Uric Acid as a Risk Factor for Cardiovascular Disease and Mortality in Overweight/Obese Individuals

Background

The predictive value of serum uric acid (SUA) for adverse cardiovascular events among obese and overweight patients is not known, but potentially important because of the relation between hyperuricaemia and obesity.

Methods

The relationship between SUA and risk of cardiovascular adverse outcomes (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality, respectively, was evaluated in a post-hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Participants enrolled in SCOUT were obese or overweight with pre-existing diabetes and/or cardiovascular disease (CVD). Cox models were used to assess the role of SUA as an independent risk factor.

Results

9742 subjects were included in the study; 83.6% had diabetes, and 75.1% had CVD. During an average follow-up time of 4.2 years, 1043 subjects had a primary outcome (myocardial infarction, resuscitated cardiac arrest, stroke, or cardiovascular death), and 816 died. In a univariate Cox model, the highest SUA quartile was associated with an increased risk of cardiovascular adverse outcomes compared with the lowest SUA quartile in women (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.20–2.10). In multivariate analyses, adjusting for known cardiovascular risk factors the increased risk for the highest SUA quartile was no longer statistically significant among women (HR: 0.99; 95% CI: 0.72–1.36) nor was it among men. Analyses of all-cause mortality found an interaction between sex and SUA. In a multivariate Cox model including women only, the highest SUA quartile was associated with an increased risk in all-cause mortality compared to the lowest SUA quartile (HR: 1.51; 95% CI: 1.08–2.12). No relationship was observed in men (HR: 1.06; 95% CI: 0.82–1.36).

Conclusion

SUA was not an independent predictor of cardiovascular disease and death in these high-risk overweight/obese people. However, our results suggested that SUA was an independent predictor of all-cause mortality in women.     

Diversity of Cacao Trees in Waslala,Nicaragua: Associations between Genotype Spectra,Product Quality and Yield Potential

The sensory quality and the contents of quality-determining chemical compounds in unfermented and fermented cocoa from 100 cacao trees (individual genotypes) representing groups of nine genotype spectra (GG), grown at smallholder plantings in the municipality of Waslala, Nicaragua, were evaluated for two successive harvest periods. Cocoa samples were fermented using a technique mimicking recommended on-farm practices. The sensory cocoa quality was assessed by experienced tasters, and seven major chemical taste compounds were quantified by near infrared spectrometry (NIRS). The association of the nine, partially admixed, genotype spectra with the analytical and sensory quality parameters was tested. The individual parameters were analyzed as a function of the factors GG and harvest (including the date of fermentation), individual trees within a single GG were used as replications. In fermented cocoa, significant GG-specific differences were observed for methylxanthines, theobromine-to-caffeine (T/C) ratio, total fat, procyanidin B5 and epicatechin, as well as the sensory attributes global score, astringency, and dry fruit aroma, but differences related to harvest were also apparent. The potential cocoa yield was also highly determined by the individual GG, although there was significant tree-to-tree variation within every single GG. Non-fermented samples showed large harvest-to-harvest variation of their chemical composition, while differences between GG were insignificant. These results suggest that selection by the genetic background, represented here by groups of partially admixed genotype spectra, would be a useful strategy toward enhancing quality and yield of cocoa in Nicaragua. Selection by the GG within the local, genetically segregating populations of seed-propagated cacao, followed by clonal propagation of best-performing individuals of the selected GG could be a viable alternative to traditional propagation of cacao by seed from open pollination. Fast and gentle air-drying of the fermented beans and their permanent dry storage were an efficient and comparatively easy precondition for high cocoa quality.     

Viability Is Associated with Melanin-Based Coloration in the Barn Swallow (Hirundo rustica)

Pigmentation of body surface in animals can have multiple determinants and accomplish diverse functions. Eumelanin and pheomelanin are the main animal pigments, being responsible of yellow, brownish-red and black hues, and have partly common biosynthetic pathways. Many populations of vertebrates show individual variation in melanism, putatively with large heritable component. Genes responsible for eu- or pheomelanogenesis have pleiotropic but contrasting effects on life-history traits, explaining the patterns of covariation observed between melanization and physiology (e.g. immunity and stress response), sexual behavior and other characters in diverse taxa. Yet, very few studies in the wild have investigated if eu- and pheomelanization predict major fitness traits like viability or fecundity. In this correlative study, by contrasting adult barn swallows (Hirundo rustica) matched for age, sex, breeding site, and year and date of sampling, we show that males but not females that survived until the next year had paler, relatively more eu- than pheomelanic pigmentation of ventral body feathers. Better performance of individuals that allocate relatively more to eumelanogenesis was expected based on previous evidence on covariation between eumelanic pigmentation and specific traits related to immunity and susceptibility to stress. However, together with the evidence of no covariation between viability and melanization among females, this finding raises the question of the mechanisms that maintain variation in genes for melanogenesis. We discuss the possibility that eu- and pheomelanization are under contrasting viability and sexual selection, as suggested by larger breeding and sperm competition success of darker males from other barn swallow subspecies.     

Compound Ex Vivo and In Silico Method for Hemodynamic Analysis of Stented Arteries

Hemodynamic factors such as low wall shear stress have been shown to influence endothelial healing and atherogenesis in stent-free vessels. However, in stented vessels, a reliable quantitative analysis of such relations has not been possible due to the lack of a suitable method for the accurate acquisition of blood flow. The objective of this work was to develop a method for the precise reconstruction of hemodynamics and quantification of wall shear stress in stented vessels. We have developed such a method that can be applied to vessels stented in or ex vivo and processed ex vivo. Here we stented the coronary arteries of ex vivo porcine hearts, performed vascular corrosion casting, acquired the vessel geometry using micro-computed tomography and reconstructed blood flow and shear stress using computational fluid dynamics. The method yields accurate local flow information through anatomic fidelity, capturing in detail the stent geometry, arterial tissue prolapse, radial and axial arterial deformation as well as strut malapposition. This novel compound method may serve as a unique tool for spatially resolved analysis of the relationship between hemodynamic factors and vascular biology. It can further be employed to optimize stent design and stenting strategies.     

Global environmental changes: setting priorities for Latin American coastal habitats

As the effects of the Global Climate Changes on the costal regions of Central and South Americas advance, there is proportionally little research being made to understand such impacts. This commentary puts forward a series of propositions of strategies to improve performance of Central and South American science and policy making in order to cope with the future impacts of the Global Climate Changes in their coastal habitats.     

Poly(HEMA) brushes emerging as a new platform for direct detection of food pathogen in milk samples

Surface plasmon resonance (SPR) biosensors capable of in real time detection of Cronobacter at concentrations down to 10? cells mL?1 in samples of consumer fresh-whole fat milk, powder whole-fat milk preparation, and powder infant formulation were developed for the first time. Antibodies against Cronobacter were covalently attached onto polymer brushes of poly(2-hydroxyethyl methacrylate) (poly(HEMA)) grafted from the SPR chip surface. The lowest detection limit, 10? cells mL?1, was achieved in phosphate buffered saline (pH 7.4) with sensors prepared by covalent immobilization of the same antibodies onto a self assembled monolayer (SAM) of hexa(ethylene glycol) undecanethiol (EG?). However, when the EG? based sensors were challenged with milk samples the non-specific response due to the deposition of non-targeted compounds from the milk samples was much higher than the specific response to Cronobacter hampering the detection in milk. Similar interfering fouling was observed on antifouling polymer brushes of hydroxy-capped oligoethylene glycol methacrylate and even a 10 times higher fouling was observed on the widely used SAM of mixed hydroxy- and carboxy-terminated alkanethiols. Only poly(HEMA) brushes totally suppressed the fouling from milk samples. The robust well-controlled surface initiated atom transfer radical polymerization of HEMA allowed the preparation of highly dense brushes with a minimal thickness so that the capture of antigens by the antibodies immobilized on the brush layer could take place close to the gold SPR surface to provide a stronger optical response while the fouling was still suppressed. A minimum thickness of 19 nm of poly(HEMA) brush layer was necessary to suppress completely non-specific sensor response to fouling from milk.     

Acetylcholine binding protein (AChBP) as template for hierarchical in silico screening procedures to identify structurally novel ligands for the nicotinic receptors

Hierarchical in silico screening protocols against the agonist bound acetylcholine binding protein (AChBP) crystal structure were efficient in identifying novel chemotypes for AChBP and the human α7 receptor. Two hit structures were cocrystallized with AChBP revealing intermolecular cation-π interactions with loop C but lacking intermolecular hydrogen bonding. The compounds act as competitive α7 receptor antagonists and as non-competitive α4β2 receptor inhibitors. These results underline the usability of AChBP in structure-based in silico screening strategies in finding novel scaffolds for the α7 receptor, but also illustrates some limitations of using AChBP as bait to find competitive α4β2 receptor ligands and α7 receptor agonists.     

Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

Background

Patients with Adult Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover.

Objectives

To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls).

Methods

²H₂O as precursor of disaturated-phosphatidylcholine-palmitate and 1¹³C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the ²H and ¹³C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured.

Results

1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p < 0.01), while the fractional synthesis rate of surfactant protein-B was not different. 3) In ARDS/ALI patients the concentrations of disaturated-phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively).

Conclusions

1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.