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Resumen Antecedentes y objetivo La resonancia magnetica (RM) con acido gadoxetico es una tecnica ampliamente usada en la practica clinica en Espana para el diagnostico, tratamiento y seguimiento de pacientes con metastasis hepaticas, aunque existe variabilidad en su uso. El objetivo de este trabajo fue emitir recomendaciones acerca del uso de la RM con acido gadoxetico en la deteccion y diagnostico de metastasis hepaticas en el contexto de la practica clinica en Espana. Material y metodos Este proyecto ha sido realizado por un grupo de nueve expertos que analizaron una serie de recomendaciones sobre el uso de acido gadoxetico extraidas de documentos de consenso internacionales. A partir de este analisis, los expertos decidieron rechazar, adoptar, contextualizar o adaptar cada una de las recomendaciones. Una vez establecidas, las recomendaciones finales fueron votadas por el mismo grupo de expertos. Resultados Los expertos consensuaron 5 recomendaciones relacionadas con el uso de esta tecnica de imagen en el manejo de metastasis hepaticas en tres situaciones clinicas: 1) en la deteccion, 2) en el diagnostico y caracterizacion preoperatoria y 3) en la deteccion tras un tratamiento quimioterapico. Conclusion Los resultados apoyan el beneficio clinico de la RM con acido gadoxetico en la deteccion de metastasis hepaticas, favoreciendo la planificacion preoperatoria, especialmente en aquellas menores de 1 cm, facilitando asi el diagnostico temprano de la diseminacion metastasica.

Magnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain.This project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts.The experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment.The results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1 cm, thus facilitating early diagnosis of metastatic spread.

Cannabis sativa is a global multi-billion-dollar cash crop with numerous industrial uses, including in medicine and recreation where its value is largely owed to the production of pharmacological and psychoactive metabolites known as cannabinoids. Often underappreciated in this role, the lipoxygenase (LOX)-derived green leaf volatiles (GLVs), also known as the scent of cut grass, are the hypothetical origin of hexanoic acid, the initial substrate for cannabinoid biosynthesis. The LOX pathway is best known as the primary source of plant oxylipins, molecules analogous to the eicosanoids from mammalian systems. These molecules are chemically and functionally diverse group of fatty acid-derived signals that govern nearly all biological processes including plant defense and development. The interaction between oxylipin and cannabinoid biosynthetic pathways remains to be explored.Despite their unique importance in this crop, there has not been a comprehensive investigation focusing on the genes responsible for oxylipin biosynthesis in any Cannabis species. This study documents the first genome-wide catalogue of the Cannabis sativa oxylipin biosynthetic genes and identified 21 LOX, five allene oxide synthases (AOS), three allene oxide cyclases (AOC), one hydroperoxide lyase (HPL), and five 12-oxo-phytodienoic acid reductases (OPR). Gene collinearity analysis found chromosomal regions containing several isoforms maintained across Cannabis, Arabidopsis, and tomato. Promoter, expression, weighted co-expression genetic network, and functional enrichment analysis provide evidence of tissue- and cultivar-specific transcription and roles for distinct isoforms in oxylipin and cannabinoid biosynthesis.This knowledge facilitates future targeted approaches towards Cannabis crop improvement and for the manipulation of cannabinoid metabolism.

Cannabis sativa is a global multi-billion-dollar cash crop with numerous industrial uses, including in medicine and recreation where its value is largely owed to the production of pharmacological and psychoactive metabolites known as cannabinoids. Often underappreciated in this role, the lipoxygenase (LOX)-derived green leaf volatiles (GLVs), also known as the scent of cut grass, are the hypothetical origin of hexanoic acid, the initial substrate for cannabinoid biosynthesis. The LOX pathway is best known as the primary source of plant oxylipins, molecules analogous to the eicosanoids from mammalian systems. These molecules are a group of chemically and functionally diverse fatty acid-derived signals that govern nearly all biological processes including plant defense and development. The interaction between oxylipin and cannabinoid biosynthetic pathways remains to be explored. Despite their unique importance in this crop, there has not been a comprehensive investigation focusing on the genes responsible for oxylipin biosynthesis in any Cannabis species. This study documents the first genome-wide catalogue of the Cannabis sativa oxylipin biosynthetic genes and identified 21 LOX, five allene oxide synthases (AOS), three allene oxide cyclases (AOC), one hydroperoxide lyase (HPL), and five 12-oxo-phytodienoic acid reductases (OPR). Gene collinearity analysis found chromosomal regions containing several isoforms maintained across Cannabis, Arabidopsis, and tomato. Promoter, expression, weighted co-expression genetic network, and functional enrichment analysis provide evidence of tissue- and cultivar-specific transcription and roles for distinct isoforms in oxylipin and cannabinoid biosynthesis. This knowledge facilitates future targeted approaches towards Cannabis crop improvement and for the manipulation of cannabinoid metabolism.

Funding Acknowledgements Type of funding sources: None. Introduction An increase it is being seen in patients who are referred for consultation due to dyspnea persistent after having overcome COVID19. The cause for this sequel is still not entirely clear, but our group has observed -in another study- that the consumption of oxygen (VO2) determined by cardiopulmonar exercise test (CPET) in these patients is low with respect to its predicted (p50). The objective of the present work was to demonstrate this hypothesis against to a control group with similar characteristics, who have not suffered from COVID19. Methods We conducted a prospective study with military personnel who are part of a corps of army elite. All subjects have performed the same training daily during the last 2 years. They were divided into 3 groups: the first (G1) made up of those who had not suffered from the COVID19 disease; a second group (G2) that had suffered from it, but did not report impairment of functional class (CF); and a third group (G3) who maintained dyspnea persistent 3 months after suffering from the disease. Analytical with NT-proBNP, echocardiogram, basal spirometry, and CPET were performed. None required hospital admission. Results 36 subjects were included, distributed as follows: G1 (n = 14), G2 (n = 15), G3 (n = 7). The 3 groups had a similar age and BMI. None of the subjects presented alterations in baseline spirometry, neither structural heart disease in the echo, and nor relevant analytical alterations, being NT-proBNP less than 125 pg/ml in all of them. In relation to the response variables cardiovascular, statistical differences (p = 0.03) were observed in peak oxygen consumption predicted among the three groups (% predicted peak VO2), being significantly lower in the G3 subjects. In addition, a trend was observed -in absolute values- of peak VO2 to be lower in G3 -not significant probably due to the small sample size-. They were not objectified significant differences in PulseO2, nor in OUES. No patient presented alterations in the ventilatory efficiency parameters, or in final BR. Conclusions In our sample, patients who remained with persistent dyspnea after COVID-19, have a lower functional capacity compared to healthy subjects of the same characteristics, and with respect to subjects who after COVID19 do not present any symptoms. This subjective deterioration of the FC can be objectively quantified using CPET, thus reaffirming its value in this context.

To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p

Introduction The primary study objective was to characterize the pattern of in-hospital mortality in dogs with gastric dilatation and volvulus (GDV), with a focus on preoperative nonsurvival. Materials and methods A retrospective review of medical records from a 10-year period was undertaken at a university teaching hospital. Data collected included signalment, physical examination parameters at hospital presentation, blood lactate concentration, and outcome. Results A total of 498 dogs were included. Overall, 319 (64.1%) survived to discharge and 179 (35.9%) were nonsurvivors. Of the nonsurvivors, 149 (31.3% of all dogs) were euthanized and 30 (6%) died. Of those dogs euthanized, the majority (n = 116) were euthanized at the time of hospital presentation prior to surgery (ie, without intent to treat). When dogs that were euthanized prior to surgery were excluded, 83.5% of dogs survived to discharge. Median group age was higher in those euthanized than in the group of dogs that survived to discharge. Conclusions Preoperative euthanasia and hence nonsurvival without intent to treat accounted for the majority of GDV mortality in this study. Given the high rate of nonsurvival without intent to treat it is likely that efforts focused at disease prevention will ultimately affect a much greater improvement in overall disease mortality than those focused on improving treatment.

Colletotrichum graminicola is a hemibiotrophic fungus that causes anthracnose leaf blight (ALB) and anthracnose stalk rot (ASR) in maize. Despite substantial economic losses caused by these diseases, the defence mechanisms against this pathogen remain poorly understood. Several hormones are suggested to aid in defence against C. graminicola, such as jasmonic acid (JA) and salicylic acid (SA), but supporting genetic evidence was not reported. Green leaf volatiles (GLVs) are a group of well‐characterized volatiles that induce JA biosynthesis in maize and are known to function in defence against necrotrophic pathogens. Information regarding the role of GLVs and JA in interactions with (hemi)biotrophic pathogens remains limited. To functionally elucidate GLVs and JA in defence against a hemibiotrophic pathogen, we tested GLV‐ and JA‐deficient mutants, lox10 and opr7 opr8, respectively, for resistance to ASR and ALB and profiled jasmonates and SA in their stalks and leaves throughout infection. Both mutants were resistant and generally displayed elevated levels of SA and low amounts of jasmonates, especially at early stages of infection. Pretreatment with GLVs restored susceptibility of lox10 mutants, but not opr7 opr8 mutants, which coincided with complete rescue of JA levels. Exogenous methyl jasmonate restored susceptibility in both mutants when applied before inoculation, whereas methyl salicylate did not induce further resistance in either of the mutants, but did induce mutant‐like resistance in the wild type. Collectively, this study reveals that GLVs and JA contribute to maize susceptibility to C. graminicola due to suppression of SA‐related defences., Jasmonic acid and green leaf volatiles act as key susceptibility factors of maize to Colletotrichum graminicola by suppressing salicylic acid‐mediated defence during the biotrophic phase of growth.

Funding Acknowledgements Type of funding sources: None. Introduction The transcatheter aortic valve implantation (TAVI) it´s an alternative to surgery in patients with low, moderate and high risk. The indexed systolic volume (ISV) is a parameter that has been associated with adverse events in this scenario. However, there are conflicting reports. The aim of this study was to evaluate the impact of the ISV in patients with severe aortic stenosis in which TAVI was performed. Methods Observational, retrospective and single institution study of patients in which a TAVI was performed between 2010 and 2020. The baseline characteristics of the patients were recorded and then the data were analyzed in two cohorts depending on the presence or not of an increase 3.5 ml/m2 of the ISV after TAVI in relation to the baseline (cohort A and cohort B). The cut-off point of 3.5 ml/m2 was chosen due to the fact that it was the median of the difference in the ISV before and after the TAVI. Results A total of 131 patients were included with a mean age of 84 years old (81-86). 74 patients (56.5%) presented an increase 3.5 ml/m2 of the ISV after TAVI, while there was an increment less than 3.5 ml/m2 in 57 patients (43.5%). The cohort A patients were older and had less prevalence of high blood pressure (Picture 1). Differences in survival weren´t found between the two cohorts, neither in the patients that before the TAVI had an ISV Conclusions In our population, an increase of the ISV after TAVI wasn´t associated with less adverse events in the follow up. The survival was similar between the patients that before the TAVI had an ISV

Introduction Persistent dyspnea in patients who have suffered from COVID-19 disease has become a constant in cardiology in recent months. Healther workers have been one of the population groups mainly affected during the pandemic. Chronic involvement by COVID-19 infection, such as dyspnea, is frequent, and so far, of unknown mechanism. CardioPulmonary Exercise Test (CPET) is currently the gold standard technique in the differential diagnosis of dyspnea. Therefore, CPET could be useful in the evaluation of patients after infection by the SARS-COV2 virus; a role still unknown in this context. Objective Evaluate the parameters obtained in CPET in patients who had suffered from COVID-19 disease and who presented persistent dyspnea. Methods We conducted a single-center and prospective study that included healthcare workers who suffered from COVID-19 disease with mild-moderate intensity symptoms, without the need for hospitalization, between March-December 2020 and who presented dyspnea on exertion at least 3 months after infection, in the absence of structural heart disease. An echo was performed, and a baseline spirometry followed by a CPET. Some of the variables collected such as VO2, OUES and PulseO2 have been quantified as a percentage (%) of the predicted according to predicted equations. Results 64 healthy patients with an active baseline life (without exertional dyspnea prior to infection) were included. 7 patients were excluded for presenting previously unknown structural heart disease. Of the 57 patients (Figure 1), more than half had a functional capacity lower than predicted (50th percentile), highlighting, among the cardiovascular response variables, a peak VO2 of 79% (SD: 14.0%) of the predicted, denoting slightly depressed functional capacity. In addition, in this subgroup, a VO2 at the level of the first ventilatory threshold (VT1) of 51.1% (SD: 4.2%) is observed over the predicted value -value that is considered in the lower limits of normality-; and a PulseO2 (systolic volume reflex) and an OUES in normal ranges with respect to those predicted. In the total of the 57 patients, no alterations were observed in the ventilatory efficiency parameters with effort, nor in the baseline spirometry, nor in the breathing reserve (BR), nor in final oxygen saturation (SatO2). Conclusion CPET has made it possible to identify that more than half of the patients show a deterioration -at least slight- in functional capacity (the majority of which are women) reaffirming the value of this test. The combination of this pattern that we observed in our serie is usually seen in patients with physical deconditioning and/or obesity, and is secondary to alterations in the peripheral use of oxygen, mainly at the muscular level. Based on this, a direct or indirect potential myopathic effect of the virus cannot be ruled out as responsible for the deterioration of the functional class of patients after COVID-19 disease. Funding Acknowledgement Type of funding sources: None.

Nervous necrosis virus (NNV), genus Betanodavirus, the etiological agent of the viral encephalopathy and retinopathy (VER), presents a genome with two positive-sense single-stranded RNA segments. Striped jack nervous necrosis virus (SJNNV) and red-spotted grouper nervous necrosis virus (RGNNV), together with reassortants RGNNV/SJNNV, are the betanodaviruses predominantly isolated in Southern Europe. An RGNNV/SJNNV reassortant isolated from Senegalese sole (wt160) causes high mortalities in this fish species. This virus presents differences in the sequence of the 3’ non-coding region (NCR) of both segments compared to RGNNV and SJNNV reference strains. Previously, it has been reported that the reversion of two of these differences (nucleotides 1408 and 1412) in the RNA2 3’NCR to the SJNNV-type (recombinant r1408-1412) resulted in a decrease in sole mortality. In the present study, we have applied an OpenArray® to analyse the involvement of sole immune response in the virulence of several recombinants: the r1408-1412 and two recombinants, developed in the present study, harbouring mutations at positions 3073 and 3093 of RNA1 3’NCR to revert them to RGNNV-type. According to the correlation values and to the number of expressed genes, the infection with the RNA2-mutant provoked the most different immune response compared to the immune response triggered after the infection with the rest of the viruses, and the exclusive and high upregulation of genes related to the complement system. The infection with the RNA1-mutants also provoked a decrease in mortality and their replication was delayed at least 24 h compared to the wt160 replication, which could provoke the lag observed in the immune response. Furthermore, the infection with the RNA1-mutants provoked the exclusive expression of pkr and the downregulation of il17rc.

With domestication, northward spread, and breeding, maize defence against root-herbivores relied on induced defences, decreasing levels of phytohormones involved in resistance, and increasing levels of a phytohormone involved in tolerance. We addressed whether a suite of maize (Zea mays mays) phytohormones and metabolites involved in herbivore defence were mediated by three successive processes: domestication, spread to North America, and modern breeding. With those processes, and following theoretical predictions, we expected to find: a change in defence strategy from reliance on induced defences to reliance on constitutive defences; decreasing levels of phytohormones involved in herbivore resistance, and; increasing levels of a phytohormone involved in herbivore tolerance. We tested those predictions by comparing phytohormone levels in seedlings exposed to root herbivory by Diabrotica virgifera virgifera among four plant types encompassing those processes: the maize ancestor Balsas teosinte (Zea mays parviglumis), Mexican maize landraces, USA maize landraces, and USA inbred maize cultivars. With domestication, maize transitioned from reliance on induced defences in teosinte to reliance on constitutive defences in maize, as predicted. One subset of metabolites putatively involved in herbivory defence (13-oxylipins) was suppressed with domestication, as predicted, though another was enhanced (9-oxylipins), and both were variably affected by spread and breeding. A phytohormone (indole-3-acetic acid) involved in tolerance was enhanced with domestication, and with spread and breeding, as predicted. These changes are consistent with documented changes in herbivory resistance and tolerance, and occurred coincidentally with cultivation in increasingly resource-rich environments, i.e., from wild to highly enriched agricultural environments. We concluded that herbivore defence evolution in crops may be mediated by processes spanning thousands of generations, e.g., domestication and spread, as well as by processes spanning tens of generations, e.g., breeding and agricultural intensification.

Multiple long-distance signals have been identified for pathogen-induced systemic acquired resistance, but mobile signals for symbiont-induced systemic resistance (ISR) are less well understood. We used ISR-positive and -negative mutants of maize (Zea mays) and the beneficial fungus Trichoderma virens and identified 12-oxo-phytodienoic acid (12-OPDA) and α-ketol of octadecadienoic acid (KODA) as important ISR signals. We show that a maize 13-lipoxygenase mutant, lox10, colonized by the wild-type T. virens (TvWT) lacked ISR response against Colletotrichum graminicola but instead displayed induced systemic susceptibility. Oxylipin profiling of xylem sap from T. virens-treated plants revealed that 12-OPDA and KODA levels correlated with ISR. Transfusing sap supplemented with 12-OPDA or KODA increased receiver plant resistance in a dose-dependent manner, with 12-OPDA restoring ISR of lox10 plants treated with TvWT or T. virens Δsm1, a mutant unable to induce ISR. Unexpectedly, jasmonic acid (JA) was not involved, as the JA-deficient opr7 opr8 mutant plants retained the capacity for T. virens-induced ISR. Transcriptome analysis of TvWT-treated maize B73 revealed upregulation of 12-OPDA biosynthesis and OPDA-responsive genes but downregulation of JA biosynthesis and JA response genes. We propose a model that differential regulation of 12-OPDA and JA in response to T. virens colonization results in ISR induction.

Lymphocystis disease, caused by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of tumour-like lesions on the skin of affected animals associated with several environmental factors and/or with stress due to the intensive culture conditions of fish farms. In a previous study, the genomes of a new LCDV species, LCDV-Sa, were detected, together with 2 previously unknown viruses, Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1). Gilthead seabream from 17 fish farms in Spain, Italy and Turkey were sampled between 2009 and 2015 to investigate the role of the newly described SaPV1 and SaPyV1 viruses in lymphocystis disease development. Our results show that in diseased fish, either or both of the new viruses are almost invariably detected together with LCDV (98%). In asymptomatic fish, these viruses were detected in a much lower percentage (28%) and mostly in concurrence with LCDV (24%). These data confirm the suspected association among the 3 different viruses during lymphocystis disease development in gilthead seabream and warrant future studies to establish their respective contributions.

With domestication, northward spread, and breeding, maize defence against root-herbivores relied on induced defences, decreasing levels of phytohormones involved in resistance, and increasing levels of a phytohormone involved in tolerance. We addressed whether a suite of maize (Zea mays mays) phytohormones and metabolites involved in herbivore defence were mediated by three successive processes: domestication, spread to North America, and modern breeding. With those processes, and following theoretical predictions, we expected to find: a change in defence strategy from reliance on induced defences to reliance on constitutive defences; decreasing levels of phytohormones involved in herbivore resistance, and; increasing levels of a phytohormone involved in herbivore tolerance. We tested those predictions by comparing phytohormone levels in seedlings exposed to root herbivory by Diabrotica virgifera virgifera among four plant types encompassing those processes: the maize ancestor Balsas teosinte (Zea mays parviglumis), Mexican maize landraces, USA maize landraces, and USA inbred maize cultivars. With domestication, maize transitioned from reliance on induced defences in teosinte to reliance on constitutive defences in maize, as predicted. One subset of metabolites putatively involved in herbivory defence (13-oxylipins) was suppressed with domestication, as predicted, though another was enhanced (9-oxylipins), and both were variably affected by spread and breeding. A phytohormone (indole-3-acetic acid) involved in tolerance was enhanced with domestication, and with spread and breeding, as predicted. These changes are consistent with documented changes in herbivory resistance and tolerance, and occurred coincidentally with cultivation in increasingly resource-rich environments, i.e., from wild to highly enriched agricultural environments. We concluded that herbivore defence evolution in crops may be mediated by processes spanning thousands of generations, e.g., domestication and spread, as well as by processes spanning tens of generations, e.g., breeding and agricultural intensification.

Funding Acknowledgements Type of funding sources: None. INTRODUCTION CRH in patients with ischemic heart disease is recommended by the different clinical practice guidelines with an IA level of evidence, with an important role in reducing cardiovascular mortality and hospital readmissions during follow-up. OBJECTIVE The goal of this study is to show the 4-year clinical results of a population of patients who participated in an CRH program after an Acute Coronary Syndrome (ACS). METHODS Between May/2014 and September/2017, 221 patients who had recently presented an ACS completed the 12 weeks of phase II of the CRH program at our center. In May/2020 we collected epidemiological, clinical and echocardiographic information at the time of the acute cardiovascular event; and we evaluate the current vital status of the patients and the incidence of readmissions for: angina, HF, new ACS, or arrhythmic events. RESULTS Of the 221 patients, 182 were men (82%). The mean age of our population was 58.3 ± 7.8 years. 58% (129 patients) suffered from ST-elevation ACS. The mean time of hospital stay was 6.20 ± 2.9 days. An echocardiogram was performed at discharge, which showed an average LVEF of 56 ± 6%. Eight patients (4%) developed early Ventricular Fibrilation (VF) during the acute phase of ACS. Among the classic CVRF, smoking (79%) was the most prevalent, followed by dyslipidemia (53%) and hypertension (47%). The mean time from hospital discharge to the start of phase II RHC was 42 ± 16 days. The overall incidence of events was 9%: 10 patients suffered reinfarction during follow-up, and 7 were readmitted for unstable angina, all of whom underwent PCI; no patient was admitted for HF; and none of the 8 patients with early VF had a new tachyarrhythmia, registering a single admission for VT during follow-up. None of the patients had sustained ventricular tachyarrhythmias during exercise-training. At the mean 4.5-year follow-up, 218 patients were still alive (98%). CONCLUSION The incidence of CV events in the follow-up of our cohort was low, which can be explained by the fact that it is a young population, with an LVEF at low limits of normality at discharge, which is one of the most important predictors in the prognosis after an ischemic event. As an improvement, we must shorten the time until the start of phase II of the program. CRH shows once again its clinical benefit after an ACS, in consonance with the existing evidence. Abstract Figure. Outcomes of a CRH program.

Funding Acknowledgements Type of funding sources: None. INTRODUCTION After publication of the 2019 ESC Guidelines for dyslipidemia, the LDL cholesterol target in patients with very high cardiovascular risk was reduced from 70 mg/dl to 55 mg/dl. Currently, there is more and more evidence that getting these levels is very important in prognosis, to avoid new cardiovascular events. The paradigm of this situation could be represented by young patients after STEMI, in which secondary prevention is essential to achieve a long-life expectancy. OBJECTIVE The aim of the present study is to analyze the impact the new guidelines have had on the control of LDL cholesterol in a population of young patients after STEMI, one year after their publication. METHODS A total of 101 consecutive young patients (aged ≤ 40 years) presenting with STEMI admitted at our center between 2006 and 2017 were included. There were no exclusion criteria. We collect demographic, clinical and treatment information, and laboratory values in september/2019 and again one year later. RESULTS Out of 101 patients, 89 were male (88.1%). Mean age was 35.87 ± 4.07 years. Among the classic cardiovascular risk factors, dyslipidemia (44.5%) was the second one most prevalent in our cohort, after smoking (93.1%). In September/2019, only 66.3% of our patients had a recent LDL-cholesterol control, and only 20.9% of them had a target LDL-cholesterol lower than 55 mg/dl ("LDL-c -goal"). During the following year, a new determination of LDL cholesterol was only carried out in 18 patients out of the total sample, with these results: 15 patients had an LDL> 55 mg/dl; 2 patients maintained an "LDL-c-goal", and only a single patient achieved optimal control (from 81 mg/dl to 39 mg/dl) coinciding with the change from low to high intensity statin. Regarding lipid-lowering treatment, in September/2019 the 87.7% of our population were taking statins, 21.9% ezetimibe, and 0.0% PCSK9-inhibitors. In that moment, in 6 patients, the lipid-lowering treatment was reduced (all of them had LDL values were between 65-105 mg/dl). One year later, in September/2020, 82.2% were taking statins, 21.9% ezetimibe, and in 1 patient was started with the PCSK-9 inhibitor. Thirteen patients (12.9%) had suffered a reinfarction during follow-up, but none in the last year. CONCLUSIONS Despite of the new LDL-cholesterol target established by the ESC Guidelines, we have not improved our lipid control in a population with high cardiovascular risk -with a percentage of cardiovascular events during mean follow-up that is not negligible-, being only 1 of each 5 patients correctly treated. We must carry out a closer clinical and analytical follow-up, by increasing our efforts in secondary prevention, and perhaps the Cardiac Rehabilitation Units can play an essential role in this objective. It is possible that the Covid-19 pandemic could have influenced these results. Abstract Figure. Lipid-lowering treatment.

Recently, crop breeders have widely adopted a new biotechnology-based process, termed Seed Production Technology (SPT), to produce hybrid varieties. The SPT does not produce nuclear male-sterile lines, and instead utilizes transgenic SPT maintainer lines to pollinate male-sterile plants for propagation of nuclear-recessive male-sterile lines. A late-stage pollen-specific promoter is an essential component of the pollen-inactivating cassette used by the SPT maintainers. While a number of plant pollen-specific promoters have been reported so far, their usefulness in SPT has remained limited. To increase the repertoire of pollen-specific promoters for the maize community, we conducted a comprehensive comparative analysis of transcriptome profiles of mature pollen and mature anthers against other tissue types. We found that maize pollen has much less expressed genes (&gt, 1 FPKM) than other tissue types, but the pollen grain has a large set of distinct genes, called pollen-specific genes, which are exclusively or much higher (100 folds) expressed in pollen than other tissue types. Utilizing transcript abundance and correlation coefficient analysis, 1215 mature pollen-specific (MPS) genes and 1009 mature anther-specific (MAS) genes were identified in B73 transcriptome. These two gene sets had similar GO term and KEGG pathway enrichment patterns, indicating that their members share similar functions in the maize reproductive process. Of the genes, 623 were shared between the two sets, called mature anther- and pollen-specific (MAPS) genes, which represent the late-stage pollen-specific genes of the maize genome. Functional annotation analysis of MAPS showed that 447 MAPS genes (71.7% of MAPS) belonged to genes encoding pollen allergen protein. Their 2-kb promoters were analyzed for cis-element enrichment and six well-known pollen-specific cis-elements (AGAAA, TCCACCA, TGTGGTT, [TA]AAAG, AAATGA, and TTTCT) were found highly enriched in the promoters of MAPS. Interestingly, JA-responsive cis-element GCC box (GCCGCC) and ABA-responsive cis-element-coupling element1 (ABRE-CE1, CCACC) were also found enriched in the MAPS promoters, indicating that JA and ABA signaling likely regulate pollen-specific MAPS expression. This study describes a robust and straightforward pipeline to discover pollen-specific promotes from publicly available data while providing maize breeders and the maize industry a number of late-stage (mature) pollen-specific promoters for use in SPT for hybrid breeding and seed production.

Diatoms are important organisms in freshwater ecosystems due to their position as primary producers and therefore, analyzing their communities provides relevant information on ecosystem functioning. Diatoms have historically been identified based on morphological traits, which is time-consuming and requires well-trained specialists. Nevertheless, DNA barcoding offers an alternative approach to overcome some limitations of the morphological method. Here, we assess if both approaches are comparable methods to study patterns and mechanisms (including environmental filtering and dispersal limitation) of epiphytic diatom metacommunities using a comprehensive dataset from 22 Mediterranean ponds at different taxonomic resolutions. We used a fragment of rbcL barcode gene combined with High-Throughput Sequencing to infer diatom community composition. The overall degree of correspondence between both approaches was assessed by Procrustean rotation analysis and Procrustean randomization tests, whereas the role of local environmental variables and geographical distances was studied using a comprehensive combination of BIOENV, Mantel tests and distance-based redundancy analysis. Our results showed a relatively poor correspondence in the compositional variation of diatom metacommunity between both approaches. We speculate that the incompleteness of the reference database and the bioinformatics processing are the biases most likely affecting the molecular approach, whereas the limited counting effort and the presence of cryptic species are presumably the major biases related with the morphological method. On the other hand, variation in diatom community composition detected with both approaches was strongly related to the environmental template, which may be related with the narrow ecological niche and the strong preferences for particular substrata of some diatom species. Nevertheless, we found no significant relationship between compositional variation and geographical distances at regional extent. Overall, our work highlights the importance of DNA metabarcoding to address empirical research questions of community ecology in freshwaters, especially once the reference databases include most genotypes of occurring taxa and bioinformatics biases are overcome.

The TIFY gene family is a plant-specific gene family encoding a group of proteins characterized by its namesake, the conservative TIFY domain and members can be organized into four subfamilies: ZML, TIFY, PPD and JAZ (Jasmonate ZIM-domain protein) by presence of additional conserved domains. The TIFY gene family is intensively explored in several model and agriculturally important crop species and here, yet the composition of the TIFY family of maize has remained unresolved. This study increases the number of maize TIFY family members known by 40%, bringing the total to 47 including 38 JAZ, 5 TIFY, and 4 ZML genes. The majority of the newly identified genes were belonging to the JAZ subfamily, six of which had aberrant TIFY domains, suggesting loss JAZ-JAZ or JAZ-NINJA interactions. Six JAZ genes were found to have truncated Jas domain or an altered degron motif, suggesting resistance to classical JAZ degradation. In addition, seven membranes were found to have an LxLxL-type EAR motif which allows them to recruit TPL/TPP co-repressors directly without association to NINJA. Expression analysis revealed that ZmJAZ14 was specifically expressed in the seeds and ZmJAZ19 and 22 in the anthers, while the majority of other ZmJAZs were generally highly expressed across diverse tissue types. Additionally, ZmJAZ genes were highly responsive to wounding and JA treatment. This study provides a comprehensive update of the maize TIFY/JAZ gene family paving the way for functional, physiological, and ecological analysis.

Funding Acknowledgements Type of funding sources: None. Dilated cardiomyopathy (DCM) is a complex myocardial disease, with a high burden of symptoms and decreased life expectancy. Mitral regurgitation (MR) is a frequent comorbid condition and it is thought that it deteriorates left ventricle (LV) volume and ejection fraction. Guideline directed medical therapy for heart failure improves myocardial function and decreases morbidity and mortality, and there is ongoing interest in the application of novel percutaneous techniques like mitral edge-to-edge repair or resynchronization therapy in order to decrease cardiovascular events (CVE). Our objective was to analyze if MR is associated with late gadolinium enhancement (LGE), left ventricle (LV) or right ventricle (RV) dysfunction and cardiovascular events in patients with DCM. A retrospective, case control study was designed including 173 patients (mean age 60 years, 73% males, 36% dyslipemia, 30% diabetes, 20% hypertension, 8% current smokers) with diagnosis of DCM and cardiac magnetic resonance study in our center between 2014-2020 according to the latest European Society of Cardiology (ESC) definition and the latest updated position paper. Clinical data, use of guideline directed medical therapy and devices, cardiac imaging tests, mortality and CVE were collected and analyzed. Mitral regurgitation was calculated on CMR and was included if it was more than mild. After a mean follow up of 18 months, 53 patients (30%) suffered a CVE (16% heart failure, 14% incident arrythmia, 0,5% stroke 8% death). Patients with MR (n= 48; 28%) had worse LV ejection fraction (-4,8% mean; p=,02), worse RV ejection fraction (-5,5% mean; p=,03), more hospitalizations due to heart failure (OR 1,78; p=,01), had a trend toward increased mortality although it was not statistically significant (p=,01) and a trend towards late gadolinium enhancement (p,13). There was no association with incident arrythmias (p=,5) or stroke (p=,9) In multivariate analyses (log regression, multiple linear regression) MR was maintained as an independent predictor of worse RV ejection fraction (mean -3,9%; p=,03), and hospitalization for heart failure (OR 3,8; p=,043). There was also a trend toward increased mortality (p=,1) in our population. Figure. In patients with DCM, MR is associated with decreased LV and RV ejection fraction, hospitalization due to heart failure and has a tendency to be associated with mortality. Specific treatment for mitral regurgitation, including percutaneous edge-to-edge repair or surgery according to current guidelines, might decrease the severity of MR in these patients and that could lead to an improved prognosis and less morbidity. Further studies should review the impact of an interventional strategy in mitral regurgitation in patients with DCM. Abstract Figure. Mitral regurgitation in DCM: prognosis.

Seed maceration and contamination with mycotoxin fumonisin inflicted by Fusarium verticillioides is a major disease concern for maize producers worldwide. Meta-analyses of quantitative trait loci for Fusarium ear rot resistance uncovered several ethylene (ET) biosynthesis and signaling genes within them, implicating ET in maize interactions with F. verticillioides. We tested this hypothesis using maize knockout mutants of the 1-aminocyclopropane-1-carboxylate (ACC) synthases ZmACS2 and ZmACS6. Infected wild-type seed emitted five-fold higher ET levels compared with controls, whereas ET was abolished in the acs2 and acs6 single and double mutants. The mutants supported reduced fungal biomass, conidia, and fumonisin content. Normal susceptibility was restored in the acs6 mutant with exogenous treatment of ET precursor ACC. Subsequently, we showed that fungal G-protein signaling is required for virulence via induction of maize-produced ET. F. verticillioides Gβ subunit and two regulators of G-protein signaling mutants displayed reduced seed colonization and decreased ET levels. These defects were rescued by exogenous application of ACC. We concluded that pathogen-induced ET facilitates F. verticillioides colonization of seed, and, in turn, host ET production is manipulated via G-protein signaling of F. verticillioides to facilitate pathogenesis. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

The transcriptomic response of Senegalese sole (Solea senegalensis) triggered by two betanodaviruses with different virulence to that fish species has been assessed using an OpenArray® platform based on TaqMan™ quantitative PCR. The transcription of 112 genes per sample has been evaluated at two sampling times in two organs (head kidney and eye/brain-pooled samples). Those genes were involved in several roles or pathways, such as viral recognition, regulation of type I (IFN-1)-dependent immune responses, JAK-STAT cascade, interferon stimulated genes, protein ubiquitination, virus responsive genes, complement system, inflammatory response, other immune system effectors, regulation of T-cell proliferation, and proteolysis and apoptosis. The highly virulent isolate, wSs160.3, a wild type reassortant containing a RGNNV-type RNA1 and a SJNNV-type RNA2 segments, induced the expression of a higher number of genes in both tested organs than the moderately virulent strain, a recombinant harbouring mutations in the protruding domain of the capsid protein. The number of differentially expressed genes was higher 2 days after the infection with the wild type isolate than at 3 days post-inoculation. The wild type isolate also elicited an exacerbated interferon 1 response, which, instead of protecting sole against the infection, increases the disease severity by the induction of apoptosis and inflammation-derived immunopathology, although inflammation seems to be modulated by the complement system. Furthermore, results derived from this study suggest a potential important role for some genes with high expression after infection with the highly virulent virus, such as rtp3, sacs and isg15. On the other hand, the infection with the mutant does not induce immune response, probably due to an altered recognition by the host, which is supported by a different viral recognition pathway, involving myd88 and tbkbp1. Funding for open access charge: Universidad de Málaga / CBUA. This work has been supported by the projects AGL2014-54532-C2 and RTI2018-094687-B-C22 form the Spanish Government (Ministerio de Economía y Competitividad), co-funded by the FEDER.

Excess of deaths is a technique used in epidemiology to assess the deaths caused by an unexpected event. For the present COVID-19 pandemic, we discuss the performance of some linear and nonlinear time series forecasting techniques widely used for modeling the actual pandemic and provide estimates for this metric from January 2020 to April 2021. We apply the results obtained to evaluate the evolution of the present pandemic in Brazil and Spain, which allows in particular to compare how well (or bad) these countries have managed the pandemic. For Brazil, our calculations refute the claim made by some officials that the present pandemic is "a little flu". Some studies suggest that the virus could be lying dormant across the world before been detected for the first time. In that regard, our results show that there is no evidence of deaths by the virus in 2019, This work was supported in the form of funding in part by Ministerio de Ciencia e Innovacio´n of Spain (Grant No. PID2019-108079GB-C22/AEI/10.13039/501100011033)awarded to NT

Background Recent studies have shown that the extent of extravalvular (extra-aortic valve) cardiac damage in patients with severe aortic stenosis (AS) have important prognostic implications for clinical outcomes after aortic valve replacement (AVR). Aims The aim of the present study is to evaluate the prognostic impact of a defined staging classification (“Généreux Staging Classification”) (GSC) characterizing the extent of extravalvular cardiac damage in patients with severe AS undergoing percutaneous transcatheter aortic valve implantation (TAVI). Methods A total of 102 consecutive patients, admitted in our institution between 2011–2017, with severe AS (echo-defined by peak aortic velocity, mean transvalvular gradient or aortic valve area) and symptoms related to AS (dyspnea, heart failure, angina or syncope) undergoing TAVI, were included. These patients were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to TAVI, regarding the GSC: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4). Two-year outcomes were compared using Kaplan– Meier techniques and multivariable Cox proportional hazards models were used to identify 2-year predictors of mortality. Results Out of 102 patients, 57 were male (55.9%). Mean age was 83.46±4.23 years. 2 patients (2.1%) were classified as Stage 0; 20 patients (20.3%) as Stage 1; 55 patients (54.2%) as Stage 2; 22 (21.6%) as Stage 3; and 3 patients (2.9%) as Stage 4. Two-year mortality was 0.0% in Stage 0, 5.0% in Stage 1, 5.5% in Stage 2, and 44.0% in Stages 3–4. After multivariable and univariate analysis, stage of cardiac damage was independently associated as predictor for all-cause mortality at 2-years, after TAVI (HR 2.8 [1.3±6.2], p Conclusions Given the strong association demonstrated in this study between advanced staging of cardiac damage and worse clinical outcomes after TAVI in short-middle term survival, consideration of the GSC in patients with severe AS in future recommendations for risk stratification might be useful. Two-year all-cause death in TAVI by GSC. Funding Acknowledgement Type of funding source: None

There is an ongoing debate regarding the use of beta blockers (BB) in heart failure with preserved or intermediate ejection fraction. Most studies with BB included patients with moderate to severe left ventricle (LV) dysfunction and some trials challenge the assumption that BB are an effective therapy in these patients. Furthermore, there are some causes of heart failure where the use of BB is not well defined, particularly patients with DCM and mildly reduced LV ejection fraction. Our objective was to analyze the use of beta blockers in patients with dilated cardiomyopathy and to assess its relationship with LV or right ventricle (RV) ejection fraction, late gadolinium enhancement and cardiovascular events (CVE). A retrospective, case control study was designed including 173 patients (mean age 60 years, 73% males, 36% dyslipemia, 30% diabetes, 20% hypertension, 8% currents smoker, 12% previous atrial fibrillation) with diagnosis of DCM and CMR study in our center between 2014–2020 according to the latest European Society of Cardiology (ESC) definition and the latest updated position paper. Clinical data, use of guideline directed medical therapy and devices, cardiac imaging tests, mortality and CVE were collected and analyzed. After a mean follow up of 18 months, 53 patients (30%) suffered a CVE (16% heart failure, 14% incident arrythmia, 0.5% stroke 8% death). The use of beta blockers (n=152; 87%) was associated with a reduced risk for arrythmias (OR=0.019; p=0.0006) in a univariate analysis. It was not associated with RV ejection fraction (p=0.3), hospitalization for heart failure (p=0.03), mortality (p=0.26), or late gadolinium enhancement (p=0.8). For multivariate analyses (log regression, multiple linear regression) we adjusted for age, cardiovascular risk factors, medications, presence of atrial fibrillation, use of devices, LV and RV ejection fraction and presence of late gadolinium enhancement. In our multivariate analyses the use of beta blockers was an independent predictor of improved left ventricle ejection fraction (5.8% mean; p=0.009) and was associated with a marked decrease in the risk of incident arrythmias (OR=0.028; p=0.002) and in mortality (OR=0.068; p=0.041). In patients with DCM, the use of beta blockers is associated with improved LV ejection fraction and a statistically significant reduction in mortality and incident arrythmias. Beta blockers should be recommended irrespective of LV ejection fraction in order to decrease morbidity and mortality in patients with dilated cardiomyopathy. Further studies should assess the contribution of beta blockers in specific etiologies of dilated cardiomyopathy where they could be most helpful and could help to identify the best candidates for early initiation of heart failure therapy. Funding Acknowledgement Type of funding source: None

We study an energy-dependent potential related to the Rosen&ndash, Morse potential. We give in closed-form the expression of a system of eigenfunctions of the Schr&ouml, dinger operator in terms of a class of functions associated to a family of hypergeometric para-orthogonal polynomials on the unit circle. We also present modified relations of orthogonality and an asymptotic formula. Consequently, bound state solutions can be obtained for some values of the parameters that define the model. As a particular case, we obtain the symmetric trigonometric Rosen&ndash, Morse potential for which there exists an orthogonal basis of eigenstates in a Hilbert space. By comparing the existent solutions for the symmetric trigonometric Rosen&ndash, Morse potential, an identity involving Gegenbauer polynomials is obtained.

Plant physiological processes generally are regulated by phytohormones, including plant biochemical responses to herbivory. Here, we addressed whether a suite of maize (Zea mays mays) phytohormones, including some precursor and derivative metabolites, relevant to herbivory defence were mediated by the crop’s domestication, northward spread, and modern breeding. For this, we compared phytohormone and metabolite levels among four plant types representing the evolutionary and agronomic transitions from maize’s wild ancestor, Balsas teosinte (Zea mays parviglumis), to Mexican and US maize landraces, and to highly-bred US maize cultivars, as affected by root herbivory by Western corn rootworm (Diabrotica virgifera virgifera). Following ecological-evolutionary hypotheses, we expected to find changes in: (i) maize defence strategy, from reliance on induced to constitutive defences; (ii) levels of phytohormones relevant to herbivore resistance consistent with gradual weakening of defences, and; (iii) levels of a phytohormone relevant to herbivory tolerance because it positively affects plant growth. We found that with its domestication, maize seemed to have transitioned from reliance on induced defences in Balsas teosinte to reliance on constitutive defences in maize. Also, we found that while one subset of phytohormones relevant to herbivory was suppressed (13-oxylipins), another was enhanced (9-oxylipins) with domestication, and both subsets were variably affected by spread and breeding. Finally, an auxin phytohormone directly linked to growth (indole-3-acetic acid), increased significantly with domestication, and seemingly with spread and breeding. We concluded that rootworm defences in maize were mediated by domestication and ensuing processes, such as spread and breeding, and argued that agricultural intensification mediated maize defence evolution in parallel with modern breeding.

Throughout infection, plant-parasitic nematodes activate a complex host defense response that will regulate their development and aggressiveness. Oxylipins—lipophilic signaling molecules—are part of this complex, performing a fundamental role in regulating plant development and immunity. At the same time, the sedentary root-knot nematode Meloidogyne spp. secretes numerous effectors that play key roles during invasion and migration, supporting construction and maintenance of nematodes' feeding sites. Herein, comprehensive oxylipin profiling of tomato roots, performed using LC–MS/MS, indicated strong and early responses of many oxylipins following root-knot nematode infection. To identify genes that might respond to the lipidomic defense pathway mediated through oxylipins, RNA-Seq was performed by exposing Meloidogyne javanica second-stage juveniles to tomato protoplasts and the oxylipin 9-HOT, one of the early-induced oxylipins in tomato roots upon nematode infection. A total of 7512 differentially expressed genes were identified. To target putative effectors, we sought differentially expressed genes carrying a predicted secretion signal peptide. Among these, several were homologous with known effectors in other nematode species; other unknown, potentially secreted proteins may have a role as root-knot nematode effectors that are induced by plant lipid signals. These include effectors associated with distortion of the plant immune response or manipulating signal transduction mediated by lipid signals. Other effectors are implicated in cell wall degradation or ROS detoxification at the plant–nematode interface. Being an integral part of the plant's defense response, oxylipins might be placed as important signaling molecules underlying nematode parasitism.

Oxylipins are a newly emerging group of signals that serve defence roles or promote virulence. To identify specific host and fungal genes and oxylipins governing the interactions between maize and Fusarium verticillioides, maize wild-type and lipoxygenase3 (lox3) mutant were inoculated with either F. verticillioides wild-type or linoleate-diol-synthase 1-deleted mutant (ΔFvlds1D). The results showed that lox3 mutants were more resistant to F. verticillioides. The reduced colonization on lox3 was associated with reduced fumonisin production and with a stronger and earlier induction of ZmLOX4, ZmLOX5 and ZmLOX12. In addition to the reported defence function of ZmLOX12, we showed that lox4 and lox5 mutants were more susceptible to F. verticillioides and possessed decreased jasmonate levels during infection, suggesting that these genes are essential for jasmonic acid (JA)-mediated defence. Oxylipin profiling revealed a dramatic reduction in fungal linoleate diol synthase 1 (LDS1)-derived oxylipins, especially 8-HpODE (8-hydroperoxyoctadecenoic acid), in infected lox3 kernels, indicating the importance of this molecule in virulence. Collectively, we make the following conclusions: (1) LOX3 is a major susceptibility factor induced by fungal LDS1-derived oxylipins to suppress JA-stimulating 9-LOXs; (2) LOX3-mediated signalling promotes the biosynthesis of virulence-promoting oxylipins in the fungus; and (3) both fungal LDS1- and host LOX3-produced oxylipins are essential for the normal infection and colonization processes of maize seed by F. verticillioides.