Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

"Copyright: © 2015 Madhukaran, Kishore, Jamil, Teo, Choolani and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms."C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation

Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome

INTRODUCTION: Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but is associated with a small risk of miscarriage. Meanwhile, noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS that removes the risk of miscarriage, but confers a small risk of false-positive and false-negative results. Their implementations into clinical practice require an understanding of stakeholder preferences. METHODS: A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes (accuracy, time of results, risk of miscarriage and amount of information provided) were assessed, and conditional logit regression was used to analyse data. Data on demographics and ranked preferences for test attributes were collected, and a direct choice between NIPT, IPD or neither test was given. RESULTS: Women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice between NIPT, IPD or neither test, women aged over 35 years, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT than IPD. Chinese women preferred NIPT whereas Indian women preferred IPD. CONCLUSION: Our data highlight the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non-biased counselling

Factors associated with mobile health information seeking among Singaporean women

This study examined effects of age and social psychological factors on women’s willingness to be mobile health information seekers. A national survey of 1,878 Singaporean women was conducted to obtain information on women’s mobile phone usage, experiences of health information seeking, and appraisals of using mobile phones to seek health information. Results showed that young, middle-aged, and older women exhibited distinct mobile phone usage behaviors, health information-seeking patterns, and assessments of mobile health information seeking. Factors that accounted for their mobile information-seeking intention also varied. Data reported in this study provide insights into mobile health interventions in the future

A comparison of intrauterine haemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassaemia in a HbbTh3/+ murine model

Major haemoglobinopathies place tremendous strain on global resources. Intrauterine haemopoietic cell (IUHCT) and gene (IUGT) therapies can potentially reduce perinatal morbidities with greater efficacy than postnatal therapy alone. We performed both procedures in the thalassaemic HbbTh3/+ murine model. Intraperitoneal delivery of coisogenic cells at E13-14 produced dose-dependent chimerism. High-dose adult bone marrow (BM) cells maintained 0.2-3.1% chimerism over ~24 weeks and treated heterozygotes demonstrated higher chimerism than wild-type pups (1.6 vs. 0.7%). Fetal liver cells produced higher chimerism compared to adult BM when transplanted at the same doses, maintaining 1.8-2.4% chimerism over ~32 weeks. We boosted transplanted mice postnatally with adult BM cells following busulfan conditioning. Engraftment was maintained at >1% only in recipients which were chimeric prior to boosting. IUHCT-treated non-chimeras and non-IUHCT mice showed micro- or no chimerism. Additional fludarabine treatment produced higher chimerism than busulfan alone. Engraftment was more effective following higher starting chimerism prior to boosting and in heterozygotes. Chimeric heterozygotes expressed 2.2-15.1% donor cells with eventual decline at 24 weeks (vs. <1% in non-chimeras) and demonstrated improved haematological indices and smaller spleens compared to untreated heterozygotes. Intravenous delivery of GLOBE lentiviral-vector expressing HBB (human β-globin) resulted in vector concentration of 0.001-0.6 copies/cell. Most haematological indices were higher in treated than untreated heterozygotes including haemoglobin and mean corpuscular volume, though still lower than in wild-types. Thus both direct IUGT and IUHCT strategies can be used to achieve haematological improvement but require further dose optimisation. IUHCT will be useful combined with postnatal transplantation to further enhance engraftment

El principio de no vinculación de cláusulas abusivas conforme a la reciente jurisprudencia del TJUE

The controverted floor clauses have now turned out to be a legal issue of great interest in the sphere of abusive clauses and consumer protection. The European Court of Justice has expressed its view recently over these clauses and has concluded that the Spanish State cannot modulate the nulity effects of an abusive clause as it goes a gainst the principle of non - binding and deterrant effect of the European Council’s 93/13/CEE Directive that was emitted the 5th of April 1993, on abusive clauses in contracts celebranted with consumers. With this, the European Council has come to establish the obligation of providing consumers a complete restitution of the amounts of money that were unfairly paid by the customers. Without a doubt, this judicial sentencia has highlighted the long way towards the European Integration process that we still have to go through, driving forward new and specific policies a protection that is not only real, but equal to any European Consume

Microfluidic Blood Cell Sorting: Now and Beyond

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106971/1/smll201302907.pd

Quantitative Proteomics Analysis of Maternal Plasma in Down Syndrome Pregnancies Using Isobaric Tagging Reagent (iTRAQ)

Currently no specific biomarkers exist for the screening of pregnancies at risk for down syndrome (DS). Since a quantitative proteomic approach with isobaric labelling (iTRAQ) has recently been suggested to be highly suitable for the discovery of novel plasma biomarkers, we have now used this method to examine for potential quantitative changes in the plasma proteome of the pregnancies bearing DS fetuses in comparison to normal healthy babies. In our study, we used plasma from six women with DS pregnancies and six with uncomplicated pregnancies care were taken to match cases and controls for gestational and maternal age, as these could be a confounder. In our quantitative proteomics analysis we were able to detect 178 proteins using iTRAQ labelling in conjunction with 4800 MALDI TOF/TOF. Amongst these we observed changes in βHCG, a known screening marker for DS, indicating that our assay was functional. We found a number of elevated proteins Ig lambda chain C region, serum amyloid P-component, amyloid beta A4, and under expressed proteins like gamma-actin and titin in DS pregnancies. These proteins are also found in the sera of patients with Alzheimer disease, which share similar pathologies of DS. Our study therefore indicates that the iTRAQ labelling approach may be indeed useful for the detection of novel biomarkers

Does an educational video for aneuploidy screening improve informed choice among pregnant women? A randomised controlled trial

BACKGROUND: Poor knowledge and the lack of deliberation have been cited as reasons for women making uninformed choices about aneuploidy screening. Adequate pre-test counselling is of particular importance where non-invasive prenatal screening (NIPS) is being increasingly offered as a primary screening test. DESIGN: Women attending the antenatal clinic with a singleton pregnancy below 14 weeks were randomised to receive routine counselling or the intervention-a 16-min educational video on aneuploidy screening before their consult. The primary outcome, rate of informed choice, was assessed using an adapted multidimensional measure of informed choice questionnaire, where informed choice was defined as good knowledge and value-consistent behaviour. Secondary outcomes included informed choice with deliberation, decisional conflict and anxiety. RESULTS: Two hundred and eighty-six women were recruited. 69.8% of women in the intervention group made an informed choice compared with 53.6% in the control group (Risk Ratio [RR] 1.30, p = 0.014). A significantly higher number of women in the intervention group had good knowledge compared to controls (81% vs. 60.9%; RR 1.33, p = 0.001). Decisional conflict did not differ between groups, but women in the intervention group had higher anxiety scores (p < 0.001). CONCLUSION: The study intervention was effective in helping women make informed choice. Qualitative studies to determine the reason for increased anxiety are needed. TRIAL REGISTRATION: Trial registry: ClinicalTrials.gov; Identifier: NCT05492981