Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections

Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot immunoassay (DBI) was compared to a commercially available DEN antigen detection kit (denKEY Blue kit; Globio Co., Beverly, Mass.) and a reverse transcription-PCR (RT-PCR) kit. Serial serum or plasma samples (n = 181) obtained from 55 acute DEN-infected patients were used. In samples obtained from 32 of these 55 DEN-infected patients, viral RNA could be detected by RT-PCR. DEN antigen was detected in only 10 of these 55 patient samples by using the denKEY kit. When these samples were treated with acid to release the immune-complex-associated NS-1 antigen for detection by DBI, 43 of these 55 patients were found to be positive for DEN NS-1 antigen. In nondiss

Glioblastoma hijacks microglial gene expression to support tumor growth

Background: Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells.Methods: We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor.Results: We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma.Conclusion: Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.</p

Infinitesimal Gribov copies in gauge-fixed topological Yang-Mills theories

We study the Gribov problem in four-dimensional topological Yang-Mills theories following the Baulieu-Singer approach in the (anti-)self-dual Landau gauges. This is a gauge-fixed approach that allows to recover the topological spectrum, as first constructed by Witten, by means of an equivariant (or constrained) BRST cohomology. As standard gauge-fixed Yang-Mills theories suffer from the gauge copy (Gribov) ambiguity, one might wonder if and how this has repercussions for this analysis. The resolution of the small (infinitesimal) gauge copies, in general, affects the dynamics of the underlying theory. In particular, treating the Gribov problem for the standard Landau gauge condition in non-topological Yang-Mills theories strongly affects the dynamics of the theory in the infrared. In the current paper, although the theory is investigated with the same gauge condition, the effects of the copies turn out to be completely different. In other words: in both cases, the copies are there, but the effects are very different. As suggested by the tree-level exactness of the topological model in this gauge choice, the Gribov copies are shown to be inoffensive at the quantum level. To be more precise, following Gribov, we discuss the path integral restriction to the Gribov horizon. The associated gap equation, which fixes the so-called Gribov parameter, is however shown to only possess a trivial solution, making the restriction obsolete. We relate this to the absence of radiative corrections in both gauge and ghost sectors. We give further evidence by employing the renormalization group which shows that, for this kind of topological model, the gap equation indeed forbids the introduction of a massive Gribov parameter.Comment: 21 pages. Final version accepted for publication in Physics Letters

Strong evidences of hadron acceleration in Tycho's Supernova Remnant

Very recent gamma-ray observations of G120.1+1.4 (Tycho's) supernova remnant (SNR) by Fermi-LAT and VERITAS provided new fundamental pieces of information for understanding particle acceleration and non-thermal emission in SNRs. We want to outline a coherent description of Tycho's properties in terms of SNR evolution, shock hydrodynamics and multi-wavelength emission by accounting for particle acceleration at the forward shock via first order Fermi mechanism. We adopt here a quick and reliable semi-analytical approach to non-linear diffusive shock acceleration which includes magnetic field amplification due to resonant streaming instability and the dynamical backreaction on the shock of both cosmic rays (CRs) and self-generated magnetic turbulence. We find that Tycho's forward shock is accelerating protons up to at least 500 TeV, channelling into CRs about the 10 per cent of its kinetic energy. Moreover, the CR-induced streaming instability is consistent with all the observational evidences indicating a very efficient magnetic field amplification (up to ~300 micro Gauss). In such a strong magnetic field the velocity of the Alfv\'en waves scattering CRs in the upstream is expected to be enhanced and to make accelerated particles feel an effective compression factor lower than 4, in turn leading to an energy spectrum steeper than the standard prediction {\propto} E^-2. This latter effect is crucial to explain the GeV-to-TeV gamma-ray spectrum as due to the decay of neutral pions produced in nuclear collisions between accelerated nuclei and the background gas. The self-consistency of such an hadronic scenario, along with the fact that the concurrent leptonic mechanism cannot reproduce both the shape and the normalization of the detected the gamma-ray emission, represents the first clear and direct radiative evidence that hadron acceleration occurs efficiently in young Galactic SNRs.Comment: Minor changes. Accepted for publication in Astronomy & Astrophysic

Innervation of the pelvic floor muscles: a reappraisal for the levator ani nerve

OBJECTIVE: We investigated the clinical anatomy of the levator ani nerve and its topographical relationship with the pudendal nerve. METHODS: Ten female pelves were dissected and a pudendal nerve blockade was simulated. The course of the levator ani nerve and pudendal nerve was described quantitatively. The anatomical data were verified using (immuno-)histochemically stained sections of human fetal pelves. RESULTS: The levator ani nerve approaches the pelvic-floor muscles on their visceral side. Near the ischial spine, the levator ani nerve and the pudendal nerve lie above and below the levator ani muscle, respectively, at a distance of approximately 6 mm from each other. The median distance between the levator ani nerve and the point of entry of the pudendal blockade needle into the levator ani muscle was only 5 mm. CONCLUSION: The levator ani nerve and the pudendal nerve are so close at the level of the ischial spine that a transvaginal "pudendal nerve blockade" would, in all probability, block both nerves simultaneously. The clinical anatomy of the levator ani nerve is such that it is prone to damage during complicated vaginal childbirth and surgical interventions

BLADDER, ANORECTAL AND SEXUAL FUNCTION AFTER NERVE-SPARING RADICAL HYSTERECTOMY FOR THE TREATMENT OF CERVICAL CANCER; A LONGITUDINAL PROSPECTIVE COHORT STUDY

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The contribution of the levator ani nerve and the pudendal nerve to the innervation of the levator ani muscles; a study in human fetuses.

OBJECTIVES: The contributions of the pudendal and levator ani nerves to the innervation of the levator ani muscle (LAM) are disputed. Because of the relatively large size of the nerves in early life, we investigated this issue in human fetuses. METHODS: (Immuno)histochemically stained serial sections of nine human fetuses (9-22 wk of gestation) were investigated. Both the left and right sides of the fetal pelves were studied individually and 3D reconstructions were prepared. RESULTS: The levator ani nerve innervated the LAM in every pelvis, whereas a contribution of the pudendal nerve to the innervation of the LAM could be demonstrated in only 10 pelvic halves (56%). In 10 halves, we observed a communicating nerve branch between the pudendal and levator ani nerves that pierced the pelvic floor between the LAM and the coccygeus muscle. No sex differences were observed, but the innervation pattern did differ between the left and right side of a pelvis. CONCLUSIONS: The LAM often has a dual somatic innervation with the levator ani nerve as its constant and main neuronal supply

Dialectspreekwoordenboek van de gemeente Gennep. Een keuze uit spreekwoorden, uitdrukkingen, versjes en liedjes in het dialect van Gennep, Heijen, Milsbeek, Ottersum en Ven-Zelderheide

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