The Value of Suction Drainage Fluid Culture during Aseptic and Septic Orthopedic Surgery: A Prospective Study of 901 Patients

There are no guidelines on the value of suction drainage fluid culture (SDC), and it is difficult to determine whether the organisms cultured from suction drainage fluid samples are pathogenic or simply contaminants. We performed 2989 cultures of suction drainage fluid samples obtained, during a 1-year period, from 901 patients who underwent aseptic or septic orthopedic surgery (946 operations). The culture results were analyzed to evaluate their ability to detect postoperative infection after aseptic operations or to detect either a persistent or new episode of sepsis in patients known to have infection. For aseptic operations, the sensitivity of SDC was 25%, the specificity was 99%, the positive predictive value was 25%, and the negative predictive value was 99%. For septic operations, the sensitivity of SDC was 81%, the specificity was 96%, the positive predictive value was 87%, and the negative predictive value was 94%. We conclude that, for aseptic orthopedic surgery, SDC is not useful in detecting postoperative infection. However, for septic orthopedic surgery, it is of clinical importanc

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Papillomavirus Capsid Binding and Uptake by Cells From Different Tissues and Species

The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake

The 2017 May 20th^{\rm th} stellar occultation by the elongated centaur (95626) 2002 GZ32_{32}

We predicted a stellar occultation of the bright star Gaia DR1 4332852996360346368 (UCAC4 385-75921) (m$_{\rm V}$= 14.0 mag) by the centaur 2002 GZ$_{32}$ for 2017 May 20$^{\rm th}$. Our latest shadow path prediction was favourable to a large region in Europe. Observations were arranged in a broad region inside the nominal shadow path. Series of images were obtained with 29 telescopes throughout Europe and from six of them (five in Spain and one in Greece) we detected the occultation. This is the fourth centaur, besides Chariklo, Chiron and Bienor, for which a multi-chord stellar occultation is reported. By means of an elliptical fit to the occultation chords we obtained the limb of 2002 GZ$_{32}$ during the occultation, resulting in an ellipse with axes of 305 $\pm$ 17 km $\times$ 146 $\pm$ 8 km. From this limb, thanks to a rotational light curve obtained shortly after the occultation, we derived the geometric albedo of 2002 GZ$_{32}$ ($p_{\rm V}$ = 0.043 $\pm$ 0.007) and a 3-D ellipsoidal shape with axes 366 km $\times$ 306 km $\times$ 120 km. This shape is not fully consistent with a homogeneous body in hydrostatic equilibrium for the known rotation period of 2002 GZ$_{32}$. The size (albedo) obtained from the occultation is respectively smaller (greater) than that derived from the radiometric technique but compatible within error bars. No rings or debris around 2002 GZ$_{32}$ were detected from the occultation, but narrow and thin rings cannot be discarded.Comment: Accepted for publication in MNRAS (8-Dec.-2020), 15 pages, 9 figure

Recent EUROfusion Achievements in Support of Computationally Demanding Multiscale Fusion Physics Simulations and Integrated Modeling

Integrated modeling (IM) of present experiments and future tokamak reactors requires the provision of computational resources and numerical tools capable of simulating multiscale spatial phenomena as well as fast transient events and relatively slow plasma evolution within a reasonably short computational time. Recent progress in the implementation of the new computational resources for fusion applications in Europe based on modern supercomputer technologies (supercomputer MARCONI-FUSION), in the optimization and speedup of the EU fusion-related first-principle codes, and in the development of a basis for physics codes/modules integration into a centrally maintained suite of IM tools achieved within the EUROfusion Consortium is presented. Physics phenomena that can now be reasonably modelled in various areas (core turbulence and magnetic reconnection, edge and scrape-off layer physics, radio-frequency heating and current drive, magnetohydrodynamic model, reflectometry simulations) following successful code optimizations and parallelization are briefly described. Development activities in support to IM are summarized. They include support to (1) the local deployment of the IM infrastructure and access to experimental data at various host sites, (2) the management of releases for sophisticated IM workflows involving a large number of components, and (3) the performance optimization of complex IM workflows.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014 to 2018 under grant agreement 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission or ITER.Peer ReviewedPostprint (published version

Perturbation of the Dimer Interface of Triosephosphate Isomerase and its Effect on Trypanosoma cruzi

Most of the enzymes of parasites have their counterpart in the host. Throughout evolution, the three-dimensional architecture of enzymes and their catalytic sites are highly conserved. Thus, identifying molecules that act exclusively on the active sites of the enzymes from parasites is a difficult task. However, it is documented that the majority of enzymes consist of various subunits, and that conservation in the interface of the subunits is lower than in the catalytic site. Indeed, we found that there are significant differences in the interface between the two subunits of triosephosphate isomerase from Homo sapiens and Trypanosoma cruzi (TcTIM), which causes Chagas disease in the American continent. In the search for agents that specifically inhibit TcTIM, we found that 2,2′-dithioaniline (DTDA) is far more effective in inactivating TcTIM than the human enzyme, and that its detrimental effect is due to perturbation of the dimer interface. Remarkably, DTDA prevented the growth of Escherichia coli cells that had TcTIM instead of their own TIM and killed T. cruzi epimastigotes in culture. Thus, this study highlights a new approach base of targeting molecular interfaces of dimers

Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value

A large topographic feature on the surface of the trans-Neptunian object (307261) 2002 MS4_4 measured from stellar occultations

This work aims at constraining the size, shape, and geometric albedo of the dwarf planet candidate 2002 MS4 through the analysis of nine stellar occultation events. Using multichord detection, we also studied the object's topography by analyzing the obtained limb and the residuals between observed chords and the best-fitted ellipse. We predicted and organized the observational campaigns of nine stellar occultations by 2002 MS4 between 2019 and 2022, resulting in two single-chord events, four double-chord detections, and three events with three to up to sixty-one positive chords. Using 13 selected chords from the 8 August 2020 event, we determined the global elliptical limb of 2002 MS4. The best-fitted ellipse, combined with the object's rotational information from the literature, constrains the object's size, shape, and albedo. Additionally, we developed a new method to characterize topography features on the object's limb. The global limb has a semi-major axis of 412 $\pm$ 10 km, a semi-minor axis of 385 $\pm$ 17 km, and the position angle of the minor axis is 121 $^\circ$ $\pm$ 16$^\circ$. From this instantaneous limb, we obtained 2002 MS4's geometric albedo and the projected area-equivalent diameter. Significant deviations from the fitted ellipse in the northernmost limb are detected from multiple sites highlighting three distinct topographic features: one 11 km depth depression followed by a 25$^{+4}_{-5}$ km height elevation next to a crater-like depression with an extension of 322 $\pm$ 39 km and 45.1 $\pm$ 1.5 km deep. Our results present an object that is $\approx$138 km smaller in diameter than derived from thermal data, possibly indicating the presence of a so-far unknown satellite. However, within the error bars, the geometric albedo in the V-band agrees with the results published in the literature, even with the radiometric-derived albedo