Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia pseudomallei </it>and <it>Burkholderia mallei </it>cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which <it>B. pseudomallei </it>and <it>B. mallei </it>adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms.</p> <p>Results</p> <p>Comparative sequence analyses identified a gene product in the published genome of <it>B. mallei </it>strain ATCC23344 (locus # BMAA0649) that resembles the well-characterized <it>Yersinia enterocolitica </it>autotransporter adhesin YadA. The gene encoding this <it>B. mallei </it>protein, designated <it>boaA</it>, was expressed in <it>Escherichia coli </it>and shown to significantly increase adherence to human epithelial cell lines, specifically HEp2 (laryngeal cells) and A549 (type II pneumocytes), as well as to cultures of normal human bronchial epithelium (NHBE). Consistent with these findings, disruption of the <it>boaA </it>gene in <it>B. mallei </it>ATCC23344 reduced adherence to all three cell types by ~50%. The genomes of the <it>B. pseudomallei </it>strains K96243 and DD503 were also found to contain <it>boaA </it>and inactivation of the gene in DD503 considerably decreased binding to monolayers of HEp2 and A549 cells and to NHBE cultures.</p> <p>A second YadA-like gene product highly similar to BoaA (65% identity) was identified in the published genomic sequence of <it>B. pseudomallei </it>strain K96243 (locus # BPSL1705). The gene specifying this protein, termed <it>boaB</it>, appears to be <it>B. pseudomallei</it>-specific. Quantitative attachment assays demonstrated that recombinant <it>E. coli </it>expressing BoaB displayed greater binding to A549 pneumocytes, HEp2 cells and NHBE cultures. Moreover, a <it>boaB </it>mutant of <it>B. pseudomallei </it>DD503 showed decreased adherence to these respiratory cells. Additionally, a <it>B. pseudomallei </it>strain lacking expression of both <it>boaA </it>and <it>boaB </it>was impaired in its ability to thrive inside J774A.1 murine macrophages, suggesting a possible role for these proteins in survival within professional phagocytic cells.</p> <p>Conclusions</p> <p>The <it>boaA </it>and <it>boaB </it>genes specify adhesins that mediate adherence to epithelial cells of the human respiratory tract. The <it>boaA </it>gene product is shared by <it>B. pseudomallei </it>and <it>B. mallei </it>whereas BoaB appears to be a <it>B. pseudomallei</it>-specific adherence factor.</p

Nonsmooth analysis of doubly nonlinear evolution equations

In this paper we analyze a broad class of abstract doubly nonlinear evolution equations in Banach spaces, driven by nonsmooth and nonconvex energies. We provide some general sufficient conditions, on the dissipation potential and the energy functional,for existence of solutions to the related Cauchy problem. We prove our main existence result by passing to the limit in a time-discretization scheme with variational techniques. Finally, we discuss an application to a material model in finite-strain elasticity.Comment: 45 page

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.</p

Harmonization of Food-Frequency Questionnaires and Dietary Pattern Analysis in 4 Ethnically Diverse Birth Cohorts

Background: Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice. Objectives: We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes. Methods: The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a previously validated instrument designed by the Fred Hutchinson Cancer Research Center, whereas FAMILY, START, and ABC used questionnaires specifically designed for use in white European, South Asian, and Aboriginal people, respectively. The serving sizes and consumption frequencies of individual food items within the 4 FFQs were harmonized and aggregated into 36 common food groups. Principal components analysis was used to identify dietary patterns that were internally validated against self-reported vegetarian status and externally validated against a modified Alternative Healthy Eating Index (mAHEI). Results: Three maternal dietary patterns were identified—“plant-based,” “Western,” and “health-conscious”—which collectively explained 29% of the total variability in eating habits observed in the NutriGen Alliance. These patterns were strongly associated with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r2 = 0.30, P < 0.001; for a plant-based diet), and average adherence to the plant-based diet was higher in participants in the fourth quartile of the mAHEI than in the first quartile (mean difference: 46.1%; r2 = 0.81, P < 0.001). Conclusion: Dietary data collected by using FFQs from ethnically diverse pregnant women can be harmonized to identify common dietary patterns to investigate associations between maternal dietary intake and health outcomes

Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies

The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk

“My Lung Disease Won’t Go Away, it’s There to Stay”: Profiles of Adaptation to Functional Limitations in Workers with Asthma and COPD

Purpose Earlier research has shown that adaptation (i.e., the way in which employees cope with limitations resulting from their disease) is associated with sick leave. Our aim was to investigate signs of adequate or inadequate adaptation in employees with asthma and COPD. Methods A Q-methodological study was carried out among 34 workers with asthma or COPD. Results Four adaptation profiles were distinguished: the eager, the adjusted, the cautious, and the worried workers. The adaptation profiles provide insight into the different ways in which workers with asthma and COPD cope with their illness at work. Conclusions The adaptation profiles serve as a starting point for the design of appropriate (occupational) care. The eager workers experience little difficulties at work; the cautious workers may need assistance in learning how to accept their disease; the worried workers need reassurance, and may need reactivation; the adjusted workers deserve extra attention, and, when necessary, advice on how to live with their asthma or COPD