Relevance of a combined UV and single mass spectrometry detection for the determination of tenofovir in human plasma by HPLC in therapeutic drug monitoring

A sensitive high-performance liquid chromatography method coupled to UV and single mass spectrometry (MS) detection was developed for the determination of tenofovir in human plasma. A solid phase extraction procedure (Bond-Elut C18 Varian cartridges) provided high extraction efficiency (91% for tenofovir and 68.8% for the internal standard, 3-methylcytidine). An atlantis-dC-18 analytical column is used with an isocratic mode elution of a mixture (pH 2.5) of ammonium acetate/methanol (98.5:1.5, v/v). Detection was performed at 260 nm and by using the ion at m/z 288. The signals from both detectors were validated over the range of 10-1000 ng mL(-1) and were found to be linear, accurate and precise. At the lowest limit of quantification, 10 ng mL(-1) for UV and 5 ng mL(-1) for MS, the average coefficient of variation was 6.9 and 3.9%, respectively. To investigate the potential of the validated method for clinical studies, more than 170 samples from HIV-infected adult patients were then analyzed with this assay. A good correlation was observed between the results obtained with both detectors. However, in several cases discordant results were observed between UV and MS detections. Therefore, tenofovir can sometimes suffer from interferences using either UV or single MS detection. We concluded that the double detection allows to obtain a more specific quantification of tenofovir. The present assay is sound and can be used for therapeutic drug monitoring allowing a higher reliability of the results which are transmitted to the medical team.     

Identification of DNA motifs implicated in maintenance of bacterial core genomes by predictive modeling

Bacterial biodiversity at the species level, in terms of gene acquisition or loss, is so immense that it raises the question of how essential chromosomal regions are spared from uncontrolled rearrangements. Protection of the genome likely depends on specific DNA motifs that impose limits on the regions that undergo recombination. Although most such motifs remain unidentified, they are theoretically predictable based on their genomic distribution properties. We examined the distribution of the “crossover hotspot instigator,” or Chi, in Escherichia coli, and found that its exceptional distribution is restricted to the core genome common to three strains. We then formulated a set of criteria that were incorporated in a statistical model to search core genomes for motifs potentially involved in genome stability in other species. Our strategy led us to identify and biologically validate two distinct heptamers that possess Chi properties, one in Staphylococcus aureus, and the other in several streptococci. This strategy paves the way for wide-scale discovery of other important functional noncoding motifs that distinguish core genomes from the strain-variable regions.     

Clinical consequences of consecutive self-expanding transcatheter heart valve iterations

Netherlands Heart Journal - To compare early clinical outcomes after transcatheter aortic valve implantation (TAVI) with three consecutive generations of self-expanding valves (SEVs). Clinical...     

All-Optical Logic Gates Using a Plasmonic MIM Waveguide and Elliptical Ring Resonator

Plasmonics - All-optical logic gates OR, XOR, AND, and NOT based on two-dimensional (2D) plasmonic metal-insulator-metal (MIM) coupled with an elliptical ring resonator (ERR) are presented,...     

Reclassification of aortic stenosis by fusion of echocardiography and computed tomography in low-gradient aortic stenosis

Netherlands Heart Journal - The integration of computed tomography (CT)-derived left ventricular outflow tract area into the echocardiography-derived continuity equation results in the...     

Correction to: The Mitochondrial Genetic Diversity of the Olive Field Mouse Abrothrix olivacea (Cricetidae; Abrotrichini) is Latitudinally Structured Across Its Geographic Distribution

Journal of Mammalian Evolution -     

Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes

Pyrroloquinoline quinone (PQQ) acts as a powerful modulator of PGC-1α activation and therefore regulates multiple pathways involved in cellular energy homeostasis. In the present study, we assessed the effects of L6 myotubes incubation with 0.5, 1, and 3 μM PQQ solution for 2 and 24 hr with respect to the cells' lipid metabolism. We demonstrated that PQQ significantly elevates PGC-1α content in a dose- and time-dependent manner with the highest efficiency for 0.5 and 1 µM. The level of free fatty acids was diminished (24 hr: −66%), while an increase in triacylglycerol (TAG) amount was most pronounced after 0.5 μM (2 hr: +93%, 24 hr: +139%) treatment. Ceramide (CER) content was elevated after 2 hr incubation with 0.5 µM and after prolonged exposure to all PQQ concentrations. The cells treated with PQQ for 2 hr exhibited decreased sphinganine (SFA) and sphinganine-1-phosphate (SFA1P) level, while 24 hr incubation resulted in an elevated sphingosine (SFO) amount. In summary, PGC-1α activation promotes TAG and CER synthesis.     

Paleobiogeographic implications of the Middle Eocene ostracods from Cairo–Suez district,Egypt

The main targets of this paper are to examine the Middle Eocene ostracod assemblages collected from a succession exposed in the Cairo–Suez district, Egypt and to detect their paleobiogeographical implications. The studied succession is subdivided into two rock units: the Observatory and Qurn formations, in ascending order. The analysis of the ostracod assemblages led to the identification of 18 species, none of which is new. Three local biozones are established, Digmocythere ismaili - Xestoleberis kenawyi Assemblage Zone, Grinioneis moosi - Loxoconcha pseudopunctatella Assemblage Zone and Cativella qurnenis - Soudanella triangulata Assemblage Zone. The multivariate analyses indicate that there are three distinct bioprovinces, one of them represents the North Africa bioprovince, including Egypt, Libya, and Tunisia. The second bioprovince represents the Middle East, including Jordan and Israel. The third represents the West Africa bioprovince, including Senegal, Togo, Ivory Coast and Nigeria. Therefore, this deduction supports a migration of Eocene ostracods along the southern Tethys.