Short cell cycle duration is a phenotype of human epidermal stem cells.

BACKGROUND: A traditional view is that stem cells (SCs) divide slowly. Meanwhile, both embryonic and pluripotent SCs display a shorter cell cycle duration (CCD) in comparison to more committed progenitors (CPs). METHODS: We examined the in vitro proliferation and cycling behavior of somatic adult human cells using live cell imaging of passage zero keratinocytes and single-cell RNA sequencing. RESULTS: We found two populations of keratinocytes: those with short CCD and protracted near exponential growth, and those with long CCD and terminal differentiation. Applying the ergodic principle, the comparative numbers of cycling cells in S phase in an enriched population of SCs confirmed a shorter CCD than CPs. Further, analysis of single-cell RNA sequencing of cycling adult human keratinocyte SCs and CPs indicated a shortening of both G1 and G2M phases in the SC. CONCLUSIONS: Contrary to the pervasive paradigm, SCs progress through cell cycle more quickly than more differentiated dividing CPs. Thus, somatic human adult keratinocyte SCs may divide infrequently, but divide rapidly when they divide. Additionally, it was found that SC-like proliferation persisted in vitro.

Impact of Atrial Fibrillation Burden on Health Care Costs and Utilization.

BACKGROUND: Integrating patient-specific cardiac implantable electronic device (CIED)-detected atrial fibrillation (AF) burden with measures of health care cost and utilization allows for an accurate assessment of the AF-related impact on health care use. OBJECTIVES: The goal of this study was to assess the incremental cost of device-recognized AF vs no AF; compare relative costs of paroxysmal atrial fibrillation (pAF), persistent atrial fibrillation (PeAF), and permanent atrial fibrillation (PermAF) AF; and evaluate rates and sources of health care utilization between cohorts. METHODS: Using the de-identified Optum Clinformatics U.S. claims database (2015-2020) linked with the Medtronic CareLink database, CIED patients were identified who transmitted data ≥6 months postimplantation. Annualized per-patient costs in follow-up were analyzed from insurance claims and adjusted to 2020 U.S. dollars. Costs and rates of health care utilization were compared between patients with no AF and those with device-recognized pAF, PeAF, and PermAF. Analyses were adjusted for geographical region, insurance type, CHA2DS2-VASc score, and implantation year. RESULTS: Of 21,391 patients (mean age 72.9 ± 10.9 years; 56.3% male) analyzed, 7,798 (36.5%) had device-recognized AF. The incremental annualized increased cost in those with AF was $12,789 ± $161,749 per patient, driven by increased rates of health care encounters, adverse clinical events associated with AF, and AF-specific interventions. Among those with AF, PeAF was associated with the highest cost, driven by increased rates of inpatient and outpatient hospitalization encounters, heart failure hospitalizations, and AF-specific interventions. CONCLUSIONS: Presence of device-recognized AF was associated with increased health care cost. Among those with AF, patients with PeAF had the highest health care costs. Mechanisms for cost differentials include both disease-specific consequences and physician-directed interventions.