SUMMARY The evolutionarily ancient arm of the E2f family of transcription factors consisting of the two atypical members E2f7 and E2f8 is essential for murine embryonic development. However, the critical tissues, cellular processes and molecular pathways regulated by these two factors remain unknown. Using a series of fetal and placental lineage-specific cre mice we show that E2F7/E2F8 functions in extra-embryonic trophoblast lineages are both necessary and sufficient to carry fetuses to term. Expression profiling and biochemical approaches exposed the canonical E2F3a activator as a key family member that antagonizes E2F7/E2F8 functions. Remarkably, the concomitant loss of E2f3a normalized placental gene expression programs, corrected placental defects and fostered the survival of E2f7/E2f8 deficient embryos to birth. In summary, we identified a placental transcriptional network tightly coordinated by activation and repression through two distinct arms of the E2F family that is essential for extra-embryonic cell proliferation, placental development and fetal viability.

Our data suggest restoring femoral offset is the most important technical factor in preventing THA dislocation.

The semi-sitting position has lost favor among neurosurgeons partly due to unproven assumptions of increased complications. Many complications have been associated with this position; the most feared: venous air embolism and paradoxical air embolism. We report on this retrospective study of the outcome over 4 years of 48 neurosurgical patients operated on consecutively using a standardized protocol: 41 (85%) in the semi-sitting position, and seven (15%) in the prone position. Procedures included: tumor resection (34), posterior fossa decompression (12), cyst resection (1) and resection of arteriovenous malformation (1). Pre-operative workup was standardized. Vigilant intra-operative observation was done by an experienced neuroanesthetist. Pertinent data was extracted from surgical records. Of the 48 patients, 10 (20.8%) were found to have a patent foramen ovale (PFO) on trans-esophageal echocardiography. Of these, four (40%) patients underwent procedures in the semi-sitting position while six (60%) did not. A clinically significant venous air embolism (VAE) was detected during 2 of the 41 semi-sitting procedures (4.9%). Neither patient suffered any obvious sequelae. No other morbidity was encountered associated with surgical position. Our study suggests that a model similar to ours is effective in preventing major complications associated with the semi-sitting position. The semi-sitting position is a safe, practical position that should be considered in appropriate cases. The fear of dreadful complications seems unwarranted.