Antithrombin testing and treatment in pregnancy: Their real-world relationship to clinical outcomes.

Background: Antithrombin (AT) deficiency is a severe thrombophilia associated with increased rates of maternal morbidity, mortality, and greater healthcare resource utilization during pregnancy and postpartum.

Methods: Two large U.S.

Performance comparison of 6 in-hospital patient monitoring systems in the detection and alarm of ventricular cardiac arrhythmias.

Background: Patient monitoring devices are critical for alerting of potential cardiac arrhythmias during hospitalization; however, there are concerns of alarm fatigue due to high false alarm rates.

Objective: The purpose of this study was to evaluate the sensitivity and false alarm rate of hospital-based continuous electrocardiographic (ECG) monitoring technologies.

Methods: Six commonly used multiparameter bedside monitoring systems available in the United States were evaluated: B125M (GE HealthCare), ePM10 and iPM12 (Mindray), Efficia and IntelliVue (Philips), and Life Scope (Nihon Kohden).

Influence of wastewater treatment plants and water input sources on size, shape, and polymer distributions of microplastics in St. Andrew Bay, Florida, USA.

Microplastic (MP) pollution is an ongoing problem in coastal systems, where wastewater treatment plants (WWTPs) deposit particles daily. This study examined MP characteristics at WWTP outflow and control sites in St. Andrew Bay in Northwestern Florida, USA.

Two-year retrospective cohort results on use of a dynamic unilateral brace for treatment of clubfoot: Can compliance and prevention of recurrence both be achieved?

Objectives: The Ponseti method has led to vast improvements in outcomes for infants born with clubfoot deformity, but challenges with compliance during the bracing phase of the protocol remain. Unilateral braces promise higher compliance but often have led to unacceptably high recurrence.

Methods: We have developed a novel unilateral brace for clubfoot deformity that strategically applies patient-specific, anatomically-targeted forces to the lower limb to maintain correction.

OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification.

Cell plasticity plays a key role in embryos by maintaining the differentiation potential of progenitors. Whether postnatal somatic cells revert to an embryonic-like naïve state regaining plasticity and redifferentiate into a cell type leading to a disease remains intriguing. Using genetic lineage tracing and single-cell RNA sequencing, we reveal that Oct4 is induced by nuclear factor κB (NFκB) at embyronic day 9.

NFκB (Nuclear Factor κ-Light-Chain Enhancer of Activated B Cells) Activity Regulates Cell-Type-Specific and Context-Specific Susceptibility to Calcification in the Aortic Valve.

Objective: Although often studied independently, little is known about how aortic valve endothelial cells and valve interstitial cells interact collaborate to maintain tissue homeostasis or drive valve calcific pathogenesis. Inflammatory signaling is a recognized initiator of valve calcification, but the cell-type-specific downstream mechanisms have not been elucidated. In this study, we test how inflammatory signaling via NFκB (nuclear factor κ-light-chain enhancer of activated B cells) activity coordinates unique and shared mechanisms of valve endothelial cells and valve interstitial cells differentiation during calcific progression.

Valve interstitial cell tensional homeostasis directs calcification and extracellular matrix remodeling processes via RhoA signaling.

Aims: Valve interstitial cells are active and aggressive players in aortic valve calcification, but their dynamic mediation of mechanically-induced calcific remodeling is not well understood. The goal of this study was to elucidate the feedback loop between valve interstitial cell and calcification mechanics using a novel three-dimensional culture system that allows investigation of the active interplay between cells, disease, and the mechanical valve environment.

Methods & Results: We designed and characterized a novel bioreactor system for quantifying aortic valve interstitial cell contractility in 3-D hydrogels in control and osteogenic conditions over 14 days.

Notch-Tnf signalling is required for development and homeostasis of arterial valves.

Aims: Congenital anomalies of arterial valves are common birth defects, leading to valvar stenosis. With no pharmaceutical treatment that can prevent the disease progression, prosthetic replacement is the only choice of treatment, incurring considerable morbidity and mortality. Animal models presenting localized anomalies and stenosis of congenital arterial valves similar to that of humans are critically needed research tools to uncover developmental molecular mechanisms underlying this devastating human condition.

Endothelial-derived oxidative stress drives myofibroblastic activation and calcification of the aortic valve.

Aims: Oxidative stress is present in and contributes to calcification of the aortic valve, but the driving factors behind the initiation of valve oxidative stress are not well understood. We tested whether the valve endothelium acts as an initiator and propagator of oxidative stress in aortic valve disease.

Methods And Results: Calcified human aortic valves showed side-specific elevation of superoxide in the endothelium, co-localized with high VCAM1 expression, linking oxidative stress, inflammation, and valve degeneration.

Heterogeneous susceptibility of valve endothelial cells to mesenchymal transformation in response to TNFα.

Lack of understanding of the early mechanisms of aortic valve stenosis and calcification hinders the development of diagnostic and therapeutic intervention strategies. Inflammation is a known component of early aortic valve disease and can induce mesenchymal transformation in a subset of aortic valve endothelial cells. Here we present a three-dimensional culture system that allows transforming and non-transforming cells to be independently isolated and analyzed.

Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells.

Objective: Inflammatory activation of valve endothelium is an early phase of aortic valve disease pathogenesis, but subsequent mechanisms are poorly understood. Adult valve endothelial cells retain the developmental ability to undergo endothelial-to-mesenchymal transformation (EndMT), but a biological role has not been established. Here, we test whether and how inflammatory cytokines (tumor necrosis factor-α and interleukin-6) regulate EndMT in embryonic and adult valve endothelium.

Valvular heart diseases in the developing world: developmental biology takes center stage.

Heart valve disease is a significant and increasing global problem of which, in the developing world, the primary sufferers are the children and young adults regarded as the critical 'engine' of future economic growth. Yet, up to 10 times the current number of known sufferers remain undiagnosed in these countries. Among the most prevalent and neglected diseases are rheumatic heart disease and endomyocardial fibrosis.

The mechanobiology of mitral valve function, degeneration, and repair.

In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation.

Sarcoidosis presenting as bilateral vocal cord paralysis from bilateral compression of the recurrent laryngeal nerves from thoracic adenopathy.

Bilateral true vocal fold paralysis is rarely attributable to inflammatory diseases. We describe what appears to be the first case in the medical literature of sarcoidosis presenting as isolated, bilateral true vocal cord paralysis resulting from compressive bilateral mediastinal adenopathy. The presenting symptoms, clinical outcome, radiographs and laryngeal findings are discussed in detail.

Spindle checkpoint protein dynamics at kinetochores in living cells.

Background: To test current models for how unattached and untense kinetochores prevent Cdc20 activation of the anaphase-promoting complex/cyclosome (APC/C) throughout the spindle and the cytoplasm, we used GFP fusions and live-cell imaging to quantify the abundance and dynamics of spindle checkpoint proteins Mad1, Mad2, Bub1, BubR1, Mps1, and Cdc20 at kinetochores during mitosis in living PtK2 cells.

Results: Unattached kinetochores in prometaphase bound on average only a small fraction (estimated at 500-5000 molecules) of the total cellular pool of each spindle checkpoint protein. Measurements of fluorescence recovery after photobleaching (FRAP) showed that GFP-Cdc20 and GFP-BubR1 exhibit biphasic exponential kinetics at unattached kinetochores, with approximately 50% displaying very fast kinetics (t1/2 of approximately 1-3 s) and approximately 50% displaying slower kinetics similar to the single exponential kinetics of GFP-Mad2 and GFP-Bub3 (t1/2 of 21-23 s).

A prospective, randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery.

Objective: The objectives are 2-fold: (1). to serially determine endothelin (ET) levels in arterial vascular compartments in patients undergoing coronary artery bypass surgery using either cardiopulmonary bypass or off-pump techniques, and (2). to define potential relationships between endothelial levels and specific perioperative parameters of patient recovery.