Dispersed DNA variants underlie hearing loss in South Florida's minority population.

BACKGROUND: We analyzed the genetic causes of sensorineural hearing loss in racial and ethnic minorities of South Florida by reviewing demographic, phenotypic, and genetic data on 136 patients presenting to the Hereditary Hearing Loss Clinic at the University of Miami. In our retrospective chart review, of these patients, half self-identified as Hispanic, and the self-identified racial distribution was 115 (86%) White, 15 (11%) Black, and 6 (4%) Asian. Our analysis helps to reduce the gap in understanding the prevalence, impact, and genetic factors related to hearing loss among diverse populations. RESULTS: The causative gene variant or variants were identified in 54 (40%) patients, with no significant difference in the molecular diagnostic rate between Hispanics and Non-Hispanics. However, the total solve rate based on race was 40%, 47%, and 17% in Whites, Blacks, and Asians, respectively. In Non-Hispanic Whites, 16 different variants were identified in 13 genes, with GJB2 (32%), MYO7A (11%), and SLC26A4 (11%) being the most frequently implicated genes. In White Hispanics, 34 variants were identified in 20 genes, with GJB2 (22%), MYO7A (7%), and STRC-CATSPER2 (7%) being the most common. In the Non-Hispanic Black cohort, the gene distribution was evenly dispersed, with 11 variants occurring in 7 genes, and no variant was identified in 3 Hispanic Black probands. For the Asian cohort, only one gene variant was found out of 6 patients. CONCLUSION: This study demonstrates that the diagnostic rate of genetic studies in hearing loss varies according to race in South Florida, with more heterogeneity in racial and ethnic minorities. Further studies to delineate deafness gene variants in underrepresented populations, such as African Americans/Blacks from Hispanic groups, are much needed to reduce racial and ethnic disparities in genetic diagnoses.

Exosomes as drug delivery vehicles and biomarkers for neurological and auditory systems.

Exosomes are small extracellular membrane particles that play a crucial role in intracellular signaling. Research shows that exosomes have the potential to be used as biomarkers or drug delivery systems in specific organs, such as the neurological system and the inner ear. Exosomes in neurological and auditory systems release different molecules when under stress versus in healthy states, highlighting their potential use as biomarkers in the identification of diseased states. Studies have suggested that exosomes can be harnessed for drug delivery to hard-to-reach organs, such as cochlear sensory hair cells and the brain due to their ability to cross the blood-labyrinth and blood-brain barriers. In this article, we describe the biogenesis, classification, and characterization methods of exosomes. We then discuss recent studies that indicate their potential usage as biomarkers and drug delivery systems to help treat inner ear and neurological disorders.

Beneficial Effects of Milk Having A2 ß-Casein Protein: Myth or Reality?

Diet has been shown to play an important role in maintaining normal homeostasis in the human body. Milk and milk products are a major component of the Western diet, but their consumption may predispose sensitive individuals to adverse health outcomes. Current literature about milk products recognizes various bioactive components including lactate, whey protein, and ß-casein protein. Specifically, cow milk has 2 major subvariants of its ß-casein protein, A1 and A2, due to a single nucleotide difference that changes the codon at position 67. Whereas the A2 polymorphism is unlikely to undergo enzymatic cleavage during digestion, the A1 polymorphism is more likely to undergo enzymatic cleavage resulting in the product peptide ß-casomorphin-7, a known µ-opioid receptor agonist. The objective of this article is to review the current understanding of the 2 major ß-casein subvariants and their effects on various organ systems that may have an impact on the health of an individual. Synthesis of the current existing literature on this topic is relevant given the increased association of milk consumption with adverse effects in susceptible individuals resulting in a rising interest in consuming milk alternatives. We discuss the influence of the ß-casein protein on the gastrointestinal system, endocrine system, nervous system, and cardiovascular system as well as its role in antioxidants and methylation. A1 milk consumption has been associated with enhanced inflammatory markers. It has also been reported to have an opioid-like response that can lead to manifestations of clinical symptoms of neurological disorders such as autism spectrum disorder. On the other hand, A2 milk consumption has been associated with beneficial effects and is easier to digest in sensitive individuals. Further research is warranted to investigate the short- and long-term effects of consumption of A1 ß-casein in comparison with milk with A2 ß-casein proteins.

A perspective on stem cell therapy for ear disorders.

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.

Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function.

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.

Indispensable Role of Ion Channels and Transporters in the Auditory System.

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.

Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.

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.

The Advances in Hearing Rehabilitation and Cochlear Implants in China.

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.

Atypical radiographic features of skull base cholesterol granuloma.

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.

Middle fossa vestibular neurectomy for refractory vertigo: less is more.

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.

Dose-Painting Linear Accelerator Radiosurgery of Glomus Jugulare With Dosimetric Comparison to Gamma Knife.

Objectives In this study, we outline our rationale for delivering a dose of ≥15 Gy in stereotactic radiosurgery (SRS) of glomus jugulare tumor (GJT) while ensuring the avoidance of complications associated with doses >13 Gy to the facial nerve. To avoid such complications, we initially utilized the Gamma Knife Perfexion (GK) system (Elekta Instrument AB, Stockholm, Sweden) at our institution but encountered challenges related to lengthy treatment times and difficulty in sculpting doses to minimize doses to spare the facial nerve. As a potential solution, we propose the use of HyperArc (Varian Medical Systems, Palo Alto, CA), a newly developed automated delivery platform for linear accelerator (LINAC)-based SRS. HyperArc offers the potential for faster treatment and more complex shaping of the radiotherapy dose with multiple arcs and multi-leaf collimators. Methods We retrospectively reviewed nine cases of patients with GJT treated with HyperArc. Patients' demographic and treatment data were collected. Additionally, simulated GK treatment plans were created and compared with HyperArc plans to assess time savings, PTV coverage, and plan quality. Results One male and eight female patients, with a mean age of 63.9 years, were included. Treatments were delivered on average in 29 minutes, achieving 95-100% of the tumor while limiting the facial nerve to <13 Gy. Treatments replanned using our GK system could achieve only 92-99% tumor coverage while respecting facial nerve constraints, with average treatment times of 180 minutes. Comparable plan quality parameters were attained with both modalities. Conclusions The HyperArc system provides a qualitatively satisfactory and rapid treatment delivery of a highly sculpted radiotherapy dose to maximize tumor coverage and minimize facial nerve complications.

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with the Neurexin 1 (NRXN1) gene emerging as a key player. This comprehensive systematic review elucidates the contribution of NRXN1 gene variants in the pathophysiology of ASD. Methods: The protocol for this systematic review was designed a priori and was registered in the PROSPERO database (CRD42023450418). A risk of bias analysis was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool. We examined various studies that link NRXN1 gene disruptions with ASD, discussing both the genotypic variability and the resulting phenotypic expressions. Results: Within this review, there was marked heterogeneity observed in ASD genotypic and phenotypic manifestations among individuals with NRXN1 mutations. The presence of NRXN1 mutations in this population emphasizes the gene's role in synaptic function and neural connectivity. Conclusion: This review not only highlights the role of NRXN1 in the pathophysiology of ASD but also highlights the need for further research to unravel the complex genetic underpinnings of the disorder. A better knowledge about the multifaceted role of NRXN1 in ASD can provide crucial insights into the neurobiological foundations of autism and pave the way for novel therapeutic strategies.

Vestibular Schwannoma and Tinnitus: A Systematic Review of Microsurgery Compared to Gamma Knife Radiosurgery.

Background: Vestibular schwannoma (VS) is a benign tumor of the eighth cranial nerve formed from neoplastic Schwann cells. Although VS can cause a variety of symptoms, tinnitus is one of the most distressing symptoms for patients and can greatly impact quality of life. The objective of this systematic review is to comprehensively examine and compare the outcomes related to tinnitus in patients undergoing treatment for VS. Specifically, it evaluates patient experiences with tinnitus following the removal of VS using the various surgical approaches of traditional surgical resection and gamma knife radiosurgery (GKS). By delving into various aspects such as the severity of tinnitus post-treatment, the duration of symptom relief, patient quality of life, new onset of tinnitus after VS treatment, and any potential complications or side effects, this review aims to provide a detailed analysis of VS treatment on tinnitus outcomes. Methods: Following PRISMA guidelines, articles were included from PubMed, Science Direct, Scopus, and EMBASE. Quality assessment and risk of bias analysis were performed using a ROBINS-I tool. Results: Although VS-associated tinnitus is variable in its intensity and persistence post-resection, there was a trend towards a decreased tinnitus burden in patients. Irrespective of the surgical approach or the treatment with GKS, there were cases of persistent or worsened tinnitus within the studied cohorts. Conclusion: The findings of this systematic review highlight the complex relationship between VS resection and tinnitus outcomes. These findings underscore the need for individualized patient counseling and tailored treatment approaches in managing VS-associated tinnitus. The findings of this systematic review may help in guiding clinicians towards making more informed and personalized healthcare decisions. Further studies must be completed to fill gaps in the current literature.

Incidence of Otolaryngological Manifestations in Individuals with Autism Spectrum Disorder: A Special Focus on Auditory Disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by stereotyped and repetitive behavior patterns. In addition to neurological and behavioral problems, individuals with ASD commonly experience otolaryngological comorbidities. Individuals with ASD often have auditory disorders including hearing loss and auditory processing disorders such as central auditory processing disorder (CAPD), as well as both chronic and recurrent otitis media. These challenges negatively impact a person's ability to effectively communicate and may further impact their neurological functioning, particularly when not appropriately treated. Individuals diagnosed with ASD also have difficulty sleeping which contributes to increased irritability and may further aggravate the core behavioral symptoms of autism. The individuals with ASD also have a higher rate of sinusitis which contributes to the worsening of the autism behavior phenotype. The high prevalence of otolaryngological comorbidities in individuals with ASD warrants a better collaboration between their various healthcare providers and otolaryngologists with expertise in auditory, sleep, and sinus disorders in pursuit of improving the quality of life of affected individuals and their families/caregivers.

Targeting Gut Dysbiosis and Microbiome Metabolites for the Development of Therapeutic Modalities for Neurological Disorders.

The gut microbiota, composed of numerous species of microbes, works in synergy with the various organ systems in the body to bolster our overall health and well-being. The most well-known function of the gut microbiome is to facilitate the metabolism and absorption of crucial nutrients, such as complex carbohydrates, while also generating vitamins. In addition, the gut microbiome plays a crucial role in regulating the functioning of the central nervous system (CNS). Host genetics, including specific genes and single nucleotide polymorphisms (SNPs), have been implicated in the pathophysiology of neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD). The gut microbiome dysbiosis also plays a role in the pathogenesis of these neurodegenerative disorders, thus perturbing the gut-brain axis. Overproduction of certain metabolites synthesized by the gut microbiome, such as short-chain fatty acids (SCFAs) and p-cresyl sulfate, are known to interfere with microglial function and trigger misfolding of alpha-synuclein protein, which can build up inside neurons and cause damage. By determining the association of the gut microbiome and its metabolites with various diseases, such as neurological disorders, future research will pave the way for the development of effective preventive and treatment modalities.

Functional Hearing Preservation in Cochlear Implantation: The Miami Cocktail Effect.

OBJECTIVE: To investigate if pharmacological treatment with prednisone and L-N-acetylcysteine (STE + NAC) influence functional hearing preservation in cochlear implant (CI) surgery. STUDY DESIGNS: Preimplantation and postimplantation longitudinal case-control study. SETTING: Tertiary referral center. PATIENTS: Pediatric and adult recipients of CI with preimplantation functional hearing defined as an average of air-conducted thresholds at 125, 250, and 500 Hz (low-frequency pure-tone average [LFPTA]) <80 dB. INTERVENTIONS: Preimplantation and postimplantation audiometry. Weight-adjusted oral prednisone and L-N-acetylcysteine starting 2 days before surgery (Miami cocktail). Prednisone was continued for 3 days and L-N-acetylcysteine for 12 days after surgery, respectively. Cochlear implantation with conventional length electrodes. MAIN OUTCOME MEASURES: Proportion of patients with LFPTA <80 dB, and LFPTA change at 1-year postimplantation. RESULTS: All 61 patients received intratympanic and intravenous dexamethasone intraoperatively, with 41 patients receiving STE + NAC and 20 patients not receiving STE + NAC. At 1-year postimplantation, the proportion of functional hearing preservation was 83% in the STE + NAC group compared with 55% of subjects who did not receive STE + NAC ( p = 0.0302). The median LFPTA change for STE + NAC-treated and not treated subjects was 8.33 dB (mean, 13.82 ± 17.4 dB) and 18.34 dB (mean, 26.5 ± 23.4 dB), respectively ( p = 0.0401, Wilcoxon rank test). Perioperative STE + NAC treatment resulted in 10 dB of LFPTA better hearing than when not receiving this treatment. Better low-frequency preimplantation hearing thresholds were predictive of postimplantation functional hearing. No serious side effects were reported. CONCLUSION: Perioperative STE + NAC, "The Miami Cocktail," was safe and superior to intraoperative steroids alone in functional hearing preservation 1-year after cochlear implantation.

New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2022.

Objective: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. Data Sources: Publicly available FDA data on drugs and devices approved in 2022. Review Methods: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgery's (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. Conclusion: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. Implications for Practice: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.

Quality of Life, Neurosensory Disorders and Co-Occurring Medical Conditions in Individuals on the Spectrum, with a Special Focus on Females Diagnosed with Autism: A Systematic Review.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has a high prevalence and a significant economic impact. Our knowledge regarding neurosensory disorders and co-occurring medical conditions in the ASD population is limited, particularly for autistic women. Most of the studies include male participants or do not make comparisons with their female counterparts. The objective of this systematic review article is to explore the quality of life as well as the prevalence of neurosensory disorders and co-occurring medical conditions in individuals on the spectrum, with a special focus on autistic females. The literature search was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42022330368). We concluded that numerous medical areas were of concern. Autistic females are more likely than their male counterparts with ASD to suffer from psychiatric conditions such as post-traumatic stress syndrome, depression, and eating disorders. They are also more likely to report GI-related disturbances and chronic pain. Further investigations are warranted to determine quality of life, as well as the prevalence and severity of neurosensory disorders in individuals with ASD, specifically studies comparing autistic females with their male counterparts. The information derived from these studies will help develop better support systems for individuals with autism, particularly females on the spectrum, in pursuit of improving their quality of life.

Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder.

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology. Individuals with autism spectrum disorder show deficits in a variety of areas including cognition, memory, attention, emotion recognition, and social skills. With no definitive treatment or cure, the main interventions for individuals with autism spectrum disorder are based on behavioral modulations. Recently, noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity, particularly in individuals with autism spectrum disorder. Preliminary evidence from small cohort studies, pilot studies, and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder. However, little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation. The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.