BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Abstract Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes ( p \u2009<\u20090.01), lower values of BAFF Index (11.9\u2009\ub1\u20096.1 vs 17.5\u2009\ub1\u20095.2, p \u2009<\u20090.01), and higher CSF CXCL13 levels (27.7\u2009\ub1\u200933.5 vs 0.9\u2009\ub1\u20091.5, p \u2009<\u20090.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis ( r \u2009>\u20090.5 and p \u2009<\u20090.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB\u2212 ( p \u2009<\u20090.05) and HC ( p \u2009<\u20090.01), and correlated to CSF CXCL13 concentrations ( r 0.77, p \u2009<\u20090.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41\u2009\ub1\u20090.1 vs 2.49\u2009\ub1\u20090.1\ua0mm, p \u2009<\u20090.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB\u2212. Conclusions The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by ..

Special Issue dedicated to Stefano De Marchi on the occasion of his 60th birthday

As colleagues and friends we dedicate this issue to Stefano De Marchi on the occasion of his 60th birthday, publishing works of some of his collaborators. Stefano has made many important contributions to approximation theory and beyond and is one of the “founding fathers” of this journal. Here we briefly reminisce and recount some of our experiences with Stefano in the spirit of the occasion

Protease treatment affects both invasion ability and biofilm formation in Listeria monocytogenes

Listeria monocytogenes is a notably invasive bacterium associated with life-threatening food-borne disease in humans. Several surface proteins have been shown to be essential in the adhesion of L. monocytogenes, and in the subsequent invasion of phagocytes. Because the control of the invasion of host cells by Listeria could potentially hinder its spread in the infected host, we have examined the effects of a protease treatment on the ability of L. monocytogenes to form biofilms and to invade tissues. We have chosen serratiopeptidase (SPEP), an extracellular metalloprotease produced by Serratia marcescens that is already widely used as an anti-inflammatory agent, and has been shown to modulate adhesin expression and to induce antibiotic sensitivity in other bacteria. Treatment of L. monocytogenes with sublethal concentrations of SPEP reduced their ability to form biofilms and to invade host cells. Zymograms of the treated cells revealed that Ami4b autolysin, internalinB, and ActA were sharply reduced. These cell-surface proteins are known to function as ligands in the interaction between these bacteria and their host cells, and our data suggest that treatment with this natural enzyme may provide a useful tool in the prevention of the initial adhesion of L. monocytogenes to the human gu

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening: The Application of a Second-Tier Test

Abstract The isodecyl neopentanoate is an ingredient used in the cosmetic industry to prepare a nipple fissure balm. We report on 12 newborns that showed elevated C5-acylcarnitine levels upon newborn screening following treatment with balm. The first 3 neonates were immediately recalled for confirmatory tests and resulted negative for both isovaleric acidemia and short/branched chain acyl-CoA dehydrogenase deficiency. In the other 9 cases, the immediate recall was avoided by applying a new second-tier test able to confirm the presence of pivaloylcarnitine. The concentration of C5-acylcarnitine was measured in the days following the suspension of balm application. Abnormal concentrations of C5-acylcarnitine did not seem to be associated with free carnitine deficiency, probably due to the short time of exposure. A direct correlation between balm ingestion and the elevation in pivaloylcarnitine has been demonstrated in 10 adult volunteers. The commercial balm containing a pivalic acid derivative is causal of false-positive results during newborn screening, and it could have the potential to cause secondary carnitine deficiency when used chronically

Light yield non-proportionality of inorganic crystals and its effect on cosmic-ray measurements

The multi-TeV energy region of the cosmic-ray spectra has been recently explored by direct detection experiments that used calorimetric techniques to measure the energy of the cosmic particles. Interesting spectral features have been observed in both all-electron and nuclei spectra. However, the interpretation of the results is compromised by the disagreements between the data obtained from the various experiments, that are not reconcilable with the quoted experimental uncertainties. Understanding the reason for the discrepancy among the measurements is of fundamental importance in view of the forthcoming high-energy cosmic-ray experiments planned for space, as well as for the correct interpretation of the available results. The purpose of this work is to investigate the possibility that a systematic effect may derive from the non-proportionality of the light response of inorganic crystals, typically used in high-energy calorimetry due to their excellent energy-resolution performance. The main reason for the non-proportionality of the crystals is that scintillation light yield depends on ionisation density. Experimental data obtained with ion beams were used to characterize the light response of various scintillator materials. The obtained luminous efficiencies were used as input of a Monte Carlo simulation to perform a comparative study of the effect of the light-yield non-proportionality on the detection of high-energy electromagnetic and hadronic showers. The result of this study indicates that, if the calorimeter response is calibrated by using the energy deposit of minimum ionizing particles, the measured shower energy might be affected by a significant systematic shift, at the level of few percent, whose sign and magnitude depend specifically on the type of scintillator material used. © 2022 IOP Publishing Ltd and Sissa Medialab

The SSDC Role in the LICIACube Mission: Data Management and the MATISSE Tool

Light Italian Cubesat for Imaging of Asteroids (LICIACube) is an Italian mission managed by the Italian Space Agency (ASI) and part of the NASA Double Asteroid Redirection Test (DART) planetary defense mission. Its main goals are to document the effects of the DART impact on Dimorphos, the secondary member of the (65803) Didymos binary asteroid system, characterizing the shape of the target body and performing dedicated scientific investigations on it. Within this framework, the mission Science Operations Center will be managed by the Space Science Data Center (ASI-SSDC), which will have the responsibility of processing, archiving, and disseminating the data acquired by the two LICIACube onboard cameras. In order to better accomplish this task, SSDC also plans to use and modify its scientific webtool Multi-purpose Advanced Tool for Instruments for the solar system Exploration (MATISSE), making it the primary tool for the LICIACube data analysis, thanks to its advanced capabilities for searching and visualizing data, particularly useful for the irregular shapes common to several small bodies

VADER: Probing the Dark Side of Dimorphos with LICIACube LUKE

The ASI cubesat LICIACube has been part of the first planetary defense mission DART, having among its scopes to complement the DRACO images to better constrain the Dimorphos shape. LICIACube had two different cameras, LEIA and LUKE, and to accomplish its goal, it exploited the unique possibility of acquiring images of the Dimorphos hemisphere not seen by DART from a vantage point of view, in both time and space. This work is indeed aimed at constraining the tridimensional shape of Dimorphos, starting from both LUKE images of the nonimpacted hemisphere of Dimorphos and the results obtained by DART looking at the impacted hemisphere. To this aim, we developed a semiautomatic Computer Vision algorithm, named VADER, able to identify objects of interest on the basis of physical characteristics, subsequently used as input to retrieve the shape of the ellipse projected in the LUKE images analyzed. Thanks to this shape, we then extracted information about the Dimorphos ellipsoid by applying a series of quantitative geometric considerations. Although the solution space coming from this analysis includes the triaxial ellipsoid found by using DART images, we cannot discard the possibility that Dimorphos has a more elongated shape, more similar to what is expected from previous theories and observations. The result of our work seems therefore to emphasize the unique value of the LICIACube mission and its images, making even clearer the need of having different points of view to accurately define the shape of an asteroid.This work was supported by the Italian Space Agency (ASI) within the LICIACube project (ASI-INAF agreement AC No. 2019-31-HH.0) and by the DART mission, NASA contract 80MSFC20D0004