A two-component fluid-solid finite element model of the red blood cell

The state of the art models for the red blood cell consist of two components: A solid network of fibers (worm-like chains) that correspond to the cytoskeleton, and a fluid surface with bending stiffness that corresponds to the lipid bilayer (X. Li et.al., Phil. Trans. R. Soc. A, 372:20130389 (2014)). The fluid and solid components are connected at the junctions of the network, where trans-membrane proteins anchor the bilayer to the cytoskeleton, but this connection is not rigid and under large deformations it is possible that cytoskeleton and bilayer detach from one another. It is well know that the interactions between the lipid bilayer membrane and the skeletal network (fluid-solid interactions) are responsible for the physical properties of red blood cell. However, quantifying these interactions and studying the related dynamics is still a topic discussed and full of open questions (S. Lux, Blood, 127:187–199 (2016)). In this work we will report on our first advances towards the development of a finite element method for this strongly coupled system. It leads to a fluid-structure interaction problem, with the salient feature that both the fluid and the structure are in fact two-dimensional bodies evolving in three-dimensional space.Publicado en: Mecánica Computacional vol. XXXV, no. 9.Facultad de Ingenierí

A two-component fluid-solid finite element model of the red blood cell

The state of the art models for the red blood cell consist of two components: A solid network of fibers (worm-like chains) that correspond to the cytoskeleton, and a fluid surface with bending stiffness that corresponds to the lipid bilayer (X. Li et.al., Phil. Trans. R. Soc. A, 372:20130389 (2014)). The fluid and solid components are connected at the junctions of the network, where trans-membrane proteins anchor the bilayer to the cytoskeleton, but this connection is not rigid and under large deformations it is possible that cytoskeleton and bilayer detach from one another. It is well know that the interactions between the lipid bilayer membrane and the skeletal network (fluid-solid interactions) are responsible for the physical properties of red blood cell. However, quantifying these interactions and studying the related dynamics is still a topic discussed and full of open questions (S. Lux, Blood, 127:187–199 (2016)). In this work we will report on our first advances towards the development of a finite element method for this strongly coupled system. It leads to a fluid-structure interaction problem, with the salient feature that both the fluid and the structure are in fact two-dimensional bodies evolving in three-dimensional space.Publicado en: Mecánica Computacional vol. XXXV, no. 9.Facultad de Ingenierí

A two-component fluid-solid finite element model of the red blood cell

The state of the art models for the red blood cell consist of two components: A solid network of fibers (worm-like chains) that correspond to the cytoskeleton, and a fluid surface with bending stiffness that corresponds to the lipid bilayer (X. Li et.al., Phil. Trans. R. Soc. A, 372:20130389 (2014)). The fluid and solid components are connected at the junctions of the network, where trans-membrane proteins anchor the bilayer to the cytoskeleton, but this connection is not rigid and under large deformations it is possible that cytoskeleton and bilayer detach from one another. It is well know that the interactions between the lipid bilayer membrane and the skeletal network (fluid-solid interactions) are responsible for the physical properties of red blood cell. However, quantifying these interactions and studying the related dynamics is still a topic discussed and full of open questions (S. Lux, Blood, 127:187–199 (2016)). In this work we will report on our first advances towards the development of a finite element method for this strongly coupled system. It leads to a fluid-structure interaction problem, with the salient feature that both the fluid and the structure are in fact two-dimensional bodies evolving in three-dimensional space.Publicado en: Mecánica Computacional vol. XXXV, no. 9.Facultad de Ingenierí

Performance of commerical blood tests for the diagnosis of latent tuberculosis infection in children and adolescents

BACKGROUND: The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells).OBJECTIVE:To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection.METHODS:We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB.RESULTS:Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children /=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube.CONCLUSIONS:Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age

The Efficacy of Umbelliferone, Arbutin, and N-Acetylcysteine to Prevent Microbial Colonization and Biofilm Development on Urinary Catheter Surface: Results from a Preliminary Study

We evaluated, in a preliminary study, the efficacy of umbelliferone, arbutin, and N-acetylcysteine to inhibit biofilm formation on urinary catheter. We used 20 urinary catheters: 5 catheters were incubated with Enterococcus faecalis (control group); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 1); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (400 mg) (group 2); and 5 catheters were incubated with E. faecalis in presence of umbelliferone (300 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 3). After 72 hours, planktonic microbial growth and microorganisms on catheter surface were assessed. In the control group, we found a planktonic load of ≥105 CFU/mL in the inoculation medium and retrieved 3.69 × 106 CFU/cm from the sessile cells adherent to the catheter surface. A significantly lower amount in planktonic (p < 0.001) and sessile (p = 0.004) bacterial load was found in group 3, showing <100 CFU/mL and 0.12 × 106 CFU/cm in the incubation medium and on the catheter surface, respectively. In groups 1 and 2, 1.67 × 106 CFU/cm and 1.77 × 106 CFU/cm were found on catheter surface. Our results document that umbelliferone, arbutin, and N-acetylcysteine are able to reduce E. faecalis biofilm development on the surface of urinary catheters

Concomitant radiotherapy and TKI in metastatic EGFR- or ALK-mutated non-small cell lung cancer: a multicentric analysis on behalf of AIRO lung cancer study group

PurposeTo investigate the role of radiotherapy (RT) in the management of EGFR- or ALK-mutated metastatic non-small cell lung cancer (NSCLC) treated with TKI.Materials and methodsClinical data of 106 patients (pts) from five Institutions treated with RT concomitant to TKI were retrospectively revised. Overall survival (OS) and toxicities were analyzed as endpoints of the study.ResultsMedian age of pts was 65years. TKIs were given for EGFR (81%)- or ALK (19%)-mutated metastatic NSCLC. Stereotactic RT (SRT) was delivered to 49 pts (46%). Patients with four or less metastasis were defined as oligometastatic/oligoprogressive (OM/OP); sites of RT were brain, bone, lung or others in 46%, 27%, 14% and 13%, respectively. Median OS was 23months. At univariate analysis SRT, ECOG PS 0-1, OM/OP disease, lung sites and a TKI duration longer than median favorably affected OS (all p14months (HR 0.17, 95% CI 0.10-0.30; p<0.001) as independent factors related to better OS. Toxicities were rare.ConclusionsSRT seems to positively affect OS with limited toxicity in selected patients

Multidrug-resistant tuberculosis outbreak in an Italian prison: Tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice

A mathematical model of a single seed oleosome

© 2020 The Authors In this work we report for the first time a mathematical approach to model the behaviour of a single oleosome (oil body) within a seed cellular environment. To describe the behaviour of the oleosome membrane, we adopted a dynamical continuum model based on the principle of the virtual work where the intrinsic energy of the lipid membrane is assumed to obey the Canham–Helfrich model with the rheology of the viscous interface governed by the Boussinesq–Scriven law. To show the suitability of this approach to study the mechanical behaviour of oleosomes, we present some numerical simulations of a single oleosome deformation occurring under in vivo and ex vivo conditions. This work aims to show how the mathematical and computational modelling allows studying the impact of otherwise hard-to-measure physical quantities in this field of biological applications

Early nasal high-flow versus Venturi mask oxygen therapy after lung resection: A randomized trial

Background: Data on high-flow nasal oxygen after thoracic surgery are limited and confined to the comparison with low-flow oxygen. Different from low-flow oxygen, Venturi masks provide higher gas flow at a predetermined fraction of inspired oxygen (FiO 2 ). We conducted a randomized trial to determine whether preemptive high-flow nasal oxygen reduces the incidence of postoperative hypoxemia after lung resection, as compared to Venturi mask oxygen therapy. Methods: In this single-center, randomized trial conducted in a teaching hospital in Italy, consecutive adult patients undergoing thoracotomic lung resection, who were not on long-term oxygen therapy, were randomly assigned to receive high-flow nasal or Venturi mask oxygen after extubation continuously for two postoperative days. The primary outcome was the incidence of postoperative hypoxemia (i.e., ratio of the partial pressure of arterial oxygen to FiO 2 (PaO 2 /FiO 2 ) lower than 300 mmHg) within four postoperative days. Results: Between September 2015 and April 2018, 96 patients were enrolled; 95 patients were analyzed (47 in high-flow group and 48 in Venturi mask group). In both groups, 38 patients (81% in the high-flow group and 79% in the Venturi mask group) developed postoperative hypoxemia, with an unadjusted odds ratio (OR) for the high-flow group of 1.11 [95% confidence interval (CI) 0.41-3] (p = 0.84). No inter-group differences were found in the degree of dyspnea nor in the proportion of patients needing oxygen therapy after treatment discontinuation (OR 1.34 [95% CI 0.60-3]), experiencing pulmonary complications (OR 1.29 [95% CI 0.51-3.25]) or requiring ventilatory support (OR 0.67 [95% CI 0.11-4.18]). Post hoc analyses revealed that PaO 2 /FiO 2 during the study was not different between groups (p = 0.92), but patients receiving high-flow nasal oxygen had lower arterial pressure of carbon dioxide, with a mean inter-group difference of 2 mmHg [95% CI 0.5-3.4] (p = 0.009), and were burdened by a lower risk of postoperative hypercapnia (adjusted OR 0.18 [95% CI 0.06-0.54], p = 0.002). Conclusions: When compared to Venturi mask after thoracotomic lung resection, preemptive high-flow nasal oxygen did not reduce the incidence of postoperative hypoxemia nor improved other analyzed outcomes. Further adequately powered investigations in this setting are warranted to establish whether high-flow nasal oxygen may yield clinical benefit on carbon dioxide clearance