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Journal of Hepatology Oct 2023Neuropsychological and psychophysical tests are recommended to assess the risk of overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is... (Observational Study)
Observational Study
BACKGROUND & AIMS
Neuropsychological and psychophysical tests are recommended to assess the risk of overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. In this study, we aimed to determine the role of neuropsychological or psychophysical tests and ammonia, and to develop a model (AMMON-OHE) to stratify the risk of subsequent OHE development in outpatients with cirrhosis.
METHODS
This observational, prospective study included 426 outpatients without previous OHE from three liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk and random survival forest analyses were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units.
RESULTS
Significant differences were found in time-to-OHE (log-rank p <0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (hazard ratio 4.4; 95% CI 2.4-8.1; p <0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor of the development of OHE (hazard ratio 1.4; 95% CI 1.1-1.9; p = 0.015). The AMMON-OHE model (sex, diabetes, albumin, creatinine and AMM-ULN) showed a C-index of 0.844 and 0.728 for the prediction of a first episode of OHE in two external validation cohorts.
CONCLUSIONS
In this study, we developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at the highest risk of developing a first episode of OHE.
IMPACT AND IMPLICATIONS
In this study, we aimed to develop a model to predict which patients with cirrhosis are at risk of developing overt hepatic encephalopathy (OHE). Using data from three units and including 426 outpatients with cirrhosis, we developed the AMMON-OHE model - comprising sex, diabetes, albumin, creatinine and ammonia levels - which demonstrated good predictive ability. The AMMON-OHE model performs better than PHES and CFF to predict the first episode of OHE in outpatients with cirrhosis. This model was validated in 267 and 381 patients from two independent liver units. The AMMON-OHE model is available online for clinical use.
Topics: Humans; Hepatic Encephalopathy; Outpatients; Prospective Studies; Ammonia; Creatinine; Liver Cirrhosis; Psychometrics
PubMed: 37277075
DOI: 10.1016/j.jhep.2023.05.022 -
Journal of Enzyme Inhibition and... Dec 2023Urease is a kind of nickel-dependent metalloenzyme, which exists in the biological world widely, and can catalyse the hydrolysis of urea into ammonia and carbon dioxide... (Review)
Review
Urease is a kind of nickel-dependent metalloenzyme, which exists in the biological world widely, and can catalyse the hydrolysis of urea into ammonia and carbon dioxide to provide a nitrogen source for organisms. Urease has important uses in agriculture and medicine because it can catalyse the production of ammonia. Therefore, in this review, metal-based inhibitors of urease will be summarised according to different transition metal ions. Including the urease inhibition, structure-activity relationship, and molecular docking. Importantly, among these reviewed effective urease inhibitors, most of copper metal complexes exhibited stronger urease inhibition with IC values ranging from 0.46 μM to 41.1 μM. Significantly, the collected comprehensive information looks forward to providing rational guidance and effective strategies for the development of novel, potent, and safe metal-based urease inhibitors, which are better for practical applications in the future.
Topics: Urease; Ammonia; Molecular Docking Simulation; Metals; Metalloproteins
PubMed: 36446640
DOI: 10.1080/14756366.2022.2150182 -
Nature Communications Sep 2023For decarbonization of ammonia production in industry, alternative methods by exploiting renewable energy sources have recently been explored. Nonetheless, they still...
For decarbonization of ammonia production in industry, alternative methods by exploiting renewable energy sources have recently been explored. Nonetheless, they still lack yield and efficiency to be industrially relevant. Here, we demonstrate an advanced approach of nitrogen fixation to synthesize ammonia at ambient conditions via laser-induced multiphoton dissociation of lithium oxide. Lithium oxide is dissociated under non-equilibrium multiphoton absorption and high temperatures under focused infrared light, and the generated zero-valent metal spontaneously fixes nitrogen and forms a lithium nitride, which upon subsequent hydrolysis generates ammonia. The highest ammonia yield rate of 30.9 micromoles per second per square centimeter is achieved at 25 °C and 1.0 bar nitrogen. This is two orders of magnitude higher than state-of-the-art ammonia synthesis at ambient conditions. The focused infrared light here is produced by a commercial simple CO laser, serving as a demonstration of potentially solar pumped lasers for nitrogen fixation and other high excitation chemistry. We anticipate such laser-involved technology will bring unprecedented opportunities to realize not only local ammonia production but also other new chemistries .
PubMed: 37704640
DOI: 10.1038/s41467-023-41441-0 -
Essays in Biochemistry Aug 2023Aerobic nitrification is a key process in the global nitrogen cycle mediated by microorganisms. While nitrification has primarily been studied in near-neutral... (Review)
Review
Aerobic nitrification is a key process in the global nitrogen cycle mediated by microorganisms. While nitrification has primarily been studied in near-neutral environments, this process occurs at a wide range of pH values, spanning ecosystems from acidic soils to soda lakes. Aerobic nitrification primarily occurs through the activities of ammonia-oxidising bacteria and archaea, nitrite-oxidising bacteria, and complete ammonia-oxidising (comammox) bacteria adapted to these environments. Here, we review the literature and identify knowledge gaps on the metabolic diversity, ecological distribution, and physiological adaptations of nitrifying microorganisms in acidic and alkaline environments. We emphasise that nitrifying microorganisms depend on a suite of physiological adaptations to maintain pH homeostasis, acquire energy and carbon sources, detoxify reactive nitrogen species, and generate a membrane potential at pH extremes. We also recognize the broader implications of their activities primarily in acidic environments, with a focus on agricultural productivity and nitrous oxide emissions, as well as promising applications in treating municipal wastewater.
Topics: Nitrification; Ammonia; Ecosystem; Oxidation-Reduction; Bacteria
PubMed: 37449414
DOI: 10.1042/EBC20220194 -
ISME Communications Jan 2024The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual...
The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we identify and distinguish functional implementations, which are sequence spaces that have different ways of carrying out the function. In contrast, we found that orthology delineation did not consistently align with ecologically (or functionally) distinct implementations of the function. We demonstrate the value of our approach with two case studies: the ammonia oxidation and polyamine uptake guilds from the Malaspina circumnavigation cruise, revealing novel ecological dynamics of the latter in marine ecosystems. Thus, the quantification of guilds helps us to assess the functional role of different taxonomic groups with profound implications on the study of microbial communities.
PubMed: 38707845
DOI: 10.1093/ismeco/ycae042