Atherogenesis and atherosclerosis in primary antiphospholipid syndrome

ABSTRACT: In the late seventies the term “Haematological Stress Syndrome” defined some haematological abnormalities appearing in the course of acute and chronic disorders, such as raised plasma levels of fibrinogen (FNG) and factor VIII, reduced fibrinolytic activity and hyperviscosity. In the early nineties the “Membrane stress syndrome hypothesis” proposed the unification of the concepts of haematological stress syndrome with those of oxidation, inflammation and immune activation to explain the pathogenesis of the antiphospholipid syndrome (APS) Antiphospholipid antibodies, coagulation, fibrinolysis and thrombosis. This chapter investigated the occurrence of the “Haematological Stress Syndrome” and thrombosis in 144 participants positive for aPL detected by clotting and immune tests. Among the clotting assays for the detection of lupus anticoagulant, dilute Russell's viper venom time better correlated with a history of venous thrombosis than activated partial thromboplastin time (p<0.0002 vs p<0.009) and was the only test correlated with a history of arterial thrombosis (p<0.01). By regression analysis, serum levels of IgG anticardiolipin antibodies (aCL) associated with the number of venous occlusions (p<0.001). With regards to FNG and von Willebrand factor (vWF), the former rose by 36% (95% CI; 21%, 53%) and the latter by 50% (95% CI; 29%, 75%) at the first venous occlusion and remained unchanged after subsequent occlusions. At variance FNG rose by 45% (95% CI; 31%, 60%) per arterial occlusion and vWF by 27% (95% CI; 10%, 47%) per arterial occlusion throughout. The coagulation/fibrinolytic balance was cross-sectionally evaluated on 18 thrombotic PAPS patients, 18 subjects with persistence of idiopathic aPL and in healthy controls. Markers of thrombin generation prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and of fibrin turnover D-Dimer (D-D) were higher in thrombotic (p=0.006)and non-thrombotic subjects (p=0.0001) than in controls as were those of D-D (p<0.0001 and p=0.003 respectively). TAT levels did not differ. Gender analysed data revealed blunted tPA release (hence a negative venous occlusion test) in thrombotic females but neither in thrombotic males (p=0.01) nor in asymptomatic subjects of either sex. Also, in both patient groups females had higher mean PAI than males (p<0.0002) and control females (p<0.02). The activity of factor XIII (FXIIIa) was evaluated was evaluated in 29 patients with PAPS, 14 persistent carriers of aPL without thrombosis, 24 thrombotic patients with inherited thrombophilia, 28 healthy controls and 32 patients with mitral and aortic valve prosthesis as controls for FXIII only. FXIIIa was highest in PAPS (p=0.001), particularly in patients with multiple (n=12) than single occlusion (p=0.02) and in correlation with PAI (p=0.003) and FNG (p=0.005). Moreover FXIIIa was strongly associated with IgG aCL and IgG anti-2GPI (p=0.005 for both) in the PAPS group and to a lesser degree in the aPL group (FXIIIa with IgG aCL, p=0.02, with IgG anti-2GPI, p=0.04). Altogether these results indicate: 1) a differential relationship of aPL, vWF and FNG with venous and arterial thrombosis; 2) heightened thrombin generation, accelerated fibrin turnover and fibrinolysis abnormalities also in asymptomatic carriers of aPLs; 3) enhanced FXIIIa that may contribute to atherothrombosis via increased fibrin/fibrinogen cross-linking. Lipid profile, lipid peroxidation and anti-lipoprotein antibodies in thrombotic primary antiphospholipid syndrome. Given the atherogenic lipid profile of SLE, the same possibility was explored in PAPS by comparing high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), triglycerides (TG), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-2GPI) and C-reactive protein (CRP) in 34 thrombotic PAPS patients compared to 36 thrombotic patients with inherited thrombophilia (IT), to 18 subjects persistently positive for antiphospholipid antibodies (aPL) with no underlying autoimmune or non-autoimmune disorders and to 28 healthy controls. Average concentrations of HDL (p<0.0001), LDL (p<0.0001), CHO (p=0.0002), ApoAI (p=0.002) were lower in PAPS whereas average TRY was higher (p=0.01) than other groups. Moreover PAPS showed higher IgG anti-HDL (p=0.01) and IgG anti-ApoAI (p<0.0001) as well as greater average oxLDL-2GPI (p=0.001) and CRP (p=0.003). Within PAPS, IgG anti-HDL correlated negatively to HDL (p=0.004) and was an independent predictor of oxLDL-2GPI (p=0.009). HDL and ApoAI correlated negatively with CRP (p=0.001 and p=0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favouring low-grade inflammation and enhanced oxidation in thrombotic PAPS. Indeed plasma 8-epi-prostaglandin F2α (a very specific marker of lipid peroxidation) was significantly higher in 10 patients with PAPS than 10 age and sex matched healthy subjects (p=0.0002) and strongly related to the titre of plasma IgG aCL (r=0.89, p=0.0004). Hence oxidative stress, a major player in atherogenesis, also characterises PAPS. Nitric oxide and nitrative stress in thrombotic primary antiphosholipid syndrome. Oxidative stress goes hand in hand with nitrative stress and to address the latter plasma nitrotyrosine (NT, marker of nitrative stress), nitrite (NO2-) and nitrate (NO3-) were measured in 46 thrombotic PAPS patients, 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE) and 29 healthy controls (CTR). Average crude NT was higher in PAPS and SLE (p=0.01) whereas average plasma NO2- was lower in PAPS and average NO3- highest in SLE (p<0.0001). In PAPS, IgG aCL titer and number of vascular occlusions negatively predicted NO2-, (p=0.03 and p=0.001, respectively) whereas arterial occlusions and smoking positively predicted NO3- (p=0.05 and p=0.005). Moreover CRP (an inflammatory marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade inflammation and both phenomena may have implications for thrombosis and atherosclerosis in PAPS Inflammation and immune activation in thrombotic primary antiphospholipid syndrome. To investigate inflammation and immune activation in thrombotic PAPS high-sensitivity CRP (hs-CRP), serum amyloid A (SAA), oxLDL-2GPI, CRP bound to oxLDL-2GPI (CRP-oxLDL-2GPI) (as inflammatory markers) neopterin (NPT) and soluble CD14 (sCD14) (as immune activation markers) were measured by ELISA in 41 PAPS patients, in 44 patients with inherited thrombophilia (IT) and 39 controls (CTR). Compared to other groups, PAPS presented with higher plasma concentrations of inflammatory, hs-CRP (p=0.0004), SAA (p<0.01), CRP-oxLDL-2GPI (p=0.0004) and immune activation markers, NPT (p<0.0001) and sCD14 (p=0.007). By regression analysis SAA independently predicted thrombosis number (p=0.003) and NPT independently predicted thrombosis type (arterial, p=0.03) and number (p=0.04). These data confirm that low-grade inflammation and immune activation occur and relate to vascular features of PAPS. Antiphosholipid antibodies, haemostatic variables and atherosclerosis in thrombotic primary antiphospholipid syndrome To evaluate whether IgG aCL titre, haemostatic variables and the lipid profile bore any relationship to the intima media thickness (IMT) of carotid arteries high-resolution sonography was applied to the common carotid (CC), carotid bifurcation (CB) and internal carotid (IC) of 42 aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. The following were measured: plasma FNG, vWF, PAI, homocysteine (HC), CHO, TG, HDL, LDL, platelet numbers and aCL of IgG and IgM isotype. By multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (p always <0.005). Plasma FNG and HC independently predicted IMT at the CB (p=0.001 and p<0.0001, respectively) and IC (p=0.03 and p<0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL in addition to traditional risk factors. The atherosclerosis hypothesis was investigated in an age and sex-matched case-double-control study including 49 thrombotic PAPS patients (18 M, 31 F, mean age 37 ± 11), 49 thrombotic patients for IT and 49 healthy subjects. Average IMT was always greater in PAPS than control patients (CC: p=0.004, CB: p=0.013, IC: p=0.001). By dividing participants into age tertiles the IMT was greater in the second (CC: p=0.003, CB: p=0.023, IC: p=0.003) and third tertiles (CC: p=0.03, CB: p=0.004, IC: p=0.007). Conclusion: Coagulation activation, fibrinolysis depression, hightened fibrin turnover, oxidative and nitrative stress in parallel with low grade inflammation and immune activation characterise thrombotic PAPS: all these are early atherogenic processes and contribute to the demonstrated premature atherosclerosis that should be considered a clinical feature of PAPS.

The impact of type of language and number of reasons on purchase intent

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Evaluation of platelet number and function and fibrinogen level in patients bitten by snakes of the Bothrops genus

Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10 males and 4females, aged 13-59years bitten by Bothrops genus snakes. There was a statistical difference (p < 0.05) among plasma fibrinogen levels evaluated 24 and 48 hours after envenomation. There was a tendency towards normalization after 48 hours of treatment. The low platelet number was clear in 24-48 hour evaluations with a tendency towards normalization after 48 hours of treatment (p<0.05). Fibrinogen levels and fibrin degradation product (FDP) levels appeared to be altered in 83.33% of patients evaluated. The authors suggest that platelet hypoaggregation is related to decreased fibrinogen and increased FDP levels.

Assembly and function of a protein cross-linking enzyme during bacterial spore morphogenesis

Sporulation in Bacillus subtilis culminates with the formation of a dormant endospore. The endospore (or spore) is one of the most resilient cell types known and can remain viable in the environment for extended periods of time. Contributing to the spore’s resistance and its ability to interact with and monitor its immediate environment is the coat, the outermost layer of B. subtilis spores. The coat is composed by over 70 different proteins, which are produced at different stages in sporulation and orderly assembled around the developing spore.(...)

A SARIMA forecasting model to predict the number of cases of dengue in Campinas, State of São Paulo, Brazil

INTRODUCTION: Forecasting dengue cases in a population by using time-series models can provide useful information that can be used to facilitate the planning of public health interventions. The objective of this article was to develop a forecasting model for dengue incidence in Campinas, southeast Brazil, considering the Box-Jenkins modeling approach. METHODS: The forecasting model for dengue incidence was performed with R software using the seasonal autoregressive integrated moving average (SARIMA) model. We fitted a model based on the reported monthly incidence of dengue from 1998 to 2008, and we validated the model using the data collected between January and December of 2009. RESULTS: SARIMA (2,1,2) (1,1,1)12 was the model with the best fit for data. This model indicated that the number of dengue cases in a given month can be estimated by the number of dengue cases occurring one, two and twelve months prior. The predicted values for 2009 are relatively close to the observed values. CONCLUSIONS: The results of this article indicate that SARIMA models are useful tools for monitoring dengue incidence. We also observe that the SARIMA model is capable of representing with relative precision the number of cases in a next year.

Relatório de estágio na Caixa Geral de Depósitos

This report will describe the activities undertaken during my internship at the Personnel Department (DPE-UPE4.1) in Caixa Geral de Depósitos (CGD), Lisbon, between September 22, 2014, and February 28, 2015. I consider that it is important to note from the outset i) that the subject of my training was suggested by my supervisor in the DPE and accepted by me; and ii) that the internship consisted essentially of carrying out research and information gathering into the different social systems that coexist within the bank and the application of each legal system in solving concrete situations of the CGD employees. The research and analysis of information was important not only for my study but for the CGD itself, as it enables the department to have such an important matter, full of specific characteristics, condensed into a single document, i.e. this report. This is a complex reality. The various welfare systems differ according to the contractual agreement linking the employee to the employer at the date when the labour contract is signed, and also the unique/singular characteristics of the CGD. In the early stage I started by trying to understand the financial institution and its organization and role and the department where I worked. So I analyzed the CGD Statutes and the legal measures that crystallized the scheme for its employees and I also researched its domestic and international operations. The first month was devoted to the research and analysis of such legislation to understand the creation of the CGD and its path to date. In the second and third months I studied the legal social systems that are applied to different groups of CGD workers. This period was quite important to identify and understand the differences between those regimes of CGD employees as well as the procedure inherent in each case. I highlighted the non-implementation of “the social protection regime of convergence” to the workers of this institution; the differences regarding the allocation of sickness subsidies paid to workers who belong to Social Security and CGA contributors, as well as the enforcement of internal rules to all the workers when a work-related accident happens. Then I focused on to assessing and examining external legislation and several internal regulations in order to obtain solutions to questions raised and situations involving by the workers, in order to understand how the DPE solves these situations. Over the last three months of internship, after this more theoretical work, I began the analysis of concrete situations involving employees carrying out their duties in Portugal and abroad. Some of these situations had been received by the department before the beginning of my internship and others over this period. When I was “working” in the DPE I analyzed “cases” that had been solved and some others without a final solution because they were still in courts. As for the last ones (new cases) I was able to follow their assessment and sometimes their outcome. Some of them became study cases for me. Over these five months of my internship, several cases were analyzed and discussed by legal experts of DPE in which I could participate. I always worked hard. I know that this action contributed to elucidate me about the treatment of the issues, and allowed me to have a direct contact with some workers and be part of a dynamic work team. For these reasons, my internship report is not merely descriptive of activities. It consists of an analysis of rules (legislation) and a regulatory framework of activities and it is also a description of several specific situations solved or in a solution process. Through this work I intend to make known the particular reality of a modern Portuguese financial institution not only because of its importance in our country but also such a large number of employees work here (in Portugal and abroad). I should add that throughout my internship I was allowed to attend conferences, within the scope of the bank in order to get a broader view of some issues related to the daily life of the DPE and the CGD. So, I participated in I Jornadas Bancárias and the Conferência Internacional do Contrato a Termo, given that the CGD is a bank and the DPE deals with legal and labour relations.

Evaluation of two sweeping methods for estimating the number of immature Aedes aegypti (Diptera: Culicidae) in large containers

Introduction Here, we evaluated sweeping methods used to estimate the number of immature Aedes aegypti in large containers. Methods III/IV instars and pupae at a 9:1 ratio were placed in three types of containers with, each one with three different water levels. Two sweeping methods were tested: water-surface sweeping and five-sweep netting. The data were analyzed using linear regression. Results The five-sweep netting technique was more suitable for drums and water-tanks, while the water-surface sweeping method provided the best results for swimming pools. Conclusions Both sweeping methods are useful tools in epidemiological surveillance programs for the control of Aedes aegypti.

Relatório de estágio na Caixa Geral de Depósitos

This report will describe the activities undertaken during my internship at the Personnel Department (DPE-UPE4.1) in Caixa Geral de Depósitos (CGD), Lisbon, between September 22, 2014, and February 28, 2015. I consider that it is important to note from the outset i) that the subject of my training was suggested by my supervisor in the DPE and accepted by me; and ii) that the internship consisted essentially of carrying out research and information gathering into the different social systems that coexist within the bank and the application of each legal system in solving concrete situations of the CGD employees. The research and analysis of information was important not only for my study but for the CGD itself, as it enables the department to have such an important matter, full of specific characteristics, condensed into a single document, i.e. this report. This is a complex reality. The various welfare systems differ according to the contractual agreement linking the employee to the employer at the date when the labour contract is signed, and also the unique/singular characteristics of the CGD. In the early stage I started by trying to understand the financial institution and its organization and role and the department where I worked. So I analyzed the CGD Statutes and the legal measures that crystallized the scheme for its employees and I also researched its domestic and international operations. The first month was devoted to the research and analysis of such legislation to understand the creation of the CGD and its path to date. In the second and third months I studied the legal social systems that are applied to different groups of CGD workers. This period was quite important to identify and understand the differences between those regimes of CGD employees as well as the procedure inherent in each case. I highlighted the non-implementation of “the social protection regime of convergence” to the workers of this institution; the differences regarding the allocation of sickness subsidies paid to workers who belong to Social Security and CGA contributors, as well as the enforcement of internal rules to all the workers when a work-related accident happens.Then I focused on to assessing and examining external legislation and several internal regulations in order to obtain solutions to questions raised and situations involving by the workers, in order to understand how the DPE solves these situations. Over the last three months of internship, after this more theoretical work, I began the analysis of concrete situations involving employees carrying out their duties in Portugal and abroad. Some of these situations had been received by the department before the beginning of my internship and others over this period. When I was “working” in the DPE I analyzed “cases” that had been solved and some others without a final solution because they were still in courts. As for the last ones (new cases) I was able to follow their assessment and sometimes their outcome. Some of them became study cases for me. Over these five months of my internship, several cases were analyzed and discussed by legal experts of DPE in which I could participate. I always worked hard. I know that this action contributed to elucidate me about the treatment of the issues, and allowed me to have a direct contact with some workers and be part of a dynamic work team. For these reasons, my internship report is not merely descriptive of activities. It consists of an analysis of rules (legislation) and a regulatory framework of activities and it is also a description of several specific situations solved or in a solution process. Through this work I intend to make known the particular reality of a modern Portuguese financial institution not only because of its importance in our country but also such a large number of employees work here (in Portugal and abroad). I should add that throughout my internship I was allowed to attend conferences, within the scope of the bank in order to get a broader view of some issues related to the daily life of the DPE and the CGD. So, I participated in I Jornadas Bancárias and the Conferência Internacional do Contrato a Termo, given that the CGD is a bank and the DPE deals with legal and labour relations.

Análise de complexidade de programas em ferramentas de apoio à decisão

Dissertação de mestrado em Engenharia de Sistemas

An algorithmic approach to estimating the minimal number of periodic points for smooth self-maps of simply-connected manifolds

For a given self-map f of M, a closed smooth connected and simply-connected manifold of dimension m ≥ 4, we provide an algorithm for estimating the values of the topological invariant Dm r [f], which equals the minimal number of r-periodic points in the smooth homotopy class of f. Our results are based on the combinatorial scheme for computing Dm r [f] introduced by G. Graff and J. Jezierski [J. Fixed Point Theory Appl. 13 (2013), 63–84]. An open-source implementation of the algorithm programmed in C++ is publicly available at http://www.pawelpilarczyk.com/combtop/.

Low f-number microlenses for integration on optical microsystems

This paper presents microlenses (MLs) with low f-number made of AZ4562 photoresist for integration on optical microsystems. The fabrication process was based on the thermal reflow and rehydration. Large series of MLs were fabricated with a width of 35 μm, a thickness of 5 μm, and spaced apart by 3 μm. The MLs were fabricated directly on the surface of a die with type n+/p-substrate junction photodiode fabricated in a standard CMOS process. The measured focal length was 49 μm with a tolerance of ±2 μm (maximum error of ±4%), resulting in a numerical aperture of 33.6 × 10-2 (±1.3 × 10-2). The measurements also revealed an f-number of 1.4.

Plantae Asiaticae rariores, or, Descriptions and figures of a select number of unpublished East Indian plants /by N. Wallich.

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Plantae Asiaticae rariores, or, Descriptions and figures of a select number of unpublished East Indian plants /by N. Wallich.

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Plantae Asiaticae rariores, or, Descriptions and figures of a select number of unpublished East Indian plants /by N. Wallich.

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