Hysterotomy level at Cesarean section and occurrence of large scar defects : a randomized single-blind trial

Objective: To study the association between the level of Cesarean hysterotomy and the presence of large uterine scar defects 6–9 months after delivery. Methods: This was a two-center, randomized, single-blind trial of a surgical procedure with masked assessment of the principal outcome under study. Women without a history of Cesarean section (CS) who underwent emergency CS at cervical dilatation ≥ 5 cm were randomized to high or low incision. Hysterotomy was performed 2 cm above and 2 cm below the plica vesicouterina in the high and low incision groups, respectively. Women were examined using saline contrast sonohysterography to assess the appearance of the hysterotomy scar 6–9 months after delivery. The main outcome was presence of a large scar defect, defined as the remaining myometrial thickness over the defect being ≤ 2.5 mm. Secondary outcomes were perinatal outcome, operative complications within 8 weeks after delivery and long-term outcome in a subsequent pregnancy. Results: Of 122 patients enrolled in the trial, 114 were assessed by ultrasound examination, of whom 55 were randomized to high and 59 to low CS incision. Large scar defects were seen in four (7%) women in the high-incision group and in 24 (41%) in the low-incision group (P < 0.001; odds ratio, 8.7 (95% CI, 2.8–27.4)). There were no differences in operative complications and perinatal outcomes between the two groups. The median follow-up time was 4 years and 7 months, during which 56 (49%) women had a subsequent pregnancy. No significant differences were observed in the rate of complications in subsequent pregnancy and delivery between women who had low and those who had high incision at the index CS. Conclusion: Low Cesarean hysterotomy level in women in advanced labor is associated with higher incidence of large scar defects detected by transvaginal ultrasound examination 6–9 months after delivery

The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid

Intraneuronal β-amyloid (Aβi) accumulates early in Alzheimer's disease (AD) and inclusion body myositis. Several organelles, receptor molecules, homeostatic processes, and signal transduction components have been identified as sensitive to Aβ. Although prior studies implicate the insulin-PI3K-Akt signaling cascade, a specific step within this or any essential metabolic or survival pathway has not emerged as a molecular target. We tested the effect of Aβ42 on each component of this cascade. In AD brain, the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control. In cell culture, Aβi expression inhibited both insulin-induced Akt phosphorylation and activity. In vitro experiments identified that β-amyloid (Aβ), especially oligomer preparations, specifically interrupted the PDK-dependent activation of Akt. Aβi also blocked the association between PDK and Akt in cell-based and in vitro experiments. Importantly, Aβ did not interrupt Akt or PI3K activities (once stimulated) nor did it affect more proximal signal events. These results offer a novel therapeutic strategy to neutralize Aβ-induced energy failure and neuronal death