First Results on Dark Matter Substructure from Astrometric Weak Lensing.

Low-mass structures of dark matter (DM) are expected to be entirely devoid of light-emitting regions and baryons. Precisely because of this lack of baryonic feedback, small-scale substructures of the Milky Way are a relatively pristine testing ground for discovering aspects of DM microphysics and primordial fluctuations on subgalactic scales. In this Letter, we report results from the first search for Galactic DM subhalos with time-domain astrometric weak gravitational lensing.

Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD.

Prospective pharmacological studies on breathomics profiles in COPD patients have not been previously reported. We assessed the effects of treatment and withdrawal of an extrafine inhaled corticosteroid (ICS)-long-acting β-agonist (LABA) fixed dose combination (FDC) using a multidimensional classification model including breathomics. A pilot, proof-of-concept, pharmacological study was undertaken in 14 COPD patients on maintenance treatment with inhaled fluticasone propionate/salmeterol (500/50 μg b.

The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease.

Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs.

Dupilumab for the treatment of asthma.

Dupilumab (REGN668/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma. Dupilumab is directed against the α-subunit of the interleukin (IL)-4 receptor and blocks the IL-4 and IL-13 signal transduction. Areas covered: Pathophysiological role of IL-4 and IL-13 in asthma; mechanism of action of dupilumab; pharmacology of IL-4 receptor; phase I and phase II studies with dupilumab; regulatory affairs.

Nailfold capillaroscopic parameters and skin telangiectasia patterns in patients with systemic sclerosis.

Objective: To correlate nailfold capillaroscopic parameters with the presence of skin telangiectases (TAs) in systemic sclerosis patients (SSc).

Methods: Thirty-three consecutive patients (28 women and 5 men, mean age 59±21years) affected by SSc according to the ACR/EULAR criteria, 30 with limited (lcSSc) and 3 with diffuse (dcSSc) skin disease, displaying the presence of skin TAs on face, hands, forearms, neck, and décolleté were recruited. Nailfold videocapillaroscopy (NVC) was performed to classify the patients into one of the three main patterns of SSc microangiopathy ("early", "active", "late"), and to calculate the microangiopathy evolution score (MES).

Skin lesion image segmentation using Delaunay Triangulation for melanoma detection.

Developing automatic diagnostic tools for the early detection of skin cancer lesions in dermoscopic images can help to reduce melanoma-induced mortality. Image segmentation is a key step in the automated skin lesion diagnosis pipeline. In this paper, a fast and fully-automatic algorithm for skin lesion segmentation in dermoscopic images is presented.

Investigational prostaglandin D2 receptor antagonists for airway inflammation.

Introduction: By activating DP1 and DP2 receptors on immune and non-immune cells, prostaglandin D2 (PGD2), a major metabolic product of cyclo-oxygenase pathway released after IgE-mediated mast cell activation, has pro-inflammatory effects, which are relevant to the pathophysiology of allergic airway disease. At least 15 selective, orally active, DP2 receptor antagonists and one DP1 receptor antagonist (asapiprant) are under development for asthma and/or allergic rhinitis.

Areas Covered: In this review, the authors cover the pharmacology of PGD2 and PGD2 receptor antagonists and look at the preclinical, phase I and phase II studies with selective DP1 and DP2 receptor antagonists.

Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers.

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured.

Electronic Nose and Exhaled Breath NMR-based Metabolomics Applications in Airways Disease.

Breathomics, the multidimensional molecular analysis of exhaled breath, includes analysis of exhaled breath with gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses), and metabolomics of exhaled breath condensate (EBC), a non-invasive technique which provides information on the composition of airway lining fluid, generally by high-resolution nuclear magnetic resonance (NMR) spectroscopy or MS methods. Metabolomics is the identification and quantification of small molecular weight metabolites in a biofluid. Specific profiles of volatile compounds in exhaled breath and metabolites in EBC (breathprints) are potentially useful surrogate markers of inflammatory respiratory diseases.

Canakinumab in adults with steroid-refractory pyoderma gangrenosum.

Background: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.

Objectives: To determine whether canakinumab is an effective and safe treatment in PG.

Methods: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study.

Liquid chromatography-mass spectrometry measurement of leukotrienes in asthma and other respiratory diseases.

Leukotrienes (LTs), including cysteinyl-LTs (LTC4, LTD4 and LTE4) and LTB4, are potent inflammatory lipid mediators which have been involved in the pathophysiology of respiratory diseases. LC-MS/MS techniques for measuring LT concentrations in sputum supernatants, serum, urine and exhaled breath condensate (EBC) have been developed. In asthmatic adults, reported LTB4 and LTE4 concentrations in sputum range from 79 to 7,220 pg/ml and from 11.

Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD.

Electronic noses (e-noses), artificial sensor systems generally consisting of chemical sensor arrays for the detection of volatile compound profiles, have potential applications in respiratory medicine. We assessed within-day and between-day repeatability of an e-nose made from 32 sensors in patients with stable chronic obstructive pulmonary disease (COPD). We also compared between-day repeatability of an e-nose, fraction of exhaled nitric oxide (FENO) and pulmonary function testing.

The electronic nose in respiratory medicine.

Several volatile organic compounds have been identified in exhaled breath in healthy subjects and patients with respiratory diseases by gas chromatography/mass spectrometry. Identification of selective patterns of volatile organic compounds in exhaled breath could be used as a biomarker of inflammatory lung diseases. An electronic nose (e-nose) is an artificial sensor system that generally consists of an array of chemical sensors for detection of volatile organic compound profiles (breathprints) and an algorithm for pattern recognition.

Diagnostic performance of an electronic nose, fractional exhaled nitric oxide, and lung function testing in asthma.

Background: Analysis of exhaled breath by biosensors discriminates between patients with asthma and healthy subjects. An electronic nose consists of a chemical sensor array for the detection of volatile organic compounds (VOCs) and an algorithm for pattern recognition. We compared the diagnostic performance of a prototype of an electronic nose with lung function tests and fractional exhaled nitric oxide (FENO) in patients with atopic asthma.

Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma.

Background: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (Feno) concentrations in children with asthma, but the effect of LTRA withdrawal on Feno and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by Feno and lung function in children with asthma.

Methods: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo.

Effects of a leukotriene receptor antagonist on exhaled leukotriene E4 and prostanoids in children with asthma.

Background: Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown.

Objective: (1) To study the effect of montelukast, a LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with asthma and atopic children; (2) to measure exhaled nitric oxide.

Delayed allergic reaction to suxamethonium driven by oligoclonal Th1-skewed CD4+CCR4+IFN-gamma+ memory T cells.

Background: Muscle relaxants represent the drugs most frequently involved in intraoperative anaphylaxis during surgical procedures. Our aim was to report the case of a delayed reaction to suxamethonium and analyze specific T cell lines with regard to their specificity, phenotype and cytokine profile.

Methods: We generated a drug-specific T cell line from a biopsy at the site of positive intradermal reactions and analyzed the immunophenotype, T cell receptor Vbeta domain expression and cytokine profile.

Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children.

Background: The role of leukotriene (LT) B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC) has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children.

Ion trap liquid chromatography/tandem mass spectrometry analysis of leukotriene B4 in exhaled breath condensate.

The objective of this study is the measurement of leukotriene B7 (LTB4), a potent inflammatory mediator, in exhaled breath condensate by using liquid chromatography/mass spectrometry (LC/MS and LC/MS/MS). Condensation of exhaled breath is a non-invasive method to collect airway secretions. Deuterated (d4)-LTB4 was used as internal standard.

Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children.

Background: Lipid mediators play an important pathophysiologic role in atopic asthmatic children, but their role in the airways of atopic nonasthmatic children is unknown.

Objective: We sought (1) to measure leukotriene (LT) E 4 , LTB 4 , 8-isoprostane, prostaglandin E 2 , and thromboxane B 2 concentrations in exhaled breath condensate in atopic asthmatic and atopic nonasthmatic children; (2) to measure exhaled nitric oxide (NO) as an independent marker of airway inflammation; and (3) to study the effect of inhaled corticosteroids on exhaled eicosanoids.

Methods: Twenty healthy children, 20 atopic nonasthmatic children, 30 steroid-naive atopic asthmatic children, and 25 atopic asthmatic children receiving inhaled corticosteroids were included in a cross-sectional study.

Validation of 8-isoprostane and prostaglandin E(2) measurements in exhaled breath condensate.

Objective: To qualitatively validate radioimmunoassays for 8-isoprostane and prostaglandin (PG) E(2) in exhaled breath condensate.

Subjects: Twenty-two subjects with different lung diseases attended the outpatient clinic on one occasion for exhaled breath condensate collection.

Methods: Samples were pooled together and purified by reverse phase high performance liquid chromatography (RP-HPLC).

Validation of leukotriene B4 measurements in exhaled breath condensate.

Objective: To qualitatively validate an enzyme immunoassay to measure leukotriene B4 in exhaled breath condensate. Exhaled breath condensate is a new non-invasive method to monitor airway inflammation.

Subjects: Twenty-two subjects with different lung diseases attended the outpatient clinic on one occasion for exhaled breath condensate collection.

Immediate allergic reactions to beta-lactams: diagnosis and therapy.

Beta-lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of beta-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common beta-lactam ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock.