory function being the most common neurosensory disorder affecting 1 in 500 newborns, as well as having an impact on the majority of elderly population. Damage to auditory sensory cells is not reversible, and if sufficient damage and cell death have taken place, the resultant deficit may lead to permanent deafness. Cochlear implants are considered to be one of the most successful and consistent treatments for deaf patients, but only offer limited recovery at the expense of loss of residual hearing. Recently there has been an increased interest in the auditory research community to explore the regeneration of mammalian auditory hair cells and restoration of their function. In this review article, we examine a variety of recent therapies, including genetic, stem cell and molecular therapies as well as discussing progress being made in genome editing strategies as applied to the restoration of hearing function.

Conclusions: This study recommends using soft surgical principal and round window insertion to protect residual hearing with favorable anatomical exposure. Further studies are needed to evaluate the impact of the electrical stimulation on the organ of corti and hearing., Objective: The objective of this study is to analyze various factors that impact on preservation of residual hearing post-implantation., Methods: A retrospective study was performed to analyze loss of residual hearing in a cohort of 225 patients implanted in a large academic center. Sixty-four patients met the inclusion criteria. The impact of age at implantation, gender, etiology of hearing loss, cochleostomy vs round window insertion, partial vs full insertion, and effect of initial stimulation were analyzed using appropriate statistical analysis., Results: The overall hearing preservation rate for all implanted patients was 64%. Loss of residual hearing was significantly more observed in cases of cochleostomy and/or non-soft surgical techniques. No correlation was observed with age at implantation, gender, side of implant, device manufacturer, and presence of pre-lingual deafness vs post-lingual, full or partial electrode insertion. In addition, there was a small but significant decrease in hearing between pre-stimulation and post-stimulation audiograms at 6000 Hz.

Ear is a complex system where appropriate ionic composition is essential for maintaining the tissue homeostasis and hearing function. Ion transporters and channels present in the auditory system plays a crucial role in maintaining proper ionic composition in the ear. The extracellular fluid, called endolymph, found in the cochlea of the mammalian inner ear is particularly unique due to its electrochemical properties. At an endocochlear potential of about +80 mV, signaling initiated by acoustic stimuli at the level of the hair cells is dependent on the unusually high potassium (K + ) concentration of endolymph. There are ion channels and transporters that exists in the ear to ensure that K + is continually being cycled into the stria media endolymph. This review is focused on the discussion of the molecular and genetic basis of previously and newly recognized ion channels and transporters that support sensory hair cell excitation based on recent knock-in and knock-out studies of these channels. This article also addresses the molecular and genetic defects and the pathophysiology behind Meniere's disease as well as how the dysregulation of these ion transporters can result in severe defects in hearing or even deafness. Understanding the role of ion channels and transporters in the auditory system will facilitate in designing effective treatment modalities against ear disorders including Meniere's disease and hearing loss. J. Cell. Physiol. 232: 743-758, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cholesterol granulomas (CGs) are the most common benign lesions of the petrous apex (PA) and have distinct computed tomography (CT) and magnetic resonance imaging (MRI) characteristics. On CT, CGs of the PA (PACG) present as expansile lesions with erosion of bony trabeculae. MRI shows a hyperintense lesion on T1-and T2-weighted images and do not enhance with gadolinium. The objective is to describe the radiographic features of CGs of the skull base that do not arise from the PA. This study is a retrospective review. Three patients were operated on for suspected recurrent endolymphatic sac tumor, intracranial cholesteatoma, and recurrent sphenoid wing meningioma based on CT and MRI findings. Pathology results were consistent with CG in all three cases. All patients had bone erosion on CT. These skull base CGs did not demonstrate similar MRI features. These lesions were hyperintense, iso-to-hyperintense, and hypointense on T1-weighted MRI, respectively. These CGs were hyperintense in two cases and iso-to-hyperintense in one case on T2-weighted MRI. These lesions either demonstrated central or rim enhancement after gadolinium administration. Skull base CGs that do not arise from the PA demonstrate a broad spectrum of radiographic characteristics on MRI that are not typical of PACG.

Unlabelled: Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups., Control Group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cells in vitro. Their combination provided close to 96% protection, demonstrating an additive effect.

Objectives: To evaluate the prevalence of tinnitus and hyperacusis in individuals with Asperger's Syndrome (AS)., Methods: A home-developed case-history survey and three item-weighted questionnaires: Tinnitus Reaction Questionnaire (TRQ), Tinnitus Handicap Inventory (THI), and the Hyperacusis Questionnaire (HQ) were employed. These tools categorize the subjective response to tinnitus and hyperacusis. The research tools were mailed to a mailing list of individuals with Asperger's Syndrome., Results: A total of 55 subjects diagnosed with AS were included in the analysis (15.5% response rate). Sixty-nine percent of all respondents (38/55) reported hyperacusis with an average HQ score of 20.7. Furthermore, 35% (19/55) reported perceiving tinnitus with average scores of 27 for the TRQ and 23 for the THI. Thirty-one percent (17/55) reported both hyperacusis and tinnitus. The prevalence of hyperacusis in the AS respondents remained relatively constant across age groups., Conclusions: Hyperacusis and tinnitus are more prevalent in the ASD population subgroup diagnosed with AS under DSM-IV criteria than in the general public. Hyperacusis also appears to be more prevalent in the AS population than in the ASD population at large. Future research is warranted to provide insight into the possible correlation between tinnitus and hyperacusis symptoms and the abnormal social interactions observed in this group., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval window of the inner ear, causing conductive hearing loss. In addition, the inflammatory mediators generated during CSOM can penetrate into the inner ear through the round window. This can cause the loss of hair cells in the cochlea, leading to sensorineural hearing loss. Pseudomonas aeruginosa and Staphylococcus aureus are the most predominant pathogens that cause CSOM. Although the pathogenesis of AOM is well studied, very limited research is available in relation to CSOM. With the emergence of antibiotic resistance as well as the ototoxicity of antibiotics and the potential risks of surgery, there is an urgent need to develop effective therapeutic strategies against CSOM. This warrants understanding the role of host immunity in CSOM and how the bacteria evade these potent immune responses. Understanding the molecular mechanisms leading to CSOM will help in designing novel treatment modalities against the disease and hence preventing the hearing loss.

Hypothesis: Dexamethasone (DXM) protects against cisplatin-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants in vitro by reducing levels of oxidative stress and NADPH-Oxidase-3 (NOX-3)., Background: Intratympanic DXM has demonstrated protective effects against cisplatin-induced hearing loss in a few animal studies and one clinical trial. However, levels of protection with intratympanic DXM vary significantly between studies, which may not be a result of the intrinsic properties of DXM but rather reflect the diffusion of DXM into the cochlea. The molecular mechanisms and degree of DXM protection against cisplatin ototoxicity are currently unknown., Methods: OC explants from 3-day-old rats were cultured with no treatment or various concentrations of cisplatin (2, 5, or 10 μM) and DXM (75, 150, or 300 μg/mL) in vitro. HC viability and TUNEL assay were performed after 72 hours in vitro and levels of oxidative stress and NOX-3 were evaluated with confocal microscopy after 48 hours in vitro. Analysis of variance with Tukey's post hoc testing was performed., Results: Cisplatin initiated dose-dependent losses of outer HCs (OHCs) in the basal turns of exposed explants (p < 0.001). DXM protected against cisplatin (2 μM)-induced OHC loss in a dose-dependent manner with complete protection at 300 μg/mL of DXM (p < 0.001). DXM (150 μg/mL) significantly reduced levels of oxidative stress, NOX-3, and apoptosis in the basal turn of explants exposed to cisplatin (2 μM)., Conclusions: DXM protects against cisplatin-induced loss of OHCs in the basal turn of rat OC explants as demonstrated by reductions in oxidative stress and NOX-3 production and decreased levels of apoptotic cell death.

Objective: To assess the outcome of cochlear implantation in children with autism spectrum disorder (ASD)., Study Design: Retrospective case review and survey., Setting: Tertiary referral center., Patients: Children who meet criteria for cochlear implantation and diagnosis of ASD., Main Outcome Measures: Receptive and expressive language scores and parental survey data., Results: Fifteen patients with history of ASD and cochlear implantation were analyzed and compared with 15 patients who received cochlear implant and have no other disability. Postoperatively, more than 67% of children with ASD significantly improved their speech perception skills, and 60% significantly improved their speech expression skills, whereas all patients in the control group showed significant improvement in both aspects. The top 3 reported improvements after cochlear implantation were name recognition, response to verbal requests, and enjoyment of music. Of all behavioral aspects, the use of eye contact was the least improved. Survey results in regard to improvements in patient interaction were more subtle when compared with those related to sound and speech perception. The most improved aspects in the ASD patients' lives after cochlear implantation seemed to be attending to other people's requests and conforming to family routines. Of note, awareness of the child's environment is the most highly ranked improvement attributed to the cochlear implant., Conclusion: Cochlear implants are effective and beneficial for hearing impaired members of the ASD population, although development of language may lag behind that of implanted children with no additional disabilities. Significant speech perception and overall behavior improvement are noted.

Conservation of a patient's residual hearing and prevention of fibrous tissue/new bone formation around an electrode array are some of the major challenges in cochlear implant (CI) surgery. Although it is well-known that fibrotic tissue formation around the electrode array can interfere with hearing performance in implanted patients, and that associated intracochlear inflammation can initiate loss of residual hearing, little is known about the molecular and cellular mechanisms that promote this response in the cochlea. In vitro studies in neonatal rats and in vivo studies in adult mice were performed to gain insight into the pro-inflammatory, proliferative, and remodeling phases of pathological wound healing that occur in the cochlea following an electrode analog insertion. Resident Schwann cells (SC), macrophages, and fibroblasts had a prominent role in the inflammatory process in the cochlea. Leukocytes were recruited to the cochlea following insertion of a nylon filament in adult mice, where contributed to the inflammatory response. The reparative stages in wound healing are characterized by persistent neuro-inflammation of spiral ganglion neurons (SGN) and expression of regenerative monocytes/macrophages in the cochlea. Accordingly, genes involved in extracellular matrix (ECM) deposition and remodeling were up-regulated in implanted cochleae. Maturation of scar tissue occurs in the remodeling phase of wound healing in the cochlea. Similar to other damaged peripheral nerves, M2 macrophages and de-differentiated SC were observed in damaged cochleae and may play a role in cell survival and axonal regeneration. In conclusion, the insertion of an electrode analog into the cochlea is associated with robust early and chronic inflammatory responses characterized by recruitment of leukocytes and expression of pro-inflammatory cytokines that promote intracochlear fibrosis and loss of the auditory hair cells (HC) and SGN important for hearing after CI surgery.

Conclusion: Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing., Objectives: Cochlear implant EIT can initiate sensory cell losses via necrosis and PCD within the organ of Corti, which can lead to a loss of residual hearing. PCD appears to be a major factor in HC loss post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs and HCs within the traumatized organ of Corti; and (2) identify the molecular mechanisms active within the HCs and SCs that are undergoing PCD., Methods: Adult guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated contralateral ears as controls. Immunostaining of dissected organ of Corti surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2,3-nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral control ears., Results: At 6 h post-EIT the SCs immunolabeled for the presence of phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was observed at 12 h in both the HCs and SCs of middle and basal cochlear turns. Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post-EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h post-EIT.

Objective: This study aimed to evaluate outcomes of the middle fossa (MF) superior vestibular neurectomy in unilateral Ménière's disease., Patients and Methods: Case series with preoperative and postoperative analysis of the 1995 American Academy of Otolaryngology hearing stage and vertigo class, gait instability, and results of vestibular-evoked myogenic potentials (VEMP)., Results: Four out of the 5 patients had total vertigo control (class A) and 1 had near total control (class B) by the last visit (mean follow-up, 23.6 months). There were no changes in hearing thresholds and hearing stage. Four patients had resolution of their gait instability by 2 months after surgery. Postoperative VEMP responses were preserved in all 3 patients with positive VEMP preoperatively., Conclusion: This is the first report of the anatomical and functional preservation of the inferior vestibular nerve in vestibular neurectomy for the treatment of refractory vertigo in unilateral Ménière's disease, with VEMP testing before and after vestibular neurectomy. The modified technique limits the surgical dissection and may help avoid complications such as postoperative hearing loss and persistent gait instability. This approach is indicated when other more conservative measures have failed, and patient selection is paramount to avoid long-term complications.

Objectives/hypothesis: To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111., Study Design: An animal model of cochlear implantation., Methods: Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT., Results: ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae., Conclusions: Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Hypothesis: Mannitol has otoprotective effects against tumor necrosis factor (TNF) α-induced auditory hair cell (HC) loss., Background: Mannitol has been demonstrated to possess cytoprotective effects in several organ systems. Its protective effect on postischemic hearing loss has also been shown. Mannitol's otoprotective mechanism and site of action are at present unknown., Materials and Methods: Organ of Corti (OC) explants were dissected from 3 day-old rat pups. The safety (nonototoxicity) of mannitol was assessed at 4 different concentrations (1-100 mM). Three experimental arms were designed including: a control group, TNFα group, and TNFα + mannitol group. Cell viability was determined by counts of fluorescein isothiocyanate (FITC) phalloidin stained HC. Immunofluorescence assay of phospho-c-Jun and the proapoptotic mediators, cleaved caspase-3, apoptosis inducing factor (AIF), and endonuclease G (Endo G) were performed., Results: Analysis of HC density confirmed the safety of mannitol at concentration ranges of 1 to 100 mM. The ototoxic effect of TNFα was demonstrated (p < 0.05). The otoprotective effect of 100 mM mannitol in TNFα-challenged OC explants was also demonstrated (p < 0.001). Mannitol treatment reduced the high levels of phospho-c-Jun observed in the TNFα-challenged group. AIF cluster formation and EndoG translocation into the nuclei of HCs were also reduced by mannitol treatment., Conclusion: Mannitol significantly reduces the ototoxic effects of TNFα against auditory HC's potentially by inhibiting c-Jun N terminal kinase (JNK) activation pathway and AIF, EndoG nuclear translocation. This local otoprotective effect may have therapeutic implications in inner ear surgery, for example, cochlear implants, protection of residual hearing, as well as implications for postischemic inner ear insults.

This review covers the most recent clinical and surgical advances made in the development and application of cochlear implants (CIs). In recent years, dramatic progress has been made in both clinical and basic science aspect of cochlear implantation. Today's modern CI uses multi-channel electrodes with highly miniaturized powerful digital processing chips. This review article describes the function of various components of the modern multi-channel CIs. A selection of the most recent clinical and surgical innovations is presented. This includes the preliminary results with electro-acoustic stimulation or hybrid devices and ongoing basic science research that is focused on the preservation of residual hearing post-implantation. The result of an original device that uses a binaural stimulation mode with a single implanted receiver/stimulator is also presented. The benefit and surgical design of a temporalis pocket technique for the implant's receiver stimulator is discussed. Advances in biomedical engineering and surgical innovations that lead to an increasingly favorable clinical outcome and to an expansion of the indication of CI surgery are presented and discussed., (Copyright © 2012 Wiley Periodicals, Inc.)

The cochlear implant (CI) is the first effective treatment for deafness and severe losses in hearing. As such, the CI is now widely regarded as one of the great advances in modern medicine. This article reviews the key events and discoveries that led up to the current CI systems, and we review and present some among the many possibilities for further improvements in device design and performance. The past achievements include: (1) development of reliable devices that can be used over the lifetime of a patient; (2) development of arrays of implanted electrodes that can stimulate more than one site in the cochlea; and (3) progressive and large improvements in sound processing strategies for CIs. In addition, cooperation between research organizations and companies greatly accelerated the widespread availability and use of safe and effective devices. Possibilities for the future include: (1) use of otoprotective drugs; (2) further improvements in electrode designs and placements; (3) further improvements in sound processing strategies; (4) use of stem cells to replace lost sensory hair cells and neural structures in the cochlea; (5) gene therapy; (6) further reductions in the trauma caused by insertions of electrodes and other manipulations during implant surgeries; and (7) optical rather electrical stimulation of the auditory nerve. Each of these possibilities is the subject of active research. Although great progress has been made to date in the development of the CI, including the first substantial restoration of a human sense, much more progress seems likely and certainly would not be a surprise., (Copyright © 2012 Wiley Periodicals, Inc.)

Congenital abnormalities of the outer ear pose a reconstructive challenge for plastic surgeons and otologists. Many patients with microtia of the auricle have concurrent atresia of the external auditory canal. The hearing loss associated with canal atresia can have long-lasting effects if not treated promptly and appropriately. The diagnosis and workup for canal atresia requires an otologic evaluation. Audiologic and radiologic evaluations direct treatment, which varies depending on unilateral or bilateral presence of atresia. Rehabilitation of hearing loss can be performed via hearing aids, bone-anchored conductive devices or canalplasty. Due to the complexity of treatments, communication between the reconstructive plastic surgeon and the otologist is necessary to detect hearing loss and determine the best method of restoring hearing in conjunction with microtia repair.

The prominent ear can produce significant social and psychological effects on an individual. Through the last century, many procedures have been described to correct this deformity. In this review, the authors navigate through the history of otoplasty for the protruded ear, and describe some of the breakthroughs in the procedure. Furthermore, they discuss key measurements that must be kept in mind in preoperative and intraoperative settings. They also describe in more detail some of the more common methods for correcting the protruded ear, as well as postoperative management and common complications faced after surgery.