Epithelial sheets define organ architecture during development. Here, we employed an iterative multiscale computational modeling and quantitative experimental approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix, and cell-cell adhesion in shaping Drosophila wing imaginal discs. Basally generated actomyosin forces generate epithelial bending of the wing disc pouch. Surprisingly, acute pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. Computational simulations show that ECM tautness provides only a minor contribution to modulating tissue shape. Instead, passive ECM pre-strain serves to maintain the shape independent from actomyosin contractility. These results provide general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature. Thus, the results suggest an important design principle of separable contributions from ECM prestrain and actomyosin tension during epithelial organogenesis and homeostasis.

There has been an increase in the use of pulmonary artery (PA) catheters in heart failure (HF) in the United States in recent years. However, patterns of hospital use and trends in patient outcomes are not known. In the National Inpatient Sample 2001 to 2012, using International Classification of Diseases-Ninth Revision codes, we identified 11 888 525 adult (≥18 years) HF hospitalizations nationally, of which an estimated 75 209 (SE 0.6%) received a PA catheter. In 2001, the number of hospitals with ≥1 PA catheterization was 1753, decreasing to 1183 in 2011. The mean PA catheter use per hospital trended from 4.9 per year in 2001 (limits 1-133) to 3.8 per year in 2007 (limits 1-46), but increased to 5.5 per year in 2011 (limits 1-70). During 2001 to 2006, PA catheterization declined across hospitals; however, in 2007 to 2012, there was a disproportionate increase at hospitals with large bedsize, teaching programs, and advanced HF capabilities. The overall in-hospital mortality with PA catheter use was higher than without PA catheter use (13.1% versus 3.4%; P<0.0001); however, in propensity-matched analysis, differences in mortality between these groups have attenuated over time-risk-adjusted odds ratio for mortality for PA catheterization, 1.66 (95% confidence interval, 1.60-1.74) in 2001 to 2003 down to 1.04 (95% confidence interval, 0.97-1.12) in 2010 to 2012. There is substantial hospital-level variability in PA catheterization in HF along with increasing volume at fewer hospitals over-represented by large, academic hospitals with advanced HF capabilities. This is accompanied by a decline in excess mortality associated with PA catheterization.

How a developing organ robustly coordinates the cellular mechanics and growth to reach a final size and shape remains poorly understood. Through iterations between experiments and model simulations that include a mechanistic description of interkinetic nuclear migration, we show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension. We show that increasing cell proliferation via different growth-promoting pathways results in two distinct phenotypes. Triggering proliferation through insulin signaling increases basal curvature, but an increase in growth through Dpp signaling and Myc causes tissue flattening. These distinct phenotypic outcomes arise from differences in how each growth pathway regulates the cellular cytoskeleton, including contractility and cell-ECM adhesion. The coupled regulation of proliferation and cytoskeletal regulators is a general strategy to meet the multiple context-dependent criteria defining tissue morphogenesis.

Hypertensive emergency is a clinical entity with potentially serious health implications and high healthcare utilization. There is a lack of nationally representative data on incidence, causes, and predictors of 30-day readmission after hospitalization for hypertensive emergency. We used the 2013 to 2014 Nationwide Readmissions Database to identify index hospitalizations for hypertensive emergency. Primary outcome was all-cause unplanned 30-day readmission. Multivariable hierarchical logistic regression was used to identify independent predictors of readmission. There were 166 531 index hospitalizations for hypertensive emergency representative of 355 627 (SE, 9401) hospitalizations nationwide in 2013 to 2014. Mean age was 66.0 (SE, 0.14) years, and 53.7% were women. The overall incidence of unplanned 30-day readmissions was 17.8%. The most common causes of readmission were heart failure (14.2%), hypertension with complications (10.2%), sepsis (5.9%), acute kidney injury (5.1%), and cerebrovascular accident (5.1%). Noncardiovascular causes accounted for 57.9% of readmissions. We found age <65 years (odds ratio, 1.21; 95% CI, 1.17-1.25; P<0.001), female sex (odds ratio, 1.09; 95% CI, 1.07-1.12; P<0.001), comorbid disease burden, substance use disorders, and socioeconomic risk factors to be significant predictors of readmission. One out of 6 patients hospitalized for hypertensive emergency had an unplanned 30-day readmission. Heart failure, uncontrolled hypertension, and stroke were among the most frequent causes of readmission; however, over half of all readmissions were because of noncardiovascular causes.