Enteric glia: A new player in inflammatory bowel diseases

In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases

Near-field microwave techniques for micro – and nano - scale characterization in materials science

In this paper, the basic principles of Near-Field Microscopy will be reviewed with focus on the micro- and nano-scale resolution configurations for material science measurements. Results on doping profile, dielectric and magnetic properties will be presented, with details on the calibration protocols needed for quantitative estimation of the dielectric constant and of the permeability

An evidence map and synthesis review with meta-analysis on the risk of incisional hernia in colorectal surgery with standard closure.

Purpose To assess the incidence of incisional hernia (IH) across various type of incisions in colorectal surgery (CS) creating a map of evidence to define research trends, gaps and areas of future interest. Methods Systematic review of PubMed and Scopus from 2010 onwards. Studies included both open (OS) and laparoscopic (LS). The primary outcome was incidence of IH 12 months after index procedure, secondary outcomes were the study features and their influence on reported proportion of IH. Random effects models were used to calculate pooled proportions. Meta-regression models were performed to explore heterogeneity. Results Ninetyone studies were included reporting 6473 IH. The pooled proportions of IH for OS were 0.35 (95% CI 0.27–0.44) I2 0% in midline laparotomies and 0.02 (95% CI 0.00–0.07), I2 52% for off-midline. In case of LS the pooled proportion of IH for midline extraction sites were 0.10 (95% CI 0.07–0.16), I2 58% and 0.04 (95% CI 0.03–0.06), I2 86% in case of off-midline. In Port-site IH was 0.02 (95% CI 0.01–0.04), I2 82%, and for single incision surgery (SILS) of 0.06—95% CI 0.02–0.15, I2 81%. In case of stoma reversal sites was 0.20 (95% CI 0.16–0.24). Conclusion Midline laparotomies and stoma reversal sites are at high risk for IH and should be considered in research of preventive strategies of closure. After laparoscopic approach IH happens mainly by extraction sites incisions specially midline and also represent an important area of analysis.pre-print3102 K

S100B‑p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin‑4 and metalloproteinase‑2 inhibition in C6 glioma cells

S100 calcium‑binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B‑p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5 diphenyltetrazolium bromide‑formazan assay. Significant dose‑dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 μM (58.5±5%; P<0.05), 0.5 μM (40.6±7%; P<0.01) and 5 μM (13±4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 μM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl‑2 (‑60%, P<0.001; ‑80.13%, P<0.001; ‑95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 μM pentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, P<0.05; 1244±94.3%, P<0.01; and 2244±111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase‑2 (42±2.3%, P<0.05; 71±2.5%, P<0.01; and 95.8±3.3%, P<0.001, respectively) and aquaporin 4 (38±2.5%, P<0.05; 69±2.6%, P<0.01; and 88±3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 μM pentamidine compared with untreated cells (88±4.2%, P<0.05; 64±2%, P<0.01; and 42±3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B‑p53 inhibitors may represent a novel approach for the treatment of glioma

A 1 m3^3 Gas Time Projection Chamber with Optical Readout for Directional Dark Matter Searches: the CYGNO Experiment

The aim of the CYGNO project is the construction and operation of a 1~m$^3$ gas TPC for directional dark matter searches and coherent neutrino scattering measurements, as a prototype toward the 100-1000~m$^3$ (0.15-1.5 tons) CYGNUS network of underground experiments. In such a TPC, electrons produced by dark-matter- or neutrino-induced nuclear recoils will drift toward and will be multiplied by a three-layer GEM structure, and the light produced in the avalanche processes will be readout by a sCMOS camera, providing a 2D image of the event with a resolution of a few hundred micrometers. Photomultipliers will also provide a simultaneous fast readout of the time profile of the light production, giving information about the third coordinate and hence allowing a 3D reconstruction of the event, from which the direction of the nuclear recoil and consequently the direction of the incoming particle can be inferred. Such a detailed reconstruction of the event topology will also allow a pure and efficient signal to background discrimination. These two features are the key to reach and overcome the solar neutrino background that will ultimately limit non-directional dark matter searches.Comment: 5 page, 7 figures, contribution to the Conference Records of 2018 IEEE NSS/MI

Characterization and Performance of PADME's Cherenkov-Based Small-Angle Calorimeter

The PADME experiment, at the Laboratori Nazionali di Frascati (LNF), in Italy, will search for invisible decays of the hypothetical dark photon via the process $e^+e^-\rightarrow \gamma A'$, where the $A'$ escapes detection. The dark photon mass range sensitivity in a first phase will be 1 to 24 MeV. We report here on measurement and simulation studies of the performance of the Small-Angle Calorimeter, a component of PADME's detector dedicated to rejecting 2- and 3-gamma backgrounds. The crucial requirement is a timing resolution of less than 200 ps, which is satisfied by the choice of PbF$_2$ crystals and the newly released Hamamatsu R13478UV photomultiplier tubes (PMTs). We find a timing resolution of 81 ps (with double-peak separation resolution of 1.8 ns) and a single-crystal energy resolution of 5.7%/$\sqrt{E}$ with light yield of 2.07 photo-electrons per MeV, using 100 to 400 MeV electrons at the Beam Test Facility of LNF. We also propose the investigation of a two-PMT solution coupled to a single PbF$_2$ crystal for higher-energy applications, which has potentially attractive features.Comment: 12 pages, 19 figures. v2: added section on radiation damage studie

Reduced biliverdin reductase-a expression in visceral adipose tissue is associated with adipocyte dysfunction and nafld in human obesity

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes’ size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02–1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76–1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity

Long-term sex-dependent vulnerability to metabolic challenges in prenatally stressed rats

Prenatal stress (PNS) might affect the developmental programming of adult chronic diseases such as metabolic and mood disorders. The molecular mechanisms underlying such regulations may rely upon long-term changes in stress-responsive effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect neuronal plasticity underlying mood disorders and may also play a role in metabolic regulation. Based upon previous data, we hypothesized that PNS might lead to greater vulnerability to an obesogenic challenge experienced at adulthood. In order to investigate our hypothesis, pregnant Sprague-Dawley female rats underwent a chronic procedure of restraint stress during the last week of gestation. The adult offspring were then challenged with a high fat diet (HFD) over 8 weeks and tested for metabolic and emotional endpoints. Moreover, brain specific changes in Bdnf expression levels were also assessed. Overall, HFD resulted in increased caloric intake, insulin resistance, impaired glucose tolerance and higher circulating levels of leptin, while PNS increased the leptin/adiponectin ratio, an index of metabolic risk in adult male subjects. Interestingly, HFD consumption increased anxiety-like behaviors in the Elevated Plus Maze, particularly in males, and this effect was buffered by PNS. Levels of Bdnf were finely modulated by PNS and HFD in a region- and sex-dependent fashion: female offspring overall showed greater plasticity, possibly mediated through increased total Bdnf mRNA expression both in the hippocampus and in the hypothalamus. In conclusion, while the experience of maternal stress during intrauterine life promotes metabolic dysfunction induced by a HFD at adulthood, the interaction between PNS and HFD is positive in male subjects, and in agreement with the match-mismatch hypothesis, resulting in a reduction of anxious behaviors

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

First evidence of luminescence in a He/CF4_4 gas mixture induced by non-ionizing electrons

Optical readout of Gas Electron Multipliers (GEM) provides very interesting performances and has been proposed for different applications in particle physics. In particular, thanks to its good efficiency in the keV energy range, it is being developed for low-energy and rare event studies, such as Dark Matter search. So far, the optical approach exploits the light produced during the avalanche processes in GEM channels. Further luminescence in the gas can be induced by electrons accelerated by a suitable electric field. The CYGNO collaboration studied this process with a combined use of a triple-GEM structure and a grid in an He/CF$_4$ (60/40) gas mixture at atmospheric pressure. Results reported in this paper allow to conclude that with an electric field of about 11~kV/cm a photon production mean free path of about 1.0~cm was found