Analysis 2.2. Comparison 2 Calcium channel blockers compared with any other tocolytic agent (subgrouped by other tocolytic), Outcome 2 Very preterm birth (before completion of 34 weeks of gestation

Analysis 2.2. Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 2 Stillbirth. i Prophylactic antibiotics for inhibiting preterm labour with intact membranes (Review)

No abstract

Analysis 2.3. Comparison 2 Any antibiotic compared with placebo or no antibiotic (subgrouped by timing of induction of labour), Outcome 3 Maternal infectious morbidity (chorioamnionitis and/or endometritis).. .. .. .. Analysis 2.4. Comparison 2 Any antibiotic compared with placebo or no antibiotic (subgrouped by timing of induction of labour), Outcome 4 Stillbirth.

Background: Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. Methods: We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth.

SummaryThe ability of antigens to elicit immune responses depends upon their initial recognition, uptake, processing and presentation by dendritic cells. This fact has been recognized by many workers and dendritic cells are now regarded as natural 'adjuvants' in the business of vaccine design. One way of persuading dendritic cells to become interested in foreign material is to decorate it with lipid moieties found in bacteria. This approach has been used in the context of synthetic peptide-based immunogens and depending on the nature of the epitopes included, can provide highly immunogenic structures capable of eliciting antibody or cytotoxic T cell responses. In this paper we describe the results of experiments in which the stimulatory effects of peptide-based vaccine candidates on human dendritic cells are examined. Our findings indicate that lipidated structures comprising vaccine target sequences of viral origin coupled to the synthetic lipid groups of bacteria are able to induce the maturation of dendritic cells, as measured by the expression of cell surface MHC class II molecules.

We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes of HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens that also included lipid moieties and helper T (T h ) cell epitopes. Mice inoculated with these polyepitopes generated strong antibody responses. Antibody titers were highest in mice inoculated with polyepitope immunogens which contained the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). Antisera were tested for their potential to neutralize HCV by 3 currently available assays. Antibodies elicited in mice by the polyepitope-based vaccine candidates were able to (1) bind to E2 expressed on the surface of E1/E2-transfected human embryonic kidney (HEK) 293T cells, (2) H epatitis C virus (HCV) is a human pathogen that has major global significance. It is estimated that 170 million people worldwide and more than 10% of the population in some countries are infected with HCV. 1 A range of illnesses have been associated with HCV including acute and chronic hepatitis, cirrhosis of the liver, and HCC. Hepatitis C infection is now the leading indication for liver transplantation in countries such as the United States. In the absence of a vaccine, treatment is confined to the use of the combination of interferon-␣ and pegylated interferon-␣ together with the antiviral drug ribavirin. [2][3][4][5] The development of a vaccine against HCV could prevent HCV-associated diseases. However, there are 2 major impediments to the development of a HCV vaccine: the vast diversity of viral genotypes and quasispecies and the complex nature of the immune response required to clear infection. Antibodies directed to epitopes in the viral glycoprotein E2 (including HVR1) are neutralizing. [6][7][8][9][10][11][12][13][14] Further evidence supporting the protective role of neutralizing antibody was recently highlighted by the demonstration of the presence of neutralizing antibodies in immune globulin prepared from anti-HCV serum. 13 This immune globulin protected chimpanzees from infection with HCV genotypes 1a and 2a, 13 strengthening the argument that neutralizing antibodies can be cross-protective. In addition, it has been shown that it is possible to prevent entry of retroviral particles pseudotyped with the

The genetic deletion of catechol O-methyltransferase (COMT) in mice produces a preeclampsia-like phenotype, with mice exhibiting hypertension, proteinuria, and histological changes, consistent with human pathological features. 2-Methoxyoestradiol, a metabolite of COMT, increases human trophoblast invasiveness in vitro under hypoxic conditions, providing further support that decreased COMT expression may have a role in preeclampsia. However, evidence confirming decreased COMT expression in human disease has been limited to small studies of placentas obtained from cases of term preeclampsia. We examined COMT expression in placentas obtained from healthy term pregnancies (n = 14), preterm normotensive pregnancies (n = 8), and pregnancies complicated by severe preterm preeclampsia (delivery at < 34 weeks' gestation; n = 22). Among our preeclamptic cohort were 10 pregnancies further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets); and one pregnancy complicated by an eclamptic seizure. COMT expression was analyzed by RT-PCR, Western analysis, and IHC. COMT was mainly expressed in the syncytiotrophoblast. We did not find a significant difference in placental COMT expression in severe preeclampsia compared with either term or preterm normotensive cohorts. Our results suggest that severe preeclampsia may not be associated with a decrease in placental COMT expression.