Guía de práctica clínica para la evaluación y el manejo de la hemorragia digestiva alta en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the evaluation and management of upper gastrointestinal bleeding for the Peruvian Social Security (EsSalud)

Objetivo: Proveer recomendaciones clínicas basadas en evidencia para la evaluación y el manejo de pacientes con hemorragia digestiva alta (HDA) en el seguro social del Perú (EsSalud). Materiales y métodos: Se conformó un grupo elaborador local (GEG-Local) conformado por especialistas en gastroenterología y metodólogos. El GEG-Local formuló 11 preguntas clínicas a ser respondidas por la presente guía de práctica clínica (GPC). Se buscaron y seleccionaron GPC de HDA publicadas a partir del 2012, que respondieran a las preguntas planteadas y obtuvieran un puntaje mayor a 60% en los dominios 1 y 3 del instrumento Appraisal of Guidelines for Research and Evaluation II (AGREE-II). Durante septiembre del 2017 se realizaron búsquedas bibliográficas en Pubmed, para actualizar 9 preguntas clínicas de las GPC preseleccionadas, y para responder 2 preguntas de novo. La calidad de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG-Local revisó la evidencia y formuló las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y manejo, usando la metodología GRADE Finalmente, la GPC fue aprobada con Resolución N° 80-IETSI-ESSALUD-2017. Resultados: La presente GPC abordó 11 preguntas clínicas, divididas en cuatro temas: valoración de riesgo, manejo inicial, manejo de HDA no variceal, y manejo de HDA variceal. En base a dichas preguntas se formularon 10 recomendaciones (7 recomendaciones fuertes y 3 recomendaciones débiles), 24 puntos de buena práctica clínica, y 2 flujogramas. Conclusión: Este artículo es el resumen de la GPC de EsSalud, en la cual se valoró la evidencia científica disponible sobre evaluación y manejo de HDA.

Objective: To provide evidence-based clinical recommendations for the evaluation and management of patients with upper gastrointestinal bleeding (UGB) in the Peruvian Social Security (EsSalud). Materials and methods: A local guideline development group (local GDG) was established, including specialists in gastroenterology and methodologists. The local GDG formulated 11 clinical questions to be answered by this clinical practice guide (CPG). We searched and selected CPG of UGB published from 2012, which answered the posed questions and obtained a score higher than 60% in domains 1 and 3 of the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. During September 2017, bibliographic searches were conducted in Pubmed, to update 9 clinical questions of the preselected CPGs, and to answer 2 de novo questions. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG reviewed the evidence and formulated the recommendations, points of good clinical practice and the flowchart of evaluation and management, using the GRADE methodology Lastly, the CPG was approved with Resolución N° 80-IETSI-ESSALUD-2017. Results: This CPG addressed 11 clinical questions, divided into four themes: risk assessment, initial management, management of non-variceal UGB, and management of variceal UGB. Based on these questions, 10 recommendations (7 strong recommendations and 3 weak recommendations), 24 points of good clinical practice, and 2 flow charts were formulated. Conclusion: This article is the summary of the EsSalud' CPG, where the available scientific evidence on evaluation and management of UGB was evaluated.

Quantitative trait loci affecting growth-related traits in wild barley (Hordeum spontaneum) grown under different levels of nutrient supply.

The genetic basis of phenotypic plasticity of relative growth rate (RGR), its components and associated morphological traits was studied in relation to nutrient limitation. In all, 140 F(3) lines from a cross, made between two Hordeum spontaneum (wild barley) accessions sampled in Israel, were subjected to growth analysis under two nutrient levels. Quantitative trait loci (QTLs) were detected for RGR and three of its components, leaf area ratio (LAR), specific leaf area and leaf mass fraction (LMF). Indications for close linkage (potential pleiotropy) were found, for example, for LAR and LMF. An interesting case is on chromosome 6, at which QTLs for RGR and seed mass were detected in the same region. These QTLs had opposite additive effects, supporting earlier results that plants growing from lighter seeds had a higher RGR. Only two QTLs were significant under both nutrient conditions, suggesting large QTL x environment interactions for most traits. For 21 out of 26 QTLs, however, the additive genetic effect was of identical sign in both nutrient environments, but reached the significance threshold in only one of them. Nevertheless, some QTLs detected in one of the two environments had virtually no effect in the other, and QTLs for plasticity were detected for RGR, LAR and LMF, as well as for some morphological traits. QTLs with opposite effects under high and low nutrients were not found. Thus, at the genetic level, there was no evidence for a trade-off between faster growth at high versus low nutrient levels.

The relationship between relative growth rate and susceptibility to aphids in wild barley under different nutrient levels.

The Resource Availability Hypothesis (RAH) states that plants with a low Relative Growth Rate (RGR) and high levels of defence against herbivores or pathogens are favoured in habitats with low resource availability, whereas plants with a high potential RGR and low levels of defence are favoured in environments with high resource availability. High levels of defence are expected to result in lower reproduction and/or growth of the herbivores or pathogens. To test this hypothesis, four accessions of each of nine natural Hordeum spontaneum (wild barley) populations were grown in a climate chamber under two levels of nutrient supply. Susceptibility to Schizaphis graminum (greenbug) was quantified by placing a single adult greenbug on each plant and measuring its realised fecundity after 8 days. Data on potential RGR were available from a previous experiment. No support for the RAH was found. The correlation between potential RGR and greenbug reproduction was not significant, neither at the high nor at the low level of nutrient supply. Furthermore, on average plants grown under high and low nutrients did not differ in susceptibility. However, accessions-within-populations differed in the way susceptibility was affected by nutrient supply, and most accessions had a higher susceptibility under nutrient-poor conditions. It could be that these accessions differed in the spectrum of secondary metabolites they produced. Whatever the cause, the genetic variation for the reaction in susceptibility to nutrient supply suggests that selection could act in favour of more or less plasticity in plants without any apparent change in potential RGR.

Mitochondrial effects of triarylmethane dyes.

The mitochondrial effects of submicromolar concentrations of six triarylmethane dyes, with potential applications in antioncotic photodynamic therapy, were studied. All dyes promoted an inhibition of glutamate or succinate-supported respiration in uncoupled mitochondria, in a manner stimulated photodynamically. No inhibition of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) supported respiration was observed, indicating that these dyes do not affect mitochondrial complex IV. When mitochondria were energized with TMPD in the absence of an uncoupler, treatment with victoria blue R, B, or BO, promoted a dissipation of mitochondrial membrane potential and increase of respiratory rates, compatible with mitochondrial uncoupling. This effect was observed even in the dark, and was not prevented by EGTA, Mg2+ or cyclosporin A, suggesting that it is promoted by a direct effect of the dye on inner mitochondrial membrane permeability to protons. Indeed, victoria blue R, B, and BO promoted swelling of valinomycin-treated mitochondria incubated in a hyposmotic K+-acetate-based medium, confirming that these dyes act as classic protonophores such as FCCP. On the other hand, ethyl violet, crystal violet, and malachite green promoted a dissipation of mitochondrial membrane potential, accompanied by mitochondrial swelling, which was prevented by EGTA, Mg2+, and cyclosporin A, demonstrating that these drugs induce mitochondrial permeability transition. This mitochondrial permeabilization was followed by respiratory inhibition, attributable to cytochrome c release, and was caused by the oxidation of NAD(P)H promoted by these drugs.