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      An exploratory assessment of stretch-induced transmural myocardial fiber kinematics in right ventricular pressure overload

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          Abstract

          Right ventricular (RV) remodeling and longitudinal fiber reorientation in the setting of pulmonary hypertension (PH) affects ventricular structure and function, eventually leading to RV failure. Characterizing the kinematics of myocardial fibers helps better understanding the underlying mechanisms of fiber realignment in PH. In the current work, high-frequency ultrasound imaging and structurally-informed finite element (FE) models were employed for an exploratory evaluation of the stretch-induced kinematics of RV fibers. Image-based experimental evaluation of fiber kinematics in porcine myocardium revealed the capability of affine assumptions to effectively approximate myofiber realignment in the RV free wall. The developed imaging framework provides a noninvasive modality to quantify transmural RV myofiber kinematics in large animal models. FE modeling results demonstrated that chronic pressure overload, but not solely an acute rise in pressures, results in kinematic shift of RV fibers towards the longitudinal direction. Additionally, FE simulations suggest a potential protective role for concentric hypertrophy (increased wall thickness) against fiber reorientation, while eccentric hypertrophy (RV dilation) resulted in longitudinal fiber realignment. Our study improves the current understanding of the role of different remodeling events involved in transmural myofiber reorientation in PH. Future experimentations are warranted to test the model-generated hypotheses.

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          In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

          Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
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            Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy.

            Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and -43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wall.
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              Scale-space and edge detection using anisotropic diffusion

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                Author and article information

                Contributors
                kangkim@upmc.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 February 2021
                11 February 2021
                2021
                : 11
                : 3587
                Affiliations
                [1 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Department of Bioengineering, , University of Pittsburgh, ; Pittsburgh, PA USA
                [2 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Department of Mechanical Engineering and Materials Science, , University of Pittsburgh, ; Pittsburgh, PA USA
                [3 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Division of Cardiology, Department of Medicine, , University of Pittsburgh School of Medicine, ; 623A Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213 USA
                [4 ]GRID grid.412689.0, ISNI 0000 0001 0650 7433, Heart and Vascular Institute, , University of Pittsburgh Medical Center (UPMC), ; Pittsburgh, PA USA
                [5 ]GRID grid.412689.0, ISNI 0000 0001 0650 7433, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, , University of Pittsburgh and University of Pittsburgh Medical Center (UPMC), ; Pittsburgh, PA USA
                [6 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, McGowan Institute for Regenerative Medicine, , University of Pittsburgh, ; Pittsburgh, PA USA
                [7 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Center for Ultrasound Molecular Imaging and Therapeutics, , University of Pittsburgh, ; Pittsburgh, PA USA
                Article
                83154
                10.1038/s41598-021-83154-8
                7878470
                99e7ea3b-28b2-4809-a140-7e65cb280e74
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 June 2020
                : 22 January 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000968, American Heart Association;
                Award ID: AHA-20PRE35210429
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5T32HL076124-12
                Award ID: NIH 1 S10 RR027383-01
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                heart failure,hypertension,cardiomyopathies,cardiac hypertrophy,biomedical engineering,mechanical engineering

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