Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-α were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i) loss of body weight, (ii) mortality rate, (iii) lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts), (iv) lung edema, (v) histological evidence of lung injury and collagen deposition, (vi) lung myeloperoxidase, IL-1 and TNF-α staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment

Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time.</p> <p>Objective</p> <p>The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women.</p> <p>Methods</p> <p>Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis.</p> <p>Results</p> <p>Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05).</p> <p>Conclusion</p> <p>In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time.</p

Fire and brief human occupations in Iberia during MIS 4: Evidence from Abric del Pastor (Alcoy, Spain)

There is a relatively low amount of Middle Paleolithic sites in Europe dating to MIS 4. Of the few that exist, several of them lack evidence for anthropogenic fire, raising the question of how this period of global cooling may have affected the Neanderthal population. The Iberian Peninsula is a key area to explore this issue, as it has been considered as a glacial refugium during critical periods of the Neanderthal timeline and might therefore yield archaeological contexts in which we can explore possible changes in the behaviour and settlement patterns of Neanderthal groups during MIS 4. Here we report recent data from Abric del Pastor, a small rock shelter in Alcoy (Alicante, Spain) with a stratified deposit containing Middle Palaeolithic remains. We present absolute dates that frame the sequence within MIS 4 and multi-proxy geoarchaeological evidence of in situ anthropogenic fire, including microscopic evidence of in situ combustion residues and thermally altered sediment. We also present archaeostratigraphic evidence of recurrent, functionally diverse, brief human occupation of the rock shelter. Our results suggest that Neanderthals occupied the Central Mediterranean coast of the Iberian Peninsula during MIS 4, that these Neanderthals were not undergoing climatic stress and they were habitual fire users.This research was funded by a Leakey Foundation General Grant, Spanish Ministry of Science, Innovation and Universities Projects HAR2008-06117/HIST and HAR2015-68321-P, Junta de Castilla y León-FEDER Project BU235P18, the LabEx Sciences Archéologiques de Bordeaux (LaScArBx ANR-10-LABX-52) and ERC Consolidator Grant ERC-CoG-2014. Archaeological excavations at Abric del Pastor are supported by the Archaeological Museum of Alcoy and the Government of Valencia Cultural Heritage Department

Bioavailable iron in the Southern Ocean: the significance of the iceberg conveyor belt

Productivity in the Southern Oceans is iron-limited, and the supply of iron dissolved from aeolian dust is believed to be the main source from outside the marine reservoir. Glacial sediment sources of iron have rarely been considered, as the iron has been assumed to be inert and non-bioavailable. This study demonstrates the presence of potentially bioavailable Fe as ferrihydrite and goethite in nanoparticulate clusters, in sediments collected from icebergs in the Southern Ocean and glaciers on the Antarctic landmass. Nanoparticles in ice can be transported by icebergs away from coastal regions in the Southern Ocean, enabling melting to release bioavailable Fe to the open ocean. The abundance of nanoparticulate iron has been measured by an ascorbate extraction. This data indicates that the fluxes of bioavailable iron supplied to the Southern Ocean from aeolian dust (0.01–0.13 Tg yr-1) and icebergs (0.06–0.12 Tg yr-1) are comparable. Increases in iceberg production thus have the capacity to increase productivity and this newly identified negative feedback may help to mitigate fossil fuel emissions

The role of place branding and image in the development of sectoral clusters: the case of Dubai

This paper contextualizes how place branding and image influence the development of Dubai’s key sectoral clusters, including the key determinants of growth and success under the impression of Porter’s cluster theory. The approach is exploratory and of a qualitative inductive nature. Data was collected through conducting 21 semi-structured interviews with Dubai’s marketing/communication managers and stakeholders. Findings suggest that Dubai’s traditional clusters, namely, trading, tourism and logistics that have strong place branding and image show strong signs of success owing to Dubai’s geographical location (i.e., physical conditions). Among the new clusters, the financial sector is also benefitting from place branding. The results suggest that the success of traditional clusters have a positive spill over effect on the new clusters, in particular on construction and real estate. For policy makers it is worth to note that the recent success of the financial services cluster in Dubai will have positive impact on both, the traditional as well new clusters. The marketing and brand communication managers must consider the correlation and interplay of strength of activities amongst trading, tourism and logistics clusters and its implication while undertaking place branding for clients in their sector

A New Crocodylian from the Late Maastrichtian of Spain: Implications for the Initial Radiation of Crocodyloids

The earliest crocodylians are known primarily from the Late Cretaceous of North America and Europe. The representatives of Gavialoidea and Alligatoroidea are known in the Late Cretaceous of both continents, yet the biogeographic origins of Crocodyloidea are poorly understood. Up to now, only one representative of this clade has been known from the Late Cretaceous, the basal crocodyloid Prodiplocynodon from the Maastrichtian of North America.The fossil studied is a skull collected from sandstones in the lower part of the Tremp Formation, in Chron C30n, dated at -67.6 to 65.5 Ma (late Maastrichtian), in Arén (Huesca, Spain). It is located in a continuous section that contains the K/P boundary, in which the dinosaur faunas closest to the K/P boundary in Europe have been described, including Arenysaurus ardevoli and Blasisaurus canudoi. Phylogenetic analysis places the new taxon, Arenysuchus gascabadiolorum, at the base of Crocodyloidea.The new taxon is the oldest crocodyloid representative in Eurasia. Crocodyloidea had previously only been known from the Palaeogene onwards in this part of Laurasia. Phylogenetically, Arenysuchus gascabadiolorum is situated at the base of the first radiation of crocodyloids that occurred in the late Maastrichtian, shedding light on this part of the cladogram. The presence of basal crocodyloids at the end of the Cretaceous both in North America and Europe provides new evidence of the faunal exchange via the Thulean Land Bridge during the Maastrichtian

Foraging for foundations in decision neuroscience: insights from ethology

Modern decision neuroscience offers a powerful and broad account of human behaviour using computational techniques that link psychological and neuroscientific approaches to the ways that individuals can generate near-optimal choices in complex controlled environments. However, until recently, relatively little attention has been paid to the extent to which the structure of experimental environments relates to natural scenarios, and the survival problems that individuals have evolved to solve. This situation not only risks leaving decision-theoretic accounts ungrounded but also makes various aspects of the solutions, such as hard-wired or Pavlovian policies, difficult to interpret in the natural world. Here, we suggest importing concepts, paradigms and approaches from the fields of ethology and behavioural ecology, which concentrate on the contextual and functional correlates of decisions made about foraging and escape and address these lacunae

Digitally‐Enabled, Patient‐Centred Care in Rhinitis and Asthma Multimorbidity: The ARIA‐MASK‐air ® Approach

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.info:eu-repo/semantics/publishedVersio

Deciduous Trees and the Application of Universal DNA Barcodes: A Case Study on the Circumpolar Fraxinus

The utility of DNA barcoding for identifying representative specimens of the circumpolar tree genus Fraxinus (56 species) was investigated. We examined the genetic variability of several loci suggested in chloroplast DNA barcode protocols such as matK, rpoB, rpoC1 and trnH-psbA in a large worldwide sample of Fraxinus species. The chloroplast intergenic spacer rpl32-trnL was further assessed in search for a potentially variable and useful locus. The results of the study suggest that the proposed cpDNA loci, alone or in combination, cannot fully discriminate among species because of the generally low rates of substitution in the chloroplast genome of Fraxinus. The intergenic spacer trnH-psbA was the best performing locus, but genetic distance-based discrimination was moderately successful and only resulted in the separation of the samples at the subgenus level. Use of the BLAST approach was better than the neighbor-joining tree reconstruction method with pairwise Kimura's two-parameter rates of substitution, but allowed for the correct identification of only less than half of the species sampled. Such rates are substantially lower than the success rate required for a standardised barcoding approach. Consequently, the current cpDNA barcodes are inadequate to fully discriminate Fraxinus species. Given that a low rate of substitution is common among the plastid genomes of trees, the use of the plant cpDNA “universal” barcode may not be suitable for the safe identification of tree species below a generic or sectional level. Supplementary barcoding loci of the nuclear genome and alternative solutions are proposed and discussed