Multivariate tools to investigate the spatial contaminant distribution in a highly anthropized area (Gulf of Naples, Italy)

The Gulf of Naples located in a high anthropized coastal area is subjected to an infrastructural intervention for the installation of a submarine power pipeline. In order to evaluate the distribution of contaminants in the seafloor sediments, a preliminary study has been conducted in the area using multivariate techniques. The statistic approach was performed to gain insights on the occurrence of organic and inorganic contaminants within the area, aiming to identify the relevant hot spots. Three geographical sub-areas influenced by different contaminant association were recognized: Torre Annunziata (TA), Capri (CA), and middle offshore (MO). TA and CA resulted marked by a severe contamination pattern due to anthropogenic pressures. In addition, the influence of the depositional basin in governing the contamination trend has been pointed out. The supervised technique PLS_DA resulted to be a powerful tool in addressing the complexity of the huge dataset acquired during the marine survey, highlighting the main trends in the variability of quality indicators, orienting thus the deeper investigations during follow-up monitoring activities

Group B Streptococcus early-onset disease and observation of well-appearing newborns

Background International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. Methods This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks\u2019 gestation) registered in 2003\u20132009 (baseline period: 266,646 LBs) and in 2010\u20132016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). Results There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000\u20130.0000 vs 6 hours, IQR 0.0000\u201315.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. Conclusions Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy

Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence)

Background Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. Main body The aim of this work is to provide recommendations for the diagnosis and management of people affected by Poland syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years affected subjects. The literature search was performed in the second half of 2019. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conclusion Being Poland syndrome a rare syndrome most recommendations here presented are good clinical practice based on the consensus of the participant experts

High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients

BACKGROUND: Metastatic melanoma is an untreatable cancer lacking reliable and non-invasive markers of disease progression. Exosomes are small vesicles secreted by normal as well as tumor cells. Human tumor-derived exosomes are involved in malignant progression and we evaluated the presence of exosomes in plasma of melanoma patients as a potential tool for cancer screening and follow-up. METHODOLOGY/PRINCIPAL FINDINGS: We designed an in-house sandwich ELISA (Exotest) to capture and quantify exosomes in plasma based on expression of housekeeping proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western blot and flow cytometry analysis of exosomes were used to confirm the Exotest-based findings. The Exotest allowed sensitive detection and quantification of exosomes purified from human tumor cell culture supernatants and plasma from SCID mice engrafted with human melanoma. Plasma levels of exosomes in melanoma-engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy donors (n = 58). Consistently, plasma exosomes expressing CD63 (504+/-315) or caveolin-1 (619+/-310) were significantly increased in melanoma patients as compared to healthy donors (223+/-125 and 228+/-102, respectively). While the Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%). Moreover, caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in the patients group. CONCLUSIONS/SIGNIFICANCE: We describe a new non-invasive assay allowing detection and quantification of human exosomes in plasma of melanoma patients. Our results suggest that the Exotest for detection of plasma exosomes carrying tumor-associated antigens may represent a novel tool for clinical management of cancer patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Bacterial succession and community dynamics of the emerging leaf phyllosphere in spring

Every year, deciduous trees shed their leaves, and when new leaves emerge next spring, they establish a characteristic bacterial leaf community. In this exploratory study, we assessed the bacterial phyllosphere (aboveground plant surfaces) of eight London plane trees (Platanus × acerifolia) in Antwerp and Milan by sampling weekly during leaf emergence and expansion. We sampled the surfaces of different tree compartments: leaves, leaf buds, branches, and trunk, for up to 6 weeks. Phyllosphere community composition was most strongly determined by tree compartment. Only the communities on the emerging leaves showed changing dynamics over time. The rate of change in the leaf phyllosphere composition, expressed as the beta dissimilarity between consecutive time points, was very high following leaf emergence, with decreasing speed over time, indicating that these communities stabilize over time. We also identified cooccurring groups of bacteria associated with potential stages of ecological succession on the leaves and accordingly named them general cluster, early cluster, middle cluster, and late cluster. Taxa of the general cluster were not only more abundant than the others on leaves, but they were also widespread on other tree compartments. The late cluster was most pronounced in trees surrounded by trafficked urban land use. This study mainly generates hypotheses on the ecological succession on the emerging leaves of deciduous trees in urban environments and contributes to understanding the development of the tree leaf phyllosphere in spring. IMPORTANCE Improving our understanding of phyllosphere ecology is key in successfully applying bacterial biological agents or modulating the leaf microbiome in order to achieve valuable ecosystem services, such as plant protection, plant growth, air purification, and developing a healthy human immune system. Modulation of the phyllosphere microbiome in the field works only with variable success. To improve the impact of our applications in the field, a better understanding of the ecological principles governing phyllosphere dynamics is required. This exploratory study demonstrates how the combination of different analyses of a chronosequence of bacterial communities can provide new ecological insights. With a limited number of sampled trees, we demonstrated different indications of ecological succession of bacterial communities in the leaves and observed a potential impact of intensely trafficked land use becoming apparent in the leaf bacterial communities approximately 3 weeks after leaf emergence, consisting of a separate stage in community development

Twenty-year clinical experience with fixed functional appliances

ABSTRACT Introduction: Considering the large number of fixed functional appliances, choosing the best device for your patient is not an easy task. Objective: To describe the development of fixed functional appliances as well as our 20-year experience working with them. Methods: Fixed functional appliances are grouped into flexible, rigid and hybrid. They are different appliances, whose action is described here. Four clinical cases will be reported with a view to illustrating the different appliances. Conclusions: Rigid fixed functional appliances provide better skeletal results than flexible and hybrid ones. Flexible and hybrid appliances have similar effects to those produced by Class II elastics. They ultimately correct Class II with dentoalveolar changes. From a biomechanical standpoint, fixed functional appliances are more recommended to treat Class II in dolichofacial patients, in comparison to Class II elastics