Stratified Analysis of Maternal Age and Risk of Cesarean Section

<p>Adjusted odds ratio for a 5-y increase in maternal age (bars are 95% CIs) stratified by maternal age, year of delivery, week of gestation, and deprivation category. Interactions were statistically significant for year of delivery (<i>p</i> < 0.001), week of gestation (<i>p</i> = 0.002), and deprivation category (<i>p</i> = 0.002) using the likelihood ratio test. Odds ratios are adjusted for maternal age, height, deprivation category, onset of labor, week of gestation, sex, birth weight percentile of infant, and year. The vertical dashed line indicates unity.</p

Time Trends in Maternal Age Distribution and Cesarean Section Rates in Scotland between 1980 and 2005

<div><p>(A) Proportion of women per year delivering within the age ranges 30–34, 35–39, and ≥40 y.</p> <p>(B) Proportion of women per year delivered by emergency cesarean section.</p></div

Maternal Age and the Risk of Cesarean Delivery

<p>Proportion of women being delivered by emergency intrapartum cesarean section in relation to age of mother (<i>n</i> = 583,847). Bars are binomial 95% CIs.</p

Myometrial Contractility in Relation to Maternal Age

<div><p>(A) Trace of isometric tension from myometrial strip obtained from a 40-y-old woman being delivered by planned cesarean section. The blue line represents the 15 min before addition of potassium, and the red line 7 min in the presence of 50 mM of potassium. The area under the curve is the space between the tension trace and the baseline, indicated by the blue and red lines. The log₁₀ of the ratio of these two areas is the contraction unit. The spontaneous contraction before the addition of potassium and the contraction following potassium being washed out are both multiphasic.</p> <p>(B) Mean spontaneous contractile activity (quantified as contraction units) of isolated strips of myometrium obtained from women (<i>n</i> = 62) at the time of planned cesarean section in relation to the age of the donor. Regression line: <i>y</i> = 0.1078 + (−0.0174 × age); 95% CI for slope, −0.0326 to −0.0022.</p> <p>(C) Proportion of spontaneous contractions that were multiphasic in relation to maternal age (<i>n</i> = 62, 181 samples). See text for regression analysis of (B) and (C).</p></div

Maternal Age and the Duration of Labor and Risk of Operative Vaginal Birth

<div><p>(A) Mean duration of spontaneous labor in relation to maternal age (<i>n</i> = 409,703). Bars are 95% CIs of the mean.</p> <p>(B) Proportion of nulliparous women who required operative vaginal delivery in relation to maternal age among the 518,787 women delivered by a means other than emergency cesarean section. Bars are binomial 95% CIs.</p></div

A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles

The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (<b>32</b>–<b>34</b>), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (<b>1</b>), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G₂/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity

Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung

<div><p>The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels <i>in utero</i> by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age) and 144 days (0.99) of gestation, and by 2–4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids <i>in utero</i>. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.</p></div

Immunohistochemical localisation of Ob-Rb in fetal ovine lungs during late gestation.

<p>Fetal lungs at 100d (A), 115d (B), 130d (C) and 144d (E, F); negative control at 130d (D). Arrowheads show leptin staining in fetal bronchial and bronchiolar epithelium, and cartilage chondrocytes (C), type II pneumocytes (F, black) and alveolar macrophages (F, red).</p

Mean (± SEM) pulmonary Ob-Rb protein levels in sheep fetuses (A) from 100 to 144d of gestation and after glucocorticoids exposure by (B) fetal cortisol infusion and (C) maternal dexamethasone treatment.

<p>For the developmental study, values with different superscripts are significantly different from each other (P<0.05; one-way ANOVA followed by Tukey test; n = 5 for each age). * significantly different from respective control saline group, P<0.05, unpaired t-test (n = 5–6 for each group).</p

Mean (± SEM) relative mRNA abundance, normalised to respective control saline group, of leptin receptors (Ob-Rb and Ob-R) in the lungs of sheep fetuses exposed to glucocorticoids by fetal cortisol infusion (A, B) and maternal dexamethasone treatment (C, D; n = 5–6 for each group).

<p>* significantly different from respective control saline group, P<0.05, unpaired t-test.</p