Inflammatory Processes in Kawasaki Disease Reach their Peak at the Sixth Day of Fever Onset: Laboratory Profiles According to Duration of Fever

We evaluated the inflammatory indices according to the fever duration in children with Kawasaki disease (KD), and determined duration when the inflammatory processes in KD reach their peak. Children with KD (n=152) were classified into 7 groups according to fever duration: at the third day or earlier (n=20), fourth (n=33), fifth (n=46), sixth (n=15), seventh (n=15), eighth (n=9), and at the ninth day or later after fever onset (n= 14). The levels of various laboratory indices were determined 3 times: before, 24 hr and 7 days after intravenous immunoglobulin administration (2 g/kg). WBC and neutrophil counts, and C-reactive protein level were the highest at the sixth day. Levels of hemoglobin, albumin, and high density lipoprotein cholestrol were the lowest at the sixth day. Although these indices were not significant statistically between groups, the indices showed either bell-shaped or U-shaped distribution of which peak or trench were at the sixth day. These findiugs showed that the inflammatory processes in KD reach peak on the sixth day of fever onset. This finding is important because a higher single-dose intravenous immunoglobulin treatment before the peak day may help reduce the coronary artery lesions in KD

An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases

Blocking representation in the ERA-Interim driven EURO-CORDEX RCMs

While Regional Climate Models (RCMs) have been shown to yield improved simulations compared to General Circulation Model (GCM), their representation of large-scale phenomena like atmospheric blocking has been hardly addressed. Here, we evaluate the ability of RCMs to simulate blocking situations present in their reanalysis driving data and analyse the associated impacts on anomalies and biases of European 2-m air temperature (TAS) and precipitation rate (PR). Five RCM runs stem from the EURO-CORDEX ensemble while three RCMs are WRF models with different nudging realizations, all of them driven by ERA-Interim for the period 1981?2010. The detected blocking systems are allocated to three sectors of the Euro-Atlantic region, allowing for a characterization of distinctive blocking-related TAS and PR anomalies. Our results indicate some misrepresentation of atmospheric blocking over the EURO-CORDEX domain, as compared to the driving reanalysis. Most of the RCMs showed fewer blocks than the driving data, while the blocking misdetection was negligible for RCMs strongly conditioned to the driving data. A higher resolution of the RCMs did not improve the representation of atmospheric blocking. However, all RCMs are able to reproduce the basic anomaly structure of TAS and PR connected to blocking. Moreover, the associated anomalies do not change substantially after correcting for the misrepresentation of blocking in RCMs. The overall model bias is mainly determined by pattern biases in the representations of surface parameters during non-blocking situations. Biases in blocking detections tend to have a secondary influence in the overall bias due to compensatory effects of missed blockings and non-blockings. However, they can lead to measurable effects in the presence of a strong blocking underestimation.This work was funded by the Austrian Science Fund (FWF) under the project: Understanding Contrasts in high Mountain hydrology in Asia (UNCOMUN: I 1295-N29). This research was supported by the Faculty of Environmental, Regional and Educational Sciences (URBI), University of Graz, as well as the Federal Ministry of Science, Research and Economy (BMWFW) by funding the OeAD Grant Marietta Blau. This work was partially supported (JMG and SH) by the project MULTI-SDM (CGL2015-66583- R, MINECO/FEDER). DB was supported by the PALEOSTRAT (CGL2015-69699-R) project funded by the Spanish Ministry of Economy and Competitiveness (MINECO)