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We report the first synthesis of the complex amino acid labionin in a fully orthogonally protected and stereopure form. The structure-which incorporates five orthogonal protecting groups and three stereogenic centers-was assembled using two key synthetic steps: (1) a thia-Michael addition for installing the thioether bridge; (2) an electrophilic azidation for creating the central quaternary ?-amino acid carbon in a stereochemically pure form. This work is expected to enable the solid phase synthesis of both natural and synthetic analogues labyrinthopeptins.

Metastatic melanoma is still associated with a poor prognosis, and there is increasing interest in immunotherapy alone or in combination with other adjuvant therapies. Γδ T lymphocytes play a pivot role in the immune response against cancer, but while γδ-based immunotherapy is already a clinical reality for several solid tumors, data on melanoma are still limited and fragmented. This systematic review presents preclinical and clinical evidence for a role of γδ T lymphocytes in immunotherapeutic strategies for advanced melanoma and discusses research state of the art and future perspectives. Current strategies focus on in vivo stimulation, and ex vivo adoptive therapy and vaccination; results are promising, but further studies are needed to better investigate the interactions in tumoral microenvironment and to improve clinical efficacy of immunotherapeutic protocols.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) and its etiology is multifactorial and involves a combination of genetic environmental factors. The interaction of these factors causes an imbalance of the microbiota, leading to the activation of several immunological and inflammatory mechanism. From an immunological point of view, there seems to be an involvement of the TIM-3/GALECTIN-9 pathway and of the autoregulation of lyTh1. These studies show that in patients with CD the autoregulation of lyth1 is lost due to a reduced concentration of galectin-9 and a reduced TIM-3 expression in LyTh1. This could be one of the reason for the state of perpetual activation of lyTh1, resulting in the chronic inflammation process.

Obiettivi: valutare l’efficacia di interventi per la prevenzione del tabagismo negli adolescenti, attuati nella città di Empoli (FI) dal 1985 al 2000.Metodi: analisi dei dati raccolti con le indagini epidemiologiche sull’abitudine al fumo nell’Empolese. Esame delle campagne di informazione e interventi educativi, in particolare di “Empoli contro il fumo”, avviata nel 1990, rivolta alla popolazione generale, con articolazioni riguardanti specificamente gli adolescenti (Operazione Smoke Buster, 1993 1996). Verifica degli obiettivi raggiunti con un’indagine svolta nel 2000, denominata “Fumo/non fumo”, mediante un questionario somministrato alla popolazione generale dagli studenti delle scuole elementari e medie, perseguendo così la doppia finalità conoscitiva e educativa.Risultati: nel 1990 si registra un tasso di fumatori pari al 19% dei cittadini empolesi. Con il progetto “Fumo/non fumo” – prima fase sono stati somministrati 3.000 questionari, a soggetti di età compresa tra 10 e 85 anni (media 40 anni), di cui il 53% femmine. Il 41% degli intervistati si definisce ‘non fumatore’, il 19% ex fumatore, il 12% ‘fumatore occasionale’ e il 28% fumatore abituale. Si documenta un evidente aumento del numero dei fumatori: il 9% nell’arco di dieci anni.Conclusioni: considerata l’età media della popolazione in studio nell’indagine Fumo /Non fumo, le stime che ne emergono possono essere considerate come indicatori dell’efficacia dei progetti di prevenzione su adolescenti/ giovani degli anni ottanta novanta. Nonostante i limiti metodologici delle indagini epidemiologiche considerate, che potrebbero aver sottostimato il numero dei fumatori negli anni ’90 e sovrastimato nel 2000, è doveroso considerare criticamente gli interventi preventivi attuati nell’Empolese nel recente passato, ponendo dubbi sulla loro efficacia nel lungo periodo.Infatti, la percentuale dei fumatori, diminuita sensibilmente nel corso degli anni Ottanta e nei primi anni Novanta, è nuovamente aumentata nei dieci anni successivi. Verosimilmente, la principale criticità è da ricercare nella mancanza di sistematicità e continuità dei programmi di prevenzione del tabagismo.

Obiettivo: l’alta prevalenza negli anziani e l’elevato costo sociale della frattura dell’estremità prossimale del femore (FPF), ha motivato una descrizione epidemiologica del fenomeno nella nostra area. Metodi: per la popolazione dei circa 800.000 residenti nel territorio della ASL di Firenze, basandosi sulle schede di dimissione ospedaliera, è stata studiata la distribuzione dei ricoveri per ASL, per diagnosi, per sesso e per fasce di età. Escludendo i ricoveri ripetuti, è stato stimato il tasso di incidenza. È stata calcolata la degenza media e il tempo di attesa per un eventuale intervento chirurgico. Risultati: il tasso di incidenza stimato sui ricoveri è elevato, sebbene costante negli anni: i valori medi nel periodo sono di 2627,08/100.000 per i soggetti con 85 o più anni d’età e di 1264,25/100.000 nella fascia d’età 80-84 anni. Tale tasso presenta un andamento esponenziale in funzione dell’età a partire da 50 anni e nelle fasce d’età avanzata le femmine mostrano una incidenza circa doppia. Anche la degenza media risulta più elevata nelle fasce di età più anziane. Per i 4 interventi chirurgici più frequenti abbiamo dimostrato che la media della degenza pre-intervento è significativamente maggiore nei deceduti rispetto ai dimessi a domicilio. Conclusioni: il tasso di incidenza di FPF è risultato superiore alla media nazionale sebbene stabile negli anni. La distribuzione dell’incidenza per fasce di età e sesso rispecchia i valori di letteratura. La correlazione tra degenza media pre-intervento e mortalità intaospedaliera è un reperto interessante che richiede ulteriori analisi per una corretta interpretazione.

The study describes the occurrence of pleural and peritoneal malignant mesothelioma in the Colleferro industrial area (Province of Rome, 9 municipalities, population 63,000, period 1993-98) which is the site of a large chemical plant (BPD) producing organic chemicals, acid mixtures, insecticides, explosives and dynamite, and was involved in manufacturing/maintenance of railroad rolling stock. Asbestos was extensively used in these plants in the past. Mesothelioma cases were actively searched from data in files of pathology archives, hospital admission and discharge (records), and death certificates recorded at local health authority register. 23 potential cases were identified for whom clinical charts and pathological slides were reviewed. A multidisciplinary evaluation of all collected information confirmed 18 cases of cyto-histologically proven malignant mesothelioma (pleural/peritoneal ratio of 2.75:1) among residents and/or workers at BPD. The remaining 5 cases were defined as not mesothelioma; however, two were cases of lung cancer (both occupationally exposed to asbestos). All subjects with malignant mesothelioma had been occupationally exposed to asbestos (14 males and 3 females), except one (1 female with domestic exposure). No mesothelioma case was attributable to environmental exposure. Of the 17 cases with occupational asbestos exposure, 15 occurred in BPD workers employed in manufacturing/maintenance of railroad rolling stock (3 cases), general maintenance services (5 cases), or in the armaments sector (7 cases) and 2 in residents but not BPD workers (1 baker, 1 pipefitter). The incidence rate in residents of the 9 municipalities was 5.5 in males and 1.3 in females (standardized on the Italian population x100,000, census 1981). For Colleferro municipality only, the incidence was 10.1 in males and 4.1 in females, which are the highest rates reported so far in Italy. Besides confirming the risk of mesothelioma risk in railroad rolling stock manufacturing and asbestos-insulated pipe maintenance workers, this study identifies a cluster of malignant mesothelioma in explosives production workers.

An anonymous unlinked seroprevalence study of HIV, HBV and HCV infections has been conducted on 485 sera consecutively submitted to the virology laboratory to be tested for HBsAg; sera came from patients attending general surgery at San Camillo Hospital in Rome. Carriers of HBsAg were 12 (2.5%); antibodies against HIV have been identified in 4 sera (0.8%) and against HCV in 35 (7.2) by ELISA (first generation assay); 25/35 of anti HCV ELISA positive sera were reactive also by RIBA (first generation assay). The observed prevalences of potentially infectious patients represent a risk of occupational transmission for health care workers. Vaccination against HBV, adherence with universal precautions and development of safer surgical devices and techniques are needed to prevent the risk of exposure and, consequently, of occupational acquired infections.

We evaluated mortality among subjects employed in an oil refinery plant in Rome, Italy. We studied two subgroups of refinery employees: blue collar and white collar workers. A total of 682 men (505 blue collars, 148 white collars, 29 unknown) employed between 1965 and 1992, were followed up for mortality since employment in the plant to July 1999. Standardized Mortality Ratios (SMR), and their 90% Confidence Intervals (90% CI), comparing mortality rates of the cohort members with those of the general population of the Lazio region. For blue collar workers, we performed analyses by latency since first employment and by duration of employment for selected cancer sites. We observed 94 total deaths (100.8 expected) (SMR = 0.93; 90% CI = 0.78-1.11) among blue collar workers and 16 total deaths (31.7 expected) (SMR = 0.50; 90% CI = 0.32-0.77) among white collar workers, and a large deficit of deaths from non-neoplastic cardiovascular diseases (respectively SMR = 0.60; 90% CI = 0.41-0.86 and SMR = 0.18; 90% CI = 0.03-0.56). All cancer mortality was slightly increased only in blue collars (SMR = 1.27 CI = 0.97-1.65). There was an excess risk from cancer of the lung (20 obs SMR = 1.80, 90% CI = 1.19-2.62), bladder (5 obs SMR = 3.19, 90% CI = 1.26-6.72), and benign/unspecified cancer of the brain (4 obs SMR = 4.11, 90% CI = 1.12-10.6). The lower mortality from cardiovascular disease indicates the presence of a strong healthy worker effect. The findings of elevated mortality from cancer of the lung and bladder in blue collar workers are in agreement with those of other studies. Confounding factors from cigarette smoking might have played only a marginal role in influencing the results. Exposure to polynuclear aromatic hydrocarbons (PAHs) is a plausible explanation for the excesses found.

We evaluated the association between exposure to environmental tobacco smoke (ETS) from husbands who smoke and plasma levels of antioxidant vitamins among nonsmoking women. A total of 1249 women from four areas in Italy answered a self-administered questionnaire, reported their diets on a food frequency questionnaire, had a medical examination, and gave their blood for alpha and beta-carotene, retinol, L-ascorbic acid, alpha-tocopherol, and lycopene determinations. Urinary cotinine was used to evaluate the level of recent exposure to ETS. After adjusting for study center, age and education, we found no association between ETS exposure and daily nutrient intake of beta-carotene, retinol, L-ascorbic acid, and alpha-tocopherol. However, we found an inverse dose-response relationship between intensity of current husband's smoke and concentrations of plasma beta-carotene and L-ascorbic acid. The associations remained even after controlling for daily beta-carotene and vitamin C intake and for other potential confounders (vitamin supplementation, alcohol consumption, and body mass index). Moreover, when urinary cotinine was considered as the exposure variable, a significant inverse association with plasma beta-carotene was found. The findings may be of interest to explain the biological mechanism that link ETS exposure with lung cancer and ischemic heart diseases.

OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. METHODS: The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers. RESULTS: Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45(+) infiltrate consisted of CD3(+) and CD3(-) lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45(+) cells were T-bet(+), CD56(-), NKP44(-), and CD117(-), defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet. CONCLUSIONS: These data indicate that, in patients with active NCWS, IFN-γ-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS.

2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most widespread environmental brominated flame-retardant congeners which has also been detected in animal and human tissues. Several studies have reported the effects of PBDEs on different health issues, including neurobehavioral and developmental disorders, reproductive health, and alterations of thyroid function. Much less is known about its immunotoxicity. The aim of our study was to investigate the effects that treatment of THP-1 macrophage-like cells with PBDE-47 could have on the content of small extracellular vesicles’ (sEVs) microRNA (miRNA) cargo and their downstream effects on bystander macrophages. To achieve this, we purified sEVs from PBDE-47 treated M(LPS) THP-1 macrophage-like cells (sEVsPBDE+LPS) by means of ultra-centrifugation and characterized their miRNA cargo by microarray analysis detecting the modulation of 18 miRNAs. Furthermore, resting THP-1 derived M(0) macrophage-like cells were cultured with sEVsPBDE+LPS, showing that the treatment reshaped the miRNA profiles of 12 intracellular miRNAs. This dataset was studied in silico, identifying the biological pathways affected by these target genes. This analysis identified 12 pathways all involved in the maturation and polarization of macrophages. Therefore, to evaluate whether sEVsPBDE+LPS can have some immunomodulatory activity, naïve M(0) THP-1 macrophage-like cells cultured with purified sEVsPBDE+LPS were studied for IL-6, TNF-α and TGF-β mRNAs expression and immune stained with the HLA-DR, CD80, CCR7, CD38 and CD209 antigens and analyzed by flow cytometry. This analysis showed that the PBDE-47 treatment does not induce the expression of specific M1 and M2 cytokine markers of differentiation and may have impaired the ability to make immunological synapses and present antigens, down-regulating the expression of HLA-DR and CD209 antigens. Overall, our study supports the model that perturbation of miRNA cargo by PBDE-47 treatment contributes to the rewiring of cellular regulatory pathways capable of inducing perturbation of differentiation markers on naïve resting M(0) THP-1 macrophage-like cells.

The finding that γδ T cells are present among tumor-infiltrating lymphocytes in humans suggests they participate in tumor immune surveillance, but their relevance is unclear because the relative abundance of tumor-infiltrating γδ T cells correlates with positive or negative, or even do not correlate with prognosis. This likely depends on the fact that tumor-infiltrating γδ T cells may play substantially different effector or regulatory functions, and correlation with patient's prognosis relies on distinct γδ T cell subsets in the context of the tumor. There is interest to exploit γδ T cells in tumor immunotherapy, but to make this approach successful there is urgent need to fully understand the biological functions of γδ T cells and of how they can be manipulated in vivo and ex vivo to safely provide benefit to the host. This review focuses on our previous and ongoing studies of tumor-infiltrating γδ T lymphocytes in different types of human cancer. Moreover, we discuss the interaction of tumor-infiltrating γδ T cells with other cells and molecules present in the tumor microenvironment, and their clinical relevance on the ground, that deep knowledge in this field can be used further for better immunotherapeutic intervention in cancer.

The metabolic changes that occur in tumor microenvironment (TME) can influence not only the biological activity of tumor cells, which become more aggressive and auto sustained, but also the immune response against tumor cells, either producing ineffective responses or polarizing the response toward protumor activity. γδ T cells are a subset of T cells characterized by a plasticity that confers them the ability to differentiate towards different cell subsets according to the microenvironment conditions. On this basis, we here review the more recent studies focused on altered tumor metabolism and γδ T cells, considering their already known antitumor role and the possibility of manipulating their effector functions by in vitro and in vivo approaches. γδ T cells, thanks to their unique features, are themselves a valid alternative to overcome the limits associated with the use of conventional T cells, such as major histocompatibility complex (MHC) restriction, costimulatory signal and specific tumor-associated antigen recognition. Lipids, amino acids, hypoxia, prostaglandins and other metabolic changes inside the tumor microenvironment could reduce the efficacy of this important immune population and polarize γδ T cells toward IL17 producing cells that play a pro tumoral role. A deeper knowledge of this phenomenon could be helpful to formulate new immunotherapeutic approaches that target tumor metabolisms.

The diffusion of no-tillage (NT) is to be encouraged because of the benefits it can provide in terms of improving soil fertility and counteracting global warming and climate change as part of climate-smart agriculture practices. However, the introduction of this management can be difficult, especially in the first years of application, and can lead to unpredictable yield results depending on the soil type. Therefore, the aim of this experiment was to evaluate the early effect of NT use, compared to the conventional mouldboard ploughing (CT), on two different soils, a clay-loam (GAL) and a sandy-clay-loam soil (SMA), by monitoring a set of 43 different soil and plant variables that were expected to vary with tillage and/or soil type. At both experimental sites, NT showed lower wheat total biomass (−29%) and grain yields (−17%) than CT with a more pronounced decrease in GAL than in SMA. Yield differences were accompanied by modifications in nutrient, microbial community and soil enzyme activity dynamics which highlighted higher stress in GAL, than in SMA soil, attributable to lower crop residues decomposition and substrate availability. Therefore, our findings suggest that the negative consequences due to the transition to NT depend on specific soil characteristics, like texture and organic matter concentration, with different repercussions on soil quality as well as on wheat growth and productivity.

Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ T cells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ T cells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 T cells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 T cells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 T cells in chronic inflamed IBD. In CAC patients no significant cytokine production was detected in tissue-resident Vδ1 T cells, but Vδ2 T cells produced remarkable amounts of IFN-γ and TNF-α; these data were confirmed by the analysis of an independent cohort of IBD transcriptomes. Moreover, transcriptomes of IBD patients revealed a clear-cut clusterization of genes related with the maintenance of the inflammatory status. In conclusion, our results demonstrating that Vδ2 T cells have a proinflammatory profile in chronic IBD are suggestive of their participation in IBD and CAC pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection dysregulates the immune system by lymphopenia of B cells, monocytes, eosinophils, basophils, and cytotoxic cells such as CD8, γδ T cells, and natural killer (NK) cells. Despite many studies being conducted to better understand the effects of SARS-CoV-2 on the immune system, many mechanisms still remain unclear, hindering the development of novel therapeutic approaches and strategies to improve the host’s immune defense. This mini-review summarizes the findings on the role of γδ T cells in coronavirus disease 2019 (COVID-19), providing an overview of the excellent anti-viral therapeutic potential of γδ T cells, that had not yet been exploited in depth.

The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversion of metastatic cells to nonmetastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like properties, and spawned metastatic capacity. Targeting IL4 signaling sensitized breast cancer cells to anticancer therapy and strengthened immune responses by enhancing the number of IFNγ-positive CTLs. Our results showed the role of IL4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies. Cancer Res; 77(12); 3268–79. ©2017 AACR.

The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating. However, Vδ2 T cells were present at higher frequencies in circulation than in the tissue of either cancer patients or healthy donors. Tregs were decreased in the peripheral blood of SCC patients, but were significantly increased in the tumor compartment of these patients. Tumor-infiltrating γδ T cells preferentially showed an effector memory phenotype and made either IL17 or IFNγ depending on the tumor stage, whereas circulating γδ T cells of SCC patients preferentially made IFNγ. Different cell types in the tumor microenvironment produced chemokines that could recruit circulating γδ T cells to the tumor site and other cytokines that could reprogram γδ T cells to produce IL17. These findings suggest the possibility that γδ T cells in SCC are recruited from the periphery and their features are then affected by the tumor microenvironment. Elevated frequencies of infiltrating Vδ2 T cells and Tregs differently correlated with early and advanced tumor stages, respectively. Our results provide insights into the functions of tumor-infiltrating γδ T cells and define potential tools for tumor immunotherapy. Cancer Immunol Res; 5(5); 397–407. ©2017 AACR.

Introduction: Cancer immunotherapy relies on the development of an efficient and long-lasting anti-tumor response, generally mediated by cytotoxic T cells. gamma delta T cells possess distinctive features that justify their use in cancer immunotherapy. Areas covered: Here we will review our current knowledge on the functions of human gamma delta T cells that may be relevant in tumor immunity and the most recent advances in our understanding of how these functions are regulated in the tumor microenvironment. We will also discuss the major achievements and limitations of gamma delta T cell-based immunotherapy of cancer. Expert opinion: Several small-scale clinical trials have been conducted in cancer patients using either in vivo activation of gamma delta T cells or adoptive transfer of ex vivo-expanded gamma delta T cells. Both strategies are safe and give some clinical benefit to patients, thus providing a proof of principle for their utilization in addition to conventional therapies. However, low objective response rates have been obtained in both settings and therefore larger and well-controlled trials are needed. Discovering the factors which influence the success of gamma delta T cell-based immunotherapy will lead to a better understanding of their mechanism of action and to harness these cells for effective and durable anti-tumor responses.

In this work, we have investigated the properties of novel fluorescent semi(thio)carbazone systems with anions by UV-vis, spectrofluorimetric and NMR studies, in acetonitrile and DMSO solutions. Conformational preferences were determined by theoretical calculations within the DFT approach. For the free receptors, these studies pointed out a marked prevalence of anti conformations, which are stabilized by intramolecular H-bonds between the (thio)urea NH group and the imino nitrogen atom. For the julolidine-based thiosemicarbazone system, intermolecular interactions involving the thiourea NH groups and the S atoms of two receptor molecules were also found in the crystals, leading to the formation of supramolecular dimers. Theoretical studies showed that anion binding involved a change of the conformation of the receptors from anti to syn. In the syn isomers, two NH groups actually point in the same direction, thus favouring the binding of anions, e.g. the Y-shaped acetate ion. This thorough study on the novel semi(thio)carbazones provides useful information for the application of this type of molecule in all the fields of chemistry, in which urea-based systems are employed (e.g. anion recognition and transport, catalysis, soft materials, etc.).

γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production of IFN- γ which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant γδ T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage.

INTRODUZIONE: Le pagine Web aziendali, di reclutamento, sono la prima fonte di candidature per la maggior parte delle organizzazioni, soprattutto per quelle di grandi dimensioni (Brown, Cober, Kane, & Levy, 2006). La letteratura, fino a questo momento, si è occupata delle caratteristiche dei siti di reclutamento, quali l’usabilità, la fiducia, le informazioni disponibili oppure del brand aziendale (e.g. Thompson, Braddy, & Wuensch, 2008). Il presente lavoro, vuole integrare la letteratura, considerando il ruolo delle caratteristiche estetiche di tali siti Web: si prenderanno in considerazione l’estetica “classica”, ossia la chiarezza, la precisione del sito, e l’estetica “espressiva”, cioè l’originalità e la creatività dello stesso (Lavie & Tractinsky, 2004). Inoltre verrà considerata la qualità delle informazioni presenti inerenti ad esempio i ruoli per cui ci si può candidare oppure le caratteristiche da possedere per ricoprire i ruoli. SCOPO: L’intento è quello di verificare un modello longitudinale nel quale l’ intenzione di candidarsi in un sito dipende dall’attrattività aziendale, dall’estetica del sito e dalle informazioni presenti. METODO: Per fare ciò è stato impiegato un campione, di studenti universitari, formato da 617 casi. Le ipotesi sono state verificate tramite i Modelli di Equazioni Strutturali (SEM). RISULTATI: Le evidenze indicano che le due modalità di estetica hanno un ruolo diverso nel processo che porta a sviluppare l’intenzione a candidarsi e che comunque ambedue impattano sulla fruibilità delle informazioni. CONCLUSIONI: Si è dimostrato che l’estetica del sito web aziendale è importante nel predire l’intenzione di candidarsi presso una specifica organizzazione e che i siti Web aziendali contengono segnali estetici che sono fattori di influenza delle valutazioni e degli atteggiamenti dei potenziali candidati nei confronti dell’organizzazione e dei loro siti Web.

Given that higher education requires high levels of individual and public investment, it is expected that universities will provide graduates with the skills that employers need and, consequently, that graduates will be able to find a job easily. Actually, possessing graduate-level credentials is not a guarantee for employment success and there is a heated debate concerning the graduates’ employability. Many theoretical models have been developed in order to predict the graduates’ potentiality to be employed (i.e. Berntson & Marklund, 2007; Fugate, Kinicki, & Ashforth, 2004; Van der Heijde & Van der Heijden, 2006). The present symposium intends to discuss how it is possible to intervene to support the transition from university to the labour market, starting from some evidence about personal resources and contextual factors that may foster graduates’ employability and enhance their career opportunities. Chiesa and colleagues’ study explored the relationship between dispositional employability and emerging construct of career goal management strategies in college students who are going to graduate. Magrin and colleagues focused on the condition of college students with disabilities and the role of resilience and employability resources, both in preventing negative expectation about the impact of disability on the employment opportunities and promoting the perception of employability. Lo Presti and colleagues investigated the complex relationship between career competencies, employability and subjective career success of recent graduates, clarifying the moderator effect of vocational choice, networking, and employment prospects. Bison and colleagues described the career developments of the graduates starting from few months to 24 months after completing their university degree exploring the relationship between personal resources, employment opportunities and economic conditions.

Introduzione. Le competenze non tecniche (Non-Technical Skills) vengono definite come competenze cognitive, sociali e personali, complementari alle competenze tecniche che contribuiscono all’attivazione di performance lavorative sicure ed efficaci (Flin, O’Connor e Crichton, 2010). A tutt’oggi, nonostante sia stata dimostrata la rilevanza delle NTS nel campo della sicurezza, non esistono strumenti attendibili in italiano utili a misurare la presenza e i livelli di NTS in italiano. Obiettivo. Il presente studio ha quindi l’obiettivo di analizzare le proprietà psicometriche della scala per valutare le NTS per la sicurezza sul lavoro. Metodo. Sono stati condotti due studi strettamente interrelati. Lo Studio 1 ha valutato la validità di contenuto della scala mediante inter-rater agreement, mentre lo studio 2 ha indagato l’affidabilità dei fattori mediante una analisi fattoriale esplorativa (EFA) utilizzando la rotazione obliqua. I partecipanti dello Studio 1 erano 12 studenti di una magistrale di psicologia, mentre i partecipanti dello Studio 2 erano 133 operai di una azienda che produceva macchine agricole. Risultati. Nel primo studio sono stati definiti gli item della scala che è stata somministrata nello studio successivo. Lo studio 2 ha confermato la presenza di sei NTS: consapevolezza situazionale, decision-making, comunicazione, team work, leadership, capacità di gestire la fatica. Gli alpha di Cronbach si collocavano in un range da un minimo di .74 a un massimo di .90. Discussione. Questi risultati rappresentano uno dei primi progetti di validazione di una misura focalizzata sulle Non-Technical Skills per la sicurezza. Tale strumento è utile poiché può aiutare oltre la ricerca scientifica anche le organizzazioni interessate ad incrementare i livelli di sicurezza nella propri luoghi di lavoro.

In this paper volatile organic compounds (VOCs) from durum wheat cultivars and landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC’s profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices. The VOC data is accompanied by SDS-PAGE analyses of the storage proteins (gliadins and glutenins). Statistical analyses was carried out both on the signals obtained by MS and on the protein profiles. The difference between the VOC profile of two cultivars or two preparations of the same sample - matrices, in this case kernel vs wholemeal flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as low as pptv - made it possible to recognize these differences. The effects of grinding on the VOC profiles were analyzed using SIMPER and Tanglegram statistical methods. Our results show that it is possible describe samples using VOC profiles and protein data.

// Elena Lo Presti 1,2 , Nadia Caccamo 1,2 , Valentina Orlando 1,2 , Francesco Dieli 1,2 and Serena Meraviglia 1,2 1 Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy 2 Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy Correspondence to: Serena Meraviglia, email: // Keywords : γδ T cells, plasmacytoid dendritic cells, IL-17, TLR activation, proliferation, Immunology and Microbiology Section, Immune response, Immunity Received : July 20, 2016 Accepted : August 02, 2016 Published :August 31, 2016 Abstract Vγ9Vδ2 T cells and plasmacytoid dendritic cells (pDCs) are two distinct cell types of innate immunity that participate in early phases of immune response. We investigated whether a close functional relationship exists between these two cell populations using an in vitro co-culture in a human system. pDCs that had been activated by IL-3 and the TLR9 ligand CpG induced substantial activation of Vγ9Vδ2 T cells upon co-culture, which was cell-to-cell contact dependent, as demonstrated in transwell experiments, but that did not involve any of the costimulatory molecules potentially expressed by pDCs or Vγ9V2 T cells, such as ICOS-L, OX40 and CD40L. Activated pDCs selectively induced IL-17, but not IFN-γ, responses of Vγ9Vδ2T cells, which was dominant over the antigen-induced response, and this was associated with the expansion of memory (both central and effector memory) subsets of Vγ9Vδ2 T cells. Overall, our results provide a further piece of information on the complex relationship between these two populations of cells with innate immunity features during inflammatory responses.

There is increasing clinical evidence indicating that the immune system may either promote or inhibit tumor progression. Several studies have demonstrated that tumors undergoing remission are largely infiltrated by T lymphocytes [tumor-infiltrating lymphocytes (TILs)], but on the other hand, several studies have shown that tumors may be infiltrated by TILs endowed with suppressive features, suggesting that TILs are rather associated with tumor progression and unfavorable prognosis. γδ T lymphocytes are an important component of TILs that may contribute to tumor immunosurveillance, as also suggested by promising reports from several small phase-I clinical trials. Typically, γδ T lymphocytes perform effector functions involved in anti-tumor immune responses (cytotoxicity, production of IFN-γ and TNF-α, and dendritic cell maturation), but under appropriate conditions they may divert from the typical Th1-like phenotype and polarize to Th2, Th17, and Treg cells thus acquiring the capability to inhibit anti-tumor immune responses and promote tumor growth. Recent studies have shown a high frequency of γδ T lymphocytes infiltrating different types of cancer, but the nature of this association and the exact mechanisms underlying it remain uncertain and whether or not the presence of tumor-infiltrating γδ T lymphocytes is a definite prognostic factor remains controversial. In this paper, we will review studies of tumor-infiltrating γδ T lymphocytes from patients with different types of cancer, and we will discuss their clinical relevance. Moreover, we will also discuss on the complex interplay between cancer, tumor stroma, and γδ T lymphocytes as a major determinant of the final outcome of the γδ T lymphocyte response. Finally, we propose that targeting γδ T lymphocyte polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of cancer.