α-Synuclein impairs macroautophagy: implications for Parkinson’s disease

α-Synuclein impairs autophagosome formation and mislocalizes Atg9 by inhibiting Rab1a

Characterization of Rhodamine-123 as a Tracer Dye for Use In In vitro Drug Transport Assays

Fluorescent tracer dyes represent an important class of sub-cellular probes and allow the examination of cellular processes in real-time with minimal impact upon these processes. Such tracer dyes are becoming increasingly used for the examination of membrane transport processes, as they are easy-to-use, cost effective probe substrates for a number of membrane protein transporters. Rhodamine 123, a member of the rhodamine family of flurone dyes, has been used to examine membrane transport by the ABCB1 gene product, MDR1. MDR1 is viewed as the archetypal drug transport protein, and is able to efflux a large number of clinically relevant drugs. In addition, ectopic activity of MDR1 has been associated with the development of multiple drug resistance phenotype, which results in a poor patient response to therapeutic intervention. It is thus important to be able to examine the potential for novel compounds to be MDR1 substrates. Given the increasing use rhodamine 123 as a tracer dye for MDR1, a full characterisation of its spectral properties in a range of in vitro assay-relevant media is warranted. Herein, we determine λmax for excitation and emission or rhodamine 123 and its metabolite rhodamine 110 in commonly used solvents and extraction buffers, demonstrating that fluorescence is highly dependent on the chemical environment: Optimal parameters are 1% (v/v) methanol in HBSS, with λex = 505 nm, λem = 525 nm. We characterise the uptake of rhodamine 123 into cells, via both passive and active processes, and demonstrate that this occurs primarily through OATP1A2-mediated facilitated transport at concentrations below 2 µM, and via micelle-mediated passive diffusion above this. Finally, we quantify the intracellular sequestration and metabolism of rhodamine 123, demonstrating that these are both cell line-dependent factors that may influence the interpretation of transport assays

CropPol: a dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved

Unexpected heaping in reported gestational age for women undergoing medical abortion

Background: In August 2006, the Planned Parenthood Federation of America (Planned Parenthood) conducted an extensive audit of first-trimester medical abortions with oral mifepristone plus buccal misoprostol through 56 days of gestation so that patients could be given accurate information about the success rate of the new regimen. Objectives: We sought to evaluate the effectiveness of this buccal misoprostol regimen and to examine correlates of its success during routine service delivery. Methods: Audits in 10 large urban service points were conducted in 2006 to estimate the success rates of the buccal regimen. Success was defined as medical abortion without vacuum aspiration. Results: We discovered unexpected heaping of reported gestational age (GA) on days divisible by 7. Conclusion: Such heaping, which has not been reported in the literature, would make it more difficult to detect a modest trend in declining effectiveness with increasing GA, if there were one. High coefficients of variation of sac size and crown-rump length characterize the early gestational weeks. We suspect, but are unable to prove, that the source of the heaping found in our investigation is a tendency for operators of ultrasound machines at some sites to simplify reporting by rounding a portion of the results to a date corresponding to the nearest complete gestational week. We believe that immediate supervisory awareness and feedback may reduce the extent of the problem. However, the problem may persist in multiple-site studies given the underlying variability of ultrasound measurements with differently calibrated machines and different rules for recording data, some of which may permit acceptance of an estimate based on the stated date of the last menses, if it differs by no more than 2 or 3 days from the ultrasound result

First trimester medication abortion practice in the United States and Canada

We conducted a cross-sectional survey of abortion facilities from professional networks in the United States (US, n = 703) and Canada (n = 94) to estimate the prevalence of medication abortion practices in these settings and to look at regional differences. Administrators responded to questions on gestational limits, while up to five clinicians per facility reported on 2012 medication abortion practice. At the time of fielding, mifepristone was not approved in Canada. 383 (54.5%) US and 78 (83.0%) Canadian facilities participated. In the US, 95.3% offered first trimester medication abortion compared to 25.6% in Canada. While 100% of providers were physicians in Canada, just under half (49.4%) were advanced practice clinicians in the US, which was more common in Eastern and Western states. All Canadian providers used misoprostol; 85.3% with methotrexate. 91.4% of US providers used 200 mg of mifepristone and 800 mcg of misoprostol, with 96.7% reporting home misoprostol administration. More than three-quarters of providers in both countries required an in-person follow-up visit, generally with ultrasound. 87.7% of US providers routinely prescribed antibiotics compared to 26.2% in Canada. Nonsteroidal anti-inflammatory drugs were the most commonly reported analgesic, with regional variation in opioid narcotic prescription. In conclusion, medication abortion practice follows evidence-based guidelines in the US and Canada. Efforts to update practice based on the latest evidence for reducing in-person visits and increasing provision by advanced practice clinicians could strengthen these services and reduce barriers to access. Research is needed on optimal antibiotic and analgesic use

Medical abortion practices: a survey of National Abortion Federation members in the United States

Background: Little is known about clinical implementation of medical abortion in the United States following approval of mifepristone as an abortifacient by the Food and Drug Administration (FDA) in 2000. We collected information regarding medical abortion practices of National Abortion Federation (NAF) members for the year 2001. Methods: Questionnaires were mailed to 337 active US NAF member facilities. Results: A total of 258 facilities responded (77%); 252 nonhospital facilities were included in the analysis. Most of these facilities (87%) offered medical abortion in 2001, providing an estimated 28,400 medical abortions, approximately 52% of medical abortions in the US that year. Over 75% began offering mifepristone/misoprostol abortions within 5 months of the start of mifepristone distribution. Almost all (99%) reported using mifepristone/misoprostol regimens, with most offering one or more evidence-based alternative regimens (83%); a few (4%) used the FDA-approved regimen. Conclusion: After FDA approval of mifepristone, NAF member facilities rapidly adopted evidence-based mifepristone/misoprostol regimens. (C) 2008 Elsevier Inc. All rights reserved

Do women want to talk about birth control at the time of a first-trimester abortion?

OBJECTIVE:To investigate if women desire talking to a counselor or physician about contraception when seeking first-trimester medical or surgical abortion. STUDY DESIGN:We conducted a cross-sectional study by distributing self-administered anonymous surveys to women at three clinics in Sacramento, California; Chicago, Illinois; and Cleveland, Ohio, from October 2014 to February 2015. Participants completed surveys after registration and before any in-office counseling. We asked whether women want to discuss contraception, specific topics they want to discuss, reasons why they may not want to talk about contraception and whether they want to receive contraception services as part of their abortion care. We conducted regression analyses to assess associations between patient characteristics and the desire for counseling. RESULTS:Among 3041 eligible women, 1959 (64.4%) completed surveys. Overall, 1208 (61.7%) did not want to discuss contraception prior to having an abortion, primarily citing that they already know which method they want. We found no association between the desire to discuss contraception and age, race, planned abortion method, clinic site and number of unplanned pregnancies. Among those who desired to talk about contraception, subjects preferred to discuss which contraceptive methods are easier to use and more effective as compared to previously used methods. Regardless of their desire for a discussion about contraception, 1386 (70.8%) of subjects wanted to leave the clinic with a specific method, including a long-acting reversible method [intrauterine device or implant (190, 13.7%)] or other hormonal method [pills, patch, ring or injectable (680, 49.1%)]. CONCLUSIONS:The majority of women seeking first-trimester abortion do not come to the clinic wanting to discuss contraception, most commonly because they have a preferred method in mind. IMPLICATIONS:Providers should ask women presenting for abortion if they want to discuss contraception and not assume that they need or desire such information. Focused discussions, starting with the preferred method if known, may better satisfy women's preferences. Providers should account for such desires when allocating resources for contraception services during abortion care