A geogenic approach for the Radon monitoring and the exposure assessment at a regional scale: The results of the Rad_Campania project

Abstract. The aim of this paper is to analyse and discuss the results of the regional program Rad Campania for the monitoring and the assessment of the radon risk. An innovative methodology, based on a geogenic approach, was developed, supported by a comprehensive campaign of radon measurement performed in soil gas, natural waters, drinking natural water samples and indoor air. Data refer to field measurements carried out in three provinces of the Campania Region (Italy): Salerno, Avellino and Benevento. The programme was completed with the main purpose to investigate the peculiarities of the radon issue at a provincial scale and to redact a map of the radon potential from soil as a tool for authorities to recognise critical areas ("Radon prone areas") to monitor. Since the experience demonstrates that the high radon potential from soil is not indicative of high indoor radon concentrations, in this paper the authors have tried to identify a possible general correlation between geological features of the soil and structural characteristics of the buildings, elaborating more in depth all data collected. The main purpose is to categorize and analyse the performance of different kind of construction, typical of the local area, in order to develop, in a future work, an indicator of the building performances as a useful tool, for authorities, to recognise constructions potentially more exposed to high indoor radon activity concentrations. Results and perspectives have been discussed

Metastatic melanoma cells with BRAF G469A mutation: nab‑paclitaxel better than vemurafenib?

Purpose BRAF G469A is a missense mutation within exon 11 of the BRAF gene resulting in a constitutively activated enzyme frequently associated with MAP kinase cascade signaling activation. No evidence currently exists about its role in determining sensitivity/resistance to BRAF inhibitors, utilized in the treatment of patients carrying BRAF V600 mutations, and to chemotherapy. The newly established metastatic melanoma (MM) cell line MO-1 was characterized for its sensitivity to vemurafenib and nabpaclitaxel, both already utilized for the treatment of MM. Methods All analyses were carried out by comparing results with those found in MM cells wild type for BRAF or mutated in V600. In addition, cellular effectors were investigated by ELISA kits, western blotting and flow cytometry. Results The exposure to vemurafenib inhibited MO-1 cell proliferation at concentrations similar to those obtained in vemurafenib-resistant melanoma models, and an explanation of this sensitivity is the strong activation of Erk1/2 . and the low expression of MITF. Nab-paclitaxel strongly reduced proliferation of MO-1 cells perhaps for the very low expression level of PMEL17, transcriptionally regulated by MITF and negatively involved in determining sensitivity to taxanes. Conclusions Thus, the mutation BRAF G469A in MM might be related to a weak effectiveness of therapy with BRAF inhibitors and a promising therapeutic approach may be with nab-paclitaxel

The Genetic Germline Background of Single and Multiple Primary Melanomas

Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM

The Genetic Germline Background of Single and Multiple Primary Melanomas

Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM

New Optimization Methods for Converging Perturbative Series with a Field Cutoff

We take advantage of the fact that in lambda phi ^4 problems a large field cutoff phi_max makes perturbative series converge toward values exponentially close to the exact values, to make optimal choices of phi_max. For perturbative series terminated at even order, it is in principle possible to adjust phi_max in order to obtain the exact result. For perturbative series terminated at odd order, the error can only be minimized. It is however possible to introduce a mass shift in order to obtain the exact result. We discuss weak and strong coupling methods to determine the unknown parameters. The numerical calculations in this article have been performed with a simple integral with one variable. We give arguments indicating that the qualitative features observed should extend to quantum mechanics and quantum field theory. We found that optimization at even order is more efficient that at odd order. We compare our methods with the linear delta-expansion (LDE) (combined with the principle of minimal sensitivity) which provides an upper envelope of for the accuracy curves of various Pade and Pade-Borel approximants. Our optimization method performs better than the LDE at strong and intermediate coupling, but not at weak coupling where it appears less robust and subject to further improvements. We also show that it is possible to fix the arbitrary parameter appearing in the LDE using the strong coupling expansion, in order to get accuracies comparable to ours.Comment: 10 pages, 16 figures, uses revtex; minor typos corrected, refs. adde

Aurora kinase B inhibition reduces the proliferation of metastatic melanoma cells and enhances the response to chemotherapy

Background: The poor response to chemotherapy and the brief response to vemurafenib in metastatic melanoma patients, make the identification of new therapeutic approaches an urgent need. Interestingly the increased expression and activity of the Aurora kinase B during melanoma progression suggests it as a promising therapeutic target. Methods: The efficacy of the Aurora B kinase inhibitor barasertib-HQPA was evaluated in BRAF mutated cells, sensitive and made resistant to vemurafenib after chronic exposure to the drug, and in BRAF wild type cells. The drug effectiveness has been evaluated as cell growth inhibition, cell cycle progression and cell migration. In addition, cellular effectors of drug resistance and response were investigated. Results: The characterization of the effectors responsible for the resistance to vemurafenib evidenced the increased expression of MITF or the activation of Erk1/2 and p-38 kinases in the newly established cell lines with a phenotype resistant to vemurafenib. The sensitivity of cells to barasertib-HQPA was irrespective of BRAF mutational status. Barasertib-HQPA induced the mitotic catastrophe, ultimately causing apoptosis and necrosis of cells, inhibited cell migration and strongly affected the glycolytic metabolism of cells inducing the release of lactate. In association i) with vemurafenib the gain in effectiveness was found only in BRAF(V600K) cells while ii) with nab-paclitaxel, the combination was more effective than each drug alone in all cells. Conclusions: These findings suggest barasertib as a new therapeutic agent and as enhancer of chemotherapy in metastatic melanoma treatment

The relevance of BRAF G469A mutation in determining the response to therapy in metastatic melanoma

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Actividad antibacteriana de alcaloides de Tabernaemontana catharinensis A.DC.

Se estudió la actividad antibacteriana de extractos secos metanólicos y fracción alcaloidea obtenidos de la cortezadel tronco de Tabernaemontana catharinensis A. DC., por el método de difusión de Kirby-Bauer.Se detectó actividad frente a Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Staphylococcus aureus meticilinoresistentes, Streptococcus faecalis, Salmonella enteritidis, Shigella flexneri, Staphylococcus epidermidis, Acynetobacterlwoffii