Efficient labeling of protein-based targeting ligands with various cargos (drugs, imaging agents, nanoparticles, etc.) is essential to the fields of molecular imaging and targeted therapeutics. Many common bioconjugation techniques, however, are inefficient, non-stoichiometric, not site-specific, and/or incompatible with certain classes of protein scaffolds. Additionally, these techniques can result in a mixture of conjugated and unconjugated products, which are often difficult to separate. In this study, a bacterial sortase enzyme was utilized to condense targeting ligand purification and site-specific conjugation at the C-terminus into a single step. A model was produced to determine optimal reaction conditions for high conjugate purity and efficient utilization of cargo. As proof-of-principle, the sortase-tag expressed protein ligation (STEPL) technique was used to generate tumor-specific affinity ligands with fluorescent labels and/or azide modifications at high purity (>95%) such that is was not necessary to remove unconjugated impurities. Click chemistry was then used for the highly efficient and site-specific attachment of the azide-modified targeting ligands onto nanoparticles.
ObjectiveTo quantify which publicly reported hospital quality metrics have the greatest impact on a patient’s simulated hospital selection for hip or knee arthroplasty.DesignDiscrete choice experiment.SettingTwo university-affiliated orthopaedic clinics in the greater Baltimore area, Maryland, USA.ParticipantsOne hundred and twenty-eight patients who were candidates for total hip or knee arthroplasty.Primary and secondary outcome measuresThe effect and magnitude of acceptable trade-offs between publicly reported hospital quality parameters on patients’ decision-making strategies using a Hierarchical Bayes model.ResultsPublicly reported information on patient perceptions of attention to alleviation of postoperative pain had the most influence on simulated hospital choice (20.7%), followed by methicillin-resistantStaphylococcus aureus(MRSA) rates (18.8%). The understandability of the discharge instructions was deemed the least important attribute with a relative importance of 6.9%. Stratification of these results by insurance status and duration of pain prior to surgery revealed that patient demographics and clinical presentation affect the decision-making paradigm.ConclusionsPublicly available information regarding hospital performance is of interest to hip and knee arthroplasty patients. Patients are willing to accept suboptimal understanding of discharge instructions, lower hospital ratings and suboptimal cleanliness in exchange for better postoperative pain management, lower MRSA rates, and lower complication rates.
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