Búsqueda de agentes fitosanitarios provenientes de especies del género Piper (Piperaceae) para el control de Fusarium oxysporum f.sp. passiflorae

El presente trabajo contribuyó en la búsqueda de agentes fitosanitarios para el control de Fusarium oxysporum f.sp.passiflorae mediante el estudio fitoquímico del extracto de inflorescencias de Piper cumanense, que permitió el aislamiento y la identificación de diferentes compuestos, cinco derivados de ácido benzoico abiertos y cerrados (cromenos) entre ellos un nuevo compuesto llamado ácido (2S)-2-metil-2-(4’-metil-pent-3’-enil-8-(3’’- metil-but-2’’-enil)-)-4-oxo-cromano-6-carboxílico N9, el cual se denominó ácido oxocuménico, un sesquiterpeno y mezcla de esteroles. Se realizó la síntesis de análogos y derivados de cromenos, obteniendo 41 compuestos sintéticos. Posteriormente se evaluó la actividad antifúngica y los efectos tóxicos de los compuestos naturales y sintéticos, encontrando que los compuestos naturales ácido-2,2-dimetil-2H-cromeno-6-carboxilico N10 y ácido (2’Z) cumenico N2, presentaron los menores valores de CI50 7,2 y 18,7 μg/mL respectivamente. El compuesto N10 es el único compuesto de los evaluados que presentó actividad fungicida. Los compuestos sintéticos la cromona y el cromanol bromado S3b y S4b, fueron los compuestos con los menores valores de CI50 6,0 y 6,4 μg/mL correspondientemente. Estos compuestos naturales y sintéticos también presentaron los menores efectos tóxicos. En comparación con el control positivo Benomil ® utilizados por los campesinos en el control de esta enfermedad en los cultivos de Gulupa, estos compuestos presentan concentraciones y efectos tóxicos bajos, haciéndolos agentes fitosanitarios promisorios. Por último, se planteó un modelo computacional basado en farmacóforo, utilizando las características farmacofóricas de los compuestos más activos para predecir 16 nuevos compuestos activos.Abstract: The present study contributed in the search of phytosanitary agents for the control of Fusarium oxysporum f.sp.passiflorae by means of the phytochemical study of the inflorescence extract of Piper cumanense, which allowed the isolation and identification of different compounds, five benzoic acid derivatives, opened and closed (chromenes) including a new compound called (2S)-2-methyl-2-(4'-methyl-pent-3'-enyl-8-(3 "-methylbut- 2"-enyl)-4-oxo-chroman-6-carboxylic acid N9, which was called oxocumnic acid, a sesquiterpene and a mixture of sterols. As a result of the synthesis of chromosome analogs and derivatives, 41 synthetic compounds were obtained. Later the antifungal activity and the toxic effects of the natural and synthetic compounds were evaluated, finding that the natural compounds 2,2-dimethyl-2H-chromene-6-carboxylic acid N10 and (2'Z) cumenic acid N2, showed the lowest values of IC50 7.2 and 18.7 μg/mL respectively. The compound N10 is the only compound of the evaluated that presented fungicidal activity. The synthetic compounds chromone and brominated chromanol S3b and S4b, were the compounds with the lowest values of IC50 6.0 and 6.4 μg/mL correspondingly. These natural and synthetic compounds also had the least toxic effects. In comparison with the Benomil® positive control used by farmers in the control of this disease in Gulupa crops, these compounds have low toxic concentrations and effects, making them promising plant protection agents. Finally, a computational model based on pharmacophore was proposed, using the pharmacoforic characteristics of the most active compounds to predict 16 new active compounds.Doctorad

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Contribución al estudio fitoquímico de la parte aérea de piper cf. cumanense kunth (piperaceae Contribución al estudio fitoquímico de la parte aérea de piper cf. cumanense kunth (piperaceae)

A partir de los extractos etanólicos de hojas e inflorescencias de la especie Piper cf. cumanense Kunth (Piperaceae) cultivada, se aislaron diferentes metabolitos y se identificaron dos nuevos compuestos, derivados de ácido benzoico, llamados “ácido cumanensico” y “ácido cumenico”; junto con cuatro compuestos conocidos como campesterol, estigmasterol, β–sitosterol y oxido de cariofileno. La elucidación estructural de los compuestos aislados se realizó utilizando técnicas espectroscópicas y por comparación con los datos reportados en la literatura. Se obtuvieron aceites esenciales por la técnica de arrastre de vapor de hojas frescas de tipo cultivada y silvestre; su determinación se realizó por CG-EM, mediante comparación de los índices de retención y espectros de masa, con los datos reportados en la literatura, encontrando que un aceite presenta como componentes mayoritarios compuestos tipo monoterpeno, a diferencia del otro que presenta una composición de sesquiterpenos. Se evaluó la actividad insecticida sobre Sitophilus zeamais, Tribolium castaneum y Spodoptera frugiperda y antifúngica in vitro sobre Fusarium oxysporum f sp. dianthi, de los extractos, compuestos nuevos y aceites esenciales.Se observó que los aceites esenciales poseen una actividad fumigante del 83 al 85% de mortalidad contra S. zeamais. En la actividad antifúngica la cantidad mínima inhibitoria para el ácido cumanensico fue de 1μg y para el ácido cumenico fue de 10 μg, comparable a la del control positivo Benomyl (1 μg). / Abstract. From the ethanolic leaf and inflorescences of the cultivated specie Piper cf. cumanense Kunth (Piperaceae), different metabolites were isolated and two new compounds were identified, they derive from acid benzoic, called “cumanensic acid” and “cumenic acid” together with four additional compounds kind of sterols known as campesterol, stigmasterol, β-sitosterol and “caryophyllene oxide”. Structural elucidation of the isolated compounds was made using spectroscopic techniques and by comparison with information reported in literature. Essential oils were obtained by the technique of steam distillation of fresh leaves cultivated and wild type, their determination was performed by GC-MS through comparison of retention indices and mass spectra with data reported in the literature, finding presented as an oil major components monoterpeno type compounds, unlike the other having a composition of sesquiterpenes. Insecticidal activity was evaluated on Sitophilus zeamais, Tribolium castaneum and Spodoptera frugiperda and antifungal in vitro on Fusarium oxysporum f sp. dianthi, using the extracts, new compounds and essential oils. It was observed that the essential oils have a fumigant activity from 83% to 85% of mortality against S. zeamais. In the antifungal activity the minimum inhibitory amount for the cumanensic acid was of 1 μg and for the cumenic acid was of 10 μg, comparable to positive control Benomyl (1 μg)Maestrí

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)