Diagnostic Performance of First Trimester Screening of Preeclampsia Based on Uterine Artery Pulsatility Index and Maternal Risk Factors in Routine Clinical Use

Preeclampsia is a pregnancy-specific disorder defined by new onset of hypertension and proteinuria after 20 weeks of gestation. The early detection of patients at risk of developing preeclampsia is crucial, however, predictive models are still controversial. We aim to evaluate the diagnostic performance of a predictive algorithm in the first trimester of pregnancy, in order to identify patients that will subsequently develop preeclampsia, and to study the effect of aspirin on reducing the rate of this complication in patients classified as high risk by this algorithm. A retrospective cohort including 1132 patients attending prenatal care at Clínica Dávila in Santiago, Chile, was conceived. The risk of developing preeclampsia (early and late onset) was calculated using algorithms previously described by Plasencia et al. Patients classified as high risk, in the first trimester of pregnancy, by these algorithms, were candidates to receive 100 mg/daily aspirin as prophylaxis at the discretion of the attending physician. The overall incidence of preeclampsia in this cohort was 3.5% (40/1132), and the model for early onset preeclampsia prediction detected 33% of patients with early onset preeclampsia. Among the 105 patients considered at high risk of developing preeclampsia, 56 received aspirin and 49 patients did not. Among those who received aspirin, 12% (7/56) developed preeclampsia, which is equal to the rate of preeclampsia (12% (6/49)) of those who did not receive this medication. Therefore, the diagnostic performance of an algorithm combining uterine artery Doppler and maternal factors in the first trimester predicted only one third of patients that developed preeclampsia. Among those considered at high risk for developing the disease using this algorithm, aspirin did not change the incidence of preeclampsia, however, this could be due either to the small study sample size or the type of the study, a retrospective, non-interventional cohort study

Neural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality

Summary: Emerging evidence suggests that Parkinson's disease (PD), besides being an age-associated disorder, might also have a neurodevelopment component. Disruption of mitochondrial homeostasis has been highlighted as a crucial cofactor in its etiology. Here, we show that PD patient-specific human neuroepithelial stem cells (NESCs), carrying the LRRK2-G2019S mutation, recapitulate key mitochondrial defects previously described only in differentiated dopaminergic neurons. By combining high-content imaging approaches, 3D image analysis, and functional mitochondrial readouts we show that LRRK2-G2019S mutation causes aberrations in mitochondrial morphology and functionality compared with isogenic controls. LRRK2-G2019S NESCs display an increased number of mitochondria compared with isogenic control lines. However, these mitochondria are more fragmented and exhibit decreased membrane potential. Functional alterations in LRRK2-G2019S cultures are also accompanied by a reduced mitophagic clearance via lysosomes. These findings support the hypothesis that preceding mitochondrial developmental defects contribute to the manifestation of the PD pathology later in life. : Walter, Bolognin and colleagues show the detection of mitochondrial phenotypes in NESCs derived from Parkinson's disease (PD) patients carrying the LRRK2-G2019S mutation. This supports the use of stem cells as a relevant model to study PD-associated mitochondrial defects associated to PD. Keywords: Parkinson's disease, LRRK2, neurodevelopment, stem cells, mitochondria, autophagy, mitophag