Prematurity is associated with the diagnosis of pulmonary vein stenosis. It is interesting to note that many of these patients also have intracardiac shunt lesions, which may act in concert with preterm endothelium to produce pulmonary vein stenosis.

Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to study human physiology and disease at the cellular level. They also have the potential to be leveraged in the practice of precision medicine, for example, personalized drug testing. This statement comprehensively describes the provenance of iPSC lines, their use for cardiovascular disease modeling, their use for precision medicine, and strategies through which to promote their wider use for biomedical applications. Human iPSCs exhibit properties that render them uniquely qualified as model systems for studying human diseases: they are of human origin, which means they carry human genomes; they are pluripotent, which means that in principle, they can be differentiated into any of the human body’s somatic cell types; and they are stem cells, which means they can be expanded from a single cell into millions or even billions of cell progeny. iPSCs offer the opportunity to study cells that are genetically matched to individual patients, and genome-editing tools allow introduction or correction of genetic variants. Initial progress has been made in using iPSCs to better understand cardiomyopathies, rhythm disorders, valvular and vascular disorders, and metabolic risk factors for ischemic heart disease. This promising work is still in its infancy. Similarly, iPSCs are only just starting to be used to identify the optimal medications to be used in patients from whom the cells were derived. This statement is intended to (1) summarize the state of the science with respect to the use of iPSCs for modeling of cardiovascular traits and disorders and for therapeutic screening; (2) identify opportunities and challenges in the use of iPSCs for disease modeling and precision medicine; and (3) outline strategies that will facilitate the use of iPSCs for biomedical applications. This statement is not intended to address the use of stem cells as regenerative therapy, such as transplantation into the body to treat ischemic heart disease or heart failure.

Background-Diastolic run off into the pulmonary circulation and labile coronary perfusion are thought to contribute to morbidity and mortality after the Norwood procedure (NP). We compared outcomes from the use of a RV to PA conduit (RV/PA) or a modified Blalock-Taussig shunt (BTS), physiologically distinct sources of pulmonary blood flow.

Efficient generation of cardiomyocytes from human pluripotent stem cells is critical for their regenerative applications. Microgravity and 3D culture can profoundly modulate cell proliferation and survival. Here, we engineered microscale progenitor cardiac spheres from human pluripotent stem cells and exposed the spheres to simulated microgravity using a random positioning machine for 3 days during their differentiation to cardiomyocytes. This process resulted in the production of highly enriched cardiomyocytes (99% purity) with high viability (90%) and expected functional properties, with a 1.5 to 4-fold higher yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D-standard gravity culture. Increased induction, proliferation and viability of cardiac progenitors as well as up-regulation of genes associated with proliferation and survival at the early stage of differentiation were observed in the 3D culture under simulated microgravity. Therefore, a combination of 3D culture and simulated microgravity can be used to efficiently generate highly enriched cardiomyocytes.

Extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support of critically ill patients is used frequently in the pediatric population. ECMO is burdened by complications, including thrombosis and hemorrhage. Here we demonstrate the focused location of clots, their histologic composition, and the relationship of in situ thrombus to local hemodynamics in ECMO circuits. Pediatric ECMO circuits from Children's Healthcare of Atlanta, Emory University (Atlanta, GA) were obtained after removal from extracorporeal support over a 2.5 year period (n = 50). All clots and material deposited within the circuit were recorded. Location of clot was compared with local hemodynamics. Most clots were adherent to the junctions made by the tubing and connectors, as opposed to being randomly disturbed throughout the circuit tubing (p << 0.05). Loose, nonadherent clots were also found at the entry side of oxygenators. The clots colocated directly with zones of low shear rate. Histology revealed a fibrinous composition, consistent with coagulation potentiated by low shear. Centrifugal pump circuits (n = 16) had more clots than roller pump (n = 34) circuits (p << 0.05). In addition, all centrifugal pumps had clots that formed at the top of the pump shaft. The ECMO circuits from our single-center study demonstrate the concentrated location of fibrin clots at low shear zones created by tubing-connector junctions. Type of pump also influences the frequency of clot formation. Since the mechanism of the majority of ECMO circuit thrombosis is low shear and fibrin driven, optimization of hemodynamics and anticoagulation regimen may reduce clot formation and bleeding.

SummaryCardiomyocytes derived from human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, disease modeling, and drug discovery, all of which require enriched cardiomyocytes, ideally ones with mature phenotypes. However, current methods are typically performed in 2D environments that produce immature cardiomyocytes within heterogeneous populations. Here, we generated 3D aggregates of cardiomyocytes (cardiospheres) from 2D differentiation cultures of hPSCs using microscale technology and rotary orbital suspension culture. Nearly 100% of the cardiospheres showed spontaneous contractility and synchronous intracellular calcium transients. Strikingly, from starting heterogeneous populations containing ∼10%–40% cardiomyocytes, the cell population within the generated cardiospheres featured ∼80%–100% cardiomyocytes, corresponding to an enrichment factor of up to 7-fold. Furthermore, cardiomyocytes from cardiospheres exhibited enhanced structural maturation in comparison with those from a parallel 2D culture. Thus, generation of cardiospheres represents a simple and robust method for enrichment of cardiomyocytes in microtissues that have the potential use in regenerative medicine as well as other applications.

In this paper we will look at the distribution with which passwords are chosen. Zipf's Law is commonly observed in lists of chosen words. Using password lists from four different online sources, we will investigate if Zipf's law is a good candidate for describing the frequency with which passwords are chosen. We look at a number of standard statistics, used to measure the security of password distributions, and see if modelling the data using Zipf's Law produces good estimates of these statistics. We then look at the the similarity of the password distributions from each of our sources, using guessing as a metric. This shows that these distributions provide effective tools for cracking passwords. Finally, we will show how to shape the distribution of passwords in use, by occasionally asking users to choose a different password.

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