Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

Documentation of pharmaceutical care: Validation of an intervention oriented classification system.

During the dispensing process, pharmacists may come across technical and clinical issues requiring a pharmaceutical intervention (PI). An intervention-oriented classification system is a helpful tool to document these PIs in a structured manner. Therefore, we developed the PharmDISC classification system (Pharmacists' Documentation of Interventions in Seamless Care). The aim of this study was to evaluate the PharmDISC system in the daily practice environment (in terms of interrater reliability, appropriateness, interpretability, acceptability, feasibility, and validity); to assess its user satisfaction, the descriptive manual, and the online training; and to explore first implementation aspects. Twenty-one pharmacists from different community pharmacies each classified 30 prescriptions requiring a PI with the PharmDISC system on 5 selected days within 5 weeks. Interrater reliability was determined using model PIs and Fleiss's kappa coefficients (κ) were calculated. User satisfaction was assessed by questionnaire with a 4-point Likert scale. The main outcome measures were interrater reliability (κ); appropriateness, interpretability, validity (ratio of completely classified PIs/all PIs); feasibility, and acceptability (user satisfaction and suggestions). The PharmDISC system reached an average substantial agreement (κ = 0.66). Of documented 519 PIs, 430 (82.9%) were completely classified. Most users found the system comprehensive (median user agreement 3 [2/3.25 quartiles]) and practical (3[2.75/3]). The PharmDISC system raised the awareness regarding drug-related problems for most users (n = 16). To facilitate its implementation, an electronic version that automatically connects to the prescription together with a task manager for PIs needing follow-up was suggested. Barriers could be time expenditure and lack of understanding the benefits. Substantial interrater reliability and acceptable user satisfaction indicate that the PharmDISC system is a valid system to document PIs in daily community pharmacy practice