Biomech Model Mechanobiol
December 2024
The heart is a dynamic pump whose function is influenced by its mechanical properties. The viscoelastic properties of the heart, i.e.
View Article and Find Full Text PDFControlling cellular shape with micropatterning extracellular matrix (ECM) proteins on hydrogels has been shown to improve the reproducibility of the cell structure, enhancing our ability to collect statistics on single-cell behaviors. Patterning methods have advanced efforts in developing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a promising human model for studies of the heart structure, function, and disease. Patterned single hiPSC-CMs have exhibited phenotypes closer to mature, primary CMs across several metrics, including sarcomere alignment and contractility, area and aspect ratio, and force production.
View Article and Find Full Text PDFObjectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.
Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.
The sense of touch is conferred by the conjoint function of somatosensory neurons and skin cells. These cells meet across a gap filled by a basal lamina, an ancient structure found in metazoans. Using Caenorhabditis elegans, we investigate the composition and ultrastructure of the extracellular matrix at the epidermis and touch receptor neuron (TRN) interface.
View Article and Find Full Text PDFCardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time.
View Article and Find Full Text PDFHypertrophy Cardiomyopathy (HCM) is the most prevalent hereditary cardiovascular disease - affecting >1:500 individuals. Advanced forms of HCM clinically present with hypercontractility, hypertrophy and fibrosis. Several single-point mutations in b-myosin heavy chain (MYH7) have been associated with HCM and increased contractility at the organ level.
View Article and Find Full Text PDFIntroduction: Traction force microscopy (TFM) is a widely used technique to measure cell contractility on compliant substrates that mimic the stiffness of human tissues. For every step in a TFM workflow, users make choices which impact the quantitative results, yet many times the rationales and consequences for making these decisions are unclear. We have found few papers which show the complete experimental and mathematical steps of TFM, thus obfuscating the full effects of these decisions on the final output.
View Article and Find Full Text PDFDetermining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain () can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions.
View Article and Find Full Text PDFMechanical ventilation is rarely a simple matter. Skill and knowledge are required to operate the ventilator modes, choose the optimal settings, and understand many monitored variables. Supporting the patient safely and effectively is the top priority in providing mechanical ventilation.
View Article and Find Full Text PDFBiophys Rev (Melville)
June 2023
The integrity of epithelia is maintained within dynamic mechanical environments during tissue development and homeostasis. Understanding how epithelial cells mechanosignal and respond collectively or individually is critical to providing insight into developmental and (patho)physiological processes. Yet, inferring or mimicking mechanical forces and downstream mechanical signaling as they occur in epithelia presents unique challenges.
View Article and Find Full Text PDFBackground: Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 10/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations.
View Article and Find Full Text PDFThis article provides a step-by-step guide for nurses to interpret arterial blood gas (ABG) results, focusing on five key components: SaO2, PaO2, pH, PaCO2, and HCO3-. It explains how to assess a patient's oxygenation status, compensation levels, and determine if there is an acid-base disturbance and if that disturbance is respiratory or metabolic.
View Article and Find Full Text PDFRationale: Over 200 mutations in the sarcomeric protein β-myosin heavy chain (MYH7) have been linked to hypertrophic cardiomyopathy (HCM). However, different mutations in MYH7 lead to variable penetrance and clinical severity, and alter myosin function to varying degrees, making it difficult to determine genotype-phenotype relationships, especially when caused by rare gene variants such as the G256E mutation.
Objective: This study aims to determine the effects of low penetrant MYH7 G256E mutation on myosin function.
Protein micropatterning enables robust control of cell positioning on electron-microscopy substrates for cryogenic electron tomography (cryo-ET). However, the combination of regulated cell boundaries and the underlying electron-microscopy substrate (EM-grids) provides a poorly understood microenvironment for cell biology. Because substrate stiffness and morphology affect cellular behavior, we devised protocols to characterize the nanometer-scale details of the protein micropatterns on EM-grids by combining cryo-ET, atomic force microscopy, and scanning electron microscopy.
View Article and Find Full Text PDFGeriatr Orthop Surg Rehabil
November 2022
Introduction: Certain titanium alloy stems have been shown to be susceptible to failure at the neck with catastrophic trunnion failure. Failure has been particularly noted in the single wedge Accolade 1 stem design. Other stems also used this alloy including the anatomic designed Citation stem.
View Article and Find Full Text PDFWnt signal transduction is controlled by the destruction complex (DC), a condensate comprising scaffold proteins and kinases that regulate β-catenin stability. Overexpressed DC scaffolds undergo liquid-liquid phase separation (LLPS), but DC mesoscale organization at endogenous expression levels and its role in β-catenin processing were previously unknown. Here, we find that DC LLPS is nucleated by the centrosome.
View Article and Find Full Text PDFCytosolic Ca2+ is a highly dynamic, tightly regulated and broadly conserved cellular signal. Ca2+ dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here, we examine Ca2+ dynamics in the adult Drosophila intestine, a self-renewing epithelial organ in which stem cells continuously produce daughters that differentiate into either enteroendocrine cells or enterocytes.
View Article and Find Full Text PDFThis paper provides a synopsis of discussions related to the Learning Environments track of the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. The Learning Environments track had six interactive workshops that provided facilitated discussion and provide recommendations in the areas of: (1) Authentic project/problem identification in clinical, industrial, and global settings, (2) Experiential problem/project-based learning within courses, (3) Experiential learning in co-curricular learning settings, (4) Team-based learning, (5) Teaching to reach a diverse classroom, and (6) innovative platforms and pedagogy.
View Article and Find Full Text PDFHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating.
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