Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.info:eu-repo/semantics/publishedVersio

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.info:eu-repo/semantics/publishedVersio

A Systematic Search in Registries to Compare the Czech Republic and Portugal in Terms of Funding Policies and Scientific Outcomes

Funding: In the Czech Republic, this work was supported by the European Regional Development Fund - Project CZECRIN_4 PACIENTY (No. CZ.02.1.01/0.0/0.0/16_013/0001826) and Large Research infrastructure CZECRIN – LM2015090. CM and FS were supported by Fundação para a Ciência e a Tecnologia (FCT, through the membership fees to ECRIN-ERIC published at Portaria nº 237/2014). The funders did not interfere with the design of the study, collection, analysis and interpretation of data as well as with the writing of the manuscript.Objectives: Clinical trials provide one of the highest levels of evidence to support medical practice. Investigator initiated clinical trials (IICTs) answer relevant questions in clinical practice that may not be addressed by industry. For the first time, two European Countries are compared in terms of IICTs, respective funders and publications, envisaging to inspire others to use similar indicators to assess clinical research outcomes. Methods: A retrospective systematic search of registered IICTs from 2004 to 2017, using four clinical trials registries was carried out in two European countries with similar population, GDP, HDI and medical schools but with different governmental models to fund clinical research. Each IICT was screened for sponsors, funders, type of intervention and associated publications, once completed. Results: IICTs involving the Czech Republic and Portugal were n = 439 (42% with hospitals as sponsors) and n = 328 (47% with universities as sponsors), respectively. The Czech Republic and Portuguese funding agencies supported respectively 61 and 27 IICTs. Among these, trials with medicinal products represent 52% in Czech Republic and 4% in Portugal. In the first, a higher percentage of IICTs’ publications in high impact factor journals with national investigators as authors was observed, when compared to Portugal (75% vs 15%). Conclusion: The better performance in clinical research by Czech Republic might be related to the existence of specific and periodic funding for clinical research, although further data are still needed to confirm this relationship. In upcoming years, the indicators used herein might be useful to tracking clinical research outcomes in these and other European countries.publishersversionpublishe

IT Service Management: Sistema de monitorização baseado em ferramentas open source

O IT Service Management (ITSM) descreve a forma como uma organização gere os seus serviços de Tecnologias da Informação (TI). Define as funções e responsabilidades de cada departamento e indivíduo em relação aos serviços de TI. Propõe um conjunto de boas práticas e processos, que visam a auxiliar as organizações na gestão eficiente da infraestrutura de TI (i.e., componentes e serviços). Contribui para uma maior produtividade, redução de custos e aumento da satisfação do cliente. O Information Technology Infrastructure Library (ITIL) é uma framework utilizada no contexto da gestão do ITSM. É um conjunto específico de processos e diretrizes para o fornecimento de serviços de TI. Esta apresentação centra-se na implementação de um sistema de monitorização de TI baseado em ferramentas open source, capaz de monitorizar e analisar em tempo real o funcionamento da infraestrutura de TI de uma organização. Este sistema pode desempenhar um papel fundamental na definição da estratégia de TI mais adequada para o negócio. Tem implicação na melhoria da qualidade dos serviços e no aumento do valor agregado ao negócio.info:eu-repo/semantics/publishedVersio

IT service management: concepts and processes

Num mundo cada vez mais tecnológico, a alta disponibilidade dos sistemas é cada vez mais exigente aos serviços de Tecnologias de Informação (TI). O Information Technology Service Management (ITSM) pode ter um papel fundamental na gestão de TI, auxiliando clientes e parceiros para que o serviço prestado apresente a melhor relação custo/benefício, e diminuindo o tempo de inatividade e as interrupções dos serviços. Procura-se potenciar o valor do negócio. Neste contexto, o Information Technology Infrastructure Library (ITIL) aparece como uma framework que tem como objetivo auxiliar e facilitar a definição do negócio e a implementação da gestão de ITSM. Este artigo centra-se na análise e discussão dos conceitos inerentes aos processos de TI,auxiliando quem está a dar os primeiros passos nesta área. Ao longo do documento serão descritas as fases que compõem o ITSM e o ITIL, sob a forma de um guia orientador.In an increasingly technological world, high availability of systems is increasingly demanding of Information Technology (IT) services. Information Technology Service Management (ITSM) can play a key role in IT management, helping customers and partners to provide the most cost-effective service and reducing downtime and service interruptions. The aim is to enhance business value. In this context, the Information Technology Infrastructure Library (ITIL) appears as a framework that aims to assist and facilitate the business definition and implementation of ITSM management. This article focuses on the analysis and discussion of the concepts inherent to IT processes, helping those who are taking their first steps in this area. Throughout the document the phases that make up ITSM and ITIL will be described, in the form of a guiding guide.info:eu-repo/semantics/publishedVersio

Antibodies Against β2-Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

To explore whether antibodies against β2-glycoprotein I (β2GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: β2GPI−oxLDL complexes, IgG anti-β2GPI−oxLig-1, IgG anti-β2GPI−oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography. β2GPI−oxLDL complex was highest in the control group (p < 0.01), whereas, IgG anti-β2GPI−oxLig1 and IgG anti-β2GPI−oxLDL were highest in PAPS (p < 0.0001). In healthy controls, β2GPI−oxLDL complexes positively correlated to IMT of the IC (p = 0.007) and negatively to PONa after correction for age (p < 0.03). PONa inversely correlated with age (p = 0.008). In PAPS, IgG anti-2GPI−oxLig-1 independently predicted PONa (p = 0.02) and IMT of B (p = 0.003), CC, (p = 0.03) and of IC (p = 0.04). In PAPS, PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003, respectively). IgG anti-2GPI−oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity

Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability

The challenges and opportunities of addressing particle size effects in sediment source fingerprinting: A review

publisher: Elsevier articletitle: The challenges and opportunities of addressing particle size effects in sediment source fingerprinting: A review journaltitle: Earth-Science Reviews articlelink: http://dx.doi.org/10.1016/j.earscirev.2017.04.009 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved

Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions

ELISA methods comparison for the detection of auto-antibodies against apolipoprotein A1

BACKGROUND: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. Across studies, different ELISA methods have been used to measure the level of circulating anti-apoA1 IgG which could lead to substantial result differences between assays. OBJECTIVES: To make a comparative study of available anti-apoA1 IgG detection methods and to determine whether the choice of matrix sample (serum vs plasma) could influence the results. METHODS: Blood samples were obtained from 160 healthy blood donors and collected on 4 different matrixes (serum, plasma-EDTA, -citrate, -lithium-heparinate). Anti-apoA1 IgG was measured using two homemade (Geneva's and Lisbon's) and one commercial ELISA kits. Passing-Bablok and Bland-Altman were used to compare the results. Anti-apoA1 IgG seropositivity cut-offs were defined according to the user's/manufacturer's criterion. RESULTS: The current results showed substantial differences between those 3 assays. The dynamic ranges were significantly different, the commercial kit displaying the narrowest one. Passing-Bablok analysis demonstrated important proportional and constant biases between assays. The anti-apoA1 IgG seropositivity rate in Geneva, Lisbon and commercial assays varied between 24.5% and 1.9%. Matrix comparisons demonstrated that the matrix choice (plasma versus serum) influenced anti-apoA1 IgG results as well as the seropositivity rate in an assay-dependent manner. The coating antigen source was identified as important factor underlying results heterogeneity across assays. CONCLUSIONS: These results highlight the impact of the method and the cut-off used on anti-apoA1 IgG results and emphasize the need of standardizing existing assays. Given the important matrix influence, we suggest to use serum as matrix of choice.info:eu-repo/semantics/publishedVersio