Genetik der essentiellen arteriellen Hypertonie [Essential hypertension - which genes can be held responsible for it?].

Hypertension is a common heritable cardiovascular risk factor. Some rare monogenic forms of hypertension have been described, but the majority of patients suffer from essential hypertension, for whom the underlying genetic mechanisms are not clear. Essential hypertension is a complex trait, involving multiple genes and environmental factors. Recently, progress in the identification of common genetic variants associated with essential hypertension has been made due to large-scale international collaborative projects. In this article we review the new research methods used as well as selected recent findings in this field.

Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity.

As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force. Subsequent lipid sorting activates an abortive phagocytic response that leads to antigen uptake. Such activated DCs, without further association with alum, show high affinity and stable binding with CD4(+) T cells via the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1). We propose that alum triggers DC responses by altering membrane lipid structures. This study therefore suggests an unexpected mechanism for how this crystalline structure interacts with the immune system and how the DC plasma membrane may behave as a general sensor for solid structures.

Universal Design for Better Living The Essential Bathroom, May 2004

An easy-living home requires a full-sized bathroom on the main level. Family members will appreciate the extra space and guests of all ages and abilities will feel more welcome. At a minimum, you’ll need a five foot circle of open floor space for maneuvering a wheelchair between bathroom fixtures. A small powder room won’t work for guests who use walkers or wheelchairs. A shower stall—with no curb to step over—is more convenient than a tub for most guests. Make sure the doorway opening for the bathroom is at least 32 inches wide (preferably 36 inches). Universal design features, such as these, make homes better for everyone.

A coiled coil trigger site is essential for rapid binding of synaptobrevin to the SNARE acceptor complex.

Exocytosis from synaptic vesicles is driven by stepwise formation of a tight alpha-helical complex between the fusing membranes. The complex is composed of the three SNAREs: synaptobrevin 2, SNAP-25, and syntaxin 1a. An important step in complex formation is fast binding of vesicular synaptobrevin to the preformed syntaxin 1.SNAP-25 dimer. Exactly how this step relates to neurotransmitter release is not well understood. Here, we combined different approaches to gain insights into this reaction. Using computational methods, we identified a stretch in synaptobrevin 2 that may function as a coiled coil "trigger site." This site is also present in many synaptobrevin homologs functioning in other trafficking steps. Point mutations in this stretch inhibited binding to the syntaxin 1.SNAP-25 dimer and slowed fusion of liposomes. Moreover, the point mutations severely inhibited secretion from chromaffin cells. Altogether, this demonstrates that the trigger site in synaptobrevin is crucial for productive SNARE zippering.

Life-Cycle Effects on Household Expenditures: A Latent-Variable Approach

Using data from the Spanish household budget survey, we investigate life- cycle effects on several product expenditures. A latent-variable model approach is adopted to evaluate the impact of income on expenditures, controlling for the number of members in the family. Two latent factors underlying repeated measures of monetary and non-monetary income are used as explanatory variables in the expenditure regression equations, thus avoiding possible bias associated to the measurement error in income. The proposed methodology also takes care of the case in which product expenditures exhibit a pattern of infrequent purchases. Multiple-group analysis is used to assess the variation of key parameters of the model across various household life-cycle typologies. The analysis discloses significant life-cycle effects on the mean levels of expenditures; it also detects significant life-cycle effects on the way expenditures are affected by income and family size. Asymptotic robust methods are used to account for possible non-normality of the data.

Genometrics as an essential tool for the assembly of whole genome sequences: the example of the chromosome of Bifidobacterium longum NCC2705.

BACKGROUND: Analysis of the first reported complete genome sequence of Bifidobacterium longum NCC2705, an actinobacterium colonizing the gastrointestinal tract, uncovered its proteomic relatedness to Streptomyces coelicolor and Mycobacterium tuberculosis. However, a rapid scrutiny by genometric methods revealed a genome organization totally different from all so far sequenced high-GC Gram-positive chromosomes. RESULTS: Generally, the cumulative GC- and ORF orientation skew curves of prokaryotic genomes consist of two linear segments of opposite slope: the minimum and the maximum of the curves correspond to the origin and the terminus of chromosome replication, respectively. However, analyses of the B. longum NCC2705 chromosome yielded six, instead of two, linear segments, while its dnaA locus, usually associated with the origin of replication, was not located at the minimum of the curves. Furthermore, the coorientation of gene transcription with replication was very low. Comparison with closely related actinobacteria strongly suggested that the chromosome of B. longum was misassembled, and the identification of two pairs of relatively long homologous DNA sequences offers the possibility for an alternative genome assembly proposed here below. By genometric criteria, this configuration displays all of the characters common to bacteria, in particular to related high-GC Gram-positives. In addition, it is compatible with the partially sequenced genome of DJO10A B. longum strain. Recently, a corrected sequence of B. longum NCC2705, with a configuration similar to the one proposed here below, has been deposited in GenBank, confirming our predictions. CONCLUSION: Genometric analyses, in conjunction with standard bioinformatic tools and knowledge of bacterial chromosome architecture, represent fast and straightforward methods for the evaluation of chromosome assembly.

Pneumopathie interstitielle granulomato-lymphocytaire dans l'immunodéficience commune variable [Granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency].

Common variable immunodeficiency (CVID) is the most frequent primary immune deficiency. Recurrent infections are classical consequences of CVID, but their impact has been largely reduced by immunoglobulin replacement. CVID is also associated with various inflammatory and autoimmune manifestations resulting from abnormal cellular immunity. The lungs are especially affected by a recently described entity called granulomatous lymphocytic interstitial lung disease (GLILD). GLILD currently constitutes an important cause of morbidity and mortality in these patients. It is distinct from bronchiectasis secondary to recurrent infections, and presents similarities but also striking differences with sarcoidosis.

Essential role of platelet activation via protease activated receptor 4 in tissue factor-initiated inflammation.

INTRODUCTION: Tissue factor (TF) activation of the coagulation proteases enhances inflammation in animal models of arthritis and endotoxemia, but the mechanism of this effect is not yet fully understood - in particular, whether this is primarily due to fibrin formation or through activation of protease activated receptors (PARs). METHODS: We induced extravascular inflammation by injection of recombinant soluble murine TF (sTF1-219) in the hind paw. The effects of thrombin inhibition, fibrinogen and platelet depletion were evaluated, as well as the effects of PAR deficiency using knockout mice deficient for each of the PARs. RESULTS: Injection of soluble TF provoked a rapid onset of paw swelling. Inflammation was confirmed histologically and by increased serum IL-6 levels. Inflammation was significantly reduced by depletion of fibrinogen (P < 0.05) or platelets (P = 0.015), and by treatment with hirudin (P = 0.04) or an inhibitor of activated factor VII (P < 0.001) compared with controls. PAR-4-deficient mice exhibited significantly reduced paw swelling (P = 0.003). In contrast, a deficiency in either PAR-1, PAR-2 or PAR-3 did not affect the inflammatory response to soluble TF injection. CONCLUSION: Our results show that soluble TF induces acute inflammation through a thrombin-dependent pathway and both fibrin deposition and platelet activation are essential steps in this process. The activation of PAR-4 on platelets is crucial and the other PARs do not play a major role in soluble TF-induced inflammation.

Genetics of essential tremor.

Essential tremor (ET) is a prevalent condition manifesting with progressive action tremor. Although ET was traditionally viewed as a sporadic disease, a significant proportion of cases report a positive family history of tremor. Autosomal dominant inheritance can be demonstrated in many families. Previously, genome-wide linkage studies in families mapped three loci for ET, hereditary essential tremor-1 (ETM1), ETM2 and ETM3. However, no causal mutation has been replicated in candidate genes within these loci, including dopamine D3 receptor (DRD3) and HS1-binding protein 3 (HS1BP3). Recently, the first genome-wide association study in ET followed by replication studies conducted in diverse populations identified a significant association between the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) SNP rs9652490 and risk for ET Although further novel variants were indentified in LINGO1 and its paralog LINGO2 that may be associated with risk for ET, the pathogenic mechanisms involved remain elusive. Given the possibility that ET as a complex trait may be influenced by the combined effects of rare variants, novel high-throughput technologies sequencing all exons across the genome (exome sequencing) or the whole genome (genome sequencing) may become crucial in understanding/deciphering the genetic background of ET.

Informatics competencies essential to decision making in nursing management

Abstract OBJECTIVE To identify informatics abilities essential to decision making in nursing management. METHOD Survey study with specialist nurses in health informatics and management. An electronic questionnaire was built based on the competencies Information Literacy (five categories; 40 abilities) and Information Management (nine categories; 69 abilities) of the TIGER - Technology Informatics Guiding Education Reform - initiative, with the guiding question: Which informatics abilities are essential to decision making in management? Answers were sorted in a Likert scale, ranging from 1 to 5. Rasch analysis was conducted with the software WINSTEPS ®. Results were presented in logits, with cutoff value zero. RESULTS Thirty-two specialists participated, coming from all regions of Brazil. In the information literacy competency, 18 abilities were considered essential and in Information Management, 38; these were sorted according to their degree of essentiality. CONCLUSION It is believed that the incorporation of these abilities in teaching can support the education of nurse managers and contribute to evidence-based practice, incorporation of information and communication technologies in health and information management.

Lyfe-cycle effects on household expenditures: A latent-variable approach

Using data from the Spanish household budget survey, we investigate life-cycle effects on several product expenditures. A latent-variable model approach is adopted to evaluate the impact of income on expenditures, controlling for the number of members in the family. Two latent factors underlying repeated measures of monetary and non-monetary income are used as explanatory variables in the expenditure regression equations, thus avoiding possible bias associated to the measurement error in income. The proposed methodology also takes care of the case in which product expenditures exhibit a pattern of infrequent purchases. Multiple-group analysis is used to assess the variation of key parameters of the model across various household life-cycle typologies. The analysis discloses significant life-cycle effects on the mean levels of expenditures; it also detects significant life-cycle effects on the way expenditures are affected by income and family size. Asymptotic robust methods are used to account for possible non-normality of the data.

Perfil dos Turistas que Visitam a Ilha de São Vicente

O presente trabalho tem por objectivo definir o perfil do turista que visitou a ilha de São Vicente e avaliar o grau de satisfação do turista enquanto consumidor de diferentes bens e serviços, nos meses de Maio e Junho do decorrente ano. Para se fazer uma abordagem qualitativa falou-se da problemática do mercado turístico - procura e oferta turística – e a importância da segmentação desse sistema turístico juntamente com algumas teorias do comportamento do consumidor. Por sua vez, para o estudo do perfil e satisfação dos turistas utilizou-se uma abordagem quantitativa, através da aplicação de questionários no Aeroporto Internacional Cesária Évora e entrevistas aos estabelecimentos hoteleiros, 150 e 7 respectivamente. Após a análise explicativa, com base na bibliografia seleccionada, nas entrevistas e questionários realizados, os resultados da pesquisa indicam que estudar o perfil e a satisfação dos turistas permite fazer um levantamento de diversas variáveis importantes como, por exemplo, a nacionalidade do turista, a principal razão e objectivo da viagem e o que gostaram, ou desejavam ver no destino. E assim, entender-se o perfil do visitante e propor-se estratégias, que contribuam para um planeamento sustentável do desenvolvimento turístico na região pretendida. A complexidade do processo de decisão do turista por um ou outro destino é que verdadeiramente motiva esta pesquisa. The objective of the following work is to define the profile of a tourist that visited São Vicente, and evaluate the levels of satisfaction of the tourist as a consumer of different items and services, on May and June of the current year. For a quality methodological approach, the problematic of the touristic industry (demand and touristic offer) – the essential of subdivision of these touristic systems alongside with the principles of the consumer behavior were discussed. In continuity, to define the profile and satisfaction of the tourists, a quantity approach was also used, through the application of questionnaires at the International Airport Cesária Évora and interviews throughout hotel establishments, 150 and 7 respectively. After an explanatory analyses, based on a selected bibliography, the applied interviews and questionnaires, the outcome of this research shows that by studying the profile and the satisfaction of the tourists allows to have variable important results, for example, the tourist´s nationality, the main reason and objective of the trip and what they enjoyed or would like to see on their destination. Thus, understanding the visitor´s profile and suggesting strategies, that contributes for a sustainable planning of a touristic development on the intended region. The process complexity of the decision making of the tourist for one destination is truly the main motivation for this research.