76 research outputs found

    Financial system architecture and the patterns of international trade

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    Countries differ on the extent to which their financial system relies on banks or on the financial market. We offer a model featuring a possible two way relationship between countries’ financial system architecture and their comparative advantage. Countries specialising in bank dependent sectors favour the development of the banking sector. Simultaneously, countries with more efficient capital markets develop comparative advantage in sectors with strong dependence on market finance. To empirically investigate our model’s predictions, we construct a measure of sector bank dependence and establish a strong relationship between countries’ comparative advantage and their financial system architecture

    Attitudes towards persons with mental health conditions and psychosocial disabilities as rights holders in Ghana: a World Health Organization study

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    Background: There are currently major efforts underway in Ghana to address stigma and discrimination, and promote the human rights of those with mental health conditions, within mental health services and the community, working with the World Health Organization’s QualityRights initiative. The present study aims to investigate attitudes towards people with lived experience of mental health conditions and psychosocial disabilities as rights holders. Methods: Stakeholders within the Ghanaian mental health system and community, including health professionals, policy makers, and persons with lived experience, completed the QualityRights pre-training questionnaire. The items examined attitudes towards coercion, legal capacity, service environment, and community inclusion. Additional analyses explored how far participant factors may link to attitudes. Results: Overall, attitudes towards the rights of persons with lived experience were not well aligned with a human rights approach to mental health. Most people supported the use of coercive practices and often thought that health practitioners and family members were in the best position to make treatment decisions. Health/mental health professionals were less likely to endorse coercive measures compared to other groups. Conclusion: This was the first in-depth study assessing attitudes towards persons with lived experience as rights holders in Ghana, and frequently attitudes did not comply with human rights standards, demonstrating a need for training initiatives to combat stigma and discrimination and promote human rights

    Chemical Composition of and Inhibition of Angiotensin-Converting Enzyme by Senecio samnitum huet

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    Abstract Extracts of Senecio samnitum Huet and derived methyl ester of chlorogenic acid have been shown to inhibit angiotensin-converting enzyme (ACE) by using an in vitro bioassay based on the enzymatic cleavage of the chromophore-fluorophore labeled substrate dansyltriglycine into dansylglycine, which is quantitatively measured by high-performance liquid chromatography (HPLC). GC=MS and NMR identified compounds present within the studied S. samnitum extracts. The most effective fraction was obtained in ethyl acetate, which gave 52.56 AE 0.23% (SD) inhibition at 300 mg=ml. The major constituent of this fraction, the methyl ester of chlorogenic acid, showed significant ACE inhibition of 56.78 AE 0.25% at a concentration of 82.5 mg=ml

    Hypoxia-Induced Down-Regulation of Neprilysin by Histone Modification in Mouse Primary Cortical and Hippocampal Neurons

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    Amyloid β-peptide (Aβ) accumulation leads to neurodegeneration and Alzheimer's disease (AD). Aβ metabolism is a dynamic process in the Aβ production and clearance that requires neprilysin (NEP) and other enzymes to degrade Aβ. It has been reported that NEP expression is significantly decreased in the brain of AD patients. Previously we have documented hypoxia is a risk factor for Aβ generation in vivo and in vitro through increasing Aβ generation by altering β-cleavage and γ-cleavage of APP and down-regulating NEP, and causing tau hyperphosphorylation. Here, we investigated the molecular mechanisms of hypoxia-induced down-regulation of NEP. We found a significant decrease in NEP expression at the mRNA and protein levels after hypoxic treatment in mouse primary cortical and hippocampal neurons. Chromatin immunoprecipitation (ChIP) assays and relative quantitative PCR (q-PCR) revealed an increase of histone H3-lysine9 demethylation (H3K9me2) and a decrease of H3 acetylation (H3-Ace) in the NEP promoter regions following hypoxia. In addition, we found that hypoxia caused up-regulation of histone methyl transferase (HMT) G9a and histone deacetylases (HDACs) HDAC-1. Decreased expression of NEP during hypoxia can be prevented by application with the epigenetic regulators 5-Aza-2′-deoxycytidine (5-Aza), HDACs inhibitor sodium valproate (VA), and siRNA-mediated knockdown of G9a or HDAC1. DNA methylation PCR data do not support that hypoxia affects the methylation of NEP promoters. This study suggests that hypoxia may down-regulate NEP by increasing H3K9me2 and decreasing H3-Ace modulation

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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