Diagnostic accuracy of plasma NT-proBNP levels for excluding cardiac abnormalities in the very elderly

<p>Abstract</p> <p>Background</p> <p>In the elderly the diagnosis of chronic heart failure is often challenging and the availability of echocardiography can be limited. Plasma levels of NT-proBNP are valuable tools to diagnose patients with heart failure. However, the performance of this biomarker to detect cardiac abnormalities in the very elderly remains unclear. The aims of this study were to investigate the relation between NT-proBNP and cardiac abnormalities and to evaluate the use of NT-proBNP to exclude structural and functional cardiac abnormalities in a community-based sample of "well-functioning" nonagenarians.</p> <p>Methods</p> <p>A diagnostic cross-sectional study embedded within the Leiden 85-plus Study in the municipality of Leiden, the Netherlands. Plasma NT-proBNP levels were measured and 2-dimensional echocardiography was performed in a subgroup of 80 well-functioning nonagenarians. Linear regression analysis was used to explore the relation between NT-proBNP and cardiac abnormalities and ROC curve analysis was used to assess the performance of NT-proBNP to exclude cardiac abnormalities. The upper limit of the lowest tertile of NT-proBNP was used as a cut-off value.</p> <p>Results</p> <p>NT-proBNP levels were associated with abnormal left ventricular (LV) dimensions, LV systolic and diastolic function, left atrial enlargement and valvular heart disease. LV mass, E/A ratio and degree of aortic regurgitation were identified as independent predictors of NT-proBNP. NT-proBNP levels were higher with greater number of echocardiographic abnormalities (P < 0.001). A cut-off level of 269.5 pg/mL identified patients with abnormal LV dimensions or depressed LV systolic function (sensitivity 85%, negative predictive value (NPV) 77%, area under the curve 0.75 (95% CI 0.64-0.85)). In addition, high NPV were found for LV systolic dysfunction, left atrial enlargement, severe valvular heart disease and pulmonary hypertension. The test performance of NT-proBNP to exclude any echocardiographic abnormality showed a sensitivity of 82% and a NPV of 65%.</p> <p>Conclusions</p> <p>In this convenience sample of well-functioning nonagenarians NT-proBNP was related to a wide variety of functional and structural echocardiographic abnormalities. Moreover, NT-proBNP could be used to exclude echocardiographic abnormalities in well-functioning nonagenarians and might be used to indicate who needs to be referred for further cardiovascular examination.</p

Trees on networks: resolving statistical patterns of phylogenetic similarities among interacting proteins

<p>Abstract</p> <p>Background</p> <p>Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting genes or their protein products.</p> <p>Results</p> <p>We develop suitable statistical resampling schemes that can incorporate these two potential sources of correlation into a single inferential framework. To illustrate our approach we apply it to protein interaction data in yeast and investigate whether the phylogenetic trees of interacting proteins in a panel of yeast species are more similar than would be expected by chance.</p> <p>Conclusions</p> <p>While we find only negligible evidence for such increased levels of similarities, our statistical approach allows us to resolve the previously reported contradictory results on the levels of co-evolution induced by protein-protein interactions. We conclude with a discussion as to how we may employ the statistical framework developed here in further functional and evolutionary analyses of biological networks and systems.</p

Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma

Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we found sEGFR and EGF levels significantly lowered in patients with respect to healthy donors. In HNC patients, significantly diminished levels were found in the case of sEGFR, EGF and also AR. In both malignancies, no significant association was found between the serum levels of the molecules and the patients' gender, age or smoking habit. Only a significant association was found between the decrease of sEGFR and the absence of distant metastasis in NSCLC and the tumour stage in HNC. The most interesting result was that combining sEGFR and EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing specificity (97.8% in both cases). The use of discriminant analysis and logistic regression improved the sensitivity for NSCLC and the specificity for HNC. These data demonstrate a potentially interesting value of the serum levels of sEGFR and EGF, especially when combined, as markers for NSCLC and HNC

Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures

Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level

Defensive responses by a social caterpillar are tailored to different predators and change with larval instar and group size

Gregariousness in animals is widely accepted as a behavioral adaptation for protection from predation. However, predation risk and the effectiveness of a prey’s defense can be a function of several other factors, including predator species and prey size or age. The objective of this study was to determine if the gregarious habit of Malacosoma disstria caterpillars is advantageous against invertebrate natural enemies, and whether it is through dilution or cooperative defenses. We also examined the effects of larval growth and group size on the rate and success of attacks. Caterpillars of M. disstria responded with predator-specific behaviors, which led to increased survival. Evasive behaviors were used against stinkbugs, while thrashing by fourth instar caterpillars and holding on to the silk mat by second instar caterpillars was most efficient against spider attacks. Collective head flicking and biting by groups of both second and fourth instar caterpillars were observed when attacked by parasitoids. Increased larval size decreased the average number of attacks by spiders but increased the number of attacks by both stinkbugs and parasitoids. However, increased body size decreased the success rate of attacks by all three natural enemies and increased handling time for both predators. Larger group sizes did not influence the number of attacks from predators but increased the number of attacks and the number of successful attacks from parasitoids. In all cases, individual risk was lower in larger groups. Caterpillars showed collective defenses against parasitoids but not against the walking predators. These results show that caterpillars use different tactics against different natural enemies. Overall, these tactics are both more diverse and more effective in fourth instar than in second instar caterpillars, confirming that growth reduces predation risk. We also show that grouping benefits caterpillars through dilution of risk, and, in the case of parasitoids, through group defenses. The decreased tendency to aggregate in the last larval instar may therefore be linked to decreasing predation risk