Treatment with COLchicine in hospitalized patients affected by COVID-19: The COLVID-19 trial

Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. Conclusion: Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome

A great tradition and a challenge for the future

An overview of the journal's role over the past 70 year

I paesaggi della salute sulle Alpi. Un piano di conservazione e gestione per il parco terapeutico del sanatorio di Sondalo

The Florence Charters underlined how important the concept of the time cycle is to ensure the conservation of a historic garden (art. 11), considering both the succession of its life phases and the cycle of the seasons (art. 2). Today's programming maintenance and management activities are even more important because climate change exposes historic gardens to unexpected risks for the balance of the plant system, the water structure, and the morphology of the land itself, mainly when characterized by a steep slope. The Conservation Management Plan is a useful tool for planning the management and conservation of collections, archaeological sites, buildings, and gardens. It has also been successfully applied to twentieth-century architecture as part of the Getty Foundation's Keeping It Modern program (2014-2020). In continuity with that experience, this text illustrates the results obtained by applying the Conservation and Management Plan to the park of the former Villaggio Sanatoriale di Sondalo in Alta Valtellina, a healing garden built between 1932 and 1940 and characterized by the integration of modern architecture, environmental therapy, and garden design. After the damage caused by the Vaia storm in 2018, a CMP was applied to protect the complex from the risks due to climate change, to plan maintenance, and to manage the agronomic-forestry, landscape, and architectural qualities of this large therapeutic garden in the centre of the Alps

Colossal electroresistance response accompanied by metal-insulator transition in a mixed-valent vanadate

Colossal electroresistance (CER) in manganites, i.e., a large change in electrical resistance as a function of varying applied electric field or applied electric current, has often been described as complimentary to the colossal magnetoresistance (CMR) effect. Mixed valence vanadates with active and empty orbitals, unlike manganites, have not naturally been discussed in this context, as double exchange based CMR is not realizable in them. However, presence of coupled spin and orbital degrees of freedom, metal-insulator transition (MIT) accompanied by orbital order-disorder transition, still make the vanadates important. Here we probe a Fe-doped hollandite lead vanadate (PFVO), which exhibits a clear MIT as a function of temperature. Most importantly, a giant fall in the resistivity, indicative of a CER, as well as a systematic shift in the MIT towards higher temperatures are observed with increasing applied current. Detailed structural, magnetic, thermodynamic, and transport studies point towards a complex interplay between the structural distortion, orbital order/disorder effect, and the resultant MIT and magnetic ordering in this system

An evidence of local structural disorder across spin-reorientation transition in DyFeO3: An extended x-ray absorption fine structure (EXAFS) study

The present work is aimed at exploring the local atomic structure modifications related to the spin reorientation transition (SRT) in DyFeO3 orthoferrite exploiting x-ray absorption fine structure (XAFS) spectroscopy. For this purpose we studied by XAFS the evolution of the local atomic structure around Fe and Dy as function of temperature (10-300 K) in a DyFeO3 sample having the SRT around 50-100 K. For sake of comparison we studied a YFeO3 sample having no SRT. The analysis of the extended region has revealed an anomalous trend of Fe-O nearest neighbour distribution in DFO revealing (i) a weak but significant compression with increasing temperature above the SRT and (ii) a peculiar behavior of mean square relative displacement (MSRD) [sigma(2)] of Fe-0 bonds showing an additional static contribution in the low temperature region, below the SRT. These effects arc absent in the YFO sample supporting these anomalies related to the SRT. Interestingly the analysis of Dy L-3-edge data also reveal anomalies in the Dy-O neighbour distribution associated to the SRT, pointing out a role of magnetic Re ions across T-SRT,T-Fe. These results point out micro-structural modification at both Fe and Dy sites associated to the magnetic transitions in DFO, it can be stated in general terms that such local distortions across Fe3+ and magnetic Re3+ may be present in other orthoferrites exhibiting multiferroic nature

Linear and nonlinear 3D-QSAR approaches in tandem with ligand-based homology modeling as a computational strategy to depict the pyrazolo-triazolo-pyrimidine antagonists binding site of the human adenosine A2A receptor

The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Surface Analysis, RSA) 3D-QSAR models to quantitatively predict the binding affinity of human adenosine A3 receptor antagonists. Moreover, we have also reported a novel GPCR modeling approach, called Ligand-Based Homology Modeling (LBHM), as a tool to simulate the conformational changes of the receptor induced by ligand binding. In the present study, the application of both linear and nonlinear 3D-QSAR methods and LBHM computational techniques has been used to depict the hypothetical antagonist binding site of the human adenosine A2A receptor. In particular, a collection of 127 known human A2A antagonists has been utilized to derive two 3D-QSAR models (autoMEPs/PLS&RSA). In parallel, using a rhodopsin-driven homology modeling approach, we have built a model of the human adenosine A2A receptor. Finally, 3D-QSAR and LBHM strategies have been utilized to predict the binding affinity of five new human A2A pyrazolo-triazolo-pyrimidine antagonists finding a good agreement between the theoretical and the experimental predictions