Prognostic Implication of Physical Signs of Congestion in Acute Heart Failure Patients and Its Association with Steady-State Biomarker Levels

Background

Congestive physical findings such as pulmonary rales and third heart sound (S3) are hallmarks of acute heart failure (AHF). However, their role in outcome prediction remains unclear. We sought to investigate the association between congestive physical findings upon admission, steady-state biomarkers at the time of discharge, and long-term outcomes in AHF patients.

Methods

We analyzed the data of 133 consecutive AHF patients with an established diagnosis of ischemic or non-ischemic (dilated or hypertrophic) cardiomyopathy, admitted to a single-center university hospital between 2006 and 2010. The treating physician prospectively recorded major symptoms and congestive physical findings of AHF: paroxysmal nocturnal dyspnea, orthopnea, pulmonary rales, jugular venous distension (JVD), S3, and edema. The primary endpoint was defined as rehospitalization for HF.

Results

Majority (63.9%) of the patients had non-ischemic etiology and, at the time of admission, S3 was seen in 69.9% of the patients, JVD in 54.1%, and pulmonary rales in 43.6%. The mean follow-up period was 726 ± 31days. Patients with pulmonary rales (p < 0.001) and S3 (p  =  0.011) had worse readmission rates than those without these findings; the presence of these findings was also associated with elevated troponin T (TnT) levels at the time of discharge (odds ratio [OR] 2.8; p  =  0.02 and OR 2.6; p  =  0.05, respectively).

Conclusion

Pulmonary rales and S3 were associated with inferior readmission rates and elevated TnT levels on discharge. The worsening of the readmission rate owing to congestive physical findings may be a consequence of on-going myocardial injury.     

Reconstructing an ancestral genotype of two hexachlorocyclohexane-degrading Sphingobium species using metagenomic sequence data

Over the last 60 years, the use of hexachlorocyclohexane (HCH) as a pesticide has resulted in the production of >4 million tons of HCH waste, which has been dumped in open sinks across the globe. Here, the combination of the genomes of two genetic subspecies (Sphingobium japonicum UT26 and Sphingobium indicum B90A; isolated from two discrete geographical locations, Japan and India, respectively) capable of degrading HCH, with metagenomic data from an HCH dumpsite (∼450 mg HCH per g soil), enabled the reconstruction and validation of the last-common ancestor (LCA) genotype. Mapping the LCA genotype (3128 genes) to the subspecies genomes demonstrated that >20% of the genes in each subspecies were absent in the LCA. This includes two enzymes from the ‘upper'' HCH degradation pathway, suggesting that the ancestor was unable to degrade HCH isomers, but descendants acquired lin genes by transposon-mediated lateral gene transfer. In addition, anthranilate and homogentisate degradation traits were found to be strain (selectively retained only by UT26) and environment (absent in the LCA and subspecies, but prevalent in the metagenome) specific, respectively. One draft secondary chromosome, two near complete plasmids and eight complete lin transposons were assembled from the metagenomic DNA. Collectively, these results reinforce the elastic nature of the genus Sphingobium, and describe the evolutionary acquisition mechanism of a xenobiotic degradation phenotype in response to environmental pollution. This also demonstrates for the first time the use of metagenomic data in ancestral genotype reconstruction, highlighting its potential to provide significant insight into the development of such phenotypes.     

Absolute configuration and anticancer activity of taxiresinol and related lignans of Taxus wallichiana

Absolute configuration of taxiresinol 1, a lignan from the heartwood of Taxus wallichiana has been determined as 8R, 8'R, and 7'R with the help of chemical correlation method and X-ray crystallography. The anticancer activity of taxiresinol 1 and other two lignans 2, 3 were also studied. Taxiresinol 1 showed notable anticancer activity in the in vitro bioassays against colon, liver, ovarian and breast cancer cell lines.     

Purification and Characterization of a Lectin with High Hemagglutination Property Isolated from <Emphasis Type="Italic">Allium altaicum</Emphasis>

A lectin was purified from the leaves of Allium altaicum and corresponding gene was cloned. The lectin namely Allium altaicum agglutinin (AAA) was ~24 kDa homodimeric protein and similar to a typical garlic leaf lectin. It was synthesized as 177 amino acid residues pre-proprotein, which consisted of 28 and 43 amino acid long N and C-terminal signal peptides, respectively. The plant expressed this protein more in scapes and flowers in comparison to the bulbs and leaves. Hemagglutination activity (with rabbit erythrocytes) was 1,428 fold higher as compared to Allium sativum leaf agglutinin (ASAL) although, the insecticidal activity against cotton aphid (Aphis gossypii) was relatively low. Glycan array revealed that AAA had higher affinity towards GlcAb1-3Galb as compared to ASAL. Homology analysis showed 57–94% similarity with other Allium lectins. The mature protein was expressed in E. coli as a fusion with SUMO peptide in soluble and biologically active form. Recombinant protein retained high hemagglutination activity.     

High fat diet prevents over-crowding induced decrease of sex ratio in mice

Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. In the present study, we tested the effect of housing mice under crowded condition on the sex ratio and whether the fat content of the diet has any influence on the outcome of pregnancies. Three-week-old mice were placed on the control diet (NFD) for 3 weeks. Thereafter the mice were allotted randomly to two groups of 7 cages each with 4, 6, 8, 10, 12, 14, and 16 mice in every cage to create increasing crowding gradient and fed either NFD or high fat diet (HFD). After 4 weeks, dams were bred and outcomes of pregnancy were analyzed. The average dam body weight (DBW) at conception, litter size (LS) and SR were significantly higher in HFD fed dams. Further, male biased litters declined with increasing crowding in NFD group but not in HFD. The LS and SR in NFD declined significantly with increasing crowding, whereas only LS was reduced in HFD group. We conclude that female mice housed under overcrowding conditions shift offspring SR in favor of daughters in consistent with the TW hypothesis and high fat diet reduces this influence of overcrowding.     

Antimicrobial organophilic montmorillonite nanoparticles: screening and detection assay

The present study presents the development of a standard protocol for detection and screening of nanoparticle(s) for their antimicrobial activity with particular reference to organophilic montmorillonite (Ommt). For this purpose, Ommt nanoparticles have been synthesized through cation exchange of commercial montmorillonite (K10) with a cetyl pyridinium bromide. The formation of Ommt has been ascertained through UV-visible, Fourier transform infrared spectroscopy, X-ray diffraction spectra, and transmission electron microscopy. Subsequently, "zone of inhibition" and "bacterial killing" assays were performed by incubating the four Gram-negative test bacteria with Ommt, to determine antimicrobial activity and reduction in colony forming unit per mL (confirmative test), respectively. The developed assay will provide an easy approach over conventional disc diffusion antibiotic sensitivity test, to study the impact of different nanoparticles against different bacterial species.     

Arsenic (As) Inhibits Radicle Emergence and Elongation in <Emphasis Type="Italic">Phaseolus aureus</Emphasis> by Altering Starch-Metabolizing Enzymes Vis-à-Vis Disruption of Oxidative Metabolism

The present study investigated the effect of Arsenic (As; 5, 10, 50 μM) on protein and sugar metabolism vis-à-vis oxidative damage during early germination process and radicle emergence (at 12, 24 and 48 h stage) in Phaseolus aureus. As-exposure (50 μM) significantly enhanced protein content (by 40–60%), whereas carbohydrate content declined (by 31–44%) over that in the control. It was associated with a decline in the activities of proteases (47–53%), and increase in the activities of α- and β-amylases, starch phosphorylases, and acid invertases by 3.0, 2.6, 4.8, and 1.7 times after 48 h exposure to 50 μM As. The alteration in protein and carbohydrate metabolic machinery was also accompanied by As-induced reactive oxygen species (ROS)-mediated oxidative damage. As treatment enhanced malondialdehyde and hydrogen peroxide content by 46–252% and 23–216%, and hydroxyl and superoxide ion generation by 15–104% and 17–278%, respectively. As-induced lipid peroxidation and membrane disruption was confirmed by enhanced electrolyte leakage (by 49%) and reduced cell viability (by 43%). Furthermore, in response to 50 μM As, the activities of superoxide dismutases, catalases, ascorbate peroxidases, guaiacol peroxidases, and glutathione reductases increased by 77%, 70%, 116%, 43% and 120%, respectively, in radicles at 48 h stage over that in the control. The study concludes that As inhibits radicle emergence and elongation in germinating P. aureus seeds by altering biochemical processes related to sugar metabolism and inducing an ROS-mediated oxidative damage.