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

A Comparative Effectiveness Analysis of the Implementation of Surgical Safety Checklists in a Tertiary Care Hospital

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Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation

Aims To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. Methods and results Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57-1.42), P = 0.64 and 1.00 (0.60-1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09-0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10-0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03-0.70, P = 0.016) for HF mortality. Conclusion Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF deat

Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action

In NIH3T3 cells, 0.001 nM of the synthetic androgen R1881 induces and stimulates association of androgen receptor (AR) with Src and phosphatidylinositol 3-kinase (Pl3-kinase), respectively, thereby triggering S-phase entry. 10 nM R1881 stimulates Rac activity and membrane ruffling in the absence of the receptor–Src–PI3-kinase complex assembly. The antiandrogen Casodex and specific inhibitors of Src and PI3-kinase prevent both hormonal effects, DNA synthesis and cytoskeletal changes. Neither low nor high R1881 concentration allows receptor nuclear translocation and receptor-dependent transcriptional activity in fibroblasts, although they harbor the classical murine AR. The very low amount of AR in NIH3T3 cells (7% of that present in LNCaP cells) activates the signaling pathways, but apparently is not sufficient to stimulate gene transcription. This view is supported by the appearance of receptor nuclear translocation as well as receptor-mediated transcriptional activity after overexpression of AR in fibroblasts. In addition, AR-negative Cos cells transiently transfected with a very low amount of hAR cDNA respond to low and high R1881 concentrations with signaling activation. Interestingly, they do not show significant transcriptional activation under the same experimental conditions. Fibroblasts are the first example of cells that respond to steroid hormones with activation of signaling pathways in the absence of endogenous receptor transcriptional activity. The data reported also show that hormone concentration can be crucial in determining the type of cell responsiveness

In vitro-deranged intestinal immune response to gliadin in type 1 diabetes.

Dietary gluten has been associated with an increased risk of type 1 diabetes. We have evaluated inflammation and the mucosal immune response to gliadin in the jejunum of patients with type 1 diabetes. Small intestinal biopsies from 17 children with type 1 diabetes without serological markers of celiac disease and from 50 age-matched control subjects were examined by immunohistochemistry. In addition, biopsies from 12 type 1 diabetic patients and 8 control subjects were cultured with gliadin or ovalbumin peptic-tryptic digest and examined for epithelial infiltration and lamina propria T-cell activation. The density of intraepithelial CD3(+) and gammadelta(+) cells and of lamina propria CD25(+) mononuclear cells was higher in jejunal biopsies from type 1 diabetic patients versus control subjects. In the patients' biopsies cultured with peptic-tryptic gliadin, there was epithelial infiltration by CD3(+) cells, a significant increase in lamina propria CD25(+) and CD80(+) cells and enhanced expression of lamina propria CD54 and crypt HLA-DR. No such phenomena were observed in control subjects, even those with celiac disease-associated HLA haplotypes. In conclusion, signs of mucosal inflammation were present in jejunal biopsies from type 1 diabetic patients, and organ culture studies indicate a deranged mucosal immune response to gliadin

Nonsingular isogeometric boundary element method for Stokes flows in 3D

Isogeometric analysis (IGA) is emerging as a technology bridging computer aided geometric design (CAGD), most commonly based on Non-Uniform Rational B-Splines (NURBS) surfaces, and engineering analysis. In finite element and boundary element isogeometric methods (FE-IGA and IGA-BEM), the NURBS basis functions that describe the geometry define also the approximation spaces. In the FE-IGA approach, the surfaces generated by the CAGD tools need to be extended to volumetric descriptions, a major open problem in 3D. This additional passage can be avoided in principle when the partial differential equations to be solved admit a formulation in terms of boundary integral equations, leading to boundary element isogeometric analysis (IGA-BEM). The main advantages of such an approach are given by the dimensionality reduction of the problem (from volumetric-based to surface-based), by the fact that the interface with CAGD tools is direct, and by the possibility to treat exterior problems, where the computational domain is infinite. By contrast, these methods produce system matrices which are full, and require the integration of singular kernels. In this paper we address the second point and propose a nonsingular formulation of IGA-BEM for 3D Stokes flows, whose convergence is carefully tested numerically. Standard Gaussian quadrature rules suffice to integrate the boundary integral equations, and carefully chosen known exact solutions of the interior Stokes problem are used to correct the resulting matrices, extending the work by Klaseboer et al. (2012) [27] to IGA-BEM

An upwind vertex centred finite volume algorithm for nearly and truly incompressible explicit fast solid dynamic applications: Total and Updated Lagrangian formulations

This paper presents an explicit vertex centred finite volume method for the solution of fast transient isothermal large strain solid dynamics via a system of first order hyperbolic conservation laws. Building upon previous work developed by the authors, in the context of alternative numerical discretisations, this paper explores the use of a series of enhancements (both from the formulation and numerical standpoints) in order to explore some limiting scenarios, such as the consideration of near and true incompressibility. Both Total and Updated Lagrangian formulations are presented and compared at the discrete level, where very small differences between both descriptions are observed due to the excellent discrete satisfaction of the involutions. In addition, a matrix-free tailor-made artificial compressibility algorithm is discussed and combined with an angular momentum projection algorithm. A wide spectrum of numerical examples is thoroughly examined. The scheme shows excellent (stable, consistent and accurate) behaviour, in comparison with other methodologies, in compressible, nearly incompressible and truly incompressible bending dominated scenarios, yielding equal second order of convergence for velocities, deviatoric and volumetric components of the stress

Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene to knock-in mice affected by catecholaminergic polymorphic ventricular tachycardia is able to cure the disease from birth to advanced age

Background. Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2R33Q/R33Q (R33Q) mutation. Methods and Results. We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias. Conclusions. Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis

Long living individuals show delay of aging, which is characterized by the progressive loss of cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, endothelial dysfunction, and impairment of tissue repair after ischemic injury

A new framework for large strain electromechanics based on convex multi-variable strain energies: Finite Element discretisation and computational implementation

In Gil and Ortigosa (2016), Gil and Ortigosa introduced a new convex multi-variable framework for the numerical simulation of Electro Active Polymers (EAPs) in the presence of extreme deformations and electric fields. This extends the concept of polyconvexity to strain energies which depend on non-strain based variables. The consideration of the new concept of multi-variable convexity guarantees the well posedness of generalised Gibbs’ energy density functionals and, hence, opens up the possibility of a new family of mixed variational principles. The aim of this paper is to present, as an example, the Finite Element implementation of two of these mixed variational principles. These types of enhanced methodologies are known to be necessary in scenarios in which the simpler displacement-potential based formulation yields non-physical results, such as volumetric locking, bending and shear locking, pressure oscillations and electro-mechanical locking, to name but a few. Crucially, the use of interpolation spaces in which some of the unknown fields are described as piecewise discontinuous across elements can be used in order to efficiently condense these fields out. This results in mixed formulations with a computational cost comparable to that of the displacement-potential based approach, yet far more accurate. Finally, a series of very challenging numerical examples are presented in order to demonstrate the accuracy, robustness and efficiency of the proposed methodology