Differential diagnosis of cardiovascular symptoms: setting the expectations for the ultrasound examination and medical education.

Within the past several decades, dramatic changes have been made in the field of diagnostic imaging. Many of these changes have been with ultrasound, which has been transformative in the efficiency and accuracy of diagnostics. Emergency physicians, intensivists, and other acute care clinicians are using and relying on critical care ultrasound imaging to better triage and diagnose patients at the point of care. As this new frontier of medicine continues to forge forward using this new and improving technology, we strongly believe in integrating ultrasound training earlier into the medical education curriculum. This paper reviews and discusses the transformation of medical diagnostics within the last few decades and describes changes that should be expected as point-of-care cardiac ultrasound evolves within medical education.

A designed protein interface that blocks fibril formation.

Protein fibril formation is implicated in many diseases, and therefore much effort has been focused toward the development of inhibitors of this process. In a previous project, a monomeric protein was computationally engineered to bind itself and form a heterodimer complex following interfacial redesign. One of the protein monomers, termed monomer-B, was unintentionally destabilized and shown to form macroscopic fibrils. Interestingly, in the presence of the designed binding partner, fibril formation was blocked. Here we describe the complete characterization of the amyloid properties of monomer-B and the inhibition of fiber formation by the designed binding partner, monomer-A. Both proteins are mutants of the betal domain of streptococcal protein-G. The free monomer-B protein forms amyloid-type fibrils, as determined by transmission electron microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific dye. Fibril formation kinetics are influenced by pH, protein concentration, and seeding with preformed fibrils. Under all conditions tested, monomer-A was able to inhibit the formation of monomer-B fibrils. This inhibition is specific to the engineered interaction, as incubation of monomer-B with wild-type protein-G (a structural homologue) did not result in inhibition under the same conditions. Thus, this de novo-designed heterodimeric complex is an excellent model system for the study of protein-based fibril formation and inhibition. This system provides additional insight into the development of pharmaceuticals for amyloid disorders, as well as the potential use of amyloid fibrils for self-assembling nanostructures.