824 resultados para PANDEMIC INFLUENZA A (H1N1)


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Human body is in continuous contact with microbes. Although many microbes are harmless or beneficial for humans, pathogenic microbes possess a threat to wellbeing. Antimicrobial protection is provided by the immune system, which can be functionally divided into two parts, namely innate and adaptive immunity. The key players of the innate immunity are phagocytic white blood cells such as neutrophils, monocytes, macrophages and dendritic cells (DCs), which constantly monitor the blood and peripheral tissues. These cells are armed for rapid activation upon microbial contact since they express a variety of microbe-recognizing receptors. Macrophages and DCs also act as antigen presenting cells (APCs) and play an important role in the development of adaptive immunity. The development of adaptive immunity requires intimate cooperation between APCs and T lymphocytes and results in microbe-specific immune responses. Moreover, adaptive immunity generates immunological memory, which rapidly and efficiently protects the host from reinfection. Properly functioning immune system requires efficient communication between cells. Cytokines are proteins, which mediate intercellular communication together with direct cell-cell contacts. Immune cells produce inflammatory cytokines rapidly following microbial contact. Inflammatory cytokines modulate the development of local immune response by binding to cell surface receptors, which results in the activation of intracellular signalling and modulates target cell gene expression. One class of inflammatory cytokines chemokines has a major role in regulating cellular traffic. Locally produced inflammatory chemokines guide the recruitment of effector cells to the site of inflammation during microbial infection. In this study two key questions were addressed. First, the ability of pathogenic and non-pathogenic Gram-positive bacteria to activate inflammatory cytokine and chemokine production in different human APCs was compared. In these studies macrophages and DCs were stimulated with pathogenic Steptococcus pyogenes or non-pathogenic Lactobacillus rhamnosus. The second aim of this thesis work was to analyze the role of pro-inflammatory cytokines in the regulation of microbe-induced chemokine production. In these studies bacteria-stimulated macrophages and influenza A virus-infected lung epithelial cells were used as model systems. The results of this study show that although macrophages and DCs share several common antimicrobial functions, these cells have significantly distinct responses against pathogenic and non-pathogenic Gram-positive bacteria. Macrophages were activated in a nearly similar fashion by pathogenic S. pyogenes and non-pathogenic L. rhamnosus. Both bacteria induced the production of similar core set of inflammatory chemokines consisting of several CC-class chemokines and CXCL8. These chemokines attract monocytes, neutrophils, dendritic cells and T cells. Thus, the results suggest that bacteria-activated macrophages efficiently recruit other effector cells to the site of inflammation. Moreover, macrophages seem to be activated by all bacteria irrespective of their pathogenicity. DCs, in contrast, were efficiently activated only by pathogenic S. pyogenes, which induced DC maturation and production of several inflammatory cytokines and chemokines. In contrast, L. rhamnosus-stimulated DCs matured only partially and, most importantly, these cells did not produce inflammatory cytokines or chemokines. L. rhamnosus-stimulated DCs had a phenotype of "semi-mature" DCs and this type of DCs have been suggested to enhance tolerogenic adaptive immune responses. Since DCs have an essential role in the development of adaptive immune response the results suggest that, in contrast to macrophages, DCs may be able to discriminate between pathogenic and non-pathogenic bacteria and thus mount appropriate inflammatory or tolerogenic adaptive immune response depending on the microbe in question. The results of this study also show that pro-inflammatory cytokines can contribute to microbe-induced chemokine production at multiple levels. S. pyogenes-induced type I interferon (IFN) was found to enhance the production of certain inflammatory chemokines in macrophages during bacterial stimulation. Thus, bacteria-induced chemokine production is regulated by direct (microbe-induced) and indirect (pro-inflammatory cytokine-induced) mechanisms during inflammation. In epithelial cells IFN- and tumor necrosis factor- (TNF-) were found to enhance the expression of PRRs and components of cellular signal transduction machinery. Pre-treatment of epithelial cells with these cytokines prior to virus infection resulted in markedly enhanced chemokine response compared to untreated cells. In conclusion, the results obtained from this study show that pro-inflammatory cytokines can enhance microbe-induced chemokine production during microbial infection by providing a positive feedback loop. In addition, pro-inflammatory cytokines can render normally low-responding cells to high chemokine producers via enhancement of microbial detection and signal transduction.

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The aim of this study was to estimate the development of fertility in North-Central Namibia, former Ovamboland, from 1960 to 2001. Special attention was given to the onset of fertility decline and to the impact of the HIV epidemic on fertility. An additional aim was to introduce parish registers as a source of data for fertility research in Africa. Data used consisted of parish registers from Evangelical Lutheran congregations, the 1991 and 2001 Population and Housing Censuses, the 1992 and 2000 Namibia Demographic and Health Surveys, and the HIV sentinel surveillances of 1992-2004. Both period and cohort fertility were analysed. The P/F ratio method was used when analysing census data. The impact of HIV infection on fertility was estimated indirectly by comparing the fertility histories of women who died at an age of less than 50 years with the fertility of other women. The impact of the HIV epidemic on fertility was assessed both among infected women and in the general population. Fertility in the study population began to decline in 1980. The decline was rapid during the 1980s, levelled off in the early 1990s at the end of war of independence and then continued to decline until the end of the study period. According to parish registers, total fertility was 6.4 in the 1960s and 6.5 in the 1970s, and declined to 5.1 in the 1980s and 4.2 in the 1990s. Adjustment of these total fertility rates to correspond to levels of fertility based on data from the 1991 and 2001 censuses resulted in total fertility declining from 7.6 in 1960-79 to 6.0 in 1980-89, and to 4.9 in 1990-99. The decline was associated with increased age at first marriage, declining marital fertility and increasing premarital fertility. Fertility among adolescents increased, whereas the fertility of women in all other age groups declined. During the 1980s, the war of independence contributed to declining fertility through spousal separation and delayed marriages. Contraception has been employed in the study region since the 1980s, but in the early 1990s, use of contraceptives was still so limited that fertility was higher in North-Central Namibia than in other regions of the country. In the 1990s, fertility decline was largely a result of the increased prevalence of contraception. HIV prevalence among pregnant women increased from 4% in 1992 to 25% in 2001. In 2001, total fertility among HIV-infected women (3.7) was lower than that among other women (4.8), resulting in total fertility of 4.4 among the general population in 2001. The HIV epidemic explained more than a quarter of the decline in total fertility at population level during most of the 1990s. The HIV epidemic also reduced the number of children born by reducing the number of potential mothers. In the future, HIV will have an extensive influence on both the size and age structure of the Namibian population. Although HIV influences demographic development through both fertility and mortality, the effect through changes in fertility will be smaller than the effect through mortality. In the study region, as in some other regions of southern Africa, a new type of demographic transition is under way, one in which population growth stagnates or even reverses because of the combined effects of declining fertility and increasing mortality, both of which are consequences of the HIV pandemic.

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This is a study of crises caused by HIV/AIDS among the Akan of Ghana. It creates more awareness about the epidemic and has indicated other possible paths for campaign strategies. The pandemic has many devastating consequences; yet new infections are recorded daily despite campaigns against the disease. The search for therapy often sees the use of multiple outlets, which expresses Ghana's pluralistic medical system based on Kleinman's sector analytical model involving Western medicine, self-therapy, and folk healing. But it also leaves individuals and kin members in financial quandary. The fieldwork for this study is mainly through participant observation lasting 13 months (February 2003 to March 2004) among the Akan; in addition, some archival materials have been used. The Akan people live in the coastal south and forest zone of Ghana. Every Akan village or town is made up of corporate lineages, and social organisation is based on matrilineal descent. The society is holistic because the matrilineages seek the welfare of all their members. Meyer Fortes, R. S. Rattray and others on the Akan noticed this encompassing nature in the lineage organisation; but they did not make it salient (or failed to notice it) during illness, efforts for healing, and the care of the sick member. HIV/AIDS is an illness which shows the encompassing nature of the Akan matrilineage. It also reveals many contradictions in the group, viz. stigmatisation, abandonment, and attitudes that do not express altruism in a group expected to be closely-knit based on members' belief that they are of the 'same blood'. The crises have been analyzed in the total social system because the disease creates breaches at various levels of social interaction. An analysis of crises in a group is not far-fetched; Victor Turner has shown the way among the Ndembu and has revealed the contraditions in the seemingly uneventful life in the group. This study has identified that in dealing with HIV/AIDS patients and crises about the disease we are dealing with 'holistic' patients. Their cases produce many changes in the matrilineal structure--many orphans are being created and the care of patients is increasingly falling on the elderly. HIV/AIDS also challenges Akan cosmology because, for example, an AIDS death in local notions is a 'bad' demise which fails to produce ancestors who reproduce the society through reincarnation. Campaigns could emphasize this notion. The study begins with a description of the holistic nature of Akan matriliny, and the patients have been described as 'holistic' because their crises affect other people in the holistic society. Chapter 2 discusses the importance of ancestors as the starting points for social order who are constantly revered (in rites invoving the chief, Chapter 4). Chapter 3 focuses on funerals as an important social performance for the welfare of the dead and the living. Chapter 5 concentrates on HIV/AIDS as an illness threat marked by dominant discourses such as poverty, sexuality, migration, and condom use. Chapter 6 analyzes the attempts for therapy, and traditional healers' claims to have a cure. The efforts for therapy continues with spiritual church healing in Chapter 7, and chapter 8 is devoted to care of the patients and its inherent crises. Chapter 9 analyzes the effects of HIV/AIDS afflictions and AIDS deaths on the matrilineal group and in society. The study ends with a short part, devoted to Recommendations based on the findings in this investigation.

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From the moment Queensland's Chief Health Officer, Dr Jeannette Young, laid down the gauntlet to Queensland pharmacists kicking off the Queensland Pharmacists Immunisation Pilot (QPIP) for the 2014 influenza season, community pharmacy in Australia was never going to be the same.

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Innate immunity and host defence are rapidly evoked by structurally invariant molecular motifs common to microbial world, called pathogen associated molecular patterns (PAMPs). In addition to PAMPs, endogenous molecules released in response to inflammation and tissue damage, danger associated molecular patterns (DAMPs), are required for eliciting the response. The most important PAMPs of viruses are viral nucleic acids, their genome or its replication intermediates, whereas the identity and characteristics of virus infection-induced DAMPs are poorly defined. PAMPs and DAMPs engage a limited set of germ-line encoded pattern recognition receptors (PRRs) in immune and non-immune cells. Membrane-bound Toll-like receptors (TLRs), cytoplasmic retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptor (NLRs) are important PRRs involved in the recognition of the molecular signatures of viral infection, such as double-stranded ribonucleic acids (dsRNAs). Engagement of PRRs results in local and systemic innate immune responses which, when activated against viruses, evoke secretion of antiviral and pro-inflammatory cytokines, and programmed cell death i.e., apoptosis of the virus-infected cell. Macrophages are the central effector cells of innate immunity. They produce significant amounts of antiviral cytokines, called interferons (IFNs), and pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18. IL-1β and IL-18 are synthesized as inactive precursors, pro-IL-1β and pro-IL-18, that are processed by caspase-1 in a cytoplasmic multiprotein complex, called the inflammasome. After processing, these cytokines are biologically active and will be secreted. The signals and secretory routes that activate inflammasomes and the secretion of IL-1β and IL-18 during virus infections are poorly characterized. The main goal of this thesis was to characterize influenza A virus-induced innate immune responses and host-virus interactions in human primary macrophages during an infection. Methodologically, various techniques of cellular and molecular biology, as well as proteomic tools combined with bioinformatics, were utilized. Overall, the thesis provides interesting insights into inflammatory and antiviral innate immune responses, and has characterized host-virus interactions during influenza A virus-infection in human primary macrophages.

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Kirjallisuuskatsauksen aihe on ajankohtainen Suomessa ja muualla maailmassa. Sikainfluenssa on sikojen tarttuva hengitystiesairaus, jonka aiheuttaja on herkästi kärsäkontaktissa leviävä influenssa A – virus. Siat sairastuvat usein yllättäen ja samanaikaisesti. Sikainfluenssa voi olla oireeton tai vähäoireinen, mikä hankaloittaa taudin havaitsemista. Sikainfluenssa aiheuttaa sikatiloille tuotantotappioita ja sioille hyvinvointiongelmia. Sikainfluenssa on maailmalla yleinen sikojen hengitystiesairaus. Suomi oli sikainfluenssasta vapaa maa vuoteen 2007 saakka ja vuonna 2009 noin kolmasosa suomalaisista sikaloista oli seropositiivisia sikainfluenssan suhteen. Influenssa A – viruksia esiintyy yleisesti eläimillä ja ihmisillä. Influenssa A – virusten kantajia luonnossa ovat vesilinnut, jotka levittävät influenssaviruksia ulosteissaan. Influenssa A – virukset pystyvät muuntumaan uusiksi alatyypeiksi ja sikaa pidetään eläinlajina, jossa influenssa A – virukset muuntuvat lajista toiseen tarttuviksi. Sikainfluenssa on zoonoosi. Sikainfluenssaviruksia on useita eri alatyyppejä. Maailmalla esiintyvien sikainfluenssavirusten alkuperä ja ominaisuudet vaihtelevat maantieteellisen sijainnin mukaan. Euroopassa, Pohjois-Amerikassa ja Aasiassa nykyään esiintyvät sikainfluenssavirukset ovat kehittyessään eriytyneet geneettisesti ja antigeenisesti toisistaan. Sikapopulaatioissa kiertää yleensä useita eri sikainfluenssavirustyyppejä yhtä aikaa. Tärkeimpiä ja useimmiten eristettyjä sikainfluenssavirusten alatyyppejä ovat H1N1, H1N2 ja H3N2. Sikainfluenssan diagnosointi on tärkeää, jotta virusten leviämistä voidaan ehkäistä ja tautitilanne pysyy ajantasaisena. Sikainfluenssa diagnosoidaan osoittamalla sikainfluenssavirus 1-3 vuorokautta kliinisten oireiden alkamisen jälkeen otetuista virusnäytteistä tai virusvasta-aineet serologisin testein pariseeruminäytteistä. Viruksen osoitusmenetelmät (viruseristys ja RT-PCR) ovat luotettavia ja niillä sikainfluenssavirukset voidaan tyypittää. Serologisten testien (hemagglutinaation inhibitio ja ELISA) luotettavuudessa on puutteita ja etenkin ELISA-testien luotettavuus perustuu tietoon sikapopulaatiossa liikkuvien sikainfluenssavirusten alatyypeistä. Sikainfluenssan jatkuva ja tehokas tautiseuranta on oleellista, jotta serologiset testit saadaan optimoitua. Alueellisesti sikainfluenssan esiintyvyyttä lisäävät suuri sikatiheys, tilojen lyhyet välimatkat, eläinkuljetukset sekä sikojen kontaktit ulkopuolisiin henkilöihin ja tavaroihin. Sikalan bioturvallisuus on tärkein tekijä estettäessä sikainfluenssavirusten pääsy sikalaan. Sikainfluenssan vastustaminen on tärkeää, koska se on osa sikojen hengitystiesairauskompleksia sekä predisponoiva tekijä muiden sikapatogeenien aiheuttamille hengitystiesairauksille. Sikainfluenssan vastustuksessa voidaan suurilla sikatiloilla käyttää apuna kahta tai kolmea virustyyppiä sisältäviä rokotteita, jotka vähentävät sikainfluenssan kliinisiä oireita ja viruksen eritystä ympäristöön.

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Tuberculosis continues to kill 1.4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.

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Cardiovascular diseases are nowadays the first cause of mortality worldwide, causing around the 30% of global deaths each year. The risk of suffering from cardiovascular illnesses is strongly related to some factors such as hypertension, high cholesterol levels, diabetes, obesity The combination of these different risk factors is known as metabolic syndrome and it is considered a pandemic due to the high prevalence worldwide. The pathology of the disorders implies a combined cardiovascular therapy with drugs which have different targets and mechanisms of action, to regulate each factor separately. The simultaneous analysis of these drugs turns interesting but it is a complex task since the determination of multiple substances with different physicochemical properties and physiological behavior is always a challenge for the analytical chemist. The complexity of the biological matrices and the difference in the expected concentrations of some analytes require the development of extremely sensitive and selective determination methods. The aim of this work is to fill the gap existing in this field of the drug analysis, developing analytical methods capable of quantifying the different drugs prescribed in combined cardiovascular therapy simultaneously. Liquid chromatography andem mass spectrometry (LCMS/MS) has been the technique of choice throughout the main part of this work, due to the high sensitivity and selectivity requirements.

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Computational protein design (CPD) is a burgeoning field that uses a physical-chemical or knowledge-based scoring function to create protein variants with new or improved properties. This exciting approach has recently been used to generate proteins with entirely new functions, ones that are not observed in naturally occurring proteins. For example, several enzymes were designed to catalyze reactions that are not in the repertoire of any known natural enzyme. In these designs, novel catalytic activity was built de novo (from scratch) into a previously inert protein scaffold. In addition to de novo enzyme design, the computational design of protein-protein interactions can also be used to create novel functionality, such as neutralization of influenza. Our goal here was to design a protein that can self-assemble with DNA into nanowires. We used computational tools to homodimerize a transcription factor that binds a specific sequence of double-stranded DNA. We arranged the protein-protein and protein-DNA binding sites so that the self-assembly could occur in a linear fashion to generate nanowires. Upon mixing our designed protein homodimer with the double-stranded DNA, the molecules immediately self-assembled into nanowires. This nanowire topology was confirmed using atomic force microscopy. Co-crystal structure showed that the nanowire is assembled via the desired interactions. To the best of our knowledge, this is the first example of a protein-DNA self-assembly that does not rely on covalent interactions. We anticipate that this new material will stimulate further interest in the development of advanced biomaterials.

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More than thirty years after the discovery that Human Immunodeficiency Virus (HIV) was the causative agent of Acquired Immunodeficiency Syndrome (AIDS), the disease remains pandemic as long as no effective universal vaccine is found. Over 34 million individuals in the world are infected with the virus, and the vast majority of them have no access to the antiretroviral therapies that have largely reduced HIV to a chronic disease in the developed world. The first chapter of this thesis introduces the history of the virus. The key to the infectious mechanism of the virus lies in its envelope glycoprotein (Env), a trimeric spike on the viral surface that utilizes host T cell receptors for entry. Though HIV-1 Env is immunogenic, most infected patients do not mount an effective neutralizing antibody response against it. Broadly-neutralizing anti-Env antibodies (bNAbs) present in the serum of a minority of infected individuals are usually sufficient to prevent the progression to full blown AIDS. Thus, the molecular details of these bNAbs as well as the antibody-antigen interface are of prime interest for structural studies, as insight gained would contribute to the design of a more effective immunogen and potential vaccine candidate. The second chapter of this thesis describes the low-resolution crystal structure of one such antibody, 2G12 dimer, which targets a high mannose epitope on the surface of Env. Patients infected with HIV-2, a related virus with ~35% sequence identity in the Env region, can generally mount a robust antibody response sufficient for viral control for reasons still unknown. The final two chapters of this thesis focus on the first reported structural studies of HIV-2 Env, the molecular details of which may inform HIV-1 therapy and immunogen design.

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Dendritic cells (DCs) are essential in order to combat invading viruses and trigger antiviral responses. Paradoxically, in the case of HIV-1, DCs might contribute to viral pathogenesis through trans-infection, a mechanism that promotes viral capture and transmission to target cells, especially after DC maturation. In this review, we highlight recent evidence identifying sialyllactose-containing gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans-infection of T cells. In contrast, DC-SIGN, long considered to be the main receptor for DC capture of HIV-1, plays a minor role in mature DC-mediated HIV-1 capture and trans-infection.

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A presente tese trata da garantia do acesso à justiça ao jurisdicionado do século XXI, membro de uma sociedade marcadamente globalizada. Embora o jurisdicionado, centro da moderna ciência processual, estabeleça com grande frequência relações que ultrapassam os limites políticos dos países, o Direito Processual, no Brasil, continua fundado em bases estritamente internas, gerando uma arriscada litigiosidade contida. Por essa razão, desenvolve-se, ao longo do presente trabalho, um raciocínio consistente e coordenado, voltado ao resgate do acesso à justiça ao jurisdicionado de nosso tempo. Para tanto, no capítulo 1, são examinados os dois grandes eixos evolutivos: os eixos social e jurídico. A partir dessa análise, conclui-se que ambos os eixos evolutivos convergem para, a um só tempo, incentivar e justificar a releitura do Direito Processual. No capítulo 2, analisamos o primado dos princípios fundamentais processuais, que ocupa posição de destaque no estudo do Direito Processual na atualidade e exerce papel de protagonismo na concepção do Direito Processual Civil Transnacional. Verificamos que a consagração dos mesmos princípios processuais fundamentais em diferentes partes do mundo promove a convergência entre os sistemas jurídico-processuais nacionais quanto à sua essência, fomentando o espírito de cooperação entre os países. No capítulo 3, aportamos no estudo do microssistema do Direito Processual Civil Transnacional, apresentando o seu conceito, bem como as principais teorias a seu respeito, como forma de delinear os seus contornos. No capítulo 4, desenvolvemos a análise do princípio fundamental do acesso à justiça, que consiste no ponto central do Direito Processual Transnacional, segundo uma nova metodologia, que alia os subprincípios do acesso à justiça concebidos por Paulo Cezar Pinheiro Carneiro à visão tridimensional do Direito talhada por Mauro Cappelletti. Através dessa metodologia, descortinamos os principais problemas e oferecemos soluções eficazes para a efetiva garantia do acesso à justiça no âmbito transnacional. No capítulo 5, examinamos a experiência precursora da União Europeia no trato do tema, que influencia a sua abordagem em todo o resto do mundo. Após contextualizar a problemática, analisamos o instituto vanguardista denominado Título Executivo Europeu como instrumento concreto de garantia do acesso à justiça no âmbito transnacional. No capítulo 6, transpomos todos os pilares teóricos e principiológicos desenvolvidos ao longo da tese para o Brasil, como forma de buscar aprimorar o nosso sistema jurídico-processual no tocante à garantia do acesso à justiça no âmbito transnacional. Para tanto, analisamos os contornos e o atual estágio evolutivo de integração do Mercosul, importante bloco regional do qual o Brasil faz parte. Por fim, invocando as modernas premissas teóricas apresentadas nos capítulos anteriores, concluímos que a legislação atualmente em vigor no Mercosul e no Brasil permite admitir o cabimento da instauração da execução, no Brasil, de sentenças oriundas de outros países do Mercosul, prescindindo do exercício do juízo de delibação pelo Superior Tribunal de Justiça. Essa solução representa um avanço concreto em prol da efetiva garantia do acesso à justiça no âmbito transnacional ao jurisdicionado no Brasil, sendo um exemplo do ciclo virtuoso que o Direito Processual Transnacional pretende inaugurar.

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The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

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A AIDS é a primeira pandemia do mundo globalizado que por meio de uma resposta condicionada por fatores estruturais retratam essa forma global de funcionar: enfraquecimento dos Estados nacionais, forte ênfase na eficiência tecnocrática, aumento da pobreza além de as organizações internacionais terem ocupado o lugar dos experts, indicando o melhor modelo de saúde a ser seguido. Este estudo é uma pesquisa documental que pretende mapear as orientações da organização de Cooperação e Desenvolvimento Econômico (OCDE) em relação às questões referentes à sexualidade e ao combate da epidemia de HIV/AIDS a partir dos documentos publicados em seu site. A OCDE se constitui num fórum de países desenvolvidos que pretendem contribuir para o desenvolvimento da economia mundial a partir de uma efetiva cooperação entre seus membros. Congrega os participantes em comunidades de influência partilhando perspectivas de ações sobre questões cuja expertise modela as agendas nacionais e de outras organizações internacionais. Dentre os resultados encontrados, destaca-se a ideia do primado do econômico em detrimento de outras dimensões (social, política e cultural), principalmente nos debates sobre a globalização. A lógica econômica é o referencial de todo o tipo de intervenção silenciando os outros discursos como a discussão da sexualidade e dos direitos. Se queremos prevenir a transmissão do HIV pela via sexual, a mais importante em termos globais, significa que necessariamente temos que interferir na sexualidade das pessoas. Dois campos então se apresentam: um que se apoia na ideia que a sexualidade é uma dimensão fundamental da vida humana, é parte de uma política de afirmação de direitos e, portanto, indispensável na discussão sobre saúde, procurando interferir o mínimo possível para que as pessoas levem a vida mais próxima do normal; e o outro campo, que trabalha na direção contrária, com a máxima interferência e sem respeito às escolhas das pessoas.

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Introduction In the preantibiotic era Streptococcus pyogenes was a common cause of severe pneumonia but currently, except for postinfluenza complications, it is not considered a common cause of community-acquired pneumonia in adults. Aim and Material and Methods This study aimed to identify current clinical episodes of S. pyogenes pneumonia, its relationship with influenza virus circulation and the genotypes of the involved isolates during a decade in a Southern European region (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm, multilocus-sequence typing, and superantigen profile determination. Results Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range 0.29-2.29). Thirty-seven episodes were community-acquired, 21 involved an invasive infection and 10 developed STSS. The associated mortality rate was 20%, with half of the patients dying within 24 hours after admission. Influenza coinfection was confirmed in four patients and suspected in another. The 52.5% of episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected persons were elderly individuals and adults with severe comorbidities, although 13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones were identified, the most prevalent being emm1/ST28 (43.6%) causing the most severe cases. Conclusions S. pyogenes pneumonia had a continuous presence frequently unrelated to influenza infection, being rapidly fatal even in previously healthy individuals.