Targeted nanoparticles for the delivery of novel bioactive molecules to pancreatic cancer cells

Pancreatic cancer (PaCa) is a multifaceted disorder with an extremely poor prognosis. There is an urgent need to identify new and safe drugs as well as to develop novel tumor-targeted controlled release systems for effective treatment of late stage and resistant PaCa. Active targeting via the inclusion of specific ligands on the nanoparticles (NPs) is envisioned to provide a powerful therapeutic strategy. Herein, we present a study on the design and the development of novel DFCencapsulated biocompatible polymeric NPs, functionalized with peptides to selectively bind to Plec-1 (PTP), or densely decorated by low molecular weight organic molecules as alternative targeting ligands (2-ABA), and evaluated a) the impact on ligand binding and b) the in vitro antiproliferative efficacy against a panel of PaCa cells

Rosmarinus officinalis L.: chemical modifications of the essential oil and evaluation of antioxidant and antimicrobial activity.

Rosmarinus officinalis essential oil was separated into its hydrocarbon and oxygenated fractions. The major compounds in the hydrocarbon fraction were α-pinene (44.2%), camphene (24.5%), and limonene (11.7%), while in the oxygenated fraction they were 1,8-cineole (37.6%), camphor (16.5%), and bornyl acetate (21.4%). The hydrocarbon fraction was submitted to a hydroformylation process and the antioxidant activity of the product was screened by the DPPH and β-carotene/linoleic acid tests. The hydroformylated fraction maintained the antioxidant activity of the whole oil. The MIC (minimal inhibitory concentration) and the MBC (minimal bactericidal concentration) of the essential oil, hydrocarbon, oxygenated and hydroformylated fractions were also tested on several microorganisms. Aeromonas sobria and Candida strains were the most susceptible micro-organisms. The hydroformylated fraction exhibited a MBC against Candida strains resistant to the other fractions

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD)

Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials

Fate of selected pathogens in spiked «SALAME NOSTRANO» produced without added nitrates following the application of NONIT™ technology

This study evaluated the effect of a novel formulation for starter culture associated with specific ripening conditions (NoNit™ technology) vs. a commercial» starter on the fate of selected pathogens and hygiene indicators during the fermentation and ripening of experimentally spiked salame nostrano (Italian dry sausage). Selected strains of Staphylococcus aureus 27R, Escherichia coli CSH26 K 12, Listeria innocua ATCC 33090 and Salmonella Derby 27 were inoculated into salami batter and challenged with two formulations of starter cultures (a commercial formulation and the NoNit™ formulation, consisting of Lactococcus lactis ssp. lactis, strain 340; L. lactis ssp. lactis, strain 16; Lactobacillus casei ssp. casei, strain 208 and Enterococcus faecium strain 614) with ripening at a low temperature. The proposed technology (NoNit™) performed better than the commercial formulation and limited the growth of spiked Escherichia coli, Staphylococcus aureus (including the production of enterotoxin), Salmonella Derby and Listeria innocua, yet maintained the basic product appearance and texture.Supplementary Data 1 : Reduction of selected microorganisms challenged vs. NoNitTM in milk.Supplementary Data 2 : Reduction of selected microorganisms challenged vs. NoNitTM in salami.Supplementary Data 3 : Curve for acidification kinetic for NoNitTM alone and in associations with selected pathogens.A grant from the Sviluppumbria S.p.A., programme iStart 2014, grant n. 28/2014.http://www.elsevier.com/locate/meatsci2019-05-01hj2019Paraclinical Science

Genetic diversity of Italian goat breeds assessed with a medium-density SNP chip

Background: Among the European countries, Italy counts the largest number of local goat breeds. Thanks to the recent availability of a medium-density SNP (single nucleotide polymorphism) chip for goat, the genetic diversity of Italian goat populations was characterized by genotyping samples from 14 Italian goat breeds that originate from different geographical areas with more than 50 000 SNPs evenly distributed on the genome. Results: Analysis of the genotyping data revealed high levels of genetic polymorphism and an underlying North-south geographic pattern of genetic diversity that was highlighted by both the first dimension of the multi-dimensional scaling plot and the Neighbour network reconstruction. We observed a moderate and weak population structure in Northern and Central-Southern breeds, respectively, with pairwise FST values between breeds ranging from 0.013 to 0.164 and 7.49 % of the total variance assigned to the between-breed level. Only 2.11 % of the variance explained the clustering of breeds into geographical groups (Northern, Central and Southern Italy and Islands). Conclusions: Our results indicate that the present-day genetic diversity of Italian goat populations was shaped by the combined effects of drift, presence or lack of gene flow and, to some extent, by the consequences of traditional management systems and recent demographic history. Our findings may constitute the starting point for the development of marker-assisted approaches, to better address future breeding and management policies in a species that is particularly relevant for the medium-and long-term sustainability of marginal regions

Comparison of MRI lesion evolution in different central nervous system demyelinating disorders

Background and Objective: There are few studies that compare lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2-lesion evolution in myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS). Methods: In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and: 1) brain or myelitis attack; 2) available attack MRI within 6 weeks; and 3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2-lesion for each patient (index lesion). MRIs were then independently reviewed by two neuroradiologists blinded to diagnosis to determine resolution of T2-lesions by consensus. The index T2-lesion area was manually outlined acutely and at follow-up to assess variation in size. Results: We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]) and MS (37 [16-61]) (p&lt;0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2-lesion was more frequent in MOGAD (brain, 13/18[72%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 3/21[14%]; spine, 0/34[0%]) and MS (brain, 7/42[17%]; spine, 0/29[0%]), p&lt;0.001. Resolution of all T2-Lesions occurred most often in MOGAD (brain, 7/18[39%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 2/21[10%]; spine, 0/34[0%]), and MS (brain, 2/42[5%]; spine, 0/29[0%]), p&lt; 0.01. There was a larger median (range) reduction in T2-lesion area in mm2 on follow-up axial brain MRI with MOGAD (213[55-873]) than AQP4-IgG-NMOSD (104[0.7-597]) (p=0.02) and MS, 36[0-506]) (p&lt; 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262[0-888]) and AQP4-IgG-NMOSD (309[0-1885]) were similar (p=0.4) and greater than MS (23[0-152]) (p&lt;0.001)

Il falso dilemma pubblico-privato. L’anomalia della scuola italiana nel contesto europeo

Il modello organizzativo del sistema scolastico italiano in prospettiva storica e comparata nel contesto europeo; prospettive per un adeguamento della scuola italiana al “sistema medio europeo”.- Indice #4- Introduzione, Marcello Pacini #8- Nota metodologica #14- Cap.I Il modello organizzativo del sistema scolastico italiano #18- Cap.II Il sistema medio europeo. Sistemi e problemi di un'analisi comparata #54- Cap.III Verso la deburocratizzazione. Prospettive per un adeguamento della scuola italiana al “sistema medio europeo” #114- Allegato I La struttura del sistema scolastico italiano #146- Relazioni e interventi di discussione sulla ricerca #206- Intervento On. Francesco Casati, Presidente della Commissione Istruzione e Belle Arti della Camera dei Deputati #208- Intervento Sen. Luigi Covatta, Sottosegretario di Stato alla Pubblica Istruzione #212- Intervento Sen. Salvatore Valitutti, Presidente della Commissione Istruzione Pubblica e Belle Arti del Senato della Repubblica #215- Intervento Emanuele Caruso, Dirigente Generale dell'Istruzione Tecnica, Ministero della Pubblica Istruzione #219- Intervento Mario Dupuis, Responsabile Scuola del Movimento Popolare #222- Intervento On. Laura Fincato, Vicepresidente della Commissione Istruzione e Belle Arti della Camera dei Deputati #225- Intervento Aureliana Alberici, Responsabile Scuola/Università della Direzione del P.C.I. #229- Intervento Paolo Serreri, Federazione Scuola Università C.G.I.L. #237- Intervento Daniela Silvestri, Rappresentante nazionale del Sindacato Nazionale Autonomo Lavoratori Scuola SNALS #242- Intervento Paolo Martelli, Direttore di POLITEIA - Centro per la ricerca e la formazione in politica ed etica #245- Intervento Salvatore Sechi, Professore ordinario di Storia Contemporanea, Università di Bologna #252- Intervento Piero Romei, Ricercatore dell'ISGO #257- Intervento Giovanni Bechelloni, Professore ordinario di Sociologia dei processi culturali, Università di Firenze #263- Intervento Giorgio Allulli, Censis #266- Intervento Graziella Morselli, FNISM #270- Intervento Luigi Pedrazzi, Il Mulino #274- Intervento Luciano Benadusi, Responsabile Settore Università e ricerca scientifica della Direzione Socialista #277- Intervento Mario Caronna #Coordinatore scientifico del Centro Studi di Milano #282- Intervento Adriana Rosas, Ricercatore presso il CLAS #287- Intervento Giovanni Tesoro, Ricercatore presso l’ISGO #290- Considerazioni conclusive Luisa Ribolzi, CLAS #29