COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases.

Introduction COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. Case reports All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. Conclusions In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases

CellExcite: an efficient simulation environment for excitable cells

Background Brain, heart and skeletal muscle share similar properties of excitable tissue, featuring both discrete behavior (all-or-nothing response to electrical activation) and continuous behavior (recovery to rest follows a temporal path, determined by multiple competing ion flows). Classical mathematical models of excitable cells involve complex systems of nonlinear differential equations. Such models not only impair formal analysis but also impose high computational demands on simulations, especially in large-scale 2-D and 3-D cell networks. In this paper, we show that by choosing Hybrid Automata as the modeling formalism, it is possible to construct a more abstract model of excitable cells that preserves the properties of interest while reducing the computational effort, thereby admitting the possibility of formal analysis and efficient simulation. Results We have developed CellExcite, a sophisticated simulation environment for excitable-cell networks. CellExcite allows the user to sketch a tissue of excitable cells, plan the stimuli to be applied during simulation, and customize the diffusion model. CellExcite adopts Hybrid Automata (HA) as the computational model in order to efficiently capture both discrete and continuous excitable-cell behavior. Conclusions The CellExcite simulation framework for multicellular HA arrays exhibits significantly improved computational efficiency in large-scale simulations, thus opening the possibility for formal analysis based on HA theory. A demo of CellExcite is available at http://www.cs.sunysb.edu/~eha/ webcite

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Spatial Networks of Hybrid I/O Automata for Modeling Excitable Tissue

We propose a new biological framework, spatial networks of hybrid input/output automata (SNHIOA), for the efficient modeling and simulation of excitable-cell tissue. Within this framework, we view an excitable tissue as a network of interacting cells disposed according to a 2D spatial lattice, with the electrical behavior of a single cell modeled as a hybrid input/ouput automaton. To capture the phenomenon that the strength of communication between automata depends on their relative positions within the lattice, we introduce a new, weighted parallel composition operator to specify the influence of one automata over another. The purpose of the SNHIOA model is to efficiently capture the spatiotemporal behavior of wave propagation in 2D excitable media. To validate this claim, we show how SNHIOA can be used to model and capture different spatiotemporal behavior of wave propagation in 2D isotropic cardiac tissue, including normal planar wave propagation, spiral creation, the breakup of spirals into more complex (potentially lethal) spatiotemporal patterns, and the recovery of the tissue to the rest via defibrillation

The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor Cells

In the present study, the potential functional properties of the extracts from the edible part of Capsicum annuum L. var. Peperone di Voghera (VP) were studied. The phytochemical analysis revealed a high amount of ascorbic acid, paralleled by a low carotenoid content. Normal human diploid fibroblasts (NHDF) were chosen as the in vitro model models to investigate the effects of the VP extract on oxidative stress and aging pathways. The extract of Carmagnola pepper (CP), another important Italian variety, was used as the reference vegetable. The cytotoxicity evaluation was performed firstly, using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the VP potential antioxidant and antiaging activity was investigated by immunofluorescence staining focusing on specifically selected proteins. The MTT data revealed the highest cell viability at a concentration of up to 1 mg/mL. The immunocytochemical analyses highlighted an increased expression of transcription factors and enzymes involved in redox homeostasis (Nrf2, SOD2, catalase), improved mitochondrial functionality, and the up-regulation of the longevity gene SIRT1. The present results supported the functional role of the VP pepper ecotype, suggesting a feasible use of its derived products as valuable food supplements

A Clinico-pathological "Bird's-Eye" View of Left Atrial Myocardial Fibrosis in 121 Patients with Persistent Atrial Fibrillation: Developing Architecture and Main Cellular Players

Background - Scientific research on atrial fibrosis in atrial fibrillation (AF) has mainly focused on quantitative and/or molecular features. The purpose of this study was to perform a clinico-architectural/structural investigation of fibrosis to provide one key to understanding the electrophysiological/clinical aspects of AF. Methods - We characterized the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting persistent AF (Group 1) (59 males; 60±11 years; 91 mitral disease-related AF, 30 non-mitral disease-related AF) and from 39 patients in sinus rhythm with mitral-valve regurgitation (Group 2; 32 males; 59±12 years). Ten autopsy hearts served as controls. Results - Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which we arbitrarily subdivided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and at a more advanced stage in Group 1 vs. Group 2 and, within Group 1, in patients with rheumatic disease vs. non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69-150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes-circulating and bone marrow-derived mesenchymal cells-were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. Conclusions - Atrial fibrosis is an evolving and inhomogeneous histological/architectural change which progresses through different stages ranging from isolated foci to confluent sclerotic zones which - seemingly - constrain impulse conduction across restricted regions of electrotonically-coupled cardiomyocytes. The fibrotic areas mainly consist of type I collagen extracellular matrix and, only to a lesser extent, mesenchymal cells