Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant. miR-103 reduced the expression of cyclin dependent kinase (CDK2) and its cyclin E1 target, thereby leading to inhibition of cellular proliferation. miR-103 is encoded within the fifth intron of PANK3 gene. We demonstrate that the GC receptor (GR) upregulates miR-103 by direct interaction with GC response element (GRE) in the PANK3 enhancer. Consequently, miR-103 targets the c-Myc activators c-Myb and DVL1, thereby reducing c-Myc expression. Since c-Myc is a transcription factor of the miR-17~92a poly-cistron, all six miRNAs of the latter are also downregulated. Of these, miR-18a and miR-20a are involved in GCIA, as they target GR and BIM, respectively. Consequently, GR and BIM expression are elevated, thus advancing GCIA. Altogether, this study highlights miR-103 as a useful prognostic biomarker and drug for leukemia management in the future.

Objective To validate the Maternal Fetal Medicine Unit's (MFMU) vaginal birth after cesarean delivery (VBAC) calculator in an Israeli cohort, and to detect other variables associated with VBAC and construct an improved VBAC calculator. Methods A retrospective cohort study was performed at a single university‐affiliated medical center. Women carrying a singleton, term, cephalic‐presenting fetus, with previous one low transverse cesarean delivery who opted for trial of VBAC were included. Demographic and obstetric characteristics were incorporated into the MFMU's calculator, to predict probabilities of VBAC and compare prediction performance with the original publication utilizing receiver operating characteristic (ROC) statistics. Logistic regression analysis was used to investigate other variables and construct an improved model for success of VBAC. Results Of 490 parturients, 396 (80.8%) had a successful vaginal delivery. Compared to the original publication, the MFMU's calculator underperformed: area under the ROC curve (AUC) was 0.709 (95% confidence interval [CI] 0.652–0.766, P < 0.001). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were 67.42%, 65.96%, 89.30%, 32.46%, and 32.46%, respectively. An improved model that included previous VBAC, prior vaginal delivery, spontaneous onset of delivery, and maternal diabetes resulted in improved prediction performance with an AUC of 0.771 (95% CI 0.723–0.82, P < 0.001). Conclusion MFMU's VBAC calculator needs to be validated in different populations before implementation.

OBJECTIVE:As obesity has been associated with adverse obstetric outcomes, the objective of this study was to evaluate the effect of maternal body mass index (BMI) on the duration of the second stage of labor. STUDY DESIGN: This retrospective data analysis included all spontaneous vaginal deliveries in a single tertiary medical center through 2015-2020. The duration of second stage of labor (the primary outcome) was compared between women with obesity (body mass index (BMI) 30) to women with BMI< 25 kg/m 2 . Subgroup analysis was performed by parity and use of epidural analgesia. RESULTS: Overall, 9,868 deliveries were included e 8,492 women with BMI< 25 and 1,376 women with obesity. 3,908 (39.6%) were primiparous, and epidural analgesia was used by 7,186 (72.8%) women. In subgroup analysis by parity and epidural analgesia, shorter duration of the second stage of labor was noted in women with obesity, except for multiparous women with epidural analgesia. Higher birthweight was noted in women with obesity, except for the subgroup of primiparous women without analgesia. CONCLUSION: Shorter second stage of labor was noted in women with obesity undergoing spontaneous vaginal delivery, despite higher birthweight in this cohort. This may be related to previous evidence showing higher levels of oxytocin in morbidly obese patients.