Ventriculomegaly associated with multiple echo-dense nodules is characteristic of severe fetal toxoplasmosis and carries a poor prognosis. When the ventricles have normal size or are only mildly dilated, the nodules restricted to the parenchyma development may be normal.

ObjectiveA high ratio of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF) has been linked to pre‐eclampsia (PE). We evaluated the sFlt‐1/PlGF ratio as a predictive marker for early‐onset PE in women at risk of PE.MethodsThis prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt‐1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early‐onset PE (< 34 + 0 weeks). Serum sFlt‐1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model.ResultsA total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt‐1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1–9.3), 4.0 (IQR, 2.6–6.3) and 3.3 (IQR, 2.0–5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5–43.7), 18.4 (IQR, 8.2–57.9) and 51.9 (IQR, 11.5–145.6) for women with early‐onset PE; and 6.7 (IQR, 4.6–9.9), 4.7 (IQR, 2.8–7.2) and 6.0 (IQR, 3.8–10.5) for women with late‐onset PE. Compared with early‐onset PE, the sFlt‐1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late‐onset PE (P < 0.001 at each timepoint). A prediction model for early‐onset PE was developed, which included the sFlt‐1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver–operating characteristics curves of 0.86 (95% CI, 0.77–0.95), 0.91 (95% CI, 0.85–0.97) and 0.93 (95% CI, 0.86–0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt‐1/PlGF ratio alone or uterine artery mean pulsatility index.ConclusionsThe sFlt‐1/PlGF ratio can improve prediction of early‐onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Introductory paragraphThe pancreas is a central organ for human diseases that have a dramatic societal burden, such as pancreatic cancer and diabetes 1,2 . Non-coding cis-regulatory elements (CREs) of DNA control gene expression 3,4 , being required for proper pancreas function. Most disease-associated alleles 5,6 are noncoding, often overlapping with CREs 5 , suggesting that alterations in these regulatory sequences contribute to human pancreatic diseases by impairing gene expression. However, functional testing of CREs in vivo is not fully explored. Here we analysed histone modifications, transcription, chromatin accessibility and interactions, to identify zebrafish pancreas CREs and their human functional equivalents, uncovering disease-associated sequences across species. We found a human pancreatic enhancer whose deletion impairs the tumour suppressor gene ARID1A expression, conferring a potential tumour suppressor role to this non-coding sequence. Additionally, we identified a zebrafish ptf1a distal enhancer which deletion generates pancreatic agenesis, demonstrating the causality of this condition in humans 7 and the interspecies functional equivalency of enhancers. ResultsThe pancreas of zebrafish, a vertebrate model suitable for genetic manipulation 8 , shares many similarities with the human pancreas, including transcription factors (TFs) operating in similar genetic networks of pancreas development and function 9,10 . We observed that these similarities are extensible to organ structure ( Fig.1a) and cellular composition (SupplementaryFig.1), suggesting that shared genetic networks might operate through equivalent sets of CREs in both species.To identify CREs active in the zebrafish adult pancreas, we performed ChIP-seq for H3K27ac 11 , a key histone modification associated to active enhancers and ATAC-seq 12 , to identify regions of open chromatin. We have also performed HiChIP 13 against H3K4me3 14 to determine active promoters interacting with the uncovered enhancers ( Fig.1b). We found 14753 putative active enhancers, mostly in intergenic regions (57.8%), and 23298 putative active promoters corresponding to 9848 genes ( Fig.1c; SupplementaryTable1-3). To identify a subset of pancreas enhancers with higher tissue-specificity, we asked which of them are inactive in whole embryos (dome to 48hpf), finding that 7115 (48.2%) are active only in the differentiated adult pancreas (PsE; Fig.1d; SupplementaryTable4) while the remaining 7638 (51.8%) are also active during embryonic development (DevE). Interestingly, DevE presented 4 clusters (C1-4) with different activity dynamics during development (Fig.1d; SupplementaryFig.2; SupplementaryTable5).Pancreatic enhancers should activate the expression of genes in the pancreas. To test this, we identified the nearest genes to each putative pancreas enhancer 15 , observing that genes nearby PsE are enriched for exocrine pancreas expression (p<4.27e-9; SupplementaryFig.3a; SupplementaryTable6-7), detected by in situ hybridization. These results contrast with DevE, ...

The discovery of the immunoregulatory potential of human amniotic membrane (hAM) propelled several studies focusing on its application for the treatment of immunological disorders. However, there is little information regarding the effects of hAM on distinct activation and differentiation stages of immune cells. Here, we aim to investigate the effect of human amniotic membrane extract (hAME) on the pattern of cytokine production by T cells, monocytes and myeloid dendritic cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from eight healthy individuals were stimulated in vitro in the presence or absence of hAME. Mitogen-induced proliferation of PBMCs and cytokine production among the distinct T cell functional compartments, monocyte subpopulations and mDCs were evaluated. hAME displayed an anti-proliferative effect and decreased the frequency of T cells producing tumor necrosis factor (TNF)α, interferon (IFN)γ and interleukin (IL)-2, for all T cell functional compartments. The frequency of IL-17 and IL-9-producing T cells was also reduced. The inhibition of mRNA expression of granzyme B, perforin and NKG2D by CD8 T cells and γδ T cells and the augment of FoxP3 and IL-10 in CD4 T cells and IL-10 in regulatory T cells were also observed. Furthermore, hAME inhibited IFNγ-induced protein (IP)-10 expression by classical and non-classical monocytes, without hampering the production of TNFα and IL-6 by monocytes and mDCs. These results suggest that hAME exerts an anti-inflammatory effect on T cells, still at a different extent for distinct T cell functional compartments.

Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreasdevelopment.