Differential Cannabinoid Receptor Expression during Reactive Gliosis: a Possible Implication for a Nonpsychotropic Neuroprotection

Activated microglia and astrocytes produce a large number of inflammatory and neurotoxic substances in various brain pathologies, above all during neurodegenerative disorders. In the search for new neuroprotective compounds, interest has turned to marijuana derivatives, since in several in vitro, in vivo, and clinical studies, they have shown a great ability to control neuroinflammation

genomic and functional profiling of human down syndrome neural progenitors implicates s100b and aquaporin 4 in cell injury

Down syndrome (DS) is caused by trisomy of chromosome 21 and is characterized by mental retardation, seizures and premature Alzheimer's disease. To examine neuropathological mechanisms giving rise to this disorder, we generated multiple human DS neural progenitor cell (NPC) lines from the 19-21 week frontal cortex and characterized their genomic and functional properties. Microarray profiling of DS progenitors indicated that increased levels of gene expression were not limited to chromosome 21, suggesting that increased expression of genes on chromosome 21 altered transcriptional regulation of a subset of genes throughout the entire genome. Moreover, many transcriptionally dysregulated genes were involved in cell death and oxidative stress. Network analyses suggested that upregulated expression of chromosome 21 genes such as S100B and amyloid precursor protein activated the stress response kinase pathways, and furthermore, could be linked to upregulation of the water channel aquaporin 4 (AQP4). We further demonstrate in DS NPCs that S100B is constitutively overexpressed, that overexpression leads to increased reactive oxygen species (ROS) formation and activation of stress response kinases, and that activation of this pathway results in compensatory AQP4 expression. In addition, AQP4 expression could be induced by direct exposure to ROS, and siRNA inhibition of AQP4 resulted in elevated levels of ROS following S100B exposure. Finally, elevated levels of S100B-induced ROS and loss of AQP4 expression led to increased programmed cell death. These findings suggest that dysregulation of chromosome 21 genes in DS neural progenitors leads to increased ROS and thereby alters transcriptional regulation of cytoprotective, non-chromosome 21 genes in response to ongoing cellular insults

Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic

Background and purposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils.MethodsA prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients.ResultsIn the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy.ConclusionsA systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs

"Diagnosis on the Dock" project: A proactive screening program for diagnosing pulmonary tuberculosis in disembarking refugees and new SEI model.

Abstract Objective From 2011 to 2017, the total number of refugees arriving in Europe, particularly in Italy, climbed dramatically. Our aim was to diagnose pulmonary TB in migrants coming from the African coast using a clinical-based port of arrival (PoA) screening program. Methods From 2016 to 2018, migrants coming via the Mediterranean Route were screened for body temperature and the presence of cough directly on the dock: if they were feverish with productive cough, their sputum was examined with NAAT; with a dry cough, they underwent Chest-X-ray (CXR). Those migrants with positive NAAT or CXR suggestive for TB were admitted to our ward. In addition, we plotted an SEI simulation of our project to evaluate the epidemiological impact of our screening. Results Out of 33.676 disembarking migrants, 314 (0.9%) had fever and cough: 80 (25.47%) with productive cough underwent NAAT in sputum, and 16 were positive for TB; 234 (74.52%) with dry cough had a CXR examination, and 39 were suggestive of TB, later confirmed by mycobacterial culture. The SEI-new model analysis demonstrated that our screening program significantly reduced TB spreading all over the country. Conclusions For possible future high migrant flows, PoA screening for TB has to be considered feasible and effective in decreasing TB spreading

Design and Status of the ELIMED Beam Line for Laser-Driven Ion Beams

Charged particle acceleration using ultra-intense and ultra-short laser pulses has gathered a strong interest in the scientific community and it is now one of the most attractive topics in the relativistic laser-plasma interaction research. Indeed, it could represent the future of particle acceleration and open new scenarios in multidisciplinary fields, in particular, medical applications. One of the biggest challenges consists of using, in a future perspective, high intensity laser-target interaction to generate high-energy ions for therapeutic purposes, eventually replacing the old paradigm of acceleration, characterized by huge and complex machines. The peculiarities of laser-driven beams led to develop new strategies and advanced techniques for transport, diagnostics and dosimetry of the accelerated particles, due to the wide energy spread, the angular divergence and the extremely intense pulses. In this framework, the realization of the ELIMED (ELI-Beamlines MEDical applications) beamline, developed by INFN-LNS (Catania, Italy) and installed in 2017 as a part of the ELIMAIA beamline at the ELI-Beamlines (Extreme Light Infrastructure Beamlines) facility in Prague, has the aim to investigate the feasibility of using laser-driven ion beams in multidisciplinary applications. ELIMED will represent the first user's open transport beam line where a controlled laser-driven ion beam will be used for multidisciplinary and medical studies. In this paper, an overview of the beamline, with a detailed description of the main transport elements, will be presented. Moreover, a description of the detectors dedicated to diagnostics and dosimetry will be reported, with some preliminary results obtained both with accelerator-driven and laser-driven beams

The Acquisition Camera System for SOXS at NTT

SOXS (Son of X-Shooter) will be the new medium resolution (R$\sim$4500 for a 1 arcsec slit), high-efficiency, wide band spectrograph for the ESO-NTT telescope on La Silla. It will be able to cover simultaneously optical and NIR bands (350-2000nm) using two different arms and a pre-slit Common Path feeding system. SOXS will provide an unique facility to follow up any kind of transient event with the best possible response time in addition to high efficiency and availability. Furthermore, a Calibration Unit and an Acquisition Camera System with all the necessary relay optics will be connected to the Common Path sub-system. The Acquisition Camera, working in optical regime, will be primarily focused on target acquisition and secondary guiding, but will also provide an imaging mode for scientific photometry. In this work we give an overview of the Acquisition Camera System for SOXS with all the different functionalities. The optical and mechanical design of the system are also presented together with the preliminary performances in terms of optical quality, throughput, magnitude limits and photometric properties.Comment: 9 pages, 7 figures, SPIE conferenc

Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in rat chronic granulomatous inflammation

Chronic inflammation, a condition frequently associated with several pathologies, is characterized by angiogenic and fibrogenic responses that may account for the development of granulomatous tissue. We previously demonstrated that the chymase, rat mast cell protease-5 (rMCP-5), exhibits pro-inflammatory and pro-angiogenic properties in a model of chronic inflammation sustained by mast cells (MCs), granuloma induced by the subcutaneous carrageenan-soaked sponge implant in rat. In this study, we investigated the effects of palmitoylethanolamide (PEA), an anti-inflammatory and analgesic endogenous compound, on rMCP-5 mRNA expression and Microphtalmia-associated Transcription Factor (MITF) activation in the same model of chronic inflammation. The levels of rMCP-5 mRNA were detected using semi-quantitative RT-PCR; the protein expression of chymase and extracellular signal-regulated kinases (ERK) were analyzed by western blot; MITF/DNA binding activity and MITF phosphorylation were assessed by electrophoretic mobility shift assay (EMSA) and immunoprecipitation, respectively. The administration of PEA (200, 400 and 800 µg/ml) significantly decreased rMCP-5 mRNA and chymase protein expression induced by λ-carrageenan. These effects were associated with a significant decrease of MITF/DNA binding activity and phosphorylated MITF as well as phosphorylated ERK levels. In conclusion, our results, showing the ability of PEA to inhibit MITF activation and chymase expression in granulomatous tissue, may yield new insights into the understanding of the signaling pathways leading to MITF activation controlled by PEA

New Alien Mediterranean Biodiversity Records (August 2022)

In this Collective Article on alien and cryptogenic diversity in the Mediterranean Sea we report a total of 19 species belonging to nine Phyla and coming from nine countries. Several of these records concern fish species, and of particular interest are the first records of: Terapon puta for Italian waters; Pteragopus trispilus from Malta; Plotosus lineatus from Cyprus; and the northernmost Mediterranean record of Lagocephalus sceleratus. The northernmost Mediterranean record was also reported for the sea urchin Diadema setosum. The portunid crab Thalamita poissonii was recorded for the first time in Libya. The copepod Pseudodiaptomus marinus was recorded for the first time in the Marmara Sea. The polychaete Branchiomma luctuosum was recorded for the first time from the Mediterranean coast of France. The alien anemone Diadumene lineata was recorded for the first time from Slovenia. The macroalgae Sargassum furcatum was recorded for the first time from Italy. The new Mediterranean records here reported help tracing abundance and distribution of alien and cryptic species in the Mediterranean Sea