Summary Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the ...understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C-reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population.
At the beginning of the 21st century, the therapeutic management of neurodegenerative disorders remains a major biomedical challenge, particularly given the worldwide ageing of the population over ...the past 50 years that is expected to continue in the forthcoming years. This review will focus on the promise of cannabinoid‐based therapies to address this challenge. This promise is based on the broad neuroprotective profile of cannabinoids, which may cooperate to combat excitotoxicity, oxidative stress, glia‐driven inflammation and protein aggregation. Such effects may be produced by the activity of cannabinoids through their canonical targets (e.g. cannabinoid receptors and endocannabinoid enzymes) and also via non‐canonical elements and activities in distinct cell types critical for cell survival or neuronal replacement (e.g. neurons, glia and neural precursor cells). Ultimately, the therapeutic events driven by endocannabinoid signalling reflect the activity of an endogenous system that regulates the preservation, rescue, repair and replacement of neurons and glia.
Linked Articles
This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
•Several alternatives to chemically synthesised food preservatives are reviewed.•Terpenoids from plant essential oils have interesting antibacterial properties.•Flavonoids can act as strong ...antimicrobials at micromolar concentrations.
Synthetic food additives generate a negative perception in consumers. Therefore, food manufacturers search for safer natural alternatives such as those involving phytochemicals and plant essential oils. These bioactive compounds have antimicrobial activities widely proven in in vitro tests. Foodborne diseases cause thousands of deaths and millions of infections every year, mainly due to pathogenic bacteria such as Salmonella spp., Campylobacter spp., Escherichia coli, Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. This review summarises industrially interesting antimicrobial bioactivities as well as their mechanisms of action for three main types of plant nutraceuticals, namely terpenoids (e.g. carnosic acid), polyphenols (e.g. quercetin) and thiols (e.g. allicin), which are important constituents of plant essential oils with a broad range of antimicrobial effects. These phytochemicals are widely distributed in fruits and vegetables and are especially useful in food preservation as microbial growth inhibitors.
Coronavirus disease (Covid‐19) has reached unprecedented pandemic levels and is affecting almost every country in the world. Ramping up the testing capacity of a country supposes an essential public ...health response to this new outbreak. A pool testing strategy where multiple samples are tested in a single reverse transcriptase‐polymerase chain reaction (RT‐PCR) kit could potentially increase a country's testing capacity. The aim of this study is to propose a simple mathematical model to estimate the optimum number of pooled samples according to the relative prevalence of positive tests in a particular healthcare context, assuming that if a group tests negative, no further testing is done whereas if a group tests positive, all the subjects of the group are retested individually. The model predicts group sizes that range from 11 to 3 subjects. For a prevalence of 10% of positive tests, 40.6% of tests can be saved using testing groups of four subjects. For a 20% prevalence, 17.9% of tests can be saved using groups of three subjects. For higher prevalences, the strategy flattens and loses effectiveness. Pool testing individuals for severe acute respiratory syndrome coronavirus 2 is a valuable strategy that could considerably boost a country's testing capacity. However, further studies are needed to address how large these groups can be, without losing sensitivity on the RT‐PCR. The strategy best works in settings with a low prevalence of positive tests. It is best implemented in subgroups with low clinical suspicion. The model can be adapted to specific prevalences, generating a tailored to the context implementation of the pool testing strategy.
Highlights
‐Increasing testing capacity of a country is a key Public Health strategy in the pandemic.
‐A pool testing strategy could potentially increase a country's testing capacity, especially when implemented in lower clinical suspicion groups.
‐We provide a mathematical model to estimate the optimum number of subjects to include in a pool test, based on historical prevalences of positive results.
Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and ...characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.
407 patients with ACLF and 235 patients with acute decompensation (AD).
152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%).
Bacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.
Statistical studies that consider multiscale relationships among several variables use wavelet correlations and cross-correlations between pairs of variables. This procedure needs to calculate and ...compare a large number of wavelet statistics. The analysis can then be rather confusing and even frustrating since it may fail to indicate clearly the multiscale overall relationship that might exist among the variables. This paper presents two new statistical tools that help to determine the overall correlation for the whole multivariate set on a scale-by-scale basis. This is illustrated in the analysis of a multivariate set of daily Eurozone stock market returns during a recent period. Wavelet multiple correlation analysis reveals the existence of a nearly exact linear relationship for periods longer than the year, which can be interpreted as perfect integration of these Euro stock markets at the longest time scales. It also shows that small inconsistencies between Euro markets seem to be just short within-year discrepancies possibly due to the interaction of different agents with different trading horizons.
► We present two new wavelet correlation statistical tools. ► They provide single measures for multivariate sets on a scale-by-scale basis. ► We obtain expressions for confidence intervals of such wavelet multiple correlations. ► We analyze a set of daily Eurozone stock market returns during a recent period. ► We find evidence of perfect integration of Euro stock markets at long time scales.
1) Wind connectivity has been identified as a key factor driving many biological processes.
2) Existing software available for managing wind data are often overly complex for studying many ecological ...processes and cannot be incorporated into a broad framework.
3) Here we present rWind, an R language package to download and manage surface wind data from the Global Forecasting System and to compute wind connectivity between locations.
4) Data obtained with rWind can be used in a general framework for analysis of biological processes to develop hypotheses about the role of wind in driving ecological and evolutionary patterns.
Bacterial infections are frequent in cirrhotic patients with acute decompensation or acute-on-chronic liver failure and can complicate the clinical course. Delayed diagnosis and inappropriate ...empirical treatments are associated with poor prognosis and increased mortality. Fungal infections are much less frequent, usually nosocomial and associated with extremely high short-term mortality. Early diagnosis and adequate empirical treatment of infections is therefore key in the management of these patients. In recent decades, antibiotic resistance has become a major worldwide problem in patients with cirrhosis, warranting a more complex approach to antibiotic treatment that includes the use of broad-spectrum antibiotics, new administration strategies, novel drugs and de-escalation policies. Herein, we review epidemiological changes, the main types of multidrug-resistant organisms, mechanisms of resistance, new rapid diagnostic tools and currently available therapeutic options for bacterial and fungal infections in cirrhosis.
Multimeric enzyme complexes are ubiquitous in nature and catalyze a broad range of useful biological transformations. They are often characterized by a tight allosteric coupling between subunits, ...making them highly inefficient when isolated. A good example is Tryptophan synthase (TrpS), an allosteric heterodimeric enzyme in the form of an αββα complex that catalyzes the biosynthesis of L-tryptophan. In this study, we decipher the allosteric regulation existing in TrpS from Pyrococcus furiosus (PfTrpS), and how the allosteric conformational ensemble is recovered in laboratory-evolved stand-alone β-subunit variants. We find that recovering the conformational ensemble of a subdomain of TrpS affecting the relative stabilities of open, partially closed, and closed conformations is a prerequisite for enhancing the catalytic efficiency of the β-subunit in the absence of its binding partner. The distal mutations resuscitate the allosterically driven conformational regulation and alter the populations and rates of exchange between these multiple conformational states, which are essential for the multistep reaction pathway of the enzyme. Interestingly, these distal mutations can be a priori predicted by careful analysis of the conformational ensemble of the TrpS enzyme through computational methods. Our study provides the enzyme design field with a rational approach for evolving allosteric enzymes toward improved stand-alone function for biosynthetic applications.
Enzyme‐powered micro/nanomotors have myriads of potential applications in various areas. To efficiently reach those applications, it is necessary and critical to understand the fundamental aspects ...affecting the motion dynamics. Herein, we explored the impact of enzyme orientation on the performance of lipase‐powered nanomotors by tuning the lipase immobilization strategies. The influence of the lipase orientation and lid conformation on substrate binding and catalysis was analyzed using molecular dynamics simulations. Besides, the motion performance indicates that the hydrophobic binding (via OTES) represents the best orienting strategy, providing 48.4 % and 95.4 % increase in diffusion coefficient compared to hydrophilic binding (via APTES) and Brownian motion (no fuel), respectively (with Ctriacetin of 100 mm). This work provides vital evidence for the importance of immobilization strategy and corresponding enzyme orientation for the catalytic activity and in turn, the motion performance of nanomotors, and is thus helpful to future applications.
The impact of enzyme orientation on the performance of lipase‐powered nanomotors was explored and analysed, indicating that hydrophobic interaction is the best strategy for immobilizing lipase to provide high‐efficiency catalysis. This results in high‐efficiency enhanced Brownian motion, which would be vital in promoting the future applications of enzyme‐powered micro/nanomotors.
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