Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis

Background: Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings. Objective: The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings. Methods: Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function. A random effects model was used to produce a pooled estimate. A hierarchical summary receiver operating curve model was fitted for diagnostic accuracy measures. Results: Citrulline levels are correlated strongly with small bowel length in short bowel syndrome patients (r  = 0.67). Citrulline is strongly negatively correlated (r  = –0.56) with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, Crohn’s disease, mucositis, acute rejection in intestinal transplantation). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and 84% respectively. Citrulline levels in untreated coeliac patients compared to controls were reduced by 10 µmol/l. Citrulline levels increase with gluten-free diet and with improvement of enteropathy. Citrulline is decreased in critical illness and sepsis. Conclusion: These findings allow us to advocate quite reasonably that citrulline is a marker of acute and chronic intestinal insufficiency

Review of the literature and description of a case of sclerosing encapsulating peritonitis requiring home parenteral nutrition

We present a case of a 48 year old HIV patient, who had recurrent episodes of ascites since 2007. His history includes ischaemic heart disease, for which he was treated with atenolol from 2005 to 2007, and Type 2 diabetes; he was later started on propranolol 40  mg twice a day from 2007 for Didanosine-induced portal hypertension. Because of negative cultures and neutrophil count < 250 cells/μL, spontaneous bacterial peritonitis was excluded. However, some low grade-peritoneal irritation cannot be ruled out because his CRP varied from 24 to 258, during 2007 - 2009, without any other obvious inflammatory cause. He was finally diagnosed in July 2009 with sclerosing encapsulating peritonitis (SEP) based on clinical features of intestinal obstruction, histology and imaging, including computed tomography and magnetic resonance imaging. Propranolol was stopped in November 2009.  Because of the patient's severe intestinal obstruction, he was started on parenteral nutrition 2  L/day. Since then, his CRP has returned to normal levels and there is a great improvement of his clinical features. This case demonstrates beta-blockers as a potential cause of SEP, while the presence of some low-grade peritoneal inflammation leading to SEP is also very likely

Environmental risk assessment of genetically modified plants - concepts and controversies

Background and purpose: In Europe, the EU Directive 2001/18/EC lays out the main provisions of environmental risk assessment (ERA) of genetically modified (GM) organisms that are interpreted very differently by different stakeholders. The purpose of this paper is to: (a) describe the current implementation of ERA of GM plants in the EU and its scientific shortcomings, (b) present an improved ERA concept through the integration of a previously developed selection procedure for identification of non-target testing organisms into the ERA framework as laid out in the EU Directive 2001/18/EC and its supplement material (Commission Decision 2002/623/EC), (c) describe the activities to be carried out in each component of the ERA and (d) propose a hierarchical testing scheme. Lastly, we illustrate the outcomes for three different crop case examples. Main features: Implementation of the current ERA concept of GM crops in the EU is based on an interpretation of the EU regulations that focuses almost exclusively on the isolated bacteria-produced novel proteins with little consideration of the whole plant. Therefore, testing procedures for the effect assessment of GM plants on non-target organisms largely follow the ecotoxicological testing strategy developed for pesticides. This presumes that any potential adverse effect of the whole GM plant and the plant-produced novel compound can be extrapolated from testing of the isolated bacteriaproduced novel compound or can be detected in agronomic field trials. This has led to persisting scientific criticism. Results: Based on the EU ERA framework, we present an improved ERA concept that is system oriented with the GM plant at the centre and integrates a procedure for selection of testing organisms that do occur in the receiving environment. We also propose a hierarchical testing scheme from laboratory studies to field trials and we illustrate the outcomes for three different crop case examples. Conclusions and recommendations: Our proposed concept can alleviate a number of deficits identified in the current approach to ERA of GM plants. It allows the ERA to be tailored to the GM plant case and the receiving environment

Worth the ‘EEfRT’? The Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia

Background: Of the putative psychopathological endophenotypes in major depressive disorder (MDD), the anhedonic subtype is particularly well supported. Anhedonia is generally assumed to reflect aberrant motivation and reward responsivity. However, research has been limited by a lack of objective measures of reward motivation. We present the Effort-Expenditure for Rewards Task (EEfRT or ‘‘effort’’), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans. Using the EEfRT, we test the hypothesis that effort-based decision-making is related to trait anhedonia. Methods/Results: 61 undergraduate students participated in the experiment. Subjects completed self-report measures of mood and trait anhedonia, and completed the EEfRT. Across multiple analyses, we found a significant inverse relationship between anhedonia and willingness to expend effort for rewards. Conclusions: These findings suggest that anhedonia is specifically associated with decreased motivation for rewards, and provide initial validation for the EEfRT as a laboratory-based behavioral measure of reward motivation and effort-base

Tracking the ultraviolet-induced photochemistry of thiophenone during and after ultrafast ring opening

Photoinduced isomerization reactions lie at the heart of many chemical processes in nature. The mechanisms of such reactions are determined by a delicate interplay of coupled electronic and nuclear dynamics occurring on the femtosecond scale, followed by the slower redistribution of energy into different vibrational degrees of freedom. Here we apply time-resolved photoelectron spectroscopy with a seeded extreme ultraviolet free-electron laser to trace the ultrafast ring opening of gas-phase thiophenone molecules following ultraviolet photoexcitation. When combined with ab initio electronic structure and molecular dynamics calculations of the excited- and ground-state molecules, the results provide insights into both the electronic and nuclear dynamics of this fundamental class of reactions. The initial ring opening and non-adiabatic coupling to the electronic ground state are shown to be driven by ballistic S–C bond extension and to be complete within 350 fs. Theory and experiment also enable visualization of the rich ground-state dynamics that involve the formation of, and interconversion between, ring-opened isomers and the cyclic structure, as well as fragmentation over much longer timescales

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201