Antepartum fetal health

Delivery of a healthy full term baby following an uneventful antenatal period occurs in the majority of pregnancies. These are classified as a low-risk pregnancy group. There are, however, some pregnancies that are complicated due to maternal or fetal disease that can increase the risk of perinatal morbidity and mortality. This is classified as a high-risk group. The aim of fetal surveillance is to identify these threatened fetuses with the prospect of altering the timing of delivery to prevent the worst outcome, stillbirth. This article looks at the tools available to assess antenatal fetal health in all pregnancies and their ability to identify the at-risk pregnancies that require extra surveillance to improve outcomes. This article does not address fetal surveillance during labour

Changes in Left Atrial Appendage Dimensions Following Volume Loading During Percutaneous Left Atrial Appendage Closure.

OBJECTIVES: This study sought to determine whether volume loading alters the left atrial appendage (LAA) dimensions in patients undergoing percutaneous LAA closure. BACKGROUND: Percutaneous LAA closure is increasingly performed in patients with atrial fibrillation and contraindications to anticoagulation, to lower their stroke and systemic embolism risk. The safety and efficacy of LAA closure relies on accurate device sizing, which necessitates accurate measurement of LAA dimensions. LAA size may change with volume status, and because patients are fasting for these procedures, intraprocedural measurements may not be representative of true LAA size. METHODS: Thirty-one consecutive patients undergoing percutaneous LAA closure who received volume loading during the procedure were included in this study. After an overnight fast and induction of general anesthesia, patients had their LAA dimensions (orifice and depth) measured by transesophageal echocardiography before and after 500 to 1,000 ml of intravenous normal saline, aiming for a left atrial pressure >12 mm Hg. RESULTS: Successful implantation of LAA closure device was achieved in all patients. The average orifice size of the LAA at baseline was 20.5 mm at 90 degrees , and 22.5 mm at 135 degrees . Following volume loading, the average orifice size of the LAA increased to 22.5 mm at 90 degrees , and 23.5 mm at 135 degrees . The average increase in orifice was 1.9 mm (p < 0.0001). The depth of the LAA also increased by an average of 2.5 mm after volume loading (p < 0.0001). CONCLUSIONS: Intraprocedural volume loading with saline increased the LAA orifice and depth dimensions during LAA closure. Operators should consider optimizing the left atrial pressure with volume loading before final device sizing

Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes

Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP:</p

A <em>trans</em>-acting protein effect causes severe eye malformation in the <em>mp </em>mouse

Mp is an irradiation-induced mouse mutation associated with microphthalmia, micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1(Mp)) mRNA has a frameshift and early stop codon resulting in nonsense mediated decay. Homozygous deletions of Isoc1 do not support a significant developmental role for this gene. The Fbn2-Isoc1 fusion gene (Fbn2 (Mp)) predicted protein consists of the N-terminal Fibrillin-2 (amino acids 1-2646, exons 1-62) lacking the C-terminal furin-cleavage site with a short out-of-frame extension encoded by the final exon of Isoc1. The Mp limb phenotype is consistent with that reported in Fbn2 null embryos. However, severe eye malformations, a defining feature of Mp, are not seen in Fbn2 null animals. Fibrillin-2(Mp) forms large fibrillar structures within the rough endoplasmic reticulum (rER) associated with an unfolded protein response and quantitative mass spectrometry shows a generalised defect in protein secretion in conditioned media from mutant cells. In the embryonic eye Fbn2 is expressed within the peripheral ciliary margin (CM). Mp embryos show reduced canonical Wnt-signalling in the CM - known to be essential for ciliary body development - and show subsequent aplasia of CM-derived structures. We propose that the Mp "worse-than-null" eye phenotype plausibly results from a failure in normal trafficking of proteins that are co-expressed with Fbn2 within the CM. The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing