Routes Obey Hierarchy in Complex Networks.

The last two decades of network science have discovered stunning similarities in the topological characteristics of real life networks (many biological, social, transportation and organizational networks) on a strong empirical basis. However our knowledge about the operational paths used in these networks is very limited, which prohibits the proper understanding of the principles of their functioning. Today, the most widely adopted hypothesis about the structure of the operational paths is the shortest path assumption. Here we present a striking result that the paths in various networks are significantly stretched compared to their shortest counterparts. Stretch distributions are also found to be extremely similar. This phenomenon is empirically confirmed on four networks from diverse areas of life. We also identify the high-level path selection rules nature seems to use when picking its paths

The effect of blue light exposure in an ocular melanoma animal model

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) cell lines, when exposed to blue light in vitro, show a significant increase in proliferation. In order to determine if similar effects could be seen in vivo, we investigated the effect of blue light exposure in a xenograft animal model of UM.</p> <p>Methods</p> <p>Twenty New Zealand albino rabbits were injected with 1.0 × 10⁶human UM cells (92.1) in the suprachoroidal space of the right eye. Animals were equally divided into two groups; the experimental group was exposed to blue light, while the control group was protected from blue light exposure. The eyes were enucleated after sacrifice and the proliferation rates of the re-cultured tumor cells were assessed using a Sulforhodamine-B assay. Cells were re-cultured for 1 passage only in order to maintain any in vivo cellular changes. Furthermore, Proliferating Cell Nuclear Antigen (PCNA) protein expression was used to ascertain differences in cellular proliferation between both groups in formalin-fixed, paraffin-embedded eyes (FFPE).</p> <p>Results</p> <p>Blue light exposure led to a statistically significant increase in proliferation for cell lines derived from intraocular tumors (p < 0.01). PCNA expression was significantly higher in the FFPE blue light treated group when compared to controls (p = 0.0096).</p> <p>Conclusion</p> <p>There is an increasing amount of data suggesting that blue light exposure may influence the progression of UM. Our results support this notion and warrant further studies to evaluate the ability of blue light filtering lenses to slow disease progression in UM patients.</p

Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B(4 )in asthmatic children

BACKGROUND: The role of leukotriene (LT) B(4), a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB(4 )in exhaled breath condensate (EBC) has hampered its quantitative assessment in this biological fluid. We sought to measure LTB(4 )in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO) was measured as an independent marker of airway inflammation. METHODS: Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB(4 )concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS) with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB(4 )values were expressed as the total amount (in pg) of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. RESULTS: Compared with healthy children [87.5 (82.5–102.5) pg, median and interquartile range], exhaled LTB(4 )was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7) pg, p < 0.001], but not in atopic nonasthmatic children [96.5 (87.3–102.5) pg, p = 0.59)]. Asthmatic children who were receiving inhaled corticosteroids had lower concentrations of exhaled LTB(4 )than steroid-naïve asthmatics [125.0 (25.0–245.0) pg vs 255.1 (175.0–314.7) pg, p < 0.01, respectively]. Exhaled NO was higher in atopic nonasthmatic children [16.2 (13.5–22.4) ppb, p < 0.05] and, to a greater extent, in atopic steroid-naïve asthmatic children [37.0 (31.7–57.6) ppb, p < 0.001] than in healthy children [8.3 (6.1–9.9) ppb]. Compared with steroid-naïve asthmatic children, exhaled NO levels were reduced in asthmatic children who were receiving inhaled corticosteroids [15.9 (11.5–31.7) ppb, p < 0.01]. CONCLUSION: In contrast to exhaled NO concentrations, exhaled LTB(4 )values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB(4 )in asthmatic children. LC/MS/MS analysis of exhaled LTB(4 )might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children

Isolation, characterisation, and selection of wine yeast strains in Etyek-Buda wine district, Hungary

Initiated by the Association “Wine Route of Etyek Wine District”, the objectives of this study were to isolate and identify autochthonous yeast strains from local wines and to determine their oenologically important properties. The first aim of this work was to characterize the taxonomic and phenotypic diversity of the representative Saccharomyces yeast strains that dominate the spontaneous fermentations in this wine district. The results obtained by molecular ribotyping (ARDRA) revealed a strong dominance of S. cerevisiae, but S. bayanus var. uvarum was also present sporadically. Some of the natural isolates exhibited high volatile acid production or poor fermentation capacity, which imply a quality risk in spontaneous fermentations. Most of the isolates, however, displayed good oenological features during lab scale fermentations. As the second aim of this work, the most promising, selected strains were further tested for oenological properties in microvinification scale and, finally, in large scale fermentations. The analytical and sensory analysis proved that selected strains, including S. bayanus var. uvarum, can be used as local starter cultures, which may contribute to the typicality of the local wines in comparison with commercial starters

Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

<p>Abstract</p> <p>Background</p> <p>Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients.</p> <p>Methods</p> <p>The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed.</p> <p>Results</p> <p>In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline F_ENOand the increase in F_ENOor BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed.</p> <p>Conclusion</p> <p>The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients.</p

Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study

BACKGROUND: It has been suggested that cysteinyl leukotrienes (cysLTs) play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC). The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children. METHODS: 29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. RESULTS: EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range) 36.62 (22.60–101.05) versus 249.1 (74.21–526.36) pg/ml, p = 0.004). There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003). CONCLUSION: EBC cysLTs appear to be associated with RBM thickening in asthma

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS

ERS statement: A core outcome set for clinical trials evaluating the management of COPD exacerbations

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use