Estimating Temporal Changes in Extreme Rainfall in Sicily Region (Italy)

An intensification of extreme rainfall events have characterized several areas of peninsular and insular Italy since the early 2000s, suggesting an upward ongoing trend likely driven by climate change. In the present study temporal changes in 1-, 3-, 6-, 12- and 24-h annual maxima rainfall series from more than 200 sites in Sicily region (Italy) are examined. A regional study is performed in order to reduce the uncertainty in change detection related to the limited length of the available records of extreme rainfall series. More specifically, annual maxima series are treated according to a regional flood index - type approach to frequency analysis, by assuming stationarity on a decadal time scale. First a cluster analysis using at-site characteristics is used to determine homogeneous rainfall regions. Then, potential changes in regional L-moment ratios are analyzed using a 10-year moving window. Furthermore, the shapes of regional growth curves, derived by splitting the records into separate decades, are compared. In addition, a jackknife procedure is used to assess uncertainty in the fitted growth curves and to identify significant trends in quantile estimates. Results reveal that L-moment ratios show a general decreasing trend and that growth curves for the last decade (2000–2009) usually do not stand above the others, with the only exception of the ones related to the outer western part of Sicily. On the other hand, rainfall quantile estimates for the same period are the highest values almost all over the region. An explanation can be found in the increase of subregional average medians, largely caused by recent severe local storms.     

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells.     

Lectins,trypsin and α-amylase inhibitors in dietary supplements containing <Emphasis Type="Italic">Phaseolus vulgaris</Emphasis>

Some dietary supplements used to control overweight are based on protein concentrates from Phaseolus vulgaris, or kidney bean, known to contain high levels of α-amylase inhibitor, which may reduce the adsorption and prevent the digestion of carbohydrates. These concentrates of kidney bean also contain significant levels of antinutritional factors such as lectins and trypsin inhibitors. In recent years the concentrates of kidney bean have been processed to inactivate lectins and trypsin-inhibitor activity while preserving substantial α-amylase inhibitor activity. The aim of this study was to investigate and to compare the activity of the α-amylase inhibitor in some commercial supplements, and to determine the levels of residual lectins and trypsin inhibitors. The results show that the technological treatment used to reduce the levels of lectins and trypsin inhibitors partially decreases the activity of the amylase inhibitor. This study suggests the need for better standardization of the technological treatment of protein concentrates to ensure both the efficacy and safety of these dietary supplements.     

Revision,calibration, and application of the volume method to evaluate the geothermal potential of some recent volcanic areas of Latium,Italy

The volume method is used to evaluate the productive potential of unexploited and minimally exploited geothermal fields. The distribution of P_CO2 in shallow groundwaters delimits the geothermal fields. This approach is substantiated by the good correspondence between zones of high CO₂ flux, and the areal extension of explored geothermal systems of high enthalpy (Monte Amiata and Latera), medium enthalpy (Torre Alfina) and low enthalpy (Viterbo). Based on the data available for geothermal fields either under exploitation or investigated by long-term production tests, a specific productivity of 40 t h⁻¹ km⁻³ is assumed. The total potential productivity for the recent volcanic areas of Latium is about 28 × 10³ t h⁻¹, with 75% from low-enthalpy geothermal fields, 17% from medium-enthalpy systems, and 8% from high-enthalpy reservoirs. The total extractable thermal power is estimated to be 2220–2920 MW, 49–53% from low-enthalpy geothermal fields, 28–32% from medium-enthalpy systems, and 19–20% from high-enthalpy reservoirs.     

Ultrastructural analysis of human bone marrow mesenchymal stem cells during in vitro osteogenesis and chondrogenesis

The main purpose of this article was to describe the morphology of mesenchymal stem cells (MSCs) differentiated in vitro towards osteogenic and chondrogenic lineages and to focus on the ultrastructural features associated with these processes. Human mononuclear cells (hMNC) were isolated, expanded, and analyzed for the expression of specific cell surface markers to demonstrate their stem cell characteristics. Human mononuclear cells were differentiated in vitro in an osteogenic and in a chondrogenic sense for 7, 14, 21, and 28 days. Subsequently, they were processed using electron microscopic analysis (FEISEM). Alizarin red and alcian blue staining were carried out to demonstrate the deposition of mineral salts and proteoglycans in the extracellular matrix. Undifferentiated MSCs showed a cell surface covered by filopodia and ondulopodia. During differentiation, the MSCs changed their shape from a round to a fibroblastic-like shape. At the end of the differentiation, several filaments with a parallel orientation in the osteogenic samples as well as a network organization in the chondrogenic samples were detected in the extracellular spaces. This study demonstrated that there are morphological features associated with the undifferentiated and differentiated states of the MSCs, which could be utilized as new parameters for identifying and classifying these cells.     

Do Synovial Inflammation and Meniscal Degeneration Impact Clinical Outcomes of Patients Undergoing Arthroscopic Partial Meniscectomy? A Histological Study

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery.     

Thiolated Hydroxypropyl-β-cyclodextrin: A Potential Multifunctional Excipient for Ocular Drug Delivery

The goal of this study was the design and evaluation of a thiolated cyclodextrin providing high drug solubilizing and mucoadhesive properties for ocular drug delivery. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was thiolated via a microwave-assisted method, resulting in a degree of thiolation of 33%. Mucoadhesive properties of thiolated HP-β-CD (HP-β-CD-SH) were determined via rheological measurements and ex vivo studies on isolated porcine cornea. Due to thiolation of HP-β-CD, a 2-fold increase of mucus viscosity and a 1.4-fold increase in residence time on isolated corneal tissue were achieved. After instillation, the mean precorneal residence time and AUC of dexamethasone (DMS) eye drops were 4-fold and 11.7-fold enhanced by HP-β-CD-SH, respectively. Furthermore, in the presence of HP-β-CD-SH, a constant high level of DMS in aqueous humour between 30 and 150 min after administration was observed. These results suggest that HP-β-CD-SH is an excellent excipient for ocular formulations of poorly soluble drugs in order to prolong their ocular residence time and bioavailability.     

Intracavitary therapy of neoplastic effusions with cytokines: comparison among interferon alpha, beta and interleukin-2

Preliminary studies have suggested that the intracavitary administration of cytokines may represent a new effective palliative therapy of malignant effusions. To define further the therapeutic role of cytokines in the treatment of neoplastic fluid accumulation, 70 cancer patients with pleural, pericardial or peritoneal cytologically proven neoplastic effusions were randomized to receive intracavitary cycles with interleukin-2 (IL-2; 6 x 10(6) IU), interferon (IFN alpha; 2 x 10(7) U) or IFN beta (6 x 10(6) U) every week for 2 or 3 weeks. A clinical control of fluid accumulation was obtained in 39/70 (56%) patients. In patients with mesothelioma, the response rate was significantly higher with IL-2 than with IFN alpha or -beta, while there was no difference in patients with tumors other than mesothelioma. Moreover, the duration of the period during which drainage was not required was significantly longer in patients treated with Il-2 than in the other groups. Toxicity was low in all patients. According to preliminary data, this study demonstrates that intracavitary administration of cytokines, including IL-2, IFN alpha and -beta, is a new well-tolerated palliative therapy for malignant effusions, with an efficacy substantially comparable to that described with the most commonly used treatments with tetracyclines or cytostatic agents.     

Treatment of cancer-related thrombocytopenia by low-dose subcutaneous interleukin-2 plus the pineal hormone melatonin: a biological phase II study

Despite the platelet production in response to IL-2, cancer immunotherapy with IL-2 tends to induce thrombocytopenia, which probably depends on an enhanced peripheral destruction. On the basis of our previous studies, this effect may be neutralized by a concomitant administration of the pineal hormone melatonin (MLT). This study was performed to investigate the influence of an immunotherapeutic combination with low-dose IL-2 and MLT on platelet number in advanced cancer patients showing persistent thrombocytopenia. The study included 14 advanced solid tumor patients, affected by thrombocytopenia due to different causes (portal hypertension: 9; previous chemotherapies: 3; DIC: 2). IL-2 was injected at 3 million IU/day subcutaneously for 6 days/week for 4 weeks, in association with MLT (40 mg/day orally). A normalization of platelet number occurred in 10/14 (71%) patients, and platelet mean number significantly increased on treatment. No important therapy-related toxicity was observed. This preliminary study would suggest that the concomitant administration of MLT is able not only to neutralize IL-2-induced thrombocytopenia, but also to increase platelet number in thrombocytopenic cancer patients.