Quantifying the Area at Risk in Reperfused ST-Segment-Elevation Myocardial Infarction Patients Using Hybrid Cardiac Positron Emission Tomography-Magnetic Resonance Imaging

BACKGROUND: Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients. METHODS AND RESULTS: Hybrid positron emission tomography and magnetic resonance using (18)F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. CONCLUSIONS: Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments

Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial

Background: Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. Methods: STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. Results: Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: −12.2 (95% CI −20.3 to −4.4)%, P = .003) and LVESV (mean difference: −18.2 (95% CI −30.1 to −6.3)%, P = .003). Conclusion: This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings

Optimal assignment methods for ligand-based virtual screening

<p>Abstract</p> <p>Background</p> <p>Ligand-based virtual screening experiments are an important task in the early drug discovery stage. An ambitious aim in each experiment is to disclose active structures based on new scaffolds. To perform these "scaffold-hoppings" for individual problems and targets, a plethora of different similarity methods based on diverse techniques were published in the last years. The optimal assignment approach on molecular graphs, a successful method in the field of quantitative structure-activity relationships, has not been tested as a ligand-based virtual screening method so far.</p> <p>Results</p> <p>We evaluated two already published and two new optimal assignment methods on various data sets. To emphasize the "scaffold-hopping" ability, we used the information of chemotype clustering analyses in our evaluation metrics. Comparisons with literature results show an improved early recognition performance and comparable results over the complete data set. A new method based on two different assignment steps shows an increased "scaffold-hopping" behavior together with a good early recognition performance.</p> <p>Conclusion</p> <p>The presented methods show a good combination of chemotype discovery and enrichment of active structures. Additionally, the optimal assignment on molecular graphs has the advantage to investigate and interpret the mappings, allowing precise modifications of internal parameters of the similarity measure for specific targets. All methods have low computation times which make them applicable to screen large data sets.</p

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Long-range transport of airborne microbes over the global tropical and subtropical ocean

The atmosphere plays a fundamental role in the transport of microbes across the planet but it is often neglected as a microbial habitat. Although the ocean represents two thirds of the Earth’s surface, there is little information on the atmospheric microbial load over the open ocean. Here we provide a global estimate of microbial loads and air-sea exchanges over the tropical and subtropical oceans based on the data collected along the Malaspina 2010 Circumnavigation Expedition. Total loads of airborne prokaryotes and eukaryotes were estimated at 2.2 × 1021 and 2.1 × 1021 cells, respectively. Overall 33–68% of these microorganisms could be traced to a marine origin, being transported thousands of kilometres before re-entering the ocean. Moreover, our results show a substantial load of terrestrial microbes transported over the oceans, with abundances declining exponentially with distance from land and indicate that islands may act as stepping stones facilitating the transoceanic transport of terrestrial microbes.En prens

Megascopic Quantum Phenomena. A Critical Study of Physical Interpretations

A megascopic revalidation is offered providing responses and resolutions of current inconsistencies and existing contradictions in present-day quantum theory. As the core of this study we present an independent proof of the Goldstone theorem for a quantum field formulation of molecules and solids. Along with phonons two types of new quasiparticles appear: rotons and translons. In full analogy with Lorentz covariance, combining space and time coordinates, a new covariance is necessary, binding together the internal and external degrees of freedom, without explicitly separating the centre-of-mass, which normally applies in both classical and quantum formulations. The generally accepted view regarding the lack of a simple correspondence between the Goldstone modes and broken symmetries, has significant consequences: an ambiguous BCS theory as well as a subsequent Higgs mechanism. The application of the archetype of the classical spontaneous symmetry breaking, i.e. the Mexican hat, as compared to standard quantum relations, i.e. the Jahn-Teller effect, superconductivity or the Higgs mechanism, becomes a disparity. In short, symmetry broken states have a microscopic causal origin, but transitions between them have a teleological component. The different treatments of the problem of the centre of gravity in quantum mechanics and in field theories imply a second type of Bohr complementarity on the many-body level opening the door for megascopic representations of all basic microscopic quantum axioms with further readings for teleonomic megascopic quantum phenomena, which have no microscopic rationale: isomeric transitions, Jahn-Teller effect, chemical reactions, Einstein-de Haas effect, superconductivity-superfluidity, and brittle fracture.Comment: 117 pages, 17 sections, final revised version from 20 May 2019 but uploaded after the DOI was know

MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion

Mitochondria are double-membraned organelles with variable shapes influenced by metabolic conditions, developmental stage, and environmental stimuli. Their dynamic morphology is a result of regulated and balanced fusion and fission processes. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and the maintenance of membrane potential. Mitofusins are dynamin-related GTPases that are essential for mitochondrial fusion. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via combined oligomerization and GTP hydrolysis. However, the molecular mechanisms of this process remain unknown. Here we present crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of MFN1 and resembles the ‘neck’ of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote GTPase domain dimerization in the transition state. Disruption of GTPase domain dimerization abolishes the fusogenic activity of MFN1. Moreover, a conserved aspartate residue trigger was found to affect mitochondrial elongation in MFN1, probably through a GTP-loading-dependent domain rearrangement. Thus, we propose a mechanistic model for MFN1-mediated mitochondrial tethering, and our results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders

Finding the Needles in the Metagenome Haystack

In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth’s diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments

A marine biogenic source of atmospheric ice nucleating particles

The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties1,2. The formation of ice in clouds is facilitated by the presence of airborne ice nucleating particles1,2. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice3-11. Sea spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer12-19. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice nucleating material is likely biogenic and less than ~0.2 μm in size. We find that exudates separated from cells of the marine diatom T. Pseudonana nucleate ice and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol in combination with our measurements suggest that marine organic material may be an important source of ice nucleating particles in remote marine environments such as the Southern Ocean, North Pacific and North Atlantic