Anthracycline-induced acute cardiotoxicity in adults treated for leukaemia: Analysis of the clinico-pathological aspects of documented acute anthracycline-induced cardiotoxicity in patients treated for acute leukaemia at the University Hospital of Zürich, Switzerland, bet ween 1990 and 1996

Background: Acute cardiotoxicity due to anthracyclines is a rare, but life-threatening event. Interindividual sensitivity to anthracyclines is highly variable and cannot be predicted for the individual patient. Patients and methods: This is a retrospective study. Medical charts and autopsy report of patients treated for acute leuke mia between 1990 and 1996 at the University Hospital of Zürich, Switzerland were reviewed and searched for anthracycline-associated acute cardiotoxicity. Patients with pre-existing heart disease known to be associated with cardiotoxicity were excluded. Results: Seven patients treated for leukemia with proven anthracycline-associated acute cardiotoxicity were included. In six patients the direct cause of death was acute cardiotoxicity due to the treatment. One patient recovered from cardiac failure but died a few months later from refractory leukemia. Clinical symptoms were those of a heart failure. Pathological findings were dilatative cardiac hypertrophy and pericardial effusion. Microscopically the typical findings of myocardial fibrosis and perinuclear vacuolisated myocytes were seen. Conclusions: The awareness of acute adverse effects on cardiac performance by anthracyclines faciliates early recognition and prevention of heart failure. Reliable tests are needed for the early diagnosis of subclinical myocardial damage in order to identify patients at ris

Sub-wavelength surface IR imaging of soft-condensed matter

Outlined here is a technique for sub-wavelength infrared surface imaging performed using a phase matched optical parametric oscillator laser and an atomic force microscope as the detection mechanism. The technique uses a novel surface excitation illumination approach to perform simultaneously chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures

Soil conservation and sustainable development goals(SDGs) achievement in Europe and central Asia: Which role for the European soil partnership?

Voluntary soil protection measures are not sufficient to achieve sustainable soil management at a global scale. Additionally, binding soil protection legislation at national and international levels has also proved to be insufficient for the effective protection of this almost non-renewable natural resource. The European Soil Partnership (ESP) and its sub-regional partnerships (Eurasian Sub-Regional Soil Partnership, Alpine Soil Partnership) were established in the context of FAO's Global Soil Partnership (GSP) with the mission to facilitate and contribute to the exchange of knowledge and technologies related to soils, to develop dialogue and to raise awareness for the need to establish a binding global agreement for sustainable soil management. The ESP has taken a role of an umbrella network covering countries in Europe and Central Asia. It aims to improve the dialogue in the whole region and has encouraged establishing goals that would promote sustainable soil management, taking into account various national and local approaches and priorities, as well as cultural specificities. The ESP first regional implementation plan for the 2017–2020 period was adopted and implemented along the five GSP pillars of action. Building on the experience of the last four years, this study demonstrates that establishing sub-regional and national partnerships is an additional step in a concrete sustainable soil management implementation process. It also suggests that a complementary approach between legal instruments and voluntary initiatives linked to the development of efficient communication and strong commitment is the key to success

External mechanical loading overrules cell-cell mechanical communication in sprouting angiogenesis during early bone regeneration

Sprouting angiogenesis plays a key role during bone regeneration. For example, insufficient early revascularization of the injured site can lead to delayed or non-healing. During sprouting, endothelial cells are known to be mechano-sensitive and respond to local mechanical stimuli. Endothelial cells interact and communicate mechanically with their surroundings, such as outer-vascular stromal cells, through cell-induced traction forces. In addition, external physiological loads act at the healing site, resulting in tissue deformations and impacting cellular arrangements. How these two distinct mechanical cues (cell-induced and external) impact angiogenesis and sprout patterning in early bone healing remains however largely unknown. Therefore, the aim of this study was to investigate the relative role of externally applied and cell-induced mechanical signals in driving sprout patterning at the onset of bone healing. To investigate cellular self-organisation in early bone healing, an in silico model accounting for the mechano-regulation of sprouting angiogenesis and stromal cell organization was developed. Computer model predictions were compared to in vivo experiments of a mouse osteotomy model stabilized with a rigid or a semirigid fixation system. We found that the magnitude and orientation of principal strains within the healing region can explain experimentally observed sprout patterning, under both fixation conditions. Furthermore, upon simulating the selective inhibition of either cell-induced or externally applied mechanical cues, external mechanical signals appear to overrule the mechanical communication acting on a cell-cell interaction level. Such findings illustrate the relevance of external mechanical signals over the local cell-mediated mechanical cues and could be used in the design of fracture treatment strategies for bone regeneration

Combined inhibition of p97 and the proteasome causes lethal disruption of the secretory apparatus in multiple myeloma cells.

Inhibition of the proteasome is a widely used strategy for treating multiple myeloma that takes advantage of the heavy secretory load that multiple myeloma cells (MMCs) have to deal with. Resistance of MMCs to proteasome inhibition has been linked to incomplete disruption of proteasomal endoplasmic-reticulum (ER)-associated degradation (ERAD) and activation of non-proteasomal protein degradation pathways. The ATPase p97 (VCP/Cdc48) has key roles in mediating both ERAD and non-proteasomal protein degradation and can be targeted pharmacologically by small molecule inhibition. In this study, we compared the effects of p97 inhibition with Eeyarestatin 1 and DBeQ on the secretory apparatus of MMCs with the effects induced by the proteasome inhibitor bortezomib, and the effects caused by combined inhibition of p97 and the proteasome. We found that p97 inhibition elicits cellular responses that are different from those induced by proteasome inhibition, and that the responses differ considerably between MMC lines. Moreover, we found that dual inhibition of both p97 and the proteasome terminally disrupts ER configuration and intracellular protein metabolism in MMCs. Dual inhibition of p97 and the proteasome induced high levels of apoptosis in all of the MMC lines that we analysed, including bortezomib-adapted AMO-1 cells, and was also effective in killing primary MMCs. Only minor toxicity was observed in untransformed and non-secretory cells. Our observations highlight non-redundant roles of p97 and the proteasome in maintaining secretory homeostasis in MMCs and provide a preclinical conceptual framework for dual targeting of p97 and the proteasome as a potential new therapeutic strategy in multiple myeloma

The Cherenkov Telescope Array Large Size Telescope

The two arrays of the Very High Energy gamma-ray observatory Cherenkov Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA to achieve a low-energy threshold of 20 GeV, which is critical for important studies in astrophysics, astroparticle physics and cosmology. This work presents the key specifications and performance of the current LST design in the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223