Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2017
2017
2017
2017
RATIONALE
During each beat, cardiac myocytes (CMs) generate the mechanical output necessary for heart function through contractile mechanisms that involve shortening of sarcomeres along myofibrils. Human-induced pluripotent stem cells (hiPSCs) can be differentiated into CMs (hiPSC-CMs) that model cardiac contractile mechanical output more robustly when micropatterned into physiological shapes. Quantifying the mechanical output of these cells enables us to assay cardiac activity in a dish.
OBJECTIVE
We sought to develop a computational platform that integrates analytic approaches to quantify the mechanical output of single micropatterned hiPSC-CMs from microscopy videos.
METHODS AND RESULTS
We micropatterned single hiPSC-CMs on deformable polyacrylamide substrates containing fluorescent microbeads. We acquired videos of single beating cells, of microbead displacement during contractions, and of fluorescently labeled myofibrils. These videos were independently analyzed to obtain parameters that capture the mechanical output of the imaged single cells. We also developed novel methods to quantify sarcomere length from videos of moving myofibrils and to analyze loss of synchronicity of beating in cells with contractile defects. We tested this computational platform by detecting variations in mechanical output induced by drugs and in cells expressing low levels of myosin-binding protein C.
CONCLUSIONS
Our method can measure the cardiac function of single micropatterned hiPSC-CMs and determine contractile parameters that can be used to elucidate mechanisms that underlie variations in CM function. This platform will be amenable to future studies of the effects of mutations and drugs on cardiac function.
View on PubMed2017
INTRODUCTION
This study examined state-level variation in chronic kidney disease (CKD) awareness using national estimates of disease awareness among adults in the U.S. with CKD.
METHODS
Data on U.S. adults were obtained from two national, population-based surveys: (1) the Behavioral Risk Factor Surveillance System (BRFSS 2011; n=506,467), a state-level phone survey containing information on self-reported kidney disease; and (2) the National Health and Nutrition Examination Survey (NHANES 2005-2012; n=20,831), containing physical health examination, surveys containing data on self-reported kidney disease, risk factors, and laboratory values. CKD was defined as an estimated glomerular filtration rate of 15-59 mL/minute/1.73 m or urinary albumin-to-creatinine ratio >30 mg/g. As BRFSS does not include laboratory data, CKD status for each person was imputed (multiple) based on a logistic regression model predicting NHANES CKD status. CKD awareness in each state was estimated as the weighted proportion of BRFSS participants with imputed CKD who reported having kidney disease.
RESULTS
Overall, estimated CKD awareness was 9.0% (95% CI=8.0%, 10.0%), ranging from 5.8% (95% CI=4.8%, 6.8%) in Iowa to 11.7% (95% CI=9.7%, 13.7%) in Arizona. Awareness was greater among adults with hypertension (12.0%) and diabetes (15.3%) than among adults without those conditions, and lower in Hispanics (6.0%) than in non-Hispanic whites (8.8%), non-Hispanic blacks (9.9%), and other racial/ethnic groups (12.7%).
CONCLUSIONS
Among individuals with CKD, awareness of their condition was very low and varied approximately twofold among states. This is the first study to estimate awareness of kidney disease by state for the U.S. adult population.
View on PubMed2017
2017