Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

BACKGROUND: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients. METHODS: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. RESULTS: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac. CONCLUSION: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs

A disk of dust and molecular gas around a high-mass protostar

The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (> 8 x Sun's mass) stars has heretofore remained poorly understood. Recent observational studies suggest that high-mass stars may form in essentially the same way as low-mass stars, namely via an accretion process, instead of via merging of several low-mass (< 8 Msun) stars. However, there is as yet no conclusive evidence. Here, we report the discovery of a flattened disk-like structure observed at submillimeter wavelengths, centered on a massive 15 Msun protostar in the Cepheus-A region. The disk, with a radius of about 330 astronomical units (AU) and a mass of 1 to 8 Msun, is detected in dust continuum as well as in molecular line emission. Its perpendicular orientation to, and spatial coincidence with the central embedded powerful bipolar radio jet, provides the best evidence yet that massive stars form via disk accretion in direct analogy to the formation of low-mass stars

COMPROMETIMENTO ORGANIZACIONAL E PROFISSIONAL DA EQUIPE DE SAÚDE

Scope of study: This research was carried out at a primary health care unit in Arequipa, Peru. Objective: To identify and analyze the organizational and professional commitment of workers in a primary health care team. Method: Case study involving 12 health professionals, in the light of Meyer and Allen’s theoretical model for Organizational and Professional Commitment, using semi structured interviews analyzed according to content analysis through subject matter. Results: The analysis led to the categorization by thematic groups on Affective, Instrumental and Normative bases. The first six were related to organizational commitment and the last four to professional commitment. Conclusions: We consider that commitment contributes to the identification of workers with their professional and organizational roles, showing greater motivation and, therefore, more involvement. Health organizations are expected to implement strategies and promote conditions that facilitate affective commitment in their employees. Campo de Estudio: La presente investigación fue realizada en un Servicio de Salud de Atención Primaria en Arequipa–Perú. Objetivo: identificar y analizar el compromiso organizacional y profesional de trabajadores que integran un equipo de atención primaria. Método: Estudio de caso realizado con 12 profesionales de salud, fundamentado en el modelo teórico de Meyer y Allen para el Compromiso Organizacional y Profesional, utilizando entrevistas semi-estructuradas analizadas según análisis de contenido por temática. Resultados: Del análisis resultó la categorización por núcleos temáticos en sus bases Afectiva, Instrumental y Normativa, siendo los seis primeros subtemas relacionados al compromiso organizacional y los cuatro últimos relacionados al compromiso profesional. Conclusiones: Comprendemos que el compromiso contribuye a que los trabajadores se identifiquen con sus roles profesionales y organizacionales, volviéndolos más motivados y por tanto más involucrados. Se espera que organizaciones de salud implementen estrategias y promuevan condiciones que favorezcan el compromiso afectivo entre sus empleados.  Campo do Estudo: A presente pesquisa foi realizada em uma Unidade de Atenção Primaria de Arequipa – Perú. Objetivo: identificar e analisar o comprometimento organizacional e profissional de trabalhadores que compõem una equipe de atenção primaria. Método: Estudo de caso realizado com 12 profissionais da saúde, à luz do modelo teórico de Meyer e Allen para o Comprometimento Organizacional e Profissional, utilizando entrevistas semi-estructuradas. Resultados: Da análise resultou a categorização por núcleos temáticos nas bases Afetiva, Instrumental e Normativa, os seis primeiros relacionados ao comprometimento organizacional, e os quatro últimos relacionados ao comprometimento profissional. Conclusões: Compreendemos que o comprometimento contribui na identificação dos seus trabalhadores com seus papeis profissionais e organizacionais, mostrando-se mais motivados, portanto, mais envolvidos. Espera-se que organizações de saúde implementem estratégias, e promovam condições que facilitem o comprometimento afetivo nos seus funcionário

INTERFAZ ENTRE COMPROMETIMENTO PROFISSIONAL E ORGANIZACIONAL: RECURSOS HUMANOS NO SETOR SAÚDE

El vínculo que el individuo establece con su organización es sumamente importante. Compromiso organizacional y profesional son focos a ser tratados como constructos multidimensionales, siendo importantes cuando son utilizados en forma conjunta al investigar un mismo objeto de estudio. De naturaleza exploratoria, el objetivo del presente estudio es analizar la relación de los compromisos organizacional y profesional de los trabajadores de la salud. Considerando que este vínculo puede tener importantes consecuencias para una organización que emplea profesionales, el gran vacio creado entre ambos constructos es algo que debe ser evaluado. Entender cómo se relacionan y cómo deben conciliarse estos dos compromisos es de especial importancia para la comprensión de los subsidios que estos puede traer para la organización y para la profesión. Los resultados muestran que estudios sobre compromiso en el trabajo dentro del sector salud son necesarios una vez que contribuyen a la comprensión de actitudes y comportamientos de los actores en el aspecto profesional y organizacional.O vínculo que o indivíduo desenvolve com a sua organização é sumamente importante. Comprometimento organizacional e comprometimento profissional são focos a serem tratados como construtos multidimensionais, sendo importantes quando utilizados conjuntamente na investigação de um mesmo objeto de estudo. De natureza exploratória, o objetivo do presente estudo é analisar a relação dos comprometimentos organizacional e profissional de trabalhadores da saúde. Considerando que este vínculo pode ter importantes conseqüências para uma organização que emprega profissionais, a grande brecha criada entre ambos os construtos é um fato que tem que ser avaliado. Entender como se relacionam e como devem ser conciliados esses dois comprometimentos é essencial para a compreensão dos subsídios que eles trazem para a organização e para a profissão. Os resultados encontrados mostram que estudos sobre comprometimento no trabalho no setor saúde são necessários uma vez que contribuem para o entendimento de atitudes e comportamentos dos atores face à profissão e à organização

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Generation of genipin cross-linked fibrin-agarose hydrogel tissue-like models for tissue engineering applications

Generation of biomimetic and biocompatible artificial tissues is the basic research objective for tissue engineering (TE). In this sense, the biofabrication of scaffolds that resemble the tissues’ extracellular matrix (ECM) is an essential aim in this field. Uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH respectively) emerged as promising scaffold in TE, but its structure and biomechanical properties must be improved in order to broad their TE applications. Here we generated and characterized novel membranelike models with increased structural and biomechanical properties based on the chemical cross-linking of FAH and NFAH with genipin (GP at 0.1, 0.25, 0.5 and 0.75%). Furthermore, scaffolds were subjected to rheological (G, G’, G” modulus), ultrastructural and ex vivo biocompatibility analyses. Results showed that all GP concentrations increased the stiffness (G) and especially the elasticity (G’) of FAH and NFAH. Ultrastructural analyses demonstrated that GP and nanostructuration of FAH allowed controlling the porosity of FAH. In addition, biological studies revealed that higher concentration of GP significantly decreased the cell viability. Finally, this study demonstrated the possibility to generate natural FAH and NFAH with improved structural and biomechanical properties by using GP. However, further in vivo studies are needed in order to demonstrate the biocompatibility, biodegradability and regeneration capability of these cross-linked scaffolds

A remarkable recurrent nova in M31: Discovery and optical/UV observations of the predicted 2014 eruption

The Andromeda Galaxy recurrent nova M31N 2008-12a had been caught in eruption eight times. The inter-eruption period of M31N 2008-12a is ~1 year, making it the most rapidly recurring system known, and a strong single-degenerate Type Ia Supernova progenitor candidate. Following the 2013 eruption, a campaign was initiated to detect the predicted 2014 eruption and to then perform high cadence optical photometric and spectroscopic monitoring using ground-based telescopes, along with rapid UV and X-ray follow-up with the Swift satellite. Here we report the results of a high cadence multicolour optical monitoring campaign, the spectroscopic evolution, and the UV photometry. We also discuss tantalising evidence of a potentially related, vastly-extended, nebulosity. The 2014 eruption was discovered, before optical maximum, on October 2, 2014. We find that the optical properties of M31N 2008-12a evolve faster than all Galactic recurrent novae known, and all its eruptions show remarkable similarity both photometrically and spectroscopically. Optical spectra were obtained as early as 0.26 days post maximum, and again confirm the nova nature of the eruption. A significant deceleration of the inferred ejecta expansion velocity is observed which may be caused by interaction of the ejecta with surrounding material, possibly a red giant wind. We find a low ejected mass and low ejection velocity, which are consistent with high mass-accretion rate, high mass white dwarf, and short recurrence time models of novae. We encourage additional observations, especially around the predicted time of the next eruption, towards the end of 2015

Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

<p>Abstract</p> <p>Background</p> <p>Paroxysms are recurrent febrile episodes, characteristic of <it>Plasmodium vivax </it>infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes <it>in vitro </it>in the presence of parasite and host factors released during paroxysms.</p> <p>Methods</p> <p>Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms.</p> <p>Results</p> <p>Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute <it>P. vivax </it>infections was neutralized by immune sera raised against schizont extracts of either <it>P. vivax </it>or <it>Plasmodium falciparum</it>. However, immune sera against <it>P. vivax </it>were more effective than that against <it>P. falciparum </it>indicating that the parasite activity involved may be antigenically at least partially parasite species-specific.</p> <p>Conclusion</p> <p>Leukocyte aggregation was identified as associated with paroxysms in <it>P. vivax </it>infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of <it>P. vivax </it>malaria.</p

Investigating the coenzyme specificity of phenylacetone monooxygenase from Thermobifida fusca

Type I Baeyer–Villiger monooxygenases (BVMOs) strongly prefer NADPH over NADH as an electron donor. In order to elucidate the molecular basis for this coenzyme specificity, we have performed a site-directed mutagenesis study on phenylacetone monooxygenase (PAMO) from Thermobifida fusca. Using sequence alignments of type I BVMOs and crystal structures of PAMO and cyclohexanone monooxygenase in complex with NADP+, we identified four residues that could interact with the 2′-phosphate moiety of NADPH in PAMO. The mutagenesis study revealed that the conserved R217 is essential for binding the adenine moiety of the nicotinamide coenzyme while it also contributes to the recognition of the 2′-phosphate moiety of NADPH. The substitution of T218 did not have a strong effect on the coenzyme specificity. The H220N and H220Q mutants exhibited a ~3-fold improvement in the catalytic efficiency with NADH while the catalytic efficiency with NADPH was hardly affected. Mutating K336 did not increase the activity of PAMO with NADH, but it had a significant and beneficial effect on the enantioselectivity of Baeyer–Villiger oxidations and sulfoxidations. In conclusion, our results indicate that the function of NADPH in catalysis cannot be easily replaced by NADH. This finding is in line with the complex catalytic mechanism and the vital role of the coenzyme in BVMOs