Obstetrical aspects in congenital ichtyosis

We present a case of congenital ichthyosis because obstetrical literature is scarce and most obstetricians could need a reminder and update. Congenital ichthyosis (CI) comprises a variety of skin disorders characterised by abnormal keratinization of the epidermis, which are mostly transmitted in an autosomal recessive manner. This condition is rare (seven per million people) with various clinical neonatal expressions and diversified prognosis, from self-healing to lethal. Even less severe phenotypes have significant associated morbidity and mortality. CI babies are often born prematurely and are at highest risk for complications during the postnatal period .CI, while fairly rare, is a condition well described in the literature, mainly from the neonatal point of view. We describe a case in which congenital ichthyosis was diagnosed after birth, and summarise the present literature with particular attention on obstetric implications as the prenatal diagnosis, genetic and ultrasound testing, perinatal complications and care for future pregnancies

Can the cerebroplacental ratio (CPR) predict intrapartum fetal compromise? : a prospective observational study

Objective: To investigate the potential clinical use of serial fetal CPR measurements during the last month of pregnancy for the prediction of adverse perinatal outcome in unselected low-risk pregnancies. Methods: A multicenter prospective observational cohort study in 315 consecutively recruited low-risk pregnancies. All eligible pregnancies underwent serial sonographic evaluation of fetal weight and Doppler indices at two week intervals, from 36 weeks gestation until delivery. Data were converted into centiles correcting for gestational age. These data were not available for the obstetrical team and hence, could not influence management decisions. Primary outcomes were operative delivery for presumed fetal compromise and a composite neonatal outcome (arterial cord Ph 90th centile). Results: Three hundred fifteen women were recruited in this study. We ecxluded 32 pregnancies because of small for gestational age babies (SGA), leaving 293 women and 583 CPR values for data-analysis. There were 85 (27%) adverse neonatal outcomes and 29 patients (9%) underwent operative delivery for presumed fetal compromise. Both primary and secondary outcomes were not significant different between the different CPR groups. Furthermore, we examined if individual serial CPR measurements could predict adverse outcome and found no linear correlation between repeated measurements of CPR and adverse outcomes. Conclusion: Our study shows that routine serial screening by CPR measurements provides poor prediction for adverse perinatal outcome in uncomplicated pregnancies

How an extended perinatal audit may improve perinatal policy

Objective: A perinatal audit has the intention of quality of care improvement based on analysis of perinatal death, with our without analysis of maternal morbidity and/or mortality. Additional analysis of cases of intrapartum asphyxia could provide more insight into ways to improve quality of perinatal care. Methods: Analysis of cases of perinatal death and asphyxia in Jan Yperman Hospital, Ieper, Belgium, in 2012. Results: Three perinatal deaths occurred, none were preventable. Nineteen cases of proven metabolic acidosis have been identified. Three cases are considered possibly preventable, four cases are considered preventable. In three (possibly) preventable cases, foetal monitoring was absent during the active second stage of labour. In two preventable cases, intervention following a significant ST event in the second stage of labour was delayed. In one case intervention was delayed in the first stage of labour, while in another, indicated operative delivery in the second stage was not conducted. Conclusions: Integrating intrapartum asphyxia in the perinatal audit gives an opportunity to identify and eliminate weak points in the perinatal care chain, thereby optimizing quality of care. Lessons learned from our internal audit are the value of foetal monitoring and adequate action on significant ST events during second stage of labour

The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)

A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through "domestication"-the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse transposition and instead acquire novel functions for their hosts. In Arabidopsis, ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN 1 (ALP1) arose by domestication of the nuclease component of Harbinger class TE and acquired a new function as a component of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a histone H3K27me3 methyltransferase involved in regulation of host genes and in some cases TE. It was not clear how ALP1 associated with PRC2, nor what the functional consequence was. Here, we identify ALP2 genetically as a suppressor of Polycomb-group (PcG) mutant phenotypes and show that it arose from the second, DNA binding component of Harbinger transposases. Molecular analysis of PcG compromised backgrounds reveals that ALP genes oppose silencing and H3K27me3 deposition at key PcG target genes. Proteomic analysis reveals that ALP1 and ALP2 are components of a variant PRC2 complex that contains the four core components but lacks plant-specific accessory components such as the H3K27me3 reader LIKE HETEROCHROMATION PROTEIN 1 (LHP1). We show that the N-terminus of ALP2 interacts directly with ALP1, whereas the C-terminus of ALP2 interacts with MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a core component of PRC2. Proteomic analysis reveals that in alp2 mutant backgrounds ALP1 protein no longer associates with PRC2, consistent with a role for ALP2 in recruitment of ALP1. We suggest that the propensity of Harbinger TE to insert in gene-rich regions of the genome, together with the modular two component nature of their transposases, has predisposed them for domestication and incorporation into chromatin modifying complexes

A Novel Soluble Immune-Type Receptor (SITR) in Teleost Fish: Carp SITR Is Involved in the Nitric Oxide-Mediated Response to a Protozoan Parasite

Background- The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways. Methodology/Principal Findings - Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production. Conclusion/Significance - We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Correlation analysis for energy losses, waiting times and durations of type I edge-localized modes in the Joint European Torus

Several important ELM control techniques are in large part motivated by the empirically observed inverse relationship between average ELM energy loss and ELM frequency in a plasma. However, to ensure a reliable effect on the energy released by the ELMs, it is important that this relation is verified for individual ELM events. Therefore, in this work the relation between ELM energy loss (W-ELM) and waiting time (Delta t(ELM)) is investigated for individual ELMs in a set of ITER-like wall plasmas in JET. A comparison is made with the results from a set of carbon-wall and nitrogen-seeded ITER-like wall JET plasmas. It is found that the correlation between W-ELM and Delta t(ELM) for individual ELMs varies from strongly positive to zero. Furthermore, the effect of the extended collapse phase often accompanying ELMs from unseeded JET ILW plasmas and referred to as the slow transport event (STE) is studied on the distribution of ELM durations, and on the correlation between W-ELM and Delta t(ELM). A high correlation between W-ELM and Delta t(ELM), comparable to CW plasmas is only found in nitrogen-seeded ILW plasmas. Finally, a regression analysis is performed using plasma engineering parameters as predictors for determining the region of the plasma operational space with a high correlation between W-ELM and Delta t(ELM)