Influenza Virus Infection of Marine Mammals

EcoHealth - Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens...     

Fluid flow and plaque formation in an aortic bifurcation

Considering steady laminar flow in a two-dimensional symmetric branching channel with local occlusions, a finite element model has been developed to study velocity fields including reverse flow regions, pressure profiles and wall shear stress distributions for different Reynolds numbers, bifurcation angles and lumen reductions. The flow analysis has been extended to include a new submodel for the pseudo-transient formation of plaque at sites and deposition rates defined by the physical characteristics of the flow. Specifically, simulating the onset of atherosclerotic lesions, sinusoidal plaque layers have been placed in areas of critically low wall shear stresses, and simulating the growth of particle depositions, plaque layers have been added in a stepwise fashion in regions of critically high and low shear. Thus two somewhat conflicting hypothetical correlations between critical wall shear stress levels and atheroma have been tested and a solution has been postulated. The validated computer simulation model is a predictive tool for analyzing the effects of local changes in wall curvature due to surgical reconstruction and/or atherosclerotic lesions, and for investigating the design of aortic bifurcations which mitigate plaque formation.     

On prediction of the strength levels and failure patterns of human vertebrae using quantitative computed tomography (QCT)-based finite element method

This paper presents an effective patient-specific approach for prediction of failure initiation and growth in human vertebra using the general framework of the quantitative computed tomography (QCT)-based finite element method (FEM). The studies were carried out on 13 vertebrae (lumbar and thoracic), excised from 3 cadavers with the average age of 42 years old. Initially, 4 samples were QCT scanned and the images were directly converted into voxel-based 3D finite element models for linear and nonlinear analyses. The equivalent plastic strains obtained from the nonlinear analyses were used to predict the occurrence of local failures and development of the failure patterns. In the linear analyses, the strain energy density measure was used to identify the critical elements and predict the failure patterns. Subsequently, the samples were destructively tested in uniaxial compression and the experimental load–displacement diagrams were obtained. The plain radiographic images of the tested samples were also examined for observation of the failure patterns. In continuation, the presence of osteolytic defects in vertebrae was simulated by creation of artificial cavities within 9 remaining samples using a computer numerical control (CNC) milling machine. The same protocol was followed for scanning, modeling, and destructive testing of these samples. A strong correlation was found between the predicted and measured strengths. Finally, a typical vertebroplasty treatment was simulated by injection of low-viscosity bone cement within 3 compressed samples. The failure patterns and the associated load levels for these samples were also predicted using the QCT voxel-based FEM.     

Preparation,Characterization, and Optimization of Folic Acid-Chitosan-Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery

The objective of this study was to investigate the combined influence of independent variables in the preparation of folic acid-chitosan-methotrexate nanoparticles (FA-Chi-MTX NPs). These NPs were designed and prepared for targeted drug delivery in tumor. The NPs of each batch were prepared by coaxial electrospray atomization method and evaluated for particle size (PS) and particle size distribution (PSD). The independent variables were selected to be concentration of FA-chitosan, ratio of shell solution flow rate to core solution flow rate, and applied voltage. The process design of experiments (DOE) was obtained with three factors in three levels by Design expert software. Box-Behnken design was used to select 15 batches of experiments randomly. The chemical structure of FA-chitosan was examined by FTIR. The NPs of each batch were collected separately, and morphologies of NPs were investigated by field emission scanning electron microscope (FE-SEM). The captured pictures of all batches were analyzed by ImageJ software. Mean PS and PSD were calculated for each batch. Polynomial equation was produced for each response. The FE-SEM results showed the mean diameter of the core-shell NPs was around 304 nm, and nearly 30% of the produced NPs are in the desirable range. Optimum formulations were selected. The validation of DOE optimization results showed errors around 2.5 and 2.3% for PS and PSD, respectively. Moreover, the feasibility of using prepared NPs to target tumor extracellular pH was shown, as drug release was greater in the pH of endosome (acidic medium). Finally, our results proved that FA-Chi-MTX NPs were active against the human epithelial cervical cancer (HeLa) cells.     

The Transition from Quiescent to Activated States in Human Hematopoietic Stem Cells Is Governed by Dynamic 3D Genome Reorganization

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Analysis of particle trajectories in aortic artery bifurcations with stenosis

The fluid-particle dynamics in a two-dimensonal symmetric branching channel with local occlusions representing a diseased segment of an aortic artery bifurcation has been analyzed. The validated finite element model simulates the trajectories and landing or impact sites of spherical particles for laminar flow in bifurcation channels with generalized wall conditions. Two hypotheses relating critical wall shear stress levels and plaque formation, previously postulated by Kleinstreuer et al. (1988) and Nazemi et al. (1989), have been confirmed. Low shear stress may contribute to the onset of atherosclerotic lesions and areas of critically low and higher shear stresses are susceptible to accelerated growth of plaque.     

Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target

Traumatic brain injury (TBI) is known as an acute degenerative pathology of the central nervous system, and has been shown to increase brain aquaporin 4 (AQP4) expression. Various molecular mechanisms affect AQP4 expression, including neuronal high mobility group box 1, forkhead box O3a, vascular endothelial growth factor, hypoxia-inducible factor-1 α (HIF-1 α) sirtuin 2, NF-κB, Malat1, nerve growth factor and Angiotensin II receptor type 1. In addition, inhibition of AQP4 with FK-506, MK-801 (indirectly by targeting N-methyl-d-aspartate receptor), inactivation of adenosine A2A receptor, levetiracetam, adjudin, progesterone, estrogen, V1aR inhibitor, hypertonic saline, erythropoietin, poloxamer 188, brilliant blue G, HIF-1alpha inhibitor, normobaric oxygen therapy, astaxanthin, epigallocatechin-3-gallate, sesamin, thaliporphine, magnesium, prebiotic fiber, resveratrol and omega-3, as well as AQP4 gene silencing lead to reduced edema upon TBI. This review summarizes current knowledge and evidence on the relationship between AQP4 and TBI, and the potential mechanisms involved.