Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors.

Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells.

Infectious complications following endoscopic retrograde cholangiopancreatography: an automated surveillance system for detecting postprocedure bacteremia.

We have developed an automated surveillance system to detect bloodstream infection (BSI) occurring after endoscopic retrograde cholangiopancreatography (ERCP). We retrospectively applied this automated surveillance tool to all patients who underwent ERCP at out institution between July 2004 and April 2006 to determine the baseline rates of BSI after ERCP and identify the epidemiology of the pathogens. A total of 2052 ERCPs were performed during the study period; 46 BSIs occurred within 30 days after ERCP (overall rate of post-ERCP BSI, 2.

Kinetics and thermodynamics make different contributions to RNA folding in vitro and in yeast.

RNAs somehow adopt specific functional structures despite the capacity to form alternative nonfunctional structures with similar stabilities. We analyzed RNA assembly during transcription in vitro and in yeast using hairpin ribozyme self-cleavage to assess partitioning between functional ribozyme structures and nonfunctional stem loops. Complementary insertions located upstream of the ribozyme inhibited ribozyme assembly more than downstream insertions during transcription in vitro, consistent with a sequential folding model in which the outcome is determined by the structure that forms first.

Evidence against a direct role for the Upf proteins in frameshifting or nonsense codon readthrough.

The Upf proteins are essential for nonsense-mediated mRNA decay (NMD). They have also been implicated in the modulation of translational fidelity at viral frameshift signals and premature termination codons. How these factors function in both mRNA turnover and translational control remains unclear.

An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae.

A new in vivo assay system has been developed to study programmed frameshifting in the yeast Saccharomyces cerevisiae. Frameshift signals are inserted between the Renilla and firefly luciferase reporter genes contained in a yeast expression vector and the two activities are directly measured from cell lysates in one tube. Similar to other bicistronic reporter systems, this one allows the efficient estimation of recoding efficiency by comparison of the normalized activity ratios from each luciferase protein.

Decreased peptidyltransferase activity correlates with increased programmed -1 ribosomal frameshifting and viral maintenance defects in the yeast Saccharomyces cerevisiae.

Increased efficiencies of programmed -1 ribosomal frameshifting in yeast cells expressing mutant forms of ribosomal protein L3 are unable to maintain the dsRNA "Killer" virus. Here we demonstrate that changes in frameshifting and virus maintenance in these mutants correlates with decreased peptidyltransferase activities. The mutants did not affect Ty1-directed programmed +1 ribosomal frameshifting or nonsense-mediated mRNA decay.

The 9-A solution: how mRNA pseudoknots promote efficient programmed -1 ribosomal frameshifting.

There is something special about mRNA pseudoknots that allows them to elicit efficient levels of programmed -1 ribosomal frameshifting. Here, we present a synthesis of recent crystallographic, molecular, biochemical, and genetic studies to explain this property. Movement of 9 A by the anticodon loop of the aminoacyl-tRNA at the accommodation step normally pulls the downstream mRNA a similar distance along with it.

Cerclage and cervical insufficiency: an evidence-based analysis.

Since the cervical cerclage was introduced to clinical practice 50 years ago, the efficacy of the operation has not been established by evidence-based standards for many indications. Serious flaws in the methods employed to study the safety and efficacy of cerclage have led to confusion and misuse of the operation, although some investigators maintain that current standards make randomized clinical trials of this traditional surgery unethical. At present, five randomized clinical trials have offered significant information about elective cerclages performed for historical indications, and the expected neonatal survival rate with properly selected elective cerclages is around 87%.

An "integrated model" of programmed ribosomal frameshifting.

Many viral mRNAs, including those of HIV-1, can make translating ribosomes change reading frame. Altering the efficiencies of programmed ribosomal frameshift (PRF) inhibits viral propagation. As a new target for potential antiviral agents, it is therefore important to understand how PRF is controlled.

New targets for antivirals: the ribosomal A-site and the factors that interact with it.

Many viruses use programmed -1 ribosomal frameshifting to ensure the correct ratio of viral structural to enzymatic proteins. Alteration of frameshift efficiencies changes these ratios, in turn inhibiting viral particle assembly and virus propagation. Previous studies determined that anisomycin, a peptidyl transferase inhibitor, specifically inhibited -1 frameshifting and the ability of yeast cells to propagate the L-A and M(1) dsRNA viruses (J.

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women.

Objective: To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy.

Methods: Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.

Risk factors and outcome of varicella-zoster virus pneumonia in pregnant women.

To determine the factors associated with an increased risk of developing varicella-zoster virus (VZV) pneumonia during pregnancy, a case-control analysis was done in which 18 pregnant women with VZV pneumonia were compared with 72 matched control subjects. VZV infection was identified clinically, and VZV pneumonia was diagnosed by dyspnea and findings on chest radiographs. Of 347 pregnant women with VZV infection, 18 (5.

Exposure to interparental conflict and children's adjustment and physical health: the moderating role of vagal tone.

Physiological regulation, as indexed by baseline vagal tone and delta vagal tone (the change in vagal tone during an attention-demanding or challenging task), was examined as a moderator in the relations between exposure to verbal and physical parental marital conflict and children's adjustment and physical health. Higher vagal tone was posited to serve a protective function (i.e.

Appraisals of marital conflict and children's adjustment, health, and physiological reactivity.

Children's appraisals of marital conflict were examined as moderators and mediators of conflict and children's adjustment, physical health, and physiological reactivity. Mothers completed measures of marital conflict and children's adjustment and physical health, and elementary school children provided information on their parents' marital conflict, appraisals of perceived threat and self-blame in relation to parents' conflicts, and their internalizing symptomatology. Children's heart rate, systolic and diastolic blood pressure, and skin conductance response and level were examined during both a baseline and an interadult argument.

A novel X chromosome-linked genetic cause of recurrent spontaneous abortion.

Objective: Unexplained recurrent spontaneous abortion is a common women's health problem that affects approximately 1 of every 200 women who wish to have children. It has long been assumed that a large proportion of recurrent spontaneous abortion results from genetic problems, but no causative genes have been identified to date. Here, we tested the hypothesis that a subset of women with recurrent spontaneous abortion are carriers of X-linked recessive disorders that result in the loss of male pregnancies.

Ty1 retrotransposition and programmed +1 ribosomal frameshifting require the integrity of the protein synthetic translocation step.

Programmed ribosomal frameshifting is utilized by a number of RNA viruses to ensure the correct ratio of viral structural to enzymatic proteins for viral particle assembly. Altering frameshifting efficiencies upsets this ratio, inhibiting virus propagation. Two yeast viruses that induce host cell ribosomes to shift translational reading frame were used as tools to explore the interactions between viruses and host cellular protein synthetic machinery.

Employing the clinical service unit model.

Duke University Hospital has instituted a decision tool that enables administrators and medical directors to manage from both the operational (departmental) perspective as well as from the patient population perspective. The tool automates routine reporting, aligns business information with a new, cross-functional management structure, and provides a focus for improvement opportunities.

A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.

Objective: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven.

Serologic and virologic evidence for frequent intrauterine transmission of human parvovirus B19 with a primary maternal infection during pregnancy.

Objective: To define the intrauterine viral transmission rate during primary maternal parvovirus B19 infection and identify factors that may influence this rate.

Methods: Forty-three pregnant women at two medical centers were identified with a primary B19 infection and followed to delivery. At delivery maternal and infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR testing.

Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms.

Objective: To assess the risk of maternal parvovirus B19 infection from exposure to various sources and the fetal morbidity of those infections.

Methods: We obtained demographic and occupational information about pregnant women exposed to sources of B19 and about the nature and duration of the exposures. We performed serologic testing 10-14 days after exposure using an indirect capture enzyme-linked immunosorbent assay.

Low-dose aspirin and prednisone treatment of pregnancy loss caused by lupus anticoagulants.

The objective of this study was to ascertain the complications and the efficacy of low-dose aspirin (LDA) and prednisone therapy in women with pregnancy loss and "lupus anticoagulants" (LAC). During the period 1985 to 1993, 255 patients with two or more pregnancy losses (RPL) were tested for LAC with an activated partial thromboplastin time (aPTT) and a tissue thromboplastin inhibition index (TTI, normal value < 1.3).

Prevention of neonatal group B streptococcal infection.

The optimal clinical strategy to prevent neonatal group B streptococcal infection has not been established. The Maternal-Fetal Medicine Units Network assessed the feasibility of a randomized clinical trial to compare the effectiveness of two methods of prevention of streptococcal infection. The attack rates of early-onset group B streptococcal disease were estimated for the following: 1) a hypothetical program of universal prenatal screening and selective intrapartum chemoprophylaxis, and 2) a hypothetical program of selective intrapartum chemoprophylaxis based on clinical risk factors.

Association between familial autoimmune diseases and recurrent spontaneous abortions.

Problem: To examine the aggregation of autoimmune disease in the families of women experiencing recurrent spontaneous abortions.

Method: The 95 participants in this case-control study were recruited from Magee Womens Hospital, Pittsburgh, Pennsylvania from June 1988 to May 1991. The women having recurrent spontaneous abortions (N = 45) reported at least three early fetal losses, and the controls (N = 50) reported a minimum of three pregnancies with at least two live births and no more than one induced or involuntary pregnancy loss.