Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis

PMCID: PMC3856490This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PMCID: PMC385649

In Vitro Fertilization and Risk for Hypertensive Disorders of Pregnancy: Associations With Treatment Parameters

With an increasing proportion of pregnancies being conceived using assisted-reproductive technology, important changes to in vitro fertilization (IVF) such as the use of cryopreserved oocytes or embryos have been made. It is now established that adverse maternal and infant perinatal outcomes are associated with both assisted reproductive technologies and subfertility

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Model Development and Validation of Personal Exposure to Volatile Organic Compound Concentrations

Background: Direct measurement of exposure to volatile organic compounds (VOCs) via personal monitoring is the most accurate exposure assessment method available. However, its wide-scale application to evaluating exposures at the population level is prohibitive in terms of both cost and time. Consequently, indirect measurements via a combination of microenvironment concentrations and personal activity diaries represent a potentially useful alternative. Objective: The aim of this study was to optimize a model of personal exposures (PEs) based on microenvironment concentrations and time/activity diaries and to compare modeled with measured exposures in an independent data set. Materials: VOC PEs and a range of microenvironment concentrations were collected with active samplers and sorbent tubes. Data were supplemented with information collected through questionnaires. Seven models were tested to predict PE to VOCs in 75% (n = 370) of the measured PE data set, whereas the other 25% (n = 120) was used for validation purposes. Results: The best model able to predict PE with independence of measurements was based upon stratified microenvironment concentrations, lifestyle factors, and individual-level activities. The proposed model accounts for 40–85% of the variance for individual VOCs and was validated for almost all VOCs, showing normalized mean bias and mean fractional bias below 25% and predicting 60% of the values within a factor of 2. Conclusions: The models proposed identify the most important non-weather-related variables for VOC exposures; highlight the effect of personal activities, use of solvents, and exposure to environmental tobacco smoke on PE levels; and may assist in the development of specific models for other locations.peer-reviewe

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease