Dual-AAV vector-mediated expression of improves vestibular function in a mouse model of Usher syndrome 1B.

Usher syndrome is the most common cause of deafness-blindness in the world. Usher syndrome type 1B (USH1B) is associated with mutations in . Patients with USH1B experience deafness, blindness, and vestibular dysfunction.

Combined AAV-mediated gene replacement therapy improves auditory function in a mouse model of human DFNB42 deafness.

Hearing loss is a common disorder affecting nearly 20% of the world's population. Recently, studies have shown that inner ear gene therapy can improve auditory function in several mouse models of hereditary hearing loss. In most of these studies, the underlying mutations affect only a small number of cell types of the inner ear (e.

Immune responses in the mammalian inner ear and their implications for AAV-mediated inner ear gene therapy.

Adeno-associated virus (AAV)-mediated inner ear gene therapy is a promising treatment option for hearing loss and dizziness. Several studies have shown that AAV-mediated inner ear gene therapy can be applied to various mouse models of hereditary hearing loss to improve their auditory function. Despite the increase in AAV-based animal and clinical studies aiming to rescue auditory and vestibular functions, little is currently known about the host immune responses to AAV in the mammalian inner ear.

Engineering olivocochlear inhibition to reduce acoustic trauma.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice.

AAV8BP2 and AAV8 transduce the mammalian cochlear lateral wall and endolymphatic sac with high efficiency.

Inner ear gene therapy using adeno-associated viruses (AAVs) has been successfully applied to several mouse models of hereditary hearing loss to improve their auditory function. While most inner ear gene therapy studies have focused on the mechanosensory hair cells and supporting cells in the organ of Corti, the cochlear lateral wall and the endolymphatic sac have not garnered much attention. The cochlear lateral wall and the endolymphatic sac play critical roles in inner ear ionic and fluid homeostasis.

Assessment of Sudden Sensorineural Hearing Loss After COVID-19 Vaccination.

Importance: Emerging reports of sudden sensorineural hearing loss (SSNHL) after COVID-19 vaccination within the otolaryngological community and the public have raised concern about a possible association between COVID-19 vaccination and the development of SSNHL.

Objective: To examine the potential association between COVID-19 vaccination and SSNHL.

Design, Setting, And Participants: This cross-sectional study and case series involved an up-to-date population-based analysis of 555 incident reports of probable SSNHL in the Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System (VAERS) over the first 7 months of the US vaccination campaign (December 14, 2020, through July 16, 2021).

Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss.

Hearing loss is a common disability affecting the world's population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the neonatal age, when mouse inner ear has not fully developed. However, the human inner ear is fully developed at birth.

Pediatric Bilateral Sensorineural Hearing Loss: Minimum Test Battery and Referral Criteria for Cochlear Implant Candidacy Evaluation.

Among the various cochlear implant systems approved by the Food and Drug Administration, current labeling for pediatric usage encompasses (1) bilateral profound bilateral sensorineural hearing loss in children aged 9 to 24 months and bilateral severe to profound sensorineural hearing loss in children older than 2 years; (2) use of appropriately fitted hearing aids for 3 months (this can be waived if there is evidence of ossification); and (3) demonstration of limited progress with auditory, speech, and language development. Pediatric guidelines require children to have significantly worse speech understanding before qualifying for cochlear implantation. The early years of life have been shown to be critical for speech and language development, and auditory deprivation is especially detrimental during this crucial time.

Preliminary Analysis of Association Between COVID-19 Vaccination and Sudden Hearing Loss Using US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data.

This cross-sectional study examines the national incidence of sudden sensorineural hearing loss after COVID-19 vaccination using data from the CDC Vaccine Adverse Events Reporting System.

Validation of a 3D-printed human temporal bone model for otology surgical skill training.

Hypothesis: Three-dimensional (3D) printed temporal bones are comparable to cadaveric temporal bones as a training tool for otologic surgery.

Background: Cadaveric temporal bone dissection is an integral part of otology surgical training. Unfortunately, availability of cadaveric temporal bones is becoming much more limited and concern regarding chemical and biological risks persist.

Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer.

Background: Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC.

Methods: HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018.

Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges.

Approximately 3 in 1000 children in the US under 4 years of age are affected by hearing loss. Currently, cochlear implants represent the only line of treatment for patients with severe to profound hearing loss, and there are no targeted drug or biological based therapies available. Gene replacement is a promising therapeutic approach for hereditary hearing loss, where viral vectors are used to deliver functional cDNA to "replace" defective genes in dysfunctional cells in the inner ear.

Natural History of Untreated Transverse/Sigmoid Sinus Thrombosis Following Posterior Fossa Surgery: Case Series and Literature Review.

Background: Transverse or sigmoid sinus thrombosis occurs in 4% to 11% of patients following posterior fossa surgery. Anticoagulation has been the mainstay treatment, mostly based on extrapolation from the literature on spontaneous sinus thrombosis.

Objective: To analyze the rate and associated complications of postoperative transverse/sigmoid sinus thrombosis for patients undergoing posterior fossa tumor resection.

SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct.

Background: Recessive mutations of coding regions and splice sites of the SLC26A4 gene cause hearing loss with enlargement of the vestibular aqueduct (EVA). Some patients also have a thyroid iodination defect that can lead to multinodular goiter as part of Pendred syndrome. A haplotype of variants upstream of SLC26A4, called CEVA, acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4.

Surgical Methods for Inner Ear Gene Delivery in Neonatal Mouse.

Inner ear gene therapy offers great potential as a treatment for hearing loss and dizziness. The surgical method used to deliver gene therapy into the inner ear is a critical step in determining the success of inner ear gene therapy. Here we describe two commonly used surgical methods for gene delivery in neonatal mouse inner ear: the round window approach and the posterior semicircular canal approach.

AAV2.7m8 is a powerful viral vector for inner ear gene therapy.

Adeno-associated virus (AAV) has been successfully used to deliver gene therapy to improve auditory function in mouse models of hereditary hearing loss. Many forms of hereditary hearing loss have mutations which affect the cochlear hair cells, the mechanosensory cells which allow for sound detection and processing. While most conventional AAVs infect inner hair cells (IHCs) with various efficiencies, they infect outer hair cells (OHCs) and supporting cells at lower levels in the cochlea.

Sex differences in HPV immunity among adults without cancer.

The incidence of human papillomavirus (HPV)-associated head and neck cancers is rising, particularly among men. Whether observed epidemiological differences in sex are explained by differences in sexual exposure and/or by immune response is unclear. In this cross-sectional, multi-institutional study, seroprevalence of antibodies to HPV L1 capsid antigen was compared by patient characteristics among 374 adult patients without cancer.

A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration.

Mutations in CEP290 cause ciliogenesis defects, leading to diverse clinical phenotypes, including Leber congenital amaurosis (LCA). Gene therapy for CEP290-associated diseases is hindered by the 7.4 kb CEP290 coding sequence, which is difficult to deliver in vivo.

Posterior Semicircular Canal Approach for Inner Ear Gene Delivery in Neonatal Mouse.

Inner ear gene therapy offers great promise as a potential treatment for hearing loss and dizziness. One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. In this study, we describe the posterior semicircular canal approach as a viable method for inner ear gene delivery in neonatal mice.

Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome.

Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional.