Pavement Management System model using a LCCA- microsimulation integrated approach

The maintenance and the rehabilitation of the urban road pavements are not often based on systematic program and scheduling but rather on emergency or on other not identified reasons. Moreover the Life Cycle Cost Analysis (LCCA), the only peculiar procedure for the management pavement, finds its own application for highway and motorway, even if it is possible to search the best investment for the urban interstate and arterials. By the light of the quantity of the involved resources, it seems necessary to define an operative methodology for programming the maintenance and rehabilitation activities for the urban pavement. The paper is oriented towards the development of a multidisciplinary approach to make decision on management of urban pavement using the basic concepts of the LCCA and micro-simulation model to define a scheme of work zone that minimizes the delay on the traffic flow. The best rehabilitation strategy should be characterized by the lowest users’ cost that depends on the time period of the work zone, which is conditioned by both own scheme and the provided treatment, and on “social cost” as increased travel time for queue generation . Different scenarios for different work zone plans were developed and a micro-simulation model was used to assess increased total travel time of a traffic flow within the maintenance area. In this work an analysis by means of the above mentioned approach was carried out on real scenario in the city of Palermo in order to point out the several frames of the adopted methodolog

The wild taxa utilized as vegetables in Sicily (Italy): A traditional component of the Mediterranean diet

Background: Wild vegetables in the Mediterranean Basin are still often consumed as a part of the diet and, in particular, there is a great tradition regarding their use in Sicily. In this study, an ethnobotanical field investigation was carried out to (a) identify the wild native taxa traditionally gathered and consumed as vegetables in Sicily, comparing the collected ethnobotanical data with those of other countries that have nominated the Mediterranean diet for inclusion in the UNESCO Representative List of the Intangible Cultural Heritage of Humanity and (b) highlight new culinary uses of these plants. Methods: Interviews were carried out in 187 towns and villages in Sicily between 2005 and 2015. A total of 980 people over the age of 50 were interviewed (mainly farmers, shepherds, and experts on local traditions). Plants recorded were usually collected in collaboration with the informants to confirm the correct identification of the plants. The frequencies of citation were calculated. Results: Two hundred fifty-three taxa (specific and intraspecific) belonging to 39 families, and 128 genera were recorded (26 were cited for the first time). The most represented families were Asteraceae, Brassicaceae, Apiaceae, Amaryllidaceae, Malvaceae, and Polygonaceae. Only 14 taxa were cited by 75% of the people interviewed. The aerial parts of wild plants, including leaves, tender shoots, and basal rosettes, are the main portions collected, while the subterranean parts are used to a lesser extent. For some vegetables, more parts are utilized. Most of the reported vegetables are consumed cooked. In addition to the widely known vegetables (Borago officinalis, Beta spp., Cichorium spp., Brassica spp., Carduus spp., etc.), the so-called ancient vegetables are included (Onopordum illyricum, Centaurea calcitrapa, Nasturtium officinale, Scolymus spp., Smyrnium rotundifolium), and some unique uses were described. Comparing the Sicilian findings to those from other countries, a very high number of vegetable taxa were detected, 72 of which are eaten only in Sicily, while 12 are consumed in all the Mediterranean countries examined. Conclusions: The research shows a high level of Sicilian knowledge about using wild plants as a traditional food source. Wild vegetables are healthy and authentic ingredients for local and ancient recipes, which are fundamental to the revitalization of quality food strictly connected to traditional agroecosystems

Exploiting Exosomes for Differential Diagnosis of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by a clonal plasma cell proliferation. Usually, all MM are preceded by an asymptomatic premalignant stage termed monoclonal gammopathy of undetermined significance (MGUS). Differential diagnosis requires the evidence of end-organ damage, but recently new biomarkers are emerging to help clinicians to distinguish MM from the premalignant phase. Circulating exosomes in serum seem to be a powerful tool to be analyzed for liquid biopsy, and in this chapter, we show that MM and MGUS exosomes are different in concentration, biological activity, and biochemical markers. These differences seem to be related to the free light chains (FLCs) associated with exosomes and their propathogenic properties. The cellular processing FLC-decorated exosomes and their ability to activate proinflammatory mechanisms are different in MM and MGUS patients. These elements can be evaluated to create an innovative multiparameter panel to monitor MGUS to MM switching

C-src Enriched Serum Microvesicles Are Generated in Malignant Plasma Cell Dyscrasia

Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM). MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Light Chains (FLC) are present in the serum and urine of many patients with plasma cell diseases. The biological differences between monoclonal FLCs, produced under malignant or benign dyscrasias, has not yet been characterized. In the present study, we show that endothelial and heart muscle cell lines internalize kappa and lambda FLCs. After internalization, FLCs are rerouted in the extracellular space via microvesicles and exosomes that can be re-internalized in contiguous cells. Only FLCs secreted from malignant B Lymphocytes were carried in Hsp70, annexin V, and c-src positive vesicles. In both MM and AL Amyloidosis patients we observed an increase in microvesicles and exosomes production. Isolated serum vesicles from MM, AL Amyloidosis and monoclonal gammopathy of undetermined significance (MGUS) patients contained FLCs. Furthermore MM and AL amyloidosis vesicles were strongly positive for Hsp70, annexin V, and c-src compared to MGUS and control patients. These are the first data implying that FLCs reroute via microvesicles in the blood stream, and also suggest a potential novel mechanism of c-src activation in plasma cell dyscrasia

Cultured human amniocytes express hTERT, which is distributed between nucleus and cytoplasm and is secreted in extracellular vesicles

7noopenopenRadeghieri, Annalisa; Savio, Giulia; Zendrini, Andrea; Di Noto, Giuseppe; Salvi, Alessandro; Bergese, Paolo; Piovani, GiovannaRadeghieri, Annalisa; Savio, Giulia; Zendrini, Andrea; DI NOTO, Giuseppe; Salvi, Alessandro; Bergese, Paolo; Piovani, Giovann

Comparison of Hevylite™ IgA and IgG assay with conventional techniques for the diagnosis and follow-up of plasma cell dyscrasia

Background: Heavy/light chain assay allows the characterization and quantification of immunoglobulin light chains bound to heavy chains for each Ig’k and Ig’ immunoglobulin class, discriminating between the involved/uninvolved isotypes in plasma cell dyscrasia. The Ig’k/Ig’ ratio (heavy/light chain ratio) enables to monitor the trend of monoclonal component during therapy and disease evolution. Objective: In this study, we evaluate the impact of the heavy/light chain assay in monitoring multiple myeloma patients in comparison with conventional techniques. Methods: Serum samples of 28 patients with IgG or IgA monoclonal component were collected for a mean of 109 days and analyzed. The heavy/light chain assay was compared with classical immunoglobulin quantification (Ig’Tot), serum immunofixation electrophoresis, serum protein electrophoresis, and serum-free light chains quantification. Serum samples from 30 healthy patients were used as control (polyclonal). Results: Heavy/light chain ratio and serum immunofixation electrophoresis were comparable in 86% of the cases, and free light chain ratio and heavy/light chain ratio in 71.8%. Heavy/light chain assay and Ig’Tot measurements showed a concentration-dependent agreement in monoclonal patients. The heavy/light chain assay was able to quantify the monoclonal component migrating in SPE b region: this occurred in 10% of our IgG and 50% of our IgA patients. Conclusions: The concordance scores indicate that heavy/light chain and Ig’Tot assays show differences at high monoclonal component values. The heavy/light chain ratio, serum immunofixation electrophoresis, and free light chain ratio showed partial concordance. Our study confirmed that, in the context of heavy/light chain assay, heavy/light chain Ig’k and Ig’ absolute values and heavy/light chain ratio are both important tools to monitor the presence of monoclonal component that are difficult to be identified in SPE

Food intolerance and chronic constipation: manometry and histology study.

BACKGROUND: Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown. AIMS: To evaluate the histology and manometry pattern in patients with food intolerance-related constipation. PATIENTS AND METHODS: Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry. RESULTS: A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucus than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation

Gender influence on professional satisfaction and gender issue perception among young oncologists. A survey of the Young Oncologists Working Group of the Italian Association of Medical Oncology (AIOM)

Background: The professional gender gap is increasingly recognised in oncology. We explored gender issues perception and gender influence on professional satisfaction/gratification among young Italian oncologists. Methods: Italian oncologists aged 6440 years and members of the Italian Association of Medical Oncology were invited to participate in an online survey addressing workload/burnout, satisfaction in professional abilities and relations, relevant factors for professional gratification, and gender barriers. \u3c72 test for general association or \u3c72 test for trend was used to analyse the data. Results: 201 young oncologists participated in the survey: 67% female, 71% aged 30-40 years, 41% still in training and 82% without children. Women and men were equally poorly satisfied by the relations with people occupying superior hierarchical positions. There was heterogeneity between women and men in current (p=0.011) and expected future (p=0.007) satisfaction in professional abilities: women were more satisfied by current empathy and relations with colleagues and were more confident in their future managerial and team leader skills. The most important elements for professional gratification indicated by all participants were, in general, work-life balance (36%) and intellectual stimulation/research (32%); specifically for women, work-life balance (48%) and intellectual stimulation/research (20%); and specifically for men, career (29%) and social prestige/recognition (26%). Heterogeneity within the same gender emerged. For example, the elements indicated by men as the most important were intellectual stimulation/research (39%) and work-life balance (21%) in general, versus social prestige/recognition (24%) and career (24%), respectively, specifically for men (p<0.0001). More women versus men perceived gender issue as an actual problem (60% vs 38%, p=0.03); men underestimated gender barriers to women's career (p=0.011). Conclusions: Satisfaction in professional abilities varied by gender. Work-life balance is important for both women and men. Stereotypes about gender issues may be present. Gender issue is an actual problem for young oncologists, mostly perceived by women

Immunoglobulin free light chains and GAGs mediate multiple myeloma extracellular vesicles uptake and secondary NfkB nuclear traslocation

Multiplemyeloma(MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasmacells in the bone marrow. Monoclonal plasmacells often secrete high amounts of immunoglobulin free light chains(FLCs)that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lines and secreted in extracellular vesicles(EVs). MM serum derived EVs presented phenotypic differences if compared with monoclonal gammopathy of undetermined significance (MGUS)serum derived EVs suggesting their involvement in MM pathogenesis or progression. To investigate the effect of circulating EVs on endothelial and myocardial cells, we purified MM and MGUS serum derived EVs with differential ultracentrifugation protocols and tested their biological activity. We found that MM and MGUS EVs induced different proliferation and internalization rates in endothelial and myocardial cells, thus we tried to find specific targets in MM EVs docking and processing. Pre-treatment of EVs withanti-FLCs antibodies or heparin blocked the MM EVs uptake, highlighting that FLCs and glycosaminoglycans are involved. Indeed, only MM EVs exposure induced a strong nuclear factor kappa B nuclear translocation that was completely abolished afteranti-FLCs antibodies and heparin pre-treatment. The protein tyrosine kinase c-src is present on MM circulating EVs and redistributes to the cell plasma membrane after MM EVs exposure.The anti-FLCs antibodies and heparin pre-treatments were able to block the intracellular redistribution of the c-src kinase and the subsequent c-src kinase containing EVs production. Our results open new insights in EVs cellular biology and in MM therapeutic and diagnostic approaches