RESUMEN
The identification of promising metabolic engineering targets is a key issue in metabolic control analysis (MCA). Conventional approaches make intensive use of model-based studies, such as exploiting post-pulse metabolic dynamics after proper perturbation of the microbial system. Here, we present an easy-to-use, purely data-driven approach, defining pool efflux capacities (PEC) for identifying reactions that exert the highest flux control in linear pathways. Comparisons with linlog-based MCA and data-driven substrate elasticities (DDSE) showed that similar key control steps were identified using PEC. Using the example of l-methionine production with recombinant Escherichia coli, PEC consistently and robustly identified main flux controls using perturbation data after a non-labeled 12C-l-serine stimulus. Furthermore, the application of full-labeled 13C-l-serine stimuli yielded additional insights into stimulus propagation to l-methionine. PEC analysis performed on the 13C data set revealed the same targets as the 12C data set. Notably, the typical drawback of metabolome analysis, namely, the omnipresent leakage of metabolites, was excluded using the 13C PEC approach.
Asunto(s)
Escherichia coli , Metaboloma/genética , Metionina , Modelos Biológicos , Escherichia coli/genética , Escherichia coli/metabolismo , Metionina/biosíntesis , Metionina/genéticaRESUMEN
OBJECTIVE: Identify which biomarkers performed in the first emergency analysis help to stratify COVID-19 patients according to mortality risk. METHODS: Observational, descriptive and cross-sectional study performed with data collected from patients with suspected COVID-19 in the Emergency Department from February 24 to March 16, 2020. The univariate and multivariate study was performed to find independent mortality markers and calculate risk by building a severity score. RESULTS: A total of 163 patients were included, of whom 33 died and 29 of them were positive for the COVID-19 PCR test. We obtained as possible factors to conform the Mortality Risk Score age> 75 years ((adjusted OR = 12,347, 95% CI: 4,138-36,845 p = 0.001), total leukocytes> 11,000 cells / mm3 (adjusted OR = 2,649, 95% CI: 0.879-7.981 p = 0.083), glucose> 126 mg / dL (adjusted OR = 3.716, 95% CI: 1.247-11.074 p = 0.018) and creatinine> 1.1 mg / dL (adjusted OR = 2.566, 95% CI: 0.889- 7.403, p = 0.081) This score was called COVEB (COVID, Age, Basic analytical profile) with an AUC 0.874 (95% CI: 0.816-0.933, p <0.001; Cut-off point = 1 (sensitivity = 89.66 % (95% CI: 72.6% -97.8%), specificity = 75.59% (95% CI: 67.2% -82.8%). A score <1 has a negative predictive value = 100% (95% CI: 93.51% -100%) and a positive predictive value = 18.59% (95% CI: 12.82% -25.59%). CONCLUSIONS: Clinical severity scales, kidney function biomarkers, white blood cell count parameters, the total neutrophils / total lymphocytes ratio and procalcitonin are early risk factors for mortality. The variables age, glucose, creatinine and total leukocytes stand out as the best predictors of mortality. A COVEB score <1 indicates with a 100% probability that the patient with suspected COVID-19 will not die in the next 30 days.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/mortalidad , Neumonía Viral/sangre , Neumonía Viral/mortalidad , Factores de Edad , Anciano , Análisis de Varianza , Área Bajo la Curva , Biomarcadores/sangre , Glucemia/análisis , COVID-19 , Infecciones por Coronavirus/diagnóstico , Creatinina/sangre , Estudios Transversales , Servicio de Urgencia en Hospital , Femenino , Humanos , Hipertensión/mortalidad , Recuento de Leucocitos , Masculino , Oportunidad Relativa , Pandemias , Neumonía Viral/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo/métodos , SARS-CoV-2 , Sensibilidad y EspecificidadRESUMEN
Reducing the size of low-solubility iron (Fe)-containing compounds to nanoscale has the potential to improve their bioavailability. Because Fe and zinc (Zn) deficiencies often coexist in populations, combined Fe/Zn-containing nanostructured compounds may be useful for nutritional applications. Such compounds are developed here and their solubility in dilute acid, a reliable indicator of iron bioavailability in humans, and sensory qualities in sensitive food matrices are investigated. Phosphates and oxides of Fe and atomically mixed Fe/Zn-containing (primarily ZnFe2O4) nanostructured powders were produced by flame spray pyrolysis (FSP). Chemical composition and surface area were systematically controlled by varying precursor concentration and feed rate during powder synthesis to increase solubility to the level of ferrous sulfate at maximum Fe and Zn content. Solubility of the nanostructured compounds was dependent on their particle size and crystallinity. The new nanostructured powders produced minimal color changes when added to dairy products containing chocolate or fruit compared to the changes produced when ferrous sulfate or ferrous fumarate were added to these foods. Flame-made Fe- and Fe/Zn-containing nanostructured powders have solubilities comparable to ferrous and Zn sulfate but may produce fewer color changes when added to difficult-to-fortify foods. Thus, these powders are promising for food fortification and other nutritional applications.
Asunto(s)
Tecnología de Alimentos/métodos , Hierro/química , Nanoestructuras/química , Ciencias de la Nutrición , Zinc/química , Disponibilidad Biológica , Técnicas Biosensibles , Cristalización , Compuestos Férricos/química , Humanos , Hierro/farmacocinética , Microscopía Electrónica de Transmisión , Microscopía de Túnel de Rastreo , Tamaño de la Partícula , Fosfatos/análisis , Polvos , Solubilidad , Propiedades de Superficie , Difracción de Rayos X , Zinc/farmacocinética , Óxido de Zinc/químicaRESUMEN
The consensus paper for the implementation and development of the sepsis code, finished in April 2017 is presented here. It was adopted by the Regional Office of Health as a working document for the implementation of the sepsis code in the Community of Madrid, both in the hospital setting (acute, middle and long-stay hospitals) and in Primary Care and Out-of-Hospital Emergency Services. It is now published without changes with respect to the original version, having only added the most significant bibliographical references. The document is divided into four parts: introduction, initial detection and assessment, early therapy and organizational recommendations. In the second to fourth sections, 25 statements or proposals have been included, agreed upon by the authors after several face-to-face meetings and an extensive "online" discussion. The annex includes nine tables that are intended as a practical guide to the activation of the sepsis code. Both the content of the recommendations and their formal writing have been made taking into account their applicability in all areas to which they are directed, which may have very different structural and functional characteristics and features, so that we have deliberately avoided a greater degree of concretion: the objective is not that the sepsis code is organized and applied identically in all of them, but that the health resources work in a coordinated manner aligned in the same direction.