A cost-effective FE method for 2D Navier–Stokes equations

A cost-effective approach to the solution of 2D Navier–Stokes equations for incompressible fluid flow problems is presented. The aim is to reach a good compromise between numerical properties and computational efficiency. In order to achieve the set goal, the nonlinear convective terms are approximated by means of characteristics and spatial approximations of equal order are performed by polynomials of degree two. In this way, the computational kernels are reduced to elliptic ones for which solution very efficient techniques are available. The time-advancing is afforded by a fractional step method combined with a stabilization technique suitably simplified, so that the inf-sup condition is easily overcome. The algebraic systems generated by the new technique are solved by an iterative solver (Bi-CGSTAB), preconditioned by means of a suitable Schwarz additive scalable preconditioner. The properties of the new method have been confirmed from the comparison among the results obtained by it, and those obtained ..

Autologous fat grafting after sarcoma surgery : evaluation of oncological safety

Background: The regenerative effectiveness of lipoaspirate procedures relies on the presence of mesenchymal stem cells, but the stromal microenvironment and hormonal secretions of the adipose tissue may be involved in cancer growth. Only few oncological outcome studies of fat grafting at the surgical site of malignant neoplasms of mesenchymal origin are available; none of these studies examined a series of sarcoma cases. Objectives: We analyzed outcome in terms of local or distant spread and overall survival to investigate the oncological safety of fat grafting in patients with sarcoma. Patients and methods: Sixty consecutive patients who had undergone 143 fat grafting procedures after surgical resection of bone and soft tissue sarcomas of the head, trunk, and limbs with clear resection margins were enrolled from 2004 to 2015 in our tertiary care center. A multidisciplinary sarcoma team administered adjuvant therapies. Patients were recurrence free at fat grafting. Results: The overall median follow-up was 7.5 years. At follow-up after fat grafting (2.4 years), one patient had distant metastasis and two had local relapse. Kaplan–Meier analysis showed disease-free survival rate of 95.4% (CI: 89.1–100.0) at 24 months. The risk of local recurrence (LR) within 24 months was 4.6% (CI: 0.0–20.9). The probability of not having LR after fat grafting was ≥ 89.1%. Conclusion: We found no evidence of an increased cancer risk after fat grafting procedures in patients with sarcoma, but a stimulatory role of fat cannot be excluded for bone sarcomas based on the cases reported here, and further studies are therefore needed

Autologous fat grafting after sarcoma surgery : evaluation of oncological safety

Background: The regenerative effectiveness of lipoaspirate procedures relies on the presence of mesenchymal stem cells, but the stromal microenvironment and hormonal secretions of the adipose tissue may be involved in cancer growth. Only few oncological outcome studies of fat grafting at the surgical site of malignant neoplasms of mesenchymal origin are available; none of these studies examined a series of sarcoma cases. Objectives: We analyzed outcome in terms of local or distant spread and overall survival to investigate the oncological safety of fat grafting in patients with sarcoma. Patients and methods: Sixty consecutive patients who had undergone 143 fat grafting procedures after surgical resection of bone and soft tissue sarcomas of the head, trunk, and limbs with clear resection margins were enrolled from 2004 to 2015 in our tertiary care center. A multidisciplinary sarcoma team administered adjuvant therapies. Patients were recurrence free at fat grafting. Results: The overall median follow-up was 7.5 years. At follow-up after fat grafting (2.4 years), one patient had distant metastasis and two had local relapse. Kaplan\u2013Meier analysis showed disease-free survival rate of 95.4% (CI: 89.1\u2013100.0) at 24 months. The risk of local recurrence (LR) within 24 months was 4.6% (CI: 0.0\u201320.9). The probability of not having LR after fat grafting was 65 89.1%. Conclusion: We found no evidence of an increased cancer risk after fat grafting procedures in patients with sarcoma, but a stimulatory role of fat cannot be excluded for bone sarcomas based on the cases reported here, and further studies are therefore needed

Structural and functional diversity of ferredoxin-NADP+ reductases

Although all ferredoxin-NADP+ reductases (FNRs) catalyze the same reaction, i.e. the transfer of reducing equivalents between NADP(H) and ferredoxin, they belong to two unrelated families of proteins: the plant-type and the glutathione reductase-type of FNRs. Aim of this review is to provide a general classification scheme for these enzymes, to be used as a framework for the comparison of their properties. Furthermore, we report on some recent findings, which significantly increased the understanding of the structure–function relationships of FNRs, i.e. the ability of adrenodoxin reductase and its homologs to catalyze the oxidation of NADP+ to its 4-oxo derivative, and the properties of plant-type FNRs from non-photosynthetic organisms. Plant-type FNRs from bacteria and Apicomplexan parasites provide examples of novel ways of FAD- and NADP(H)-binding. The recent characterization of an FNR from Plasmodium falciparum brings these enzymes into the field of drug design

Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics

Pathophysiology of hypoxemia in mechanically-ventilated patients with COVID-19: A computed tomography study

The pathogenesis of hypoxemia during acute respiratory distress syndrome caused by SARS-CoV-2 infection (C-ARDS) is debated. Some observations led to hypothesize ventilation to perfusion mismatch, rather than anatomical shunt, as the main determinant of hypoxemia. In this observational study 24 C-ARDS patients were studied 1 (0–1) days after intubation. Patients underwent a CT scan analysis to estimate anatomical shunt and a clinical test to measure venous admixture at two fractions of inspired oxygen (FiO2), to eliminate oxygen-responsive mechanisms of hypoxemia (ventilation to perfusion mismatch and diffusion limitation). In 10 out of 24 patients venous admixture was higher than anatomical shunt both at clinical (≈50 %) and 100 % FiO2. These patients were ventilated with a higher PEEP and had lower amount of anatomical shunt compared with patients with venous admixture equal/lower than anatomical shunt. In a subset of C-ARDS patients early after endotracheal intubation, hypoxemia might be explained by an abnormally high perfusion of a relatively low anatomical shunt

Impact of lower limb movement on the hemodynamics of femoropopliteal arteries: A computational study

Femoropopliteal arteries (FPAs) are subjected to a wide range of deformations, mainly determined by leg movement. FPAs are often affected by atherosclerotic plaque development, presumably influenced by the biomechanics of surrounding tissues. Although abnormal hemodynamics in FPAs appears to be an important factor in driving plaque development, to date it has been investigated in few studies, in which the leg was modeled in either fixed straight or bent configuration. Hence, the current work investigates the impact of leg movement on FPA hemodynamics. An idealized model of FPA was created to perform moving-boundary computational fluid dynamics analyses. By mimicking hip rotation, knee flexion and complete movement of walking, the hemodynamics was compared between moving- and fixed-boundary models. Moreover, additional features affecting the hemodynamics (e.g. flow-rate curve amplitude, walking speed) were examined. Significant hemodynamic differences were found between the moving- and fixed-boundary models, with the leg movement inducing higher time-averaged wall shear stress (TAWSS) (up to 66%). The flow-rate amplitude and walking period were the most influential parameters (differences in TAWSS up to 68% and 74%, respectively). In conclusion, this numerical approach highlighted the importance of considering leg movement to investigate FPA hemodynamics, and it could be employed in future patient-specific analyses

Machine learning predicts lung recruitment in acute respiratory distress syndrome using single lung CT scan

Background: To develop and validate classifier models that could be used to identify patients with a high percentage of potentially recruitable lung from readily available clinical data and from single CT scan quantitative analysis at intensive care unit admission. 221 retrospectively enrolled mechanically ventilated, sedated and paralyzed patients with acute respiratory distress syndrome (ARDS) underwent a PEEP trial at 5 and 15 cmH2O of PEEP and two lung CT scans performed at 5 and 45 cmH2O of airway pressure. Lung recruitability was defined at first as percent change in not aerated tissue between 5 and 45 cmH2O (radiologically defined; recruiters: Δ45-5non-aerated tissue > 15%) and secondly as change in PaO2 between 5 and 15 cmH2O (gas exchange-defined; recruiters: Δ15-5PaO2 > 24 mmHg). Four machine learning (ML) algorithms were evaluated as classifiers of radiologically defined and gas exchange-defined lung recruiters using different models including different variables, separately or combined, of lung mechanics, gas exchange and CT data. Results: ML algorithms based on CT scan data at 5 cmH2O classified radiologically defined lung recruiters with similar AUC as ML based on the combination of lung mechanics, gas exchange and CT data. ML algorithm based on CT scan data classified gas exchange-defined lung recruiters with the highest AUC. Conclusions: ML based on a single CT data at 5 cmH2O represented an easy-to-apply tool to classify ARDS patients in recruiters and non-recruiters according to both radiologically defined and gas exchange-defined lung recruitment within the first 48 h from the start of mechanical ventilation

Evaluation of extraction-free RT-qPCR methods for SARS-CoV-2 diagnostics

Extraction-based real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) is currently the “gold standard” in SARS-CoV-2 diagnostics. However, some extraction-free RT-qPCR techniques have recently been developed. In this study, we compared the sensitivity of traditional extraction-based, heated extraction-free, and unheated extraction-free RT-qPCR methods for SARS-CoV-2 detection in nasopharyngeal swabs from symptomatic individuals. The unheated extraction-free method showed perfect agreement with the standard extraction-based RT-qPCR. By contrast, the heat-treated technique was associated with an 8.2% false negativity rate. Unheated extraction-free RT-qPCR for the molecular diagnosis of SARS-CoV-2 is a valuable alternative to the traditional extraction-based methods and may accelerate turnaround times by about two hours

Teratogenic potential of nanoencapsulated vitamin A evaluated on an alternative model organism, the tunicate Ciona intestinalis

Nano-encapsulation is a technology used to pack substances in order to enhance their stability and bioavailability, but this packing may interact with living systems, causing unexpected toxicity. Vitamin A (vit A) is a substance that has received attention, because in developed countries, the increasing availability of supplements is leading to its excessive intake. This study aims to compare teratogenic effects caused by exposure to the traditional formulation of vit A versus nano-encapsulated vit A. We used ascidian embryos as an alternative model. Ascidians are marine organisms closely related to vertebrates that share with them a body plan and developmental programme, including the morphogenetic role of retinoic acid (RA). Our data showed that the adverse effects of exposure to the same concentration of the two formulations were different, suggesting that the nano-encapsulation increased the bioavailability of the molecule, which could be better absorbed and metabolised to RA, the effective teratogenic substance