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This deliverable describes the activities carried out within Work Package 15 (WP15) of the ARIADNEplus project by the different partners and describes the results achieved. The work package consists of several individual tasks and subtasks with the overall goal to develop and provide useful services to archaeologists. This means the work package is by nature heterogeneous with stand-alone tasks and services. Efforts have been made to facilitate collaboration between the individual tasks through joint work package meetings. This has resulted in new cross-task contacts being made, and some sharing of expertise to improve services has been done. A service design template aligning the ARIADNEplus services with the requirements from European Open Science Cloud (EOSC) has been created. In connection with this, the ARIADNEplus AO-CAT ontology has been adapted to the requirements from EOSC Resource Data Model (Task 15.1). The Visual Media Service (Task 15.2.1) has had a new format added, allowing for 2D visualisation of LIDAR data in DEM format. In addition, three other standards have been added: gITF, ThreeJS and IIIF, supporting various functionality in the service. The service has also been adapted to support integration with the ARIADNEplus infrastructure in D4Science. A visual wizard has been defined to guide Visual Media Service users to add hotspots to a 3D scene easily and quickly. This extension, initially implemented in 3DHOP will allow archaeologists to create interactive links from the digital 3D model to the related documentation without writing any source code (Task 15.2.2). Task 15.2.3 reworked the Online 3D Database System for Endangered architectural and archaeological Heritage in the south Eastern MEditerRAnea area (EpHEMERA). EpHEMERA is a service provided by the Cyprus Institute to visualize in 3D archaeological excavations, ancient buildings, and their related documentation. In EpHEMERA, it is possible to visualise, online and through standard web browsers, 3D architectural and archaeological models (classified according to a specific type of risk), query the database system and retrieve metadata attached to each digital object, and extract geometric and morphological information about the Cultural Heritage asset. The visualisation and annotation tool of the TSS project have been ported to the OpenLime library and integrated into the Visual Media Service (Task 15.2.1). An additional layer of SVG annotations have been developed and added to the service. The Annotation service have been used and improved in three different pilot projects. (Task 15.3.2) Various strands of work have been done improving services for text mining and Natural Language Processing (Task 15.4). One of these efforts has been building upon the outcomes of the preceding ARIADNE project. A set of archaeological Named Entity Recognition NLP pipelines were reconfigured and deployed for easier use on the General Architecture for Text Engineering (GATE) cloud. Another effort has been on extracting temporal archaeological information using two different parallel approaches, normalisation and named entity recognition. A Python development platform has been used to unify the various services. A Vocabulary Annotation Tool (Task 15.3.1) was developed using the same platform, as part of Task 15.4. The tool facilitates the locating and tagging of vocabulary terms within free text and outputs suggested subject annotations in a range of formats. The GeoPortal service (Task 15.5) is a new REST service designed to manage complex spatio-temporal documents defined by metadata profiles. It was released as a component of the gCube framework. A prototype using the service was deployed and operated to manage archaeological excavation projects (Task 15.7). Two services for querying the RDF AO-Cat metadata records aggregated by the ARIADNEplus Infrastructure was established (Task 15.6): a full-text index service and a SPARQL endpoint. The full- text index service is based on OpenSearch and supports the needed query functionality of the ARIADNEplus portal. The SPARQL endpoint allows performance of semantic queries on the RDF records within the ARIADNEplus data and knowledge cloud.

In the article titled "Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes" [1], there was an error in Figure 6. In the part of Figure 6(a), "HCC 24h" is incorrect. The corrected figure is shown below, and is listed as (Figure present).

The goal of this paper is defining a Cultural Heritage Artefact Partonomy (CHAP) concerning coroplastic Cypriot art. In particular, two case studies have been considered: the terracotta statues from the port of Salamis, attributed to the Neo-Cypriote style (ca. 600-500 BC), and the small clay statuettes from the Ayia Irini sanctuary, mostly attributed to the Cypro-Archaic period (700-500 BC). Although their differences in size, style and decorations, the items of this study represent male standing bearded figures, sometimes holding animals, arms or music instruments, and provide interesting examples for the description of human figures and their attributes in ancient times. Moreover, 3D digital models have been created digitising the physical artefacts for archaeological purposes. The objective of this work is framed within the EU GRAVITATE project, which proposes an innovative approach to the study of heritage artefacts, including 3D virtual reconstruction, classification and morphological analysis, steps that are limited by the impossibility to re-unite them physically, either because they are stored in various museums or because physical refitting fails. In this perspective, a controlled vocabulary for the documentation and retrieval of 3D digital fragments and their parts has been developed and proposed here. CHAP is a SKOS vocabulary, aligned and mapped to CIDOC CRM to integrate the description of the relationships between the parts and the overall context of the two archaeological collections. Focussing on both the artefacts and their digital counterparts, CHAP refers also to the CIDOC-CRMdig extension, where possible missing components have been identified and undertaken., Papers and presentations of CIDOC conference will be published in CIDOC ICOM site late January 2019.

BACKGROUND: IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum. Since IgG4-related disease is a multiorgan lymphoproliferative syndrome, it requires a careful differential diagnosis from other distinct disorders (sarcoidosis, immune rheumatic diseases, hematologic diseases, malignancies). Another distinctive feature is a fairly fast response to steroids, that represents the first-choice therapy. Immunosuppressant drugs (azathioprine, mycophenolate mofetil, methotrexate) might be chosen as glucocorticoid-sparing medications or to maintain steroid-induced remission (Fig. 1). METHODS: We report the case of a 70-year-old man and we performed a brief review of loiterature. RESULTS: Our patient has a clinical history including bronchial asthma, aortic aneurysm, histologically confirmed retroperitoneal fibrosis causing hydroureteronephrosis, prostatitis, interstitial pulmonary fibrosis, sclerosing chronic pancreatitis (histologically documented), previous chronic cholecystitis (histologically confirmed), previous pericarditis, xeroftalmia, polyclonal hypergammaglobulinemia, eosinophilia. His serum IgG4 levels were significantly increased (5560 mg/dl). In regard to the above mentioned elements a systemic disease characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in several tissues, was suspected. Immune-rheumatic diseases and infectious diseases were excluded. Steroid treatment was started achieving a significant swift response. CONCLUSION: Until now IgG4 related disease has been considered rare in the West and exclusive of Japanese and Korean countries, our case report leads us to reflect on the necessity to take into account this disease in patients with multisystemic involvement.

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to analyze the role of arterial stiffness, endothelial dysfunction and immunoinflammatory markers as surrogate endpoint, assessing the correlations between these markers and evaluating the therapeutic perspectives that these offer.

The typical approach for archaeological analysis is mainly qualitative and, as such, subjective. Even when some measures are reported in the documentation of artefacts, they are often approximate or ambiguous. Conversely, the quantitative approach is based on objective metrics to produce replicable results and, coupled with digital tools, can assist the qualitative analysis in archaological research with no risk of damage. In this paper, we present a geometric-quantitative approach for the analysis of archaeological finds and the preliminary results of an ongoing joint research project of two doctoral students within the frame of the EU GRAVITATE project., Eurographics Workshop on Graphics and Cultural Heritage, Virtual Archaeology, 255, 258, Andreas Scalas, Valentina Vassallo, Michela Mortara, Michela Spagnuolo, and Sorin Hermon, CCS Concepts: Computing methodologies --> Shape analysis; Mesh geometry models; Shape representations

Objectives: To evaluate whether a training intervention can improve the ability of geriatricians to recognize depression in older persons. Design: Multicenter, cluster randomized clinical trial. Setting: Fourteen geriatric outpatient clinics in Italy, each representing the unit of randomization. Participants: After training, a total of 1,914 outpatients aged 65 years and older in both arms, not on antidepressant at entry, were blindly evaluated by the clinic geriatrician, in charge of routine clinical management, and by a field researcher, who formally diagnosed depression by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), taken as the criterion standard. Intervention: After randomization, geriatricians belonging to the intervention arm were assigned to receive a residential 3-day educational program on depression. Those in the control arm received a generic course on disease management in elderly people. Measurements: Sensitivity and specificity of the diagnosis of depression made by geriatricians, compared with the DSM-IV diagnosis. Results: Sensitivity and specificity were significantly higher in trained than in untrained geriatricians (49 vs 35% and 91 vs 88%, respectively; P=.002 in marginal regression models). Effectiveness of training was confirmed, adjusting for age, sex, and cognitive performance (P=.02). Conclusion: The ability of geriatricians to diagnose depression in older outpatients can be improved with a specific training intervention. Improvement of diagnostic performance might translate into more-appropriate clinical management.

Among the physical methods of treatment of mental disorder, convulsive methods give the most positive results. They consist in the artificial induct' on of convulsions, very much similar to epileptic seizures, by means of pentamethylcne-tetrazol or electric current. The original working hypothesis (VON MEDUNA) was an alleged biological antagonism between Schizophrenia and Epilepsy, which has been mainly disproved., N/A

Enhancing Streptomyces cellulase production by supplying lignocellulose biomasses has been poorly investigated so far. In this research the biosynthesis of Streptomyces roseochromogenes ATCC13400 cellulases was increased for the first time by addition of a cellulose fraction (2.5 g·L−1) to the growth medium, isolated from the marine origin Posidonia oceanica sea balls, generally called egagropili.. In shake flasks the cellulase production increased of 4.3 folds, compared to the control, up to 268 U·L−1 in 72 h, with a productivity of 3.7 U·L−1·h−1, while in batch it was further enhanced up to 347 U·L−1 in 45 h with a doubled productivity of 7.7 U·L−1·h−1 A downstream protocol was set up by coupling two ultrafiltration steps on 10 and 3 kDa membranes to recover the enzymes from the supernatant. A pool of three cellulases, having molecular weights between 115 and 47 kDa, was recovered. The optimal conditions for their enzymatic activity were 60 °C and pH 5.0, and they showed CMCase, FPase and β-glucosidase action. In conclusion, S. roseochromogenes might be considered a new cell factory for cellulase biotechnological production that might be enhanced by using the cellulose from egagropili, a well-known marine origin plant waste, as the substrate.

Pharma-grade extractive chondroitin sulfate (CS) is widely used for osteoarthritis (OA) treatment. Recently, unsulfated biofermentative chondroitin (BC) proved positive effects in OA in vitro model. This study, based on primary pathological human synoviocytes, aimed to analyze, by a multiplex assay, a panel of OA-related biomarkers in response to short-term treatments with bovine (CSb), pig (CSp) and fish (CSf) chondroitins, in comparison to BC. As expected, all samples had anti-inflammatory properties, however CSb, CSf and especially BC affected more cytokines and chemokines. Based on these results and molecular weight similarity, CSf and BC were selected to further explore the synoviocytes’ response. In fact, Western blot analyses showed CSf and BC were comparable, downregulating OA-related biomarkers such as the proteins mTOR, NF-kB, PTX-3 and COMP-2. Proteomic analyses, performed by applying a nano-LC-MS/MS TMT isobaric labelling-based approach, displayed the modulation of both common and distinct molecules to chondroitin treatments. Thus, CSf and BC modulated the biological mediators involved in the inflammation cascade, matrix degradation/remodeling, glycosaminoglycans’ synthesis and cellular homeostasis. This study helps in shedding light on different molecular mechanisms related to OA disease that may be potentially affected not only by animal-source chondroitin sulfate but also by unsulfated biofermentative chondroitin.

Aims: We sought to compare the effects of furosemide+hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the ‘between-group’ analysis. Nevertheless, patients treated with high-dose furosemide+HSS showed significantly higher absolute delta values of IL-6 (2.3±1.2 vs. 1.7±0.9, P&nbsp

Background We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. Case presentation The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico “P. Giaccone” in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positive for Y. enterocolitica allowed to establish the final diagnosis was infective micro liver abscesses consequent to infective colitis due to Y. enterocolitica, which were successfully treated with cefixime and doxycycline. Conclusions This case report should make clinicians reflect on how complex the differential diagnosis between microliver abscesses and metastasis could be and the possibility of bacteriaemia by Y. enterocolitica even without iron overload conditions.

INTRODUCTION: Although some authors evaluated the relationship between adherence to the Mediterranean Diet (MeDi) and both ischemic and hemorrhagic stroke, hemorrhagic stroke alone is not yet examined. AIMS: We conducted a retrospective study to evaluate the relationship between adherence to MeDi and intracerebral hemorrhage (ICH) and different locations of ICH (ganglionic/internal capsule, brainstem/cerebellum, or lobar). METHODS: We analyzed charts and collected data of all consecutive patients with ICH admitted to our Internal Medicine Ward from 2005 to 2014. A scale indicating the degree of adherence to the traditional MeDi Score was constructed. RESULTS: When compared with 100 subjects without ICH, 103 subjects with ICH had significantly higher mean values of LDL (91.1 ± 38.7 mg/dl vs. 79.2 ± 34.4 mg/dl; p = 0.031), triglycerides (118.9 ± 62.9 mg/dl vs. 101.6 ± 47.6 mg/dl; p = 0.026), and proteinuria (32.6 ± 50.0 mg/dl vs. 18.1 ± 39.6 mg/dl; p=0.024) and a significantly lower mean MeDi Score (3.9 ± 1.0 vs. 7.0 ± 1.4; p < 0.0001). In a multiple regression analysis, smoking, diastolic blood pressure (DBP), and the MeDi Score remained significantly associated with ICH. We also observed a significantly lower mean MeDi Score in the lobar location group when compared with the ganglionic/internal capsule group (4.3 ± 1.0 vs. 3.5 ± 0.9; p < 0.0005). DISCUSSION: Our findings regarding the higher prevalence of ICH in patients with lower adherence to MeDi may be related to the fact that patients with lower MeDi Score exhibit a worse cardiovascular risk profile with increased risk factors such as hypertension and dyslipidemia.

Several studies suggest that inflammation has a pivotal role during the progression of osteoarthritis (OA) and cytokines have been identified as the main process mediators. This study aimed to explore the ability to modulate the main OA pro‐inflammatory biomarkers of novel gels (H‐HA/BC) based on high molecular weight hyaluronan (H‐HA) and unsulfated biotechnological chondroitin (BC). For the first time, BC was tested also in combination with H‐HA on human primary cells isolated from pathological knee joints. Specifically, the experiments were performed using an OA in vitro model based on human chondrocytes and synoviocytes. To evaluate the anti‐inflammatory effects of H‐HA/BC in comparison with H‐HA and BC single gels, NF‐kB, COMP‐2, MyD88, MMP‐13 and a wide range of cytokines, known to be specific biomarkers in OA (e.g., IL‐6, IL‐8, and TNF‐α), were evaluated. In addition, cell morphology and proliferation occurring in the presence of either H‐HA/BC or single components were assessed using time‐lapse video microscopy. It was shown that synovial fluids and cells isolated from OA suffering patients, presented a cytokine pattern respondent to an ongoing inflammation status. H‐HA and BC significantly reduced the levels of 23 biomarkers associated with cartilage damage. However, H‐HA/BC decreased significantly 24 biological mediators and downregulated 19 of them more efficiently than the single components. In synoviocytes cultures, cytokine analyses proved that H‐HA/BC gels re‐established an extracellular environment more similar to a healthy condition reducing considerably the concentration of 11 analytes. Instead, H‐HA and BC significantly modulated 7 (5 only with a longer treatment) and 8 biological cytokines, respectively. Our results suggest that H‐HA/BC beyond the viscosupplementation effect typical for HA‐based gels, can improve the inflammation status in joints and thus could be introduced as a valid protective and anti‐inflammatory intraarticular device in the field of Class III medical devices for OA treatments., Unsulfated biotechnological chondroitin by itself and complexed to hyaluronic acid counteract inflammation and improve the viability of human primary cells isolated from pathological osteoarthritis joints. Their potential efficacy, especially when combined in novel gels is supported by the modulation of several key biomarkers.

Mesenchymal stromal cells (MSCs) are currently used for cartilage cell therapy because of their well proven capacity to differentiate in chondrocytes. The advantage of MSC-based therapy is the possibility of producing a high number of chondrocytes for implants. The transplant procedure, however, has some limitations, since MSCs may produce non-functional chondrocytes. This limit has been challenged by cultivating MSC in media with hydrogels containing hyaluronic acid (HA), extractive chondroitin sulfate (CS), or bio-fermentative unsulphated chondroitin (BC) alone or in combination. Nevertheless, a clear study of the effect of glycosaminoglycans (GAGs) on chondrocyte differentiation is still lacking, especially for the newly obtained unsulfated chondroitin of biotechnological origin. Are these GAGs playing a role in the commitment of stem cells to chondrocyte progenitors and in the differentiation of progenitors to mature chondrocytes? Alternatively, do they have a role only in one of these biological processes? We evaluated the role of HA, CS, and – above all – BC in cell commitment and chondrocyte differentiation of MSCs by supplementing these GAGs in different phases of in vitro cultivation. Our data provided evidence that a combination of HA and CS or of HA and BC supplemented during the terminal in vitro differentiation and not during cell commitment of MSCs improved chondrocytes differentiation without the presence of fibrosis (reduced expression of Type I collagen). This result suggests that a careful evaluation of extracellular cues for chondrocyte differentiation is fundamental to obtaining a proper maturation process.

Il saggio illustra la metodologia utilizzata per le fasi di conoscenza e progetto che hanno condotto alla redazione di una proposta urbanistica per il recupero del centro storico di un piccolo centro siciliano di origine medioevale.

Ultraviolet (UV) radiations are responsible for skin photoaging inducing alteration of the molecular and cellular pathways resulting in dryness and reduction of skin elasticity. In this study, we investigated, in vitro, the antiaging and antioxidant effects of hyaluronan formulations based hydrogel. Skinkò E, an intradermic formulation composed of hyaluronic acid (HA), minerals, amino acids, and vitamins, was compared with the sole HA of the same size. For this purpose, HaCaT cells were subjected to UV-A radiations and H2O2 exposure and then treated with growth medium (CTR) combined with M-HA or Skinkò E to evaluate their protective ability against stressful conditions. Cells reparation was evaluated using a scratch in vitro model and Time-Lapse Video Microscopy. A significant protective effect for Skinkò E was shown with respect to M-HA. In addition, Skinkò E increased cell reparation. Therefore, NF-kB, SOD-2, and HO-1 were significantly reduced at the transcriptional and protein level. Interestingly, γ-H2AX and protein damage assay confirmed the protection by hyaluronans tested against oxidative stress. G6pdΔ ES cell line, highly susceptible to oxidative stress, was used as a further cellular model to assess the antioxidant effect of Skinkò E. Western blotting analyses showed that the treatment with this new formulation exerts marked antioxidant action in cells exposed to UV-A and H2O2. Thus, the protective and reparative properties of Skinkò E make it an interesting tool to treat skin aging.

The biological activity of chondroitin sulfate (CS) and glucosamine (GlcN) food supplements (FS), sold in USA against osteoarthritis, might depend on the effective CS and GlcN contents and on the CS structural characteristics. In this paper three USA FS were compared to two pharmaceutical products (Ph). Analyses performed by HPAE-PAD, by HPCE and by SEC-TDA revealed that the CS and GlcN titers were up to −68.8% lower than the contents declared on the labels and that CS of mixed animal origin and variable molecular weights was present together with undesired keratan sulfate. Simulated gastric and intestinal digestions were performed in vitro to evaluate the real CS amount that may reach the gut as biopolymer. Chondrocytes and synoviocytes primary cells derived from human pathological joints were used to assess: cell viability, modulation of the NF-κB, quantification of cartilage oligomeric matrix protein (COMP-2), hyaluronate synthase enzyme (HAS-1), pentraxin (PTX-3) and the secreted IL-6 and IL-8 to assess inflammation. Of the three FS tested only one (US FS1) enhanced chondrocytes viability, while all of them supported synoviocytes growth. Although US FS1 proved to be less effective than Ph as it reduced NF-kB, it could not down-regulate COMP-2, HAS-1 was up-regulated but with a lower efficacy. Inflammatory cytokines were markedly reduced by Ph while a slight decrease was only found for US-FS1.

Interstitial cystitis and/or bladder pain syndrome (IC/BPS) are characterized by discomfort, abdominal pain, and pelvic pain, and they are often associated with chronic diseases. Pathological conditions related to IC/BPS can occur due to a defect in the integrity of the bladder lining. This defect has been ascribed to damage to the glycosaminoglycan (GAG) layer of the urinary epithelium. In addition, the incipient cascade of inflammation events might prompt extracellular matrix degradation. Several medical devices based on GAG instillation were proposed to re-establish epithelial integrity by GAGs binding to proteoglycans or interacting with structural urothelium. However, to date, only in vitro studies have investigated the GAG, hyaluronic acid (HA). In the present study, TNFα treatment was used to mimic IC/BPS-induced damage in bladder cells in an in vitro model. Highly purified fermentative HA and pharmaceutical grade bovine chondroitin sulfate (CSb), alone or in combination, were evaluated for the ability to counteract bladder cell damage. We evaluated NF-κB with western blots, and we analyzed interleukin 6 and 8 expression at the transcriptional and protein levels with quantitative RT-PCR, western blotting, and ELISA. We also evaluated the expression of an antibacterial peptide, human β-defensin-2. We confirmed our results in a 3D bladder epithelium model. Our results demonstrated that inflammatory status was reduced in the presence of HA, CSb, and the combination of both (HA/CSb 1.6%/2% w/v). This result suggested that these GAGs might be suitable for treating IC/BPS. All the assayed biomarkers showed that HA/CSb treatment modulated cells towards a more physiological status. Finally, we compared two commercial products suggested for the IC/BPS treatments and found that the product with more Ca++, showed enhanced anti-inflammatory activity and provided superior mucoadhesivity.

High molecular weight hyaluronan (H-HA) has a pivotal role in the maintenance of normal functions of synovial fluid and structure of the articular joint, but it has been shown that its concentration is reduced in patients affected by degenerative cartilage diseases, such as osteoarthritis (OA). The aim of this study was to investigate the anti-inflammatory effects and properties of hybrid cooperative complexes based on high and low molecular weight hyaluronan (HCC) compared to H-HA on human primary cells derived by pathological joints. In addition, the rheological behavior of HCC was evaluated in order to define their potential as viscosupplement gel in degenerated joints. The experiments were performed using an in vitro model of OA based on human chondrocytes and synoviocytes isolated from degenerated joints of patients hospitalized for surgical replacement. In order to assess the anti-inflammatory effects of HCC, we evaluated NF-kB, COMP-2, IL-6, and IL-8 as specific markers at the transcriptional and/or protein level. Moreover, the proliferative properties of HCC were assessed using time lapse video microscopy. We showed that chondrocytes and synoviocytes clearly presented an altered cytokine profile compatible with a severe ongoing inflammation status. H-HA and, above all, HCC significantly reduced levels of the specific biomarkers evaluated and improved cartilage healing. The rheological profile indicated HCC suitability for intra-articular injection in joint diseases. HCC viscoelastic properties and the protective/anti-inflammatory effect on human chondrocytes and synoviocytes suggest the novel HCC-based gels as a valid support for OA management.

Background: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hypercholesterolemia, hypertension, hyperglycemia, and a family history of atherosclerotic disease may induce functional and structural changes in the endothelium that imply the progressive loss of its protective role and the development of a proatherosclerotic state called endothelial dysfunction. Methods: The evaluation of the function of endothelial cells is based on the measurement of endothelial cell response to the stimulation by vasoactive substances. The endothelial response can be assessed in the coronary arteries and peripheral circulations. On our opinion, among the techniques, the most advantageous, reproducible, minimally invasive and statistically valid, as shown in many trials, is the Endo-PAT. This technique assesses endothelial function on peripheral arteries evaluating, at the level of the distal phalanx of the index finger, the vascular response to a period of ischemia in the arm induced through occlusion of the brachial artery (for five minutes) and subsequent restoration of blood flow. An additional method that is used to evaluate the state of wellness of large arteries is arterial stiffness. Arterial stiffness can be described as a reduced capability of a vessel to dilate or contract in response to pressure changes; it is defined using two parameters: compliance and distensibility. Result and Conclusion: The present review intends to clarify the mechanisms behind the development of endothelial dysfunction, and aims to show how widely proven is the correlation between endothelial dysfunction (assessed both by Endo-PAT and sphigmoCOR) and cardiovascular diseases, such as atherosclerosis, hypertension, diabetes mellitus, stroke, coronary artery disease and heart failure. Moreover, the assessment of endothelial dysfunction may represent an integral adjuvant test to identify the predisposed patients at risk for future cardiovascular accidents, as we suggest.

Background and aims Only one study has examined endothelial function in subjects with acute ischemic stroke and no study has yet assessed arterial stiffness and reactive hyperemia peripheral arterial tonometry (RH-PAT) in ischemic stroke and its clinical subtypes. Our study aimed to evaluate arterial stiffness and endothelial dysfunction indexes in patients with acute ischemic stroke and the relationship between endothelial dysfunction indexes and arterial stiffness markers and stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification. Methods We enrolled 98 patients with a diagnosis of acute ischemic stroke and 105 hospitalized patients without a diagnosis of acute ischemic stroke. Arterial stiffness analysis was conducted by applanation tonometry to record radial artery pressure waveform continuously; augmentation index (Aix) and pulse wave velocity (PWV) were calculated. The reactive hyperemia index (RHI) was assessed by peripheral arterial tonometry. Results In comparison to controls, ischemic stroke subjects had higher mean levels of PWV, Aix, and significantly lower mean RHI values. Compared to subjects with lacunar and cardioembolic stroke, those with Large Artery AtheroSclerosis (LAAS) subtype of stroke had higher median levels of PWV and significantly lower median levels of RHI. On multinomial logistic regression analysis of predictive variables of stroke subtype (lacunar vs. LAAS and lacunar vs. cardioembolic), we observed a negative association between RHI value and LAAS subtype and a negative association of PWV with cardioembolic subtype. Conclusions Our findings underline the relationship between endothelial and arterial stiffness index correlations in patients with acute ischemic stroke, also suggesting the use of a combination of PAT and arterial stiffness indexes to better categorize patients with ischemic stroke.

Introduction Patients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin. Aims We evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites. Methods 59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125-250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A, n:38), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, n: 21). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment. Results Subjects in group A were observed to have a significant reduction of serum levels of TNF-α, IL-1β, IL-6, ANP, BNP, and visfatin, thus regarding primary efficacy endpoints, in Group A vs. Group B we observed higher Δ-TNF-α, Δ-IL-1β, Δ-IL-6, Δ-ANP, Δ-BNP, Δ-visfatin, Δ-Leptin at discharge. Discussion Our findings underline the possible inflammatory and metabolic effect of saline overload correction in treatment of cirrhosis complications such as refractory ascites, suggesting a possible role of inflammatory and metabolic-nutritional variables as severity markers in these patients.

Benign myoepithelioma is a very rare form of salivary gland tumor, composed entirely of myoepithelial cells. It accounts for approximately 1% of all salivary gland tumors and is most frequently located in the parotid gland and in the minor salivary glands of the hard palate. We describe herein the ninth reported case of myoepithelioma of the submandibular gland. Benign myoepithelioma must be differentiated from several benign and malignant epithelial and mesenchymal tumors. Immunohistochemical staining can help differentiate between these conditions, but histopathology remains the gold standard for diagnosing this neoplastic process.