202 research outputs found

    Case-control study to detect protective factors on pig farms with low Salmonella prevalence

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    The prevalence of Salmonella in UK pigs is amongst the highest in Europe, highlighting the risk to public health and the need to investigate on-farm controls. The objective of this study was to identify factors currently in operation on pig farms that had maintained a low Salmonella seroprevalence. For this purpose a case-control study was designed and pig farms with a low (\u3c10%) seroprevalence were compared against two randomly selected control farms, sharing the same geographical region and production type. A total of 11,452 samples, including pooled and individual floor faeces and environmental samples from pigs and their vicinity were tested and prevalence examined. In addition, detailed questionnaires were completed during the farm visits to collect descriptive data for risk factor analysis. It was shown that control farms had significantly higher prevalence compared to the case farms (19.4% and 4.3% for pooled and 6.7% and 0.1% for individual samples, respectively). The two risk factor analyses identified multiple variables associated with Salmonella prevalence including variables related to feed, effectiveness of cleaning and disinfection, biosecurity and batch production

    Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

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    The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1

    Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis

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    Background & Aims Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC’s anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis. Methods Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC’s antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses. Results CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05). At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05), and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls). CVC treatment had no notable effect on body or liver/kidney weight. Conclusions CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC’s antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475)

    Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

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    The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations. In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss could not be detected. Based on their powerful antiresorptive activity in vitro, resveratrol analogues might be attractive modulators of bone remodeling. However, further studies are required to establish their efficacy in vivo

    Exploring institutional reform of Korean civil service pension: advocacy coalition framework, policy knowledge and social innovation

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    Abstract This paper examines what factors are associated with the 2015 pension reform of Korean civil servant as social innovation. We explore what lessons we can learn from the pension reform in terms of the Advocacy Coalition Framework (ACF) model. The ACF model allows us to identify how the substantial reform is, relying on policy knowledge and entrepreneurs, possible in terms of political and social consensus. It also clearly demonstrates the possibility of systematic pension reform at an appropriate level through social learning and policy learning. Through the ACF model, we review how South Koreas civil servant pension reform act occurred at the end of May 2015. The temporal scope covers from 2009 latest reform, and the 2014s President administrative policy speech that had strongly been showed her will to reform the pension issue to the end of May 2015 when the reform bill enacted. We investigate each advocacy coalition in order to elucidate the actors that constitute the two coalition groups and to scrutinize whether a policy broker had existed in the process. We also attempt to find the relatively stable parameters and external events that affected the reform and also the belief system that shared by two advocacy coalition group. The result clearly shows that the two coalition groups shared their normative beliefs ultimately, for example, the need to change the current civil servants pension system, but, the gap in the numerical change in the policy core belief and secondary belief between the two actors had seemed to be excessively large and uncompromising. A policy broker who can coordinate the interests and interests of stakeholder groups over the government pension reform proposal was desperately needed. Negotiation and leadership of the policy entrepreneurs led to a settlement of the government pension reform proposal at the end of May 2015. Their entrepreneurial activities led to an appropriate level of social consensus on the sustainable reform of pension system through policy knowledge and learning. Further research is required to explore how models of socially innovative forms of governance are created in various pension reforms across various countries. It is also required to examine how policy entrepreneurs use policy knowledge and information for a successful institutional reform through social innovation across various countries

    Physician privacy concerns when disclosing patient data for public health purposes during a pandemic influenza outbreak

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    Background: Privacy concerns by providers have been a barrier to disclosing patient information for public health\ud purposes. This is the case even for mandated notifiable disease reporting. In the context of a pandemic it has been\ud argued that the public good should supersede an individual’s right to privacy. The precise nature of these provider\ud privacy concerns, and whether they are diluted in the context of a pandemic are not known. Our objective was to\ud understand the privacy barriers which could potentially influence family physicians’ reporting of patient-level\ud surveillance data to public health agencies during the Fall 2009 pandemic H1N1 influenza outbreak.\ud Methods: Thirty seven family doctors participated in a series of five focus groups between October 29-31 2009.\ud They also completed a survey about the data they were willing to disclose to public health units. Descriptive\ud statistics were used to summarize the amount of patient detail the participants were willing to disclose, factors that\ud would facilitate data disclosure, and the consensus on those factors. The analysis of the qualitative data was based\ud on grounded theory.\ud Results: The family doctors were reluctant to disclose patient data to public health units. This was due to concerns\ud about the extent to which public health agencies are dependable to protect health information (trusting beliefs),\ud and the possibility of loss due to disclosing health information (risk beliefs). We identified six specific actions that\ud public health units can take which would affect these beliefs, and potentially increase the willingness to disclose\ud patient information for public health purposes.\ud Conclusions: The uncertainty surrounding a pandemic of a new strain of influenza has not changed the privacy\ud concerns of physicians about disclosing patient data. It is important to address these concerns to ensure reliable\ud reporting during future outbreaks.University of Ottawa Open Access Author Fun

    Agonistic screams in wild chimpanzees (Pan troglodytes schweinfurthii) vary as a function of social role

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    Some nonhuman primates have demonstrated the capacity to communicate about external objects or events, suggesting primate vocalizations can function as referential signals. However, there is little convincing evidence for functionally referential communication in any great ape species. Here, the authors demonstrate that wild chimpanzees (Pan troglodytes schweinfurthii) of Budongo forest, Uganda, give acoustically distinct screams during agonistic interactions depending on the role they play in a conflict. The authors analyzed the acoustic structure of screams of 14 individuals, in the role of both aggressor and victim. The authors found consistent differences in the acoustic structure of the screams, across individuals, depending on the social role the individual played during the conflict. The authors propose that these 2 distinct scream variants, produced by victims and aggressors during agonistic interactions, may be promising candidates for functioning as referential signals
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