Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Effectiveness, safety and acceptability of self-assessment of the outcome of first-trimester medical abortion: a systematic review and meta-analysis

Background - For many women, the need for multiple clinical visits is a barrier to medical abortion. Objectives - We assessed the effectiveness, safety, and acceptability of self‐assessment of the outcome of medical abortion completed at home versus routine clinic follow up after medical abortion. Search strategy - We searched databases such as MEDLINE, Embase, and CENTRAL to find studies published in 1991–2018.Selection criteria Eligible studies included women of reproductive age who had undergone a medical abortion that was completed at home. The intervention and self‐assessment of the outcome of medical abortion done by urine pregnancy tests kits by women at home was compared with routine medical follow up at a clinic. Data collection and analysis - Two researchers completed the study selection, data extraction, critical appraisal, and assessment of the evidence. The outcomes were successful complete abortions, side effects and complications, and acceptability. We performed meta‐analyses when possible and GRADE to ascertain the certainty of the evidence. The protocol was registered in PROSPERO (CRD42017055316). Main results - Four randomised controlled trials (RCTs; n = 5493) met our inclusion criteria. The pooled analysis from all studies showed no significant difference in complete abortion rates between self‐assessment and routine clinic follow up: RR = 1.00, 95% CI 0.99–1.01. The ongoing pregnancy rates were similar and the pooled results for the safety outcomes showed no significant differences between the groups. There was a significantly greater preference for self‐assessment as the follow‐up method. Conclusions - The effectiveness, safety, and acceptability of self‐assessment of the outcome of medical abortion completed at home are not inferior to routine clinic follow up

Low-dose mifepristone 200 mg and vaginal misoprostol for abortion

The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women greater than or equal to 18 years, up to 8 weeks pregnant, and wanting an abortion. The women received 200 mg mifepristone orally, self administered 800 mu g misoprostol vaginally at home 48 h later, and returned 1-4 days later for ultrasound evaluation. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, persistent products of conception 5 weeks later, or other serious medical conditions. Of the 933 subjects, 906 (97%) had complete medical abortions, 22 had surgical intervention, two were protocol failures, and three were lost to follow up. Of the 746 subjects who had no or minimal bleeding before misoprostol, 80% bled within 4 h and 98% within 24 h of using misoprostol. By day 7, 95% of women had a complete abortion. Side effects were acceptable in 85% of subjects, and 94% found the procedure acceptable. Low-dose mifepristone followed by vaginal misoprostol was highly effective as an abortifacient. (C) 1999 Elsevier Science Inc. All lights reserved

Similar medical abortion rates with 6 to 8-hour or 24-hour intervals between mifepristone and vaginal misoprostol

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