Astronomy and Literature | Canon and Stylometrics

This eighth issue of Interfaces contains two thematic clusters: the first cluster, entitled The Astronomical Imagination in Literature through the Ages, is edited by Dale Kedwards; the second cluster, entitled Medieval Authorship and Canonicity in the Digital Age, is edited by Jeroen De Gussem and Jeroen Deploige

Notch-IGF1 signalling in biliary epithelial cells drives their expansion and inhibits hepatocyte differentiation

[no abstract available

Neutrophil Elastase Promotes Interleukin-1 beta Secretion from Human Coronary Endothelium

The endothelium is critically involved in the pathogenesis of atherosclerosis by producing pro-inflammatory mediators, including IL-1β. Coronary arteries from patients with ischemic heart disease express large amounts of IL-1β in the endothelium. However, the mechanism by which endothelial cells (ECs) release IL-1β remains to be elucidated. We investigated neutrophil elastase (NE), a potent serine protease detected in vulnerable areas of human carotid plaques, as a potential “trigger” for IL-1β processing and release. This study tested the hypothesis that NE potentiates the processing and release of IL-1β from human coronary endothelium. We found that NE cleaves the pro-isoform of IL-1β in ECs and causes significant secretion of bioactive IL-1β via extracellular vesicles. This release was attenuated significantly by inhibition of neutrophil elastase but not caspase-1. Transient increases in intracellular Ca2+ levels were observed prior to secretion. Inside ECs, and after NE treatment only, IL-1β was detected within LAMP-1-positive multivesicular bodies. The released vesicles contained bioactive IL-1β. In vivo, in experimental atherosclerosis, NE was detected in mature atherosclerotic plaques, predominantly in the endothelium, alongside IL-1β. This study reveals a novel mechanistic link between NE expression in atherosclerotic plaques and concomitant pro-inflammatory bioactive IL-1β secretion from ECs. This could reveal additional potential anti-IL-1β therapeutic targets and provide further insights into the inflammatory process by which vascular disease develops

2019 ESC/EAS guidelines for the management of dyslipidaemias : Lipid modification to reduce cardiovascular risk

Correction: Volume: 292 Pages: 160-162 DOI: 10.1016/j.atherosclerosis.2019.11.020 Published: JAN 2020Peer reviewe

Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5) on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system

Dietary supplementation with a specific mannan-rich yeast parietal fraction enhances the gut and skin mucosal barriers of Atlantic salmon (Salmo salar) and reduces its susceptibility to sea lice (Lepeophtheirus salmonis)

Background: Increasing reliance on non-medicinal interventions to control sea lice in the Atlantic salmon (Salmo salar) farming industry imposes a high level of skin mucosal disturbance and indirect health issues. Dietary supplementation with yeast-based MOS products is widely used to support intestinal homeostasis across farmed species. Evidence of their effect on skin mucosa is increasing in aquatic species but it remains inconsistent and someway short of a clear contribution to sea lice management. A tank-based trial was performed to test the effect of a yeast-based MOS functional compound (sMOS) on the skin mucosal layer and its protective effects against sea lice (Lepeophtheirus salmonis). Results: The test compound significantly increased skin mucus (+46%) and goblet cell density (+25%) after 6 weeks of dietary supplementation when positive effects on intestinal villi-length (+10.9%) and goblet cell density (+80.0%) were also documented. Following dietary supplementation, a 16.6% reduction in susceptibility to an acute standard copepodid challenge was measured alongside an earlier increase in skin lysozyme activity widely used as an index of innate immunity. Conclusion: The study provides functional evidence that the benefits of dietary sMOS reach beyond the intestine to the skin mucosa. Bolstering of the Atlantic salmon skin barrier and immune functions and the resulting lower susceptibility to sea lice has the potential to reduce the need for delousing interventions and the impact of non-medicinal interventions on the animal's health and welfare

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life