FM-track: a fiducial marker tracking software for studying cell mechanics in a three-dimensional environment

Tracking the deformation of fiducial markers in the vicinity of living cells embedded in compliant synthetic or biological gels is a powerful means to study cell mechanics and mechanobiology in three-dimensional environments. However, current approaches to track and quantify three-dimensional (3D) fiducial marker displacements remain ad-hoc, can be difficult to implement, and may not produce reliable results. Herein, we present a compact software package entitled “FM-Track,” written in the popular Python language, to facilitate feature-based particle tracking tailored for 3D cell micromechanical environment studies. FM-Track contains functions for pre-processing images, running fiducial marker tracking, and post-processing and visualization. FM-Track can thus aid the study of cellular mechanics and mechanobiology by providing an extensible software platform to more reliably extract complex local 3D cell contractile information in transparent compliant gel systems.https://www.sciencedirect.com/science/article/pii/S2352711019303474Published versio

Review of the Refeeding Syndrome

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142310/1/ncp0625.pd

Beyond obesity - thermogenic adipocytes and cardiometabolic health

The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent ‘re-discovery’ of cold-activated brown adipose tissue (BAT) in adult humans and inducible ‘beige’ adipocytes. Through the unique mitochondrial uncoupling protein (UCP1), these thermogenic adipocytes are capable of combusting large amounts of chemical energy as heat and in animal models can prevent obesity and cardiometabolic disease. At present, human data does not point to a role for thermogenic adipocytes in regulating body weight or fat mass but points to a pivotal role in regulating metabolic health by improving insulin resistance as well as glucose and lipid homeostasis. This review will therefore focus on the metabolic benefits of BAT activation and the mechanisms and signalling pathways by which these could occur including improvements in insulin signalling in peripheral tissues, systemic lipid and cholesterol metabolism and cardiac and vascular function

A Large-scale 3D Micromechanical Computational Myocardium Model

The right ventricle (RV) of the heart experiences substantial adaptions in structure and mechanical properties under pulmonary arterial hypertension (PAH). Developing computational models of RV myocardium can provide crucial insight into the factors influencing the onset, progression, and potential reversibility of post-PAH remodeling. However, knowledge of the mechanical interactions between myocardial constituents like myofibers and extracellular matrix (ECM) collagen, previously shown to be essential for capturing tissue behavior, remains incomplete, necessitating a micromechanical framework to link tissue-scale mechanical behavior to myocardial microanatomy. We developed a micromechanical finite element (FE) model leveraging high-fidelity imaging of myocardial microstructure to elucidate micro-scale myofiber-collagen interactions and their contribution to bulk tissue properties. We generated a 1.1-million tetrahedral mesh from a confocal microscopy dataset of a 204x204x40 μm myocardium sample. The material behaviors of the myofiber and ECM were modeled with hyperelastic, anisotropic, nearly incompressible constitutive forms derived from previous structurally-based models. The FE model was used to simulate physiologically informed equibiaxial and non-equibiaxial planar biaxial deformations, and the material parameters were fitted to the total stress-strain response of our previously developed tissue- scale model. Simulations were performed on the Stampede2 supercomputer at the Texas Advanced Computing Center using the finite element solver FEniCS, parallelized over 68 processors. We then employed a multiscale homogenization technique to predict tissue-level (5x5x0.7-mm) biaxial behavior from the localized micromechanical response via emulation of the tissue-scale histological structure and experimental biaxial deformation protocols. Recapitulation of the myocardial microanatomy successfully reproduced the tissue-level results in all deformation modes, suggesting that the micro-scale arrangement of myofibers and ECM is a primary mechanism driving myofiber-collagen coupling at the bulk tissue level. This work establishes the feasibility of incorporating microanatomy into high-fidelity supercomputer-based modeling of myocardium to investigate post-PAH remodeling of the cardiac microstructure and identify mechanical attributes critical to heart disease therapies

An Exploratory Pathways Analysis of Temporal Changes Induced by Spinal Cord Injury in the Rat Bladder Wall: Insights on Remodeling and Inflammation

Background: Spinal cord injuries (SCI) can lead to severe bladder pathologies associated with inflammation, fibrosis, and increased susceptibility to urinary tract infections. We sought to characterize the complex pathways of remodeling, inflammation, and infection in the urinary bladder at the level of the transcriptome in a rat model of SCI, using pathways analysis bioinformatics. Methodology/Principal Findings: Experimental data were obtained from the study of Nagatomi et al. (Biochem Biophys Res Commun 334: 1159). In this study, bladders from rats subjected to surgical SCI were obtained at 3, 7 or 25 days post-surgery, and Affymetrix GeneChip® Rat Genome U34A arrays were used for cRNA hybridizations. In the present study, Ingenuity Pathways Analysis (Ingenuity® Systems, www.ingenuity.com) of differentially expressed genes was performed. Analysis of focus genes in networks, functional analysis, and canonical pathway analysis reinforced our previous findings related to the presence of up-regulated genes involved in tissue remodeling, such as lysyl oxidase, tropoelastin, TGF-β1, and IGF-1. This analysis also highlighted a central role for inflammation and infection, evidenced by networks containing genes such as CD74, S100A9, and THY1. Conclusions/Significance: Our findings suggest that tissue remodeling, infection, inflammation, and tissue damage/ dysfunction all play a role in the urinary bladder, in the complex response to SCI. © 2009 Wognum et al

Biomechanical behavior of bioprosthetic heart valve heterograft tissues: characterization, simulation, and performance

The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact. In order to develop improved solutions for BHV biomaterials, it is critical to have a better understanding of the inherent biomechanical behaviors of the leaflet biomaterials, including chemical treatment technologies, the impact of repetitive mechanical loading, and the inherent failure modes. This review seeks to provide a comprehensive overview of these issues, with a focus on developing insight on the mechanisms of BHV function and failure. Additionally, this review provides a detailed summary of the computational biomechanical simulations that have been used to inform and develop a higher level of understanding of BHV tissues and their failure modes. Collectively, this information should serve as a tool not only to infer reliable and dependable prosthesis function, but also to instigate and facilitate the design of future bioprosthetic valves and clinically impact cardiology

Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices

Sub-wavelength imaging with a left-handed material flat lens

We study numerically, by means of the pseudospectral time-domain method, the unique features of imaging by a flat lens made of a left-handed metamaterial that possesses the property of negative refraction. We confirm the earlier finding that a left-handed flat lens can provide near-perfect imaging of a point source and a pair of point sources with clear evidence of the sub-wavelength resolution. We illustrate the limitation of the resolution in the time-integrated image due to the presence of surface waves.Comment: 4 pages, RevTeX, 6 figures; added references and some discussio