PEPITA: Parallelized High-Throughput Quantification of Ototoxicity and Otoprotection in Zebrafish Larvae.

Drug-induced hearing injury (ototoxicity) is a common, debilitating side effect of many antibiotic regimens that can be worsened by adverse drug interactions. Such adverse drug interactions are often not detected until after drugs are already on the market because of the difficulty of measuring all possible drug combinations. While in vivo mammalian assays to screen for ototoxic damage exist, they are currently time-consuming, costly, and limited in throughput, which limits their utility in assessing drug interaction outcomes.

screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish.

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish.

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.

Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment.

Educational Environments and Secondary School Outcomes Among Students Who Are D/deaf and Hard of Hearing in Special Education.

Purpose: The purpose of this study is to provide updated national estimates on the annual number, educational environments, and secondary school outcomes of students who are D/deaf and hard of hearing (D/HH) receiving special education (SpEd) and related services in the United States.

Method: We performed a retrospective cross-sectional descriptive analysis of Individuals with Disabilities Education Act, Part B, Section 618 data from 2012 to 2018. Participants included students 6-21 years old in SpEd with "hearing impairment" reported as their primary disability.

Impact of Eliminating Local Anesthesia on Immediate Postoperative Analgesia in Pediatric Ambulatory Adenotonsillectomy.

Unlabelled: Our goal was to standardize intraoperative analgesic regimens for pediatric ambulatory tonsillectomy by eliminating local anesthetic use and to determine its impact on postoperative pain measures, while controlling for other factors.

Methods: We assembled a quality improvement team at an ambulatory surgery center. They introduced a standardized anesthetic protocol, involving American Society of Anesthesiologists Classification 1 and 2 patients undergoing adenotonsillectomy.

Reliability of Measuring Insertion Depth in Cochlear Implanted Infants and Children Using Cochlear View Radiography.

Objectives: Cochlear implant depth of insertion affects audiologic outcomes and can be measured in adults using plain films obtained in the "cochlear view." The objective of this study was to assess interrater and intrarater reliability of measuring depth of insertion using cochlear view radiography.

Study Design: Prospective, observational.

Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic.

COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers.

Pediatric Otolaryngology Divisional and Institutional Preparatory Response at Seattle Children's Hospital after COVID-19 Regional Exposure.

Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions.

Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death.

Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides.

Canertinib induces ototoxicity in three preclinical models.

Neuregulin-1 (NRG1) ligand and its epidermal growth factor receptor (EGFR)/ERBB family regulate normal cellular proliferation and differentiation in many tissues including the cochlea. Aberrant NRG1 and ERBB signaling cause significant hearing impairment in mice. Dysregulation of the same signaling pathway in humans is involved in certain types of cancers such as breast cancer or non-small cell lung cancer (NSCLC).

Identification of small molecule inhibitors of cisplatin-induced hair cell death: results of a 10,000 compound screen in the zebrafish lateral line.

Hypothesis: The zebrafish lateral line can be used to identify small molecules that protect against cisplatin-induced hair cell death.

Background: Cisplatin is a commonly used chemotherapeutic agent, which causes hearing loss by damaging hair cells of the inner ear. There are currently no FDA-approved pharmacologic strategies for preventing this side effect.

Upper aerodigestive magnetic foreign bodies in children.

Objectives/hypothesis: Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small, spherical, neodymium magnets available since 2008 are of particular concern. We aimed to identify all cases of upper aerodigestive foreign bodies at our institution over 15.

Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.

Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death.

"In-bone" utricle cultures--a simplified, atraumatic technique for in situ cultures of the adult mouse (Mus musculus) utricle.

Hypothesis: The "in-bone" method of culturing utricles described here is a reliable and atraumatic technique for culturing mature mouse hair cells and studying hair cell death and protection.

Background: The current in vitro technique for studying hair cells of the mature mouse utricle involves removal from the temporal bone and free floating culture in media. This technique can be problematic because of variability in the preservation of the sensory epithelium and a steep learning curve that results in injury of the sensory epithelium in less experienced hands.

Quinoline ring derivatives protect against aminoglycoside-induced hair cell death in the zebrafish lateral line.

We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191-203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold.

Hair cell toxicity in anti-cancer drugs: evaluating an anti-cancer drug library for independent and synergistic toxic effects on hair cells using the zebrafish lateral line.

Inner ear hair cell loss is the most common pathology seen after ototoxic drug injury. While certain drugs such as aminoglycosides and cisplatin are well-known to have dramatic ototoxic effects, it is probable that there are other drugs that cause occult degrees of hair cell loss and lesser degrees of hearing loss. Anti-cancer drugs are particularly strong candidates due to their general cytotoxicity.

Drug screening for hearing loss: using the zebrafish lateral line to screen for drugs that prevent and cause hearing loss.

Several animal models have been used for the study of mechanosensory hair cells and hearing loss. Because of the difficulty of tissue acquisition and large animal size, these traditional models are impractical for high-throughput screening. The zebrafish has emerged as a powerful animal model for screening drugs that cause and prevent hair cell death.

Polymerase chain reaction for pathogen identification in persistent pediatric cervical lymphadenitis.

Objective: To study routine culture-negative persistent cervical lymphadenitis in children treated surgically during a 10-year period (December 26, 1997, to October 1, 2007) at a single institution.

Design: Retrospective case series.

Setting: Tertiary university-based pediatric referral center.

Identification of FDA-approved drugs and bioactives that protect hair cells in the zebrafish (Danio rerio) lateral line and mouse (Mus musculus) utricle.

The hair cells of the larval zebrafish lateral line provide a useful preparation in which to study hair cell death and to screen for genes and small molecules that modulate hair cell toxicity. We recently reported preliminary results from screening a small-molecule library for compounds that inhibit aminoglycoside-induced hair cell death. To potentially reduce the time required for development of drugs and drug combinations that can be clinically useful, we screened a library of 1,040 FDA-approved drugs and bioactive compounds (NINDS Custom Collection II).

Using the zebrafish lateral line to screen for ototoxicity.

The zebrafish is a valuable model for studying hair cell development, structure, genetics, and behavior. Zebrafish and other aquatic vertebrates have hair cells on their body surface organized into a sensory system called the lateral line. These hair cells are highly accessible and easily visualized using fluorescent dyes.

Cisplatin-induced hair cell loss in zebrafish (Danio rerio) lateral line.

We have used time-lapse imaging to study cisplatin-induced hair cell death in lateral line neuromasts of zebrafish larvae in vivo. We found that cisplatin-induced hair cell death occurred much more slowly than had been shown to occur in aminoglycoside-induced hair cell death. By prelabeling hair cells with FM1-43FX, and assessing hair cell damage, it was established that cisplatin causes hair cell loss in the lateral line in a dose-dependent fashion.