The essential mammalian enzyme O-GlcNAc Transferase (OGT) is uniquely responsible for transferring N-acetylglucosamine to over a thousand nuclear and cytoplasmic proteins, yet there is no known consensus sequence and it remains unclear how OGT recognizes its substrates. To address this question, we developed a protein microarray assay that chemoenzymatically labels de novo sites of glycosylation with biotin, allowing us to simultaneously assess OGT activity across >6000 human proteins. With this assay we examined the contribution to substrate selection of a conserved asparagine ladder within the lumen of OGT's superhelical tetratricopeptide repeat (TPR) domain. When five asparagines were mutated, OGT retained significant activity against short peptides, but showed limited limited glycosylation of protein substrates on the microarray. O-GlcNAcylation of protein substrates in cell extracts was also greatly attenuated. We conclude that OGT recognizes the majority of its substrates by binding them to the asparagine ladder in the TPR lumen proximal to the catalytic domain.
Bicycling is an increasingly common activity in the United States that is often associated with fall injuries to the head and face. Although helmets lessen head injury, their role in reducing facial injuries is less clear; therefore, it is important to understand the protective capacity for the face in current helmet design. OBJECTIVE To estimate the conventional bicycle helmet's association with the rate of facial injury after bicycle crashes. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study accessed records from January 1, 2010, to December 31, 2014, from the National Trauma Databank, which collects data from emergency departments in US hospitals. Each record pertained to 1 emergency department admission for a bicycle crash. The National Trauma Databank registry data are collected and recorded by incident, which is equivalent to an injury-related hospital admission. All injuries involving patients aged 18 to 65 years for whom data on helmet use and injury were available were included. Statistical analysis was conducted from July 19 to October 17, 2016. EXPOSURES Helmeted and nonhelmeted bicycle crashes. MAIN OUTCOMES AND MEASURES Head and facial injuries among helmeted and nonhelmeted bicycle crashes. RESULTS A total of 85 187 facial injuries met inclusion criteria (patient age 18-65 years, availability of helmet use status, and type of injury). Demographic information on bicycle riders was frequently unavailable. Among all injuries, fractures to the head (11.6% [9854]) and face (11.3% [9589]) occurred at similar rates. Helmets reduced head fractures by 52% (from 14.0% [7623] to 7.3% [2231]) and head soft-tissue injuries by 30% (from 15.0% [8151] to 10.9% [3358]), but had lower rates in protecting against facial injuries. While reducing facial injuries overall, the amount of protection with helmet use varied with facial location of the injury. Reduction in facial fractures was 35% (95% CI, 31%-39%) for upper face, 28% (95% CI, 23%-32%) for mid face, and 21% (95% CI, 15%-26%) for the lower face. Helmets were less protective against facial soft-tissue injuries, with a reduction of 33% (95% CI, 30%-36%) in the upper face, 21% (95% CI, 16%-26%) in the mid face, and 2% (95% CI, 0%-6%) in the lower face. CONCLUSIONS AND RELEVANCE Although bicycle helmets provide some protection against facial injuries after bicycle crashes, the level of protection depends on the proximity of the injury to the helmeted head. The lower face is particularly vulnerable to injury despite helmet use.
Purpose of reviewThe purpose of this narrative review is to discuss current literature about vestibular migraine and other cochleovestibular symptoms related to migraine. Recent findingsVestibular migraine affects 2.7% of the US population. Misdiagnosis is common. The pathophysiology is currently unknown but new research shows that calcitonin gene-related peptide, which is implicated in migraine headaches, is expressed in the audiovestibular periphery. A recent large-scale placebo-controlled trial looking at metoprolol for vestibular migraine was terminated early due to poor recruitment; however, at study completion, no differences were seen between treatment arms. Many other audiovestibular symptoms have been shown to be associated with migraine, including tinnitus, hearing loss, aural fullness, otalgia, and sinus symptoms. Migraine is also associated with risk for developing numerous otologic conditions, including Meniere's disease, vestibular loss, Benign Paroxysmal Positional Vertigo, and sudden sensorineural hearing loss. There is now some evidence that patients may experience fluctuating hearing loss and aural fullness without vertigo in association with migraine, which is called cochlear migraine. SummaryMigraine can cause a variety of audiologic and vestibular symptoms, and further research is required to understand how migraine affects the inner ear.
Objective To describe the prevalence and clinical characteristics of airway findings in a multi-institutional cohort of PHACE patients. Study Design Multicenter retrospective case series. Setting Multidisciplinary vascular anomalies clinics at 2 institutions. Methods Data were collected from the electronic medical record, including clinical presentation, airway findings, treatment, and outcomes. Results Of 55 PHACE patients, 22 (40%) had airway hemangiomas. Patients with airway involvement were more commonly female ( P = .034, odds ratio [OR] 23, 95% confidence interval [CI] 1.3-410) and of Caucasian ethnicity ( P = .020, OR 5.3, 95% CI 1.3-21). Anatomically, patients with bilateral S3 involvement had higher rates of airway disease ( P = .0012, OR 15, 95% CI 2.9-77). Most patients with airway hemangiomas had stridor (68%). Of the patients managed in the propranolol era (2008 or later, n = 35), 14 had airway involvement. All 14 were treated with propranolol, whereas 13 (62%) of 21 nonairway patients were treated with propranolol. The average treatment duration was longer in the airway patients (22.1 vs 16.7 months). All patients who underwent tracheostomy (n = 4) did so before 2008. Conclusion Risk factors for airway involvement in PHACE include female gender, Caucasian ethnicity, and stridor. Since the widespread use of propranolol, fewer patients have required surgical management of their airway disease. Given the high prevalence of airway involvement even in patients without stridor, assessment of the airway is a crucial component of a comprehensive PHACE workup.
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