Evaluation of assays for nucleic acid testing for the prevention of chikungunya and dengue virus transmission by blood transfusion.

Background: The large dengue (DENV) and chikungunya (CHIKV) outbreaks observed during the last decade across the world, as well as local transmissions in non-endemic areas are a growing concern for blood safety. The aim of this study was to evaluate and compare the sensitivity of nucleic acid tests (NAT) detecting DENV and CHIKV RNA.

Materials And Methods: Using DENV 1 to 4 International Standards, the limits of detection (LODs) calculated by probit analysis of two NAT assays; the cobas CHIKV/DENV assay (Roche Diagnostics) and the Procleix Dengue Virus Assay (Grifols) were compared.

Seven years (2015-2021) of blood donor screening for HEV-RNA in France: lessons and perspectives.

Background: The French health authorities are considering expanding the current selective hepatitis E virus (HEV)-RNA testing procedure to include all donations in order to further reduce transfusion-transmitted HEV infection. Data obtained from blood donors (BDs) tested for HEV-RNA between 2015 and 2021 were used to assess the most efficient nucleic acid testing (NAT) strategy.

Materials And Methods: Viral loads (VLs) and the plasma volume of blood components, as well as an HEV-RNA dose of 3.

A convenient qualitative and quantitative method to investigate RHD-RHCE hybrid genes.

Background: Molecular biology techniques, such as single specific-primer polymerase chain reaction (PCR), denaturing-high performance liquid chromatography, direct sequencing, next-generation sequencing, and microarray platforms, contribute to the efficient genotyping of the human blood group RHD gene. However, some alleles remain undetermined in rare cases in DNA samples carrying two copies of the RHD gene, which challenge the identification of D-CE hybrid genes.

Study Design And Methods: We set up, in a single-tube format, a qualitative and quantitative assay based on multiplex PCR of short fluorescent fragments (QMPSF) to simultaneously amplify all 10 RHD exons on the one hand and all 10 RHCE exons on the other hand.

Establishment of a medium-throughput approach for the genotyping of RHD variants and report of nine novel rare alleles.

Background: The routinely used serologic methods are robust in accurately typing standard D- or D+ blood. However, they result in discrepancy in weak or partial D blood, which requires genetic analysis. We have previously used denaturing high-performance liquid chromatography (DHPLC) to screen the entire RHD-coding sequence.

Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells.

In an attempt to understand the beneficial health effects of Artemisia annua other than its anti-malaria properties, extracts from different cultivars prepared as tea infusions were investigated using Caco-2 cells on the intestinal inflammation and cytochrome P450 (CYP) activities. The characterisation of their phenolic compound (PC) profile revealed rosmarinic and chlorogenic acids as the main PCs. The extracts, assayed on Caco-2 cells at a plausible intestinal concentration, significantly decreased the secretion of pro-inflammatory cytokines, IL-8 and IL-6.

Small deletions within the RHD coding sequence: a report of two novel mutational events and a survey of the underlying pathophysiologic mechanisms.

Background: Some 270 variants in the RHD gene have so far been identified. Of these, approximately 6% (n = 17) are small (≤20 bp) deletions occurring within the gene's coding sequence. Fourteen of these small deletions disrupted the reading frame of the RHD gene, resulting almost invariably in a D- phenotype.

Weak D caused by a founder deletion in the RHD gene.

Background: The RhD blood group system exemplifies a genotype-phenotype correlation by virtue of its highly polymorphic and immunogenic nature. Weak D phenotypes are generally thought to result from missense mutations leading to quantitative change of the D antigen in the red blood cell membrane or intracellularly.

Study Design And Methods: Different sets of polymerase chain reaction primers were designed to map and clone a deletion involving RHD Exon 10, which was found in approximately 3% of approximately 2000 RHD hemizygous subjects with D phenotype ambiguity.

Variant screening of the RHD gene in a large cohort of subjects with D phenotype ambiguity: report of 17 novel rare alleles.

Background: A considerable number of RHD alleles responsible for weak and partial D phenotypes have been identified over the past decade. Two particular concerns, namely, 1) that red blood cells of these phenotypes may cause anti-D immunization when transfused to D- recipients and 2) that serologic determination of these phenotypes is often doubtful, make genetic analysis of the RHD gene highly desirable.

Study Design And Methods: Blood samples that displayed D phenotype ambiguity (as determined by serologic analyses) were collected from several sites of the Etablissement Français du Sang and subjected to RHD variant screening by means of a previously established denaturing high-performance liquid chromatography method followed by direct sequencing.

How often is a work-up for Legionella pursued in patients with pneumonia? a retrospective study.

Background: It is unclear how often patients with pneumonia are assessed for Legionella in endemic areas. Additionally, the sensitivity of the IDSA/ATS criteria for recommended Legionella testing is undefined.

Methods: We performed a single-center, retrospective study of patients diagnosed with Legionella pneumonia at our hospital to determine: 1) how often Legionella diagnostic testing is obtained on patients with pneumonia at the time of hospitalization or when pneumonia developed during hospitalization; and 2) how often patient's with Legionella pneumonia met at least one of the five criteria in the IDSA/ATS guidelines recommending a work-up for Legionella.

Identification of a novel series of potent RON receptor tyrosine kinase inhibitors.

A novel series of N-(3-fluoro-4-(2-substituted-thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides targeting RON receptor tyrosine kinase was designed and synthesized. SAR study of the series allowed us to identify compounds possessing either inhibitory activity of RON kinase enzyme in the low nanomolar range with low residual activity against the closely related c-Met or potent dual inhibitory activity against RON and c-Met, with no significant activity against VEGFR2 in both cases.

Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans.

Background: Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g alpha-tocopherol/100 mL of the same mixture.

Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups.

A novel series of malonamide-type dual VEGFR2/c-Met inhibitors in which one of the amide bonds was replaced by an amide isostere-a trifluoroethylamine unit, was designed, synthesized, and evaluated for their enzymatic and cellular inhibition of VEGFR2 and c-Met enzymes. Optimization of these molecular entities resulted in identification of potent and selective inhibitors of VEGFR2 enzyme.

N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases.

A family of thieno[3,2-b]pyridine based small molecule inhibitors of c-Met and VEGFR2 were designed based on lead structure 2. These compounds were shown to have IC(50) values in the low nanomolar range in vitro and were efficacious in human tumor xenograft models in mice in vivo.

N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.

A series of N-(4-(6,7-disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC(50) values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.

N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.

A series of N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC(50) values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.

CYP1A1 induction and CYP3A4 inhibition by the fungicide imazalil in the human intestinal Caco-2 cells-comparison with other conazole pesticides.

Imazalil (IMA) is a widely used imidazole-antifungal pesticide and, therefore, a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ingested drugs and pollutants, we have investigated the effects of IMA, at realistic intestinal concentrations, on xenobiotic-metabolizing enzymes and efflux pumps by using Caco-2 cells, as a validated in vitro model of the human intestinal absorptive epithelium.

Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201.

Background: The operational and analytical performance of two automated triplex hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test (NAT) systems were compared in four screening laboratories of the French Blood Service.

Study Design And Methods: Two laboratories evaluated the Procleix Tigris system (Chiron/Gen-Probe) in individual donation (ID) format and two sites used the cobas s 201 system (Roche Molecular Systems) on minipools (MPs) of six donations. The analytical sensitivity, the specificity, and operational performance were compared.

Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases.

A series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases is described. The compounds demonstrated potency with IC(50) values in the low nanomolar range in vitro while the lead compound also showed in vivo activity against various human tumor xenograft models in mice. Further exploration of this class of compounds is underway.

Both sulfate-reducing bacteria and Enterobacteriaceae take part in marine biocorrosion of carbon steel.

Aims: In order to evaluate the part played in biocorrosion by microbial groups other than sulfate-reducing bacteria (SRB), we characterized the phylogenetic diversity of a corrosive marine biofilm attached to a harbour pile structure as well as to carbon steel surfaces (coupons) immersed in seawater for increasing time periods (1 and 8 months). We thus experimentally checked corroding abilities of defined species mixtures.

Methods And Results: Microbial community analysis was performed using both traditional cultivation techniques and polymerase chain reaction cloning-sequencing of 16S rRNA genes.

Preclinical investigations of a medium-chain triglyceride:fish oil emulsion III. Experiments in cultured endothelial cells.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion was recently reported to provoke a rapid and sustained increase in the cell phospholipid content of long-chain polyunsaturated omega3 fatty acids in both rats and human subjects. This report deals mainly with a comparison between this and other emulsions, as well as albumin-bound omega3 fatty acids, in terms of the time course, reversibility and concentration dependency for the incorporation of the omega3 fatty acids in the phospholipids of cultured endothelial cells. The results document that the new emulsion is quite efficient for a rapid and sustained enrichment of phospholipids in long-chain polyunsaturated omega3 fatty acids.