Hoxb-5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning. This notion is supported by results from BPS and CCAM tissue, in which Hoxb-5 is maintained in a manner typical of an earlier developmental stage and is associated with development of abnormal lung tissue.
Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.
Objective To analyze the economic and resource implications of using plasma soluble fms-like tyrosine kinase-1 (sFlt1) and placenta growth factor (PlGF) measurements in preeclampsia evaluation and management. Design Retrospective cost analysis of our prospective cohort study. Setting Boston, Massachusetts (USA). Population Women (n=176) presenting to the hospital at <34 weeks’ gestation for evaluation of possible preeclampsia during 2009–2010. Cases without complete cost or outcome data (n=9) and re-enrollments (n=18) were excluded. Methods Modeled comparisons between the standard approach (combination of blood pressure, urinary protein excretion, alanine aminotransferase, and platelet counts) and a novel approach (ratio of plasma sFlt1 and PlGF) using actual hospital data converted to 2012 US dollars in accordance with Centers for Medicare and Medicaid Services. Main outcome measures Direct two-week costs and resource utilization by groups having true or false positive and negative test results for adverse outcomes according to approach. Results The improved specificity of the novel approach decreased the proportion of women falsely labeled as test-positive from 42.3% (34.4% – 50.2%) to 4.0% (0.85% – 7.15%) and increased the proportion correctly labeled as test-negative from 23.5% (16.7% – 30.3%) to 61.7% (53.9% – 69.5%). This could potentially reduce average per-patient costs by $1,215. Substantial quantities of resources [47.2% (35.7% – 58.7%) of antenatal admissions and 72.5% (68.0% – 77.0%) of tests for fetal well-being] were unnecessarily used for women who were truly negative. A proportion of iatrogenic preterm deliveries among women with negative results was potentially avoidable representing further cost and resource savings. Conclusions Clinical use of the plasma sFlt1 and PlGF ratio improves risk stratification among women presenting for preeclampsia evaluation and has the potential to reduce costs and resource utilization.
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