Reduced Lagrange multiplier approach for non-matching coupled problems in multiscale elasticity

This paper presents a numerical method for the simulation of elastic solid materials coupled to fluid inclusions. The application is motivated by the modeling of vascularized tissues and by problems in medical imaging which target the estimation of effective (i.e., macroscale) material properties, taking into account the influence of microscale dynamics, such as fluid flow in the microvasculature. The method is based on the recently proposed Reduced Lagrange Multipliers framework. In particular, the interface between solid and fluid domains is not resolved within the computational mesh for the elastic material but discretized independently, imposing the coupling condition via non-matching Lagrange multipliers. Exploiting the multiscale properties of the problem, the resulting Lagrange multipliers space is reduced to a lower-dimensional characteristic set. We present the details of the stability analysis of the resulting method considering a non-standard boundary condition that enforces a local deformation on the solid-fluid boundary. The method is validated with several numerical examples

Multiscale coupling of one-dimensional vascular models and elastic tissues

We present a computational multiscale model for the efficient simulation of vascularized tissues, composed of an elastic three-dimensional matrix and a vascular network. The effect of blood vessel pressure on the elastic tissue is surrogated via hyper-singular forcing terms in the elasticity equations, which depend on the fluid pressure. In turn, the blood flow in vessels is treated as a one-dimensional network. The pressure and velocity of the blood in the vessels are simulated using a high-order finite volume scheme, while the elasticity equations for the tissue are solved using a finite element method. This work addresses the feasibility and the potential of the proposed coupled multiscale model. In particular, we assess whether the multiscale model is able to reproduce the tissue response at the effective scale (of the order of millimeters) while modeling the vasculature at the microscale. We validate the multiscale method against a full scale (three-dimensional) model, where the fluid/tissue interface is fully discretized and treated as a Neumann boundary for the elasticity equation. Next, we present simulation results obtained with the proposed approach in a realistic scenario, demonstrating that the method can robustly and efficiently handle the one-way coupling between complex fluid microstructures and the elastic matrix

Multiscale Coupling of One-dimensional Vascular Models and Elastic Tissues

We present a computational multiscale model for the efficient simulation of vascularized tissues, composed of an elastic three-dimensional matrix and a vascular network. The effect of blood vessel pressure on the elastic tissue is surrogated via hyper-singular forcing terms in the elasticity equations, which depend on the fluid pressure. In turn, the blood flow in vessels is treated as a one-dimensional network. Intravascular pressure and velocity are simulated using a high-order finite volume scheme, while the elasticity equations for the tissue are solved using a finite element method. This work addresses the feasibility and the potential of the proposed coupled multiscale model. In particular, we assess whether the multiscale model is able to reproduce the tissue response at the effective scale (of the order of millimeters) while modeling the vasculature at the microscale. We validate the multiscale method against a full scale (three-dimensional) model, where the fluid/tissue interface is fully discretized and treated as a Neumann boundary for the elasticity equation. Next, we present simulation results obtained with the proposed approach in a realistic scenario, demonstrating that the method can robustly and efficiently handle the one-way coupling between complex fluid microstructures and the elastic matrix. © 2021, The Author(s)

Clinical characteristics and cardiovascular implications of the dead patients for COVID-19:

Coronavirus Disease 2019 (COVID-19) caused by 2019 novel coronavirus (named SARS-CoV-2), has become a global pandemic. Aged population with cardiovascular diseases is usually more susceptible to SARS-CoV-2 infection with an increased risk of severe complications and elevated case-fatality rate. Despite of several researches about COVID-19, cardiovascular implications related to this infection still remain largely unclear. The aim of this study is to evaluate the clinical characteristics of dead patients with COVID-19. We enrolled all patients with more than 50 years of age with laboratory confirmed COVID-19, admitted to infectious clinical diseases PO SS Annunziata of Chieti (Italy) from March 2020 to April 2020 who died during hospitalization. Demographics, underlying comorbidities, clinical symptoms and signs, laboratory results, computed tomography of the chest, treatment measures, and outcome data were collected. We enrolled eight patients, the age was 82 ± 9.7 years, four female and four male. All patients had comorbidity, such as hypertension (7 [87.5%]), diabetes (1 [12.5%]), and heart disease (6 [75%]). Common symptoms included fever [8 (100%)], dry cough (1[12.56%]), and dyspnea (3 [37.5%]). All patients [8 (100%)] showed local and/or bilateral patchy shadowing on chest computed tomography that is the typical radiological finding in COVID-19. Lymphopenia was observed in seven patients (87.5%). All patients showed elevated troponin and prolongation of the QTc interval ( p < 0.05). In this study we demonstrated that in SARS-CoV-2 infection, the deaths occurred in the non-ICU population with more than 50 years are related to cardiac causes. In our cases elongation of QTc and alteration in troponin are present in all patients who died and could represent a data to better stratify the population at risk. More detailed research on cardiovascular involvement in COVID-19 patients with sudden deaths showed a predictive role of troponin and QTc elongation

Enhancement of Dopaminergic Differentiation in Proliferating Midbrain Neuroblasts by Sonic Hedgehog and Ascorbic Acid

We analyzed the molecular mechanisms involved in the acquisition and maturation of dopaminergic (DA) neurons generated in vitro from rat ventral mesencephalon (MES) cells in the presence of mitogens or specific signaling molecules. The addition of basic fibroblast growth factor (bFGF) to MES cells in serum-free medium stimulates the proliferation of neuroblasts but delays DA differentiation. Recombinant Sonic hedgehog (SHH) protein increases up to three fold the number of tyrosine hydroxylase (TH)-positive cells and their differentiation, an effect abolished by anti-SHH antibodies. The expanded cultures are rich in nestin-positive neurons, glial cells are rare, all TH+ neurons are DA, and all DA and GABAergic markers analyzed are expressed. Adding ascorbic acid to bFGF/SHH-treated cultures resulted in a further five- to seven-fold enhancement of viable DA neurons. This experimental system also provides a powerful tool to generate DA neurons from single embryos. Our strategy provides an enriched source of MES DA neurons that are useful for analyzing molecular mechanisms controlling their function and for experimental regenerative approaches in DA dysfunction

Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

Previous gene targeting studies in mice have implicated the nuclear protein Krüppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates. © 2010 Elsevier Inc

number of mediastinal lymph nodes as a prognostic factor in pn2 non small cell lung cancer a single centre experience and review of the literature

Lung cancer is one of the most common cause of cancer-related death for men and women in the world. The prevalent histology is non-small cell lung carcinoma (NSCLC), including squamous cell carcinoma, adenocarcinoma and large cell carcinoma (Moretti et al., 2009), with a 5year survival rate of 67% (stage IA) to <5% (stage IV) (End, 2006). Currently the most important predictor of survival in lung cancer is the stage (TNM) (Kligerman and Abbot, 2010; Goldstraw, 2009). Despite the new staging system (Kligerman and Abbot, 2010), stage III NSCLC remains a very heterogeneous disease , with a 5-year survival rate ranging from 35% to 5%. There are two major treatment targets for of patients with stage III : locoregional control and control of micrometastases, preventing distant metastatic disease (Penland et al., 2004; Bradley et al., 2005). The standard of care is represented by multimodality treatment, comprehending surgery for resectable disease, perioperative chemotherapy and radiation therapy (RT) for patients with pathological (p) N2 disease (Okamoto, 2008). In current TNM classification system, N category is defined exclusively by anatomic nodal location, though number of lymph nodes confirmed to be a fundamental prognostic factor as in other type of tumours. In our study, we assessed, in patients with stage III N2 category NSCLC disease, the prognostic value of the number of lymph nodes after multimodality treatment

Relationship between severe obesity and gut inflammation in children: what's next?

Background: Preliminary evidence suggests an association between obesity and gut inflammation. Aims: To evaluate the frequency of glucose abnormalities and their correlation with systemic and intestinal inflammation in severely obese children. Patients and Methods: Thirty-four children (25 males; median age 10.8 ± 3.4 yrs) with severe obesity (BMI >95%) were screened for diabetes with oral glucose tolerance test (OGTT), systemic inflammation with C-reactive protein (CRP) and gut inflammation with rectal nitric oxide (NO) and faecal calprotectin. Results: BMI ranged from 23 to 44 kg/m2, and BMI z-score between 2.08 e 4.93 (median 2.69 ± 0.53). Glucose abnormalities were documented in 71% of patients: type 2 diabetes in 29%, impaired fasting glucose (IFG) in 58%, and impaired glucose tolerance (IGT) in 37.5%. Thirty-one patients (91%) were hyperinsulinemic. CRP was increased in 73.5% with a correlation between BMI z-score and CRP (p 0.03). Faecal calprotectin was increased in 47% patients (mean 77 ± 68), and in 50% of children with abnormal glucose metabolism (mean 76 ± 68 ìg/g), with a correlation with increasing BMI z-score. NO was pathological in 88%, and in 87.5% of glucose impairment (mean 6.8 ± 5 ìM). Conclusions: In this study, the prevalence of glucose abnormalities in obese children is higher than in other series; furthermore, a correlation is present between markers of systemic and intestinal inflammation and glucose abnormalities

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

open16noFunding: This study was carried out as part of our routine work and supported by internal funding.Objectives: To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection.Methods: Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model.Results: In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8-20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1-4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15-1.38, P &lt; 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38-1.08, P = 0.10).Conclusions: Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.openPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, MaddalenaPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, Maddalen

Multiscale Bone Remodelling with Spatial P Systems

Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as our shape-based one already resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005