Flowering is a crucial process that demands substantial resources. Carbon metabolism must be coordinated with development through a control mechanism that optimizes fitness for any physiological need ...and growth stage of the plant. However, how sugar allocation is controlled during the floral transition is unknown. Recently, the role of a CONSTANS (CO) ortholog (Cr-CO) in the control of the photoperiod response in the green alga Chlamydomonas reinhardtii and its influence on starch metabolism was demonstrated. In this work, we show that transitory starch accumulation and glycan composition during the floral transition in Arabidopsis thaliana are regulated by photoperiod. Employing a multidisciplinary approach, we demonstrate a role for CO in regulating the level and timing of expression of the GRANULE BOUND STARCH SYNTHASE (GBSS) gene. Furthermore, we provide a detailed characterization of a GBSS mutant involved in transitory starch synthesis and analyze its flowering time phenotype in relation to its altered capacity to synthesize amylose and to modify the plant free sugar content. Photoperiod modification of starch homeostasis by CO may be crucial for increasing the sugar mobilization demanded by the floral transition. This finding contributes to our understanding of the flowering process.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and ...cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75–89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10–22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82,
p
< 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15–11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40–103.86), frailty (OR 8.73 95% CI 1.37–55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02–0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Countercurrent supercritical fluid extraction (CC-SFE) at a pilot scale plant was used for fractionation of high-added-value products from a raw extract of olive leaves in hexane. Compounds found in ...the raw extract were waxes, hydrocarbons, squalene, β-carotene, triglycerides, α-tocopherol, β-sitosterol, and alcohols. The CC-SFE extraction process was investigated according to a 23 full factorial experimental design using the following variables and ranges: extraction pressure, 75−200 bar; extraction temperature, 35−50 °C; and ethanol as modifier, 0−10%. Data were analyzed in terms of extraction yield, enrichment, recovery, and selectivity. Higher extraction yields were attained at 200 bar. For most of the compounds analyzed enrichment was attained at the same conditions, that is, 75 bar, 35 °C, and 10% ethanol. Hydrocarbons were usually recovered in the separators, whereas waxes and α-tocopherol remain in the raffinate. Selectivity data reveal that α-tocopherol is the most easily separable compound. The influence of the experimental factors on the recovery of all the compounds was studied by means of regression models. The best fitted model was attained for β-sitosterol, with R 2 = 99.25%. Keywords: Olive leaves; solid−liquid (S−L) extraction; fractionation; countercurrent supercritical fluid extraction (CC-SFE); supercritical CO2; full factorial experimental design; waxes; hydrocarbons; squalene; β-carotene; triglycerides; α-tocopherol; β-sitosterol; total alcohols
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
To evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards.
The presence of N-antigenemia ...was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis.
Prevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09–3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26–0.85).
The presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sucrose-phosphate phosphatase (SPP) catalyses the final step in the sucrose biosynthesis pathway. Arabidopsis thaliana genome codifies four SPP isoforms. In this study, the four Arabidopsis thaliana ...genes coding for SPP isoforms have been cloned, expressed in Escherichia coli and the kinetic and regulatory properties of the purified enzymes analysed. SPP2 is the isoform showing the highest activity, with SPP3b and SPP3a showing lower activity levels. No activity was detected for SPP1. We propose that this lack of activity is probably due to the absence of an essential amino acid participating in catalysis and/or in the binding of the substrate, sucrose-6-phosphate (Suc6P). The expression patterns of Arabidopsis SPP genes indicate that SPP2 and SPP3b are the main isoforms expressed in different tissues and organs, although the non-catalytic SPP1 is the main isoform expressed in roots. Thus, SPP1 could have acquired new unknown functions. We also show that the three catalytically active SPPs from Arabidopsis are dimers. By generating a chimeric SPP composed of the monomeric cyanobacterial SPP fused to the higher plant non-catalytic S6PPc domain (from SPP2), we show that the S6PPc domain is responsible for SPP dimerization. This is the first experimental study on the functionality and gene expression pattern of all the SPPs from a single plant species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a ...dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response.
A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients.
The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR CI 95%, p): RNAemia (3.92 1.183-12.968, 0.025), viral RNA load (N1) (1.962 1.244-3.096, 0.004); viral RNA load (N2) (2.229 1.382-3.595, 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia).
SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.
Background
The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID‐19 has shown mixed outcomes in controlled trials and observational studies. ...We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID‐19.
Methods
A randomised, open‐label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days.
Results
Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males 66%). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% 95% CI, −8.8 to 9.1%; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non‐invasive respiratory or high‐flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% 95% CI, −31.8 to ‐ 5.6%; p = 0.007).
Conclusions
Among severe but not critical patients with COVID‐19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.
Graphical MP3‐pulses‐COVID‐19 trial.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Starch constitutes the most important carbon reserve in plants and is composed of branched amylopectin and linear amylose. The latter is synthesized exclusively by the Granule-Bound Starch Synthase ...(GBSS, EC 2.4.1.21). Here we report a readily reproducible, specific and highly sensitive protocol, which includes the isolation of intact starch granules from Arabidopsis thaliana leaves and the subsequent determination of GBSS activity. We have applied this method to study GBSS activity in diurnal cycles in vegetative growth and during the photoperiodic transition to flowering in Arabidopsis (Tenorio et al., 2003; Ortiz-Marchena et al., 2014).
OBJETIVOS
Analizar la relación entre el número diario de urgencias por asma y la concentración ambiental media diaria del material particulado con diámetro ≤ 5 micras (PM2,5) y el dióxido de ...nitrógeno (NO2).
MATERIAL Y MÉTODOS
Estudio ecológico retrospectivo de series temporales. Se consideraron las visitas a urgencias por asma entre 2013 y 2019. La asociación entre la concentración de PM2,5 y NO2 con el número de visitas a urgencias por asma (VUA) se estudió mediante un modelo lineal generalizado con regresión de Poisson. Se ajustó por variables meteorológicas y estacionales para evitar su potencial efecto confusor. Se evaluaron cinco lags temporales (0, 1, 3, 5 y 7 días) para estudiar la influencia del retardo entre la exposición y la visita a urgencias.
RESULTADOS
Se analizaron 11.051 urgencias por asma correspondientes a 5.936 pacientes, de los cuales 4.800 eran de edad pediátrica (hicieron 9.335 VUA) y 1.136 eran mayores de 14 años (hicieron 1.716 VUA). Las VUA y la concentración de los contaminantes mostraron un marcado comportamiento estacional con valores más altos en otoño e invierno. Se observó una asociación positiva significativa entre las concentraciones de PM2,5 y NO2 y las VUA, con un riesgo relativo por incremento de 10 µg/m3 para el lag -3 de 1,073 (intervalo de confianza IC 95%: 1,042-1,106) y de 1,075 (IC 95%: 1,054-1,097), respectivamente. En términos de fracción atribuible, una disminución de 10 µg/m3 de la concentración ambiental de PM2,5 y NO2 podría evitar, respectivamente, el 6,8% (IC 95%: 4-9,5) y el 6,9% (IC 95%: 5,1-8,8) de las VUA 3 días después.
CONCLUSIONES
El incremento de la concentración de PM2,5 y NO2 se asoció con un aumento de las urgencias hospitalarias por exacerbación asmática en nuestro entorno. La disminución de la contaminación ambiental supondría un importante efecto beneficioso para la salud comunitaria, y especialmente, para personas más susceptibles como los pacientes con asma bronquial.
CEI
El estudio fue aprobado por el Comité de Ética de Investigación con medicamentos (CEIm PI208-19).
To analyze the association between atmospheric levels of nitrogen dioxide (NO2) and the number of visits by adults to an emergency department (ED) for exacerbated asthma in an urban area with low ...levels of air pollution.
Retrospective ecological time-series study. We quantified ED visits for asthma by consecutive patients over the age of 14 years between 2010 and 2018 (3287 days). The association between the mean atmospheric concentration of NO2 and the number of daily visits to the ED for asthma was analyzed with generalized linear regression analysis (Poisson modeling). The impact of exposure on individual risk was assessed by crossover analysis of case periods. We adjusted for confounding meteorologic variables, potential variability due to seasonal changes was corrected by trend analysis, and 3 time lags were assessed (0, 1, and 3 days).
We analyzed 2527 asthma emergencies in 1588 patients (70% female) with a mean (SD) age of 51 (21) years. A significant positive association (relative risk, 1.056, 95% CI, 1.006-1.108; P .05) between atmospheric NO2 concentration and greater risk of visiting an ED within 3 days was detected. An increase of 10 µg/m3 of NO2 accounted for 5.3% of the visits (attributable fraction, 5.30, 95% CI, 0.60-9.75; P .05).
In an urban area with low pollution levels, an elevation in atmospheric NO2 is associated with more hospital ED visits for asthma attacks in adults.
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