Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization.

Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase organization using quantitative reconstitution of cytoplasmic stress granules (SGs) with attached P-bodies in human cells. Protein-interaction networks can be viewed as interconnected complexes (nodes) of RNA-binding domains (RBDs), whose integrated RNA-binding capacity determines whether LLPS occurs upon RNA influx. Surprisingly, both RBD-RNA specificity and disordered segments of key proteins are non-essential, but modulate multiphase condensation. Instead, stoichiometry-dependent competition between protein networks for connecting nodes determines SG and P-body composition and miscibility, while competitive binding of unconnected proteins disengages networks and prevents LLPS. Inspired by patchy colloid theory, we propose a general framework by which competing networks give rise to compositionally specific and tunable condensates, while relative linkage between nodes underlies multiphase organization.

Targeting the Liver with Nucleic Acid Therapeutics for the Treatment of Systemic Diseases of Liver Origin.

Systemic diseases of liver origin (SDLO) are complex diseases in multiple organ systems, such as cardiovascular, musculoskeletal, endocrine, renal, respiratory, and sensory organ systems, caused by irregular liver metabolism and production of functional factors. Examples of such diseases discussed in this article include primary hyperoxaluria, familial hypercholesterolemia, acute hepatic porphyria, hereditary transthyretin amyloidosis, hemophilia, atherosclerotic cardiovascular diseases, α-1 antitrypsin deficiency-associated liver disease, and complement-mediated diseases. Nucleic acid therapeutics use nucleic acids and related compounds as therapeutic agents to alter gene expression for therapeutic purposes. The two most promising, fastest-growing classes of nucleic acid therapeutics are antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). For each listed SDLO disease, this article discusses epidemiology, symptoms, genetic causes, current treatment options, and advantages and disadvantages of nucleic acid therapeutics by either ASO or siRNA drugs approved or under development. Furthermore, challenges and future perspectives on adverse drug reactions and toxicity of ASO and siRNA drugs for the treatment of SDLO diseases are also discussed. In summary, this review article will highlight the clinical advantages of nucleic acid therapeutics in targeting the liver for the treatment of SDLO diseases. SIGNIFICANCE STATEMENT: Systemic diseases of liver origin (SDLO) contain rare and common complex diseases caused by irregular functions of the liver. Nucleic acid therapeutics have shown promising clinical advantages to treat SDLO. This article aims to provide the most updated information on targeting the liver with antisense oligonucleotides and small interfering RNA drugs. The generated knowledge may stimulate further investigations in this growing field of new therapeutic entities for the treatment of SDLO, which currently have no or limited options for treatment.

Vergence and Accommodation Deficits in Children and Adolescents with Vestibular Disorders.

SIGNIFICANCE: The high frequency of vergence and accommodation deficits coexisting in patients with a vestibular diagnosis merits a detailed visual function examination. PURPOSE: Deficits in vergence and saccades have been reported in patients with vestibular symptomatology. We retrospectively evaluated visual function deficits in adolescents with vestibular diagnoses and concussion. METHODS: The following inclusion criteria were used: vestibular and optometric evaluations between 2014 and 2020, 6 to 22 years old, and 20/25 best-corrected vision or better. Clinical criteria assigned vestibular diagnoses and concussion diagnoses. Vestibular diagnoses included vestibular migraine, benign paroxysmal positional vertigo, and persistent postural perceptual dizziness. Visual function deficits were compared with a pediatric control group (30). Nonparametric statistics assessed differences in group distribution. RESULTS: A total of 153 patients were included: 18 had vestibular diagnoses only, 62 had vestibular diagnoses related to concussion, and 73 had concussion only. Vergence deficits were more frequent in patients with vestibular diagnoses and concussion (42%) and concussion only (34%) compared with controls (3%; all P = .02). Accommodation deficits were more frequent in patients with vestibular diagnoses only (67%), vestibular diagnoses and concussion (71%), and concussion (58%) compared with controls (13%; all P = .002). Patients with vestibular migraine and concussion (21) had more vergence deficits (62%) and accommodation insufficiency (52%) than concussion-only patients (47%, P = .02; 29%, P = .04). Patients with benign paroxysmal positional vertigo and concussion (20) had lower positive fusional vergence and failed near vergence facility (35%) more than concussion-only patients (16%; P = .03). CONCLUSIONS: Visual function deficits were observed at a high frequency in patients with a vestibular diagnosis with or without a concussion and particularly in vestibular migraine or benign paroxysmal positional vertigo. Visual function assessments may be important for patients with vestibular diagnoses.

Two Cases of a Prenatally Diagnosed Double Aortic Arch with Postnatal Obliteration of the Distal Left Aortic Arch.

We report two cases of prenatally diagnosed double aortic arch with dominant right arch and a left-sided ductus arteriosus, consistent with a complete vascular ring. Postnatal transthoracic echocardiogram and cardiac magnetic resonance imaging demonstrated a spontaneous closure of the ductus arteriosus and obliteration of the left aortic arch distal to the origin of the left subclavian artery in both cases. Spontaneous closure of the ductus arteriosus involving extended ductal tissue in the left aortic arch likely led to obliteration of the distal left arch after birth. One patient presented with recurrent symptoms suggestive of dysphagia and underwent a successful surgical repair of the vascular ring with resolution of symptoms. The other patient has been asymptomatic and is 4 years old at the time of this report.

Cold Panniculitis After Ice Therapy for Supraventricular Tachycardia.

A late preterm infant presenting with supraventricular tachycardia (SVT) was admitted to the pediatric intensive care unit because of poor systolic function seen on echocardiogram. The hospitalization was complicated by multiple breakthrough episodes of SVT requiring ice placed on the face during each repeat episode. The infant was later diagnosed as having cold panniculitis secondary to the application of ice to the face on multiple occasions. In children who are hemodynamically stable during SVT episodes, ice is used as first-line treatment. It is important to be aware of how often ice is being applied to the face and the duration of time to limit complications such as cold panniculitis.

Comparing Video Head Impulse Testing With Rotary Chair in Pediatric Patients: A Controlled Trial.

OBJECTIVES: To investigate the efficacy of video head impulse testing (VHIT) in detecting vestibular loss in pediatric patients with abnormal rotary chair testing, compared to a control group with normal rotary chair testing. STUDY DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Pediatric vestibular program at tertiary level children's hospital. METHODS: Patients 3 to 18 years of age were recruited to undergo VHIT and rotary chair testing between September 2015 and November 2022. VHIT results were compared between an experimental group of 23 patients with vestibular symptoms and abnormal rotary chair testing results versus a control group of 14 patients without vestibular symptoms and with normal rotary chair testing results. RESULTS: The experimental group demonstrated reduced mean VHIT gain for the lateral semicircular canals (right = 0.83; left = 0.75) relative to the control group (right = 1.04, P = .005; left = 0.98, P < .001), but there was no significant difference between groups in superior and posterior canal responses. Among controls, there were no significant differences in mean gain values for each canal plane between age groups (3-7, 8-12, and 13-18 years) or between genders. A VHIT lateral canal gain value <0.85 and/or corrective saccades demonstrated 100% specificity and 100% positive predictive value for detecting vestibular loss on rotary chair, but only 69.6% sensitivity and 66.7% negative predictive value. CONCLUSION: VHIT is a useful test for detecting impairment of the lateral semicircular canals in children, though its sensitivity is limited relative to rotary chair. Its role in detecting vertical canal dysfunction in pediatric patients may be more limited and warrants further study.

Vestibular Preservation in Pediatric Cochlear Implantation.

OBJECTIVES: Evaluate the rate of preserved vestibular function in pediatric cochlear implant surgery. STUDY DESIGN: Retrospective case review. METHODS: Pre- and post-operative vestibular tests were compared in children who underwent cochlear implantation at a tertiary level pediatric hospital over a 4-year period. RESULTS: Data from 59 implanted ears in 44 children was included. Median age was 2.8 years at initial testing (range 7 months - 21 years) with 1:1 male/female ratio. Implant surgeries were 26 unilateral, 13 bilateral simultaneous, and 5 bilateral sequential. The majority were implanted with slim, non-styletted electrodes (86.4%) via a round window approach (91.5%). Normal pre-operative results were preserved post-operatively on rotary chair testing in 75% (21/28) of patients, cervical vestibular evoked myogenic potential testing in (75%) 30/40 of ears tested, ocular vestibular evoked myogenic potential testing in 85.7% (6/7) of ears tested, video head impulse testing in 100% (9/9) of ears tested, and computerized dynamic posturography in 100% (5/5) of patients tested. Overall, 62.5% of patients had no new deficits on any vestibular test performed post-operatively. CONCLUSIONS: Preservation rates of vestibular function following cochlear implant surgery were higher in this cohort than what has been reported in many earlier studies. Contemporary, less traumatic electrodes and insertion techniques may be a significant factor. The risk of causing a new, severe bilateral vestibular loss with long-term functional impacts appears to be low. Further study is warranted on the impacts of different cochlear implant electrode designs and insertion approaches on post-operative vestibular preservation. LEVEL OF EVIDENCE: 4, Case Series Laryngoscope, 134:1913-1918, 2024.

Evidence of vestibular dysfunction in children with enlarged vestibular aqueduct.

OBJECTIVE: To investigate the occurrence and characteristics of balance and vestibular deficits in pediatric patients with enlarged vestibular aqueduct (EVA). MATERIALS AND METHODS: Retrospective review of 53 children with EVA who underwent a comprehensive vestibular evaluation in our pediatric balance and vestibular program. Laboratory testing included videonystagmography (VNG), rotary chair, video head impulse testing (vHIT), vestibular evoked myogenic potential (VEMP), subjective visual vertical (SVV) and Sensory Organization Test (SOT) in posturography. RESULTS: The mean age of these children, 31 girls and 22 boys, was 7.1 years (SD = 4.8). Among these 53 children, 16 had unilateral EVA (7 on the left side and 9 on the right side) and 37 had bilateral EVA, in which genetic testing confirmed 5 cases of Pendred syndrome. Abnormal testing results were found in 58% (11/19) on SOT, 67% (32/48) on rotary chair, 55% (48/88 of ears) on VEMP, 30% (8/27) on vHIT, 39% (7/18) on SVV, and 8% (4/53) on VNG. CONCLUSIONS: Vestibular dysfunction may be a common finding in children with EVA. Clinicians who provide medical care for children with EVA need to be familiar with signs of potential balance and vestibular impairments. Although performing vestibular evaluation on young children with EVA can be difficult, objective testing is important in order to identify any potential vestibular deficit in these pediatric patients so that proper vestibular rehabilitation and balance retraining can be provided.

Characteristics of Benign Paroxysmal Positional Vertigo in Young Children.

OBJECTIVES: This study aimed to determine the clinical characteristics of benign paroxysmal positional vertigo (BPPV) in young children. STUDY DESIGN: Retrospective case review. METHODS: All children <10 years old that have been diagnosed with BPPV at our pediatric vestibular program between December 2012-July 2021 were selected. Clinical features were identified by medical record review, including demographics, comorbidities, canal involvement, response to treatment, and incidence of recurrence. RESULTS: A total of 34 children were diagnosed with BPPV with a mean age of 7.9 years old (SD ± 1/7; range 5-9) at the time of diagnosis and a male:female ratio of 1:1. Involved semicircular canals included posterior in 82% (n = 28), horizontal in 41% (n = 14), and superior in 24% (n = 8) of patients, respectively. Comorbid diagnoses included migraine (n = 14), concussion (n = 10), acute vestibular syndrome (n = 4), and persistent postural perceptual dizziness (n = 6). Recurrence with initially confirmed resolution occurred in 10 patients (29%) with a mean of 2.5 recurrences per patient (SD: 2.2; range 1-8). A family history of vertigo or migraine was identified in 11 and 17 patients, respectively. CONCLUSIONS: BPPV is a cause of vertigo in children that may be overlooked. A relatively high proportion of patients demonstrated horizontal or superior canal involvement, recurrence, and additional comorbid causes of dizziness. Thus, providers evaluating young children with dizziness should perform diagnostic maneuvers to evaluate BPPV of all semicircular canals and continue to monitor children after successful treatment for recurrence. LEVEL OF EVIDENCE: 4, Case Series Laryngoscope, 133:694-699, 2023.

A dual-pathway architecture enables chronic stress to promote habit formation.

Chronic stress can change how we learn and, thus, how we make decisions by promoting the formation of inflexible, potentially maladaptive, habits. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted approach in male and female mice, we reveal a dual pathway, amygdala-striatal, neuronal circuit architecture by which a recent history of chronic stress shapes learning to disrupt flexible goal-directed behavior in favor of inflexible habits. Chronic stress inhibits activity of basolateral amygdala projections to the dorsomedial striatum to impede the action-outcome learning that supports flexible, goal-directed decisions. Stress also increases activity in direct central amygdala projections to the dorsomedial striatum to promote the formation of rigid, inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to promote premature habit formation. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and other psychiatric conditions.

Marked QT prolongation and ventricular tachycardia of a transient nature in young children with cardiomyopathy.

Significant prolongation of the QT interval in pediatric patients with cardiomyopathy is rare. We report two cases of dilated myopathy with transient and dramatic QT prolongation. Both had associated ventricular arrhythmias, with one having torsade de pointes, and the other nonsustained ventricular tachycardia. Normalization of their QTc occurred as their ventricular function improved.

Pain at the Cochlear Implant Site Requiring Device Removal in Pediatric Patients.

OBJECTIVES: Idiopathic pain at the cochlear implant (CI) site outside of the immediate postoperative period is an uncommon occurrence but may necessitate device explantation. Our objective was to describe the clinical course for pediatric patients with CI site pain who ultimately required device explantation. STUDY DESIGN: Retrospective chart review. METHODS: We performed a retrospective database review of CIs performed at a tertiary referral center for pediatric cochlear implantation. We specifically evaluated pediatric patients who presented with pain at or near the CI device site and ultimately required explantation. RESULTS: Fifteen patients (16 CIs) had pain at or near the CI site requiring device explantation. Cultures taken during site exploration or device explantation identified bacteria in 86% and 81% of procedures, respectively. Propionibacterium acnes and Staphylococcus non-aureus were the most commonly identified organisms. CONCLUSIONS: The majority of patients with idiopathic pain in this cohort ultimately requiring CI explantation had chronic bacterial colonization. LEVEL OF EVIDENCE: 4 (Case series) Laryngoscope, 132:2044-2049, 2022.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: A review.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever condition in children, with most cases appearing by the age of 5. Although PFAPA is generally a self-limited condition, it can have a major impact on a child's quality of life, as well as that of their family. Recent research has continued to shed light on the genetic and immunologic factors that play a role in the pathogenesis of PFAPA. There also exists significant heterogeneity in treatment strategies, and progress has been made to develop evidence-based management strategies and establish a standard of care. This review will outline current knowledge regarding the pathogenesis of PFAPA, as well as treatment strategies and our clinical experience.

Obesity as a Possible Risk Factor for Pediatric Sensorineural Hearing Loss.

OBJECTIVES/HYPOTHESIS: Childhood hearing loss impacts linguistic, academic, social, and psychologic development, and may have lasting implications for future workforce performance. Current evidence for obesity as a pediatric sensorineural hearing loss (SNHL) risk factor is intriguing but equivocal. We hypothesized that obesity is associated with a higher risk of SNHL. We additionally examined whether underweight is associated with a higher risk of SNHL. STUDY DESIGN: Retrospective database review. METHODS: A single-institution audiologic database from 2015 to 2020 was queried for audiograms with type-A tympanograms from children aged 5 to 18 years old. Comorbidities known to be associated with hearing loss were excluded. We then examined both for sub-clinical (≥15 dB) high- or low-frequency hearing loss, and for clinical (≥21 dB) hearing loss, with the aim of examining the association between obesity and SNHL. Multivariable logistic regression was performed to adjust for age, gender, diabetes mellitus, attention deficit hyperactivity disorder, and autism. RESULTS: A total of 3,142 children were included. Obesity was not associated with risk of SNHL (adjusted OR 0.82; 95% CI: 0.60, 1.12). Underweight children had a higher risk of SNHL than normal weight children (adjusted OR 1.78; 95% CI: 1.08, 2.95). Autism was significantly associated with increased risk of sub-clinical SNHL only (adjusted OR 2.00; 95% CI 1.34, 2.98). CONCLUSIONS: No association was found between obesity and pediatric SNHL. Underweight children may represent a higher-risk population for SNHL. There appears to be an increasing risk of SNHL as children approach adolescence. Further study of systemic risk factors for SNHL is indicated. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1416-1419, 2021.

Persistent Postural-Perceptual Dizziness in Children and Adolescents.

OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is a recently defined diagnostic syndrome characterized by chronic symptoms of dizziness, unsteadiness, and/or non-spinning vertigo. Although PPPD has been studied in adults, reports in the pediatric population are few. The goal of this study was to describe the presentation and treatment of PPPD in a group of pediatric patients. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: ≤21 years old, who met Bárány Society consensus criteria for a diagnosis of PPPD and were followed for ≥6 months or until symptom resolution. MAIN OUTCOME MEASURESS: Patient demographics, comorbidities, symptom chronicity, and response to treatment(s). RESULTS: Of the 53 patients identified, 44 (83.0%) were women. Mean age at the time of initial evaluation was 14.6 years old. Common diagnoses in addition to PPPD included benign paroxysmal positional vertigo (64.2%), vestibular migraine (56.6%), and anxiety (28.3%). A high proportion of patients (43.4%) reported initially missing school or work due to their symptoms. Eighteen patients (34.0%) reported symptom resolution ranging from 2 to 48 months after diagnosis (median 9 mo). Of these patients, 15 of 18 attended physical therapy (PT), 11 of 18 attended cognitive behavioral therapy (CBT) and/or biofeedback therapy, and 10 of 18 took selective serotonin reuptake inhibitor (SSRI) medications, and 7 of 18 (40%) did a combination of all three therapies. CONCLUSION: PPPD can impact patients at a young age, and prolonged symptoms present a significant burden to children and adolescents, many of whom are unable to attend school. Treatments such as PT, CBT, and SSRI medication may be effective.

Benign Paroxysmal Positional Vertigo in Children and Adolescents With Concussion.

BACKGROUND: Dizziness after concussion is primarily attributed to effects on the brain, but traumatic inner ear disorders can also contribute. Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that can result from minor head trauma and can be easily diagnosed and rapidly treated in an office setting. The role of BPPV in pediatric postconcussive dizziness has not been well-studied. PURPOSE: To evaluate the prevalence and clinical features of BPPV in a group of pediatric patients with concussion and prolonged dizziness after concussion. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 3. METHODS: Retrospective review of 102 patients seen within the past 3 years in a pediatric multidisciplinary concussion clinic for evaluation of postconcussive dizziness. RESULTS: BPPV was diagnosed in 29.4% (30/102) of patients with postconcussion syndrome and dizziness. All patients with BPPV were treated with repositioning maneuvers, except for 5 patients who had spontaneous resolution of symptoms. Patients were evaluated at an average of 18.8 weeks (SD, 16.4 weeks) after the injury. BPPV was diagnosed at similar rates regardless of gender or age group (children vs adolescents). The mean Post-Concussion Symptom Scale (PCSS) score did not differ significantly between patients with (58.3 [SD, 22.5]) or without BPPV (55.8 [SD, 29.4]; P = 0.39). The PCSS "balance problems or dizziness" subscore also did not differ between patients with (3.3 [SD, 1.7]) or without BPPV (2.8 [SD, 1.6]; P = 0.13). CONCLUSION: BPPV is fairly common in pediatric concussion, occurring in one-third of the patients studied. BPPV is often not diagnosed and treated until many weeks after the injury. Increased awareness of the evaluation and management of BPPV among pediatric concussion providers may help expedite resolution of dizziness and hasten overall recovery in affected patients. CLINICAL RELEVANCE: BPPV is a treatable cause of dizziness caused by minor head injuries and is more common than previously reported in pediatric patients with concussion. Improved awareness of BPPV by concussion providers may expedite recovery.

Multifactorial Characteristics of Pediatric Dizziness and Imbalance.

OBJECTIVES: To examine the relative prevalence of individual diagnoses in children and adolescents presenting with dizziness and/or imbalance, and to assess the proportion of patients assigned multiple contributing diagnoses. STUDY DESIGN: Retrospective cohort study. METHODS: We retrospectively reviewed our internal database of all patients seen at our pediatric vestibular program between January 2012 and March 2019 to determine the incidence of common diagnoses and groups of diagnoses for patients ages 21 or younger. RESULTS: One thousand twenty-one patients were included with a mean age of 12.5 ± 4.9 years (range: 9 months-21 years). Of this total, 624 patients were female and 397 were male. Common diagnoses included vestibular migraine (VM; 35.0%), benign paroxysmal positional vertigo (BPPV; 21.6%), primary dysautonomia (15.7%), anxiety disorder (13.5%), and persistent postural perceptual dizziness (PPPD; 11.2%). A high proportion of patients (44.4%) received multiple contributing diagnoses. VM was frequently diagnosed with BPPV or PPPD, and 22 patients were diagnosed with all three concurrently. CONCLUSION: The causes of dizziness and imbalance in the pediatric population are diverse, and many patients have multiple diagnoses that are often interrelated. It is important that providers recognize that the causes of vestibular symptoms in children and adolescents may be multifactorial and may span across multiple specialties. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1308-E1314, 2021.

Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss.

Hearing loss (HL) is the most common sensory deficit in humans and is frequently accompanied by peripheral vestibular loss (PVL). While often overlooked, PVL is an important sensory dysfunction that may impair development of motor milestones in children and can have a significant negative impact on quality of life. In addition, many animal and in vitro models of deafness use vestibular hair cells as a proxy to study cochlear hair cells. The extent of vestibular end organ dysfunction associated with genetic pediatric hearing loss is not well-understood. We studied children with a known genetic cause of hearing loss who underwent routine preoperative vestibular testing prior to cochlear implantation between June 2014 and July 2020. Vestibular testing included videonystagmography, rotary chair, video head impulse testing, and/or vestibular evoked myogenic potentials. Etiology of HL was determined through history, physical examination, imaging, laboratory testing, and/or genetic testing. Forty-four children (21 female/23 male) met inclusion criteria; 24 had genetic non-syndromic and 20 had genetic syndromic forms of HL. Mean age at the time of testing was 2.8 ± 3.8 years (range 7 months-17 years). The most common cause of non-syndromic HL was due to mutations in GJB2 (n = 13) followed by MYO15A (3), MYO6 (2), POU3F4 (2), TMPRSS3 (1), CDH23 (1), TMC1 (1), and ESRRB (1). The most common forms of syndromic HL were Usher syndrome (4) and Waardenburg (4), followed by SCID/reticular dysgenesis (3), CHARGE (2), CAPOS (1), Coffin-Siris (1), Jervell and Lange-Nielsen (1), Noonan (1), peroxisome biogenesis disorder (1), Perrault (1), and Trisomy 21 (1). Overall, 23 patients (52%) had PVL. A larger proportion of children with syndromic forms of HL had PVL (12/20, 60%) compared with children with genetic non-syndromic HL (11/24, 46%), though without statistical significant (p = 0.3). The occurrence of PVL varied by affected gene. In conclusion, PVL is a common finding in children with syndromic and non-syndromic genetic HL undergoing vestibular evaluation prior to cochlear implantation. Improved understanding of the molecular physiology of vestibular hair cell dysfunction is important for clinical care as well as research involving vestibular hair cells in model organisms and in vitro models.

Severe motion sickness in infants and children.

INTRODUCTION: Susceptibility to severe motion sickness has not been well described in the pediatric population, particularly in very young children. This study aimed to describe and evaluate risk factors and treatment responses in a group of children with severe motion sickness, including infants and toddlers. METHODS: We conducted a retrospective review of patients less than 18 years of age seen in our pediatric vestibular program for evaluation of motion sickness over a 6-year period. RESULTS: A total of 23 patients with motion sickness were identified. Age of onset ranged from 0 to 15 years old, with a mean age of 6.6 ± 4.2 years. Eleven patients (47.8%) were diagnosed with a migraine variant. Vestibular deficits were identified in four out of 17 patients (23.5%) who underwent formal vestibular testing. Other frequent comorbid conditions included recurrent/chronic otitis media (n = 9; 39.1%) and a history of motor delay (n = 7; 30.4%). A high proportion of patients reported symptom improvement when treated with meclizine, ondansetron, cyproheptadine, or vestibular rehabilitation. DISCUSSION: Motion sickness can impact children even in infancy. Common comorbid conditions that may contribute to pediatric motion sickness include migraine disorders, vestibular impairment, otitis media, and motor delay. Treatments such as cyproheptadine and vestibular rehabilitation may be helpful but require further study.

Prevalence of hepatitis C infection in adult patients who underwent congenital heart surgery prior to screening in 1992.

Before the routine screening of donor blood for hepatitis C virus (HCV) began in 1992, patients who received blood transfusions were at increased risk for HCV infection. Patients with congenital heart disease requiring surgery were at particular risk because of the large volume of blood products required. It was hypothesized that patients who had congenital heart surgery before 1992 would have a high prevalence of HCV infection and would benefit from routine screening as part of cardiologic follow-up. HCV screening is performed on all patients in the Adult Congenital Cardiac Program at the investigators' center. Of 198 patients who underwent heart surgery before 1992, 17 (8.6%) had positive HCV antibody results, and 8 (4.0%) had positive HCV ribonucleic acid results. Only 1 of these patients had elevated serum transaminase levels at the time of screening. In conclusion, the data from this study demonstrated an approximately fivefold increased prevalence of HCV infection in adults with congenital heart disease compared with the aged-matched general population. Serum transaminase levels are not a valid screening method. The long-term significance of HCV in this population is not known. Routine HCV screening for all patients who underwent cardiac surgery before 1992 is recommended.