Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Workers with elderly dependants: employment law’s response to the latest care-giving conundrum

This paper considers how employment laws are being used in response to what we have termed ‘the eldercare/workplace conundrum’. It is well known that people are now living longer but health is still failing in a significant percentage of older people, meaning that many adults require care for longer, albeit to varying degrees and for varying amounts of time. Many of these individuals will receive care from relatives or close friends who are participating in the labour market: this is increasingly likely as adults are expected / wanting to remain in paid work for longer, often into their 60s and 70s. The requirements of elderly dependants can cause these workers huge difficulties and dilemmas as they attempt, across time, to accommodate the particular needs of the person for whom they wish to provide care, often a loved one, and meet the particular demands of their employment relationship. In this paper we consider why this is an area of social policy that warrants effective legal engagement and consider, drawing on various examples of legal responses in other countries that face similar conundrums, what might improve legal engagement in this area.

Soil phosphorus supply affects nodulation and N:P ratio in 11 perennial legume seedlings

Developing new perennial pasture legumes for low-P soils is a priority for Australian Mediterranean agro-ecosystems, where soil P availability is naturally low. As legumes tend to require higher P inputs than non-legumes, the ability of these plants to fix N2 under varying soil P levels must be determined. Therefore, the objective of this study was to investigate the influence of soil P supply on plant N status and nodule formation in 11 perennial legumes, including some novel pasture species. We investigated the effect of applying soil P, ranging from 0 to 384 μg P/g dry soil, on plant N status and nodulation in a glasshouse. Without exogenous P supply, shoot N concentration and N : P ratio were higher than at 6 μg P/g soil. Shoot N concentration and N : P ratio then changed little with further increase in P supply. There was a close positive correlation between the number of nodules and shoot P concentration in 7 of the 11 species. Total nodule dry weight and the percentage of plant dry weight that consisted of nodules increased when P supply increased from 6 to 48 μg P/g. Without exogenous P addition, N : P ratios partitioned into a two-group distribution, with species having a N : P ratio of either >70 or <50 g/g. We suggest that plants with a high N : P ratio may take up N from the soil constitutively, while those with a low N : P ratio may regulate their N uptake in relation to internal P concentration. The flexibility of the novel pasture legumes in this study to adjust their leaf N concentrations under different levels of soil P supplements other published evidence of good growth and high P uptake and P-use efficiency under low soil P supply and suggests their potential as pasture plants in low-P soils in Australian Mediterranean agro-ecosystems warrants further attention.

Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials

The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have in important role in the favourable impact of dairy on human health such as blood pressure (BP) control, blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from acute clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Chronic interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seems to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. The beneficial changes in cardiometabolic homeostasis are likely mediated through improvements in insulin resistance, however to gain more detailed understanding on the underlying mechanism of milk proteins warrants further research. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.

Constitutional Haploinsufficiency of Tumor Suppressor Genes in Mentally Retarded Patients With Microdeletions in 17p13.1

Chromosome microdeletions or duplications are detected in 10-20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of similar to 180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (similar to 1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer. Copyright (C) 2009 S. Karger AG, Basel

Double stranded DNA-binding studies of potential Rhodium(ll) antitumor complexes

In 1952, Dwyer and coworkers began testing a series of metal complexes for potential inhibition of cancer cell proliferation in animals.[l] The complexes tested were unsuitable for such studies due to their high toxicity. Therefore, no further work was done on the project. However, in 1965, Rosenberg and coworkers revisited the possibility of potential metal-based drugs. Serendipitously, they discovered that cis-diamminedichloroplatinum(lI) (cisplatin) inhibits cell division in E. coli.[2] Further studies of this and other platinum compounds revealed inhibition of tumor cell lines sarcoma 180 and leukemia LI2l0 in mice.[l] Cisplatin was approved by the Food and Drug Administration in 1970 as a chemical chemotherapeutic agent in the treatment of cancer. The drug has primarily been used in the treatment of testicular and ovarian cancers, although the powerful chemotherapeutic properties of the compound indicate use against a variety of other cancers.[3] The toxicity of this compound, however, warrants the development of other metal-based potential antitumor agents. The success of cisplatin, a transition-metal-based chemotherapeutic, opened the doors to a host of research on the antitumor effects of other transition-metal complexes. Beginning in the 1970s, researchers looked to rhodium for potential use in antitumor complexes. Dirhodium complexes with bridging equatorial ligands (Figure I) were the primary focus for this research. The overwhelming majority of these complexes were dirhodium(II) carboxylate complexes, containing two rhodium(II) centers, four equatorial ligands in a lantero formation around the metal center, and an axial ligand on either end. The family of complexes in Figure 1 will be referred to as dirhodium(II) carboxylate complexes. The dirhodium centers are each d? with a metal-metal bond between them. Although d? atoms are paramagnetic, the two unpaired electrons pair to make the complex diamagnetic. The basic formula of the dirhodium(lI) carboxylate complexes is Rh?(RCOO)?(L)? with R being methyl, ethyl, propyl, or butyl groups and L being water or the solvent in which the complex was crystalized. Of these dirbodium(II) carboxylate complexes, our research focuses on Rb la and two other similar complexes Rh2 and Rh3 (Figure 2). Rh2 is an activated form of Rhla, with four acetonitrile groups in place of two of the bidentate acetate ligands. Rh3 is similar to Rhla, with trifluoromethyl groups in place of the methyl groups on the acetate ligands.

The Cultural Construction of the Maine Sporting Camps

Maine sporting camps were a cultural and social phenomenon of the urban upper and middle class. They originated in Maine in the late 1870s and early 1880s and reached their zenith around the turn of the century with over 160 in operation in eight of the sixteen counties in Maine in 1906. The period from 1880 until World War I can be considered the 'golden era' of the Maine sporting camps. After the war, with technological advancements such as the outboard motor, the proliferation of the automobile, and the introduction of a road system into rural Maine, the camps underwent significant change that warrants an entirely different cultural analysis. A number of elements came together to produce a cultural atmosphere permissive of sporting camp creation in Maine. These include changing national views upon nature, health, sport and the leisure time in which to pursue them. In the late nineteenth century, with the rise of large industrially based cities, overcrowding fostered crime and disease. An upper and middle class emerged that desired escape and separation from the lower classes. Maine was chosen for such an escape because it offered, through sporting camps, a chance to "get back to nature," by pursuing the healthful activities of hunting and fishing. At the same time these urban sportsmen and sportswomen distinguished themselves on the social Hierarchical scale from the rural inhabitants. What happened in rural Maine during the period between 1880 and World War I was the introduction of a new cultural order on the landscape. Coming primarily from urban centers on the East Coast of the United States were men, women and children who looked to Maine for vacations. These vacations were designed to put them in touch with nature by pursuing healthful activities, especially those of fishing and hunting. Coming from an environment that emphasized social standing, they ensured that these trips would perpetuate this hierarchy. They experienced nature through the Maine sporting camps, which provided them with the services and skills necessary to experience it while enjoying a degree of luxury that they were accustomed to in the urban world. The Maine sporting camps were a cultural manifestation of the urban upper and middle class, the groups that the camps were established to serve. Despite this the camps did not represent a structural duplication of urban society. Instead, the camps represented a cultural construction that was produced by interaction between members of two different conceptual and physical worlds, the blending of which, on a social level, was determined by urban mentality and rural knowledge. In the production of a cultural world meaningful to the clients, the rural world of the Maine woods was altered to meet their needs. It was not a one-sided process, however, as the clients were forced to acknowledge the importance of the rural inhabitants on the basis of their value to the clients.

Politian: a critical analysis

Why even look at Politian, an unfinished failure? While it is true that Politian was a failure for its time and surely one of Poe's least successful attempts, it may improve on a stage with a more modern perspective. If not solely for examination of Poe's artistic effort, Politian also warrants a closer read due to its historical relevance by way of Beauchamp and Sharp. Poe, a most fastidious editor of his work, was ultimately required because of financial constraints to lay aside Politian in its unfinished state. As a result, the unedited Politian may provide insight into the writing process of Poe that other polished pieces cannot, and that, if nothing else, warrants a more precise study of his play.

Determinação de prevalência de bactérias na efusão da orelha média de crianças submetidas à mmiringotomia

Introdução: A etiologia da otite média com efusão ainda não está completamente estabelecida, mas agentes infecciosos podem contribuir para sua patogênese. Demonstrou-se que a reação em cadeia da polimerase (PCR) é superior ao exame cultural para detectar espécies bacterianas. O conhecimento sobre a epidemiologia bacteriana da otite média com efusão em áreas geográficas distintas é essencial para a implementação de tratamentos racionais, quando necessários. Objetivos: Determinar a prevalência do Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis e Alloiococcus otitidis nas efusões de orelha média de crianças com otite média recorrente e otite média com efusão crônica que foram submetidas à miringotomia, comparar os resultados obtidos por cultura e PCR, comparar os achados bacteriológicos em crianças menores e maiores de dois anos e determinar o perfil de resistência à penicilina dos germes isolados. Métodos: Analisaram-se 128 amostras de efusões de orelha média de 75 crianças entre 11 meses e 9 anos e 4 meses de idade (média = 34,7 meses). Pacientes com otite média recorrente tinham efusão documentada por ≥ 6 semanas e aqueles com otite média com efusão crônica, por ≥3 meses. Os pacientes não tinham sinais de otite média aguda ou infecção do trato respiratório e não estavam sob antibioticoterapia no momento do procedimento. A aspiração do material foi realizada por timpanocentese, utilizando-se um coletor de Alden-Senturia. Os estudos bacteriológicos foram iniciados em menos de 15 minutos após a obtenção da efusão e uma parte da amostra foi armazenada a -20oC para análise posterior pela PCR. Utilizou-se um método de PCR simultânea para a detecção de quatro patógenos. A análise estatística foi efetivada com o teste χ2 de McNemar, teste χ2 com correção de Yates e teste exato de Fisher, quando apropriados. Resultados: Cultivaram-se bactérias em 32 (25,1%) das 128 amostras e os patógenos principais foram encontrados em 25 (19,6%). O A. otitidis não foi isolado em cultura. A PCR identificou bactérias em 110 (85,9%) das amostras, e os resultados positivos foram: 67 (52,3%) para A. otitidis, 50 (39,1%) para H. influenzae, 16 (12,5%) para S. pneumoniae e 13 (10,2%) para M. catarrhalis. Todas as amostras positivas por cultura foram positivas pela PCR, mas 85 (77,2%) das efusões com resultado positivo pela PCR foram negativas por cultura, para os germes estudados. A PCR foi significativamente mais sensível que a cultura (P<0,001). O S. pneumoniae foi encontrado mais freqüentemente em otite média recorrente do que em otite média com efusão crônica (P=0,038) e o H. influenzae foi encontrado mais vezes em crianças menores de dois anos (P=0,049). Quanto ao perfil de resistência, 100% das M. catarrhalis, 62,5% dos S. pneumoniae e 23% dos H. influenzae eram resistentes à penicilina. Conclusões: A prevalência das bactérias na otite média com efusão em um grupo de crianças brasileiras é semelhante àquelas relatadas em outros países, sendo o H. influenzae o mais encontrado dentre os patógenos principais da orelha média. Essa prevalência sugere que bactérias podem desempenhar um papel na patogênese da otite média com efusão. Os resultados mostram que a PCR é mais sensível na detecção de bactérias na efusão da orelha média, comparada com cultura, e é essencial para a identificação do A. otitidis. O elevado percentual de detecção do A. otitidis sugere mais investigações sobre sua atuação no início e no prolongamento de doenças da orelha média. O S. pneumoniae foi mais freqüente em otite média recorrente do que em otite média com efusão crônica e o H. influenzae foi mais encontrado em crianças menores de dois anos. A resistência à penicilina por parte do pneumococo e da moraxela é semelhante à relatada em outros países, ao passo que a produção de β-lactamase pelo hemófilo é mais baixa que aquela referida em bactérias isoladas em amostras de efusões de otite média com efusão.

Administração de Aposentadoria na Administração Pública no Brasil

Este trabalho objetivou verificar até que ponto os programas de preparo e acompanhamento da aposentadoria tem sido privilegiados na Administração Pública Indireta no Brasil; até que ponto a administração desses programas vem influindo positivamente na produtividade da força de trabalho ativa, bem como, se a administração desses programas está garantindo maior longevidade e satisfação para os aposentados. o estudo abrange quatro órgãos representativos dos ramos de mineração, crédito, telecomunicações e petróleo, com limitação espacial restrita ao Rio de Janeiro, sede dos mesmos, enfocando a ação do programa a partir de sua implantação, até o advento da Lei 8842 de 4 de janeiro de 1994.

A profissionalização de 2. grau em São Luís do Maranhão

O presente trabalho destina-se a caracterizar e a delinear o conteúdo expresso no texto da Lei n9 5.692/71 enfatizando a questão do ensino profissionalizante. O estudo está esquematizado em seis capitulos. O primeiro, discorre sobre o processo educativo como vem ocorrendo em nossa sociedade capitalista. O segundo segue a linha de contextualização histórica e tem como escopo aflorar a ideologia do texto da Lei n9 5.692/71. O terceiro, apresenta o problema e a metodologia de um estudo de caso reali zado em são Luís do Maranhão sendo seus resultados descritos no quarto capítulo e analisados no quinto. O último capítulo contém as conclusões da autora. A pesquisa torna evidente que o texto da Lei em estudo empreende perfeitamente as funções ideológicas trabalhadas pelo Estado para atender à realidade da sociedade através da ordem vigente e dos mecanismos de conservaçao e de reprodução sociais, apesar de ser constatada a alienação dos alunos pela sua não absorçao pelo mercado de trabalho, deixando transparecer que as diferenças intelectuais e o desempenho escolar são as barreiras que ficam evidentes na sociedade de classes, permitindo ao aparelho escolar ficar livre para manter suas funções. O resultado da pesquisa nos mostra que a escola assegura a preparação da mão-de-obra, através do mecanismo camuflado de "não profissionalização" uma vez que a grande maioria dos alunos egressos se encontram desempregados. A conclusão mostra a necessidade de dinamizar o ensino profissionalizante para que ele possa contribuir mais ativa e poderosamente em relação as necessidades do contexto, pois a profissionalização como hoje é feita, não se distingue muito da confecção de máquinas ou ferramentas de produção, porque ela está muito mais a serviço do sistema de produção do que do homem, tanto assim que nela não está incluída a garantia de emprego, levando por conseguinte a "desominização" do homem.

An empirical comparison of forward-rate and spot-rate models for valuing interest-rate options

Our main goal is to investigate the question of which interest-rate options valuation models are better suited to support the management of interest-rate risk. We use the German market to test seven spot-rate and forward-rate models with one and two factors for interest-rate warrants for the period from 1990 to 1993. We identify a one-factor forward-rate model and two spot-rate models with two faetors that are not significant1y outperformed by any of the other four models. Further rankings are possible if additional cri teria are applied.

A contribuição de Diké na formação do Emílio ou o papel da jurisdição constitucional na concretização do direito social à educação

The fundamental social right to education has a lengthy constitutional argument, having been declared as a right to everyone in the Title dedicated to the fundamental rights and warrants and, later, scrutinized in the Social Order Chapter exclusively devoted to this theme, where specific rights are guaranteed and fundamental duties are imposed to family, society, and state. In that which concerns education, the 1988 Constitution is the result of a historical-normative process which, since the days of the Lusitanian Empire wavering between distinct levels of protection warrants in some way the educational process. Nevertheless, not even the State s oldest commitment to education has been fully achieved, namely, the annihilation of illiteracy. Even as other fundamental social rights, education is inflicted with the lack of effective political will to reach its fulfillment, and this is reflected in the production of doctrine and jurisprudence which reduce the efficacy of these rights. The objective of this work is to analyze what part is to be played by the constitutional jurisdiction in the reversal of this picture in regards to the fulfillment of the fundamental social right to education. Therefore it is indispensable to present a proper conception of constitutional jurisdiction its objectives, boundaries and procedures and that of the social rights in the Brazilian context so as to establish its relationship from the prism of the right to education. The main existing obstacles to the effective action of constitutional jurisdiction on the ground of social rights are identified and then proposals so as to overcome them are presented. The contemplative and constructive importance of education in the shaping of the individual as well as its instrumental relevance to the achievement of the democratic ideal through the means of the shaping of the citizen is taken into account. The historical context which leads to the current Brazilian educational system is analyzed, tracing the normative area and the essential content of the fundamental right to education aiming to delineate parameters for the adequate development of the constitutional jurisdiction in the field. This jurisdiction must be neither larger nor narrower than that which has been determined by the Constitution itself. Its activity has been in turns based on a demagogic rhetoric of those fundamental rights which present a doubtful applicability, or falling short of that which has been established showing an excessive reverence to the constituent powers. It is necessary to establish dogmatic parameters for a good action of this important tool of constitutional democracy, notably in regards to the fundamental social right to education, for the sake of its instrumental role in the achievement of the democratic ideals of liberty and equality

A construção e estruturação do território comercial no bairro Alecrim Natal/RN

The study done has as objective the comprehension of the constructed territorial spaces through the commercial perspective, because it is a social practice which enables the dynamic of the space and the appearing of territories. Related to the territory, we emphasized the interest for the idea of used territory treated by Milton Santos, because we agreed with him believing that is the use of the territory which warrants its legitimacy. Then, the spatial dimension chose concentrates itself into the district of Alecrim, localized at the east zone of Natal/RN, where it is recognized by its strong commercial dynamic which was built during years, facing some events which happened in the context of the city. However, this dynamic counts with a hard dichotomy which involves as the considered by the State formal activities, as the informal one. About the commerce of the district, it has characteristics into its activities whose make him to be considered popular, as by the existing products, as by the strong presence of informal workers that constitutes the district s landscape. The informal workers practice expresses one of the multiples constructed alternative territorialities. We believe that this fact has direct relation with the growing process of the exclusion from the formal jobs market. Still talking about the spatial dimension, this real example of the Alecrim district shows how the techniques changes, together with the capitalism process, may influence one entire spatial dynamic across years, involving many agents, since the transient people from somewhere, until the State. Shall the Geography understand the multiple forms from the space, face to the relations that occur into it and also how new territories have been built

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)