Potentially nonadentate (NO) bifunctional chelator p-SCN-Bn-Hneunpa and its immunoconjugate Hneunpa-trastuzumab for In radiolabeling are synthesized. The ability of p-SCN-Bn-Hneunpa and Hneunpa-trastuzumab to quantitatively radiolabel InCl at an ambient temperature within 15 or 30 min, respectively, is presented. Thermodynamic stability determination with In, Bi, and La resulted in high conditional stability constant (pM) values. In vitro human serum stability assays have demonstrated both In complexes to have high stability over 5 days. Mouse biodistribution of [In][In(p-NO-Bn-neunpa)], compared to that of [In][In(p-NH-Bn-CHX-A″-diethylenetriamine pentaacetic acid (DTPA))], at 1, 4, and 24 h shows fast clearance of both complexes from the mice within 24 h. In a second mouse biodistribution study, the immunoconjugates In-neunpa-trastuzumab andIn-CHX-A″-DTPA-trastuzumab demonstrate a similar distribution profile but with slightly lower tumor uptake of In-neunpa-trastuzumab compared to that ofIn-CHX-A″-DTPA-trastuzumab. These results were also confirmed by immuno-single photon emission computed tomography (immuno-SPECT) imaging in vivo. These initial investigations reveal the acyclic bifunctional chelator p-SCN-Bn-Hneunpa to be a promising chelator for In (and other radiometals) with high in vitro stability and also show Hneunpa-trastuzumab to be an excellent In chelator with promising biodistribution in mice.

Obesity is associated with chronic low-grade inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of cytokines which in turn impact on the surrounding tissue. However, inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary glucose and a major determinant of glycemia, the origin and consequence of muscle inflammation in the development of insulin resistance are poorly understood.We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and unsaturated fatty acids. Inflammatory pathway activation and cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc) exposed to 0.2 mM palmitate or palmitoleate. Conditioned media thereof, free of fatty acids, were then tested for their ability to activate RAW264.7 macrophages.Palmitate -but not palmitoleate- induced IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway. Palmitate (0.2 mM) alone did not induce insulin resistance in muscle cells, yet conditioned media from palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype.These results demonstrate that low concentrations of palmitate activate autonomous inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to insulin resistance in vivo.

The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children, and we were unable to create a specific scoring method that was able to do this.

Background: Weight is a crucial metric in the optimal care of pediatric patients in the inpatient setting. A patient's weight is not only necessary for appropriate medication dosing, but is also often an indicator of fluid and nutritional status. As such, having a documented weight is integral to clinical decision making, and failure to obtain daily weight measurements when needed can result in delays in treatment and discharge plans. The importance of daily weight monitoring as well as the challenges surrounding good adherence to daily weight orders has long been recognized. There is currently no formal standardized process for obtaining daily weights on our inpatient pediatric unit, resulting in suboptimal adherence to daily weight orders.

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