MEchanical DIlatation of the Cervix-- in a Scarred uterus (MEDICS): the study protocol of a randomised controlled trial comparing a single cervical catheter balloon and prostaglandin PGE2 for cervical ripening and labour induction following caesarean delivery.

INTRODUCTION: Labour induction in women with a previous caesarean delivery currently uses vaginal prostaglandin E2 (PGE2), which carries the risks of uterine hyperstimulation and scar rupture. We aim to compare the efficacy of mechanical labour induction using a transcervically applied Foley catheter balloon (FCB) with PGE2 in affected women attempting trial of labour after caesarean (TOLAC). METHODS AND ANALYSIS: This single-centre non-inferiority prospective, randomised, open, blinded-endpoint study conducted at an academic maternity unit in Singapore will recruit a total of 100 women with one previous uncomplicated caesarean section and no contraindications to vaginal delivery. Eligible consented participants with term singleton pregnancies and unfavourable cervical scores (≤5) requiring labour induction undergo stratified randomisation based on parity and are assigned either FCB (n=50) or PGE2 (n=50). Treatments are applied for up to 12 hours with serial monitoring of the mother and the fetus and serial assessment for improved cervical scores. If the cervix is still unfavourable, participants are allowed a further 12 hours' observation for cervical ripening. Active labour is initiated by amniotomy at cervical scores of ≥6. The primary outcome is the rate of change in the cervical score, and secondary outcomes include active labour within 24 hours of induction, vaginal delivery, time-to-delivery interval and uterine hyperstimulation. All analyses will be intention-to-treat. The data generated in this trial may guide a change in practice towards mechanical labour induction if this proves efficient and safer for women attempting TOLAC compared with PGE2, to improve labour management in this high-risk population. ETHICS AND DISSEMINATION: Ethical approval is granted by the Domain Specific Review Board (Domain D) of the National Healthcare Group, Singapore. All adverse events will be reported within 24 hours of notification for assessment of causality. Data will be published and will be available for future meta-analyses. TRIAL REGISTRATION NUMBER: NCT03471858; Pre-results.

Importance of miRNA stability and alternative primary miRNA isoforms in gene regulation during Drosophila development.

Mature microRNAs (miRNAs) are processed from primary transcripts (pri-miRNAs), and their expression is controlled at transcriptional and post-transcriptional levels. However, how regulation at multiple levels achieves precise control remains elusive. Using published and new datasets, we profile a time course of mature and pri-miRNAs in Drosophila embryos and reveal the dynamics of miRNA production and degradation as well as dynamic changes in pri-miRNA isoform selection. We found that 5' nucleotides influence stability of mature miRNAs. Furthermore, distinct half-lives of miRNAs from the mir-309 cluster shape their temporal expression patterns, and the importance of rapid degradation of the miRNAs in gene regulation is detected as distinct evolutionary signatures at the target sites in the transcriptome. Finally, we show that rapid degradation of miR-3/-309 may be important for regulation of the planar cell polarity pathway component Vang. Altogether, the results suggest that complex mechanisms regulate miRNA expression to support normal development.

Association mapping of quantitative disease resistance in a natural population of loblolly pine (Pinus taeda L.).

Genetic resistance to disease incited by necrotrophic pathogens is not well understood in plants. Whereas resistance is often quantitative, there is limited information on the genes that underpin quantitative variation in disease resistance. We used a population genomic approach to identify genes in loblolly pine (Pinus taeda) that are associated with resistance to pitch canker, a disease incited by the necrotrophic pathogen Fusarium circinatum. A set of 498 largely unrelated, clonally propagated genotypes were inoculated with F. circinatum microconidia and lesion length, a measure of disease resistance, data were collected 4, 8, and 12 weeks after inoculation. Best linear unbiased prediction was used to adjust for imbalance in number of observations and to identify highly susceptible and highly resistant genotypes ("tails"). The tails were reinoculated to validate the results of the full population screen. Significant associations were detected in 10 single nucleotide polymorphisms (SNPs) (out of 3938 tested). As hypothesized for genes involved in quantitative resistance, the 10 SNPs had small effects and proposed roles in basal resistance, direct defense, and signal transduction. We also discovered associated genes with unknown function, which would have remained undetected in a candidate gene approach constrained by annotation for disease resistance or stress response.