Crop models are used to estimate crop productivity under future climate projections, and modellers manage uncertainty by considering different scenarios and GCMs, using a range of crop simulators. ...Five crop models and 20 users were arranged in a randomized block design with four replicates. Parameters for maize (well studied by modellers) and rapeseed (almost ignored) were calibrated. While all models were accurate for maize (RRMSE from 16.5% to 25.9%), they were, to some extent, unsuitable for rapeseed. Although differences between biomass simulated by the models were generally significant for rapeseed, they were significant only in 30% of the cases for maize. This could suggest that in case of models well suited to a crop, user subjectivity (which explained 14% of total variance in maize outputs) can hide differences in model algorithms and, consequently, the uncertainty due to parameterization should be better investigated.
•Five crop models and 20 users were arranged in four randomized blocks.•The significance of model factor for maize and rapeseed was evaluated.•All models achieved good performance for maize and poor for rapeseed.•Differences between models were significant only in 30% of the cases for maize.•Parameterization uncertainty should be explicitly managed also in model ensembles.
COVID-19 represents the greatest health challenge of modern years. The spectrum of illness comprises respiratory and non-respiratory manifestations. We report the case of an adult man with COVID-19 ...who presented with rhabdomyolysis as a principal extrapulmonary manifestation. Our patient presented with dyspnea, fever, and muscle pain. After a comprehensive approach, the diagnosis of COVID-19 and rhabdomyolysis was made. He developed acute kidney injury requiring renal replacement therapy without reversibility, despite optimal treatment. We performed a literature search for similar cases, discuss the potential mechanisms implied, and propose a diagnostic-therapeutic algorithm.
Clopidogrel plus aspirin is the treatment of choice for patients undergoing percutaneous, coronary interventions with stenting, but it does not prevent restenosis. NCX-4016, a nitric oxide-releasing ...aspirin (nitroaspirin), exerts a wider range of antiplatelet actions compared to aspirin, superior antithrombotic activity and reduces restenosis after arterial injury in animals. The aim of the present study was to compare the combination of nitroaspirin plus clopidogrel with aspirin plus clopidogrel in a model of platelet pulmonary thromboembolism, bleeding and intimal thickening in mice. Drugs were administered orally for 5 days; the antithrombotic effects were evaluated against collagen plus epinephrine-induced pulmonary thromboembolism, the haemorrhagic effects by tail transection bleeding time and the effects on neointima proliferation by histomorphology of photochemically injured femoral arteries. Lung platelet emboli were reduced significantly and more effectively by nitroaspirin plus clopidogrel (-56%, p<0.05 vs control) than by aspirin plus clopidogrel (-26%, p<0.05 vs control). Ex vivo platelet aggregation was inhibited maximally by nitroaspirin plus clopidogrel. Aspirin plus clopidogrel strikingly prolonged the bleeding time while nitroaspirin plus clopidogrel induced a lesser prolongation. Nitroaspirin plus clopidogrel significantly reduced intimal thickening of the femoral artery while aspirin plus clopidogrel was ineffective. Nitroaspirin plus clopidogrel is more effective and less prohaemorrhagic than aspirin plus clopidogrel in mice; provided these data are confirmed in other animal models, nitroaspirin plus clopidogrel may represent a new regimen to be tested in patients undergoing coronary revascularization procedures.
The aim of the present study was to assess whether the addition of a nitric oxide (NO)-donating moiety to atorvastatin enhances anti-inflammatory and anti-atherogenic effects in an animal model of ...endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis.
Low-density lipoprotein receptor (LDLR)(-/-) mice kept on a high-fat diet (HFD) for 16 weeks underwent photochemical injury to the femoral artery with the local production of oxygen radicals. HFD markedly enhanced cholesterol, inflammatory biomarkers in plasma and in the femoral arterial wall, and atherosclerotic lesions in the aortic arch; inflammation and atherosclerosis were further increased by photochemically generated oxygen radicals. Treatment with the NO-donating atorvastatin NCX 6560 (11.7 mg/kg) was significantly more effective than atorvastatin (10 mg/kg) in reducing the following parameters: lipid-rich lesions in the aortic arch (surface covered: atorvastatin = 24 ± 5%; NCX 6560 = 14.7 ± 3.9%; P< 0.05); the production of radical oxygen species in the aorta (dichlorofluorescein fluorescence intensity per milligram of protein: atorvastatin = 2419 ± 136.7; NCX 6560 = 1766 ± 161.2; P< 0.05); femoral artery intima/media thickness (atorvastatin = 1.2 ± 0.11; NCX 6560 = 0.3 ± 0.14; P< 0.05); circulating interleukin-6 (atorvastatin = 34.3 ± 6.8 pg/mL; NCX 6560 = 17.7 ± 14.4 pg/mL; P< 0.05); and matrix metalloproteinase 2 in the arterial wall (atorvastatin = 55.2 ± 1.9 ng/µg of proteins; NCX 6560 = 45.8 ± 2.6 ng/µg of proteins; P < 0.05).
In conditions of severe endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis, atorvastatin, even at high doses, displays suboptimal anti-atherogenic and anti-inflammatory effects, while the addition of a NO-donating property confers enhanced anti-atherogenic and anti-inflammatory effects.
Background
Obesity has been described as a risk factor for COVID‐19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical ...illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID‐19 deserves further analysis.
Objective
To determine the mortality rate among hospitalized patients with severe COVID‐19 stratified according to BMI.
Methods
The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS‐CoV‐2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in‐hospital mortality.
Results
The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46–69 years), median BMI of 28.7 kg/m2 (IQR 25.4–32.4 kg/m2), 65.5% were male. In‐hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 1.01–1.10 and OR 4.08 1.64–10.14), after adjusting by sex and age.
Conclusions
The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID‐19 related mortality, compared to those with grade I or II obesity.
Antecedentes: En México, la enfermedad de Still del adulto (ESA) es una causa de fiebre de origen desconocido (FOD). El objetivo de este informe fue describir una serie de casos de ESA de una cohorte ...de FOD para conocer las características clínicas y bioquímicas, así como describir el índice neutrófilo/linfocito (INL), marcador clínico de inflamación en enfermedades autoinmunes.Caso clínico: Estudio observacional de 24 casos con ESA; 72 % fue del sexo femenino, la edad fue de 43 años (37.7-59.7) y las manifestaciones más frecuentes fueron rash clásico (84 %) y artralgias (100 %). Todos tuvieron factor reumatoide, anticuerpos antinucleares negativos e hiperferritinemia; 83 % tuvo INL > 3.08. El tratamiento más empleado fue la combinación de metotrexato y corticosteroides; siete pacientes ameritaron terapia biológica, uno presentó reacción de hipersensibilidad.Conclusión: Ante fiebre de origen desconocido, debe sospecharse ESA si, además, existe rash, artralgias, hiperferritinemia e INL > 3.08.
Nitric oxide (NO) is a powerful vasodilator and an inhibitor of platelet aggregation in vitro. While the ability of NO to modulate vascular tone in vivo has been proven, only a few studies have ...assessed its platelet inhibitory activity in vivo. We have employed two complementary animal models of pulmonary platelet thromboembolism to assess the antithrombotic activity of endogenous NO in vivo. The inhibition of nitric oxide synthase (NOS) by L-NAME significantly potentiated while the administration of the NOS substrate L-arginine significantly reduced the accumulation of 111In-labelled platelets in the pulmonary vasculature of rabbits induced by intravenous collagen plus epinephrine. L-NAME or L-arginine did not, however, modify 111In-labelled erythrocyte distribution in lungs and phenylephrine had no effect on platelet accumulation following collagen + adrenaline, suggesting that the effects of L-NAME were not due to vasoconstriction but rather to a direct modification of platelet function. In mice, L-NAME significantly reduced the dose of collagen + adrenaline required to induce thromboembolic mortality, increased the fall in circulating platelets and increased the % of pulmonary vessels occluded by platelet thrombi. The effects of L-NAME were reversed by L-arginine but not by a dose of nicardipine exerting maximal vasodilatation. Phenylephrine did not potentiate collagen + adrenaline-induced mortality. In the pulmonary vasculature in vivo, endogenous NO inhibits collagen + adrenaline-induced aggregation and enhances platelet disaggregation. This natural modulator function of NO is exerted via a direct effect on platelets and not as a result of haemodynamic changes.
The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery.
Lipid nanoparticles, prepared by high pressure homogenization, were ...stored at room temperature and 4°C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate® 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation.
Data showed nanoparticle stability at 4°C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4°C. Chorioallantoic membrane assay and rat brain histology showed the absence of acute toxicity corroborating previously published data.
Cetylpalmitate nanoparticle long-term physical and chemical stability, together with the in vivo safety, corroborate the existing evidences of the high value of colloidal lipids as parenteral formulations and carriers for brain drug delivery.
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