Pathways of mechanical unfolding of FnIII10: Low force intermediates

We study the mechanical unfolding pathways of the $FnIII_{10}$ domain of fibronectin by means of an Ising--like model, using both constant force and constant velocity protocols. At high forces and high velocities our results are consistent with experiments and previous computational studies. Moreover, the simplicity of the model allows us to probe the biologically relevant low force regime, where we predict the existence of two intermediates with very close elongations. The unfolding pathway is characterized by stochastic transitions between these two intermediates

Energy transfer in molecular devices

Protein machines often exhibit long-range interplay between different sites in order to achieve their biological tasks. We investigate and characterize the nonlinear energy localization and the basic mechanisms of energy transfer in protein devices. By studying two different model protein machines, with different biological functions, we show that genuinely nonlinear phenomena are responsible for energy transport between the different machine sites involved in the biological functions. The energy transfer turns out to be extremely efficient from an energetic point of view: by changing the energy initially provided to the model device, we identify a well defined range of energies where the time for the energy transport to occur is minimal and the amount of transferred energy is a maximum. Furthermore, by introducing an implicit solvent, we show that the energy is localized on the internal residues of the protein structure, thus minimizing the dissipation

Prognostic Value of Fibrinogen among COVID-19 Patients Admitted to an Emergency Department: An Italian Cohort Study

Introduction: A highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19); the disease became pandemic after a few months. Little is still known about the laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the prognostic value of clotting parameters for the prediction of severe form of COVID-19 characterized by acute respiratory distress syndrome (ARDS) at hospital admission. Material and Methods: From a large cohort of 152 patients consecutively admitted from February to March 2020 for fever and dyspnea to the emergency departments (ED) of three Italian hospitals, we evaluated 85 patients with confirmed diagnosis of COVID-19 and 67 patients with acute illness. All patients underwent medical history checks, physical examination, and laboratory evaluation. Prothrombin time (PT), activated thromboplastin time (aPTT), fibrinogen and D-dimer tests were performed and compared, first, between COVID-19 and control groups, and then between COVID-19 patients with or without ARDS. Results: COVID-19 patients were more likely to show abnormal baseline levels of PT, aPTT, D-dimer, and fibrinogen at admission compared to the control group. COVID-19 patients with ARDS showed a statistically significant increase in levels of fibrinogen compared to those without ARDS (720 (621-833) vs. 490 (397.5-601.5); p= 1.8653 x 10(-9) (0.0765). A cut-off value of 617 mg/dL had a sensitivity of 76% and a specificity of 79% in identifying COVID-19 patients with ARDS. Conclusion: A serum level of fibrinogen of 617 mg/dL in COVID-19 patients admitted to emergency department may help to identify early those with ARDS

Impact of comorbidities on the severity of chronic hepatitis B at presentation

AIM: To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B

Clotting Factors in COVID-19: Epidemiological Association and Prognostic Values in Different Clinical Presentations in an Italian Cohort

Introduction: A novel highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19) outbreak, which has spread rapidly from China to other countries. Little is known about laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the basic clotting parameters in COVID-19 patients and their prognostic role in different clinical forms of the disease. Material and Methods: We enrolled 67 COVID-19 patients admitted to the Emergency Department. A cohort of 67 age- and sex-matched non-COVID-19 patients with acute respiratory illness was used as a control group. For all patients, platelet count (PLT), prothrombin time (PT), activated thromboplastin time (aPTT), C-reactive protein (PCR), fibrinogen, and D-dimer were determined. The COVID-19 population was divided in two groups according to the presence or absence of SARS. The clotting factors values were compared between the groups. Results: At admission, the COVID-19 patients showed statistically significant increased levels of fibrinogen (601.5 (480-747) vs. 455 (352.5-588.5) mg/dL; p = 0.0000064), and a higher percentage of patients had fibrinogen levels >400 mg/dL (86% vs.58%; p = 0.0054) compared to the control group. The levels of fibrinogen were higher in COVID-19 patients with SARS compared to those without SARS (747 (600.0-834.0) vs. 567 (472.5-644.50); p = 0.0003). Conclusion: Fibrinogen seems to increase early in COVID-19 patients and may be used as a risk stratification marker for the early detection of a subgroup of COVID-19 patient at increased risk to develop SARS, who might benefit from a different and thorough clinical surveillance and treatment

Independent and incremental prognostic value of doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction

Objectives.This study sought to investigate the relative and incremental prognostic value of demographic, historical, clinical, echocardiographic and mitral Doppler variables in patients with left ventricular systolic dysfunction.Background.The prognostic value of diastolic abnormalities as assessed by mitral Doppler echocardiography has yet to be defined.Method.A total of 508 patients with left ventricular ejection fraction ≤35% were followed up for a mean (±SD) period of 29 ± 11 months.Results.During the follow-up period, 148 patients (29.1%) were admitted to the hospital for congestive heart failure, and 100 patients (19.7%) died. By Cox model analysis, Doppler-derived mitral deceleration time of early filling ≤125 ms (relative risk [RR] 1.93, 95% confidence interval [CI] 1.4 to 3.7), New York Heart Association functional class III or IV (RR 1.49, 95% CI 1.4 to 2.3), ejection fraction ≤25% (RR 1.85, 95% CI 1.6 to 2.9), third heart sound (RR 2.06, 95% CI 1.8 to 3.2), age >60 years (RR 1.95, 95% CI 1.8 to 3.1) and left atrial area >18 cm2 (RR 1.73, 95% CI 1.6 to 2.7) were all found to be independent and additional predictors of all-cause mortality, and deceleration time was the single best predictor (chi-square 37.80). When all these significant variables were analyzed in hierarchic order, after age, functional class, third sound, ejection fraction and left atrial area, deceleration time still added significant prognostic information (global chi-square from 9.2 to 104.7). Also, deceleration time was the strongest independent predictor of hospital admission for congestive heart failure (RR 4.88, 95% CI 3.7 to 6.9) and cumulative events (congestive heart failure or all-cause mortality, or both; RR 2.44, 95% CI 2.0 to 3.8) in both symptomatic and asymptomatic patients.Conclusions.Deceleration time of early filling is a powerful independent predictor of poor prognosis in patients with left ventricular systolic dysfunction, whether symptomatic or asymptomatic. A short (≤125 ms) deceleration time by mitral Doppler echocardiography adds important prognostic information compared with other clinical, functional and echocardiographic variables

A Multi-Faceted Approach to Analyse the Effects of Environmental Variables on Geographic Range and Genetic Structure of a Perennial Psammophilous Geophyte: The Case of the Sea Daffodil Pancratium maritimum L. in the Mediterranean Basin

The Mediterranean coastline is a dynamic and complex system which owes its complexity to its past and present vicissitudes, e.g. complex tectonic history, climatic fluctuations, and prolonged coexistence with human activities. A plant species that is widespread in this habitat is the sea daffodil, Pancratium maritimum (Amaryllidaceae), which is a perennial clonal geophyte of the coastal sands of the Mediterranean and neighbouring areas, well adapted to the stressful conditions of sand dune environments. In this study, an integrated approach was used, combining genetic and environmental data with a niche modelling approach, aimed to investigate: (1) the effect of climate change on the geographic range of this species at different times past (last inter-glacial, LIG; and last glacial maximum, LGM), present (CURR), near-future (FUT) and (2) the possible influence of environmental variables on the genetic structure of this species in the current period. The genetic results show that 48 sea daffodil populations (867 specimens) display a good genetic diversity in which the marginal populations (i.e. Atlantic Sea populations) present lower values. Recent genetic signature of bottleneck was detected in few populations (8%). The molecular variation was higher within the populations (77%) and two genetic pools were well represented. Comparing the different climatic simulations in time, the global range of this plant increased, and a further extension is foreseen in the near future thanks to projections on the climate of areas currently-more temperate, where our model suggested a forecast for a climate more similar to the Mediterranean coast. A significant positive correlation was observed between the genetic distance and Precipitation of Coldest Quarter variable in current periods. Our analyses support the hypothesis that geomorphology of the Mediterranean coasts, sea currents, and climate have played significant roles in shaping the current genetic structure of the sea daffodil especially during LGM because of strong variation in coastline caused by glaciations

Insight into titanium and zirconium phosphate-based materials for reactive surfaces

Transition metal phosphates are promising acid catalysts for biorefinery processes, and their efficiency can benefit from the dispersion in a porous support. Here, a one-pot hydrolytic sol-gel route is established for the synthesis of Ti–P–Si and Zr–P–Si oxides, comprising a fine distribution of titanium or zirconium oxophosphate in a silicate network. The environmental sustainability of the procedure, given by the choice of the starting materials and operating conditions, is attested by a comparative study of E factors. A deep structural and surface characterization, by solid state NMR, FTIR and XPS, reveals the evolution of the materials during thermal treatment and the presence of a diverse phosphorus unit connectivity, including P–O–Ti and P–O–Zr bonding that anchors P in the amorphous cross-linked silicate matrix. The materials are prevalently microporous, with specific surface areas around 400 m2 g−1, and show a significant surface acidity (acid sites density >0.70 mmol g−1 from NH3 titration), despite the low metal and P content. Brønsted and Lewis acidic sites coexist at the surface, the former being predominant thanks to the contribution of both P–OH groups and some silanols whose acidity is increased by nearby coordinatively unsaturated metal ions. A proof of the reactivity of these materials is obtained in the hydrolysis of sucrose, that was selected as test reaction. The proposed sol-gel route affords a tight mixing of metal and phosphorus into the silica matrix that promotes the synergy of the components, enhancing their activity, and represents an effective sustainable approach toward supported functional metal phosphates