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A non-neglectable percentage of patients with non-ST elevation myocardial infarction (NSTEMI) show non-obstructive coronary arteries (MINOCA). Specific data in older patients are scarce. We aimed to identify the clinical predictors of MINOCA in older patients admitted for NSTEMI and to explore the long-term prognosis of MINOCA. This was a single-center, observational, consecutive cohort study of older (≥70 years) patients admitted for NSTEMI between 2010 and 2014 who underwent coronary angiography. Univariate and multivariate Cox regression were performed to analyze the association of variables with MINOCA and all-cause mortality and with major adverse cardiac events (MACE), defined as a combined endpoint of all-cause mortality and nonfatal myocardial infarction and a combined endpoint of cardiovascular mortality, nonfatal myocardial infarction, and unplanned revascularization. The registry included 324 patients (mean age 78.8 ± 5.4 years), of which 71 (21.9%) were diagnosed with MINOCA. Predictors of MINOCA were female sex, left bundle branch block, pacemaker rhythm, chest pain at rest, peak troponin level, previous MI, Killip ≥2, and ST segment depression. Regarding prognosis, patients with obstructive coronary arteries (stenosis ≥50%) and the subgroup of MINOCA patients with plaques <50% had a similar prognosis; while MINOCA patients with angiographically smooth coronary arteries had a reduced risk of MACE. We conclude that the following: (1) in elderly patients admitted for NSTEMI, certain universally available clinical, electrocardiographic, and analytical variables are associated with the diagnosis of MINOCA; (2) elderly patients with MINOCA have a better prognosis than those with obstructive coronary arteries; however, only those with angiographically smooth coronary arteries have a reduced risk of all-cause mortality and MACE. [ABSTRACT FROM AUTHOR]

Background older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce. Methods the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI). Results during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02–1.04], P  < 0.001), CMR–LVEF (HR 0.97 [0.95–0.99] per percent increase, P  = 0.006) and MVO (HR 1.24 [1.09–1.4] per segment, P  = 0.001). Adding CMR data significantly improved MACE prediction compared to the model with baseline and echocardiographic characteristics (C-statistic 0.759 [0.694–0.824] vs. 0.685 [0.613–0.756], NRI = 0.6, IDI = 0.08, P  < 0.001). The best cut-offs for independent variables were GRACE score > 155, LVEF < 40% and MVO ≥ 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P  < 0.001). Conclusions CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI–CMR score should be externally validated. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST‐segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. Purpose: To explore the prognostic impact of MRI‐derived LVEF at any time post‐STEMI to predict subsequent MACE (cardiovascular death or re‐admission for acute heart failure). Study Type: Prospective. Population: One thousand thirteen STEMI patients were included in a multicenter registry. Field Strength/Sequence: 1.5‐T. Balanced steady‐state free precession (cine imaging) and segmented inversion recovery steady‐state free precession (late gadolinium enhancement) sequences. Assessment: Post‐infarction MRI‐derived LVEF (reduced [r]: <40%; mid‐range [mr]: 40%–49%; preserved [p]: ≥50%) was sequentially quantified at 1 week and after >3 months of follow‐up. Statistical Tests: Multi‐state Markov model to determine the prognostic value of each LVEF state (r‐, mr‐ or p‐) at any time point assessed to predict subsequent MACE. A P‐value <0.05 was considered to be statistically significant. Results: During a 6.2‐year median follow‐up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r‐LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r‐LVEF, mr‐LVEF, and p‐LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r‐LVEF state were 4.52‐fold more likely than those in mr‐LVEF state and 5.01‐fold more likely than those in p‐LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr‐LVEF and p‐LVEF states to MACE state (P‐value = 0.6). Data Conclusion: LVEF is an important MRI index for simple and dynamic post‐STEMI risk stratification. Detection of r‐LVEF by MRI at any time during follow‐up identifies a subset of patients at high risk of subsequent events. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Economically important cacao (Theobroma cacao Linnaeus 1753) plantations in South East Asia and Papua New Guinea (PNG) are significantly affected by the cocoa pod borer (CPB) moth. Species identity of the pest is attributed to Conopomorpha cramerella (Snellen 1904), a gracillariid moth endemic to Australasian and Oriental tropic regions that has evolved a host preference for introduced cacao. Suspected presence of cryptic CPB biotypes is largely unsupported by earlier genetic work but remains a concern to organisations developing species‐specific lure and/or control tools for managing this pest. We report the use of DNA barcoding to investigate population and species genetic diversity of CPB infecting cacao plantations in PNG at the eastern periphery of the pest's distribution. DNA barcodes from 94.4% of 179 moths from three disjunct PNG provinces (East Sepik, Bougainville and East New Britain) matched to reported C. cramerella sequence accessions. Genetic diversity among C. cramerella in PNG was limited to four closely related haplotypes, two of which were common in PNG and have previously been reported in the Malay Archipelago at different frequencies. We found evidence of significant population genetic structure between mainland and eastern offshore PNG provinces marked by a reduction of genetic diversity at the offshore provinces. We suggest C. cramerella populations in these offshore island provinces likely arose recently from a genetically depauperate cohort of founders from western sources. Ten moths were genetically unmatched to C. cramerella. Of these, six incidentally captured and degraded adults had novel unmatched DNA barcodes. Four larvae infesting cacao pods were genetically matched to Thaumatotibia zophophanes (Turner 1946) (Lepidoptera: Tortricidae) and an undefined Conopomorpha species distantly related to C. cramerella. The extent to which these two additional moth species affect the cacao industry in PNG (and potentially elsewhere) remains unknown. However, their low representation here (<2.3% of samples) indicates they may be of lesser prominence than the widespread C. cramerella. Nevertheless, organisations designing and/or implementing CPB controls tailored specifically for C. cramerella will need to ensure empirical evidence of control efficiency is monitored with respect to species identity of the captured pests. [ABSTRACT FROM AUTHOR]

Purpose: In ST-segment elevation myocardial infarction (STEMI) patients, longitudinal strain (LS) in remote non-infarcted myocardium (RNM) has not yet been characterized by tissue tracking (TT) cardiovascular magnetic resonance (CMR). In STEMI patients, we aimed to characterize RNM-LS by TT-CMR and to assess both its dynamics and its structural and prognostic implications.Methods: We recruited 271 patients with a first STEMI studied with TT-CMR 1 week after infarction. Of these patients, 145 underwent 1-week and 6-month TT-CMR and were used to characterize both the dynamics and the short-term and long-term structural implications of RNM-LS. Based on previously validated data, RNM areas were defined depending on the culprit coronary artery.Results: Reduced RNM-LS at 1 week (n = 70, 48%) was associated with larger infarct size and more depressed left ventricular ejection fraction (LVEF) at both the 1-week and 6-month TT-CMR (p value < 0.001). Late normalization of RNM-LS was frequent (28/70, 40%) and independently related to late recovery of LVEF (p value = 0.002). Patients with reduced RNM-LS at 1-week TT-CMR had more major adverse cardiac events (death, heart failure or re-infarction) in both the 271 patients included in the study group (26% vs. 11%, p value = 0.002) and in an external validation cohort made up of 177 STEMI patients (57% vs. 13%, p value < 0.001).Conclusion: After STEMI, reduced RNM-LS by TT-CMR is common and is associated with more severe short- and long-term structural damage. There is a beneficial tendency towards recovery of RNM-LS that parallels late recovery of LVEF. More events occur in patients with reduced RNM-LS. [ABSTRACT FROM AUTHOR]

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI. [ABSTRACT FROM AUTHOR]

Lycopsids are a minor component of current terrestrial herbaceous floras. However, lycopsid fossil diversity shows a great diversity and disparity including heterosporous woody plants, e.g. the giant isoetaleans that populated the extensive Pennsylvanian wetlands. The earliest known isoetaleans come from late Devonian localities from China. Here, we describe Lilingostrobus chaloneri gen. et sp. nov., a new isoetalean lycopsid from the Upper Devonian (Famennian) Xikuangshan Formation of China (Hunan Province, South China), which adds to the already impressive diversity of the Devonian lycopsids from China. Lilingostrobus shows an unusual combination of characters. This new plant is pseudoherbaceous, with a possible tufted habit, and consists of narrow axes with rare isotomies. The stem includes small quantities of secondary xylem. Each fertile axis bears one terminal strobilus comprising sporophylls ending in a very long upturned lamina. Microspores and putative megaspores have been found, but whether the plant has mono- or bisporangiate strobili is unknown. Importantly, our cladistic analysis identifies Lilingostrobus as a direct precursor of Isoetales, which provides new insights into the early evolution of lycopsids. [ABSTRACT FROM AUTHOR]

In extensive nonreperfused myocardial infarction (MI), remote fibrosis has been documented. Early reperfusion by primary angioplasty represents the gold standard method to minimize the extension of the infarction. We aimed to ascertain whether fibrosis also affects remote regions in reperfused MI in swine and patients. Swine were subjected to a transient occlusion of the left anterior descending artery followed by 1-week or 1-month reperfusion. Collagen content in the remote area macroscopically, microscopically, by magnetic resonance microimaging, and at the molecular level was similar to controls. In patients with previous MI, samples from autopsies displayed a significant increase in collagen content only in the infarct region. In patients with previous MI submitted to cardiac magnetic resonance-T1 mapping, the extracellular volume fraction in remote segments was similar to that for controls. In all scenarios, the remote region did not show a significant increase of collagen content in comparison with controls. [ABSTRACT FROM AUTHOR]

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): "Instituto de Salud Carlos III" and "Fondos Europeos de Desarrollo Regional FEDER" and Conselleria de Educación – Generalitat Valenciana. Introduction After acute myocardial infarction (AMI), the lack of oxygen and nutrients leads to cardiomyocyte necrosis and eventually to the formation of a collagen-based scar. Infarct scar characteristics, such as collagen bundle orientation, have a relevant influence on scar mechanics, the occurrence of cardiac arrhythmias, left ventricular dilation or aneurysm formation, wall stiffness, and the development of wall rupture or heart failure. However, the most adequate method for collagen bundle orientation (CBO) measurement in myocardial scar is not established. Purpose We aim to compare the measurement of collagen bundle orientation in infarct scar by Fourier analysis in three different histopathological techniques. Methods Juvenile swine (n=21) were subjected, by means of percutaneous balloon inflation, to a transient 90-min occlusion of mid left anterior descending artery followed by one month of reperfusion (chronic AMI group). Samples were obtained from the infarcted zone and stained with Masson's trichrome, Picrosirius red and Haematoxylin-Eosin (H-E) standard protocols. Five microphotographs of the myocardial scar were taken at 200x magnification with light, polarised and confocal microscopy, respectively. A single observer measured CBO by means of Fast Fourier Transform analysis using a semi-automated protocol. Comparability between techniques was studied by the Intraclass Correlation Coefficient (ICC), the coefficient of variation (CV) and the Bland-Altman (B&A) plots and limits of agreement. Results Measurement of CBO in Masson's trichrome tended to show higher (more "random-oriented") values than in Picrosirius and H-E+confocal techniques (ICC 0.79 and 0.7, p=0.001 and 0.005; B&A 0.29 to -0.02 and 0.43 to 0.01; CV 6.97% and 12.98%, respectively). However, measurement of CBO in Picrosirius and H-E+confocal techniques showed an "almost perfect" agreement (ICC 0.84, p<0.001; B&A 0.28 to -0.09; CV 17.33%). Selective staining and/or visualization of collagen in these latter techniques may underlie our findings, contrary to non-selective Masson's trichrome. Conclusion Picrosirius red staining (visualized with polarised microscopy) and Haematoxylin-Eosin (visualized with confocal microscopy) are comparable in terms of collagen bundle orientation measurement by Fourier analysis in an animal model of chronic infarct scar. Masson's trichrome (visualized with light microscopy) tends to show more "random-oriented" values, potentially due to non-specific staining and visualization of non-collagenous structures such as cells, and should not be recommended for this specific purpose. [ABSTRACT FROM AUTHOR]

In this paper, the implementation and characterization of a hand-held and simple biosensor for in-situ endotoxin determination are described. The integrated biosensor developed here is based on the electrochemical detection of endotoxin using polymyxin B as bioreceptor immobilized onto gold electrodes via a self-assembled monolayer. The cyclic voltammetry, electrochemical impedance spectroscopy, and atomic force microscopy were used to characterize the biosensor performance and properties throughout the functionalization process. In addition, a comparative analysis of the behavior and features of two alternative electrochemical techniques for endotoxin detection was carried out. The biosensing device fabricated by thin-film technologies provided a simple and robust method to detect low concentrations of endotoxin. [ABSTRACT FROM PUBLISHER]

Infarct size (IS) at 1 week after ST-elevation myocardial infarction (MI) diminishes during the first months. The incremental prognostic value of IS regression and of scar size (SS) at 6 months is unknown. We compared cardiovascular magnetic resonance (CMR)-derived IS at 1 week and SS at 6 months after MI for predicting late major adverse cardiac events (MACE). 250 patients underwent CMR at 1 week and 6 months after MI. IS and SS were determined as the extent of transmural late enhancement (in >50 % of wall thickness, ETLE). During 163 weeks, 23 late MACE (cardiac death, MI or readmission for heart failure after the 6 months CMR) occurred. Patients with MACE had a larger IS at 1 week (6 [4-9] vs. 3 [1-5], p < .0001) and a larger SS at 6 months (5 [2-6] vs. 3 [1-5], p = .005) than those without MACE. Late MACE rates in IS >median were higher at 1 week (14 vs. 4 %, p = .007) and in SS >median at 6 months (12 vs. 5 %, p = .053). The C-statistic for predicting late MACE of CMR at 1 week and 6 months was comparable (.720 vs. .746, p = .1). Only ETLE at 1 week (HR 1.31 95 % CI [1.14-1.52], p < .0001, per segment) independently predicted late MACE. CMR-derived SS at 6 months does not offer prognostic value beyond IS at 1 week after MI. The strongest predictor of late MACE is ETLE at 1 week. [ABSTRACT FROM AUTHOR]

Infection by the obligate human pathogens Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) reduces the expression of host epithelial cell transferrin receptor 1 (TfR-1) (Bonnah et al ., 2000, Cellular Microbiology 2: 207–218). In addition, the rate and pattern of TfR-1 cycling is altered, leading to diminished uptake of Tf-iron by infected host cells. As Tf-iron is important for maintaining iron homeostasis in the eukaryotic cell, these findings raised the possibility that Neisseria infection might affect further pathways of epithelial cell iron metabolism. We used a specialized cDNA microarray platform, the ‘IronChip’, to investigate the expression of genes involved in iron transport, storage and regulation. We show that mRNA expression of several host genes involved in iron homeostasis is altered. Surprisingly, the general mRNA expression profile of infected cells closely resembled that of uninfected cells grown in an iron-limited environment. An important exception to this profile is TfR-1, the mRNA level of which is strongly reduced. Low TfR-1 expression may be explained in part by decreased activity of the iron-regulatory proteins (IRPs) in MC-infected cells, which may result in the destabilization of TfR-1 mRNA. Intriguingly, low IRP activity contrasts with the decrease in H-ferritin protein levels in infected cells. This finding suggests that low IRP activity may be responsible in part for the decrease in TfR-1 mRNA levels. A discussion of these novel findings in relation to MC infection and virulence is provided. [ABSTRACT FROM AUTHOR]

Describes a pilot installation that was designed to stimulate a surface treatment tank fitted with a push-pull ventilation system. Components of the installation; Visual observation and video recording of the airflows; Differentiation of the initial semifree push curtain, the impact with the tank surface and the entrance into the exhaust.

Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption[SUP1,2]. Most cases arise from a founder mutation in HFE (845G →A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with β2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe[SUP-/-]) or homozygous with respect to the orthologous 882G→A mutation (Hfe[SUP845A/845A]) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function[SUP3]. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such asSLC11A2 (also called DMT1,DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory[SUP4-8]. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-defi-cient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1. [ABSTRACT FROM AUTHOR]

An abstract of the article "Acute heart failure with preserved ejection fraction and long-term Readmisions," by J. Nunez and colleagues is presented.

Purpose: Using cardiac imaging techniques it has been demonstrated that, after successful coronary revascularization of acute myocardial infarction (MI), microvascular obstruction (MVO) resolves spontaneously. Data on the course of this process in “in vivo” models are scarce. We aimed to characterize the dynamics of MVO in a swine model of reperfused anterior MI.Methods: Swine were subjected, by means of percutaneous balloon inflation, to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. Area at risk (thioflavin-S staining) and the extent of MVO (% of area at risk without thioflavin-S staining) were quantified. Microvessel density (using immunohistochemistry by von Willebrand factor antibody, vessels/field) and the expression of Hypoxia Induced Factor-1α (HIF-1α mRNA) were determined in controls and in the acute and chronic MI models.Results: In the acute MI model, MVO (8.4±4.5%) was detected in all cases. MVO significantly decreased in the chronic MI model (0.14±0.09%, p <0.001 vs. acute MI model, Figure). Microvessel density was significantly reduced in the acute MI model in comparison with the chronic MI model and controls (p <0.001, Figure). The expression of HIF-1α mRNA was significantly increased in the acute MI model in the infarct area (p<0.05 vs. controls) and in the chronic MI model in the infarct, adjacent and remote areas (p <0.01 vs. controls, Figure).Conclusion: In an “in vivo” controlled model of reperfused anterior MI, MVO spontaneously improves one month after reperfusion at macroscopic and microscopic levels. HIF could play a role in the molecular control of this process. [ABSTRACT FROM AUTHOR]

Purpose: In the context of myocardial infarction (MI) the availability of metabolites is clearly restricted, therefore a fuel metabolic shifts takes place. Previous studies have indicated that peroxisome proliferator activated receptor co-activator alpha (PGC-1α) pathway is a crucial regulator of cardiac metabolism in response to cardiac stress. Here we address the role of PGC-1α in regulating metabolic changes of MI.Methods: We studied a group of 12 common swine in which anterior MI was induced by means of angioplasty balloon inflation. A series of 6 swine were sacrificed at 48h post-infarction (acute infarction group) and another series of 6 swine were sacrificed at 3 weeks (chronic infarction group). Metabolites such as: glucose, pyruvate, ketone bodies, and lipids were analyzed in serum (mmol/L) at baseline, 75 min after balloon inflation, 2 h, 48 h and 3 weeks after reperfusion by means of enzymatic analysis. Results were compared to baseline levels. Genes related to PGC-1α such as: PGC-1α, ERR-α, PPAR-α, and HIF-1α, were analysed (fold change) in infarcted, adjacent and remote areas of porcine hearts 48h or 3 weeks post-infarction by molecular biology. Results were compared to 5 control swine without infarction.Results: In all groups, after 2h of infarction, a striking increase of lactate (3.2 ± 0.6 vs. 0.8 ± 0.3) and non-esterified fatty acids (0.6 ± 0.2 vs. 1.8 ± 0.3) was observed in serum compared to baseline (p<0.001 in both cases). Conversely, a significant decrease of glucose (5.2 ± 0.3 vs. 3.8 ± 0.2) and β-Hydroxybutyrate (1.8 ± 0.5 vs. 0.6 ± 0.2) occurred at the same time (p<0.001 in both cases). All values reverted progressively to baseline after 3 weeks. In comparison with controls, molecular biology analysis of acute infarcted hearts revealed a significant decrease of expression in mRNA and protein levels of transcription factors related to lipid and mitochondrial metabolism: PGC-1α(0.3 ± 0.1 vs. 1.2 ± 0.2 fold), ERR-α(0.8 ± 0.3 vs. 1.6 ± 0.2 fold) and PPAR-α(0.9 ± 0.3 vs. 1.7 ± 0.2 fold) (p<0.01 in all cases). Values didn't change after 3 weeks. However genes related to glucose metabolism were significantly increased in acute infarcts compared to controls: GLUT-1 (3.8 ± 0.4 vs. 1.1 ± 0.3 fold), HIF-1α(4.2 ± 1.3 vs. 1.0 ± 0.2 fold) (p<0.01 in both cases). These values recovered control levels after 3 weeks.Conclusion: A metabolic deregulation mediated by PGC-1α decreased expression takes place in the context of acute MI. This is mediated by a decrease of fatty acid oxidation and an increase of glucose utilization and it reverts after 3 weeks. [ABSTRACT FROM AUTHOR]

Purpose: Fibrosis plays a key role in the pathophysiology of left ventricular (LV) remodelling after myocardial infarction (MI). The dynamics of this process and whether it is a localized or diffuse phenomenon has not been totally clarified. We aimed to characterize these issues in a swine model of reperfused anterior MI.Methods: Swine were subjected by means of percutaneous balloon inflation to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. The extent of fibrosis was macroscopically (triphenyltetrazolium staining, % of LV volume) and microscopically (Sirius red staining, % of field) quantified in the infarct, adjacent and remote areas as well as in controls. TGF-β1, collagen1-A1, A2 and 3A1 gene expression was determined.Results: Macroscopically, necrosis (16±5% in the acute MI model) and fibrosis (16±4% in the chronic MI model) were detected in all cases. Macroscopic fibrosis occurred in the infarct but not in the adjacent or remote areas (Figure). At microscopic level, in comparison with controls, fibrosis was only significantly increased in the chronic MI model at the infarct area (35±4%, p<0.001) but not in the acute MI model or in the adjacent and remote areas in the chronic MI model (<4% in all cases, p=ns, Figure). TGF-β1 (p<0.05, acute and chronic MI models, Figure) and collagen1-A1, A2 and 3A1 (p<0.001, chronic MI model) gene expression were significantly increased in the infarct but not in the adjacent or remote areas (p=ns).Conclusion: In a model of anterior MI, 1-month after reperfusion, at macroscopic, microscopic and molecular levels, myocardial fibrosis appears as a localized process which mainly affects the infarct area but not the adjacent or remote regions. [ABSTRACT FROM PUBLISHER]

Programmed death-1 (PD-1) and Programmed death-1 ligand (PD-L1) regulate immune response. Previous studies associate an immune deregulation in ST-elevation myocardial infarction STEMI.We recruited 100 patients with a first STEMI treated with reperfusion. In all patients PD-1 and PD-L1 expression was studied 24 h post-reperfusion in peripheral blood mononuclear cells (PBMCs), by means of flow cytometry and molecular biology. PD-1 and PD-L1 expression was serially analyzed in the first 20 patients before reperfusion and 24h, 96h and 30 days afterwards. Results were compared with 30 age- and sex-matched controls. Cardiac Magnetic Resonance was used to quantify infarct size 1-week after infarction. In a series of 8 swine with induced STEMI, PD-1 and PD-L1 expression was analyzed at baseline, 90 min after balloon inflation, 2 h and 24 h after reperfusion in PBMCs, and in swine hearts. Results were compared to 5 controls.In patients, in comparison with controls, a significant decrease of PD-1 expression [mRNA fold change 0.8 ± 0.3 vs. 1.2 ± 0.6] and an increase of PD-L1+ expression [mRNA fold change 2.7 ± 2.1 vs. 0.9 ± 0.5] was observed 24h after infarction in PBMCs (p <0.05). STEMI patients with large infarct size showed decreased PD-1 expression, PD-L1 did not changed (Figure 1). Both in patients and swine, showed a significant increase of PD-1 and PD-L1 expression before reperfusion. Swine hearts revealed a marked infiltration of PMBCs and a significant increase of PD-1 and PD-L1 expression in the infarcted area compared to controls (Figure 2)Acute changes in the PD-1 pathway take place in acute STEMI. A lesser expresion of PD-1 in peripheral blood, which could be due to myocardial infiltration in the infarcted area of PBMCs, associates with a larger infarct size. [ABSTRACT FROM PUBLISHER]

The articel presents an abstract of the study "Hyperuricemia in Acute Heart Failure: More Than a Simple Spectator?," by J. Nunez and colleagues.