Association of Obesity With Severity of Heart Failure Exacerbation: A Population‐Based Study

Background: Obesity and heart failure (HF) are important public health problems in the United States. Although studies have reported the association between obesity and higher chronic morbidity of HF, little is known about the relations of obesity with severity of HF exacerbation and in‐hospital mortality; therefore, we aimed to investigate the associations of obesity with severity of HF exacerbation and in‐hospital mortality. Methods and Results: This retrospective cohort study of adults hospitalized for HF exacerbation used population‐based data sets (the State Inpatient Databases) of 7 US states from 2012 to 2013. The outcomes were acute severity measures—use of positive pressure ventilation and hospital length of stay—and in‐hospital mortality. We determined the associations between obesity and these outcomes, including adjustment for sociodemographic factors and comorbidities. We identified 219 465 patients hospitalized for HF exacerbation. Of those, 37 539 (17.1%) were obese. Obese patients had a significantly higher risk of positive pressure ventilation use compared with nonobese patients (13.6% versus 8.8%), with a corresponding adjusted odds ratio of 1.61 (95% confidence interval, 1.55–1.68; P<0.001). Likewise, obese patients were more likely to have hospital length of stay of ≥4 days compared with nonobese patients (62.5% versus 56.7%), with an adjusted odds ratio of 1.40 (95% confidence interval, 1.37–1.44; P<0.001). In contrast, obese patients had significantly lower in‐hospital mortality compared with nonobese patients (1.7% versus 3.3%), with an adjusted odds ratio of 0.87 (95% confidence interval, 0.80–0.95; P=0.002). Conclusions: Based on large population‐based data sets of patients with HF exacerbation, obesity was associated with higher acute severity measures but lower in‐hospital mortality

A deeply branching thermophilic bacterium with an ancient acetyl-CoA pathway dominates a subsurface ecosystem

<div><p>A nearly complete genome sequence of <em>Candidatus</em> ‘Acetothermum autotrophicum’, a presently uncultivated bacterium in candidate division OP1, was revealed by metagenomic analysis of a subsurface thermophilic microbial mat community. Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that <em>Ca.</em> ‘A. autotrophicum’ is one of the earliest diverging bacterial lineages. It possesses a folate-dependent Wood-Ljungdahl (acetyl-CoA) pathway of CO₂ fixation, is predicted to have an acetogenic lifestyle, and possesses the newly discovered archaeal-autotrophic type of bifunctional fructose 1,6-bisphosphate aldolase/phosphatase. A phylogenetic analysis of the core gene cluster of the acethyl-CoA pathway, shared by acetogens, methanogens, some sulfur- and iron-reducers and dechlorinators, supports the hypothesis that the core gene cluster of <em>Ca.</em> ‘A. autotrophicum’ is a particularly ancient bacterial pathway. The habitat, physiology and phylogenetic position of <em>Ca.</em> ‘A. autotrophicum’ support the view that the first bacterial and archaeal lineages were H₂-dependent acetogens and methanogenes living in hydrothermal environments.</p> </div

Neointimal characteristics comparison between biodegradable-polymer and durable-polymer drug-eluting stents: 3-month follow-up optical coherence tomography light property analysis from the RESTORE registry

We aimed to quantitatively assess a possible difference of the neointimal quality between biodegradable polymer- (BP-) and durable polymer drug-eluting stents (DP-DESs). We conducted a single-center all-comer prospective cohort study: the RESTORE registry (UMIN000033009). All patients who received successful OCT examination at planned 3-month follow-up after DES implantation were analyzed. Study population was divided into 2 groups, BP-DES versus DP-DES groups. We evaluated standard OCT variables, coverage percent, and the quantitative light property values including light intensity, attenuation, and backscatter. We performed OCT analyses of 121 lesions in 98 patients (BP-DES 55 lesions in 51 patients vs. DP-DES 66 lesions in DP-DES 53 patients). Lesion and procedural characteristics were overall well-balanced between both groups. At 3-month follow-up, neointimal thickness (BP-DES 49.3 [38.2, 57.7] µm versus DP-DES 54.7 [45.1, 70.7] µm, p = 0.059) and coverage percent (BP-DES 94.5 [89.8, 97.0]% vs. DP-DES 95.8 [91.1, 98.1]%, p = 0.083) did not significantly differ. Light intensity of superficial neointima in the BP-DES was lower than that in the DP-DES, whereas that of deep neointima did not differ between both groups

Transient Receptor Potential (TRP) and Cch1-Yam8 Channels Play Key Roles in the Regulation of Cytoplasmic Ca2+ in Fission Yeast

The regulation of cytoplasmic Ca2+ is crucial for various cellular processes. Here, we examined the cytoplasmic Ca2+ levels in living fission yeast cells by a highly sensitive bioluminescence resonance energy transfer-based assay using GFP-aequorin fusion protein linked by 19 amino acid. We monitored the cytoplasmic Ca2+ level and its change caused by extracellular stimulants such as CaCl2 or NaCl plus FK506 (calcineurin inhibitor). We found that the extracellularly added Ca2+ caused a dose-dependent increase in the cytoplasmic Ca2+ level and resulted in a burst-like peak. The overexpression of two transient receptor potential (TRP) channel homologues, Trp1322 or Pkd2, markedly enhanced this response. Interestingly, the burst-like peak upon TRP overexpression was completely abolished by gene deletion of calcineurin and was dramatically decreased by gene deletion of Prz1, a downstream transcription factor activated by calcineurin. Furthermore, 1 hour treatment with FK506 failed to suppress the burst-like peak. These results suggest that the burst-like Ca2+ peak is dependent on the transcriptional activity of Prz1, but not on the direct TRP dephosphorylation. We also found that extracellularly added NaCl plus FK506 caused a synergistic cytosolic Ca2+ increase that is dependent on the inhibition of calcineurin activity, but not on the inhibition of Prz1. The synergistic Ca2+ increase is abolished by the addition of the Ca2+ chelator BAPTA into the media, and is also abolished by deletion of the gene encoding a subunit of the Cch1-Yam8 Ca2+ channel complex, indicating that the synergistic increase is caused by the Ca2+ influx from the extracellular medium via the Cch1-Yam8 complex. Furthermore, deletion of Pmk1 MAPK abolished the Ca2+ influx, and overexpression of the constitutively active Pek1 MAPKK enhanced the influx. These results suggest that Pmk1 MAPK and calcineurin positively and negatively regulate the Cch1-Yam8 complex, respectively, via modulating the balance between phosphorylation and dyphosphorylation state

Axenic culture of Brachionus plicatilis using antibiotics

The rotifer Brachionus plicatilis culture is composed of complex microcosms including bacteria, protozoans, algae, and fungi. Previous studies reported methods to establish axenic rotifer cultures, but further refinement of these techniques is needed, for molecular biological research which requires pure culture to isolate nucleic acids from rotifers only. In order to render rotifer culture axenic, we tested five antibiotics: ampicillin (Amp), chloramphenicol (Cp), kanamycin (Km), nalidixic acid (Na), and streptomycin (Sm) at 30-100 μg/ml. Except for Cp, which reduces rotifer reproduction, all other antibiotics at the tested concentrations did not affect rotifer reproduction or show any toxic effects. A rotifer disinfection method was finally established by treating the resting eggs with 0.25% (w/v) sodium hypochlorite (NaOCl) for 3 min, washing with sterilized sea water, and then exposing the neonates to an Amp, Km, Na, and Sm mixture. Using four nutrient media, we confirmed that this protocol renders the rotifer culture bacterial and fungus free. The axenic rotifer culture generated here is useful not only for genetic analysis of Brachionus plicatilis, but for studying the rotifer life cycle without bacterial influence

Analysis of Expressed Sequence Tags of the Cyclically Parthenogenetic Rotifer Brachionus plicatilis

Background. Rotifers are among the most common non-arthropod animals and are the most experimentally tractable members of the basal assemblage of metazoan phyla known as Gnathifera. The monogonont rotifer Brachionus plicatilis is a developing model system for ecotoxicology, aquatic ecology, cryptic speciation, and the evolution of sex, and is an important food source for finfish aquaculture. However, basic knowledge of the genome and transcriptome of any rotifer species has been lacking. Methodology/Principal Findings. We generated and partially sequenced a cDNA library from B. plicatilis and constructed a database of over 2300 expressed sequence tags corresponding to more than 450 transcripts. About 20% of the transcripts had no significant similarity to database sequences by BLAST; most of these contained open reading frames of significant length but few had recognized Pfam motifs. Sixteen transcripts accounted for 25% of the ESTs; four of these had no significant similarity to BLAST or Pfam databases. Putative up- and downstream untranslated regions are relatively short and AT rich. In contrast to bdelloid rotifers, there was no evidence of a conserved trans-spliced leader sequence among the transcripts and most genes were single-copy. Conclusions/Significance. Despite the small size of this EST project it revealed several important features of the rotifer transcriptome and of individual monogonont genes. Because there is little genomic data for Gnathifera, the transcripts we found with no known function may represent genes that are species-, class-, phylum- or even superphylum-specific; the fact that some are among the most highly expressed indicates their importance. The absence of trans-spliced leader exons in this monogonont species contrasts with their abundance in bdelloid rotifers and indicates that the presence of this phenomenon can vary at the subphylum level. Our EST database provides a relatively large quantity of transcript-level data for B. plicatilis, and more generally of rotifers and other gnathiferan phyla, and can be browsed and searched at gmod.mbl.edu

2008 Inter-laboratory Comparison Study of a Reference Material for Nutrients in Seawater

Autoclaved natural seawater collected in the North Pacific Ocean was used as a reference material for nutrients in seawater (RMNS) during an inter-laboratory comparison (I/C) study conducted in 2008. This study was a follow-up to previous studies conducted in 2003 and 2006. A set of six samples was distributed to each of 58 laboratories in 15 countries around the globe, and results were returned by 54 of those laboratories (15 countries). The homogeneities of samples used in the 2008 I/C study, based on analyses for three determinants, were improved compared to those of samples used in the 2003 and 2006 I/C studies. Results of these I/C studies indicate that most of the participating laboratories have an analytical technique for nutrients that is sufficient to provide data of high comparability. The differences between reported concentrations from the same laboratories in the 2006 and 2008 I/C studies for the same batch of RMNS indicate that most of the laboratories have been maintaining internal comparability for two years. Thus, with the current high level of performance in the participating laboratories, the use of a common reference material and the adaptation of an internationally accepted nutrient scale system would increase comparability among laboratories worldwide, and the use of a certified reference material would establish traceability. In the 2008 I/C study we observed a problem of non-linearity of the instruments of the participating laboratories similar to that observed among the laboratories in the 2006 I/C study. This problem of non-linearity should be investigated and discussed to improve comparability for the full range of nutrient concentrations. For silicate comparability in particular, we see relatively larger consensus standard deviations than those for nitrate and phosphate

Attentional Set-Shifting Deficit in Parkinson’s Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study

The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients