Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review)

The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID‑19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID‑19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts

Summary of the Meeting on 11 December 2015 on Adaptation of Structural Design to Climate Change

The objectives of the meeting were as follows: 1. Discuss the feasibility and needs for creating snow map for structural design which accounts for the climate change: • availability of methodology and data; • scope of a snow map project – geographic, time span; • support / resources needed. 2. Set-up a group to create a document on the rational and needs for a snow map for structural design which accounts for the climate change. 3. Discuss the interaction with CEN/TC 250 Project Team (PT) on SC1.T5 (the Project Team on the CEN report on adaptation of the Eurocodes to the climate change, Task 5 of SC1, under Mandate M/515). 4. Identify other actions on structures whose effect on structures shall be consideredJRC.G.4-European laboratory for structural assessmen

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Summary of the meeting on 11 December 2015 on adaptation of structural design to climate change - Support to the implementation, harmonization and further development of the Eurocodes

It is expected that the global warming will reduce the frequency of the snow events. On the other hand, the intensity of extreme snow events may increase, since the capacity of the atmosphere to hold moisture increases with temperature. This may lead to the increase of both snow density and occurrence of extreme snowfalls in regions where temperatures still may happen to be below freezing level during precipitation events. To assess the evolution of the snow load and its impact on design of new buildings and on reliability of existing ones, a comparison of future trends, in both intensity and frequency of future precipitation in cold areas with current versions of snow load maps for structural design should be performed. The European Snow Loads Research Project was carried out under contracts with the European Commission DG III – D3 in the period 1996-1999 with the aim to provide scientific basis for harmonized definition of models for determining the actions of snow applied to the structural parts of construction works. The project was led by Pisa University. The snow load design map produced by this project is incorporated in Annex C of EN 1991-1-3 with the aim to help National Competent Authorities to redraft their national snow maps and to establish harmonized procedures to produce such maps. A pilot study on creating a snow load map for structural design taking into account the climate change was launched at a working meeting on 8 April 2014 at JRC/Ispra with the participation of Pisa University and the JRC CRM and ELSA Units. While the study has been performed in Pisa University, the JRC CRM Unit provided data on climate change projections, and the two JRC Units consulted the approach and the results. The results obtained show that the developed procedure is very appropriate for the creation of snow maps taking into account the climate change implications, since it allows to estimate characteristic ground snow loads on the basis of daily data Tmax, Tmin and h rain, which are typically available as outputs of climate change projections for all possible scenarios

Carcinogenic chromium(VI) compounds formed by intracellular oxidation of chromium(III) dietary supplements by adipocytes

International EditionChromium(III) nutritional supplements are widely consumed for their purported antidiabetic activities. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure (XANES) studies have now shown that non-toxic doses of [Cr₃O(OCOEt)⁶(OH₂)₃]⁺(A), a prospective antidiabetic drug that undergoes similar H₂O₂ induced oxidation reactions in the blood as other Cr supplements, was also oxidized to carcinogenic CrVI and CrV in living cells. Single adipocytes treated with A had approximately 1 μm large Cr hotspots containing CrIII, CrV, and CrVI (primarily CrVI thiolates) species. These results strongly support the hypothesis that the antidiabetic activity of CrIII and the carcinogenicity of CrVI compounds arise from similar mechanisms involving highly reactive CrVI and CrV intermediates, and highlight concerns over the safety of CrIII nutritional supplements.Lindsay E. Wu, Aviva Levina, Hugh H. Harris, Zhonghou Cai, Barry Lai, Stefan Vogt, David E. James, and Peter A. La

Intraoperative transfusion practices in Europe

Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl and increased to 9.8 (1.8) g dl after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold