Accuracy and Feasibility of Three-Dimensional Ultrasound Testing in Eye Clinic and Emergency Department Patients with Vision Complaints.

BACKGROUND: Ocular emergencies comprise 2-3% of emergency department (ED) visits, with retinal detachment requiring emergency surgery. Two-dimensional ultrasound is a rapid bedside tool but is highly operator dependent. OBJECTIVE: We determined three-dimensional ultrasound (3DUS) feasibility, acceptability, and usability in eye pathology detection using the ophthalmologist examination as reference standard. METHODS: We performed a prospective, blinded cohort study of a 3DUS-enabling device in 30 eye clinic and ED patients with visual symptoms and calculated 3DUS performance characteristics. Two expert readers interpreted the 3DUS images for pathology. All participants completed surveys. RESULTS: 3DUS sensitivity was 0.81, specificity 0.73, positive predictive value 0.54, negative predictive value 0.91, and likelihood ratio (LR)+/LR- 3.03 and 0.26, respectively. Novice and expert sonographers had "substantial" agreement in correct diagnosis of abnormal vs. normal (κ = 0.68, 95% confidence interval 0.48-0.88). Most patients indicated that 3DUS is fast, comfortable, helps them understand their problem, and improves provider interaction/care, and all sonographers agreed; 4/5 sonographers felt confident performing ultrasound. Expert readers correctly identified an abnormal eye in 83/120 scans (76%) and correct diagnosis in 72/120 scans (65%), with no statistical difference between novice (79%; 69%) and expert (72%; 61%) sonographers (p = 0.39, p = 0.55), suggesting reduced operator dependence. Reader diagnosis confidence and image quality varied widely. Image acquisition times were fast for novice (mean 225 ± 83 s) and expert (201 ± 51) sonographers, with fast expert reader interpretation times (225 ± 136). CONCLUSIONS: A 3DUS-enabling device demonstrates a sensitivity of 0.81 and specificity of 0.73 for disease detection, fast image acquisition, and may reduce operator dependence for detecting emergent retinal pathologies. Further technological development is needed to improve diagnostic accuracy in identifying and characterizing retinal pathology.

Interactions with the bifunctional interface of the transcriptional coactivator DCoH1 are kinetically regulated.

Pterin-4a-carbinolamine dehydratase (PCD) is a highly conserved enzyme that evolved a second, unrelated function in mammals, as a transcriptional coactivator. As a coactivator, PCD is known as DCoH or dimerization cofactor of the transcription factor HNF-1. These two activities are associated with a change in oligomeric state: from two dimers interacting as an enzyme in the cytoplasm to a dimer interacting with a dimer of HNF-1 in the nucleus. The same interface of DCoH forms both complexes. To determine how DCoH partitions between its two functions, we studied the folding and stability of the DCoH homotetramer. We show that the DCoH1 homotetramer is kinetically trapped, meaning once it forms it will not dissociate to interact with HNF-1. In contrast, DCoH2, a paralog of DCoH1, unfolds within hours. A simple mutation in the interface of DCoH2 from Ser-51 to Thr, as found in DCoH1, increases the kinetic stability by 9 orders of magnitude, to τ(½) ∼ 2 million years. This suggests that the DCoH1·HNF-1 complex must co-fold to interact. We conclude that simple mutations can dramatically affect the dissociation kinetics of a complex. Residue 51 represents a "kinetic hot spot" instead of a "thermodynamic hot spot." Kinetic regulation allows PCD to adopt two distinct functions. Mutations in DCoH1 associated with diabetes affect both functions of DCoH1, perhaps by disrupting the balance between the two DCoH complexes.