Decorin transfection induces proteomic and phenotypic modulation in breast cancer cells 8701-BC

Decorin is a prototype member of the small leucine-rich proteoglycan family widely distributed in the extracellular matrices of many connective tissues, where it has been shown to play multiple important roles in the matrix assembly process, as well as in some cellular activities. A major interest for decorin function concerns its role in tumorigenesis, as growth-inhibitor of different neoplastic cells, and potential antimetastatic agent. The aim of our research was to investigate wide-ranged effects of transgenic decorin on breast cancer cells. To this purpose we utilized the well-characterized 8701-BC cell line, isolated from a ductal infiltrating carcinoma of the breast, and two derived decorin-transfected clones, respectively, synthesizing full decorin proteoglycan or its protein core. The responses to the ectopic decorin production were examined by studying morphological changes, cell proliferation rates, and proteome modulation. The results revealed new important antioncogenic potentialities, likely exerted by decorin through a variety of distinct biochemical pathways. Major effects included the downregulation of several potential breast cancer biomarkers, the reduction of membrane ruffling, and the increase of cell-cell adhesiveness. These results disclose original aspects related to the reversion of malignant traits of a prototype of breast cancer cells induced by decorin. They also raise additional interest for the postulated clinical application of decori

Context-dependent cheating: experimental evidence from 16 countries

Policy makers use several international indices that characterize countries according to the quality of their institutions. However, no effort has been made to study how the honesty of citizens varies across countries. This paper explores the honesty among citizens across sixteen countries with 1440 participants. We employ a very simple task where participants face a trade-off between the joy of eating a fine chocolate and the disutility of having a threatened self-concept because of lying. Despite the incentives to cheat, we find that individuals are mostly honest. Further, international indices that are indicative of institutional honesty are completely uncorrelated with citizens' honesty for our sample countries

Factors that influence children's gambling attitudes and consumption intentions: Lessons for gambling harm prevention research, policies and advocacy strategies

Background: Harmful gambling is a public health issue that affects not only adults but also children. With the development of a range of new gambling products, and the marketing for these products, children are potentially exposed to gambling more than ever before. While there have been many calls to develop strategies which protect children from harmful gambling products, very little is known about the factors that may influence children's attitudes towards these products. This study aimed to explore children's gambling attitudes and consumption intentions and the range of consumer socialisation factors that may influence these attitudes and behaviours. Methods: Children aged 8 to 16 years old (n = 48) were interviewed in Melbourne, Australia. A semi-structured interview format included activities with children and open-ended questions. We explored children's perceptions of the popularity of different gambling products, their current engagement with gambling, and their future gambling consumption intentions. We used thematic analysis to explore children's narratives with a focus on the range of socialising factors that may shape children's gambling attitudes and perceptions. Results: Three key themes emerged from the data. First, children's perceptions of the popularity of different products were shaped by what they had seen or heard about these products, whether through family activities, the media (and in particular marketing) of gambling products, and/or the alignment of gambling products with sport. Second, children's gambling behaviours were influenced by family members and culturally valued events. Third, many children indicated consumption intentions towards sports betting. This was due to four key factors: (1) the alignment of gambling with culturally valued activities; (2) their perceived knowledge about sport; (3) the marketing and advertising of gambling products (and in particular sports betting); and (4) the influence of friends and family. Conclusions: This study indicates that there is a range of socialisation factors, particularly family and the media (predominantly via marketing), which may be positively shaping children's gambling attitudes, behaviours and consumption intentions. There is a need for governments to develop effective policies and regulations to reduce children's exposure to gambling products and ensure they are protected from the harms associated with gambling. © 2017 The Author(s)

Effect of a quality improvement program on compliance to the sepsis bundle in non-ICU patients: a multicenter prospective before and after cohort study

ObjectiveSepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a “simplified 1-h bundle” (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU).MethodsEmergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort).Measurements and main resultsThe effect of QIP on bundle compliance and hospital mortality was evaluated in a before–after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the “simplified rapid (1 h) intervention bundle” (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p < 0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients’ cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality.ConclusionA multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality

Molecular stability of chemically modified collagen triple helices

Ionic residues influence the stability of collagen triple helices and play a relevant role in the spontaneous aggregation of fibrillar collagens. Collagen types I and II and some of their CNBr peptides were chemically modified in mild conditions with two different protocols. Primary amino groups of Lys and Hyl were N-methylated by formaldehyde in reducing conditions or N-acetylated by sulfosuccinimidyl acetate. The positive charge of amino groups at physiological pH was maintained after the former modification, whereas it was lost after the latter. These chemical derivatizations did not significantly alter the stability of the triple helical conformation of peptide trimeric species. Also the enthalpic change on denaturation was largely unaffected by derivatizations. This implies that no significant variation of weak bonds, either in number or overall strength, and of entropy occur on modification. These properties can probably be explained by the fact that chemically modified groups maintain the ability to form hydrogen bonds

Glycosaminoglycans show a specific periodic interaction with type I collagen fibrils

Current wisdom on intermolecular interactions in the extracellular matrix assumes that small proteoglycans bind collagen fibrils on highly specific sites via their protein core, while their carbohydrate chains interact with each other in the interfibrillar space. The present study used high-resolution scanning electron microscopy to analyse the interaction of two small leucine-rich proteoglycans and several glycosaminoglycan chains with type I collagen fibrils obtained in vitro in a controlled, cell-free environment. Our results show that most ligands directly influence the collagen fibril size and shape, and their aggregation into thicker bundles. All chondroitin sulphate/dermatan sulphate glycosaminoglycans we tested, except chondroitin 4-sulphate, bound to the fibril surface in a highly specific way and, even in the absence of any protein core, formed regular, periodic interfibrillar links resembling those of the intact proteoglycan. Only intact decorin, however, was able to organize collagen fibrils into fibres compact enough to mimic in vitro the superfibrillar organization of natural tissues. Our data indicate that multiple interaction patterns may exist in vivo, may explain why decorin- or biglycan-knockout organisms show milder effects than can be expected, and may lead to the development of better, simpler engineered biomaterials. \ua9 2008 Elsevier Inc. All rights reserved