mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert).

A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function. The extent to which stem cells can regulate quiescence is unknown. Here we show that the stem cell quiescent state is composed of two distinct functional phases, G0 and an 'alert' phase we term G(Alert). Stem cells actively and reversibly transition between these phases in response to injury-induced systemic signals. Using genetic mouse models specific to muscle stem cells (or satellite cells), we show that mTORC1 activity is necessary and sufficient for the transition of satellite cells from G0 into G(Alert) and that signalling through the HGF receptor cMet is also necessary. We also identify G0-to-G(Alert) transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into G(Alert) possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into G(Alert) functions as an 'alerting' mechanism, an adaptive response that positions stem cells to respond rapidly under conditions of injury and stress, priming them for cell cycle entry.

Mifepristone prior to osmotic dilators for dilation and evacuation cervical preparation: A randomized, double-blind, placebo-controlled pilot study.

OBJECTIVES: To evaluate mifepristone impact on osmotic dilator placement and procedural outcomes when given 18 to 24 hours before dilator placement for dilation and evacuation (D&E) at 18 weeks 0 days to 23 weeks 6 days gestation. STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled trial from April 2019 through February 2021, enrolling participants undergoing osmotic dilator (Dilapan) placement for a planned, next-day D&E. Participants took mifepristone 200 mg or placebo orally 18 to 24 hours before dilator placement. We used a gestational age-based protocol for minimum number of dilators. Our primary outcome was the proportion of participants for whom 2 or more additional dilators could be placed compared to the minimum gestational age-based standard. We secondarily evaluated cervical dilation after dilator removal in the operating room, subjective procedure ease, and complication rates (cervical laceration, uterine perforation, blood transfusion, infection, hospitalization, or extramural delivery). RESULTS: Of the planned 66 participants, we enrolled 44 (stopped due to coronavirus disease 2019-related obstacles), and 41 (19 mifepristone; 22 placebo) completed the study. We placed 2 or more additional dilators compared to standard in 7 (36.8%) and 3 (13.6%) participants after mifepristone and placebo, respectively (p = 0.14). We measured greater median initial cervical dilation in the mifepristone (3.2 cm[2.6-3.6]) compared to placebo (2.6 cm[2.2-3.0]) group, p = 0.03. Surgeon's perception of procedure being "easy" (8/19[42.1] vs 9/22[40.9], respectively, p = 1.00) and complication rate (3/19[15.8%] vs 3/22[13.6], respectively, p = 1.00) did not differ. CONCLUSION: Our underpowered study did not demonstrate a difference in cervical dilator placement, but mifepristone 18 to 24 hours prior to dilators increases cervical dilation without increasing complications. IMPLICATIONS: Mifepristone 18 to 24 hours prior to cervical dilator placement may be a useful adjunct to cervical dilators based on increased cervical dilation at time of procedure; however, logistical barriers, such as an additional visit, may preclude routine adoption without definite clinical benefit.

Contraception After Surgical Abortion in Patients With Opioid Use Disorder.

OBJECTIVES: This study describes the prevalence of medications for opioid use disorder (MOUD) among surgical abortion patients, evaluates long-acting reversible contraception (LARC) uptake after surgical abortion among patients on MOUD, and identifies predictors of immediate postabortion LARC uptake among individuals on MOUD. METHODS: We performed a secondary analysis of data from a retrospective observational cohort study of LARC uptake immediately after surgical abortion up to 210/7 weeks gestation at Planned Parenthood League of Massachusetts between October 2012 and April 2017. We estimated proportions and analyzed predictors of LARC uptake among women on MOUD using logistic regression analysis to control for possible confounders. RESULTS: During the study period, 26,858 patients had an abortion procedure; 768 (2.9%; 95% confidence interval, 2.7%-3.1%) used MOUD. In the primary study, controlling for demographic factors, MOUD was not an independent predictor of LARC uptake. In this analysis, patients on MOUD differed demographically from non-MOUD users and were significantly more likely to initiate a LARC method immediately after their procedure: 30.1% versus 25.3% (p = .002), including 22.7% who obtained an intrauterine device and 7.4% who obtained an implant. Among patients on MOUD, a prior live birth and public insurance predicted LARC uptake at the time of abortion. CONCLUSION: Women on MOUD had higher postabortion LARC uptake compared with those not on MOUD in a setting with easy access to postabortion LARC. Public insurance coverage for abortion was associated with LARC uptake among women on MOUD.

US referral center experience removing nonpalpable and difficult contraceptive implants with in-office ultrasonography: A case series.

OBJECTIVES: To assess referral center outcomes with removal of difficult or nonpalpable contraceptive implants using high-frequency point-of-care ultrasonography. STUDY DESIGN: We present a case series examining patients referred to our specialty center from January 2019 through September 2020 for difficult or nonpalpable implant removal. RESULTS: Of the 54 referrals, 6 had palpable implants and 48 required ultrasonography. We localized 46 (96%) implants in-office, including 13 located subfascially; 2 Implanon implants could not be localized. We successfully completed 50 (96%) of 52 attempted in-office removals, including 12 (92%) subfascial implants. CONCLUSION: High-frequency point-of-care ultrasonography can effectively localize nonpalpable contraceptive implants leading to successful in-office removal. IMPLICATIONS: Specialists can use high-frequency point-of-care ultrasonography to localize nonpalpable implants without formal radiology scans and skilled technologists, optimizing patient time and convenience. However, the probe is expensive, and providers may need to consider this cost in the context of reimbursement for these highly specialized procedures.