Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Two-year clinical outcomes after coronary drug-eluting stent placement in Chinese men and women: a multicenter, prospective registry study

Rajiv Shrestha,1 Sandeep Gami,1 Jing Xu,2 Du-Jiang Xie,2 Zhi-Zhong Liu,2 Tian Xu,1 Fei Ye,2 Shi-Qing Din,3 Xue-Song Qian,4 Song Yang,5 Yue-Qiang Liu,6 Feng Li,7 Ai-Ping Zhang,8 Shao-Liang Chen2 1Nanjing Medical University, Nanjing, 2Nanjing First Hospital, Nanjing Medical University, Nanjing, 3Huainan Xinhua Hospital, Huainan, 4Zhangjiagang People&#39;s Hospital, Zhangjiagang, 5Yixin People&#39;s Hospital, Yixin, 6Jintan People&#39;s Hospital, Jintan, 7Huainan Oriental General Hospital, Huainan, 8Huainan People&#39;s Hospital, Huainan, People&#39;s Republic of China Background: Previous studies have reported a discrepancy in baseline characteristics and outcomes after percutaneous coronary intervention between men and women. However, this finding has never been verified in the Chinese population. The present study analyzed two-year clinical outcomes after placement of coronary drug-eluting stents in Chinese men and women. Methods: From January 2005 to December 2010, a total of 3804 Chinese patients (2776 men, 1028 women) who underwent drug-eluting stent implantation were studied prospectively. The primary endpoint was the composite major adverse cardiac event (MACE) rate, including myocardial infarction, cardiac death, and target vessel revascularization at two years. Stent thrombosis served as the safety endpoint. Propensity score matching was used to compare the adjusted MACE rate between the two groups. Results: At two-year follow-up, unadjusted rates of myocardial infarction, non-ST segment elevation myocardial infarction, target vessel revascularization, and MACE were significantly different between men (6.84%, 4.6%, 13.1%, and 21.7%, respectively) and women (3.8% [P = 0.001], 2.0% [P < 0.001] 10.3% [P = 0.025], and 16.3% [P < 0.001], respectively). After propensity score matching, there were no significant differences in composite MACE and individual endpoints at two years between the genders. Conclusion: Despite all the unfavorable risk factor clustering in women and complex coronary disease in men, the two-year clinical outcomes after coronary stent placement were comparable between Chinese women and men. Keywords: drug-eluting stent, major adverse cardiac event, gender difference, clinical follow-u

Membrane Insertion for the Detection of Lipopolysaccharides: Exploring the Dynamics of Amphiphile-in-Lipid Assays

<div><p>Shiga toxin-producing <i>Escherichia coli</i> is an important cause of foodborne illness, with cases attributable to beef, fresh produce and other sources. Many serotypes of the pathogen cause disease, and differentiating one serotype from another requires specific identification of the O antigen located on the lipopolysaccharide (LPS) molecule. The amphiphilic structure of LPS poses a challenge when using classical detection methods, which do not take into account its lipoglycan biochemistry. Typically, detection of LPS requires heat or chemical treatment of samples and relies on bioactivity assays for the conserved lipid A portion of the molecule. Our goal was to develop assays to facilitate the direct and discriminative detection of the entire LPS molecule and its O antigen in complex matrices using minimal sample processing. To perform serogroup identification of LPS, we used a method called membrane insertion on a waveguide biosensor, and tested three serogroups of LPS. The membrane insertion technique allows for the hydrophobic association of LPS with a lipid bilayer, where the exposed O antigen can be targeted for specific detection. Samples of beef lysate were spiked with LPS to perform O antigen specific detection of LPS from <i>E</i>. <i>coli</i> O157. To validate assay performance, we evaluated the biophysical interactions of LPS with lipid bilayers both in- and outside of a flow cell using fluorescence microscopy and fluorescently doped lipids. Our results indicate that membrane insertion allows for the qualitative and reliable identification of amphiphilic LPS in complex samples like beef homogenates. We also demonstrated that LPS-induced hole formation does not occur under the conditions of the membrane insertion assays. Together, these findings describe for the first time the serogroup-specific detection of amphiphilic LPS in complex samples using a membrane insertion assay, and highlight the importance of LPS molecular conformations in detection architectures.</p></div