IFN-γ and TNF-α synergize to inhibit CTGF expression in human lung endothelial cells.

Connective tissue growth factor (CTGF/CCN2) is an angiogenetic and profibrotic factor, acting downstream of TGF-β, involved in both airway- and vascular remodeling. While the T-helper 1 (Th1) cytokine interferon-gamma (IFN-γ) is well characterized as immune-modulatory and anti-fibrotic cytokine, the role of IFN-γ in lung endothelial cells (LEC) is less defined. Tumour necrosis factor alpha (TNF-α) is another mediator that drives vascular remodeling in inflammation by influencing CTGF expression. In the present study we investigated the influence of IFN-γ and TNF-α on CTGF expression in human LEC (HPMEC-ST1.6R) and the effect of CTGF knock down on human LEC. IFN-γ and TNF-α down-regulated CTGF in human LEC at the promoter-, transcriptional- and translational-level in a dose- and time-dependent manner. The inhibitory effect of IFN-γ on CTGF-expression could be almost completely compensated by the Jak inhibitor AG-490, showing the involvement of the Jak-Stat signaling pathway. Besides the inhibitory effect of IFN-γ and TNF-α alone on CTGF expression and LEC proliferation, these cytokines had an additive inhibitory effect on proliferation as well as on CTGF expression when administered together. To study the functional role of CTGF in LEC, endogenous CTGF expression was down-regulated by a lentiviral system. CTGF silencing in LEC by transduction of CTGF shRNA reduced cell proliferation, but did not influence the anti-proliferative effect of IFN-γ and TNF-α. In conclusion, our data demonstrated that CTGF was negatively regulated by IFN-γ in LEC in a Jak/Stat signaling pathway-dependent manner. In addition, an additive effect of IFN-γ and TNF-α on inhibition of CTGF expression and cell proliferation could be found. The inverse correlation between IFN-γ and CTGF expression in LEC could mean that screwing the Th2 response to a Th1 response with an additional IFN-γ production might be beneficial to avoid airway remodeling in asthma

Designing for knowledge maturing: from knowledge- driven software to supporting the facilitation of knowledge development

ABSTRACT Software engineering has been transformed in recent years by understanding the interaction with customers and the target context as an ongoing learning process. Responsiveness to change and user-centered design have been the consequences. In a similar way, knowledge and ontology engineering are undergoing fundamental changes to acknowledge the fact that they are part of a collective knowledge maturing process. We explore three examples: (i) social media based competence management in career guidance, (ii) ontology-centered reflection in multiprofessional environments in palliative care, and (iii) aligning individual mindlines in pratice networks of General Practitioners. Based on these, we extract four levels of designing for knowledge maturing and associated technical implementations. This shows that future technology support should especially target facilitation of self-organized, but tool-mediated knowledge development processes, where, e.g., workplace learning analytics can play a prominent role

Poractant alfa (Curosurf®) increases phagocytosis of apoptotic neutrophils by alveolar macrophages in vivo

<p>Abstract</p> <p>Background</p> <p>Clearance of apoptotic neutrophils in the lung is an essential process to limit inflammation, since they could become a pro-inflammatory stimulus themselves. The clearance is partially mediated by alveolar macrophages, which phagocytose these apoptotic cells. The phagocytosis of apoptotic immune cells by monocytes in vitro has been shown to be augmented by several constituents of pulmonary surfactant, e.g. phospholipids and hydrophobic surfactant proteins. In this study, we assessed the influence of exogenous poractant alfa (Curosurf^®) instillation on the in vivo phagocytosis of apoptotic neutrophils by alveolar macrophages.</p> <p>Methods</p> <p>Poractant alfa (200 mg/kg) was instilled intratracheally in the lungs of three months old adult male C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar lavage was performed and alveolar macrophages and neutrophils were counted. Phagocytosis of apoptotic neutrophils was quantified by determining the number of apoptotic neutrophils per alveolar macrophages.</p> <p>Results</p> <p>Exogenous surfactant increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6 fold. The phagocytosis of apoptotic neutrophils was increased in the presence of exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils per alveolar macrophage.</p> <p>Conclusions</p> <p>We conclude that the anti-inflammatory properties of surfactant therapy may be mediated in part by increased numbers of alveolar macrophages and increased phagocytosis of apoptotic neutrophils by alveolar macrophages.</p

Антибіотикопрофілактика в хірургії

Наук. кер.: М.Г. КононенкоГнійно-запальні післяопераційні ускладнення за останні десятиріччя набувають все більшої актуальності. Це вже стає проблемою. Такі ускладнення необхідно попереджувати. Для забезпечення тканин операційного поля антибіотиком у ефективній (бактерицидній) концентрації на весь період хірургічного втручання проводять антибіотикопрофілактику (АБП). Вона є складовою частиною комплексної профілактики гнійно-запальних ускладнень. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/2734

THE CHANGING ECONOMIC SPATIAL STRUCTURE OF EUROPE

Many theoretical and practical works aim at describing the spatial structure of Europe, where spatial relations have undergone continuous change. This article gives an overview of models describing the spatial structure of Europe. Their diversity is highlighted by listing of these models, without any claim to completeness. Our study aims at describing the economic spatial structure of Europe with bi-dimensional regression analysis based on the gravitational model. With the help of the gravity model, we get a spatial image of the spatial structure of Europe. With these images, we can justify the appropriateness of the models based on different methodological backgrounds by comparing them with our results. Our goal is not to create and show a new model that overwrites the existing ones, but rather to contribute to understanding the European spatial structure through a new methodological approach

Does risk of progression from Barrett’s esophagus to esophageal adenocarcinoma change based on the number of non-dysplastic endoscopies?

Funding: This study was funded in full by the National Institutes of Health, grant number (NIH P30DK056338‐16). The Northern Ireland Barrett’s register was funded by the UK Medical Research Council, Cancer Focus Northern Ireland (formerly the Ulster Cancer Foundation), NI HSC R&D Office, and Cancer Research UK. The Northern Ireland Cancer Registry is funded by the Public Health Agency.Peer reviewedPostprin

Mobile Robot Localization using Panoramic Vision and Combinations of Feature Region Detectors

IEEE International Conference on Robotics and Automation (ICRA 2008, Pasadena, California, May 19-23, 2008), pp. 538-543.This paper presents a vision-based approach for mobile robot localization. The environmental model is topological. The new approach uses a constellation of different types of affine covariant regions to characterize a place. This type of representation permits a reliable and distinctive environment modeling. The performance of the proposed approach is evaluated using a database of panoramic images from different rooms. Additionally, we compare different combinations of complementary feature region detectors to find the one that achieves the best results. Our experimental results show promising results for this new localization method. Additionally, similarly to what happens with single detectors, different combinations exhibit different strengths and weaknesses depending on the situation, suggesting that a context-aware method to combine the different detectors would improve the localization results.This work was partially supported by USC Women in Science and Engineering (WiSE), the FI grant from the Generalitat de Catalunya, the European Social Fund, and the MID-CBR project grant TIN2006-15140-C03-01 and FEDER funds and the grant 2005-SGR-00093

Spontaneous restoration of functional β-cell mass in obese SM/J mice

Maintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J\u27s diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J mice do not show elevated β-cell mitotic index, but rather elevated α-cell mitotic index. Functional assessment of isolated islets reveals that obese SM/J mice increase glucose-stimulated insulin secretion, decrease basal insulin secretion, and increase islet insulin content. These results establish that β-cell mass expansion and improved β-cell function underlie the resolution of hyperglycemia, indicating that obese SM/J mice are a valuable tool for exploring how functional β-cell mass can be recovered in the context of obesity

Companion Animals in Zoonoses Research – Ethical Considerations

Non-human animals are commonly classified according to their "role", such as "livestock", "wild" or "companion" animals. But what if those classifications overlap? This article presents a report of the retreat week "ZooCan – Zoonoses of companion animals as case study for animal ethics" at the University of Veterinary Medicine Hannover, Germany, in November 2022. The workshop included participants from different European countries with interdisciplinary backgrounds (animal law, bioethics, epidemiology, philosophy, biology and veterinary medicine). We address ethically relevant issues that emerge when companion animals are used as research animals, particularly in zoonoses research. The outcomes of the multi-disciplinary approach are used to i) define criteria to classify "companion" and "research" animals, ii) provide guidance to overcome the challenges with classificational overlaps, iii) give insights into cutting-edge zoonoses research with an example of SARS-CoV-2 in cats, and iv) discuss animal ethics approaches with regard to classifications