The IRELAnD study-investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial.

Background: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials.

Objective: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus.

Study Design: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers.

Glycosylated haemoglobin as an indicator of diabetes control in pregnancy: A 10-year review of the relationship between HbA1c trends and delivery outcome in type I and type II diabetes.

Background: Pregestational diabetes mellitus (PGDM) confers an increased risk of adverse maternal and neonatal outcomes [1,2]. Glycaemic control in the medium and long term is commonly evaluated by examining glycosylated haemoglobin (HbA1c) levels. However, the value of HbA1c in pregnancy may be diminished by increased level of red cell turnover characteristic of pregnancy [3,4].

Neonatal polycystic kidney disease: a novel variant.

Polycystic kidney disease (PKD) is a condition typified by multiple renal cysts and renal enlargement. Classification is usually determined by mode of inheritance-autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD). ARPKD frequently presents in fetal life, but here we report a rare case of a family with two siblings diagnosed with ADPKD manifesting in utero with novel genetic findings.

PCR vs karyotype for CVS and amniocentesis-the experience at one tertiary fetal medicine unit.

Purpose: Despite the rise of non-invasive screening tests for fetal aneuploidy, invasive testing during pregnancy remains the definitive diagnostic tool for fetal genetic anomalies. Results are rapidly available with polymerase chain reaction (PCR) tests, but cases have been reported whereby initial results were not confirmed after pregnancy termination and the fetal karyotype was ultimately normal. We sought to examine the potential discordance between PCR and karyotype for fetal aneuploidy.

The Role of Aspirin for Preeclampsia Prevention in Women with Diabetes.

Purpose Of Review: A diagnosis of type I or type 2 diabetes confers heightened risk for virtually every obstetric and perinatal complication, with the incidence of superimposed preeclampsia representing a particularly high-risk scenario. Over the past three decades, studies have investigated the role of aspirin in preeclampsia prevention, yielding some promising results for certain at-risk groups, yet unconvincing evidence of benefit among women with pre-pregnancy diabetes. The purpose of this review is to present the current evidence base for aspirin use in pregnancy as a means of mitigating preeclampsia risk in the setting of pregestational type I or type 2 diabetes.

Investigating the role of early low-dose aspirin in diabetes: A phase III multicentre double-blinded placebo-controlled randomised trial of aspirin therapy initiated in the first trimester of diabetes pregnancy.

Background: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres.

Defining the upper limit of the second stage of labor in nulliparous patients.

Background: Increased duration of the second stage of labor provides clinical challenges in decision-making regarding the optimal mode of delivery that minimizes maternal and neonatal morbidity.

Objective: In a large cohort of uncomplicated nulliparous singleton cephalic labors, we sought to examine the effect of increasing duration of second stage on delivery and perinatal outcome.

Study Design: The GENESIS Study recruited 2336 nulliparous patients with vertex presentation in a prospective double-blinded study to examine prenatal and intrapartum predictors of delivery.

Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion.

Previously, we reported that treatment of cells with sphingomyelinase inhibits human immunodeficiency virus type 1 (HIV-1) entry. Here, we determined by measuring fluorescence recovery after photobleaching that the lateral diffusion of CD4 decreased 4-fold following sphingomyelinase treatment, while the effective diffusion rate of CCR5 remained unchanged. Notably, sphingomyelinase treatment of cells did not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis.

Exposure of the membrane-proximal external region of HIV-1 gp41 in the course of HIV-1 envelope glycoprotein-mediated fusion.

The membrane-proximal external region (MPER) of HIV-1 gp41 is highly conserved and critical for the fusogenic ability of the virus. However, little is known about the activity of this region in the context of viral fusion. In this study we investigate the temporal exposure of MPER during the course of HIV-1 Env-mediated fusion.

Fenretinide inhibits HIV infection by promoting viral endocytosis.

HIV fusion is mediated by the sequential interaction of the viral envelope glycoprotein with cellular receptors at the plasma membrane. We have previously reported that the upregulation of cellular ceramide levels following fenretinide treatment inhibits HIV fusion. As ceramide facilitates the internalization of a variety of microbes, we hypothesized that it may also promote the engulfment of HIV virions.

Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection.

Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 microg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites.

Ceramide, a target for antiretroviral therapy.

Studies of ceramide metabolism and function in a wide range of biological processes have revealed a role for this lipid in regulating key cellular responses. Our research on the role of sphingolipids in HIV entry has led to the hypothesis that modulation of ceramide levels in target cells affects their susceptibility to HIV infection by rearranging HIV receptors. Cellular ceramide levels were modulated by application of pharmacological agents such as N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide), by treatment with sphingomyelinase (Smase), or by exogenous addition of long-chain ceramide, and determined after metabolic incorporation of [3H]sphingosine.

An inhibitor of glycosphingolipid metabolism blocks HIV-1 infection of primary T-cells.

Objective: HIV-1 uses CD4 and chemokine receptors to enter cells. However, other target membrane components may also be involved. This study examines the role of glycosphingolipids (GSL) in HIV-1 entry into primary lymphocytes and its modulation by an inhibitor of GSL biosynthesis.

The HIV Env-mediated fusion reaction.

The current general model of HIV viral entry involves the binding of the trimeric viral envelope glycoprotein gp120/gp41 to cell surface receptor CD4 and chemokine co-receptor CXCR4 or CCR5, which triggers conformational changes in the envelope proteins. Gp120 then dissociates from gp41, allowing for the fusion peptide to be inserted into the target membrane and the pre-hairpin configuration of the ectodomain to form. The C-terminal heptad repeat region and the leucine/isoleucine zipper region then form the thermostable six-helix coiled-coil, which drives the membrane merger and eventual fusion.

Antigenic properties of the human immunodeficiency virus transmembrane glycoprotein during cell-cell fusion.

Human immunodeficiency virus (HIV) entry is triggered by interactions between a pair of heptad repeats in the gp41 ectodomain, which convert a prehairpin gp41 trimer into a fusogenic three-hairpin bundle. Here we examined the disposition and antigenic nature of these structures during the HIV-mediated fusion of HeLa cells expressing either HIV(HXB2) envelope (Env cells) or CXCR4 and CD4 (target cells). Cell-cell fusion, indicated by cytoplasmic dye transfer, was allowed to progress for various lengths of time and then arrested.