Serological testing on the ADVIA Centaur system for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in specimens from deceased and living individuals demonstrates equivalent resultsƚ.

INTRODUCTION: To determine the suitability of human tissues and cells for transplantation, guidelines mandate infectious disease testing of serum or plasma obtained from deceased donors, which are often collected after cessation of the heartbeat. Tests used for this purpose are required to show equivalent performance when compared to pre-mortem specimens. This study evaluated whether serology assays for HIV Ag/Ab Combo, hepatitis B virus (HBc Total; HBsAgII), and HCV on the ADVIA Centaur system, were fit for testing post-mortem sera. Performance evaluation studies included precision, specificity, and sensitivity. METHODS: Blood specimens were collected within 24 h after death from 82 deceased and 83 healthy living individuals. Studies followed standard guidelines. The 20-day precision study was performed on five levels of post-mortem specimens (non-spiked and spiked). The specificity study compared 81-83 pre-mortem and 74-82 post-mortem specimens. The sensitivity study compared 50 pre-mortem and 50 post-mortem specimens spiked with positive sera for each analyte at two levels to achieve a low (near cutoff) positive result and a second higher positive result. RESULTS: Precision, specificity, and sensitivity study results met acceptance criteria for all assays and lots; post-mortem and pre-mortem results were equivalent. CONCLUSION: Based on this study, the ADVIA Centaur CHIV, HBcT, HBsAgII, and HCV assays are acceptable for use in routine testing of deceased donor sera collected after cessation of the heartbeat.

Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies.

Disregulated Wnt/beta-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, we identified anti-LRP6 antibodies that either inhibit or enhance Wnt signaling. Two classes of LRP6 antagonistic antibodies were discovered: one class specifically inhibits Wnt proteins represented by Wnt1, whereas the second class specifically inhibits Wnt proteins represented by Wnt3a. Epitope-mapping experiments indicated that Wnt1 class-specific antibodies bind to the first propeller and Wnt3a class-specific antibodies bind to the third propeller of LRP6, suggesting that Wnt1- and Wnt3a-class proteins interact with distinct LRP6 propeller domains. This conclusion is further supported by the structural functional analysis of LRP5/6 and the finding that the Wnt antagonist Sclerostin interacts with the first propeller of LRP5/6 and preferentially inhibits the Wnt1-class proteins. We also show that Wnt1 or Wnt3a class-specific anti-LRP6 antibodies specifically block growth of MMTV-Wnt1 or MMTV-Wnt3 xenografts in vivo. Therapeutic application of these antibodies could be limited without knowing the type of Wnt proteins expressed in cancers. This is further complicated by our finding that bivalent LRP6 antibodies sensitize cells to the nonblocked class of Wnt proteins. The generation of a biparatopic LRP6 antibody blocks both Wnt1- and Wnt3a-mediated signaling without showing agonistic activity. Our studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in Wnt-driven cancer.

Finding the right fit: redesign of orthopaedic orientation for a medical-surgical unit.

At most small community hospitals, orthopaedic patients are cared for on general medical-surgical units rather than on dedicated orthopaedic units. The mixed patient population of a typical medical-surgical unit limits the amount of exposure a new graduate nurse has to care for orthopaedic patients during the unit-based orientation. In 2006, a 20-bed medical-surgical unit at a community hospital in the northeast was expecting to orient eight new graduate nurses over the course of the year. The project team recognized a need to enhance the orthopaedic portion of the unit-based orientation to prepare the graduate nurses to provide "knowledgeable and safe care" (P. ) to orthopaedic patients. This article describes the development, implementation, and evaluation of a standardized, evidence-based orthopaedic curriculum piloted in 2006. The project increased the orthopaedic competency of the preceptors, provided the new graduate nurses with a standardized introduction to orthopaedic patient care, and had an unintended benefit of improving overall staff orthopaedic knowledge that improved the consistency and quality of care for orthopaedic patients at this community hospital.