From evidence to practice:development of web-based Dutch lipid reference values

Introduction: In the Netherlands, the total number of yearly measured lipid profiles exceeds 500,000. While lipid values are strongly affected by age and sex, until recently, no up-to-date age- and sex-specific lipid reference values were available. We describe the translation of big-cohort lipid data into accessible reference values, which can be easily incorporated in daily clinical practice. Methods: Lipid values (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) from all healthy adults and children in the LifeLines cohort were used to generate age- and sex-specific percentiles. A combination of RStudio, Cascading Style Sheets and HyperText Markup Language was used to interactively display the percentiles in a responsive web layout. Results: After exclusion of subjects reporting cardiovascular disease or lipid-lowering therapy at baseline, 141,611 subjects were included. On the website, input fields were created for age, sex and all main plasma lipids. Upon input of these values, corresponding percentiles are calculated, and output is displayed in a table and an interactive graph for each lipid. The website has been made available in both Dutch and English and can be accessed at www.lipidtools.com. Conclusion: We constructed the first searchable, national lipid reference value tool with graphical display in the Netherlands to use in screening for dyslipidaemias and to reduce the underuse of lipid-lowering therapy in Dutch primary prevention. This study illustrates that data collected in big-cohort studies can be made easily accessible with modern digital techniques and preludes the digital health revolution yet to come

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

Risk factors for respiratory work disability in a cohort of pulp mill workers exposed to irritant gases

<p>Abstract</p> <p>Background</p> <p>The association between chronic respiratory diseases and work disability has been demonstrated a number of times over the past 20 years, but still little is known about work disability in occupational cohorts of workers exposed to respiratory irritants. This study investigated job or task changes due to respiratory problems as an indicator of work disability in pulp mill workers occupationally exposed to irritants.</p> <p>Methods</p> <p>Data about respiratory symptoms and disease diagnoses, socio-demographic variables, occupational exposures, gassing episodes, and reported work changes due to respiratory problems were collected using a questionnaire answered by 3226 pulp mill workers. Information about work history and departments was obtained from personnel files. Incidence and hazard ratios for respiratory work disability were calculated with 95% confidence intervals (CI).</p> <p>Results</p> <p>The incidence of respiratory work disability among these pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7-10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and chronic rhinitis, when analyzed in the same model.</p> <p>Conclusions</p> <p>This cohort study of pulp mill workers found that irritant peak exposure during gassing episodes was a strong predictor of changing work due to respiratory problems, even after adjustment for asthma, chronic bronchitis, and chronic rhinitis.</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

“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

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

Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

Contains fulltext : 97744.pdf (publisher's version ) (Open Access)BACKGROUND: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. RESULTS: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. CONCLUSIONS: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens