14 research outputs found

    Stakeholders mapping for sustainable biofuels:An innovative procedure based on computational text analysis and social network analysis

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    The identification and engagement of stakeholders is a challenge whose outcomes have a strong impact on a project’s success. This is even more relevant when the project concerns the introduction of sustainable technologies; these technologies are often less competitive on the market than traditional ones, both in terms of development complexity and production costs. This paper presents a stakeholder identification and mapping procedure, based on an Interest x Influence model, that emphasizes a quantitative methodological approach. The method has been applied on publicly available online data to identify and map potential stakeholders of a European research project aiming at creating a new biomass-derived biofuel. A semi-supervised procedure, built by combining computational text analysis and social network analysis techniques, has been used to calculate Interest and Influence scores for each potential stakeholder toward the project. The results show that stakeholders can be ranked on both dimensions and mapped on a bi-dimensional space according to their level of Interest and Influence. Within projects aiming at developing technologies for sustainability in which a wide range of stakeholders are involved at a transnational level, this stakeholder mapping technique provides a useful tool that can be adopted even with little knowledge on specific fields of application. A further asset of this approach lies in the possibility of profiling stakeholders on the basis of their Interest in the target project: this allows us to know the contents of a stakeholder (or stakeholders category) Interest, and therefore to have useful information for addressing the targeted stakeholder by means of a content design which is based on specific content categories, substantiating the stakeholder(s) Interest in the specific project.</p

    Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals

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    AbstractThe branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids involved in several important brain functions. Although commonly used as nutritional supplements, excessive intake of BCAAs might favour the establishment of neurotoxic conditions as indicated by the severe neurological symptoms characterising inherited disorders of BCAA catabolism such as maple syrup urine disease (MSUD). Recent evidence indicates that BCAAs induce excitotoxicity through mechanisms that require the presence of astrocytes. In the present study, we evaluated the effects of BCAAs on microglia, the main immune cells of the brain. As an experimental model we used primary microglial cells harvested from mixed glial cultures that had been kept in normal or high BCAA medium (H-BCAA). We show that H-BCAA microglial cells exhibit a peculiar phenotype characterized by a partial skewing toward the M2 state, with enhanced IL-10 expression and phagocytic activity but also increased free radical generation and decreased neuroprotective functions. We suggest that such an intermediate M1/M2 phenotype might result in a less efficient microglial response, which would promote the establishment of a low grade chronic inflammation and increase the likelihood of neurodegeneration. Although based on in vitro evidence, our study adds on to an increasing literature indicating that the increasing use of dietary integrators might deserve consideration for the possible drawbacks. In addition to excitotoxicity, the altered immune profile of microglia might represent a further mechanism by which BCAAs might turn into toxicants and facilitate neurodegeneration

    The Role of <i>Fusobacterium nucleatum</i> in Oral and Colorectal Carcinogenesis

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    In recent years, several studies have suggested a strong association of microorganisms with several human cancers. Two periodontopathogenic species in particular have been mentioned frequently: Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis. Chronic periodontal disease has been reported to be a risk factor for oral squamous cell carcinoma (OSCC), colorectal cancer (CRC) and pancreatic cancer. F. nucleatum is a Gram-negative anaerobic bacterium that lives in the oral cavity, urogenital, intestinal and upper digestive tract. It plays a significant role as a co-aggregation factor, with almost all bacterial species that participate in oral plaque formation acting as a bridge between early and late colonizers. F. nucleatum, gives an important inflammatory contribution to tumorigenesis progression and is associated with epithelial-derived malignancies, such as OSCC and CRC. F. nucleatum produces an adhesion protein, FadA, which binds to VE-cadherin on endothelial cells and to E-cadherins on epithelial cells. The last binding activates oncogenic pathways, such as Wnt/βcatenin, in oral and colorectal carcinogenesis. F. nucleatum also affects immune response because its Fap2 protein interacts with an immune receptor named TIGIT present on some T cells and natural killer cells inhibiting immune cells activities. Morover, F. nucleatum release outer membrane vesicles (OMVs), which induce the production of proinflammatory cytokines and initiating inflammation. F. nucleatum migrates from the oral cavity and reaches the colon hematogenously but it is not known if in the bloodstream it reaches the CRC as free, erythrocyte-bound bacteria or in OMV. F. nucleatum abundance in CRC tissue has been inversely correlated with overall survival (OS). The prevention and treatment of periodontal disease through the improvement of oral hygiene should be included in cancer prevention protocols. FadA virulence factors may also serve as novel targets for therapeutic intervention of oral and colorectal cancer

    Species distribution and in vitro azole susceptibility of aspergillus section nigri isolates from clinical and environmental settings

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    Aspergillus section Nigri includes species of interest for animal and human health, although studies on species distribution are limited to human cases. Data on the antifungal susceptibilities and the molecular mechanism of triazole resistance in strains belonging to this section are scant. Forty-two black Aspergillus strains from human patients (16 isolates), animals (14 isolates), and the environment (12 isolates) were molecularly characterized and their in vitro triazole susceptibilities investigated. Aspergillus tubingensis was isolated from humans, animals, and environmental settings, whereas Aspergillus awamori and Aspergillus niger were isolated exclusively from humans. Phylogenetic analyses of-tubulin and calmodulin gene sequences were concordant in differentiating A. tubingensis from A. awamori and A. niger. Voriconazole and posaconazole (PSZ) were the most active triazoles. One A. tubingensis strain was resistant to itraconazole and PSZ and one A. niger strain to PSZ. Sequence analysis of the cyp51A gene revealed different sequence types within a species, and A. tubingensis strains were also phylogenetically distinct from A. awamori/A. niger strains according to the strain origin and susceptibility profile. Genetic analysis of the cyp51A sequences suggests that two nonsynonymous mutations resulting in amino acid substitutions in the CYP51A protein (changes of L to R at position 21 [L21R] and of Q to R at position 228 [Q228R]) might be involved in azole resistance. Though azole resistance in black Aspergillus isolates from animals and rural environments does not represent a threat to public health in Southern Italy, the use of triazoles in the clinical setting needs to better monitored. The cyp51A sequence is useful for the molecular identification of black Aspergillus, and point mutations in protein sequences could be responsible for azole resistance phenomena

    Diffusion and Persistence of Multidrug Resistant Salmonella Typhimurium Strains Phage Type DT120 in Southern Italy

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    Sixty-two multidrug resistant Salmonella enterica serovar Typhimurium strains isolated from 255 clinical strains collected in Southern Italy in 2006–2008 were characterised for antimicrobial resistance genes, pulsotype, and phage type. Most strains (83.9%) were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (ACSSuT) encoded in 88.5% by the Salmonella genomic island (SGI1) and in 11.5% by the InH-like integron (blaOXA-30–aadA1) and catA1, sul1, and tet(B) genes. STYMXB.0061 (75%) and DT120 (84.6%) were the prevalent pulsotype and phage type identified in these strains, respectively. Five other resistance patterns were found either in single or in a low number of isolates. The pandemic clone DT104 (ACSSuT encoded by SGI1) has been identified in Italy since 1992, while strains DT120 (ACSSuT encoded by SGI1) have never been previously reported in Italy. In Europe, clinical strains DT120 have been reported from sporadic outbreaks linked to the consumption of pork products. However, none of these strains were STYMXB.0061 and SGI1 positive. The prevalent identification and persistence of DT120 isolates would suggest, in Southern Italy, a phage type shifting of the pandemic DT104 clone pulsotype STYMXB.0061. Additionally, these findings raise epidemiological concern about the potential diffusion of these emerging multidrug resistant (SGI linked) DT120 strains

    Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors. A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (Gitmo)

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    Abstract PURPOSE: We performed a nationwide registry-based analysis to describe the clinical outcome of adults patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a TKI-based treatment. PATIENTS AND RESULTS: A total of 441 patients were included in the study. The median age at HSCT was 44 years (range 18-70). All the 441 patients (100%) received TKI before the HSCT (performed between 2005 and 2016). Of these patients, 404 (92%) were in cytologic complete remission (CR), while the remaining 37 (8%) had an active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of cases. The prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (TBI-based in 50%) and included ATG in 51% of cases. With a median follow-up after HSCT of 39.4 months (range: 1-145), the overall survival (OS) probability at 1, 2 and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2 and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients with CR and MRD-negative at the time of transplant compared with those of patients with CR but MRD-positive (50% OS not reached vs. 36 months, P=0.015; 50% PFS not reached vs. 26 months, P=0.003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5 years OS rate 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS and PFS of 7 and 5 months, respectively. The 5 years cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% vs. 35.4%, P=0.001). The non-relapse mortality (NRM) after 1, 2 and 5 years was 19.1% (95%CI: 15.5-22.9), 20.7% (95%CI: 17-24.7) and 24.1% (95%CI: 20-28.5), respectively. The NRM was significantly lower with a mEBMT risk score of 0-2 compared with mEBMT risk score of 65 3 (15% vs. 25%, P=0,016). CONCLUSIONS: The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allograft, in recent years at the GITMO Centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of patients MRD-negative both at HSCT and at 3 months after HSCT (5 year OS 70%)
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