The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Comparison between manual scaling and Autoscala automatic scaling applied to Sodankylä Geophysical Observatory ionograms

This paper presents a comparison between standard ionospheric parameters manually and automatically scaled from ionograms recorded at the high-latitude Sodankylä Geophysical Observatory (SGO, ionosonde SO166, 64.1° geomagnetic latitude), located in the vicinity of the auroral oval. The study is based on 2610 ionograms recorded during the period June–December 2013. The automatic scaling was made by means of the Autoscala software. A few typical examples are shown to outline the method, and statistics are presented regarding the differences between manually and automatically scaled values of F2, F1, E and sporadic E (Es) layer parameters. We draw the conclusions that: 1. The F2 parameters scaled by Autoscala, foF2 and M(3000)F2, are reliable. 2. F1 is identified by Autoscala in significantly fewer cases (about 50 %) than in the manual routine, but if identified the values of foF1 are reliable. 3. Autoscala frequently (30% of the cases) detects an E layer when the manual scaling process does not. When identified by both methods, the Autoscala E-layer parameters are close to those manually scaled, foE agreeing to within 0.4 MHz. 4. Es and parameters of Es identified by Autoscala are in many cases different from those of the manual scaling. Scaling of Es at auroral latitudes is often a difficult task

Soft tissue regeneration using leukocyte-platelet rich fibrin after exeresis of hyperplastic gingival lesions: Two case reports

Introduction The Leukocyte-PRF (Leukocyte-Platelet Rich Fibrin) belongs to a second generation of platelet concentrates which doesn’t need a biochemical blood manipulation. It is used for tissue healing and regeneration in periodontal and oral-maxillofacial surgery. We report two cases of hyperplastic gingival lesions treated by exeresis and application of PRF membranes in order to improve and accelerate tissue healing. Case Presentation Two patients (one Caucasian female, 78-year-old, and one Caucasian male, 30-year-old) were treated for hyperplastic gingival lesions. They underwent to exeresis of lesions and application of PRF membranes. Tissue healing was clinically evaluated after one, three, seven, fourteen and thirty post-operative days. No recurrences were observed after two years of semiannual follow up. Conclusion We obtained rapid and good healing of soft tissues probably due to the elevated content of leukocytes, platelets and growth factors in the leukocyte-platelet rich fibrin. According to our results we suggest L-PRF employment for wounds covering after exeresis of oral neoformations such as hyperplastic gingival lesions

A Self-Consistent Microscopic Theory of Surface Superconductivity

The electronic structure of the superconducting surface sheath in a type-II superconductor in magnetic fields $H_{c2}<H<H_{c3}$ is calculated self-consistently using the Bogoliubov-de Gennes equations. We find that the pair potential $\Delta(x)$ exhibits pronounced Friedel oscillations near the surface, in marked contrast with the results of Ginzburg-Landau theory. The role of magnetic edge states is emphasized. The local density of states near the surface shows a significant depletion near the Fermi energy due to the development of local superconducting order. We suggest that this structure could be unveiled by scanning-tunneling microscopy studies performed near the edge of a superconducting sample.Comment: 12 pages, Revtex 3.0, 3 postscript figures appende

Pain-related increase in serotonin transporter gene methylation associates with emotional regulation in 4.5-year-old preterm-born children.

The main goal of this study was to assess the association between pain-related increase in serotonin transporter gene (SLC6A4) methylation and emotional dysregulation in 4.5-year-old preterm children compared with full-term matched counterparts. METHODS: Preterm (n = 29) and full-term (n = 26) children recruited from two Italian hospitals were followed-up from October 2011 to December 2017. SLC6A4 methylation was assessed from cord blood at birth from both groups and peripheral blood at discharge for preterm ones. At 4.5 years, emotional regulation (ie, anger, fear and sadness) was assessed through an observational standardised procedure. RESULTS: Preterm children (18 females; mean age = 4.5, range = 4.3-4.8) showed greater anger display compared with full-term controls (14 females; mean age = 4.5, range = 4.4-4.9) in response to emotional stress. Controlling for adverse life events occurrence from discharge to 4.5 years and SLC6A4 methylation at birth, CpG-specific SLC6A4 methylation in the neonatal period was predictive of greater anger display in preterm children but not in full-term ones. CONCLUSION: These findings contribute to highlight how epigenetic regulation of serotonin transporter gene in response to NICU pain exposure contributes to long-lasting programming of anger regulation in preterm children

Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells

Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining

Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification

<p>Abstract</p> <p>Background</p> <p>Malaria is one of the most important infectious diseases in the world. Although most cases are found distributed in the tropical regions of Africa, Asia, Central and South Americas, there is in Europe a significant increase in the number of imported cases in non-endemic countries, in particular due to the higher mobility in today's society.</p> <p>Methods</p> <p>The prevalence of a possible asymptomatic infection with <it>Plasmodium </it>species was assessed using Nucleic Acid Sequence Based Amplification (NASBA) assays on clinical samples collected from 195 study cases with no clinical signs related to malaria and coming from sub-Saharan African regions to Southern Italy. In addition, base-line demographic, clinical and socio-economic information was collected from study participants who also underwent a full clinical examination.</p> <p>Results</p> <p>Sixty-two study subjects (31.8%) were found positive for <it>Plasmodium </it>using a pan <it>Plasmodium </it>specific NASBA which can detect all four <it>Plasmodium </it>species causing human disease, based on the small subunit 18S rRNA gene (18S NASBA). Twenty-four samples (38%) of the 62 18S NASBA positive study cases were found positive with a Pfs25 mRNA NASBA, which is specific for the detection of gametocytes of <it>Plasmodium falciparum</it>. A statistically significant association was observed between 18S NASBA positivity and splenomegaly, hepatomegaly and leukopaenia and country of origin.</p> <p>Conclusion</p> <p>This study showed that a substantial proportion of people originating from malaria endemic countries harbor malaria parasites in their blood. If transmission conditions are available, they could potentially be a reservoir. Thefore, health authorities should pay special attention to the health of this potential risk group and aim to improve their health conditions.</p

A Beta Beam complex based on the machine upgrades for the LHC

The Beta Beam CERN design is based on the present LHC injection complex and its physics reach is mainly limited by the maximum rigidity of the SPS. In fact, some of the scenarios for the machine upgrades of the LHC, particularly the construction of a fast cycling 1 TeV injector (``Super-SPS''), are very synergic with the construction of a higher $\gamma$ Beta Beam. At the energies that can be reached by this machine, we demonstrate that dense calorimeters can already be used for the detection of $\nu$ at the far location. Even at moderate masses (40 kton) as the ones imposed by the use of existing underground halls at Gran Sasso, the CP reach is very large for any value of $\theta_{13}$ that would provide evidence of $\nu_e$ appearance at T2K or NO$\nu$A ($\theta_{13}\geq 3^\circ$). Exploitation of matter effects at the CERN to Gran Sasso distance provides sensitivity to the neutrino mass hierarchy in significant areas of the $\theta_{13}-\delta$ plane