350 research outputs found

    TBX2, a Novel Regulator of Labour

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    Background and Objectives: Therapeutic interventions targeting molecular factors involved in the transition from uterine quiescence to overt labour are not substantially reducing the rate of spontaneous preterm labour. The identification of novel rational therapeutic targets are essential to prevent the most common cause of neonatal mortality. Based on our previous work showing that Tbx2 (T-Box transcription factor 2) is a putative upstream regulator preceding progesterone withdrawal in mouse myometrium, we now investigate the role of TBX2 in human myometrium. Materials and Methods: RNA microarray analysis of (A) preterm human myometrium samples and (B) myometrial cells overexpressing TBX2 in vitro, combined with subsequent analysis of the two publicly available datasets of (C) Chan et al. and (D) Sharp et al. The effect of TBX2 overexpression on cytokines/chemokines secreted to the myometrium cell culture medium were determined by Luminex assay. Results: Analysis shows that overexpression of TBX2 in myometrial cells results in downregulation of TNFα- and interferon signalling. This downregulation is consistent with the decreased expression of cytokines and chemokines of which a subset has been previously associated with the inflammatory pathways relevant for human labour. In contrast, CXCL5 (C-X-C motif chemokine ligand 5), CCL21 and IL-6 (Interleukin 6), previously reported in relation to parturition, do not seem to be under TBX2 control. The combined bioinformatical analysis of the four mRNA datasets identifies a subset of upstream regulators common to both preterm and term labour under control of TBX2. Surprisingly, TBX2 mRNA levels are increased in preterm contractile myometrium. Conclusions: We identified a subset of upstream regulators common to both preterm and term labour that are activated in labour and repressed by TBX2. The increased TBX2 mRNA expression in myometrium collected during a preterm caesarean section while in spontaneous preterm labour compared to tissue harvested during iatrogenic preterm delivery does not fit the bioinformatical model. We can only explain this by speculating that the in vivo activity of TBX2 in human myometrium depends not only on the TBX2 expression levels but also on levels of the accessory proteins necessary for TBX2 activity

    Consequences of cervical pessary for subsequent pregnancy : follow-up of randomized clinical trial (ProTWIN)

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    Funding Information: B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and has received research funding from Guerbet, Ferring and Merck. The original ProTWIN trial was funded by ZonMW grant 200310004. We did not receive any funding for this follow‐up research.Peer reviewedPublisher PD

    Феномен мастурбации: негативное или позитивное явление?

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    Рассмотрены разные взгляды на роль мастурбации в становлении сексуальности человека. Представлены результаты собственных исследований автора, проведенных с целью установить значение этого феномена для формирования сексуального поведения и сексуального здоровья.Various opinions about the role of masturbation in human sexuality development are discussed. The findings of the original research performed to evaluate the significance of this phenomenon in formation of sexual behavior and sexual health are reported

    Периоды апробации метода прогноза интегральной метанообильности шахты

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    Розроблені аналітичній та натурній методи урахування метанового потенціалу вугільних шахт, апробація яких в умовах діючих об’єктів вдовж 5 термінів (1967 – 2009 рр.) показала високу надійність метода прогнозу інтегральної метанообільності шахт ІМА (~9 тис. порівнянь). На базі цього методу пропонується розробить державний нормативний документ для урахування метанового потенціалу вугільних шахт та реалізувати науково-технічні проекти авторів, які включені в програму науково-технічного розвитку Донецької області до 2020 р.Analytic and nature methods of calculation of methane potential of the collieries which check in the conditions of operating objects during 5 periods (1967 – 2009 years) has shown high reliability concerning of the method integrated methane of abundance of object IMA (~9 000 results) are developed. On the basis of this method it is offered to develop the state standard document for calculation of methane potential of collieries and to realize author’s projects to be conclusion to the science-technical program of development of Donetsk region to 2020 year

    Few randomized trials in preterm birth prevention meet predefined usefulness criteria

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    Funding Information: Funding: The study was funded by a grant from the Netherlands Organization for Health Research and Development (ZonMw Rubicon grand #452182306). The funder had no involvement in any phase of this study. Meta-Research Innovation Center at Stanford (METRICS), Stanford University is supported by a grant from the Laura and John Arnold Foundation. JvtH is supported by postdoctoral grant from the Netherlands Organization for Health Research and Development (Rubicon grand 452,182,306). C.A. is supported by postdoctoral grants from the Knut and Alice Wallenberg Foundation (K.A.W. 2019.0561), Uppsala University, and the Sweden-America Foundation. B.M. is supported by an NHMRC Investigator grant (GNT1176437). B.M. reports consultancy for Guerbet, has been a member of the ObsEva advisory board and holds Stock options for ObsEva. The work of J.I. has been supported by an unrestricted gift from Sue and Bob O'Donnell. J.I. is a team member of the editorial board of JCE. Publisher Copyright: © 2023 The AuthorsPeer reviewe

    Assessing the usefulness of randomised trials in obstetrics and gynaecology

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    FUNDING INFORMATION The study was funded by a grant from the Netherlands Organization for Health Research and Development (ZonMw Rubicon grant #452182306). The funder had no involvement in any phase of this study.Non peer reviewedPublisher PD

    Nationwide implementation of a decision aid on vaginal birth after cesarean:a before and after cohort study

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    Woman with a history of a previous cesarean section (CS) can choose between an elective repeat CS (ERCS) and a trial of labor (TOL), which can end in a vaginal birth after cesarean (VBAC) or an unplanned CS. Guidelines describe women's rights to make an informed decision between an ERCS or a TOL. However, the rates of TOL and vaginal birth after CS varies greatly between and within countries. The objective of this study is to asses nation-wide implementation of counselling with a decision aid (DA) including a prediction model, on intended delivery compared to care as usual. We hypothesize that this may result in a reduction in practice variation without an increase in cesarean rates or complications. In a multicenter controlled before and after cohort study we evaluate the effect of nation-wide implementation of a DA. Practice variation was defined as the standard deviation (SD) of TOL percentages. A total of 27 hospitals and 1,364 women were included. A significant decrease was found in practice variation (SD TOL rates: 0.17 control group vs. 0.10 intervention group following decision aid implementation, p=0.011). There was no significant difference in the ERCS rate or overall CS rates. A 21% reduction in the combined maternal and perinatal adverse outcomes was seen. Nationwide implementation of the DA showed a significant reduction in practice variation without an increase in the rate of cesarean section or complications, suggesting an improvement in equality of care

    Induction of labor with Foley catheter and risk of subsequent preterm birth : follow‐up study of two randomized controlled trials (PROBAAT‐1 and ‐2)

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    Acknowledgements We thank all the women who participated in the PROBAAT trials and all participating institutions and their staff for their contribution to this follow-up study. Funding The original PROBAAT-2 trial was funded by FondsNutsOhra. For the PROBAAT-1 trial and this follow-up study, no funding was received. MV received a doctoral grant for teachers by the Netherlands Organisation for Scientific Research (023.011.051). BM is supported by a NHMRC Practitioner Fellowship (GNT1082548). Funding sources had no role in design, execution, analyses, interpretation, or decision to submit results.Peer reviewedPublisher PD
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