Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation

Celiac disease (CD) is a complex multi-organ disease with a high prevalence of extra-intestinal involvement, including neurological and psychiatric manifestations, such as cerebellar ataxia, peripheral neuropathy, epilepsy, headache, cognitive impairment, and depression. However, the mechanisms behind the neurological involvement in CD remain controversial. Recent evidence shows these can be related to gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and in severe cases, vitamins or nutrients deficiency. Here, we have summarized new evidence related to gut microbiota and the so-called “gut-liver-brain axis” involved in CD-related neurological manifestations. Additionally, there has yet to be an agreement on whether serological or neurophysiological findings can effectively early diagnose and properly monitor CD-associated neurological involvement; notably, most of them can revert to normal with a rigorous gluten-free diet. Moving from a molecular level to a symptom-based approach, clinical, serological, and neurophysiology data might help to disentangle the many-faceted interactions between the gut and brain in CD. Eventually, the identification of multimodal biomarkers might help diagnose, monitor, and improve the quality of life of patients with “neuroCD”.     

Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.     

Medieval glazed ceramic from Caesar's Forum (Rome,Italy): Production technology

This study is focused on Medieval Roman heavy lead-glazed ceramics from the archaeological site of the Caesar's Forum (Rome, Italy), dated from the 10th and not beyond the first decades of the 11th century. Optical microscopy (OM), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM-EDS) and electron microprobe analysis (EMPA) have been used for the archaeometric characterization of the ceramics. Petrographic analysis of the body indicated the occurrence of three petro-fabrics, mainly composed by abundant quartz, feldspars, nodules of iron oxides, rare fragments of siliceous rocks, very rare fragments of calcareous rocks, pyroxene, biotite and olivine. This mineralogical assemblage suggests that the ceramics were fired in the range 950–1050 °C, under oxidizing conditions. SEM and EMP analysis show that the ceramic body was produced with non-or moderately calcareous clays and the heavy glaze with lead oxide, silica, alumina and alkalis. The microstructure of the glaze and the relationship with the body suggest that for the production of the ceramic repertoire of the Caesar's Forum either the single or the double firing techniques were used.     

The role of LDL in the origin and progression of atherosclerosis: pathobiological concepts on the origin and development of atherosclerotic lesions and the role of the endothelium

We investigated the effects of in vivo intraperitoneal treatment with the rat monoclonal antibody (mAb), YN1.7.4 (YN1) against intercellular adhesion molecule-1 (ICAM-1) on the ovalbumin (OA)-inhalation-induced infiltration of leukocytes into the airways of OA-sensitized mice. YN1 (100 to 400 microg) given over a period of 72 h dose-dependently reduced the influx of lymphocytes and eosinophils into the bronchial lumen by > 60% and > or = 70%, respectively, when compared with saline or purified rat IgG-treated controls. Alveolar macrophages (AM) in the bronchoalveolar lavage fluid (BALF) were also decreased by > 50%. Lung tissue inflammation as determined by histopathologic examination was reduced. The number of neutrophils in the blood of OA-sensitized mice 3 days after challenge was significantly increased by treatment with YN1. However, at 24 h and 72 h after OA-challenge, the numbers of eosinophils and mononuclear cells in the bone marrow were reduced by YN1 treatment. Additionally, at 72 h after OA-challenge, the numbers of bone-marrow neutrophils were depressed. BALF levels of interleukin-5 (IL-5) and of IgA were lower for YN1-treated mice than for controls. With increasing doses of YN1, the levels of anti-ICAM-1 mAb in the plasma were proportionally increased. To correlate these results with YN1 treatment, blood and BALF T cells and BALF eosinophils were examined with flow cytometry. Blood T cells from YN1-treated mice were unable to bind phycoerythrin (PE)-labeled anti-ICAM- mAb ex vivo. These results implied that ICAM-1 on these cells was bound (occupied) by YN1 administered in vivo. Dose-related decreases were observed in the percentage and mean channel fluorescence (MCF) values of ICAM-1+ BALF T cells and eosinophils. The percentages of CD11a+ or CD49d+ eosinophils were also suppressed. Our data suggest that ICAM-1 is an important molecule involved in the recruitment of leukocytes into the airways of sensitized mice after pulmonary challenge.     

Catalytic Properties of the Antibody H11

The catalytic activity of the antibody H11 is shown to reside chiefly in its ability to hydrolyze 1-acetoxybutadiene to crotonaldehyde and to promote the cycloaddition of the intermediate enol with N-alkylmaleimides. This conclusion is based upon the demonstration that the enol tautomerizes too rapidly in solution to be a competent intermediate and that under the reaction conditions for H11, no cycloaddition occurs with crotonaldehyde and N-ethylmaleimide. As a first step towards a structural understanding of the chemistry of H11, chemical modification experiments have shown that reactions of acidic amino acids, tyrosine, lysine, and histidine, but not arginine, inhibit the reactions mediated by H11.     

Vickers Crack Nucleation of Glass Sheets Coated by Thin Silica Gel Layers

SiO₂ gel layers of different thickness have been deposited on glass sheets by dipping from gelling solutions with different concentrations of silicon alkoxide. Some mechanical properties of the coated samples such as hardness (H), elastic modulus (E), crack formation tendency, and tensile stress in the film (σ) have been measured by microindentation techniques and slide deflection. SiO₂ films deposited from more dilute solutions had lower H, E, and σ values, accounting for the observed higher resistance to crack nucleation in comparison with that found for samples prepared from more concentrated solutions.     

Leak Detection in a Branched System by Inverse Transient Analysis with the Admittance Matrix Method

The diagnosis of water distribution systems by means of the inverse transient analysis requires efficient and reliable numerical models. In the network admittance matrix method (NAMM) the 1-D waterhammer governing equations are integrated in the frequency domain and organized in a laplacian matrix form. The NAMM is particularly suitable for complex systems because of this structure and can be used for the system diagnosis, including leak sizing and location. In this paper a damaged branched system is considered and the diagnosis is performed by means of the NAMM using experimental data from laboratory transient tests. Two different boundary conditions are used in the implementation of the NAMM and the leak is located and sized with a reasonable approximation. An extended numerical investigation is also presented and allows confirmation of the results for different leak locations. The use of the NAMM for the leak detection and the validation using experimental data on a branched system are the main original contributions of this work. The successful diagnosis indicates promising results for applications in more complex systems.     

The Complexity of Solving Reachability Games Using Value and Strategy Iteration

Two standard algorithms for approximately solving two-player zero-sum concurrent reachability games are value iteration and strategy iteration. We prove upper and lower bounds of \(2^{m^{\varTheta(N)}}\) on the worst case number of iterations needed by both of these algorithms for providing non-trivial approximations to the value of a game with N non-terminal positions and m actions for each player in each position. In particular, both algorithms have doubly-exponential complexity. Even when the game given as input has only one non-terminal position, we prove an exponential lower bound on the worst case number of iterations needed to provide non-trivial approximations.     

Qualitative reachability in stochastic BPA games

We consider a class of infinite-state stochastic games generated by stateless pushdown automata (or, equivalently, 1-exit recursive state machines), where the winning objective is specified by a regular set of target configurations and a qualitative probability constraint ‘>0’ or ‘=1’. The goal of one player is to maximize the probability of reaching the target set so that the constraint is satisfied, while the other player aims at the opposite. We show that the winner in such games can be determined in P for the ‘>0’ constraint, and in NP∩co-NP for the ‘=1’ constraint. Further, we prove that the winning regions for both players are regular, and we design algorithms which compute the associated finite-state automata. Finally, we show that winning strategies can be synthesized effectively.