Siderocalin fusion proteins enable a new 86Y/90Y theranostic approach.

The mammalian protein siderocalin binds bacterial siderophores and their iron complexes through cation-π and electrostatic interactions, but also displays high affinity for hydroxypyridinone complexes of trivalent lanthanides and actinides. In order to circumvent synthetic challenges, the use of siderocalin-antibody fusion proteins is explored herein as an alternative targeting approach for precision delivery of trivalent radiometals. We demonstrate the viability of this approach in vivo, using the theranostic pair 90Y (ß-, t1/2 = 64 h)/86Y (ß+, t1/2 = 14.7 h) in a SKOV-3 xenograft mouse model. Ligand radiolabeling with octadentate hydroxypyridinonate 3,4,3-LI(1,2-HOPO) and subsequent protein binding were achieved at room temperature. The results reported here suggest that the rapid non-covalent binding interaction between siderocalin fusion proteins and the negatively charged Y(iii)-3,4,3-LI(1,2-HOPO) complexes could enable purification-free, cold-kit labeling strategies for the application of therapeutically relevant radiometals in the clinic.

Which anticoagulant is safest for frail elderly patients with nonvalvular A-fib?

In a retrospective study comparing direct oral anticoagulants vs warfarin in this population, apixaban's adverse event rate was lower regardless of frailty status.

Humanism at heart: preserving empathy in third-year medical students.

PURPOSE: Research suggests that medical student empathy erodes during undergraduate medical education. The authors evaluated the Jefferson Scale of Physician Empathy Medical Student Version (JSPE-MS) scores of two consecutive medical school classes to assess the impact of an educational intervention on the preservation of empathy. METHOD: The authors conducted a before-and-after study of 209 Robert Wood Johnson Medical School (RWJMS) students enrolled in the classes of 2009 and 2010. Students' clerkships included a mandatory, longitudinal "Humanism and Professionalism" (H&P) component, which included blogging about clerkship experiences, debriefing after significant events, and discussing journal articles, fiction, and film. Students completed the JSPE-MS during their first and last clerkships. RESULTS: The results showed that (1) contrary to previous studies' findings, third-year students did not show significant decline in empathy as measured by the JSPE-MS (these students, from two consecutive RWJMS classes, experienced the H&P intervention), (2) students selected for the Gold Humanism Honor Society (GHHS) were significantly different from their peers in empathy scores as measured by JSPE-MS, and (3) knowledge of selection for the GHHS seems to positively influence students' JSPE-MS scores. CONCLUSIONS: Maintaining empathy during the third year of medical school is possible through educational intervention. A curriculum that includes safe, protected time for third-year students to discuss their reactions to patient care situations during clerkships may have contributed to the preservation of empathy. Programs designed to validate humanism in medicine (such as the GHHS) may reverse the decline in empathy as measured by the JSPE-MS.

Using the multifaceted Rasch model to improve the TAT/PSE measure of need for achievement.

We used the Rasch (1980) model to develop new pictures for the Thematic Apperception Test (C. D. Morgan & Murray, 1938; McClelland, Atkinson, Clark, & Lowell, 1953) or picture story exercise to measure need for achievement (nAch). In Experiments 1 and 2, we analyzed stories to assess the difficulty level of a total of 8 pictures using the multifaceted Rasch model with picture difficulty, story probe difficulty, and participant ability as facets with a partial credit model (FACETS; Linacre, 2005). A total of 6 pictures were retained and 4 new ones added for Experiment 3 in which 201 participants wrote 6 stories to a random set of the 10 pictures. FACETS analysis revealed improved person separation reliability. In Experiment 4, 206 participants wrote 1 story to the Studying picture either before or after filling out a battery of achievement-related questionnaires. The 2 experimental groups did not differ in the amount of nAch in their stories. The coder facet was demonstrated with 2 independent coders using the revised coding system for nAch.