The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was related to maternal circulating concentrations of trophoblast-derived proteins at 8-14 wk gestation. Women with a pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile at 8-14 wk gestation had an increased risk of intrauterine growth restriction [adjusted odds ratio, 2.9; 95% confidence interval (CI), 2.0-4.1], extremely premature delivery (adjusted odds ratio, 2.9; 95% CI, 1.6-5.5), moderately premature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), preeclampsia (adjusted odds ratio, 2.3; 95% CI, 1.6-3.3), and stillbirth (adjusted odds ratio, 3.6; 95% CI, 1.2-11.0). The strengths of the associations were similar when the test was performed before 13 wk gestation or between 13 and 14 wk gestation. In contrast, levels of free beta-human CG, another circulating protein synthesized by the syncytiotrophoblast, were not predictive of later outcome in multivariate analysis. PAPP-A has been identified as a protease specific for IGF binding proteins. We conclude that control of the IGF system in the first and early second trimester trophoblast may have a key role in determining subsequent pregnancy outcome.
Ultrasound assessment of chorionicity has a high sensitivity and specificity. This is further improved if the assessment is performed prior to 14 weeks' gestation.
CUB screening offers a significant improvement in sensitivity over second-trimester biochemical screening and is deliverable within a routine prenatal clinical setting.
Perianal CD is the archetypal condition that exemplifies the need for an MDT approach in caring for patients with inflammatory bowel disease. A combination of treatment modalities that includes topical wound management is likely to produce the best patient outcomes.
Convergent enantioselective syntheses of angucyclinone‐type natural products rubiginones A2 (2) and C2 (1) and their 11‐methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1‐vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe3 on (SS)‐[(p‐tolylsulfinyl)methyl]‐p‐quinol (9) and the elimination of the β‐hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels–Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C‐2 or C‐3 of the dienophiles 5 or 6, derived from 5‐methoxy‐1,4‐naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C‐1 oxidation.
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