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Highlights d E-cadherin experiences higher mechanical tension in acini compared with monolayers d E-cadherin tension is positively correlated to CFTR activity d Epithelial acini have significant lumen pressure due, in part, to CFTR activity d Increased CFTR activity increases cell proliferation and blocks EMT progression

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-cadherin force-dependent manner. In this study, the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers. To determine if high levels of E-cadherin force were necessary to induce proliferation at the center of the colony, a lower-force mutant of E-cadherin was developed. Cells with lower E-cadherin force had significantly reduced proliferation for cells at the center of the colony but minimal differences for cells at the edges of the colony. Similarly, increasing substrate stiffness was found to increase E-cadherin force and increase the proliferation rate across the colony. Taken together, these results show that forces through cell-cell junctions regulate proliferation across large groups of epithelial cells. In addition, an important finding of this study is that junction forces are dynamic and modulate cellular function even in the absence of externally applied loads.

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BACKGROUND:Several studies have shown that postplacental intrauterine device (IUD) insertion is a safe, convenient, and effective option for postpartum contraception. Of the prior studies performed, few involve ultrasound-guided insertion, none involve the levonorgestrel intrauterine system, and none of the prior studies take place in a United States residency program. OBJECTIVE: To assess the safety and feasibility of ultrasound-guided postplacental insertion of levonorgestrel intrauterine system (Mirena) in a U.S. residency program. METHODS: Levonorgestrel intrauterine system IUDs were inserted within 10 minutes of placental delivery after vaginal delivery via either ringed forceps or hand technique. All insertions were ultrasound-guided. Of the 30 subjects that were enrolled, 20 received an levonorgestrel intrauterine system IUD. Subjects were examined at 4 weeks postpartum and 10 weeks postpartum for evidence of expulsion or infection. RESULTS: Of the subjects who have been followed to date, none have had evidence of intrauterine infection. There have been 2 expulsions, giving an expulsion rate of 10% at 10 weeks postpartum. CONCLUSION: This pilot study suggests that ultrasoundguided postplacental insertion of Mirena IUDs is a feasible, safe option for postpartum contraception in a U.S. residency program. OBJECTIVE:To compare the effects on ovulation incidence of 2 dosing regimens (21-and 24-day) of an oral contracep-tive (OC) containing ethinyl estradiol (EE) 20 g/drospirenone 3 mg following predefined dosing errors. METHODS: This double-blind, randomized study recruited women (18 -35 years) who had ovulated and had a follicular diameter of 15 mm or greater on day 23 during the cycle before starting study treatment. Women received 3 treatment cycles of EE 20 g/drospirenone 3 mg in a 21/7 (21 active/7 placebo) or 24/4 day (24 active/4 placebo) regimen. In treatment cycle 3, the initial 3 tablets in each pack in both dosing regimens were placebo. Ovarian activity was classified via Hoogland score. Secondary end points included serum concentrations of 17 ␤ estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). RESULTS: After 3 treatment cycles, the odds of having a lower Hoogland score with the 24-day regimen was 3.06 times higher (95% confidence interval 1.44 -6.65) than with the 21-day regimen. One ovulation was observed in the 24-day regimen (cycle 3), and 4 ovulations were observed in the 21-day regimen. More women in the 24-day regimen had Hoogland scores of 1 (no follicular activity) (51.9% versus 28.8%). Similar levels of serum estradiol, LH, and FSH suppression were achieved with both regimens, indicating good ovulation suppression. CONCLUSION: Both regimens demonstrated reliable ovulation inhibition, indicated by low Hoogland scores. Stronger suppression of follicular development was observed with the 24-day regimen when dosing errors were intentionally introduced. This should translate into improved contraceptive efficacy in clinical practice.