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Examines the effectiveness of ischemic preconditioning (IP) in reducing the risks of heart disease. Significance of IP in maintaining high energy phosphate levels; Role of energy phosphates in suppressing arrhythmias; Applications of IP to cardiopulmonary bypass surgery.

Abstract Background Studies on mycorrhiza associated bacteria suggest that bacterial-fungal interactions play important roles during mycorrhiza formation and affect plant health. We surveyed Streptomyces Actinobacteria, known as antibiotic producers and antagonists of fungi, from Norway spruce mycorrhizas with predominantly Piloderma species as the fungal partner. Results Fifteen Streptomyces isolates exhibited substantial variation in inhibition of tested mycorrhizal and plant pathogenic fungi (Amanita muscaria, Fusarium oxysporum, Hebeloma cylindrosporum, Heterobasidion abietinum, Heterobasidion annosum, Laccaria bicolor, Piloderma croceum). The growth of the mycorrhiza-forming fungus Laccaria bicolor was stimulated by some of the streptomycetes, and Piloderma croceum was only moderately affected. Bacteria responded to the streptomycetes differently than the fungi. For instance the strain Streptomyces sp. AcM11, which inhibited most tested fungi, was less inhibitory to bacteria than other tested streptomycetes. The determined patterns of Streptomyces-microbe interactions were associated with distinct patterns of secondary metabolite production. Notably, potentially novel metabolites were produced by strains that were less antagonistic to fungi. Most of the identified metabolites were antibiotics (e.g. cycloheximide, actiphenol) and siderophores (e.g. ferulic acid, desferroxiamines). Plant disease resistance was activated by a single streptomycete strain only. Conclusions Mycorrhiza associated streptomycetes appear to have an important role in inhibiting the growth of fungi and bacteria. Additionally, our study indicates that the Streptomyces strains, which are not general antagonists of fungi, may produce still un-described metabolites.

Efficient micronutrient acquisition is a critical factor in selecting micronutrient dense crops for human consumption. Enhanced exudation and re-uptake of metal chelators, so-called phytosiderophores, by roots of graminaceous plants has been implicated in efficient micronutrient acquisition. We compared PS biosynthesis and exudation as a response mechanism to either Fe, Zn or Cu starvation. Two barley (Hordeum vulgare L.) lines with contrasting micronutrient grain yields were grown hydroponically and PS exudation (LC-MS) and root gene expression (RNAseq) were determined after either Fe, Zn, or Cu starvation. The response strength of the PS pathway was micronutrient dependent and decreased in the order Fe > Zn > Cu deficiency. We observed a stronger expression of PS pathway genes and greater PS exudation in the barley line with large micronutrient grain yield suggesting that a highly expressed PS pathway might be an important trait involved in high micronutrient accumulation. In addition to several metal specific transporters, we also found that the expression of IRO2 and bHLH156 transcription factors was not only induced under Fe but also under Zn and Cu deficiency. Our study delivers important insights into the role of the PS pathway in the acquisition of different micronutrients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of the present study was to investigate the levels of YKL-40 during and after coronary artery bypass grafting surgery (CABG) and to establish possible connections between YKL-40 and markers of oxidative stress, inflammation, and myocardial injury. Patients undergoing elective CABG utilizing cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected at the onset of anesthesia, during surgery and post-operatively. Levels of YKL-40, 8-isoprostane, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and troponin T (TnT) were measured by immunoassay. YKL-40 levels increased significantly 24 h after CPB. Positive correlation was seen between post-operative TnT and YKL-40 levels (r = 0.457, p = 0.016) and, interestingly, baseline YKL-40 predicted post-operative TnT increase (r = 0.374, p = 0.050). There was also a clear association between YKL-40 and the chemotactic factors MCP-1 (r = 0.440, p = 0.028) and IL-8 (r = 0.484, p = 0.011) linking YKL-40 to cardiac inflammation and fibrosis following CABG. The present results show, for the first time, that YKL-40 is associated with myocardial injury and leukocyte-activating factors following coronary artery bypass surgery. YKL-40 may be a factor and/or biomarker of myocardial inflammation and injury and subsequent fibrosis following heart surgery.

Water deficit tolerance is critical for plant fitness and survival, especially when successive drought events happen. Specific soil microorganisms are however able to improve plant tolerance to stresses, such as those displaying a 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. Microorganisms adapted to dry conditions can be selected by plants over time because of properties such as sporulation, substrate preference, or cell-wall thickness. However, the complexity and interconnection between abiotic factors, like drought or soil management, and biotic factors, like plant species identity, make it difficult to elucidate the general selection processes of such microorganisms. Using a pot experiment in which wheat and barley were grown on conventional and organic farming soils, we determined the effect of water deficit history on soil microorganisms by comparing single and successive events of water limitation. The analysis showed that water deficit strongly impacts the composition of both the total microbial community (16S rRNA genes) and one of ACC deaminase-positive ( acdS + ) microorganisms in the rhizosphere. In contrast, successive dry conditions moderately influence the abundance and diversity of both communities compared to a single dry event. We revealed interactive effects of the farming soil type and the water deficit conditioning treatment. Indeed, possibly due to better nutrient status, plants grown on soils from conventional farming showed higher growth and were able to select more adapted microbial taxa. Some of them are already known for their plant-beneficial properties like the Actinobacteria Streptomyces , but interestingly, some Proteobacteria were also enriched after a water deficit history under conventional farming. Our approach allowed us to identify key microbial taxa promoting drought adaptation of cereals, thus improving our understanding of drought effects on plant-microbe interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gebauer, Breitkreuz, Heintz-Buschart, Reitz, Buscot, Tarkka and Bouffaud.)

Mycorrhizal fungi play an important role for the nitrogen (N) supply of trees. The influence of different mycorrhizal types on N acquisition in tree-tree interactions is, however, not well understood, particularly with regard to the competition for growth-limiting N. We studied the effect of competition between temperate forest tree species on their inorganic and organic N acquisition in relation to their mycorrhizal type (i.e., arbuscular mycorrhiza or ectomycorrhiza). In a field experiment, we quantified net N uptake capacity from inorganic and organic N sources using 15N/13C stable isotopes for arbuscular mycorrhizal tree species (i.e., Acer pseudoplatanus L., Fraxinus excelsior L., and Prunus avium L.) as well as ectomycorrhizal tree species (i.e., Carpinus betulus L., Fagus sylvatica L., and Tilia platyphyllos Scop.). All species were grown in intra- and interspecific competition (i.e., monoculture or mixture). Our results showed that N sources were not used complementarily depending on a species' mycorrhizal association, but their uptake rather depended on the competitor, indicating species-specific effects. Generally, ammonium was preferred over glutamine and glutamine over nitrate. In conclusion, our findings suggest that the inorganic and organic N acquisition of the studied temperate tree species is less regulated by mycorrhizal association but rather by the availability of specific N sources in the soil as well as the competitive environment of different tree species., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

In this review, we introduce microbially-mediated soil processes, players, their functional traits, and their links to processes at biogeochemical interfaces [e.g., rhizosphere, detritusphere, (bio)-pores, and aggregate surfaces]. A conceptual view emphasizes the central role of the rhizosphere in interactions with other biogeochemical interfaces, considering biotic and abiotic dynamic drivers. We discuss the applicability of three groups of traits based on microbial physiology, activity state, and genomic functional traits to reflect microbial growth in soil. The sensitivity and credibility of modern molecular approaches to estimate microbial-specific growth rates require further development. A link between functional traits determined by physiological (e.g., respiration, biomarkers) and genomic (e.g., genome size, number of ribosomal gene copies per genome, expression of catabolic versus biosynthetic genes) approaches is strongly affected by environmental conditions such as carbon, nutrient availability, and ecosystem type. Therefore, we address the role of soil physico-chemical conditions and trophic interactions as drivers of microbially-mediated soil processes at relevant scales for process localization. The strengths and weaknesses of current approaches (destructive, non-destructive, and predictive) for assessing process localization and the corresponding estimates of process rates are linked to the challenges for modeling microbially-mediated processes in heterogeneous soil microhabitats. Finally, we introduce a conceptual self-regulatory mechanism based on the flexible structure of active microbial communities. Microbial taxa best suited to each successional stage of substrate decomposition become dominant and alter the community structure. The rates of decomposition of organic compounds, therefore, are dependent on the functional traits of dominant taxa and microbial strategies, which are selected and driven by the local environment., Competing Interests: RK was employed by the company Forschungszentrum Jülich GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blagodatskaya, Tarkka, Knief, Koller, Peth, Schmidt, Spielvogel, Uteau, Weber and Razavi.)

Rhizosphere microbial communities adapt their structural and functional compositions to water scarcity and have the potential to substantially mitigate drought stress of crops. To unlock this potential, it is crucial to understand community responses to drought in the complex interplay between soil properties, agricultural management and crop species. Two winter wheat cultivars, demanding and non-demanding, were exposed to drought stress in loamy Chernozem and sandy Luvisol soils under conventional or organic farming management. Structural and functional adaptations of the rhizosphere bacteria were assessed by 16S amplicon sequencing, the predicted abundance of drought-related functional genes in the bacterial community based on 16S amplicon sequences (Tax4Fun) and the activity potentials of extracellular enzymes involved in the carbon cycle. Bacterial community composition was strongly driven by drought and soil type. Under drought conditions, Gram-positive phyla became relatively more abundant, but either less or more diverse in Luvisol and Chernozem soil respectively. Enzyme activities and functional gene abundances related to carbon degradation were increased under drought in the rhizosphere of the demanding wheat cultivar in organic farming. We demonstrate that soil type, farming system and wheat cultivar each constitute important factors during the structural and/or functional adaptation of rhizobacterial communities in response to drought., (© 2021 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Computational approaches that link bacterial 16S rRNA gene amplicon data to functional genes based on prokaryotic reference genomes have emerged. This study aims to validate or refute the applicability of the functional gene prediction tools for assessment and comparison of community functionality among experimental treatments, inducing either fast or slow responses in rhizosphere microbial community composition and function. Rhizosphere samples of wheat and barley were collected in two consecutive years at active and mature growth phases from organic and conventional farming plots with ambient or future-climate treatments of the Global Change Experimental Facility. Bacterial community composition was determined by 16S rRNA gene amplicon sequencing, and the activities of five extracellular enzymes involved in carbon (β-glucosidases, cellobiohydrolase, and xylosidase), nitrogen ( N -acetylglucosaminidase), and phosphorus (acid phosphatase) cycles were determined. Structural community data were used to predict functional patterns of the rhizosphere communities using Tax4Fun and PanFP. Subsequently, the predictions were compared with the measured activities. Despite the fact that different treatments mainly drove either community composition (plant growth phase) or measured enzyme activities (farming system), the predictions mirrored patterns in the treatments in a qualitative but not quantitative way. Most of the discrepancies between measured and predicted values resulted from plant growth stages (fast community response), followed by farming management and climate (slower community response). Thus, our results suggest the applicability of the prediction tools for comparative investigations of soil community functionality in less-dynamic environmental systems. IMPORTANCE Linking soil microbial community structure to its functionality, which is important for maintaining health and services of an ecosystem, is still challenging. Besides great advances in structural community analysis, functional equivalents, such as metagenomics and metatranscriptomics, are still time and cost intensive. Recent computational approaches (Tax4Fun and PanFP) aim to predict functions from structural community data based on reference genomes. Although the usability of these tools has been confirmed with metagenomic data, a comparison between predicted and measured functions is so far missing. Thus, this study comprises an expansive reality test on the performance of these tools under different environmental conditions, including relevant global change factors (land use and climate). The work provides a valuable validation of the applicability of the prediction tools for comparison of soil community functions across different sufficiently established soil ecosystems and suggest their usability to unravel the broad spectrum of functions provided by a given community structure.

The characterized 10 Streptomyces isolates were previously selected by their abilities to solubilize phosphates. To investigate whether these isolates represent multifaceted plant growth-promoting rhizobacteria (PGPR), their potassium-solubilizing, auxin-producing and inhibitory activities were determined. The 10 Streptomyces spp. yielded a variable biomass in the presence of insoluble orthoclase as the sole potassium (K) source, indicating that they were able to extract different amounts of K from this source for their own growth. Three strains (AZ, AYD and DE2) released soluble K from insoluble orthoclase in large amounts into the culture broth. The production levels ranged from 125.4 mg/L to 216.6 mg/L after 5 days of culture. Only two strains, Streptomyces enissocaesilis (BYC) and S . tunisiensis (AI), released a larger amount of soluble K from orthoclase and yielded much more biomass. This indicated that the rate of K released from this insoluble orthoclase exceeded its consumption rate for bacterial growth and that some strains solubilized K more efficiently than others. The results also suggest that the K solubilization process of AZ, AYD and DE2 strains, the most efficient K-solubilizing strains, involves a slight acidification of the medium. Furthermore, these 10 Streptomyces spp. were able to secrete indole acetic acid (IAA) in broth medium and ranged from 7.9 ± 0.1 µg/mL to 122.3 ± 0.1 µg/mL. The results of the antibiosis test proved the potential of the 10 tested strains to limit the growth of fungi and bacteria. In dual culture, S . bellus (AYD) had highest inhibitory effect against the three identified fungal causal agents of root rot of sugar beet: Fusarium equiseti and two F . fujikuroi at 55, 43 and 36%, respectively. Streptomyces enissocaesilis (BYC), S . bellus (AYD) and S . saprophyticus (DE2) exhibited higher multifaceted PGPR with their potassium-solubilizing, auxin-producing and inhibitory activities, which could be expected to lead to effectiveness in field trials of sugar beet.

Production and release of organic acids and phosphatase enzymes by microbes are important for inorganic and organic phosphorus cycling in soil. The presence of microorganisms with corresponding traits in the plant rhizosphere lead to improved plant P uptake and ultimately growth promotion. We studied the potential of two rhizosphere-competent strains, Pantoea sp. MR1 and Ochrobactrum sp. SSR, for solubilization of different organic and inorganic P sources in vitro. In a pot experiment we further revealed the impact of the two strains on wheat seedling performance in soil amended with either phytate, rock phosphate or K 2 HPO 4 as solely P source. To directly link P-solubilizing activity to the strain-specific genetic potential, we designed novel primers for glucose dehydrogenase (gcd), phosphatase (pho) and phytase (phy) genes, which are related to the organic and inorganic P solubilization potential. Quantitative tracing of these functional genes in the inoculated soils of the conducted pot experiment further allowed to compare strain abundances in the soil in dependency on the present P source. We observed strain- and P source-dependent patterns of the P solubilization in vitro as well as in the pot experiment, whereby P release, particularly from phytate, was linked to the strain abundance. We further revealed that the activity of microbial phosphatases is determined by the interplay between functional gene abundance, available soil P, and substrate availability. Moreover, positive impacts of microbial seed inoculation on wheat root architecture and aboveground growth parameters were observed. Our results suggest that screening for rhizosphere-competent strains with gcd, pho and phy genes may help to identify new microbial taxa that are able to solubilize and mineralize inorganic as well as organic bound P. Subsequently, the targeted use of corresponding strains may improve P availability in agricultural soils and consequently reduce fertilizer application., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Numerous studies have shown that plants selectively recruit microbes from the soil to establish a complex, yet stable and quite predictable microbial community on their roots - their "microbiome." Microbiome assembly is considered as a key process in the self-organization of root systems. A fundamental question for understanding plant-microbe relationships is where a predictable microbiome is formed along the root axis and through which microbial dynamics the stable formation of a microbiome is challenged. Using maize as a model species for which numerous data on dynamic root traits are available, this mini-review aims to give an integrative overview on the dynamic nature of root growth and its consequences for microbiome assembly based on theoretical considerations from microbial community ecology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bonkowski, Tarkka, Razavi, Schmidt, Blagodatskaya, Koller, Yu, Knief, Hochholdinger and Vetterlein.)

In aquatic ecosystems, the biocide triclosan represents a hazard for the non-target microalgae. So far, algal responses were mainly investigated at apical levels hampering the acquisition of a holistic view on primary, adaptive, and compensatory stress responses. We assessed responses of the chlorophyte Scenedesmus vacuolatus to triclosan at apical (growth, photosynthesis) and molecular (transcriptome, metabolome) levels for comparative pathway sensitivity analysis. For each responsive signal (contigs, metabolites), a concentration-response curve was modeled and effect concentrations were calculated leading to the setting of cumulative sensitivity distributions. Molecular responses showed higher sensitivity than apical observations. The functional annotation of contigs and metabolites revealed 118 metabolic pathways putatively impaired by triclosan, highlighting a wide repercussion on the algal metabolism. Metabolites involved in the lipid metabolism showed decreasing trends along the concentration gradient and a globally highest sensitivity, pointing to the primary target of triclosan. The pathways involved in xenobiotic degradation and membrane transporters were mainly regulated in the transcriptome with increasing response trends comprising compensatory responses. The suggested novel approach, combining apical and multi-omics analyses in a concentration-response framework improves mechanistic understanding and mode of action analysis on non-targeted organisms and is suggested to better implement high-throughput multi-omics data in environmental risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known Competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Production of antibiotics to inhibit competitors affects soil microbial community composition and contributes to disease suppression. In this work, we characterized whether Streptomyces bacteria, prolific antibiotics producers, inhibit a soil borne human pathogenic microorganism, Streptomyces sudanensis. S. sudanensis represents the major causal agent of actinomycetoma - a largely under-studied and dreadful subcutaneous disease of humans in the tropics and subtropics. The objective of this study was to evaluate the in vitro S. sudanensis inhibitory potential of soil streptomycetes isolated from different sites in Sudan, including areas with frequent (mycetoma belt) and rare actinomycetoma cases of illness., Results: Using selective media, 173 Streptomyces isolates were recovered from 17 sites representing three ecoregions and different vegetation and ecological subdivisions in Sudan. In total, 115 strains of the 173 (66.5%) displayed antagonism against S. sudanensis with different levels of inhibition. Strains isolated from the South Saharan steppe and woodlands ecoregion (Northern Sudan) exhibited higher inhibitory potential than those strains isolated from the East Sudanian savanna ecoregion located in the south and southeastern Sudan, or the strains isolated from the Sahelian Acacia savanna ecoregion located in central and western Sudan. According to 16S rRNA gene sequence analysis, isolates were predominantly related to Streptomyces werraensis, S. enissocaesilis, S. griseostramineus and S. prasinosporus. Three clusters of isolates were related to strains that have previously been isolated from human and animal actinomycetoma cases: SD524 (Streptomyces sp. subclade 6), SD528 (Streptomyces griseostramineus) and SD552 (Streptomyces werraensis)., Conclusion: The in vitro inhibitory potential against S. sudanensis was proven for more than half of the soil streptomycetes isolates in this study and this potential may contribute to suppressing the abundance and virulence of S. sudanensis. The streptomycetes isolated from the mycetoma free South Saharan steppe ecoregion show the highest average inhibitory potential. Further analyses suggest that mainly soil properties and rainfall modulate the structure and function of Streptomyces species, including their antagonistic activity against S. sudanensis.

Climate change models predict more frequent and prolonged drought events in Central Europe, which will exert extraordinary pressure on agroecosystems. One of the consequences is drought-related nutrient limitations for crops negatively affecting agricultural productivity. These effects can be mitigated by beneficial plant growth promoting rhizobacteria. In this study, we investigated the potential of cultivable bacterial species for phosphate solubilization in the rhizosphere of winter wheat at two relevant growth stages - stem elongation and grain filling stages. Rhizosphere samples were collected in the Global Change Experimental Facility in Central Germany, which comprises plots with conventional and organic farming systems under ambient and future climate. Phosphate-solubilizing bacteria were selectively isolated on Pikovskaya medium, phylogenetically classified by 16S rRNA sequencing, and tested for in vitro mineral phosphate solubilization and drought tolerance using plate assays. The culture isolates were dominated by members of the genera Phyllobacterium, Pseudomonas and Streptomyces. Cultivation-derived species richness and abundance of dominant taxa, especially within the genera Phyllobacterium and Pseudomonas , as well as composition of Pseudomonas species were affected by wheat growth stage. Pseudomonas was found to be more abundant at stem elongation than at grain filling, while for Phyllobacterium the opposite pattern was observed. The abundance of Streptomyces isolates remained stable throughout the studied growth stages. The temporal shifts in the cultivable fraction of the community along with considerable P solubilization potentials of Phyllobacterium and Pseudomonas species suggest functional redundancy between and among genera at different wheat growth stages. Phosphate-solubilizing Phyllobacterium species were assigned to Phyllobacterium ifriqiyense and Phyllobacterium sophorae. It is the first time that phosphate solubilization potential is described for these species. Since Phyllobacterium species showed the highest drought tolerance along all isolates, they may play an increasingly important role in phosphate solubilization in a future dryer climate., (Copyright © 2020 Breitkreuz, Buscot, Tarkka and Reitz.)

Soil detritivores such as Collembola impact plant growth, tissue nutrient concentration and gene expression. Using a model system with pedunculate oak ( Quercus robur ) microcuttings that display a typical endogenous rhythmic growth with alternating shoot (SF) and root flushes (RF), we investigated the transcriptomic response of oak with and without mycorrhiza ( Piloderma croceum ) to the presence of Collembola ( Protaphorura armata ), and linked it to changes in resource allocation by pulse labelling the plants with 13 C and 15 N. Collembola impacted Gene Ontology (GO) terms as well as plant morphology and elemental ratios with the effects varying markedly with developmental phases. During SF Collembola increased GO terms related to primary growth and this was mirrored in increased 13 C and 15 N excess in aboveground plant compartments. During RF, Collembola increased GO terms related to plant secondary metabolism and physical fortification. Further, Collembola presence resulted in an increase in plant defence-related GO terms suggesting that Collembola in the rhizosphere prime oak shoots against the attack by fungi or herbivores. Notably, the impact of Collembola on growth, resource allocation and oak gene expression was modified by presence of P. croceum . The results indicate that oaks clearly react to the presence of Collembola in the rhizosphere and respond in a complex way by changing the expression of genes of both primary and secondary metabolism, and this resulted in concomitant changes in plant morphology and physiology., Competing Interests: We do not have competing interests.

Omics approaches (e.g., transcriptomics, metabolomics) are promising for ecological risk assessment (ERA) since they provide mechanistic information and early warning signals. A crucial step in the analysis of omics data is the modeling of concentration-dependency which may have different trends including monotonic (e.g., linear, exponential) or biphasic (e.g., U shape, bell shape) forms. The diversity of responses raises challenges concerning detection and modeling of significant responses and effect concentration (EC) derivation. Furthermore, handling high-throughput data sets is time-consuming and requires effective and automated processing routines. Thus, we developed an open source tool (DRomics, available as an R-package and as a web-based service) which, after elimination of molecular responses (e.g., gene expressions from microarrays) with no concentration-dependency and/or high variability, identifies the best model for concentration-response curve description. Subsequently, an EC (e.g., a benchmark dose) is estimated from each curve, and curves are classified based on their model parameters. This tool is especially dedicated to manage data obtained from an experimental design favoring a great number of tested doses rather than a great number of replicates and also to handle properly monotonic and biphasic trends. The tool finally provides restitution for a table of results that can be directly used to perform ERA approaches.

Background and Aims:: The lungs participate in the modulation of the circulating inflammatory factors induced by coronary artery bypass grafting. We investigated whether aprotinin-which has been suggested to interact with inflammation-influences lung passage of key inflammatory factors after coronary artery bypass grafting., Material and Methods:: A total of 40 patients undergoing coronary artery bypass grafting were randomized into four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Pulmonary artery and radial artery blood samples were collected for the evaluation of calculated lung passage (pulmonary artery/radial artery) of the pro-inflammatory factors interleukin 6 and interleukin 8, 8-isoprostane, myeloperoxidase and the anti-inflammatory interleukin 10 immediately after induction of anesthesia (T1), 1 min after releasing aortic cross clamp (T2), 15 min after releasing aortic cross clamp (T3), 1 h after releasing aortic cross clamp (T4), and 20 h after releasing aortic cross clamp (T5)., Results:: Pulmonary artery/radial artery 8-isoprostane increased in patients with high aprotinin dose as compared with lower doses (1.1 range 0.97 vs 0.9 range 1.39, p = 0.001). The main effect comparing high aprotinin dose with lower doses was significant (F(1, 38) = 7.338, p = 0.01, partial eta squared = 0.16) further supporting difference in the effectiveness of high aprotinin dose for pulmonary artery/radial artery 8-isoprostane., Conclusion:: According to the pulmonary artery/radial artery equation, the impact of aprotinin on 8-isoprostane after coronary artery bypass grafting is dose dependent. Aprotinin may aid the lung passage of circulating factors toward a beneficial anti-inflammatory milieu.

Oaks are an important part of our natural and cultural heritage. Not only are they ubiquitous in our most common landscapes 1 but they have also supplied human societies with invaluable services, including food and shelter, since prehistoric times 2 . With 450 species spread throughout Asia, Europe and America 3 , oaks constitute a critical global renewable resource. The longevity of oaks (several hundred years) probably underlies their emblematic cultural and historical importance. Such long-lived sessile organisms must persist in the face of a wide range of abiotic and biotic threats over their lifespans. We investigated the genomic features associated with such a long lifespan by sequencing, assembling and annotating the oak genome. We then used the growing number of whole-genome sequences for plants (including tree and herbaceous species) to investigate the parallel evolution of genomic characteristics potentially underpinning tree longevity. A further consequence of the long lifespan of trees is their accumulation of somatic mutations during mitotic divisions of stem cells present in the shoot apical meristems. Empirical 4 and modelling 5 approaches have shown that intra-organismal genetic heterogeneity can be selected for 6 and provides direct fitness benefits in the arms race with short-lived pests and pathogens through a patchwork of intra-organismal phenotypes 7 . However, there is no clear proof that large-statured trees consist of a genetic mosaic of clonally distinct cell lineages within and between branches. Through this case study of oak, we demonstrate the accumulation and transmission of somatic mutations and the expansion of disease-resistance gene families in trees.

Aims: Although obesity is a risk factor for coronary heart disease (CHD), it might be associated with a favourable prognosis in patients with CHD. The aim of the study was to evaluate this so called 'obesity paradox' during a follow-up period of 20 years in patients who had undergone coronary artery bypass grafting (CABG)., Methods and Results: The study population consisted of 922 CHD patients who had undergone CABG between 1993 and 1994. Pre and perioperative data was collected from patient records and supplemented with patient questionnaires, telephone contacts and data from national archives. The 10-year postoperative prognosis of normal-weight patients (body mass index (BMI) 18.5-24.9 kg/m 2 ) was inferior to that of overweight (BMI 25.0-29.9 kg/m 2 ) and obese patients (BMI⩾30.0 kg/m 2 ) and to the background population. Beyond 10 years the prognosis of obese patients deteriorated when compared with the overweight group. At the end of the 20-year follow-up, survival of the normal weight group was 0.68 (95% confidence interval (CI), 0.49-0.87; p<0.001), the overweight group 0.82 (95% CI, 0.71-0.92; p<0.001), and the obese group 0.67 (95% CI, 0.49-0.85; p<0.001), when compared with their background populations (=1.00). Obese patients developed diabetes more frequently and died more frequently of cardiovascular disease than patients in the two other study groups during the second postoperative decade ( p<0.01)., Conclusion: During long-term follow-up the obesity paradox seems to disappear due to progression of cardiometabolic disease in patients who have undergone CABG.

Low pulmonary vascular resistance index (PVRI) reflects favorable redundant pulmonary circulation following coronary artery bypass grafting with cardiopulmonary bypass surgery (CPB). This randomized study investigated whether aprotinin given in different modalities impacts PVRI after coronary artery bypass grafting. A total of 40 patients undergoing coronary artery bypass grafting were randomized to four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. The results showed that PVRI remained relative low in all patients provided aprotinin regardless of treatment dosage; PVRI increased at 4 h after restarting ventilation after CPB in patients without aprotinin as compared with aprotinin (266 ± 137, 266 ± 115, 244 ± 86 vs. 386 ± 121, dynes-s-cm - 5 , respectively, p = .047). Elevated postoperative PVRI was predictive for patients without aprotinin (AUC 0.668; SE 0.40; p < .0001; CI 0.590-0.746). There were no statistical differences in oxygenation index, pulmonary shunt or alveolar-arterial oxygen gradient between the groups. In conclusion, aprotinin maintains a low PVRI in elective patients with healthy lungs during CPB. We suggest that aprotinin maintains pulmonary arterial endothelial integrity.

Background  A cohort of patients having symptoms of sternal nonunion late after sternotomy was studied to find out whether the complaints were related to true sternal nonunion or decreased bone density. Methods  A survey was mailed to 2,053 cardiac surgical patients operated in our institution between July 2007 and June 2010. The patients were requested about symptoms referring to sternal instability. A group of symptomatic individuals as well as 1:1 age- and time-matched asymptomatic controls were examined with sternal palpation, ultrasound during standardized sternal pressure provocation, and computed tomography (CT). Results  The number of patients replied in the survey was 1,918 (93.4%); 2.3% (44 patients) reported sensation of movement or clicking in sternum during body movements and during coughing. Symptomatic patients living within 200 km to the hospital (21) and their asymptomatic controls (21) were selected for further clinical and imaging studies. Mean period between the initial operation and the examinations was 36 (22-56) months. Sternal palpation pain was significantly associated with reported symptoms suggestive of sternal nonunion (odds ratio [OR] 22.0; 95% confidence interval [CI] 2.5-195); however, none of the patients had clinically unstable sternum or nonunion in the sternal imaging. The symptoms of sternal instability were more frequent in patients whose bone mineralization rate (as measured with T-scores) was higher. Conclusion  Symptoms suggestive of sternal nonunion were experienced by 2.3%. However, their symptoms did not correlate with CT scans or provocation ultrasound although palpation pain was evident. Thus the pain is derived from nonmechanical etiologies. Higher bone mineralization rate correlated with abnormal symptoms of sternal wound., Competing Interests: Conflict of Interest: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Common oak trees display endogenous rhythmic growth with alternating shoot and root flushes. To explore the mechanisms involved, microcuttings of the Quercus robur L. clone DF159 were used for (13)C/(15)N labelling in combination with RNA sequencing (RNASeq) transcript profiling of shoots and roots. The effect of plant internal resource availability on the rhythmic growth of the cuttings was tested through inoculation with the ectomycorrhizal fungus Piloderma croceum. Shoot and root flushes were related to parallel shifts in above- and below-ground C and, to a lesser extent, N allocation. Increased plant internal resource availability by P. croceum inoculation with enhanced plant growth affected neither the rhythmic growth nor the associated resource allocation patterns. Two shifts in transcript abundance were identified during root and shoot growth cessation, and most concerned genes were down-regulated. Inoculation with P. croceum suppressed these transcript shifts in roots, but not in shoots. To identify core processes governing the rhythmic growth, functions [Gene Ontology (GO) terms] of the genes differentially expressed during the growth cessation in both leaves and roots of non-inoculated plants and leaves of P. croceum-inoculated plants were examined. Besides genes related to resource acquisition and cell development, which might reflect rather than trigger rhythmic growth, genes involved in signalling and/or regulated by the circadian clock were identified. The results indicate that rhythmic growth involves dramatic oscillations in plant metabolism and gene regulation between below- and above-ground parts. Ectomycorrhizal symbiosis may play a previously unsuspected role in smoothing these oscillations without modifying the rhythmic growth pattern., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

A draft genome sequence of Streptomyces sp. strain AcH 505 is presented here. The genome encodes 22 secondary metabolite gene clusters and a large arsenal of secreted proteins, and their comparative and functional analyses will help to advance our knowledge of symbiotic interactions and fungal and plant biomass degradation., (Copyright © 2015 Tarkka et al.)

Streptomyces sp. strain 150FB, isolated from the cap surface of a bolete mushroom, inhibits the growth of the mycoparasitic Sepedonium species. Functional annotation of the strain 150FB draft genome identified 22 putative secondary metabolite biosynthetic gene clusters and genes encoding secreted proteins, which may contribute to the inhibition of the mycoparasite., (Copyright © 2015 Tarkka et al.)

To elucidate the genetic bases of mycorrhizal lifestyle evolution, we sequenced new fungal genomes, including 13 ectomycorrhizal (ECM), orchid (ORM) and ericoid (ERM) species, and five saprotrophs, which we analyzed along with other fungal genomes. Ectomycorrhizal fungi have a reduced complement of genes encoding plant cell wall-degrading enzymes (PCWDEs), as compared to their ancestral wood decayers. Nevertheless, they have retained a unique array of PCWDEs, thus suggesting that they possess diverse abilities to decompose lignocellulose. Similar functional categories of nonorthologous genes are induced in symbiosis. Of induced genes, 7-38% are orphan genes, including genes that encode secreted effector-like proteins. Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of mycorrhiza-induced genes.

Background: Many northern-hemisphere forests are dominated by oaks. These species extend over diverse environmental conditions and are thus interesting models for studies of plant adaptation and speciation. The genomic toolbox is an important asset for exploring the functional variation associated with natural selection., Results: The assembly of previously available and newly developed long and short sequence reads for two sympatric oak species, Quercus robur and Quercus petraea, generated a comprehensive catalog of transcripts for oak. The functional annotation of 91 k contigs demonstrated the presence of a large proportion of plant genes in this unigene set. Comparisons with SwissProt accessions and five plant gene models revealed orthologous relationships, making it possible to decipher the evolution of the oak genome. In particular, it was possible to align 9.5 thousand oak coding sequences with the equivalent sequences on peach chromosomes. Finally, RNA-seq data shed new light on the gene networks underlying vegetative bud dormancy release, a key stage in development allowing plants to adapt their phenology to the environment., Conclusion: In addition to providing a vast array of expressed genes, this study generated essential information about oak genome evolution and the regulation of genes associated with vegetative bud phenology, an important adaptive traits in trees. This resource contributes to the annotation of the oak genome sequence and will provide support for forward genetics approaches aiming to link genotypes with adaptive phenotypes.

Sulfurospirillum multivorans, a free-living ε-proteobacterium, is among the best studied organisms capable of organohalide respiration. It is able to use several halogenated ethenes as terminal electron acceptor. In this report, the complete genome sequence of S. multivorans including a comparison with genome sequences of two related non-dehalogenating species, Sulfurospirillum deleyianum and Sulfurospirillum barnesii, is described. The 3.2 Mbp genome of S. multivorans revealed a ∼ 50 kbp gene region encoding proteins required for organohalide respiration and corrinoid cofactor biosynthesis. This region includes genes for components not detected before in organohalide-respiring organisms. A transcript analysis of genes coding for some of these proteins indicates the involvement of a putative quinol dehydrogenase in organohalide respiration. The presence of genes encoding a variety of oxidoreductases reflects the organism's metabolic versatility. This was confirmed by growth studies with different electron acceptors including perchlorate and several sulfur-containing compounds. A comparison with other ε-proteobacteria indicates horizontal acquisition of many genes in the S. multivorans genome, which might be the basis of the bacterium's catabolic flexibility., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Objectives: Adipocytokines are hormones regulating energy metabolism and appetite and according to recent reports also inflammatory responses including ischaemia-reperfusion injury. Based on experimental data, we hypothesized that the levels of adipocytokines adiponectin, adipsin, leptin and/or resistin would correlate with myocardial injury, inflammation and oxidative stress during cardiac surgery., Methods: Thirty-two patients undergoing an elective on-pump coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected after the induction of anaesthesia, and at the onset of CPB, 1 and 15 min after the removal of aortic cross-clamp and 4 and 24 h after the onset of CPB. Samples were analysed for levels of four adipocytokines (adiponectin, adipsin, leptin and resistin) and markers of oxidative stress [myeloperoxidase (MPO) and 8-isoprostane], inflammation [interleukin-6 (IL-6)] and myocardial injury [troponin T (TnT)]., Results: Adiponectin and adipsin concentrations declined, while leptin and resistin levels increased significantly by 24 h after the onset of the operation. Interestingly, basal levels of resistin (r = 0.41, P = 0.020) as well as the maximal increase occurring in resistin levels during the 24-h follow-up (r = 0.49, P = 0.005) correlated positively with TnT release. In addition, the reperfusion-induced elevation in resistin levels correlated positively with oxidative stress measured as increases in MPO concentrations., Conclusions: As an original finding, we report here that resistin levels correlate with oxidative stress and myocardial injury in patients undergoing cardiac surgery. In addition, leptin levels were increased on the first postoperative day, but only minor declines were found in adiponectin and adipsin levels. Resistin has been implicated in unfavourable metabolic, cardiovascular and inflammatory responses: it may thus serve as a useful biomarker or a drug target in conditions complicated by ischaemia-reperfusion injury., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis.

Background: The associations of metabolic syndrome (MetS) or diabetes mellitus (DM) on long-term survival after coronary artery bypass grafting (CABG) have not been extensively evaluated. The aim of the present study was to assess the impact of MetS and DM on the 16-year survival after CABG., Methods: Diabetic and metabolic status together with relevant cardiovascular data was established in 910 CABG patients operated in 1993-94. They were divided in three groups as follows: neither DM nor MetS (375 patients), MetS alone (279 patients) and DM with or without MetS (256 patients). The 16-year follow-up of patient survival was carried out using national health databases. The relative survival rates were analyzed using the Life Table method comparing the observed survival rates of three patient groups to the rates based on age-, sex- and time-specific life tables for the whole population in Finland. To study the independent significance of MetS and DM for clinical outcome, multivariate analysis was made using an optimizing stepwise procedure based on the Bayesian approach., Results: Bayesian multivariate analysis revealed together six variables to predict clinical outcome (2 months to 16 years) in relation to the national background population, i.e. age, diabetes, left ventricular ejection fraction, BMI, perfusion time during the CABG and peripheral arterial disease. Our principal finding was that after postoperative period the 16-year prognosis of patients with neither DM nor MetS was better than that of the age-, sex-and time-matched background population (relative survival against background population 1.037, p < 0.0001). The overall survival of MetS patients resembled that of the matched background population (relative survival 0.998, NS). DM was associated with significantly increased mortality (relative survival 0.86, p < 0.0001). Additionally, mortality was even higher in patients receiving insulin treatment than in those without. Excess death rate of DM patients was predominantly caused by cardiovascular causes., Conclusion: In this long-term follow-up study patient groups without diabetes had at least equal 16 years' survival after CABG than their matched background populations. Survival of DM patients started to deteriorate already few years after the operation.

Background: Decreased pulmonary vascular resistance index (PVRI) reflects favorable postoperative pulmonary circulation after coronary artery bypass grafting. This randomized study investigated whether cardiopulmonary bypass (CPB) impacts PVRI after coronary artery bypass grafting., Material and Methods: A total of 47 patients undergoing coronary artery bypass grafting were randomized into four groups according to the ventilation and surgical technique: (1) No ventilation group, with intubation tube detached from the ventilator, (2) low tidal volume group, with continuous low tidal volume ventilation, (3) continuous 10 cm H2O positive airway pressure (CPAP) group, and (4) randomly selected patients undergoing surgery without CPB. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80., Results: During the first postoperative morning there were no statistical differences in oxygenation index, pulmonary shunt or alveolar-arterial oxygen gradient between the groups, while PVRI remained elevated in patients without CPB as compared with patients with CPB (263 ± 98 vs. 122 ± 84, dyne-s-cm(-5), respectively, p < 0.001). PVRI decreased in all patients with CPB regardless of ventilation technique. In contrast, elevated postoperative PVRI values were predictive for patients without CPB (AUC 0.786; SE 0.043; p < 0.001; 95% CI. 0.701-0.870)., Conclusions: Modified ventilation does not affect PVRI in elective patients with healthy lungs during CPB. Instead, CPB per se may have an important role on diminished PVRI. We suggest that CPB preserves pulmonary arterial endothelial integrity.

Background: Confined ongoing ischemia after ischemia-reperfusion injury (IRI) may alter myocardial recovery. We evaluated in a rat cardiac transplantation model whether distal persistent myocardial ischemia (dMI) and remote preconditioning (RPreC) have a remote myocardial impact after IRI., Material and Methods: Syngeneic heterotopic cardiac transplantation was performed on 29 Fischer344 rats to induce IRI, including nine rats which underwent distal ligation of the left anterior coronary artery (LAD) to yield distal MI (IRI+ dMI). RPreC was applied by occluding the left renal artery 5 min prior to reperfusion in six rats with IRI (IRI+ RPreC) as well as in seven with distal MI (IRI+ dMI+ RPreC). Microdialysis, histology and qRT-PCR for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed after graft harvesting., Results: In contrast to IRI + dMI + RPreC (39 ± 7 μmol), glutamate decreased in IRI + RPreC and IRI + dMI as compared with IRI (26 ± 3 and 31 ± 8 vs 91 ± 20, μmol respectively, p < 0.007). The relative number of vacuolated intramyocardial artery nuclei decreased in IRI + dMI as compared with IRI (0.02 ± 0.01, range 0-12 vs. 0.42 ± 0.31, range 0-3.25 PSU respectively, p < 0.04). iNOS expression decreased in IRI + RPreC as compared with IRI (p < 0.04), and eNOS expression decreased in IRI + dMI + RPreC as compared with IRI + dMI (p < 0.006) along with increased glycerol release., Conclusions: dMI after IRI has a potentially beneficial myocardial impact after cardiac arrest, which is hampered by RPreC.

Objective: Immunoglobulin (Ig) G4-positive aortitis may determine outcome after surgery for ascending aorta. We evaluated IgG4 expression of dilated ascending aortic wall., Methods: The study consisted of 91 patients who underwent ascending aortic surgery. For histology, hematoxylin-eosin, elastase-van Gieson, and periodic acid-Schiff stainings were performed. The amount of T and B lymphocytes, plasma cells, macrophages, cell proliferation, and IgG4 positivity were determined by immunohistochemistry., Results: The aortic wall in 12 patients had IgG4 positivity that was always confined to the adventitia. Adventitial plasma cells were numerous in all but 2 of these patients (P < .0001). Aortitis was revealed in 2 patients (17%) with IgG4-positive staining of the aorta and in 6 patients (8%) with IgG4 negativity. IgG4 staining was significantly associated with total aortic wall inflammation (area under the curve, 0.865; standard error, 0.043; P = .000; 95% confidence interval, 0.779-0.950). The mean diameter of the ascending aorta was 69 ± 4.7 mm and 56 ± 1.1 mm in patients with IgG4 positivity and negativity, respectively (P < .004). Approximately half of the patients with IgG4 positivity had dissection (42%), compared with only 15 of 79 (19%) of the remaining patients (P = not significant). Two patients with IgG4 positivity had to undergo reoperation because of immediate postoperative dissection. Seven patients died, including 4 patients (33%) with IgG4 positivity; the remaining 3 patients (4%) were IgG4 negative (P < .005)., Conclusions: IgG4-positive ascending aortic wall was frequent in our study cohort (13%) and revealed aortic inflammation associated with dilatation., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model., Design: Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology., Results: Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p < 0.05, respectively). Decreased eNOS staining confirmed the presence of developing infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly lower during IRI + MI +S as compared with IRI + MI (0.02 ± 0.01 and 1.02 ± 0.02, FC, p < 0.05)., Conclusions: Administered at the onset of reperfusion and developing infarction, sildenafil has an impact on myocardial recovery after cardiac arrest and ischemia.

Background: Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events., Methods and Results: A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5×10(-8) were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (P=4.3×10(-136), effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B, P=2.5×10(-47) and 1.1×10(-11), effect sizes=10.3 U/L and 7.8 U/L, respectively). In the meta-analyses of cohorts A, C, and D (excluding cohort B without angiographic data), the top SNP did not associate significantly with the age of onset of angiographically verified coronary artery disease (hazard ratio=1.00 [0.94-1.06] per allele), 3-vessel coronary artery disease (hazard ratio=1.03 [0.94-1.13]), or myocardial infarction (hazard ratio=1.04 [0.96-1.12])., Conclusions: This novel genetic marker is an important factor regulating oxidized low-density lipoprotein levels but not a major genetic factor for the studied cardiovascular endpoints.

Objectives: Plasma hyaluronan and syndecan-1 levels represent shedding of the endothelium glycocalyx during ischemia and edema. Diazoxide, a K(ATP)-channel opener, has been shown to decrease myocardial edema during coronary artery bypass grafting (CABG). We evaluated whether diazoxide exerts an impact on plasma hyaluronan and syndecan-1 levels during CABG., Design: Representative blood samples for hyaluronan and syndecan-1, before, during and after surgery, were obtained in 13 out of 16 patients that had a history of stable coronary artery disease undergoing CABG with or without diazoxide. Electron microscopy from biopsies procured from the right atrium in 9 patients was performed to confirm ultrastructural differences among patients before and during CABG., Results: Ultrastructural differences were apparent between individual patients already before operation at base line reflecting differences in the severity of myocardial ischemia and edema. A significant decrease of hyaluronan and syndecan-1 values was observed in patients with diazoxide after surgery (p < 0.04). Significant correlation of plasma hyaluronan and syndecan-1 levels was observed in patients with diazoxide but not in controls (p < 0.005, Spearman rank rho)., Conclusion: Diazoxide may have an impact on levels of peripheral plasma hyaluronan and syndecan-1 after CABG, suggesting decreased shedding of the endothelial glycocalyx layer.