Abstract The number of deaths associated with cardiovascular diseases (CVD) increases every year, leading to an intense search for new compounds that may be employed as anticoagulants. One of the classes of bioprospected molecules comprises sulfated polysaccharides (SP) from seaweed, as heparin displays many adverse effects associated with its use. The present study aimed to characterize and evaluate the anticoagulant potential of SP extracted from the green algae Halimeda opuntia. Four PS-rich fractions, F23, F44, F60 and F75, were obtained by proteolytic digestion in papain followed by ethanol precipitation. The presence of SP was confirmed by agarose gel electrophoresis, revealing different populations in each fraction. The F44 fraction is noteworthy compared to the other fractions, presenting a 5% yield compared to the initial algae weight and anticoagulant activity revealed by the activated partial thromboplastin time (APTT) assay (intrinsic/common coagulation pathway). Surprisingly, F44 purification (SP peak P1F44) resulted in prothrombin time (PT) activity (extrinsic coagulation pathway) at a 160 µg/mL, in addition to enhanced APTT activity. The P1F44 anticoagulant activity mechanism was shown to be dependent on two coagulations factors, IIa and Xa, more potent via IIa. Future assessments will be performed to assess this fraction in the medical clinic.

Abstract Objective The use of broad-spectrum antimicrobials, such as third and fourth-generation, are responsible for emergence of multidrug-resistant microorganisms in neonatal units. Furthermore, antimicrobial daily doses are not standardized in neonatology. This study aimed to investigate the association between the use of antimicrobial broad spectrum to bacterial sensitivity profile in a referral unit of neonatal progressive care. Methods This is a cohort study conducted in a referral neonatal progressive care unit from January 2008 to December 2016. The data of all hospitalized neonates was collected daily. The infection criteria used were the standardized national criteria, based on definitions of Center for Diseases Control and Prevention. In this study, the use of antimicrobials was evaluated as antimicrobial-day (ATM-day) and the ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was also calculated. The study was approved by the Institutional Review Board of the Universidade Federal de Minas Gerais (ETIC 312/08 e CAAE 58973616.2.0000.5149). Results From 2008 to 2016, 2751 neonates were hospitalized, corresponding to 60,656 patient-days. The ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was 1,3 in the first period and 4,3 in the second period (p = 0,005). Conclusion It was observed that use of broad-spectrum antimicrobials, especially those with coverage for Gram-negative bacteria, was associated with an increase of multidrug-resistant bacteria.

RESUMO: As algas marinhas são fontes naturais de macromoléculas conhecidas como polissacarídeos sulfatados. Esta classe de compostos atraiu o interesse das Ciências Farmacêuticas devido às suas propriedades farmacológicas como anticoagulante, antiplaquetária e antitrombótica. Portanto, este estudo tem como objetivo avaliar o potencial anticoagulante de polissacarídeos sulfatados extraídos de algas de Penicillus capitatus. Os polissacarídeos sulfatados extraídos foram purificados, parcialmente caracterizados e sua atividade anticoagulante foi avaliada. O processo de extração seguido pela precipitação com etanol resultou em cinco frações. Entre as frações analisadas, F44 foi a maior concentração de polissacarídeos sulfatados. Após a purificação, as frações F23 e F44 mostraram atividade anticoagulante in vitro em um teste de tempo de tromboplastina parcialmente ativada e tempo de protrombina. Seu mecanismo preferencial é baseado nas interações entre trombina e fator Xa. Estudos adicionais sobre a estrutura farmacológica são necessários para testar a viabilidade do uso como agente terapêutico.

ABSTRACT: Marine algae are natural sources of macromolecules known as sulfated polysaccharides. This class of compounds has attracted the interest of Pharmaceutical Sciences due to its pharmacological anticoagulant, antiplatelet and antithrombotic properties. Therefore, this study evaluated the anticoagulant potential of sulfated polysaccharides extracted from the algae Penicillus capitatus. The extracted sulfated polysaccharides were purified, partially characterized and their anticoagulant activity was evaluated. The extraction process followed by ethanol precipitation resulted in five fractions. Among the analyzed fractions, F44 contained highest concentration of sulfated polysaccharides. After the purified fraction F23, F44 displayed in vitro anticoagulant activity in a time testing for activated partial thromboplastin time and prothrombin time. The preferential mechanism effect was based on interactions between thrombin and factor Xa. Additional studies on structure pharmacological are required to test the viability of the use of sulfated polysaccharides as therapeutic agents.

RESUMO Introdução: Avaliamos o risco proporcional de primeiros-ministros e ministros portugueses deixarem o cargo. Materiais e Métodos: Utilizamos dias consecutivos como ministro para cada um dos 432 cidadãos que exerceram a função ministerial desde 1976. Resultados: Explorando várias divisões desse universo, concluímos que indivíduos apoiados por maiorias parlamentares, que serviram depois de 1986, que possuíam qualificações académicas mais altas e que eram membros de partidos políticos apresentaram menores riscos de serem exonerados do cargo. Por outro lado, ser uma pessoa com mais idade, servindo em condições econômicas adversas, assumindo vários ministérios simultaneamente e sendo encarregado de ministérios específicos, não garantiu períodos políticos mais longos para os ministros portugueses. Discussão: Além de ser a primeira avaliação empírica de todos os ministros portugueses após 1974, este trabalho mostra como as habilitações mais altas são ativos importantes para os mandatos dos ministros e como as crises econômicas são altamente estimulantes para as mudanças dos gabinetes em Portugal, o que corresponde ao padrão observado na maioria dos regimes democráticos recentes.

ABSTRACT Introduction: In this study, we evaluated the proportional risk of Portuguese Prime-Ministers and Ministers leaving office. Materials and Methods: We used consecutive days in office for each one of the 432 citizens who served in a ministerial function since 1976. Results: Exploring several divisions in this population, we concluded that individuals supported by parliamentary majorities, who served after 1986, who had higher educational credentials, and who were members of political parties exhibited lower risks of being exonerated. Conversely, being an aged person, serving during bad economic conditions, assuming several ministries simultaneously and being in charge of too-specific ministries did not ensure longer political tenures for Portuguese ministers. Discussion: Besides being the first empirical assessment of all Portuguese Ministers after 1974, this work shows how higher skills are important assets for Ministers’ tenures and how economic crises are highly stimulating for cabinets’ changes in Portugal, which corresponds to the pattern observed in most recent democratic regimens.

Resumen Este artículo analiza cómo la distribución de las transferencias por los estados brasileños afecta a la evolución de la cantidad total transferida por el Gobierno Federal. Después de una revisión de la literatura, se ha estudiado un modelo basado en una función de Bergson-Samuelson. Se utilizaron datos oficiales (cuya fuente es el “National Treasure”) desde enero de 1997 a marzo de 2011 para estudiar las transferencias descentralizadas. En cuanto a la metodología, se aplicaron técnicas de cointegración para probar la dirección causal. Llegamos a la conclusión de que existe una validación estadística que muestra que cuando la distribución se vuelve más desigual, el conjunto de la transferencia constitucional brasileña tiende a aumentar. JEL: H11, C22, H23.

Résumé Cet article analyse la manière dont la distribution des transferts de fonds par les États brésiliens affecte l’évolution de la quantité totale transférée par le gouvernement fédéral. Après un examen des publications nous avons étudié un modèle basé sur une fonction de Bergson-Samuelson. Nous avons utilisé des données officielles (sources du “National Treasure”) de janvier 1997 à mars 2011 pour étudier les transferts décentralisés. Pour la méthodologie, nous avons utilisé les techniques de cointégration pour montrer la direction causale. Nous sommes arrivés à la conclusion qu’il existe une validation statistique montrant que lorsque la distribution devient plus inégale, l’ensemble du transfert constitutionnel brésilien tend à augmenter. JEL : H11, C22, H23.

Abstract This article discusses how the distribution of decentralized grants for Brazilian States affects the evolution of the total amounts given by the Brazilian government to Brazilian States. After a literature review, we discuss a model based on the Bergson-Samuelson function. We used official data (from the “Tesouro Nacional”) from January 1997 to March 2011 in order to study the decentralized grants. We also regress on other Brazilian time series in order to control for the effect of inequality series. By applying cointegration techniques and testing the causality direction, we conclude that there is statistical validation that as the distribution becomes more unequal, the total amounts of transferred grants increase. JEL: H11, C22, H23.

Resumo O objetivo deste trabalho passa por discutir o modo como a distribuição de transferências pelos Estados brasileiros afecta a evolução do montante global transferido a título constitucional pelo Governo Federal. Após uma revisão da literatura, foi estudado um modelo baseado numa função de Bergson-Samuelson. Foram usados os dados oficiais (cuja fonte é o “Tesouro Nacional”) desde janeiro de 1997 até março de 2011 para estudar as transferências descentralizadas. Regredimos também os montantes transferidos noutras séries para controlar o efeito da série relativa ao padrão de desigualdade da distribuição. Em termos metodológicos, aplicaram-se técnicas de cointegração com teste da direcção de causalidade. Concluímos que existe uma validação estatística que mostra que quando a distribuição se torna mais desigual, o conjunto de transferências constitucionais brasileiras tende a aumentar. JEL: H11, C22, H23.

Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernociception, hot plate), or during 14 days for toxicity assay. The total polysaccharides fraction (TPL-Xa: 8.1% yield) presented 43% carbohydrate (21% uronic acid) and resulted in two main fractions after chromatography (FI: 12%, FII: 22% yield). FII showed better homogeneity/purity, content of 44% carbohydrate, including 39% uronic acid, arabinose and galactose as major monosaccharides, and infrared spectra with peaks in carbohydrate range for COO- groups of uronic acid. TPL-Xa (10 mg/kg) and FII (0.1 and 1 mg/kg) presented inhibitory effect in behavior tests that evaluate nociception induced by chemical and mechanical, but not thermal stimuli. TPL-Xa did not alter parameters of systemic toxicity. In conclusion, polysaccharides rich fractions of X. americana barks inhibit peripheral inflammatory nociception, being well tolerated by animals.

ABSTRACT Background: Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important cause of nosocomial infections especially in intensive care units. This study aimed to assess clinical aspects and the genetic background of CRAb among ICU patients at a Brazilian teaching hospital. Methods: 56 critically ill patients colonized or infected by CRAb, during ICU stay, were prospectively assessed. Based on imipenem MIC ≥ 4 µg/mL, 28 CRAB strains were screened for the presence of genes encoding metallo-β-lactamases and OXA-type β-lactamases. The blaOXA-type genes were characterized by PCR using primers targeting ISAba-1 or -3. Genetic diversity of blaOXA-positive strains was determined by ERIC-PCR analysis. Results: Patient's mean age (±SD) was 61 (±15.1), and 58.9% were male. Eighty-percent of the patients presented risk factors for CRAb colonization, mainly invasive devices (87.5%) and previous antibiotic therapy (77.6%). Thirty-three patients died during hospital stay (59.0%). Resistance to carbapenems was associated with a high prevalence of blaOXA-23 (51.2%) and/or blaOXA-143 (18.6%) genes. ERIC-PCR genotyping identified 10 clusters among OXA-producing CRAb. Three CRAb strains exhibited additional resistance to polymyxin B (MIC ≥ 4 µg/mL), whereas 10 CRAb strains showed tigecycline MICs > 2 µg/mL. Conclusions: In this study, clonally unrelated OXA-123- and OXA-143-producing A. baumannii strains in ICU patients were strongly correlated to colonization with infected patients being associated with a poor outcome.

RESUMO Após o estabelecimento, em 1910, a Primeira República Portuguesa assumiu um perfil anticlerical durante os seus primeiros anos. Consequentemente, poderíamos supor que as receitas das instituições religiosas portuguesas refletiram quebras estruturais em 1910. No entanto, um dos mais importantes centros históricos de peregrinação de Portugal (o "Bom Jesus de Braga") parece ter passado esses anos sem quebras significativas. Baseando-nos em análises econométricas de séries temporais (principalmente testes sobre quebras estruturais), estudámos com detalhe a série de receitas de Bom Jesus entre 1863 e 1952 (ou seja, entre o confisco da propriedade da igreja pela monarquia constitucional e a estabilização da Segunda República). Concluiu-se que 1910 não é uma data significativa para a identificação de uma quebra estrutural na série. No entanto, os anos do último quartel do século XIX não podem ser negligenciados em termos de mudanças estruturais nas receitas do Bom Jesus

ABSTRACT Following its establishment in 1910, the First Portuguese Republic adopted a markedly anticlerical profile during its early years. Consequently, we hypothesize that the revenue of Portuguese religious institutions should reflect a clear structural break in 1910. However, one of Portugal’s most important historical pilgrimage sites (“Bom Jesus de Braga”) does not seem to have experienced a very significant break. Relying on time series econometrics (consisting primarily of recurring tests for multiple structural breaks), we studied the series of the Bom Jesus revenue between 1863 and 1952 (i.e., between the confiscation of church property by the constitutional monarchy and the stabilization of the Second Republic). It was concluded that 1910 does not represent a significant date for identifying a structural break in this series. However, the last quarter of the nineteenth century cannot be neglected in terms of the structural changes occurring in the Bom Jesus revenue

This work found the occurrence of a distinct sialic acid-rich polysaccharide in the sperm surface of the sea urchin Lytechinus variegatus, which differed significantly from a similar molecule found in the egg jelly. The sperm polysaccharide extracted by protease digestion was purified using anion exchange chromatography and characterized using agarose gel electrophoresis, gas chromatography/mass spectrometry and NMR spectroscopy. This polysaccharide was highly sulfated and composed almost exclusively of N-acetylneuraminic acid. In contrast, the sialic acid-rich polysaccharide from the egg jelly was composed of N-glycolylneuraminic acid and contains several other hexoses in its structure. This new molecule could help to characterize in further detail the mechanism of fertilization in the sea urchin model system. Sulfated polysaccharides from the jelly coat of sea urchins showed species-specificity in inducing the sperm acrosome reaction, providing an example of a signal transduction event regulated by the sulfated polysaccharide. The new sialic acid-rich polysaccharide found in the sperm head could represent a new molecule involved in the biology of the sea urchin fertilization.

BACKGROUND: Healthcare Associated Infections constitute an important problem in Neonatal Units and invasive devices are frequently involved. However, studies on risk factors of newborns who undergo surgical procedures are scarce. OBJECTIVE: To identify risk factors for laboratory-confirmed bloodstream infection in neonates undergoing surgical procedures. METHODS: This case-control study was conducted from January 2008 to May 2011, in a referral center. Cases were of 21 newborns who underwent surgery and presented the first episode of laboratory-confirmed bloodstream infection. Control was 42 newborns who underwent surgical procedures without notification of laboratory-confirmed bloodstream infection in the study period. Information was obtained from the database of the Hospital Infection Control Committee Notification of infections and related clinical data of patients that routinely collected by trained professionals and follow the recommendations of Agência Nacional de Vigilância Sanitária and analyzed with Statistical Package for Social Sciences. RESULTS: During the study period, 1141 patients were admitted to Neonatal Unit and 582 Healthcare Associated Infections were reported (incidence-density of 25.75 Healthcare Associated Infections/patient-days). In the comparative analysis, a higher proportion of laboratory-confirmed bloodstream infection was observed in preterm infants undergoing surgery (p = 0.03) and use of non-invasive ventilation was a protective factor (p = 0.048). Statistically significant difference was also observed for mechanical ventilation duration (p = 0.004), duration of non-invasive ventilation (p = 0.04), and parenteral nutrition duration (p = 0.003). In multivariate analysis duration of parenteral nutrition remained significantly associated with laboratory-confirmed bloodstream infection (p = 0.041). CONCLUSIONS: Shortening time on parenteral nutrition whenever possible and preference for non-invasive ventilation in neonates undergoing surgery should be considered in the assistance of these patients, with the goal of reducing Healthcare Associated Infections, especially laboratory-confirmed bloodstream infection.

Este documento analiza el fenómeno de la dádiva a través de un estudio de caso observado en un periódico portugués - el Jornal de Notícias. Ese periódico contiene, hace varias décadas, el Proyecto "Todo hombre es mi hermano". Este trabajo evalúa cuáles son los factores responsables por los diferentes valores atribuidos a los distintos beneficiarios de ese proyecto. Se concluye que son factores positivos la duración del pedido en las ediciones del periódico y el número de dependientes a cargo de los beneficiarios. Además se concluye que son factores negativos la presencia del beneficiario en categorías de rendimiento superior así como la autonomía de movilidad. Los resultados muestran que el fenómeno de la dádiva es complejo donde entran también, con influencia, las características endógenas del beneficiario para más allá de las dimensiones que la literatura señaló previamente.

Cet article analyse le phénomène du don à travers une étude de cas observée dans le quotidien portugais Jornal de Notícias. Depuis plusieurs décennies ce journal contient le Projet "Tout homme est mon frère". L'étude examine les facteurs responsables des différentes valeurs attribuées aux bénéficiaires de ce projet. Première conclusion: deux facteurs positifs sont la durée de la demande dans les éditions du journal et le nombre de personnes dépendantes à la charge des bénéficiaires. Autre conclusion: la présence du bénéficiaire dans des catégories de rendement supérieur comme l'autonomie de mobilité est un facteur négatif. Les résultats montrent que le don est un phénomène complexe, où les caractéristiques endogènes du bénéficiaire jouent un rôle important, d'une dimension bien supérieure à celles signalées jusque là dans la littérature spécialisée.

This paper analyzes the gift phenomenon observing data from the Project "Every Man is my brother" (or Todo Homem é Meu Irmão). This Project has been supported by the Portuguese newspaper Jornal de Notícias for more than 30 years. This work evaluates which determinants influence the values given to each case. This work concluded that the number of weeks for exposing each case in the pages of the newspaper and the number of children supported by each beneficiary positively influence the values that were given to this beneficiary. Higher individual incomes and self-mobility negatively influence the values that were given. These results show that the gift phenomenon is rather complex and it is also influenced by the endogenous characteristics of each receiver.

Este documento analisa o fenómeno da dádiva, através de um estudo de caso observado num diário português - o Jornal de Notícias. Este jornal acolhe, há várias décadas, o Projecto "Todo Homem é Meu Irmão". Este trabalho avalia quais os factores responsáveis pelos diferentes valores atribuídos aos diferentes beneficiários desse projecto. Conclui que são factores positivos a duração do pedido nas edições do jornal e o número de dependentes a cargo dos beneficiários. Conclui que são factores negativos a presença do beneficiário em categorias de rendimento superior assim como a autonomia de mobilidade. Os resultados mostram que o fenómeno da dádiva é complexo onde entram também, com influência, as características endógenas do beneficiário, para lá das dimensões que a literatura apontou previamente.

OBJETIVO: Avaliar os fatores de risco e a letalidade da infecção da corrente sanguínea laboratorialmente confirmada (ICSLC) de início tardio em uma Unidade Neonatal de Cuidados Progressivos (UNCP) brasileira. MÉTODOS: Trata-se de um estudo caso-controle realizado de 2008 a 2012. Os casos foram definidos como todos os recém-nascidos com ICSLC de início tardio, excluindo pacientes isolados com contaminantes da pele comuns. Os controles foram recém-nascidos que não mostraram qualquer evidência de ICSLC de início tardio, sendo separados por peso e tempo de permanência na UNCP. As variáveis foram obtidas na base de dados da Comissão de Controle de Infecção Hospitalar (CCIH). A análise foi realizada utilizando o Pacote Estatístico para Ciências Sociais. O teste χ² foi utilizado e a relevância estatística foi definida como p < 0,05, seguida pela análise multivariada. RESULTADOS: No estudo, 50 pacientes com ICSLC de início tardio foram combinados com 100 pacientes sem ICSLC de início tardio. No grupo de pacientes com ICSLC de início tardio, identificamos uma proporção significativamente maior de pacientes que foram submetidos a procedimentos cirúrgicos (p = 0,001) e que usaram cateter venoso central (CVC) (p = 0,012) e ventilação mecânica (p = 0,001). Na análise multivariada, cirurgia prévia e uso de CVC permaneceram significativamente associados à infecção (p = 0,006 e p = 0,047; OU: 4,47 e 8,99, respectivamente). A Enterobacteriacea foi identificada em 14 casos, com três (21,4%) óbitos, e Staphylococcus aureus foi identificado em 20 casos, com três (15%) óbitos. CONCLUSÕES: Procedimentos cirúrgicos e uso de CVC constituíram fatores de risco significativos para ICSLC. Portanto, práticas de prevenção para cirurgia segura, inserção e manipulação de CVC são essenciais para reduzir essas infecções, além de treinamento e educação contínua às equipes cirúrgicas e de assistência.

OBJECTIVE: To evaluate risk factors and lethality of late onset laboratory-confirmed bloodstream infection (ICSLC) in a Brazilian neonatal unit for progressive care (NUPC). Methods: This was a case-control study, performed from 2008 to 2012. Cases were defined as all newborns with late onset ICSLC, excluding patients with isolated common skin contaminants. Controls were newborns who showed no evidence of late onset ICSLC, matched by weight and time of permanence in the NUPC. Variables were obtained in the Hospital Infection Control Committee (HICC) database. Analysis was performed using the Statistical Package for the Social Sciences (SPSS). The chi-squared test was used, and statistical significance was defined as p < 0.05, followed by multivariate analysis. RESULTS: 50 patients with late onset ICSLC were matched with 100 patients without late onset ICSLC. In the group of patients with late onset ICSLC, a a significant higher proportion of patients who underwent surgical procedures (p = 0.001) and who used central venous catheter (CVC) (p = 0.012) and mechanical ventilation (p = 0.001) was identified. In multivariate analysis, previous surgery and the use of CVC remained significantly associated with infection (p = 0.006 and p = 0.047; OR: 4.47 and 8.99, respectively). Enterobacteriacea was identified in 14 cases, with three (21.4%) deaths, and Staphylococcus aureus was identified in 20 cases, with three (15%) deaths. CONCLUSIONS: Surgical procedures and CVC usage were significant risk factors for ICSLC. Therefore, prevention practices for safe surgery and CVC insertion and manipulation are essential to reduce these infections, in addition to training and continuing education to surgical and assistance teams.

O ácido hialurônico (AH) é uma importante macromolécula nas áreas médica e farmacêutica. O cordão umbilical e a crista de frango constituem uns dos tecidos mais ricos nesse polissacarídeo. O aproveitamento das cristas dos animais abatidos para a obtenção de HA é particularmente atraente. O presente trabalho teve como objetivo a extração, purificação e caracterização do AH. A concentração de glicosaminoglicanos encontrada na crista de frango foi ao redor de 15µg de ácido hexurônico mg-1 de peso seco. O fracionamento por cromatografia de troca iônica e a subsequente identificação das frações por eletroforese de gel de agarose mostrou que o AH corresponde a 90% do total de glicosaminoglicanos extraídos.

Hyaluronic acid (HA) is an important macromolecule in medical and pharmaceutical fields. The umbilical cord and the chicken comb are some of the tissues richest in this polysaccharide. The profit from obtaining HA from the combs of slaughtered animals is particularly attractive. This work aimed to extract, purify, and characterize HA. The glycosaminoglycan concentration in the chicken comb was found to be about 15µg of hexuronic acid mg-1 of dry tissue. Fractionation using ion exchange chromatography and subsequent identification of the fractions by agarose gel electrophoresis showed that HA corresponded to 90% of the total amount of extracted glycosaminoglycans.

Marine sulfated polysaccharides (MSP), such as sulfated fucans (SF), sulfated galactans (SG) and glycosaminoglycans (GAG) isolated from either algae or invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co)-factors of the coagulation cascade during clotting-inhibition processes. These molecular complexes between MSP and coagulation-related proteins might, at first glance, be assumed to be driven mostly by electrostatic interactions. However, a systematic comparison using several novel sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns has shown that these molecular interactions are regulated essentially by the stereochemistry of the glycans (which depends on a conjunction of anomericity, monosaccharide, conformational preference, and glycosylation and sulfation sites), rather than just a simple consequence of their negative charge density (mainly the number of sulfate groups). Here, we present an overview of the structure-function relationships of MSP, correlating their structures with their potential anticoagulant and antithrombotic actions, since pathologies related to the cardiovascular system are one of the major causes of illness and mortality in the world.