No abstract

Spontaneous preterm birth remains the leading cause of neonatal morbidity and mortality worldwide, and accounts for a significant global health burden. Several obstetric strategies to screen for spontaneous preterm delivery, such as cervical length and fetal fibronectin measurement, have emerged. However, the effectiveness of these strategies relies on their ability to accurately predict those pregnancies at increased risk for spontaneous preterm birth (SPTB). Transvaginal cervical shortening is predictive of preterm birth and when coupled with appropriate preterm birth prevention strategies, has been associated with reductions in SPTB in asymptomatic women with a singleton gestation. The use of qualitative fetal fibronectin may be useful in conjunction with cervical length assessment in women with acute preterm labor symptoms, but data supporting its clinical utility remain limited. As both cervical length and qualitative fetal fibronectin have limited capacity to predict preterm birth, further studies are needed to investigate other potential screening modalities.

Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here, we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell-cycle inhibitors CDKN2D and CDKN1B induced stem-like features. Silencing of TRIM17 and NOXA induced immune and drug resistance in tumor cells by increasing antiapoptotic MCL1. Importantly, HDAC inhibition synergized with Ag-specific adoptive T-cell therapy to control immune refractory cancers. Our results reveal that NANOG influences the epigenetic state of tumor cells via HDAC1, and they encourage a rational application of epigenetic modulators and immunotherapy in treatment of NANOG refractory cancer types. .

Objective To determine how well antenatal corticosteroids (ACS) were timed, based on the indication for administration for women delivering preterm.Design Retrospective cohort study.Setting Tertiary medical centre.Population Six hundred and thirty women who had singleton preterm births between 24 and 34 weeks' gestational age.Methods Charts from 2006 to 2011 were reviewed for indications for ACS administration, which included premature rupture of membranes, threatened preterm labour, risk factors for spontaneous preterm birth such as short ultrasound cervical length, positive fetal fibronectin, and hypertensive disorders of pregnancy. Charts were reviewed for timing of ACS administration in relation to delivery.Main outcome measures The primary outcome was optimal timing, defined as administration of ACS ≥24 hours to ≤7 days prior to delivery.Results Of 630 women who delivered preterm, 589 (93%) received ACS prior to delivery. ACS timing was optimal in 40% (238 of 589) of cases. Women with hypertensive disorders were most likely to have steroids optimally timed (62%). Asymptomatic women at increased risk for preterm delivery were less likely to receive optimally timed ACS (12%). The majority of women who received steroids >2 weeks prior to delivery (57%) received a second course.Conclusion A majority of women who delivered preterm did not receive optimally timed ACS. Diagnostic tools that identified women at risk for preterm birth were not able to identify patients for appropriate steroid timing. Given the range of clinical scenarios in which patients are at increased risk for preterm delivery, further research is needed to assist clinicians in optimising steroid administration.

In a geographically diverse U.S. population, the coronavirus disease 2019 (COVID-19) pandemic was not associated with a significant difference in adverse pregnancy outcomes, even when considering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status.