Structural analysis of monomeric retroviral reverse transcriptase in complex with an RNA/DNA hybrid.

A key step in proliferation of retroviruses is the conversion of their RNA genome to double-stranded DNA, a process catalysed by multifunctional reverse transcriptases (RTs). Dimeric and monomeric RTs have been described, the latter exemplified by the enzyme of Moloney murine leukaemia virus. However, structural information is lacking that describes the substrate binding mechanism for a monomeric RT.

Modulation of porcine endogenous retroviruses (PERVs) expression in vitro by shRNA in the presence of cyclosporine A and dexamethasone.

Background: Despite the fact that the risk of Porcine Endogenous Retroviruses (PERV) infection and propagation in human recipients is extremely low, such an event cannot be completely ruled out, especially in immunosuppressed patients. Therefore, the aim of this study was to analyze the expression of PERVs in vitro in the presence of immunosuppression agents: cyclosporine A (CsA), and dexamethasone (DEX). We investigated the possible interactions between immunosuppression drugs, CsA and DEX, and the efficiency of anti-PERV RNAi.

Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria?

Objective: To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjögren's syndrome (SS) and to suggest modifications of the American-European Consensus Group (AECG) classification criteria.

Methods: We conducted a cross-sectional study in a prospective cohort of patients with suspected primary SS that was established between 2006 and 2011. The echostructure of the bilateral parotid and submandibular glands was graded from 0 to 4, and the gland size was measured; blood flow to the parotid gland was assessed using Doppler waveform analysis.

Incidence of venous thromboembolism in psychiatric units.

Introduction: Incidence and risk factors of venous thromboembolism (VTE) are well established in surgical and medical settings, but data in psychiatric units are lacking. The aim of this study was to estimate the incidence of VTE in hospitalized psychiatric patients, and to assess the risk factors for VTE in this specific population.

Materials And Methods: All consecutive adult patients, admitted for a psychiatric disorder for at least seven days in psychiatric units were considered for inclusion.

Tryptophan hydroxylase-1 regulates immune tolerance and inflammation.

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance. Here we report the novel finding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 deficiency breaks allograft tolerance, induces tumor remission, and intensifies neuroinflammation, respectively.

Lipid lowering drugs and the risk of recurrent venous thromboembolism.

Introduction: Several studies have suggested that statins may lower the risk of venous thromboembolism (VTE), whereas fibrates may increase this risk. However, no studies have evaluated whether lipid-lowering drugs (LLD) use was associated with the risk of VTE recurrence.

Materials And Methods: In a prospective cohort study, we followed-up all patients who had been treated for a first unprovoked VTE event in our centre.

Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma.

Purpose: Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population.

Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation.

Background: Malformations and mental retardation in the offspring of women with Phenylketonuria (PKU) can be prevented by maintaining maternal blood Phenylalanine (PHE) within a target range (120-300 μmol/L) through a PHE-restricted diet. In a former French study, a high and unexpected proportion of intra uterine growth retardation (IUGR) has been reported. Guidelines have been proposed to all French centres caring for maternal PKU since 2002.

Helicity discrimination in diaryl dichalcogenides generated by inclusion complexation with chiral hosts.

Inclusion complexation of diaryl dichalcogenides with either cholic acid or chiral diols results in their helicity discrimination and an induction of optical activity that can be detected by solid-state CD measurements.

Mast cells condition dendritic cells to mediate allograft tolerance.

Peripheral tolerance orchestrated by regulatory T cells, dendritic cells (DCs), and mast cells (MCs) has been studied in several models including skin allograft tolerance. We now define a role for MCs in controlling DC behavior ("conditioning") to facilitate tolerance. Under tolerant conditions, we show that MCs mediated a marked increase in tumor necrosis factor (TNFα)-dependent accumulation of graft-derived DCs in the dLN compared to nontolerant conditions.

Lipid parameters, lipid lowering drugs and the risk of venous thromboembolism.

Background: Besides their effects on atherogenesis, lipids and lipoproteins could contribute to the development of venous thromboembolism (VTE). This association has been investigated in a few studies with conflicting results.

Methods: Plasma levels of total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I and apolipoprotein B were measured in 467 patients with a first unprovoked VTE event diagnosed between May 2000 and December 2004 and in 467 age and sex matched controls.

The accuracy of noninvasive hemoglobin measurement by multiwavelength pulse oximetry after cardiac surgery.

Background: In March 2008, a new multiwavelength pulse oximeter, the Radical 7 (Rad7; Masimo Corp., Irvine, CA), was developed that offers noninvasive measurement of hemoglobin concentration. Accuracy has been established in healthy adults and some surgical patients, but not in cardiac surgery intensive care patients, a group at high risk of postoperative bleeding events and anemia in whom early diagnosis could improve management.

A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity.

It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation.

Prognostic value of fluorine-18 fluorodeoxyglucose positron-emission tomography imaging in patients with head and neck squamous cell carcinoma.

Background: High tumor uptake of fluorodeoxyglucose (FDG) is associated with an unfavorable outcome in patients with cancer. We evaluated FDG uptake as a prognostic factor in patients with head and neck squamous cell carcinoma.

Methods: Maximum standardized uptake values (SUVmax) of tumor, liver, and pulmonary artery were recorded.

Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia.

Objective: The pathogenesis and the outcome of Pseudomonas aeruginosa ventilator-acquired pneumonia depend on the virulence factors displayed by the bacteria as well as the host response. Thus, quorum sensing, lipopolysaccharide, and type 3 secretion system have each individually been shown to be important virulence systems in laboratory reference strains. However, the relative contribution of these three factors to the in vivo pathogenicity of clinically relevant strains has never been studied.

Diagnostic accuracy of ACR/EULAR 2010 criteria for rheumatoid arthritis in a 2-year cohort.

Objective: To evaluate the diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and 1987 ACR criteria for rheumatoid arthritis (RA), and the respective role of the algorithm and scoring of the ACR/EULAR.

Methods: In total, 270 patients with recent-onset arthritis of < 1 year duration were included prospectively between 1995 and 1997 and followed for 2 years. RA was defined as the combination, at completion of followup, of RA diagnosed by an office-based rheumatologist and treatment with a disease-modifying antirheumatic drug or glucocorticoid.

Impact of rotavirus vaccination on hospitalizations for rotavirus diarrhea: the IVANHOE study.

The aim of the IVANHOE study was to determine the real-world impact of the rotavirus vaccine, controlling for epidemic-to-epidemic variation in disease burden. A population-based prospective cohort study was conducted in Brest City and 7 suburban districts (CUB area), North-western Brittany, France (210,000 inhabitants; 5500 births per year). The vaccination program started in May 2007 for a 2-year period for all infants born in the Brest birth zone through pediatricians, public outpatient clinics and general practitioners.

Prognostic value of interim FDG PET/CT in Hodgkin's lymphoma patients treated with interim response-adapted strategy: comparison of International Harmonization Project (IHP), Gallamini and London criteria.

Purpose: Interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has shown to be an accurate predictor of prognosis in Hodgkin's lymphoma (HL). However, FDG PET response criteria are a matter of ongoing debate. The aim of this study was to confirm the prognostic value of interim PET/CT in HL patients treated with an interim response-adapted strategy and to compare the respective performances of different published criteria.

Clinical relevance of classification according to weaning difficulty.

Objective: To evaluate the clinical relevance of the weaning from mechanical ventilation classification system derived from the 2005 international consensus conference, in patients who receive mechanical ventilation for more than 48 hours, and evaluate its correlation with prognosis.

Methods: We conducted a retrospective cohort study in a 12-bed intensive care unit (ICU) in a teaching hospital. We included patients who required > 48 hours of mechanical ventilation and who passed a spontaneous breathing trial (SBT).

Effects of serotonin (5-HT)6 receptor ligands on responding for cocaine reward and seeking in rats.

The endogenous brain serotonin (5-HT) system is believed to have an important modulatory influence in mediating drug reward and seeking mechanisms. Data from preclinical behavioral studies have provided emerging evidence that 5-HT(6) receptors, among other 5-HT receptors, may play a significant role in the mechanisms of action of psychostimulant addicted drugs. The aim of the present study was to investigate whether the selective pharmacological blockade or activation of 5-HT(6) receptors altered the maintenance of cocaine self-administration, reinstatement of cocaine-seeking behavior following an extinction of cocaine self-administration or cocaine-evoked conditioned place preference in rats.

Structure of UvrA nucleotide excision repair protein in complex with modified DNA.

One of the primary pathways for removal of DNA damage is nucleotide excision repair (NER). In bacteria, the UvrA protein is the component of NER that locates the lesion. A notable feature of NER is its ability to act on many DNA modifications that vary in chemical structure.

[Comparison between ETCO₂ values measured by the Smart Capnoline™ and the PACO₂ in intubated then extubated postoperative cardiac surgery patients].

Objective: To compare the PaCO(2) with the ETCO(2) obtained with the Smart Capnoline™ in the postoperative setting of cardiac surgery during ventilation and after extubation

Type Of Study: Prospective, observational.

Patients: Twenty patients after cardiac surgery.

Methods: In the intensive care unit, arterial blood gases were measured concomitantly with ETCO(2), and difference between PaCO(2) and ETCO(2) were calculated.

Vigilance in parents' experiences of fetal and infant loss.

Objective: To develop an in-depth understanding of the experiences and contexts of fetal and infant mortality from the perspective of women and men who experienced a fetal or infant loss.

Design: Qualitative, descriptive.

Setting: Small urban community of 100,000.

Using Fetal and Infant Mortality Reviews to improve birth outcomes in an urban community.

Objective: To describe the implementation of a Fetal and Infant Mortality Review (FIMR) in a small urban community to improve perinatal birth outcomes.

Design: Descriptive study.

Setting: Urban community within a Wisconsin city, population 85,000.