Diabetes: impaired damage control

A coordinated response by the innate immune system, (micro)circulation and nervous system is needed to limit tissue destruction and to initiate reparative processes after tissue damage. Alterations in danger signals in diabetes can be an important cause of the excessive tissue loss and defective tissue repair after injury and can contribute to the higher rates of cardiac failure after myocardial infarction, more severe tissue loss in the case of peripheral ischaemia and impaired wound healing. Here we discuss the mechanisms underlying this impaired damage control in diabetes, with an emphasis on the proinflammatory cytokine high mobility group box 1 and the potential role of dipeptidyl peptidase IV inhibition in improving repair responses

Theology, News and Notes - Vol. 32, No. 04

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1090/thumbnail.jp

A disease management programme for patients with diabetes mellitus is associated with improved quality of care within existing budgets

Aim  To assess the impact of a disease management programme for patients with diabetes mellitus (Type 1 and Type 2) on cost-effectiveness, quality of life and patient self-management. By organizing care in accordance with the principles of disease management, it is aimed to increase quality of care within existing budgets. Methods  Single-group, pre-post design with 2-year follow-up in 473 patients. Results  Substantial significant improvements in glycaemic control, health-related quality of life (HRQL) and patient self-management were found. No significant changes were detected in total costs of care. The probability that the disease management programme is cost-effective compared with usual care amounts to 74%, expressed in an average saving of 117 per additional life year at 5% improved HRQL. Conclusion  Introduction of a disease management programme for patients with diabetes is associated with improved intermediate outcomes within existing budgets. Further research should focus on long-term cost-effectiveness, including diabetic complications and mortality, in a controlled setting or by using decision-analytic modelling technique

The unacknowledged legacy

This paper presents a critical discussion of the treatment of mimetic art, and particularly poetry and the theatre, in the work of the Athenian philosopher Plato (427-347 BC). It centres on Plato's discussion of the corrupting powers of the arts in the Republic, and the implications that his fierce attack on poetry and theatre have for his construction of the ideal polity. The legacy of Platonic ideas in later elaborations of the corrupting power of the arts is discussed. Furthermore, the paper investigates the relationship between current debates on cultural policy and the Platonic idea that the transformative powers of the arts ought to be harnessed by the state to promote a just society. The conclusion thus reached is that “instrumental cultural policy”, rather then being a modern invention, was in fact first theorized precisely in Plato's Republic

The FLASHForward Facility at DESY

The FLASHForward project at DESY is a pioneering plasma-wakefield acceleration experiment that aims to produce, in a few centimetres of ionised hydrogen, beams with energy of order GeV that are of quality sufficient to be used in a free-electron laser. The plasma wave will be driven by high-current density electron beams from the FLASH linear accelerator and will explore both external and internal witness-beam injection techniques. The plasma is created by ionising a gas in a gas cell with a multi-TW laser system, which can also be used to provide optical diagnostics of the plasma and electron beams due to the <30 fs synchronisation between the laser and the driving electron beam. The operation parameters of the experiment are discussed, as well as the scientific program.Comment: 19 pages, 9 figure

Collateral circulation: Past and present

Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors

ZFIN: enhancements and updates to the zebrafish model organism database

ZFIN, the Zebrafish Model Organism Database, http://zfin.org, serves as the central repository and web-based resource for zebrafish genetic, genomic, phenotypic and developmental data. ZFIN manually curates comprehensive data for zebrafish genes, phenotypes, genotypes, gene expression, antibodies, anatomical structures and publications. A wide-ranging collection of web-based search forms and tools facilitates access to integrated views of these data promoting analysis and scientific discovery. Data represented in ZFIN are derived from three primary sources: curation of zebrafish publications, individual research laboratories and collaborations with bioinformatics organizations. Data formats include text, images and graphical representations. ZFIN is a dynamic resource with data added daily as part of our ongoing curation process. Software updates are frequent. Here, we describe recent additions to ZFIN including (i) enhanced access to images, (ii) genomic features, (iii) genome browser, (iv) transcripts, (v) antibodies and (vi) a community wiki for protocols and antibodies

Piloteinsatz einer E-Assessment-Plattform für die grafische Modellierung

Die KEA-Mod-Plattform ermöglicht es, Modellierungsaufgaben mit verschiedenen Modellierungssprachen wie z.B. UML, Petri-Netzen, EPK oder BPMN durch Dozierende zu erstellen und von Studierenden bearbeiten zu lassen. Die Plattform kam in einer großen Lehrveranstaltung mit ca. 250 Studierenden zum Piloteinsatz. Die Studierenden konnten mit Hilfe der Plattform und des integrierten Modellierungswerkzeugs eine Aufgabenreihe mit Modellierungsaufgaben zu Petri-Netzen bearbeiten und einreichen. Anschließend erhielten die Studierenden automatisiert generiertes Feedback. Das Poster beschreibt die Evaluation dieses Piloteinsatzes aus der Perspektive der Studierenden und bietet erste Ergebnisse in Bezug auf die Plattform-Usability und zur wahrgenommenen Lernförderlichkeit des Feedbacks

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions