412 research outputs found

    The usefulness or uselessness of novelty: re-examining assumptions about the relationship between creativity and innovation

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    Creativity and innovation continue to attract significant attention from both scholars and practitioners, yet little is known about the processes by which ideas (i.e. potential innovations) are evaluated and selected following initial generation. This research applied a behavioral decision research (BDR) perspective to test boundary conditions for a traditional assumption of the creativity and innovation literatures, the notion that increases in creative idea generation will increase the likelihood of innovation. Two studies challenge the traditional assumption by demonstrating that the creativity component of novelty can be inversely related to subsequent idea evaluation and selection. Study 1 found that idea novelty was negatively related to idea selection and recommendation after controlling for idea usefulness. Study 2 replicated the negative relationship between idea novelty and idea selection, and also found that idea novelty and novelty goals interacted to negatively influence idea selection. These findings suggest that scholars and practitioners need to devote greater attention to understanding idea evaluation and selection processes to translate creative efforts to actual innovation in organizations

    The contractile properties of vaginal myofibroblasts: Is the myofibroblasts contraction force test a valuable indication of future prolapse development?

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    Using a specific myofibroblast contraction test, we try to predict future utero-vaginal prolapse development in young primiparae women. We compare myofibroblast cultures of the vaginal wall in primiparae women (group 1), young multiparae women (group 2) and older multiparae women (group 3) who were operated on for severe utero-vaginal prolapse. A myofibroblast-mediated collagen gel contraction assay determined a contraction factor that was compared in the three groups of women. The myofibroblasts contraction factor after 24 and 48 hours was significantly higher in group 1 women (2.4 ± 0.6/4.4 ± 1.9) compared to group 2 (1.6 ± 0.3/ 1.8 ± 0.1) andgroup 3 (1.6 ± 0.3/1.8 ± 0.3), but showed no differences in group 1 women without (2.1 ± 0.5/3.5 ± 1.9) and with (2.7 ± 0.6/5.1 ± 1.7) cystocoele. Vaginal myofibroblasts of young women show better contraction forces than young women with severe utero-vaginal prolapse. The latter have a myofibroblast contraction factor similar to those of older post-menopausal women operated for the same conditio

    Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction.

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    Fibrosis is an inadequate response to tissue stress with very few therapeutic options to prevent its progression to organ dysfunction. There is an urgent need to identify drugs with a therapeutic potential for fibrosis, either by designing and developing new compounds or by repurposing drugs already in clinical use which were developed for other indications. In this Perspective, we summarize some pathways and biological targets involved in fibrosis development and maintenance, focusing on common mechanisms between organs and diseases. We review the therapeutic agents under experimental development, clinical trials, or in clinical use for the treatment of fibrotic disorders, evaluating the reasons for the discrepancies observed between preclinical and clinical results. We also discuss the improvement that we envision in the development of therapeutic molecules able to achieve improved potential for treatment, including indirect modulators, targeting approaches, or drug combinations

    Biological impact assessment of nanomaterial used in nanomedicine. introduction to the NanoTEST project.

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    Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or imaging agents, providing increased selectivity/specificity for diseased tissues. The first NPs in nanomedicine were developed for increasing the efficacy of known drugs displaying dose-limiting toxicity and poor bioavailability and for enhancing disease detection. Nanotechnologies have gained much interest owing to their huge potential for applications in industry and medicine. It is necessary to ensure and control the biocompatibility of the components of therapeutic NPs to guarantee that intrinsic toxicity does not overtake the benefits. In addition to monitoring their toxicity in vitro, in vivo and in silico, it is also necessary to understand their distribution in the human body, their biodegradation and excretion routes and dispersion in the environment. Therefore, a deep understanding of their interactions with living tissues and of their possible effects in the human (and animal) body is required for the safe use of nanoparticulate formulations. Obtaining this information was the main aim of the NanoTEST project, and the goals of the reports collected together in this special issue are to summarise the observations and results obtained by the participating research teams and to provide methodological tools for evaluating the biological impact of NPs

    Fibroblast activation protein-α in fibrogenic disorders and cancer: more than a prolyl-specific peptidase?

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    Fibroblast activation protein-α (FAP-α) belongs to the family of prolyl-specific serine proteases. FAP-α displays both exopeptidase and endopeptidase/gelatinase/collagenase activities. FAP-α protein and/or activity have been associated with fibrosis, inflammation and cancer, but the protein is undetectable in most normal tissues. FAP-α is selectively expressed at sites of tissue remodeling and repair and enhances tumor progression, suggesting that this protease may be a therapeutic target to treat human disorders associated with fibrotic dysregulation. Areas covered: In this review, we summarize the mechanisms driving tissue fibrosis and describe some of the enzymes involved in fibrosis, concentrating on FAP-α. We describe its enzymatic properties, discuss the tools developed to control its activity and the problem of selectivity toward the other proteases of the family and outline its potential biological substrates. We also consider non-enzymatic functions of this protein and suggest that repression of FAP-α expression may represent therapeutic options. Expert opinion: Questions remain regarding the biological functions of FAP-α, either dependent or independent of its enzyme activity. However, as progress is underway to develop FAP-α-specific inhibitors and therapeutic antibodies, its role in diseases associated with fibrosis is starting to emerge, ultimately leading to novel therapeutic options for inflammatory and oncologic diseases

    Differential Effects of the Mitochondria-Active Tetrapeptide SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH<sub>2</sub>) and Its Peptidase-Targeted Prodrugs in Experimental Acute Kidney Injury.

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    The mitochondria-active tetrapeptide SS-31 can control oxidative tissue damage in kidney diseases. To investigate other potential beneficial nephroprotective effects of SS-31, in vivo murine models of acute tubular injury and glomerular damage were developed. Reduction of acute kidney injury was demonstrated in mice treated with SS-31. The expression of mRNAs involved in acute inflammatory and oxidative stress responses in the diseased kidneys confirmed that SS-31 could regulate these pathways in our in vivo models. Furthermore, ex vivo histoenzymography of mouse kidneys showed that aminopeptidase A (APA), the enzyme involved in the processing of angiotensin (Ang) II to Ang III, was induced in the diseased kidneys, and its activity was inhibited by SS-31. As the renin-angiotensin system (RAS) is a main regulator of kidney functions, the modulation of Ang receptors (ATR) and APA by SS-31 was further investigated using mRNAs extracted from diseased kidneys. Following acute tubular and/or glomerular damage, the expression of the AT &lt;sub&gt;1&lt;/sub&gt; R mRNA was upregulated, which could be selectively downregulated upon SS-31 administration to the animals. At the same time, SS-31 was able to increase the expression of the AT &lt;sub&gt;2&lt;/sub&gt; R, which may contribute to limit renal damage. Consequently, SS-31-based prodrugs were developed as substrates and/or inhibitors for APA and were screened using cells expressing high levels of APA, showing its selective regulation by α-Glu-SS-31. Thus, a link between SS-31 and the RAS opens new therapeutic implications for SS-31 in kidney diseases

    P719 Determinants of tobacco consumption in the Swiss IBD cohort

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    Background: Tobacco consumption is an important environmental factor in inflammatory bowel diseases (IBD). Our aim was to identified characteristics associated with smoking in Crohn's disease (CD) and Ulcerative colitis (UC). Methods: Adult UC and CD patients included in the Swiss IBD cohort study (SIBDCS) from Nov. 2006 to Nov. 2015 were asked about their smoking status. Patients were separated in two groups (active smokers vs. non-smokers). A logistic regression analysis was performed with smoking as main outcome

    Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles.

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    Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo₂ cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell- and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo₂ cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs

    Alternate Grazing of Cattle and Horses reduces infections with Strongyle Parasites – a case study

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    Gastro-Intestinal Nematodes (GIN) impact on the health and the production of horses and cattle, especially regarding young animals.7,10 Mixed and alternate grazing of production animals (herbivores) for the prevention of GIN is an important element of pasture management with the potential benefit arising from the host-selectivity of numerous GIN species.6,9,12 Small ruminants, for example, harbour a number of strongyle parasite species, which will not lead to stable populations in cattle, and in turn, cattle strongyles such as Ostertagia ostertagi or Cooperia oncophora will not reach patency when ingested by sheep. A substantial number of studies have been performed on mixed and alternate grazing between sheep and cattle or goats and cattle and have overall proven its benefit for different climates and environments.1,3,8 Information on the effect of alternate or mixed grazing of cattle with equids is, however, scarce. This is surprising, as with the exception of liver flukes and the strongyle species Trichostrongylus axei and compared to the cattle/small ruminant grazing combination, horses share no GIN species with cattle. Only recently a French study by Forteau et. al. 5 has shown for the first time that mixed grazing of horses and cattle was beneficial for horses in terms of lower strongyle faecal egg counts. No information is, however, available as to whether the horse/cattle grazing combination is also advantageous in terms of reduced GIN infection in cattle
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