The Role of CLE Peptides in the Suppression of Mycorrhizal Colonization of Tomato.

Symbioses with beneficial microbes are widespread in plants, but these relationships must balance the energy invested by the plants with the nutrients acquired. Symbiosis with arbuscular mycorrhizal (AM) fungi occurs throughout land plants, but our understanding of the genes and signals that regulate colonization levels is limited, especially in non-legumes. Here, we demonstrate that in tomato, two CLV3/EMBRYO-SURROUNDING REGION (CLE) peptides, SlCLE10 and SlCLE11, act to suppress AM colonization of roots. Mutant studies and overexpression via hairy transformation indicate that SlCLE11 acts locally in the root to limit AM colonization. Indeed, SlCLE11 expression is strongly induced in AM-colonized roots, but SlCLE11 is not required for phosphate suppression of AM colonization. SlCLE11 requires the FIN gene that encodes an enzyme required for CLE peptide arabinosylation to suppress mycorrhizal colonization. However, SlCLE11 suppression of AM does not require two CLE receptors with roles in regulating AM colonization, SlFAB (CLAVATA1 ortholog) or SlCLV2. Indeed, multiple parallel pathways appear to suppress mycorrhizal colonization in tomato, as double mutant studies indicate that SlCLV2 and FIN have an additive influence on mycorrhizal colonization. SlCLE10 appears to play a more minor or redundant role, as cle10 mutants did not influence intraradical AM colonization. However, the fact that cle10 mutants had an elevated number of hyphopodia and that ectopic overexpression of SlCLE10 did suppress mycorrhizal colonization suggests that SlCLE10 may also play a role in suppressing AM colonization. Our findings show that CLE peptides regulate AM colonization in tomato and at least SlCLE11 likely requires arabinosylation for activity.

A dual regulatory role of the arbuscular mycorrhizal master regulator RAM1 in tomato.

The REQUIRED FOR ARBUSCULAR MYCORRHIZATION1 (RAM1) transcription factor from the GRAS family is well-known by its role as a master regulator of the arbuscular mycorrhizal (AM) symbiosis in dicot and monocot species, being essential in the transcriptional reprograming for the development and functionality of the arbuscules. In tomato, SlGRAS27 is the putative ortholog of RAM1 (here named SlRAM1), but has not yet been characterized. A reduced colonization of the root and an impaired arbuscule formation were observed in the SlRAM1 silenced plants, confirming the functional conservation of the RAM1 ortholog in tomato . However, unexpectedly, SlRAM1 overexpressing (UBIL:SlRAM1) plants also showed a decreased mycorrhizal colonization. Analysis of non-mycorrhizal UBIL:SlRAM1 roots revealed an overall regulation of AM-related genes and a reduction of strigolactone biosynthesis. Moreover, the external application of the strigolactone analogue GR244DO almost completely reversed the negative effects of SlRAM1 overexpression on the frequency of mycorrhization. However, it only partially recovered the pattern of arbuscule distribution observed in control plants. Our results strongly suggest that SlRAM1 has a dual regulatory role during mycorrhization and, apart from its recognized action as a positive regulator of arbuscule development, SlRAM1 is also involved in different mechanisms for the negative regulation of mycorrhization, including the repression of strigolactone biosynthesis.

Effect of Flu Vaccination on Severity and Outcome of Heart Failure Decompensations.

OBJECTIVE: To investigate the relationship of seasonal flu vaccination with the severity of decompensation and long-term outcomes of patients with heart failure (HF). METHODS: We analyzed 6147 consecutively enrolled patients with decompensated HF who presented to 33 Spanish emergency departments (EDs) during January and February of 2018 and 2019, grouped according to seasonal flu vaccination status. The severity of HF decompensation was assessed by the Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) + MEESSI scale, need of hospitalization and in-hospital all-cause mortality. The long-term outcomes analyzed were 90-day postdischarge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions by using 14 covariables that could act as potential confounders. RESULTS: Overall median (IQR) age was 84 (IQR = 77-89) years, and 56% were women. Vaccinated patients (n = 1139; 19%) were older, had more comorbidities and had worse baseline status, as assessed by New York Heart Association class and Barthel index, than did unvaccinated patients (n = 5008; 81%). Infection triggering decompensation was more common in vaccinated patients (50% vs 41%; P < 0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%; hospitalization occurred in 72.5% and 73.7%; in-hospital mortality was 7.4% and 7.0%; 90-day postdischarge adverse events were 57.4% and 53.2%; and the 90-day mortality rate was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated patients with HF had decreased odds for hospitalization (OR = 0.823, 95%CI = 0.709-0.955). CONCLUSION: In patients with HF, seasonal flu vaccination is associated with less severe decompensations.

Hyperkalemia in acute heart failure: Short term outcomes from the EAHFE registry.

OBJECTIVE: Both hyperkalemia (HK) and Acute Heart Failure (AHF) are associated with increased short-term mortality, and the management of either may exacerbate the other. As the relationship between HK and AHF is poorly described, our purpose was to determine the relationship between HK and short-term outcomes in Emergency Department (ED) AHF. METHODS: The EAHFE Registry enrolls all ED AHF patients from 45 Spanish ED and records in-hospital and post-discharge outcomes. Our primary outcome was all-cause in-hospital death, with secondary outcomes of prolonged hospitalization (>7 days) and 7-day post-discharge adverse events (ED revisit, hospitalization, or death). Associations between serum potassium (sK) and outcomes were explored using logistic regression by restricted cubic spline (RCS) curves, with sK =4.0 mEq/L as the reference, adjusting by age, sex, comorbidities, patient baseline status and chronic treatments. Interaction analyses were performed for the primary outcome. RESULTS: Of 13,606 ED AHF patients, the median (IQR) age was 83 (76-88) years, 54% were women, and the median (IQR) sK was 4.5 mEq/L (4.3-4.9) with a range of 4.0-9.9 mEq/L. In-hospital mortality was 7.7%, with prolonged hospitalization in 35.9%, and a 7-day post-discharge adverse event rate of 8.7%. Adjusted in-hospital mortality increased steadily from sK ≥4.8 (OR = 1.35, 95% CI = 1.01-1.80) to sK = 9.9 (8.41, 3.60-19.6). Non-diabetics with elevated sK had higher odds of death, while chronic treatment with mineralocorticoid-receptor antagonists exhibited a mixed effect. Neither prolonged hospitalization nor post-discharge adverse events was associated with sK. CONCLUSION: In ED AHF, initial sK >4.8 mEq/L was independently associated with in-hospital mortality, suggesting that this cohort may benefit from aggressive HK treatment.

Molecular Regulation of Arbuscular Mycorrhizal Symbiosis.

Plant-microorganism interactions at the rhizosphere level have a major impact on plant growth and plant tolerance and/or resistance to biotic and abiotic stresses. Of particular importance for forestry and agricultural systems is the cooperative and mutualistic interaction between plant roots and arbuscular mycorrhizal (AM) fungi from the phylum Glomeromycotina, since about 80% of terrestrial plant species can form AM symbiosis. The interaction is tightly regulated by both partners at the cellular, molecular and genetic levels, and it is highly dependent on environmental and biological variables. Recent studies have shown how fungal signals and their corresponding host plant receptor-mediated signalling regulate AM symbiosis. Host-generated symbiotic responses have been characterized and the molecular mechanisms enabling the regulation of fungal colonization and symbiosis functionality have been investigated. This review summarizes these and other recent relevant findings focusing on the molecular players and the signalling that regulate AM symbiosis. Future progress and knowledge about the underlying mechanisms for AM symbiosis regulation will be useful to facilitate agro-biotechnological procedures to improve AM colonization and/or efficiency.

DLK2 regulates arbuscule hyphal branching during arbuscular mycorrhizal symbiosis.

D14 and KAI2 receptors enable plants to distinguish between strigolactones (SLs) and karrikins (KARs), respectively, in order to trigger appropriate environmental and developmental responses. Both receptors are related to the regulation of arbuscular mycorrhiza (AM) formation and are members of the RsbQ-like family of α,ß-hydrolases. DLK2 proteins, whose function remains unknown, constitute a third clade from the RsbQ-like protein family. We investigated whether the tomato SlDLK2 is a new regulatory component in the AM symbiosis. Genetic approaches were conducted to analyze SlDLK2 expression and to understand SlDLK2 function in AM symbiosis. We show that SlDLK2 expression in roots is AM-dependent and is associated with cells containing arbuscules. SlDLK2 ectopic expression arrests arbuscule branching and downregulates AM-responsive genes, even in the absence of symbiosis; while the opposite effect was observed upon SlDLK2 silencing. Moreover, SlDLK2 overexpression in Medicago truncatula roots showed the same altered phenotype observed in tomato roots. Interestingly, SlDLK2 interacts with DELLA, a protein that regulates arbuscule formation/degradation in AM roots. We propose that SlDLK2 is a new component of the complex plant-mediated mechanism regulating the life cycle of arbuscules in AM symbiosis.

High-sensitivity cardiac troponin T 30 days all-come mortality in patients with acute heart failure. A Propensity Score-Matching Analysis Based on the EAHFE Registry. TROPICA4 Study.

BACKGROUND: Acute heart failure (AHF) patients with high troponin levels have a worse prognosis. High-sensitive troponin T (hs-TnT) has been used as a tool to stratify prognosis in many scales but always as a qualitative and not as a quantitative variable. OBJECTIVES: The main objective of this study was to determine the best hs-TnT cut-off for prediction of 30-day all-cause mortality. METHODS: The EAHFE registry, a prospective follow-up cohort of patients with AHF, was analysed. We performed a propensity score analysis of the optimal hs-TnT cut-off point previously determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 13 791 patients in the EAHFE cohort, we analysed 3190 patients in whom hs-TnT determination was available. The area under the ROC curve for 30-day all-cause mortality was 0.70 (CI95% 0.68 to 0.71; P < .001), establishing an optimal cut-off of hs-TnT of 35 ng/L. The sensitivity and specificity of this cut-off were 76.2 and 55.5%, respectively, with a negative predictive value (NPV) of 95.3%. A propensity score was made with 34 variables showing differences based on the cut-off of 35 ng/L for hs-TnT. In the analysis of the population obtained with the propensity score, patients with hs-TnT > 35 ng/L showed a greater 30-day all-cause mortality, with a HR of 2.95 (CI95% 1.83-4.75; P < .001). External validation reported similar results. CONCLUSIONS: An hs-TnT value of 35 ng/L is an adequate cut-off to evaluate the prediction of 30-day all-cause mortality with a NPV of 95.3%.

Intermuscular S-ICD Implantation in Pediatric Patients.

The use of conventional implantable cardioverter-defibrillators (ICDs) in children presents important technical challenges. We present the surgical technique necessary to adapt the subcutaneous ICD (S-ICD) implantation designed for adults, to children, including patients weighing less than 20 kg. The implant procedure implies a two-incision technique and interfascial serratus anterior-latissimus dorsi dissection to accommodate the device. S-ICD implantation was successfully performed in three patients of 19, 28, and 24 kg, respectively, two of them suffered cardiorespiratory arrest. Intermuscular thoracic implantation of S-ICD might represent an effective strategy for primary or secondary prevention of sudden cardiac death in pediatric patients.

Immunophenotypic Conversion between Primary and Relapse Breast Cancer and its Effects on Survival.

BACKGROUND: The differential expression of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) or Ki-67 between primary tumour and the recurrence has been described. We aimed to determine these changes and their prognostic implications. PATIENTS AND METHODS: We retrospectively reviewed 45 breast cancer patients with relapsed biopsy that were classified into local relapse (LR) or metastatic disease (MD) groups. We analyzed the conversion rate and the value of the immunophenotype of the primary tumour and the relapse as a prognostic factor for relapse-free survival (RFS), progression-free survival (PFS) and overall survival (OS). RESULTS: The conversion rate was 34.8% for Ki-67, 20% for ER, 20% for PR, and 15.6% for HER2. For the LR group, the RFS was 71.9 months and the OS was 141.6 months, without statistical differences according to the immunophenotype of the primary or the relapsed biopsy. For the MD group, the PFS was 20.8 months. According to immunophenotype of the relapse, the PFS were ER+ 24.7 months vs. ER- 9.3 months; PR+ 25.1 months vs. PR- 12.7 months without statistical differences according to HER2 or Ki67. The OS for MD group was 54.4 months without statistical differences according to immunophenotype. CONCLUSION: The characteristics of breast cancer can change over the time. Variations of the ER or PR status in MD group have prognostic value for PFS. To perform a biopsy of relapses is warranted in order to establish the prognostic of the current disease, and probably a more accurate treatment.

Role of gibberellins during arbuscular mycorrhizal formation in tomato: new insights revealed by endogenous quantification and genetic analysis of their metabolism in mycorrhizal roots.

Gibberellins (GAs) are key regulators of plant growth and development and recent studies suggest also a role during arbuscular mycorrhizal (AM) formation. Here, complementary approaches have been used to obtain a clearer picture that correlates AM fungal development inside roots with GA metabolism. An extensive analysis of genes associated with GA metabolism as well as a quantification of GA content in roots was made. Application of GA3 and its biosynthesis inhibitor prohexadione calcium (PrCa) combined with a GA-constitutive response mutant (procera) were used to determine whether fungal colonization is altered by the level of these hormones or by changes in the GA-signaling pathway. The increased levels of specific GAs from the 13-hydroxylation pathway in mycorrhizal roots correlate closely with the increased expression of genes coding enzymes from the GA biosynthetic trail. The imbalance of GAs in tomato roots caused by exogenous applications of GA3 or PrCa affects arbuscules in both negative and positive ways, respectively. In addition, procera plants were adversely affected by the mycorrhization process. Our findings demonstrate that an imbalance in favor of an increased amount of GAs negatively affects the frequency of mycorrhization and particularly the arbuscular abundance in tomato mycorrhizal roots and the results point out that AM formation is associated with a change in the 13-hydroxylation pathway of GAs.

Exosomes Derived from Breast Cancer Cells, Small Trojan Horses?

Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic transformation of cells in the tumor microenvironment, tumor drug resistance, and the transport of tumor factors. Tumors appear to use exosomes to dialogue with and transform neighboring cells to create an ideal environment for their growth and expansion. On the other hand, the structure and function of exosomes may make them useful in cancer diagnosis and prognosis, because they contain molecules that could serve as biomarkers, including oncogenes, miRNAs, and certain proteins. They have the ability to travel via body fluids, from which they could be isolated and used to transport drugs to specific targets. This review aims to provide an update on the role of exosomes derived from breast cancer cells.

Timing of previous heart failure hospitalization as a prognostic factor for emergency department heart failure patients.

To investigate whether the timing of a previous hospital admission for acute heart failure (AHF) is a prognostic factor for AHF patients revisiting the emergency department (ED) in the subsequent 12-month follow-up. All ED AHF patients enrolled in the previously described EAHFE registry were stratified by the presence or absence of an AHF hospitalization admission in the prior 12 months. The primary outcome was 12-month all-cause mortality post ED visit. Secondary end points were hospital admission, prolonged hospitalization (> 7 days), mortality during hospitalization and a 90-day post-discharge adverse composite event (ACE) rate, defined as ED revisits due to AHF, hospitalizations due to AHF, or all-cause mortality. Outcomes were adjusted for baseline and AHF episode characteristics.Of 5,757 patients included, the median age was 84 years (IQR 77-88); 57% were women, and 3,759 (65.3%) had an AHF hospitalization in the previous 12 months. The 12-month mortality was 37% (41.7% vs. 28.3% p < 0.001), hospital admission was 76.1% (78.8% vs. 71.1% p < 0.001) ACE was 60.2% (65.1% vs. 50.5% p < 0.001). In the adjusted analysis, patients with AHF hospitalization in the prior 12 months had a higher mortality (HR = 1.41; 95% CI 1.27-1.56), 90-day ACE rate (HR = 1.45: 95% CI 1.32-1.59), and more hospital admissions (OR = 1.32; 95% CI 1.16-1.51), with shorter times since the previous hospitalization being related to the outcomes analyzed. One-year mortality, adverse events at 90 days, and readmission rates are increased in ED AHF patients previously admitted within the last 12 months.

Impact of congestion and perfusion status in the emergency department on severity of decompensation and short-term prognosis in patients with acute heart failure.

AIMS: To assess whether symptoms/signs of congestion and perfusion in acute heart failure (AHF) evaluated at patient arrival to the emergency department (ED) can predict the severity of decompensation and short-term outcomes. METHODS AND RESULTS: We included patients from the Epidemiology of AHF Emergency Registry (EAHFE Registry). We registered seven clinical surrogates of congestion and five of hypoperfusion. Patients were grouped according to severity of congestion/hypoperfusion. We assessed the need for hospitalization, in-hospital all-cause mortality for patients needing hospitalization, and prolonged hospitalization for patients surviving the decompensation episode. Outcomes were adjusted for patient characteristics and the coexistence of congestion and hypoperfusion. We analysed 18 120 patients (median = 83 years, interquartile range = 76-88; women = 55.7%). Seventy-two per cent presented >2 signs/symptoms of congestion and 18% had at least 1 sign/symptom of hypoperfusion. Seventy-five per cent were hospitalized with in-hospital death in 9% and prolonged hospitalization in 47% discharged alive. The presence of congestion/hypoperfusion was independently associated with poorer outcomes. An increase in the number of signs/symptoms of congestion was associated with increased risk of hospitalization (P < 0.001) and prolonged stay (P = 0.011), but not mortality (P = 0.06). Increased signs/symptoms of hypoperfusion were associated with hospitalization (P < 0.001) and mortality (P < 0.001), but not prolonged stay (P = 0.227). In the combined model, including congestion and hypoperfusion, both had additive effects on hospitalization, in-hospital mortality was driven by hypoperfusion and no differences were observed for prolonged hospitalization. CONCLUSION: The presence of congestion/hypoperfusion at ED arrival is a simple clinical marker associated with a higher risk of severity/adverse short-term outcomes.

Emergency department direct discharge compared to short-stay unit admission for selected patients with acute heart failure: analysis of short-term outcomes.

Short stay unit (SSU) is an alternative to conventional hospitalization in patients with acute heart failure (AHF), but the prognosis is not known compared to direct discharge from the emergency department (ED). To determine whether direct discharge from the ED of patients diagnosed with AHF is associated with early adverse outcomes versus hospitalization in SSU. Endpoints, defined as 30-day all-cause mortality or post-discharge adverse events, were evaluated in patients diagnosed with AHF in 17 Spanish EDs with an SSU, and compared by ED discharge vs. SSU hospitalization. Endpoint risk was adjusted for baseline and AHF episode characteristics and in patients matched by propensity score (PS) for SSU hospitalization. Overall, 2358 patients were discharged home and 2003 were hospitalized in SSUs. Discharged patients were younger, more frequently men, with fewer comorbidities, had better baseline status, less infection, rapid atrial fibrillation and hypertensive emergency as the AHF trigger, and had a lower severity of AHF episode. While their 30-day mortality rate was lower than in patients hospitalized in SSU (4.4% vs. 8.1%, p < 0.001), 30-day post-discharge adverse events were similar (27.2% vs. 28.4%, p = 0.599). After adjustment, there were no differences in the 30-day risk of mortality of discharged patients (adjusted HR 0.846, 95% CI 0.637-1.107) or adverse events (1.035, 0.914-1.173). In 337 pairs of PS-matched patients, there were no differences in mortality or risk of adverse event between patients directly discharged or admitted to an SSU (0.753, 0.409-1.397; and 0.858, 0.645-1.142; respectively). Direct ED discharge of patients diagnosed with AHF provides similar outcomes compared to patients with similar characteristics and hospitalized in a SSU.

Use of digoxin in the emergency department to treat patients with acute heart failure and its impact on short-term outcomes. / Uso de digoxina endovenosa en urgencias para tratar pacientes con insuficiencia cardiaca aguda y su impacto en la evolución a corto plazo.

OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.

OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.

Late activation of the 9-oxylipin pathway during arbuscular mycorrhiza formation in tomato and its regulation by jasmonate signalling.

The establishment of an arbuscular mycorrhizal (AM) symbiotic interaction is a successful strategy for the promotion of substantial plant growth, development, and fitness. Numerous studies have supported the hypothesis that plant hormones play an important role in the establishment of functional AM symbiosis. Particular attention has been devoted to jasmonic acid (JA) and its derivates, which are believed to play a major role in AM symbiosis. Jasmonates belong to a diverse class of lipid metabolites known as oxylipins that include other biologically active molecules. Recent transcriptional analyses revealed up-regulation of the oxylipin pathway during AM symbiosis in mycorrhizal tomato roots and indicate a key regulatory role for oxylipins during AM symbiosis in tomato, particularly those derived from the action of 9-lipoxygenases (9-LOXs). Continuing with the tomato as a model, the spatial and temporal expression pattern of genes involved in the 9-LOX pathway during the different stages of AM formation in tomato was analysed. The effects of JA signalling pathway changes on AM fungal colonization were assessed and correlated with the modifications in the transcriptional profiles of 9-LOX genes. The up-regulation of the 9-LOX oxylipin pathway in mycorrhizal wild-type roots seems to depend on a particular degree of AM fungal colonization and is restricted to the colonized part of the roots, suggesting that these genes could play a role in controlling fungal spread in roots. In addition, the results suggest that this strategy of the plant to control AM fungi development within the roots is at least partly dependent on JA pathway activation.

Multifarious and Interactive Roles of GRAS Transcription Factors During Arbuscular Mycorrhiza Development.

Arbuscular mycorrhiza (AM) is a mutualistic symbiotic interaction between plant roots and AM fungi (AMF). This interaction is highly beneficial for plant growth, development and fitness, which has made AM symbiosis the focus of basic and applied research aimed at increasing plant productivity through sustainable agricultural practices. The creation of AM requires host root cells to undergo significant structural and functional modifications. Numerous studies of mycorrhizal plants have shown that extensive transcriptional changes are induced in the host during all stages of colonization. Advances have recently been made in identifying several plant transcription factors (TFs) that play a pivotal role in the transcriptional regulation of AM development, particularly those belonging to the GRAS TF family. There is now sufficient experimental evidence to suggest that GRAS TFs are capable to establish intra and interspecific interactions, forming a transcriptional regulatory complex that controls essential processes in the AM symbiosis. In this minireview, we discuss the integrative role of GRAS TFs in the regulation of the complex genetic re-programming determining AM symbiotic interactions. Particularly, research being done shows the relevance of GRAS TFs in the morphological and developmental changes required for the formation and turnover of arbuscules, the fungal structures where the bidirectional nutrient translocation occurs.

Evaluation of the effect of intravenous nitroglycerine on short-term survival of patients with acute heart failure according to congestion and perfusion status at emergency department arrival.

OBJECTIVES: We investigated if the phenotypic classification of acute heart failure (AHF) based on the number of signs/symptoms of congestion and hypoperfusion at emergency department (ED) arrival identifies subgroups in which intravenous (IV) nitroglycerine (NTG) use improves short-term survival. METHODS: We included consecutive AHF patients diagnosed in 45 Spanish EDs, who were grouped according to phenotype severity. The main outcome was 30-day all-cause death. Propensity scores (PS) for NTG use were generated using variables associated with death. Analysis of interaction was performed in subgroups of patients based on congestion, hypoperfusion, age, sex, coronary artery disease (CAD), left ventricular ejection fraction (LVEF) and SBP. RESULTS: We analyzed 16 437 AHF patients (median = 83 years; women = 56%); 1882 received NTG (11.4%). In the whole cohort, the cumulative 30-day mortality in patients receiving NTG was higher (11.5% vs. 9.6%; unadjusted HR, 1.19; 95% CI, 1.04-1.36), but not in the PS-matched cohorts (1698 pairs of patients; 11.5% vs. 10.5%; HR, 1.10; 95% CI, 0.90-1.35). Mortality was increased in NTG-treated patients with mild congestion (HR, 2.09; 95% CI, 1.19-3.67), especially in those without hypoperfusion (HR, 2.51; 95% CI, 1.24-5.10). Interaction analysis of the PS-matched cohorts confirmed detrimental effects of NTG use in less congested patients, whereas beneficial effects were only observed in patients with decreased LVEF (<50% subgroup: HR, 0.59; 95% CI, 0.37-0.92; ≥50% subgroup: HR, 1.30; 95% CI, 0.66-2.56; P = 0.002). CONCLUSION: Phenotypical classification of AHF based on congestion/hypoperfusion at ED arrival does not identify subgroups of patients in whom IV-NTG would decrease mortality, although it could potentially be beneficial in those with LVEF of less than 50%. This hypothesis will have to be confirmed in the future. Conversely, our results suggest that IV-NTG may be harmful in patients with only mild clinical congestion.

Short-term outcomes by chronic betablocker treatment in patients presenting to emergency departments with acute heart failure: BB-EAHFE.

AIMS: To evaluate the association between chronic treatment with betablockers (BB) and the severity of decompensation and short-term outcomes of patients with acute heart failure (AHF). METHODS AND RESULTS: We consecutively included all patients presenting with AHF to 45 Spanish emergency departments (ED) during six different time-periods between 2007 and 2018. Patients were stratified according to whether they were on chronic treatment with BB at the time of ED consultation. Those receiving BB were compared (adjusted odds ratio-OR-with 95% confidence interval-CI-) with those not receiving BB group in terms of in-hospital and 7-day all-cause mortality, need for hospitalization, and prolonged length of stay (≥7 days). Among the 17 923 recruited patients (median age: 80 years; 56% women), 7795 (43%) were on chronic treatment with BB. Based on the MEESSI-AHF risk score, those on BB were at lower risk. In-hospital mortality was observed in 1310 patients (7.4%), 7-day mortality in 765 (4.3%), need for hospitalization in 13 428 (75.0%), and prolonged length of stay (43.3%). After adjustment for confounding, those on chronic BB were at lower risk for in-hospital all-cause mortality (OR = 0.85, 95% CI = 0.79-0.92, P < 0.001); 7-day all-cause mortality (OR = 0.77, 95% CI = 0.70-0.85, P < 0.001); need for hospitalization (OR = 0.89, 95% CI = 0.85-0.94, P < 0.001); prolonged length of stay (OR = 0.90, 95% CI = 0.86-0.94, P < 0.001). A propensity matching approach yielded consistent findings. CONCLUSION: In patients presenting to ED with AHF, those on BB had better short-term outcomes than those not receiving BB.