Measurement of circulating 25-hydroxyvitamin D: A historical review

The constantly increasing requests for the measurement of serum 25-hydroxyvitamin D over the last years has led reagent manufacturers to market different automated and semi-automated methods, that being unfortunately not fully harmonized, yield different results. Liquid chromatography coupled to tandem mass spectrometry (LC/MS2) has more recently been introduced. This approach allows the distinction between the two forms of 25-hydroxyvitamin D and to measure other metabolites. This approach also requires harmonization to curtail the differences between the different analytical methods. To meet this requirement, the American National Institutes of Health (NIH), the CDC (Centre for Disease Control and Prevention) in Atlanta, the NIST (National Institute of Standards and Technology) and the vitamin D Reference laboratory of Ghent University have pooled their expertise to develop a standardization program. This article reviews the main elements and the difficulties of the automated and semi-automated methods for 25-hydroxyvitamin D, from sample preparation to the analytical phase, as well as those related to mass spectrometry. It also addresses the issues related to the clinical decision thresholds and the possibility of measurements in different biological liquids

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments

Low-complexity transmit diversity scheme using moderate-sized signal constellations

In the conventional space-time coding technique [1], nT radio frequency (RF) chains are employed to transmit signals simultaneously from nT transmit antennas. In this Letter, a lowcomplexity transmit diversity scheme with nT = 2 transmit antennas is proposed. The proposed system employs only one RF chain as well as a low-complexity switch for transmission

Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes.

Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport

On the climatic changes and the sunspot activity during the XVIIth century

International audienceIn this paper, four decades of true meteorological data..

Contribution to the understanding of the Ionian Basin sedimentary evolution along the eastern edge of Apulia during the Late Cretaceous in Albania

Integrated in the peri-Adriatic domain, the Ionian Basin extended along a NW-SE direction during the Late Cretaceous, limited on its sides by the Apulian and the Kruja platforms. The basinal/slope succession was studied in seven outcrops exposed in the Albanian fold-and-thrust belt. Sedimentological investigations, supported by bio- and chronostratigraphy were performed on calcareous Upper Cretaceous hemipelagites, gravity-flow deposits and slumps. The western part of the basin was studied, revealing a strong influence of the Apulian margin, alternatively shedding sediment basinward, by means of a tectonically controlled edge. The Late Albian to Cenomanian period is characterized by the settling of muddy debrites along the margin. A deep basinal environment characterizes this period which prolongs until the Santonian, with no significant influx of the platform basinward. This sedimentary setting abruptly changed at the end of the Santonian, with an important influx derived from both platforms. Coarsening and thickening upward sequences show a progressive increase in sediment shedding during the Campanian. The Late Campanian-Early Maastrichtian period points out a major change on the resedimentation processes with the settling of several slumped units reworking thick sediment packages. The latter can be traced along the Apulian margin, testifying of instabilities along the edge of Apulia

The phase diagram of the lattice Calogero-Sutherland model

We introduce a {\it lattice} version of the Calogero Sutherland model adapted to describe $1/d^2$ pairwise interacting steps with discrete positions on a vicinal surface. The configurational free energy is obtained within a transfer matrix method. The full phase diagram for attractive and for repulsive interaction is deduced. For attraction, critical temperatures of faceting transitions are found to depend on step density.Comment: latex PRBCalogSuth.tex, 6 files, 4 pages [SPEC-S00/900

IL-1 beta and TNF alpha Promote Monocyte Viability through the Induction of GM-CSF Expression by Rheumatoid Arthritis Synovial Fibroblasts

Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone . This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF . Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization