Human FACT subunits coordinate to catalyze both disassembly and reassembly of nucleosomes.

The histone chaperone FACT (facilitates chromatin transcription) enhances transcription in eukaryotic cells, targeting DNA-protein interactions. FACT, a heterodimer in humans, comprises SPT16 and SSRP1 subunits. We measure nucleosome stability and dynamics in the presence of FACT and critical component domains. Optical tweezers quantify FACT/subdomain binding to nucleosomes, displacing the outer wrap of DNA, disrupting direct DNA-histone (core site) interactions, altering the energy landscape of unwrapping, and increasing the kinetics of DNA-histone disruption. Atomic force microscopy reveals nucleosome remodeling, while single-molecule fluorescence quantifies kinetics of histone loss for disrupted nucleosomes, a process accelerated by FACT. Furthermore, two isolated domains exhibit contradictory functions; while the SSRP1 HMGB domain displaces DNA, SPT16 MD/CTD stabilizes DNA-H2A/H2B dimer interactions. However, only intact FACT tethers disrupted DNA to the histones and supports rapid nucleosome reformation over several cycles of force disruption/release. These results demonstrate that key FACT domains combine to catalyze both nucleosome disassembly and reassembly.

Active versus Passive Voiding Protocols after Same-day Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: To determine the proportion of patients discharged with a urinary catheter after a same-day benign gynecologic minimally invasive hysterectomy (MIH) according to active vs passive voiding protocols. The secondary objectives included assessing postanesthesia care unit (PACU) duration and postoperative urinary retention (POUR) rate ≤2 weeks of discharge. DESIGN: Retrospective, observational cohort study. SETTING: Large integrated healthcare system serving approximately 40% of the Northern California population. PATIENTS: Patients aged 18 years or older undergoing same-day MIH without urogynecology procedures from 2015 to 2018 were categorized into active or passive voiding trial groups. Active voiding trials were defined as patients arriving in the PACU with a catheter, retrograde filling of the bladder with 300 mL saline then allowing for voiding ≥50% within 30 minutes. If the patients were unable to void this volume, they were discharged with a catheter to be removed within 24 hours. A passive voiding trial involved filling or not filling the bladder before PACU arrival without a catheter, then allowing for voiding or performing a straight catheterization if the patients were unable to void. INTERVENTIONS: Retrospective cohort study. MEASUREMENTS AND MAIN RESULTS: A total of 1644 (83.2%) patients underwent passive voiding trials, and 333 (16.8%) underwent active voiding trials. The proportion of patients discharged with a catheter was lower in the passive voiding group than in the active voiding group (5.4% vs 10.5%; p = .001). The passive group had a shorter mean PACU time than the active group (218 ± 86 vs 240 ± 93 minutes; p <.001). The crude POUR rates for the passive and active voiding groups were 1.8% and 3.0%, respectively (p = .16). CONCLUSION: Within an integrated healthcare system, patients who underwent passive voiding trials compared with those who underwent active voiding trials were discharged home from the PACU after a shorter duration. In addition, a larger proportion of the patients who underwent passive voiding trials were discharged home without a urinary catheter. There were no differences in the POUR rates. Our findings suggest that passive voiding trials can be safely used after a benign MIH to reduce hospital duration, optimize healthcare resources, and improve patient experience.