Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3

The success of CD8+ T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance. These findings unveil a previously unexpected role for PSME3 in antigen processing and identify PSME3 as a druggable target to improve the efficacy of cancer immunotherapy

Prevalence of emergency contraceptive pill use among Spanish adolescent girls and their family and psychological profiles

The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background:Adolescent girls’ family context and psychological characteristics play important roles in their sexual behavior, including the use of the emergency contraceptive pill (ECP). This study aims to (1) determine the prevalence of ECP use among girls who have had sexual intercourse and (2) comparatively analyze their family and psychological profiles according to whether they have used ECPs. Methods:The sample of 1735 Spanish girls aged 15 to 18 came from a representative sample of the 2014 edition of the Health Behaviour in School-aged Children (HBSC) study. Of this sample, 398 girls had sexual intercourse and reported their ECP use. Data collection for the HBSC study was performed through an online questionnaire to which adolescents responded anonymously in school. Data analyses were descriptive and bivariate and were performed with the statistical program IBM SPSS Statistics 23.Results:The results demonstrated that 30.65% of girls who had sexual intercourse used ECPs. Noticeable differences in paternal knowledge and communication with the father were observed between girls who used the ECP at least once and those who did not use it. In contrast, differences between girls who used the ECP once and those who used it twice or more were pronounced with regard to parental knowledge, communication with parents, maternal affection,life satisfaction, sense of coherence and depression. Conclusions:This work demonstrates a high prevalence of ECP use and a more positive family and psychological profile for girls who used ECP once compared with those who used it twice or more.Peer reviewedFinal Published versio

Supplementary Material for: Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence

<b><i>Objective:</i></b> The aim of this study is to evaluate the interest in the in utero treatment of twin anemia-polycythemia sequence (TAPS). <b><i>Methods:</i></b> The obstetrical and neonatal data on all cases of TAPS followed up in our institution between 2006 and 2013 were reviewed. Statistical analyses were conducted using Bayesian methods. <b><i>Results:</i></b> Twenty cases of TAPS were included. Laser therapy or intrauterine transfusion (IUT) was performed on the donor twin in 9 cases. Eleven cases were included in the ‘nontreated' group (managed expectantly or diagnosed at birth). The gestational age at diagnosis was lower in the group with treated TAPS [difference (diff) = -22.20 days (-57.13, 14.28), probability (Pr) (diff >0) = 10.6%]. The rate of preterm premature rupture of membranes was higher in the group with treated TAPS [diff = 22.5% (-14, 57), Pr (diff >0) = 89%], but overall mortality was similar. The interval between diagnosis and delivery was longer [diff = 44.37 days (9.41, 77.90), Pr (diff >0) = 99.2%], the TAPS resolution rate was higher [diff = 49.9% (12, 81), Pr (diff >0) = 99.4%], and the neonatal transfusion rate was lower [diff = -30.5% (-60, 0), Pr (diff >0) = 2.6%] in the treated group. <b><i>Conclusion:</i></b> In utero treatment for TAPS is associated with a higher resolution rate of TAPS and a longer time between diagnosis and birth, but overall mortality is the same as with expectant management

Variation in referrals to secondary obstetrician-led care among primary midwifery care practices in the Netherlands: a nationwide cohort study

Contains fulltext : 154413.pdf (publisher's version ) (Open Access)BACKGROUND: The primary aim of this study was to describe the variation in intrapartum referral rates in midwifery practices in the Netherlands. Secondly, we wanted to explore the association between the practice referral rate and a woman's chance of an instrumental birth (caesarean section or vaginal instrumental birth). METHODS: We performed an observational study, using the Dutch national perinatal database. Low risk births in all primary care midwifery practices over the period 2008-2010 were selected. Intrapartum referral rates were calculated. The referral rate among nulliparous women was used to divide the practices in three tertile groups. In a multilevel logistic regression analysis the association between the referral rate and the chance of an instrumental birth was examined. RESULTS: The intrapartum referral rate varied from 9.7 to 63.7 percent (mean 37.8; SD 7.0), and for nulliparous women from 13.8 to 78.1 percent (mean 56.8; SD 8.4). The variation occurred predominantly in non-urgent referrals in the first stage of labour. In the practices in the lowest tertile group more nulliparous women had a spontaneous vaginal birth compared to the middle and highest tertile group (T1: 77.3%, T2:73.5%, T3: 72.0%). For multiparous women the spontaneous vaginal birth rate was 97%. Compared to the lowest tertile group the odds ratios for nulliparous women for an instrumental birth were 1.22 (CI 1.16-1.31) and 1.33 (CI 1.25-1.41) in the middle and high tertile groups. This association was no longer significant after controlling for obstetric interventions (pain relief or augmentation). CONCLUSIONS: The wide variation between referral rates may not be explained by medical factors or client characteristics alone. A high intrapartum referral rate in a midwifery practice is associated with an increased chance of an instrumental birth for nulliparous women, which is mediated by the increased use of obstetric interventions. Midwives should critically evaluate their referral behaviour. A high referral rate may indicate that more interventions are applied than necessary. This may lead to a lower chance of a spontaneous vaginal birth and a higher risk on a PPH. However, a low referral rate should not be achieved at the cost of perinatal safety

L’interruption volontaire de grossesse : recommandations pour la pratique clinique — Texte des recommandations (texte court).

National audienceObjectif Élaborer des recommandations pour la pratique des IVG. Matériel et méthodes Consultation de la base de données Medline, de la Cochrane Library et des recommandations des sociétés savantes françaises et étrangères. Résultats Le nombre d’IVG est stable depuis plusieurs décennies. Il existe plusieurs éléments expliquant le choix de l’IVG lorsqu’il existe une grossesse non prévue (GNP). L’initiation précoce de la contraception et le choix de la contraception en rapport avec la vie de la femme sont associés à une diminution des GNP. Les contraceptions réversibles de longue durée d’action apparaissent comme une contraception à positionner en première ligne pour l’adolescente du fait de son efficacité (grade C). L’échographie avant une IVG doit être encouragée mais n’est pas indispensable pour réaliser une IVG (accord professionnel). Dès l’apparition échographique de l’embryon, l’estimation de la datation de la grossesse se fait par la mesure de la longueur cranio-caudale (LCC) ou par la mesure du diamètre bipariétal (BIP) à partir de 11 SA (grade B). Les mesures étant fiables à ± 5 jours, l’IVG peut être réalisée lorsque les mesures de LCC et/ou de BIP sont respectivement inférieures à 90 mm et 30 mm (accord professionnel). L’IVG médicamenteuse réalisée avec la dose de 200 mg de mifépristone associé au misoprostol est efficace à tout âge gestationnel (NP1). Avant 7 SA, la prise de mifépristone sera suivie entre 24 et 48 heures de la prise de misoprostol par voie orale, buccale, sublinguale voire vaginale à la dose de 400 μg éventuellement renouvelé après 3 heures (NP1, grade A). Au-delà de 7 SA, les modes d’administration du misoprostol, par voie vaginale, sublinguale ou buccale, sont plus efficaces et mieux tolérés que la voie orale (NP1). Il est recommandé d’utiliser systématiquement une préparation cervicale lors d’une IVG instrumentale (accord professionnel). Le misoprostol est un agent de première intention pour la préparation cervicale à la dose de 400 μg (grade A). L’aspiration évacuatrice est préférable au curetage (grade B). Un utérus perforé lors d’une aspiration instrumentale ne doit pas être considéré en routine comme un utérus cicatriciel (accord professionnel). L’IVG instrumentale n’est pas associée à une augmentation du risque d’infertilité ultérieure ou de GEU (NP2). Les consultations médicales pré-IVG n’influent pas sur la décision d’interrompre ou non la grossesse et une majorité de femmes est assez sûre de son choix lors de ces consultations. L’acceptabilité de la méthode et la satisfaction des femmes semblent plus grandes lorsque celles-ci sont en mesure de choisir la méthode d’IVG (grade B). Il n’y a pas de relation entre une augmentation des troubles psychiatriques et le recours à l’IVG (NP2). Les femmes ayant des antécédents psychiatriques sont à risque accru de troubles psychiques après la survenue d’une grossesse non prévue (NP2). En cas d’IVG instrumentale, la contraception estro-progestative orale et le patch devraient être débutés dès le jour de l’IVG, l’anneau vaginal inséré dans les 5 jours suivant l’IVG (grade B). En cas d’IVG médicamenteuse, l’anneau vaginal devrait être inséré dans la semaine suivant la prise de mifépristone, la contraception estro-progestative orale et le patch devraient être débutés le jour même ou le lendemain de la prise des prostaglandines (grade C). En cas d’IVG instrumentale, l’implant devrait être inséré le jour de l’IVG (grade B). En cas d’IVG médicamenteuse, l’implant peut être inséré à partir du jour de la prise de mifépristone (grade C). Le DIU au cuivre et au lévonorgestrel doit être inséré préférentiellement le jour de l’IVG instrumentale (grade A). En cas d’IVG médicamenteuse, un DIU peut être inséré dans les 10 jours suivant la prise de mifépristone après s’être assuré par échographie de l’absence de grossesse intra-utérine (grade C). Conclusion L’application de ces recommandations devrait favoriser une prise en charge plus homogène et améliorée des femmes désirant une IVG. Summary Objective Develop recommendations for the practice of induced abortion. Materials and methods The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. Results The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP. Reversible contraceptives of long duration of action should be positioned fist in line for the teenager because of its efficiency (grade C). Ultrasound before induced abortion must be encouraged but should not be obligatory before performing IA (Professional consensus). As soon as the sonographic apparition of the embryo, the estimated date of pregnancy is done by measuring the crown-rump length (CRL) or by measuring the biparietal diameter (BIP) from 11 weeks on (grade B). Reliability of these parameters being ± 5 days, IA could be done if measurements are respectively less than 90 mm for CRL and less than 30 mm for BIP (Professional consensus). A medical IA performed with a dose of 200 mg mifepristone combined with misoprostol is effective at any gestational age (EL1). Before 7 weeks, mifepristone followed between 24 and 48 hours by taking misoprostol orally, buccally sublingually or eventually vaginally at a dose of 400 ug possibly renewed after 3 hours (EL1, grade A). Beyond 7 weeks, misoprostol given vaginally, sublingually or buccally are better tolerated with fewer side effects than oral route (EL1). It is recommended to always use a cervical preparation during an instrumental abortion (Professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 mcg (grade A). Aspiration evacuation is preferable to curettage (grade B). A perforated uterus during an instrumental suction should not be considered as a scarred uterus (Professional consensus). IA is not associated with increased subsequent risk of infertility or ectopic pregnancy (EL2). The pre-abortion medical consultations does not affect, most of the time, the decision to request an IA. Indeed, a majority of women is quite sure of her choice during these consultations. Acceptability of the method of IA and satisfaction appears to be larger when they are able to choose the abortion method (grade B). There is no relationship between an increase in psychiatric disorders and IA (EL2). Women with psychiatric histories are at increased risk of mental disorders after the occurrence of an UPP (EL2). In case of instrumental abortion, oral estrogen-progestogen contraceptives and the patch should be started from the day of the abortion, the vaginal ring inserted within 5 days of IA (grade B). In case of medical abortion, the vaginal ring should be inserted within a week of taking mifepristone, oral estrogen-progestogen contraceptives and the patch should be initiated on the same day or the day after taking prostaglandins (grade C). In case of instrumental abortion, the contraceptive implant may be inserted on the day of the abortion (grade B). In case of medical abortion, the implant can be inserted on the day of mifepristone (grade C). The copper Intrauterine Device (IUD) and levonorgestrel should be inserted preferably on the day of instrumental abortion (grade A). In case of medical abortion, an IUD can be inserted within 10 days following mifepristone after ensuring by ultrasound of the absence of intrauterine pregnancy (grade C). Conclusion The implementation of these guidelines may promote a better and more homogenous care for women requesting IA in our country

Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the Collège national des gynécologues obstétriciens français

International audienceThe literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800μg, repeated if necessary after 24 or 48h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200mg, followed 24-48h later by vaginal, sublingual or buccal misoprostol 800μg (followed 3-4h later, if necessary, by misoprostol 400μg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800-2400μg in 24h, 24-48h after at least 200mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25μg every 3-6h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600μg) and treatment (sublingual misoprostol 800μg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity