Anti-PIM2 (N-terminal) polyclonal antibody

Introduction. Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality (PRISM) are scoring systems to predict mortality likehood; thus, it is necessary to validate such predictors in Pediatric Intensive Care Units' population. Objective. To assess the validity of PRISM and PIM2 models of Mortality in Pediatrics Intensive Care Units at Hospital Infantil de Cordoba (PICUHI). Population, material and methods. 435 critically ill admitted patients were retrospectively analized in PICUHI from January 1st 2008 to January 31st 2008; 416 were included in the study, ruling out elective admitted patients with less than 12 hour at PICU length stay. There were no deaths in this Group. Original equations for each models, were used. Calibration was performed (p> 0.05) using Hosmer-Lemeshow (HL) goodness-of-fit tests. Scores were assessed through Standardized Mortality Ratio (SMR) and discrimination between patients alived and dead, was estimated calculating the area under ROC curve. Results. 416 admitted patients were included, (55.04%) were male 55.04%, median age was 3 years (1 month-17 years), with a median of 2 (1-76) admitted days in PICU. Mortality was 6.66%. PIM2 had an area under ROC curve of 0.88 (CI 95% 0.82-0.95) and PRIMS:0.85(CI95%0.78-0.92), with p 0.3570 value. HL calibration for PRISM was: x(2) 5.93 (p0.54), and PIM(2) was: x(2) 14.19 (p0.07). PRISM, Standardized Mortality Ratio (SMR) was: 1.00 (CI 95% 0.50-1.50) and PIM2 was 1.00 (CI 95% 0.55-1.55). Conclusions. Both scores discriminated and calibrated well as the p-value of the HL test, althougt the analysis of the HL table appears inadequate to PIM2 calibration, in terms of severity-adjusted mortality.

Cinnamic acid belongs to phenolic-acid class of polyphenols, one of the most abundant plant secondary metabolites. These substances are widely studied because of plethora of their biological activities. In particular, their inhibition of protein kinases contributes to the pleiotropic effects in the cell. Protein kinases are essential in controlling cell signaling networks. Selective targeting of oncogenic protein kinases increases clinical anticancer efficacy. Cinnamic acid and related compounds have inspired researchers in the design of numerous synthetic and semisynthetic inhibitors of oncogenic protein kinases for the past three decades. Interest in cinnamoyl-scaffold-containing compounds revived in recent years, which was stimulated by modern drug design and discovery methodologies such as in vitro and in silico HTS. This review presents cinnamic acid derivatives and analogs for which direct inhibition of protein kinases was identified. We also summarize significance of the above protein kinase families -validated or promising targets for anticancer therapies. The inhibition mode may vary from ATP-competitive, through bisubstrate-competitive and mixed-competitive, to non-competitive one. Kinase selectivity is often correlated with subtle chemical modifications, and may also be steered by an additional non-cinnamoyl fragment of the inhibitor. Specific cinnamic acid congeners may synergize their effects in the cell by a wider range of activities, like suppression of additional enzymes, e. g. deubiquitinases, influencing the same signaling pathways (e. g. JAK2/STAT). Cinnamic acid, due to its biological and physicochemical properties, provides nature-inspired ideas leading to novel inhibitors of oncogenic protein kinases and related enzymes, capable to target a variety of cancer cells.