Carbohydrates possess a variety of distinct features with stereochemistry playing a particularly important role in distinguishing their structure and function. Monosaccharide building blocks are ...defined by a high density of chiral centers. Additionally, the anomericity and regiochemistry of the glycosidic linkages carry important biological information. Any carbohydrate-sequencing method needs to be precise in determining all aspects of this stereodiversity. Recently, several advances have been made in developing fast and precise analytical techniques that have the potential to address the stereochemical complexity of carbohydrates. This perspective seeks to provide an overview of some of these emerging techniques, focusing on those that are based on NMR and MS-hybridized technologies including ion mobility spectrometry and IR spectroscopy.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract Background & aims Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to review the literature and provide specific, updated ...recommendations for eradication therapy in adults. Methods A systematic literature search identified studies on H. pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. Results Because of increasing failure of therapy, the consensus group strongly recommended that all H. pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant non-bismuth quadruple therapy (proton pump inhibitor, PPI + amoxicillin + metronidazole + clarithromycin, PAMC), and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBMT). PPI triple therapy (PPI + clarithromycin and either amoxicillin or metronidazole) was restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin, PAL). Rifabutin regimens should be restricted to patients who fail at least 3 prior options. Conclusions Optimal treatment of H. pylori requires careful attention to local antibiotic resistance and eradication patterns. Quadruple therapies PAMC or PBMT should play a more prominent role in H. pylori eradication and all treatments should be given for 14 days.
Gastrointestinal helminth infection still constitutes a major public health issue, particularly in the developing world. As these parasites can undergo a large part of their lifecycle within the ...intestinal tract the host has developed various structural and cellular specializations at the epithelial barrier to contend with infection. Detailed characterization of these cells will provide important insights about their contributions to the protective responses mediated against helminths. Here, we discuss how key components of the intestinal epithelium may function to limit the initial establishment of helminths, and how these cells are altered during an active response to infection.
Previously, research on the mucosal immune response to gastrointestinal helminth infection has been limited by a lack of knowledge around defined subpopulations of intestinal epithelial cells (IECs) such as tuft cells and enteroendocrine cells.Recent advances in single-cell sequencing technology have allowed for more detailed identification of IEC subsets and their potential roles during helminth infection.The characterization of IEC subsets has led to advances in our knowledge of helminth–IEC interactions (e.g., tuft cell activation by helminths, which elicits a potent type 2 immune response).This review is a call to arms for the need to dissect the mechanisms as to how helminths initiate an immune response through these subsets, as well as the need to use modern sequencing technology to further characterize IEC subsets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from ...genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies.
We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified.
For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)).
There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.
Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged ...as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology.
Type-2-cell-mediated immune responses play critical roles in regulating host resistance against helminths and promoting tissue repair and metabolic homeostasis. Harris and Loke review recent advances in the field resulting from studies of helminth-host interactions and provide insight into the activation and function of type 2 immune cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intestinal helminths, along with mutualistic microbes, have cohabited the intestine of mammals throughout evolution. Interactions between helminths, bacteria, and their mammalian hosts may shape not ...only host–helminth and host–microbiome interactions, but also the relationship between helminths and the microbiome. This ‘ménage à trois’ situation may not be completely balanced in that it may favor either the host or the parasite, possibly at the cost of the other partner. Similarly, helminths may favor the establishment of a particular microbiome with either positive or negative consequences for the overall health and well-being of the host. Recent studies indicate that infection with intestinal helminths can and does impact the intestinal microbiome, with important consequences for each partner in this tripartite relationship.
In humans, both cross-sectional and case-control studies performed in regions endemic for intestinal helminths provided evidence that infection may alter fecal bacterial communities.
In mice, infection with the large intestinal helminth Trichuris muris can promote colonization resistance against the pathogenic bacterium Bacteroides vulgatus by promoting the growth of nonpathogenic bacterial species.
In mice, infection with the small intestinal helminth Heligmosomoides polygyrus has been shown to alter the cecal microbiome and results in greater availability of bacterially derived metabolites, SCFAs, that function to dampen allergic responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The peptidoglycan sensor Nod2 and the autophagy protein ATG16L1 have been linked to Crohn’s disease (CD). Although Nod2 and the related sensor, Nod1, direct ATG16L1 to initiate anti-bacterial ...autophagy, whether ATG16L1 affects Nod-driven inflammation has not been examined. Here, we uncover an unanticipated autophagy-independent role for ATG16L1 in negatively regulating Nod-driven inflammatory responses. Knockdown of ATG16L1 expression, but not that of ATG5 or ATG9a, specifically enhanced Nod-driven cytokine production. In addition, autophagy-incompetent truncated forms of ATG16L1 regulated Nod-driven cytokine responses. Mechanistically, we demonstrated that ATG16L1 interfered with poly-ubiquitination of the Rip2 adaptor and recruitment of Rip2 into large signaling complexes. The CD-associated allele of ATG16L1 was impaired in its ability to regulate Nod-driven inflammatory responses. Overall, these results suggest that ATG16L1 is critical for Nod-dependent regulation of cytokine responses and that disruption of this Nod1- or Nod2-ATG16L1 signaling axis could contribute to the chronic inflammation associated with CD.
•ATG16L1 suppresses Nod1- and Nod2-driven cytokine responses•ATG16L1’s regulatory function is independent of its role in autophagosome formation•ATG16L1 negatively regulates Nod1 and Nod2 signaling via Rip2 activation•Crohn’s-disease-associated ATG16L1 allele is defective in Nod1 and Nod2 regulation
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Core Outcome Measures in Effectiveness Trials (COMET) database is a publically available, searchable repository of published and ongoing core outcome set (COS) studies. An annual systematic ...review update is carried out to maintain the currency of database content.
The methods used in the fourth update of the systematic review followed the same approach used in the original review and previous updates. Studies were eligible for inclusion if they reported the development of a COS, regardless of any restrictions by age, health condition or setting. Searches were carried out in March 2018 to identify studies that had been published or indexed between January 2017 and the end of December 2017.
Forty-eight new studies, describing the development of 56 COS, were included. There has been an increase in the number of studies clearly specifying the scope of the COS in terms of the population (n = 43, 90%) and intervention (n = 48, 100%) characteristics. Public participation has continued to rise with over half (n = 27, 56%) of studies in the current review including input from members of the public. The rate of inclusion of all stakeholder groups has increased, in particular participation from non-clinical research experts has risen from 32% (mean average in previous reviews) to 62% (n = 29). Input from participants located in Australasia (n = 17; 41%), Asia (n = 18; 44%), South America (n = 13; 32%) and Africa (n = 7; 17%) have all increased since the previous reviews.
This update included a pronounced increase in the number of new COS identified compared to the previous three updates. There was an improvement in the reporting of the scope, stakeholder participants and methods used. Furthermore, there has been an increase in participation from Australasia, Asia, South America and Africa. These advancements are reflective of the efforts made in recent years to raise awareness about the need for COS development and uptake, as well as developments in COS methodology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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