Paziente con carcinoma mammario metastatico, HER2-positivo, resistente a trastuzumab e pertuzumab ma responsivo a lapatinib

Lapatinib is an intracellular tyrosine kinase inhibitor of EGFR (ErbB1) and HER2 (ErbB2) receptors, approved for the treatment of metastatic breast carcinoma pre-treated with anti-HER2 antibodies. We report the case of a 60-year-old woman diagnosed with metastatic breast neoplasm, HER2-positive, progressing after treatment with trastuzumab, pertuzumab and T-DM1, who obtained a regression of hepatic metastases after treatment with lapatinib-capecitabine (Oncology)

Sedimentology and composition of sands injected during the seismic crisis of May 2012 (Emilia, Italy): clues for source layer identification and liquefaction regime

InMay 2012widespread sand blows formed along buried channels in the eastern sector of the Po Plain (Northern Italy) as a consequence of a series of seismic eventswith main shocks ofMw6.1 and 5.9. At San Carlo (Ferrara) a trench dug a few week after the earthquakes exposed sand dikes cutting through an old Reno River channel– levee system that was diverted in the 18th century and was deposited starting from the 14th century (unit A). This sequence overlies a Holocene muddy floodplain deposits and contains scattered sandy channel deposits (unit B) and a Pleistocene channel sand unit (unit C). Sands with inverse and normal grading, concave layering and vertical lamination coexisting along the dikes suggest multiple rhythmic opening and closing of the fractures that were injected and filled by a slurry of sand during the compression pulses, and emptied during the extension phase. The pulse mechanism may have lasted for several minutes and formed well stratified sand volcanoes structures that formed at the top of the fractures. Sands fromdikes and fromthe various units showwell defined compositional fields from lithoarenitic to quartz-feldspar-rich compositions. Sands from the old Reno levee and channel fill (unit A) have abundant lithic fragments derived fromthe erosion of Apennine sedimentary carbonate and terrigenous successions. Composition of the sand filling the dikes showclear affinities with sand layers of the old Reno River channel (Unit A) and clearly differ from any sand from deeper Holocene and Pleistocene layers (Unit B and C),which are richer in quartz and feldspar and poorer in sedimentary lithic fragments. Sorting related to sediment flux variations did not apparently affect the sand composition across the sedimentary structures. Textural and compositional data indicate that the liquefaction processes originated from a relatively shallow source consisting of channel sands located within Unit A at 6.8.to 7.5 m depth

Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder characterized by unexplained left ventricle hypertrophy associated with non-dilated ventricular chambers. Several genes encoding heart sarcomeric proteins have been associated to HCM, but a small proportion of HCM patients harbor alterations in other non-sarcomeric loci. The variable expression of HCM seems influenced by genetic modifier factors and new sequencing technologies are redefining the understanding of genotype–phenotype relationships, even if the interpretations of the numerous identified variants pose several challenges. Methods and results: We investigated 62 sarcomeric and non-sarcomeric genes in 41 HCM cases and in 3 HCM-related disorders patients. We employed an integrated approach that combines multiple tools for the prediction, annotation and visualization of functional variants. Genotype–phenotype correlations were carried out for inspecting the involvement of each gene in age onset and clinical variability of HCM. The 80% of the non-syndromic patients showed at least one rare non-synonymous variant (nsSNV) and among them, 58% carried alterations in sarcomeric loci, 14% in desmosomal and 7% in other non-sarcomeric ones without any sarcomere change. Statistical analyses revealed an inverse correlation between the number of nsSNVs and age at onset, and a relationship between the clinical variability and number and type of variants. Conclusions: Our results extend the mutational spectrum of HCM and contribute in defining the molecular pathogenesis and inheritance pattern(s) of this condition. Besides, we delineate a specific procedure for the identification of the most likely pathogenetic variants for a next generation sequencing approach embodied in a clinical context

A selective cellulose/hemicellulose green solvents extraction from buckwheat chaff

A two-phase extraction process was adopted to obtain cellulose and hemicellulose from buckwheat chaff by using green solvents. We are proposing a combination of propylene carbonate (PC) and ionic liquids (ILs) in a 1:5 ratio. We compared the first-generation ILs 1-butyl-2,3-dimethylimidazolium chloride (BdmimCl), and 1-butyl-3-methyl imidazolium acetate (BmimAc) with respect to the tetrabutyl ammonium acetate (TBAAc). The cellulose and hemicellulose were, firstly, extracted into the PC/IL mixture and subsequently precipitated by water addition. All precipitate materials were analysed by FTIR-ATR and TGA, while the organic phase and the supernatant after water addition were analysed by using self-diffusion NMR. The PC green co-solvent was proven to be an exceptional candidate to replace dimethyl sulfoxide. The highest amount of precipitate material after water addition was obtained with PC-BmimAc, while PC-TBAAc was showing the highest cellulose/hemicellulose selectivity. Furthermore, a preferential interaction of the supernatant cellulose residue with PC or acetate was observed by self-diffusion NMR

Biofilm and Pathogenesis-Related Proteins in the Foodborne P. fluorescens ITEM 17298 With Distinctive Phenotypes During Cold Storage

In food chain, Pseudomonas spp. cause spoilage by reducing shelf life of fresh products, especially during cold storage, with a high economic burden for industries. However, recent studies have shed new light on health risks occurring when they colonize immunocompromised patient tissues. Likewise to P. aeruginosa, they exhibit antibiotic resistance and biofilm formation, responsible for their spread and persistence in the environment. Biofilm formation might be induced by environmental stresses, such as temperature fluctuations causing physiological and metabolic changes exacerbating food spoilage (by protease and pigment synthesis), and the production of adhesion molecules, chemotactic or underestimated virulence factors. In order to provide a new insight into phenotypic biodiversity of Pseudomonas spoilers isolated from cold stored cheese, in this work 19 Pseudomonas spp. were investigated for biofilm, pigments, exopolysaccharide production and motility at low temperature. Only nine strains showed these phenotypic traits and the blue pigmenting cheese strain P. fluorescens ITEM 17298 was the most distinctive. In addition, this strain decreased the survival probability of infected Galleria mellonella larvae, showing, for the first time, a pathogenic potential. Genomic and proteomic analyses performed on the ITEM 17298 planktonic cells treated or not with lactoferrin derived antibiofilm peptides allowed to reveal specific biofilm related-pathways as well as proteins involved in pathogenesis. Indeed, several genes were found related to signaling system by cGMP-dependent protein kinases, cellulose, rhamnolipid and alginate synthesis, antibiotic resistance, adhesion and virulence factors. The proteome of the untreated ITEM 17298, growing at low temperature, showed that most of the proteins associated with biofilm regulation, pigmentation motility, antibiotic resistance and pathogenecity were repressed, or decreased their levels in comparison to that of the untreated cultures. Thus, the results of this work shed light on the complex pathways network allowing psychrotrophic pseudomonads to adapt themselves to food-refrigerated conditions and enhance their spoilage. In addition, the discovery of virulence factors and antibiotic resistance determinants raises some questions about the need to deeper investigate these underestimated bacteria in order to increase awareness and provide input to update legislation on their detection limits in foods

Characterization of the properties and trafficking of an anchorless form of the prion protein

Conversion of PrP(C) into PrP(Sc) is the central event in the pathogenesis of transmissible prion diseases. Although the molecular basis of this event and the intracellular compartment where it occurs are not yet understood, the association of PrP with cellular membranes and in particular its presence in detergent-resistant microdomains appears to be of critical importance. In addition it appears that scrapie conversion requires membrane-bound glycosylphosphatidylinositol (GPI)-linked PrP. The GPI anchor may affect either the conformation, the intracellular localization, or the association of the prion protein with specific membrane domains. However, how this occurs is not known. To understand the relevance of the GPI anchor for the cellular behavior of PrP, we have studied the biosynthesis and localization of a PrP version which lacks the GPI anchor attachment signal (PrP Delta GPI). We found that PrP Delta GPI is tethered to cell membranes and associates to membrane detergent-resistant microdomains but does not assume a transmembrane topology. Differently to PrP(C), this protein does not localize at the cell surface but is mainly released in the culture media in a fully glycosylated soluble form. The cellular behavior of anchorless PrP explains why PrP Delta GPI Tg mice can be infected but do not show the classical signs of the disorder, thus indicating that the plasma membrane localization of PrP(C) and/or of the converted scrapie form might be necessary for the development of a symptomatic disease

Deep Control of Linear Oligomerization of Glycerol Using Lanthanum Catalyst on Mesoporous Silica Gel

The valorization of glycerol (1), a waste of biodiesel production of Fatty Acid Methyl Esters (FAMEs), adopting a “green” approach, represents an important goal of sustainable chemistry. While the polymerization of 1 to hyperbranched oligomers is a well-established process, the linear analogues are difficult to obtain. In this context, we explore the reaction without the solvent of heterogeneous hybrid La(III)O-KIT-6 catalyst (2), which is based on lanthanum oxide on mesoporous silica gel, showing a superior linear selectivity compared to most of the analogous catalysts recently reported

Adaptación cultural del Cuestionario de Deseo de Marihuana (MCQ-12) para población colombiana

The current research aims to carry out the first phase of the cultural adaptation of the Marijuana Craving Questionnaire (MCQ-12) for Colombian samples. This is a quantitative and instrumental study. First, the translation process from English to Spanish was done by five psychologists. Then, the comparison and integration of these translations into a single version were carried out. After this process, the reverse translation from Spanish to English, as well as a semantic verification with a Philologist were developed. This version was submitted to validation with judges. The total content validity of the instrument was 0.84 and it was established that 10 of the 12 items fulfilled the minimum of totality in content validity. In conclusion, this version of the MCQ-12 Questionary shows adequate content validity indexes, and it is a cultural adaptation that can be applied in Colombian clinical samples.El objetivo de la presente investigación fue llevar a cabo la primera fase de la adaptación cultural del Cuestionario de Deseo de Marihuana (MCQ-12) para muestras colombianas. Este estudio es de tipo cuantitativo e instrumental. Inicialmente, se realizó un proceso de traducción al español por parte de cinco psicólogos, seguido de una comparación de las mismas, la elaboración de una única versión, su traducción inversa al inglés y una verificación semántica con una filóloga. Esta versión se sometió a la validación por jueces y se obtuvo un índice de validez de contenido total de 0.84. Así mismo, se identificó que 10 de los 12 ítems se ajustan al mínimo de totalidad en validez de contenido. En conclusión, esta versión del MCQ-12 muestra adecuados índices de validez de contenido y resulta ser una adaptación cultural que puede ser aplicada en muestras clínicas colombianas

Lipid Rafts and Clathrin Cooperate in the Internalization of PrPC in Epithelial FRT Cells

The cellular prion protein (PrP(C)) plays a key role in the pathogenesis of Transmissible Spongiform Encephalopathies in which the protein undergoes post-translational conversion to the infectious form (PrP(Sc)). Although endocytosis appears to be required for this conversion, the mechanism of PrP(C) internalization is still debated, as caveolae/raft- and clathrin-dependent processes have all been reported to be involved. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the mechanism of PrP(C) endocytosis in Fischer Rat Thyroid (FRT) cells, which lack caveolin-1 (cav-1) and caveolae, and in FRT/cav-1 cells which form functional caveolae. We show that PrP(C) internalization requires activated Cdc-42 and is sensitive to cholesterol depletion but not to cav-1 expression suggesting a role for rafts but not for caveolae in PrP(C) endocytosis. PrP(C) internalization is also affected by knock down of clathrin and by the expression of dominant negative Eps15 and Dynamin 2 mutants, indicating the involvement of a clathrin-dependent pathway. Notably, PrP(C) co-immunoprecipitates with clathrin and remains associated with detergent-insoluble microdomains during internalization thus indicating that PrP(C) can enter the cell via multiple pathways and that rafts and clathrin cooperate in its internalization. CONCLUSIONS/SIGNIFICANCE: These findings are of particular interest if we consider that the internalization route/s undertaken by PrP(C) can be crucial for the ability of different prion strains to infect and to replicate in different cell lines

Prediction and visualization data for the interpretation of sarcomeric and non-sarcomeric DNA variants found in patients with hypertrophic cardiomyopathy

AbstractGenomic technologies are redefining the understanding of genotype–phenotype relationships and over the past decade, many bioinformatics algorithms have been developed to predict functional consequences of single nucleotide variants. This article presents the data from a comprehensive computational workflow adopted to assess the biomedical impact of the DNA variants resulting from the experimental study “Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy” (Bottillo et al., 2016) [1]. Several different independently methods were employed to predict the functional consequences of alleles that result in amino acid substitutions, to study the effect of some DNA variants over the splicing process and to investigate the impact of a sequence variant with respect to the evolutionary conservation