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

Multifunctional fire-resistant and flame-triggered shape memory epoxy nanocomposites containing carbon dots

Carbon quantum dots (CDs) are widely used as semiconductor systems, due to their facile synthesis and optical characteristics. CDs have been employed to enhance the light emission, UV resistance, and anticorrosive performances of epoxy nanocomposites (ENCs). Herein, we investigated the use of CDs to prepare multifunctional cycloaliphatic ENCs showing shape recovery capability. Following a waste-to-wealth approach, CDs were obtained from humic acid by a hydrothermal route. ENCs containing CDs exhibited photoluminescence, while the simultaneous addition of CDs and hexadecyltrimethoxysilane accounted for heat/flame-triggered shape recovery capability and hydrophobicity (contact angles as high as 137°). The polar character of silane-functionalized CDs allowed for their segregation at the surface of ENCs, making them very fire resistant. In particular, the CDs exerted an outstanding thermal shielding effect on the surface of ENCs, lowering the heat transfer at the boundary layer and increasing the time to flaming combustion up to ∼ 76 %. Besides, the graphitic nature of CDs and their charring behavior led to a huge increase in the back temperature at the ignition point (up to ∼ 30 %) during burn-through tests. Notwithstanding the low loadings (not exceeding 0.3 wt%) of CDs, ENCs lost their structural integrity only after almost 1 min of blowpipe flame application to their surface, whereas the resin counterpart degraded in less than 20 s. Besides, cone calorimetry tests carried out on ENCs highlighted a significant reduction of total smoke release (up to ∼ 40 %) compared to unfilled epoxy. Finally, we demonstrated the possibility of using multifunctional ENCs containing CDs as unique identification technology for polypropylene packaging, opening new perspectives on the effective protection of genuine products from counterfeiting

Adipopenia Is the Rapid Screening Tool that Best Predicts Mortality in Patients with Decompensated Cirrhosis: Results of a Prospective Study

Background and Aims: Patients with liver cirrhosis (LC) often have malnutrition (MN), which can be associated with decompensation, infection, and death. The aims were to determine: the prevalence of MN in patients with LC and ascites, its impact on mortality, and the relationship between MN and spontaneous bacterial peritonitis (SBP). Methods: Nutritional status (NS) was analysed in cirrhotic patients, experiencing their first episode of ascites, who were consecutively admitted at two clinical liver centres between November 2014 and October 2016. The participants underwent diagnostic paracentesis and were followed up to assess their outcomes. Results: 110 participants underwent NS assessment in addition to routine clinical procedures. The prevalence of MN was 30.9% according to corrected body mass index, 67.3% according to upper mid-arm muscle area (UMA) and 40% according to upper mid-arm fat area (UFA). The percentages of the participants remaining alive were 68.1% at 3 months, 59.3% at 6 months, 45.1% at 12 months and 24.2% at the end of the study. Univariate analysis showed that SBP, model for end-stage liver disease (MELD), UFA, UMA and age were significantly associated with mortality. Multivariate analysis showed that only SBP, MELD and UFA (hazard ratio 2.2) were independently associated with mortality. There was a correlation between adipopenia, but not sarcopenia, and SBP. Conclusions: Adipopenia, as assessed by UFA, was present in 40% of the cirrhotic patients, and it was independently associated with mortality

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

Lesson learned by COVID-19 outbreak: multilevel triage strategies in patients admitted to the emergency room in southern Italy

After identifying a novel disease inducing a severe acute respiratory syndrome-related to coronavirus 2 (SARS-CoV-2) for epidemic pneumonia in China, the diffusion of infection is ongoing around the world, and Italy has been the second country in which an epidemic has been demonstrated. Clinical features of this infection may be summarized in viral pneumonia that SARS or acute respiratory distress syndrome (ARDS) may complicate. For this reason, this epidemic has been considerably more aggressive than the previous epidemic of SARS and Middle-East respiratory syndrome. Coronavirus disease 2019 (COVID-19) showed an easy diffusion from human to human and also showed to be more contagious than other viruses. So human contact should be avoided at the emergency room and for inpatients too. The Triage should be adapted to these new features in order to speed up procedures for the care of infected patients at high risk of morbidity and mortality for SARS and ARDS and for traditional access to the emergency room. Based on our experiences, this flow chart has been designed with a multi-level triage in which patients have been divided for admission to the emergency room into patients with fever/respiratory symptoms and patients without fever\respiratory symptoms, to improve medical performances while treating COVID-19. This organized, multilevel triage permitted a good selection of patients admitted to the emergency room during the epidemic of COVID-19 in Southern Italy

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