Wnt7a is a novel inducer of ß-catenin-independent tumor-suppressive cellular senescence in lung cancer.

Cellular senescence is an initial barrier for carcinogenesis. However, the signaling mechanisms that trigger cellular senescence are incompletely understood, particularly in vivo. Here we identify Wnt7a as a novel upstream inducer of cellular senescence. In two different mouse strains (C57Bl/6J and FVB/NJ), we show that the loss of Wnt7a is a major contributing factor for increased lung tumorigenesis owing to reduced cellular senescence, and not reduced apoptosis, or autophagy. Wnt7a-null mice under de novo conditions and in both the strains display E-cadherin-to-N-cadherin switch, reduced expression of cellular senescence markers and reduced expression of senescence-associated secretory phenotype, indicating a genetic predisposition of these mice to increased carcinogen-induced lung tumorigenesis. Interestingly, Wnt7a induced an alternate senescence pathway, which was independent of ß-catenin, and distinct from that of classical oncogene-induced senescence mediated by the well-known p16(INK4a) and p19(ARF) pathways. Mechanistically, Wnt7a induced cellular senescence via inactivation of S-phase kinase-associated protein 2, an important alternate regulator of cellular senescence. Additionally, we identified Iloprost, a prostacyclin analog, which initiates downstream signaling cascades similar to that of Wnt7a, as a novel inducer of cellular senescence, presenting potential future clinical translational strategies. Thus pro-senescence therapies using either Wnt7a or its mimic, Iloprost, might represent a new class of therapeutic treatments for lung cancer.

A survey of women's experiences following instrumental vaginal delivery.

There is little published data on women's experiences of having had an instrumental vaginal delivery (IVD). We conducted a postal survey of women who had IVD at our centre between November 2007 and January 2008, using a semi-structured questionnaire to ascertain perceptions. The response rate was 63% (58/92). Eleven (19%) felt that the risks and benefits of an IVD were explained to them. Although 46/58 (79%) needed an episiotomy, only 17(37%) recalled an explanation. Increased fear of childbirth following IVD was reported by 16/58 (27.5%); 14 of the 58 women (24%) preferred a caesarean section if they were to need operative delivery, rather than having an IVD in a further pregnancy. Clear information about the risks and benefits of IVD and debriefing following the procedure are desirable to women having IVD. These measures may reduce fear of childbirth and also reduce maternal request for caesarean section in future pregnancies.

A prospective observational study of emergency caesarean section rates and the effect of the labour ward experience.

The National Sentinel Audit found that one in five births in England and Wales was by caesarean section. The reasons for the increase in caesarean section rates are multi-factorial. Anecdotally, it is suggested that obstetric intervention rates and caesarean section rates vary among obstetricians without a difference in fetal and maternal outcomes. The aim of this prospective observational study of 817 deliveries was to assess the effect of experience on the caesarean section rates for different obstetricians. Obstetricians with greater than 3 years of 2nd on-call labour ward experience had a statistically significant lower caesarean rate than less experienced obstetricians 10.25% vs 25.49%, respectively (p < 0.05). Differences in instrument deliveries was also studied.

Survey of antenatal women's knowledge of maternal and fetal risks of tobacco smoking and acceptability of nicotine replacement products in pregnancy.

A survey was carried out of 145 pregnant women in the third trimester in pregnancy to assess motivators to stop tobacco smoking and assess women's knowledge of fetal and maternal risk of smoking. In addition, the survey was to assess the acceptability of nicotine replacement products use in pregnancy. The findings of this survey show that pregnant women tend to know about the maternal risks of smoking but their knowledge is deficient about fetal risks. The knowledge of the association of cot death risk and tobacco smoking appears to be the greatest motivator to stop smoking. Overall, 74% wished to stop smoking in pregnancy and 68% would accept a nicotine replacement product.