Metabolomic analysis in inflammatory bowel disease: a systematic review

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are chronic, idiopathic gastrointestinal (GI) diseases. Whilst their precise etiology is unknown, it is thought to involve a complex interaction between genetic predisposition and an abnormal host immune response to environmental exposures, likely microbial. Microbial dysbiosis has frequently been documented in IBD. Metabolomics (the study of small molecular intermediates and end products of metabolism in biological samples) provides a unique opportunity to characterize disease-associated metabolic changes and may be of particular use in quantifying gut microbial metabolism. Numerous metabolomic studies have been undertaken in inflammatory bowel disease populations, identifying consistent alterations in a range of molecules across several biological matrices. This systematic review aims to summarize these findings. METHODS: A comprehensive, systematic search was carried out using Medline and EMBASE. All studies were reviewed by two authors independently using predefined exclusion criteria. A total of sixty-four relevant papers were quality assessed and included in the review. RESULTS: Consistent metabolic perturbations were identified, including increases in levels of branched chain amino acids and lipid classes across stool, serum, plasma and tissue biopsy samples, and reduced levels of microbially modified metabolites in both urine (such as hippurate) and stool (such as secondary bile acids). CONCLUSIONS: This review provides a summary of metabolomic research in IBD to date, highlighting underlying themes of perturbed gut microbial metabolism and mammalian-microbial co-metabolism associated with disease status

Positive reinforcement by general practitioners is associated with greater physical activity in adults with type 2 diabetes

© Author(s) (or their employer(s)) 2019. Objective In a sample of adults with type 2 diabetes mellitus (T2DM), the aim of this study was to examine whether self-reported physical activity level is associated with recall of specific physical activity-related interactions used by general practitioners (GP). Research design and methods Adults with T2DM completed an online survey reporting physical activity behaviors and recall of 14 GP-patient interactions about physical activity, mapped onto discrete behavior change techniques (BCT). Stepped logistical regression examined associations between recommended physical activity (≥600 MET-min/week) and GP-patient interactions, controlling for body mass index, diabetes-related comorbidities, depressive symptoms and self-efficacy. Results In total, 381 respondents (55% men, mean±SD age: 62±10 years and T2DM duration 8±8 years) provided complete data. Most (73%) reported receiving 'general advice', while interactions related to goal setting, monitoring, and relapse prevention were least commonly reported (all <20%). Self-reported achievement of the recommended physical activity level was significantly associated with recall of GP interactions involving praise for 'efforts to be active' (OR 2.1; 95% CI 1.24 to 3.53), 'lost weight' (OR 1.81; 95% CI 1.05 to 3.12) or lowering 'glucose levels as a result of being active' (OR 1.75; 95% CI 1.03 to 2.96). Conclusions Findings suggest GPS can be somewhat effective in promoting physical activity with simple, positive, reinforcing messages/interactions. Future research to develop and evaluate very brief primary care BCT-based physical activity interventions is needed

Corporate branding’s influence on front-line employee and consumer value co-creation in UK household consumer markets

General managers are presented with an extensive opportunity to innovate and gain market advantage from front-line employees (FLEs) and consumers working together to exchange services and co-create value. To do this, general managers need to understand more about what influences the content and quality of FLE and consumer service exchanges? What predisposes FLEs to commit to service exchange and value co-creation? And what organizational phenomena can general managers use to influence this predisposition? This article presents results from an empirical research study of FLEs employed by a firm that provides installation, servicing and emergency services to domestic households across the United Kingdom. The study reveals the importance of the firm’s corporate brand in its influence upon FLE’s sense of membershipand attachment to a firm (organizational identity) and the consequent effect of this on their predisposition for serviceexchange (organizational commitment), that is, whether FLEs want to remain in their role, because they feel they ought to,want to or they have too much to lose by leaving

Virological sampling of inaccessible wildlife with drones

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. There is growing interest in characterizing the viromes of diverse mammalian species, particularly in the context of disease emergence. However, little is known about virome diversity in aquatic mammals, in part due to difficulties in sampling. We characterized the virome of the exhaled breath (or blow) of the Eastern Australian humpback whale (Megaptera novaeangliae). To achieve an unbiased survey of virome diversity, a meta-transcriptomic analysis was performed on 19 pooled whale blow samples collected via a purpose-built Unmanned Aerial Vehicle (UAV, or drone) approximately 3 km off the coast of Sydney, Australia during the 2017 winter annual northward migration from Antarctica to northern Australia. To our knowledge, this is the first time that UAVs have been used to sample viruses. Despite the relatively small number of animals surveyed in this initial study, we identified six novel virus species from five viral families. This work demonstrates the potential of UAVs in studies of virus disease, diversity, and evolution

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Lymphadenopathy after BCG vaccination in a child with chronic granulomatous disease

We report a 15-month-old boy who developed an ulcer in the left axillary fold following bacillus Calmette-Guerin vaccination. Subsequent immunologic and genetic studies led to the diagnosis of chronic granulomatous disease. His mother had "lupus-like" lesions, described in some carriers of this disease, that were thus related to her son's diagnosis. Although in healthy subjects this vaccination is usually harmless, in instances of impaired immunity it may cause adverse reactions. When a vaccine-related complication occurs, an underlying immunodeficiency should be sough

How reliably can we predict the reliability of protein structure predictions?

Background: Comparative methods have been the standard techniques for in silico protein structure prediction. The prediction is based on a multiple alignment that contains both reference sequences with known structures and the sequence whose unknown structure is predicted. Intensive research has been made to improve the quality of multiple alignments, since misaligned parts of the multiple alignment yield misleading predictions. However, sometimes all methods fail to predict the correct alignment, because the evolutionary signal is too weak to find the homologous parts due to the large number of mutations that separate the sequences. Results: Stochastic sequence alignment methods define a posterior distribution of possible multiple alignments. They can highlight the most likely alignment, and above that, they can give posterior probabilities for each alignment column. We made a comprehensive study on the HOMSTRAD database of structural alignments, predicting secondary structures in four different ways. We showed that alignment posterior probabilities correlate with the reliability of secondary structure predictions, though the strength of the correlation is different for different protocols. The correspondence between the reliability of secondary structure predictions and alignment posterior probabilities is the closest to the identity function when the secondary structure posterior probabilities are calculated from the posterior distribution of multiple alignments. The largest deviation from the identity function has been obtained in the case of predicting secondary structures from a single optimal pairwise alignment. We also showed that alignment posterior probabilities correlate with the 3D distances between C α amino acids in superimposed tertiary structures. Conclusion: Alignment posterior probabilities can be used to a priori detect errors in comparative models on the sequence alignment level. </p

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock