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An elusive problem in the adhesion G protein-coupled receptor (AGPCR) field is full understanding of the activation mechanisms of the 33-member receptor class. With the recent solution of active-state structures of nearly one-quarter of AGPCRs, clarity has been brought to how AGPCRs are activated in response to endogenous full agonists. AGPCRs are self-activated via a tethered peptide agonist (TA) that transitions from a concealed or encrypted location to a decrypted state that binds to a typical GPCR orthosteric binding pocket. Here, we summarize the key milestones that led to the discovery of the AGPCR TA activation mechanism and discuss how extracellular shear forces may initiate TA decryption in physiological contexts. We compare the new active-state AGPCR structures and note that the orthosteric site-engaged TAs adopt a remarkably similar partial a-helical hook-like conformation, despite divergence of overall receptor similarity. Further, we contrast the TA-bound AGPCR structures to a partially active AGPCR structure to highlight the transitions AGPCRs may undergo during activation. Finally, we provide commentary on the validity of alternative AGPCR activation mechanisms.

Objective To demonstrate how expanding services covered by a “bundled payment” can also expand variation in the costs of treating patients under the bundle, using the Medicare dialysis program as an example. Data Sources/Study Setting Observational claims-based study of 197,332 Medicare hemodialysis beneficiaries enrolled for at least one quarter during 2006–2008. Study Design We estimated how resource utilization (all health services, dialysis-related services, and medications) changes with intensity of secondary hyperparathyroidism (sHPT) treatment. Data Extraction Methods Using Medicare claims, a patient-quarter level dataset was constructed, including a measure of sHPT treatment intensity. Principal Findings Under the existing, narrow dialysis bundle, utilization of covered services is relatively constant across treatment intensity groups; under a broader bundle, it rises more rapidly with treatment intensity. Conclusions The broader Medicare dialysis bundle reimburses providers uniformly, even though patients treated more intensively for sHPT cost more to treat. Absent any payment adjustments or efforts to ensure quality, this flat payment schedule may encourage providers to avoid high-intensity patients or reduce their treatment intensity. The first incentive harms efficiency. The second may improve or worsen efficiency, depending on whether it reduces appropriate or inappropriate treatment.

The reaction of thiobarbituric acids with chloroacetyl chloride in presence of triethylamine afforded 5-chloroacetyl derivatives which on cyclisation with ethanolic sodium acetate gave the corresponding furo[2,3-d]pyrimidines. Further the 5-chloroacetyl derivative on reaction with ammonium dithiocarbamate and thioacetamide gave 1,3-diaryl-1,3-dihydro-2-thioxo-5-(thiazol-4-yl)-2H,5H-pyrimidine-4,6-diones