Overexpression of the vitronectin v10 subunit in patients with nonalcoholic steatohepatitis: Implications for noninvasive diagnosis of NASH

Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients. On the basis of the assumption that steatohepatitis leads to the remodelling of the liver extracellular matrix (ECM), NASH-specific fragments were in silico analysed for their involvement in the ECM molecular composition. The 10 kDa C-terminal fragment of the ECM prote in vitro nectin (VTN) was then selected as a promising circulating biomarker in discriminating NASH. The analysis of sera of patients provided these major findings: the circulating VTN fragment (i) is overexpressed in NASH patients and positively correlates with the NASH activity score (NAS); (ii) originates from the disulfide bond reduction between the V10 and the V65 subunits. In conclusion, V10 determination in the serum could represent a reliable tool for the noninvasive discrimination of NASH from simple steatosi

Anisotropy in the Turbulent Flow through Random and Emergent Rigid Vegetation on Rough Beds

In this study, we explore for the first time the turbulence anisotropy of flows through random and emergent rigid vegetation on rough beds, using the anisotropy invariant maps (AIMs). We present the results of an experimental campaign, based on Acoustic Doppler Velocimeter (ADV) measures, varying the bed sediment size (coarse sand, fine gravel, and coarse gravel), under the same hydraulic conditions. The evolution of the stress ellipsoid formed by the Reynolds stresses is discussed, together with the analysis of the anisotropic invariant function. We demonstrate that vegetation distribution is of paramount importance in the turbulence anisotropy evolution along the water depth. While in the case of a regular pattern the bed roughness is the key parameter in determining the shape of the stress ellipsoid in the near-bed region, in a random vegetation distribution this assumption is no longer valid. However, by increasing the bed roughness in such kind of arrangement, its effect on the turbulence anisotropy are visible in specific areas around the vegetation stem. This is confirmed by the analysis of the anisotropic invariant function calculated for different sections close to the stem itself

The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease

peri implantitis and periodontitis use of bacteriological test in dental practice

Peri-implantitis has been defined as an inflamematory condition involving dental implants, surrounding mucosa and bone, which lose supporting bone. Although high success rates for endosseous implants have been reported, failures occur, and some implants are lost or removed. At least 10% of the failures have been suggested to be the result of peri-implantitis. One of the major causes of the peri-implantitis is the bacterial colonization of implant surfaces but additional risk factors such as periodontitis, poor oral hygiene, tobacco consumption, prepost operative therapies and genetic susceptibility should be considered. In the present study a real-time PCR bases assay was designed to detect and quantify red complex species, then used to investigate 307 periodontal pocket samples from 127 periodontitis patients and 180 controls. Results demonstrated a significant higher prevalence of red complex species and increased amount of Porphyromonas gingivalis and Treponema denticolain periodontal pocket of periodontitis. Since a higher risk of peri-implantitis occurs in periodontally affected patients, detection and treatment of bacteria is a fundamental objective to ensure dental implant survival

In nome del padre de'lumi progetto delle basi principali della costituzione politica della nazione napolitana, rassegnato alla dilei augusta assemblea dal filo-realista-nazionale Francesco Saverio Del Gaudio

In nome del padre de'lumi progetto delle basi principali della costituzione politica della nazione napolitana, rassegnato alla dilei augusta assemblea dal filo-realista-nazionale Francesco Saverio Del Gaudio Napoli : dalla tipografia di Porcelli, 1820 66, [2] p. ; 8

In search of the seismogenic fault of the March 23rd 2018 earthquake (Mw 3.7) near Brindisi (Puglia, Southern Italy)

T The portion of the southern Adriatic Sea, adjacent to the Murge area (Apulian Foreland, Southern Italy), is considered mainly aseismic. The recent March 23rd 2018 earthquake (Mw 3.7), occurred near Brindisi (Puglia Region), giving us occasion to reconsider data coming from different sources (instrumentally-recorded, historically-documented and palaeoseismologically-interpreted earthquakes), that suggest some moderate seismic shocks in this portion of the Adriatic Sea. The present study, based on the re-interpretation of public domain seismic profiles and exploration well logs available in the ViDEPI Project, has been focused on the recognition of faults with Quaternary activity in the epicentral area. A S-dipping fault, with a main dip-slip component of movement, is suggested to be the seismogenic source. Its geometry is consistent with the fault plane solution and the depth of the hypocenter calculated by the INGV (Istituto Nazionale di Geofisica e Vulcanologia).  </div

Ranolazine reduces symptoms of palpitations and documented arrhythmias in patients with ischemic heart disease — The RYPPLE randomized cross-over trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520)

Antiplatelet therapy in elderly patients with acute coronary syndrome: Between scientific evidence and future perspectives.

Dual antiplatelet therapy (DAPT) is an important strategy for reducing cardiovascular events (CV) after an acute coronary syndrome (ACS). Elderly patients undergoing DAPT have a higher risk of bleeding than younger patients for a variety of reasons. Stratification of thrombotic/hemorrhagic risk is mandatory in order to decide on the type and duration of DAPT. The percentage of patients ≥ 75 years represented in clinical trials is not large, so very often elderly people are prescribed treatment protocols only experimented on younger patients with a lower hemorrhagic risk. However, even in patients aged ≥ 75 treated with invasive or conservative therapy, after an ACS, a DAPT with aspirin 80-100 mg/day plus a P2Y12 receptor inhibitor for 12 months is recommended. In elderly patients, DAPT should be considered a dynamic process that can be modified over time based on the patient's clinical conditions, or any other necessities (non-procrastinating surgical interventions, comorbid-like effects that can increase hemorrhagic risk). In patients with moderate-high or very high hemorrhagic risk, DAPT treatment should last less than 12 months. A prolongation of DAPT beyond 12 months in this setting is limited to a very low percentage of patients, after careful assessment of ischemic/hemorrhagic profile

Characterization of a new variant DNA (cytosine-5)-methyltransferase unable to methylate double stranded DNA isolated from the marine annelid worm Chaetopterus variopedatus

AbstractThe enzyme S-adenosylmethionine-DNA (cytosine-5)-methyltransferase has been identified, first time for invertebrates, in embryos of the marine polychaete annelid worm Chaetopterus variopedatus. The molecule has been isolated from embryos at 15 h of development. It is a single peptide of about 200 kDa molecular weight, cross-reacting with antibodies against sea urchin DNA methyltransferase. The enzymatic properties of the molecule are similar to those of Dnmt1 methyltransferases isolated from other organisms, but with the peculiarity to be unable to make ‘de novo’ methylation on double stranded DNA

Pharmacodynamic effects of atorvastatin vs. rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy — The PEARL randomized cross-over study

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