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.

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.

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.

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.

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.

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.

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.

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 observation of patients with acute heart failure prior to hospital admission: impact on short-term prognosis. / Observación en urgencias previa a la hospitalización en pacientes con insuficiencia cardiaca aguda: impacto sobre el pronóstico a corto plazo.

OBJECTIVES: To analyze whether short-term outcomes are affected when patients diagnosed with acute heart failure (AHF) spend time in an emergency department observation unit (EDOU) before hospital admission. MATERIAL AND METHODS: Baseline and emergency episode data were collected for patients diagnosed with AHF in the EDs of 15 Spanish hospitals. We analyzed crude and adjusted associations between EDOU stay and 30-day mortality (primary outcome) and in-hospital mortality and a prolonged hospital stay of more than 7 days (secondary outcomes). RESULTS: A total of 6597 patients with a median (interquartile range) age of 83 (76-88 years) were studied. Fifty-five percent were women. All were hospitalized for AHF (50% in internal medicine wards, 23% in cardiology, 11% in geriatrics, and 16 in other specialties. Of these patients, 3241 (49%) had had EDOU stays and 3350 (51%) had been admitted immediately, with no EDOU stay. Having an EDOU stay was associated with female sex, dementia or chronic obstructive pulmonary disease, long-term treatment with certain drugs for heart failure, greater baseline deterioration in function, and a higher degree of decompensation. Patients in the EDOU group were more often admitted to an internal medicine ward and had shorter stays; cardiology, geriatric, and intensive care admissions were less likely to have had an EDOU stay. Overall, 30-day mortality was 12.6% (13.7% in the EDOU group and 11.4% in the no-EDOU group; P = .004). In-hospital mortality was 10.4% overall (EDOU, 11.1% and no-EDOU, 9.6%; P = .044). Prolonged hospitalization occurred in 50.0% (EDOU, 48.7% and no-EDOU, 51.2%; P = .046). After adjusting for between-group differences, the EDOU stay was not associated with 30-day mortality (hazard ratio, 1.14; 95% CI, 0.99-1.31). Odds ratios for associations between EDOU stay and in-hospital mortality and prolonged hospital stay, respectively, were 1.09 (95% CI, 0.92-1.29) and 0.91 (95% CI, 0.82-1.01). CONCLUSION: Although mortality higher in patients hospitalized for AHF who spend time in an EDO, the association seems to be accounted for by their worse baseline situation and the greater seriousness of the decompensation episode, not by time spent in the EDOU.

OBJETIVO: Analizar si la estancia en el área de observación de urgencias (AOU) de pacientes que han sido diagnosticados de insuficiencia cardiaca aguda (ICA) y que deben ingresar está asociada con algún cambio en la evolución a corto plazo. METODO: Se recogieron datos basales y clínicos de pacientes diagnosticados de ICA en el servicio de urgencias de 15 hospitales españoles. Se analizó la asociación cruda y ajustada de la estancia en el AOU previa a la hospitalización con mortalidad a 30 días (objetivo primario) y con mortalidad intrahospitalaria e ingreso prolongado (> 7 días) (objetivos secundarios). RESULTADOS: Se incluyeron 6.597 pacientes (mediana = 83 años, RIC = 76-88; mujeres = 55%) hospitalizados por ICA (50% en medicina interna, 23% en cardiología, 11% en geriatría y 16% en otros servicios); de ellos, 3.241 (49%) permanecieron en observación en urgencias (grupo AOU) y 3.350 (51%) hospitalizaron sin observación previa (grupo no-AOU). La observación en urgencias se asoció con ser mujer, tener demencia o enfermedad pulmonar obstructiva crónica, recibir crónicamente fármacos específicos para insuficiencia cardiaca, mayor deterioro funcional basal y mayor gravedad de la descompensación. El grupo AOU más frecuentemente hospitalizó en medicina interna y corta estancia, y menos frecuentemente en cardiología, geriatría y cuidados intensivos. La mortalidad a 30 días fue del 12,6% (AOU = 13,7%, no-AOU = 11,4%, p = 0,004); la mortalidad intrahospitalaria fue del 10,4% (AOU = 11,1%, no-AOU = 9,6%, p = 0,044) y el ingreso prolongado del 50,0% (AOU = 48,7%, no-AOU = 51,2%, p = 0,046). Tras ajustar por las diferencias entre grupos, la estancia en observación en urgencias no se asoció con mortalidad a 30 días (HR = 1,14, IC 95% = 0,99-1,31), mortalidad intrahospitalaria (OR = 1,09, IC 95% = 0,92-1,29) o estancia prolongada (OR = 0,91, IC 95% = 0,82-1,01). CONCLUSIONES: Aunque los pacientes hospitalizados por ICA que permanecen en observación en urgencias presentan mayor mortalidad, esta asociación parece explicarse por su peor situación de base y la mayor gravedad del episodio de descompensación y no por su paso por el AOU.

Observación en urgencias previa a la hospitalización en pacientes con insuficiencia cardiaca aguda / Emergency department observation of patients with acute heart failure prior to hospital admission: impact on short-term prognosis

Objetivos. Analizar si la estancia en el área de observación de urgencias (AOU) de pacientes que han sido diagnosticados de insuficiencia cardiaca aguda (ICA) y que deben ingresar está asociada con algún cambio en la evolución a corto plazo.Métodos. Se recogieron datos basales y clínicos de pacientes diagnosticados de ICA en el servicio de urgencias de 15 hospitales españoles. Se analizó la asociación cruda y ajustada de la estancia en el AOU previa a la hospitalización con mortalidad a 30 días (objetivo primario) y con mortalidad intrahospitalaria e ingreso prolongado (> 7 días) (objetivos secundarios).Resultados. Se incluyeron 6.597 pacientes (mediana = 83 años, RIC = 76-88; mujeres = 55%) hospitalizados por ICA (50% en medicina interna, 23% en cardiología, 11% en geriatría y 16% en otros servicios); de ellos, 3.241 (49%) permanecieron en observación en urgencias (grupo AOU) y 3.350 (51%) hospitalizaron sin observación previa (grupo no-AOU). La observación en urgencias se asoció con ser mujer, tener demencia o enfermedad pulmonar obstructiva crónica, recibir crónicamente fármacos específicos para insuficiencia cardiaca, mayor deterioro funcional basal y mayor gravedad de la descompensación. El grupo AOU más frecuentemente hospitalizó en medicina interna y corta estancia, y menos frecuentemente en cardiología, geriatría y cuidados intensivos. La mortalidad a 30 días fue del 12,6% (AOU = 13,7%, no-AOU = 11,4%, p = 0,004); la mortalidad intrahospitalaria fue del 10,4% (AOU = 11,1%, no-AOU = 9,6%, p = 0,044) y el ingreso prolongado del 50,0% (AOU = 48,7%, no-AOU = 51,2%, p = 0,046). Tras ajustar por las diferencias entre grupos, la estancia en observación en urgencias no se asoció con mortalidad a 30 días (HR = 1,14, IC 95% = 0,99-1,31), mortalidad intrahospitalaria (OR = 1,09, IC 95% = 0,92-1,29) o estancia prolongada (OR = 0,91, IC 95% = 0,82-1,01). (AU)

Objectives. To analyze whether short-term outcomes are affected when patients diagnosed with acute heart failure (AHF) spend time in an emergency department observation unit (EDOU) before hospital admission.Methods. Baseline and emergency episode data were collected for patients diagnosed with AHF in the EDs of 15 Spanish hospitals. We analyzed crude and adjusted associations between EDOU stay and 30-day mortality (primary outcome) and in-hospital mortality and a prolonged hospital stay of more than 7 days (secondary outcomes).Results. A total of 6597 patients with a median (interquartile range) age of 83 (76-88 years) were studied. Fifty-five percent were women. All were hospitalized for AHF (50% in internal medicine wards, 23% in cardiology, 11% in geriatrics, and 16 in other specialties. Of these patients, 3241 (49%) had had EDOU stays and 3350 (51%) had been admitted immediately, with no EDOU stay. Having an EDOU stay was associated with female sex, dementia or chronic obstructive pulmonary disease, long-term treatment with certain drugs for heart failure, greater baseline deterioration in function, and a higher degree of decompensation. Patients in the EDOU group were more often admitted to an internal medicine ward and had shorter stays; cardiology, geriatric, and intensive care admissions were less likely to have had an EDOU stay. Overall, 30-day mortality was 12.6% (13.7% in the EDOU group and 11.4% in the no-EDOU group; P = .004). In-hospital mortality was 10.4% overall (EDOU, 11.1% and no-EDOU, 9.6%; P = .044). Prolonged hospitalization occurred in 50.0% (EDOU, 48.7% and no-EDOU, 51.2%; P = .046). After adjusting for between-group differences, the EDOU stay was not associated with 30-day mortality (hazard ratio, 1.14; 95% CI, 0.99-1.31). Odds ratios for associations between EDOU stay and in-hospital mortality and prolonged hospital stay, respectively, were 1.09 (95% CI, 0.92-1.29) and 0.91 (95% CI, 0.82-1.01). (AU)

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.

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.

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.

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.

A surface plasmon resonance based approach for measuring response to pneumococcal vaccine.

Incidence of pneumococcal disease has increased worldwide in recent years. Response to pneumococcal vaccine is usually measured using the multiserotype enzyme-linked immunosorbent assay (ELISA) pneumococcal test. However, this approach presents several limitations. Therefore, the introduction of new and more robust analytical approaches able to provide information on the efficacy of the pneumococcal vaccine would be very beneficial for the clinical management of patients. Surface plasmon resonance (SPR) has been shown to offer a valuable understanding of vaccines' properties over the last years. The aim of this study is to evaluate the reliability of SPR for the anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs quantification in vaccinated. Fast protein liquid chromatography (FPLC) was used for the isolation of total IgGs from serum samples of vaccinated patients. Binding-SPR assays were performed to study the interaction between anti-PnPs IgGs and PCV13. A robust correlation was found between serum levels of anti-PnPs IgGs, measured by ELISA, and the SPR signal. Moreover, it was possible to correctly classify patients into "non-responder", "responder" and "high-responder" groups according to their specific SPR PCV13 response profiles. SPR technology provides a valuable tool for reliably characterize the interaction between anti-PnPs IgGs and PCV13 in a very short experimental time.

Analysis of standards of quality for outcomes in acute heart failure patients directly discharged home from emergency departments and their relationship with the emergency department direct discharge rate.

OBJECTIVE: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be >40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality <2% (outcome A); 7-day ED revisit due to AHF < 10% (outcome B); and 30-day ED revisit/hospitalization due to AHF < 20% (outcome C). We investigated these outcomes in a nationwide cohort and their relationship with the ED DDWH percentage. METHODS: We analyzed the EAHFE registry (includes about 15% of Spanish EDs), calculated DDWH percentage of each ED, and A/B/C outcomes of DDWH patients, overall and in each individual ED. Relationship between ED DDWH and outcomes was assessed by linear and quadratic regression models, non-weighted and weighted by DDWH patients provided by each ED. RESULTS: Among 17,420 patients, 4488 had DDWH (25.8%, median ED stay = 0 days, IQR = 0-1). Only 12.9% EDs achieved DDWH > 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R2 = 0.184/0.322) and C (weighted R2 = 0.430/0.624), but not with outcome A (weighted R2 = 0.002/0.022). CONCLUSIONS: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge.

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.

Climatic drivers of Verticillium dahliae occurrence in Mediterranean olive-growing areas of southern Spain.

Verticillium wilt, caused by the soil-borne fungus Verticillium dahliae, is one of the most harmful diseases in Mediterranean olive-growing areas. Although, the effects of both soil temperature and moisture on V. dahliae are well known, there is scant knowledge about what climatic drivers affect the occurrence of the pathogen on a large scale. Here, we investigate what climatic drivers determine V. dahliae occurrence in olive-growing areas in southern Spain. In order to bridge this gap in knowledge, a large-scale field survey was carried out to collect data on the occurrence of V. dahliae in 779 olive groves in Granada province. Forty models based on competing combinations of climatic variables were fitted and evaluated using information-theoretic methods. A model that included a multiplicative combination of seasonal and extreme climatic variables was found to be the most viable one. Isothermality and the seasonal distribution of precipitation were the most important variables influencing the occurrence of the pathogen. The isothermal effect was in turn modulated by the seasonality of rainfall, and this became less negative as seasonality increases. Thus, V. dahliae occurs more frequently in olive-growing areas where the day-night temperature oscillation is lower than the summer-winter one. We also found that irrigation reduced the influence of isothermality on occurrence. Our results demonstrate that long-term compound climatic factors rather than "primary" variables, such as annual trends, can better explain the spatial patterns of V. dahliae occurrence in Mediterranean, southern Spain. One important implication of our study is that appropriate irrigation management, when temperature oscillation approaches optimal conditions for V. dahliae to thrive, may reduce the appearance of symptoms in olive trees.

Histochemical Staining and Quantification of Arbuscular Mycorrhizal Fungal Colonization.

Histochemical staining and light microscopy-based techniques have been widely used to detect and quantify arbuscular mycorrhizal fungi (AMF) in roots. Here we describe a standardized method for staining of AMF in colonized roots, and we provide possible modifications to adjust the protocol according to particular requirements, such as the type of root material or the reduction of toxic products. In addition, we also summarize some of the most common ways to quantify arbuscular mycorrhizal colonization.