Clinical applications of B-type natriuretic peptide (BNP) testing

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a ‘rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the ‘normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical contex

Plant height and hydraulic vulnerability to drought and cold

Understanding how plants survive drought and cold is increasingly important as plants worldwide experience dieback with drought in moist places and grow taller with warming in cold ones. Crucial in plant climate adaptation are the diameters of water-transporting conduits. Sampling 537 species across climate zones dominated by angiosperms, we find that plant size is unambiguously the main driver of conduit diameter variation. And because taller plants have wider conduits, and wider conduits within species are more vulnerable to conduction-blocking embolisms, taller conspecifics should be more vulnerable than shorter ones, a prediction we confirm with a plantation experiment. As a result, maximum plant size should be short under drought and cold, which cause embolism, or increase if these pressures relax. That conduit diameter and embolism vulnerability are inseparably related to plant size helps explain why factors that interact with conduit diameter, such as drought or warming, are altering plant heights worldwide

Magnetic phases of the quasi-two-dimensional compounds FexCo1 - xTa2O6

International audienceWe report new results on the magnetic properties of the FexCo1 - xTa2O6 series of compounds. Essentially using neutron-diffraction and magnetic measurements we study, in more detail, the low-x limit of the temperature versus x phase diagram, where a new bicritical point is observed. The complete phase diagram shows three different magnetic phases at low temperature, for a high, intermediate and very low iron content. These phases consist of distinct antiferromagnetic orderings, characterized by different pairs of propagation vectors. We obtain information about the intraplane exchange interactions by fitting a high-temperature series of the magnetic susceptibility. Here we improve on a previously employed model, showing that two non-equivalent next-nearest-neighbor interactions must be taken into account in order to allow for in-plane magnetic orderings that are consistent with the neutron-diffraction results

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

EFFECT OF STARTING POWDER PREMIXING ON THE INTERPHASE EXCHANGE COUPLING IN Nd₂Fe₁₄B + 10 WT % Fe NANOCOMPOSITES OBTAINED TROUGH MECHANICAL MILLING

In the frame of optimizing the potential, of had /soft nanocomposites for high performance applications, we report on the effect of starting powder premixing on the structure, microstructure and exchange coupling in hard/soft magnetic phases. Nd2Fe14B powder was first mixed with Fe powder using two different means: by hand or by using a Turbula Mixer. Moreover, in the hand mixed powders the Fe particle size was changed from 100 to 1 μm, while the samples mixed using the Turbula Mixer contained only Fe particles of around 1 μm in size. The mixed powders were subsequently milled for 6 hours in a planetary ball mill; the calculated impact energy was 77 mJ/impact and 10 kJ/g for the entire duration of process. Good exchange coupling was obtained in all three cases. The samples prepared with Fe < 1 μm particles yielding slightly better results due to better dispersion of the two phases in the final nanocomposite material. The highest energy product was achieved for the sample premixed with the Turbula Mixer ((BH)max=125 kJ/m3) after being annealed at 800 °C for 1.5 min

Global diversification of a tropical plant growth form: environmental correlates and historical contingencies in climbing palms

Tropical rain forests (TRF) are the most diverse terrestrial biome on Earth, but the diversification dynamics of their constituent growth forms remain largely unexplored. Climbing plants contribute significantly to species diversity and ecosystem processes in TRF. We investigate the broad-scale patterns and drivers of species richness as well as the diversification history of climbing and non-climbing palms (Arecaceae). We quantify to what extent macroecological diversity patterns are related to contemporary climate, forest canopy height and paleoclimatic changes. We test whether diversification rates are higher for climbing than non-climbing palms and estimate the origin of the climbing habit. Climbers account for 22% of global palm species diversity mostly concentrated in Southeast Asia. Global variation in climbing palm species richness can be partly explained by past and present-day climate and rain forest canopy height, but regional differences in residual species richness after accounting for current and past differences in environment suggest a strong role of historical contingencies in climbing palm diversification. Climbing palms show a higher net diversification rate than non-climbers. Diversification analysis of palms detected a diversification rate increase along the branches leading to the most species-rich clade of climbers. Ancestral character reconstructions revealed that the climbing habit originated between early Eocene and Miocene. These results imply that changes from non-climbing to climbing habit may have played an important role in palm diversification, resulting in the origin of one fifth of all palm species. We suggest that, in addition to current climate and paleoclimatic changes after the late Neogene, present-day diversity of climbing palms can be explained by morpho-anatomical innovations, the biogeographic history of Southeast Asia, and/or ecological opportunities due to the diversification of high-stature dipterocarps in Asian TRFs

STRUCTURAL, MAGNETIC AND ELECTRONIC PROPERTIES OF THE INTERMETALLIC COMPOUNDS FROM THE TERNARY SYSTEM Ce – Co – Mn

XRD, magnetic and XPS measurements of the three classes of intermetallic compounds with different crystallographic structures are reported. XPS spectra of Ce2Co15Mn3, CeCo7Mn5 and CeCo8Mn4 compounds pointed out the intermediate valence state of Ce atoms and that both Co and Mn atoms carry magnetic moments. The complex magnetic structure is determined by the competition between the ferromagnetic (Co–Co pairs) and antiferromagnetic (Co–Mn and Mn–Mn pairs) interactions. In CeCoMn, Ce3Co3Mn4 and Ce3Co6Mn compounds both Ce and Co atoms are non-magnetic like in the isostructural compound CeCo2. Magnetic behavior is mostly due to the Mn moments and depends essentially on the Mn - Mn distances

Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans

Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the DeltagprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the DeltagprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the DeltagprB and DeltagprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in DeltagprB, while in the DeltagprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the DeltagprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the DeltagprD strain, compared to the wild-type and DeltagprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited.220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP.This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients