EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

A method for inverse bifurcation of biochemical switches: inferring parameters from dose response curves

16 páginas, 8 figuras, 4 tablas.-- This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited[Background] Within cells, stimuli are transduced into cell responses by complex networks of biochemical reactions. In many cell decision processes the underlying networks behave as bistable switches, converting graded stimuli or inputs into all or none cell responses. Observing how systems respond to different perturbations, insight can be gained into the underlying molecular mechanisms by developing mathematical models. Emergent properties of systems, like bistability, can be exploited to this purpose. One of the main challenges in modeling intracellular processes, from signaling pathways to gene regulatory networks, is to deal with high structural and parametric uncertainty, due to the complexity of the systems and the difficulty to obtain experimental measurements. Formal methods that exploit structural properties of networks for parameter estimation can help to overcome these problems.[Results] We here propose a novel method to infer the kinetic parameters of bistable biochemical network models. Bistable systems typically show hysteretic dose response curves, in which the so called bifurcation points can be located experimentally. We exploit the fact that, at the bifurcation points, a condition for multistationarity derived in the context of the Chemical Reaction Network Theory must be fulfilled. Chemical Reaction Network Theory has attracted attention from the (systems) biology community since it connects the structure of biochemical reaction networks to qualitative properties of the corresponding model of ordinary differential equations. The inverse bifurcation method developed here allows determining the parameters that produce the expected behavior of the dose response curves and, in particular, the observed location of the bifurcation points given by experimental data.[Conclusions] Our inverse bifurcation method exploits inherent structural properties of bistable switches in order to estimate kinetic parameters of bistable biochemical networks, opening a promising route for developments in Chemical Reaction Network Theory towards kinetic model identification.We gratefully acknowledge financial support from the EU FP7 project IFNAction (contract 223608)Peer reviewe

Fungi isolated from Stewartia pseudocamellia Max. seeds and their pathogenesis

The aim of studies was to determine typical composition of fungi occurring on seeds of Stewartia pseudocamellia.The studies conducted on 100 disinfected and 100 nondisinfected seeds of these plants. Isolates of Alternaria alternata, Fusarium oxysporum, Cylindrocarpon radicicola and Rhizoctonia solani were characterized by pathogenicity towards the investigated Stewartia pseudocamellia. In the laboratory experiment, 204 isolations of microorganisms were obtained that belonged to 20 species and form of fungi and bacteria. Among fungi there were both of parasite (Alternaria alternata, Botrytis cinerea, Fusarium spp., Rhizoctonia solani) and typical saprophytic (Cladosporium spp., Penicillium spp., Aspergillus spp., Epicoccum spp., Mucor spp.). The dominant fungus on seeds was Alternaria alternata. Among the investigated isolates only one isolate (R₄) Rhizoctonia solani, was strongly pathogenic, isolates (A₁) Alternaria alternata were weakly pathogenic to seedlings of Stewartia pseudocamellia.Badania przeprowadzono na materiale pochodzącym z kolekcji dr Murasa w Tomaszkowicach - Pogórze Wielickie. Badano 100 nasion stewarcji pseudokameliowatej dezynfekowanych i 100 niedezynfekowanych. Badania patogeniczności izolatów grzybów: Alternaria alternata, Cylindocarpon radicicola, Fusarium oxysporum i Rhizoctonia solani w stosunku do siewek stewarcji pseudokameliowatej przeprowadzono w warunkach szklarniowych w pięciu powtórzeniach dla każdej kombinacji. W wyniku przeprowadzonych badań laboratoryjnych wyosobniono 204 izolaty mikroorganizmów należących do 20 gatunków i form grzybów oraz bakterie. Wśród grzybów izolowanych z dezynfekowanych nasion stewarcji przeważały gatunki zaliczane do patogenicznych dla roślin. Były to gatunki rodzajów: Alternaria, Botrytis, Fusarium i Rhizoctonia. Wyniki uzyskane z przeprowadzonych doświadczeń szklarniowych wskazują na zróżnicowany stopień patogeniczności grzybów w stosunku do siewek stewarcji pseudokameliowatej. Najbardziej patogenicznie działał izolat Rhizoctonia solani. Najmniejszą chorobotwórczość w stosunku do siewek stewarcji wykazał izolat Alternaria alternata

Nawożenie azotem stewarcji kameliowatej Stewartia pseudocamellia uprawianej w podłożu o zróżnicowanym odczynie

The study was conducted on Stewartia (Stewartia pseudocamellia Maxim.) plants, grown in containers under field conditions. The shrubs were fertilised with two nitrogen forms: ammonia NH4+ and nitrate NO3– at the substrate pH values of 3.9 and 5.5. The plants were top-dressed with reference to the analysis of the substrate. During the vegetation season the leaves were harvested twice in order to analyse the content of easily soluble forms and nutrients. In the experiment a gradual increase of acidity and salt content in the substrate was observed, as compared with the original content. After the first and second year of cultivation, low content of mineral nitrogen in the substrates was noticed. In both years of cultivation, higher contents of phosphorus and lower contents of potassium in the substrates of shrubs fertilised with ammonia form were detected. The content of easily soluble forms of elements in Stewartia leaves remained practically unchanged throughout vegetation. The study revealed a very low content of mineral nitrogen in the leaves of Stewartia. The contents of easily soluble forms of nutrients (K, Ca, Mg) determined in the leaves varied with reference to both the substrate acidity and the form of nitrogen fertiliser used. The total nutrients contents, except of the total nitrogen content, were comparable in the first and second harvest. The content of total phosphorus and magnesium in the leaves was dependent on the nitrogen form, higher contents were noted in objects fertilised with ammonia form. However, Stewartia showed greater uptake of potassium, when fertilised with the nitrate form. The experiments also revealed the effect of substrate acidity on the uptake of potassium by the plants.Badaniami objęto rośliny stewarcji (Stewartia pseudocamellia Maxim.), uprawiane w latach 1998-1999 w pojemnikach w warunkach polowych. Krzewy nawożono amonową lub azotanową formą azotu przy odczynie podłoża pH = 3,9 i 5,5. Rośliny nawożono pogłównie na podstawie analizy podłoża. W sezonie wegetacyjnym dwukrotnie pobrano liście do analiz na zawartość łatwo rozpuszczalnych form składników pokarmowych oraz ogólną ich zawartość. W czasie trwania doświadczenia obserwowano stopniowy wzrost pH oraz ogólnego stężenia soli w podłożu w stosunku do wartości wyjściowych. Po zakończeniu każdego roku uprawy stwierdzono małą zawartość azotu mineralnego w podłożach. W obu latach uprawy obserwowano większą zawartość fosforu oraz mniejszą zawartość potasu w podłożu krzewów nawożonych formą amonową w porównaniu z nawożonymi formą azotanową. Zawartość łatwo rozpuszczalnych form składników w liściach stewarcji utrzymywała się na zbliżonym poziomie przez cały okres wegetacji. Badania wykazały bardzo małą zawartość azotu mineralnego w liściach stewarcji. Oznaczone zawartości łatwo rozpuszczalnych form składników pokarmowych (K, Ca, Mg) wykazały zróżnicowanie w zależności od odczynu podłoża, jak również od formy nawozu azotowego. Całkowite zawartości składników pokarmowych w obu terminach pobierania liści były porównywalne, z wyjątkiem azotu ogólnego. Ogólna zawartość fosforu i magnezu w liściach była uzależniona od zastosowanej formy azotu, przy czym większe zawartości notowano w obiektach nawożonych formą amonową. Natomiast potas był lepiej pobierany przez stewarcje w obecności formy azotanowej w podłożu. W badaniach wykazano również wpływ odczynu podłoża na pobieranie potasu przez rośliny

Automated Biocircuit Design with SYNBADm

18 pages, 12 figuresSYNBADm is a Matlab toolbox for the automated design of biocircuits using a model-based optimization approach. It enables the design of biocircuits with pre-defined functions starting from libraries of biological parts. SYNBADm makes use of mixed integer global optimization and allows both single and multi-objective design problems. Here we describe a basic protocol for the design of synthetic gene regulatory circuits. We illustrate step-by-step how to solve two different problems: (1) the (single objective) design of a synthetic oscillator and (2) the (multi-objective) design of a circuit with switch-like behavior upon induction, with a good compromise between performance and protein production costThis research was funded by the Spanish Ministry of Science, Innovation and Universities, project SYNBIOCONTROL (ref. DPI2017-82896-C2-2-R)N

Influence of platinum ions on phenolic compounds in Lepidium sativum seedlings

Despite limiting the transport emitted pollution, contamination of the roadside environment remains an important issue. Due to necessity to decrease the lead emission, catalytic converters modifications were introduced. It caused increase of Platinum Group Elements (PGEs) emission, which was rare in the environment before. So far there is lack of information about platinum contamination to functioning of plants which are so important in the urban environment. In the experiment garden cress (Lepidium sativum) were sown into Petri dishes filled with filter paper soaked with solutions of different platinum concentration. There were used two compounds containing platinum at different oxidation states PtCl4 - ssolutions containing 0.58, 2.89, 5.79, 11.58 and 23.16 mg Pt4+•dm−3 and [Pt(NH3)4] (NO3)2 - solutions containing 0.50, 2.52, 5.04, 10.08 and 20.15 mg Pt2+•dm−3 in every combination of the experiment. In every combination there were five Petri dishes, experiment was repeated twice. To estimate plant response to stress factor, phenolic compounds contents were analyzed in the roots and shoots parts separately. The highest amount of total phenolics in roots was recorded in plants treated with highest Pt4+ dose which was 23.16 mg•dm−3, seeds treated with other doses of platinum (including those treated with highest dose of Pt2+ did not differ significantly from control plants. In the case of phenolic compounds in the aboveground parts of seedlings there was highest accumulation than in roots. Highest amounts of phenolics were recorded in plants also treated with Pt4+ in doses 11.58 and 23.16 mg•dm−3