A Case of Relapsing-Remitting Neuroborreliosis? Challenges in the Differential Diagnosis of Recurrent Myelitis

We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case

Effects of dimethyl fumarate on neuroprotection and immunomodulation

BACKGROUND: Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate is a promising novel oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. These effects are presumed to originate from a combination of immunomodulatory and neuroprotective mechanisms. We aimed to clarify whether neuroprotective concentrations of dimethyl fumarate have immunomodulatory effects. FINDINGS: We determined time- and concentration-dependent effects of dimethyl fumarate and its metabolite monomethyl fumarate on viability in a model of endogenous neuronal oxidative stress and clarified the mechanism of action by quantitating cellular glutathione content and recycling, nuclear translocation of transcription factors, and the expression of antioxidant genes. We compared this with changes in the cytokine profiles released by stimulated splenocytes measured by ELISPOT technology and analyzed the interactions between neuronal and immune cells and neuronal function and viability in cell death assays and multi-electrode arrays. Our observations show that dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of the transcription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis and recycling in neuronal cells. Concentrations that were cytoprotective in neuronal cells had no negative effects on viability of splenocytes but suppressed the production of proinflammatory cytokines in cultures from C57BL/6 and SJL mice and had no effects on neuronal activity in multi-electrode arrays. CONCLUSIONS: These results suggest that immunomodulatory concentrations of dimethyl fumarate can reduce oxidative stress without altering neuronal network activity

Identification of baryon resonances in central heavy-ion collisions at energies between 1 and 2 AGeV

The mass distributions of baryon resonances populated in near-central collisions of Au on Au and Ni on Ni are deduced by defolding the $p_t$ spectra of charged pions by a method which does not depend on a specific resonance shape. In addition the mass distributions of resonances are obtained from the invariant masses of $(p, \pi^{\pm})$ pairs. With both methods the deduced mass distributions are shifted by an average value of -60 MeV/c$^2$ relative to the mass distribution of the free $\Delta(1232)$ resonance, the distributions descent almost exponentially towards mass values of 2000 MeV/c^2. The observed differences between $(p, \pi^-)$ and $(p, \pi^+)$ pairs indicate a contribution of isospin $I = 1/2$ resonances. The attempt to consistently describe the deduced mass distributions and the reconstructed kinetic energy spectra of the resonances leads to new insights about the freeze out conditions, i.e. to rather low temperatures and large expansion velocities.Comment: 30 pages, 13 figures, Latex using documentstyle[12pt,a4,epsfig], to appear in Eur. Phys. J.

Improving precision for detecting change in the shape of the cornea in patients with keratoconus

To investigate a method for precision analysis to discriminate true corneal change from measurement imprecision in keratoconus (KC). Thirty patients with KC and 30 healthy controls were included. Coefficients of repeatability and limits of agreement (LOA) were compared using multiple measurements for inter-observer and inter-device agreement with the Pentacam HR, Orbscan IIz, and Tomey Casia SS-1000. Correlation of repeated measurements was evaluated using a linear mixed effect model (also called random effect model). A formula was derived for the theoretical expected change in precision and compared with measured change. Correlation between measurements from the same eye was small (R = 0.13). The 99.73% LOA (3 SD) of the mean of three measurements, provided better precision than 95% LOA (2 SD) of single cut-off values as expected from statistical theory for uncorrelated measurements for evidence of a significant change in corneal shape in patients with keratoconus. This enabled the determination of cut-off values for the detection of true change in corneal shape. The mean of three repeated measurements will provide better precision when there is minimal correlation. Three (rather than two) standard deviations provides a precise estimate of the LOA within or between observers and can be used as a reliable measure for identifying stage-independent corneal shape changes (progression) in keratoconus

Immunological Tolerance to Muscle Autoantigens Involves Peripheral Deletion of Autoreactive CD8+ T Cells

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4+ T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8+ T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8+ tolerance in SM-Ova mice. We show herein that Ova-specific CD8+ T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8+ T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells

Charged pions from Ni on Ni collisions between 1 and 2 AGeV

Charged pions from Ni + Ni reactions at 1.05, 1.45 and 1.93 AGeV are measured with the FOPI detector. The mean $\pi^{\pm}$ multiplicities per mean number of participants increase with beam energy, in accordance with earlier studies of the Ar + KCl and La + La systems. The pion kinetic energy spectra have concave shape and are fitted by the superposition of two Boltzmann distributions with different temperatures. These apparent temperatures depend only weakly on bombarding energy. The pion angular distributions show a forward/backward enhancement at all energies, but not the $\Theta = 90^0$ enhancement which was observed in case of the Au + Au system. These features also determine the rapidity distributions which are therefore in disagreement with the hypothesis of one thermal source. The importance of the Coulomb interaction and of the pion rescattering by spectator matter in producing these phenomena is discussed

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications.

BACKGROUND: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. METHOD: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. CONCLUSIONS: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy.(undefined)info:eu-repo/semantics/publishedVersio

Central Collisions of Au on Au at 150, 250 and 400 A MeV

Collisions of Au on Au at incident energies of 150, 250 and 400 A MeV were studied with the FOPI-facility at GSI Darmstadt. Nuclear charge (Z < 16) and velocity of the products were detected with full azimuthal acceptance at laboratory angles of 1-30 degrees. Isotope separated light charged particles were measured with movable multiple telescopes in an angular range of 6-90 degrees. Central collisions representing about 1 % of the reaction cross section were selected by requiring high total transverse energy, but vanishing sideflow. The velocity space distributions and yields of the emitted fragments are reported. The data are analysed in terms of a thermal model including radial flow. A comparison with predictions of the Quantum Molecular Model is presented.Comment: LateX text 62 pages, plus six Postscript files with a total of 34 figures, accepted by Nucl.Phys.