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Background The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes.Methods This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation.Results Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observ

N-Methylmorpholine-N-oxide (NMMO) is the solvent of choice in the lyocell process because of the interesting biodegradable, non-toxic and non-ecotoxic features that the full recovery of NMMO provides to the process. NMMO is used in its monohydrate form (1NMMO:1H2O) and cellulose dissolution occurs via hydrogen bond (HBs) formation between the oxygen at the oxide group (as the HB acceptor, HBA) and the hydroxyl groups of the cellulosic units (as the HB donor, HBD). Interestingly, HO is a serious competitor for NMMO to form HBs with cellulose so the number of HO-cellulose-HBs should be kept under control. Addition of co-solvents has become a common practice and the challenge is studying the capability of this additional co-solvent to balance the NMMO-cellulose-HBs versus HO-cellulose-HBs and thus modify the solvent capabilities of the resulting ternary mixture. Herein, we prepared ternary mixtures by addition of the respective equivalents of HO and DMSO (e.g., 1:0.5, 1:1 and 0.5:1) to anhydrous NMMO to obtain 1NMMO:1HO:0.5DMSO, 1NMMO:1HO:1DMSO and 1NMMO:0.5HO:1DMSO. We correlated the solvent capability with the HB formed among the components in the different three ternary mixtures. 1NMMO:0.5HO:1DMSO controlled the number of HO-cellulose-HBs better than the other two mixtures and this helped to maintain the resulting cellulose solution in the liquid form at room temperature.

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Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite's growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.

El Paraguay en los últimos años ha dedicado valiosos esfuerzos para impulsar una producción más sustentable de la soja, sin embargo, uno de los mayores problemas constituye el control de la roya causada por Phakopsora pachyrhizi, atendiendo a que no se dispone de fuentes de resistencia varietal. Con el objetivo de evaluar la severidad de la enfermedad mediante el control químico en dos estados fenológicos de la planta, se realizó un experimento en el campo experimental de la FCA-UNA, Distrito de Pedro Juan Caballero, Departamento de Amambay, durante el periodo agrícola  2007/2008. Todos los tratamientos de cuatro repeticiones fueron distribuidos al azar dentro de la parcela y consistieron en cinco hileras de 5 m separadas entre sí por camineros de 0,5 m; las parcelas útiles constituyeron las tres hileras centrales descontando 0,5 m de cada borde, con una densidad de 18 plantas por metro. Antes de la aplicación de los tratamientos fue realizado un muestreo para el diagnóstico fitosanitario "PRE" y la evaluación "POST" a los 60 y 85 días posteriores a la siembra. La cosecha fue realizada en el estado de R8. Las variables analizadas fueron: porcentaje de severidad, rendimiento y altura final de plantas. Las variables fueron sometidas a análisis de varianza y comparación de medias para aquellas que tuvieron diferencia significativa. Los resultados muestran que existen diferencias en el grado de incidencia y severidad del hongo, dependiendo de los fungicidas utilizados. El estudio permite concluir que, el uso de fungicidas para el control de la roya de la soja se mostró efectivo e incrementa el rendimiento. &nbsp

El Paraguay en los últimos años ha dedicado valiosos esfuerzos para impulsar una producción más sustentable de la soja, sin embargo, uno de los mayores problemas constituye el control de la roya causada por Phakopsora pachyrhizi, atendiendo a que no se dispone de fuentes de resistencia varietal. Con el objetivo de evaluar la severidad de la enfermedad mediante el control químico en dos estados fenológicos de la planta, se realizó un experimento en el campo experimental de la FCA-UNA, Distrito de Pedro Juan Caballero, Departamento de Amambay, durante el periodo agrícola  2007/2008. Todos los tratamientos de cuatro repeticiones fueron distribuidos al azar dentro de la parcela y consistieron en cinco hileras de 5 m separadas entre sí por camineros de 0,5 m; las parcelas útiles constituyeron las tres hileras centrales descontando 0,5 m de cada borde, con una densidad de 18 plantas por metro. Antes de la aplicación de los tratamientos fue realizado un muestreo para el diagnóstico fitosanitario "PRE" y la evaluación "POST" a los 60 y 85 días posteriores a la siembra. La cosecha fue realizada en el estado de R8. Las variables analizadas fueron: porcentaje de severidad, rendimiento y altura final de plantas. Las variables fueron sometidas a análisis de varianza y comparación de medias para aquellas que tuvieron diferencia significativa. Los resultados muestran que existen diferencias en el grado de incidencia y severidad del hongo, dependiendo de los fungicidas utilizados. El estudio permite concluir que, el uso de fungicidas para el control de la roya de la soja se mostró efectivo e incrementa el rendimiento. &nbsp

Background: In anesthesia with propofol, variability persists besides sophisticated effect targeting. Drug formulation may be another factor. We have analyzed, retrospectively, the pharmacokinetics (PK) and pharmacodynamics (PD) in monitored surgery patients anesthetized with one each of five formulations of propofol. Methods: Propofol 1% ('form' 1: Diprivan® (Zeneca Limited, Macclesfield, UK), 2: Recofol® (Schering Espana, Madrid, Spain), 3: Ivofol® (Juste, Madrid, Spain), 4: Propofol Abbott® (Abbott Laboratories, Madrid, Spain), 5: Fresenius® (Fresenius Kabi España, Barcelona, Spain)) was administered to 77 ASA I-II patients of age [mean (range) 44 (18-65) years]. Induction of anesthesia was with varying propofol doses up to endpoints of either 60 on the Bispectral Index™ system (BIS) in group I (n = 48, model development) or standard clinical signs in group II (n = 29, validation). Maintenance was with three 10-min infusions of 10, 8 and 6 mg kg-1 h-1. Three blood samples were obtained from each subject, immediately after induction, and at 15 and 30 min on maintenance, with BIS and hemodynamic variables recorded at these times also. Total and free blood concentrations (Cb) of propofol were determined with HPLC. Pharmacokinetic and PD models with link equilibration rate ke0, were studied with a mixed-effects procedure (NONMEM). Results: The induction dose (group I) showed large interindividual variability [mean (range) 163 (90-290 mg)] that correlated significantly with age, basal systolic blood pressure and formulation. The PK of propofol (basic model) was described by a one-compartment model with (typical value [interindividual coefficient of variation percent (CV%)]) CL=2.301 min-1 (27%) and V=8.401 (80%). Weight (WT) and formulation, within NONMEM, were found to be significant covariates for CL and V, reducing their CV% to 25% and 74%, respectively. The final PK/PD model, which includes formulation, showed a 50% reduction in the CV% for both the ke0