Ligand oligomerization state controls Tie2 receptor trafficking and angiopoietin-2-specific responses.

Angiopoietin 1 (Ang1) is an activating ligand for the endothelial receptor tyrosine kinase Tie2, whereas Ang2 acts as a context-dependent agonist or antagonist that has a destabilizing effect on the vasculature. The molecular mechanisms responsible for the versatile functions of Ang2 are poorly understood. We show here that Ang2, but not Ang1, induces Tie2 translocation to the specific cell-matrix contact sites located at the distal end of focal adhesions. The Ang2-specific Tie2 translocation was associated with distinct Tie2 activation and downstream signals which differed from those of Ang1, and led to impaired cell motility and weak cell-matrix adhesion. We demonstrate that the different oligomeric or multimeric forms of the angiopoietins induce distinct patterns of Tie2 trafficking; the lower oligomerization state of native Ang2 was crucial for the Ang2-specific Tie2 redistribution, whereas multimeric structures of Ang1 and Ang2 induced similar responses. The Ang2-specific Tie2 trafficking to cell-matrix contacts was also dependent on the cell substratum, α2ß1-integrin-containing cell-matrix adhesion sites and intact microtubules. Our data indicate that the different subcellular trafficking of Tie2-Ang2 and Tie2-Ang1 complexes generates ligand-specific responses in the angiopoietin-Tie signaling pathway, including modulation of cell-matrix interactions.

Poor Online Patient Ratings of Otolaryngologists in the United States: What are Patients Saying?

OBJECTIVES: Online patient forums have become a platform for patient education and advocacy in many areas of medicine. The anonymity provided by such forums may encourage honest, candid responses. Using patient online reviews, this study sought to explore themes that arose from negatively perceived care interactions with American otolaryngologists using the Accreditation Council for Graduate Medical Education (ACGME) competency framework. STUDY DESIGN: Qualitative thematic analysis. METHODS: Through an iterative multistep process, a qualitative thematic analysis was conducted on negative reviews (defined as ratings of two or less out of five) of all American otolaryngologists found on a popular online physician-rating website (RateMDs.com). RESULTS: A systematic search through the RateMDs website revealed 2950 separate comments of negative reviews. Of these negative reviews, 350 were randomly selected for thematic analysis. The predominant themes that emerged aligned closely with the Accreditation Council for Graduate Medical Education (ACGME) competencies, in particularly with professionalism and interprofessional skills and communication. CONCLUSIONS: The negative reviews of American otolaryngologists revealed a number of areas where improvements could be made to quality of care. Patients value evidence-based medicine delivered by compassionate and respectful physicians. Isolating and aligning predominant themes within the ACGME framework proved a productive method to collect and organize pertinent patient feedback and integrate teaching into the post-graduate training and continuing professional development in order to avoid such negatively perceived interactions in the future.