47 research outputs found

    The use of cannabinoids in colitis: a systematic review and meta-analysis

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    Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endocannabinoid system in intestinal inflammation. We collated studies examining outcomes for metaanalysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score. Results: From 2008 papers, 51 publications examining the effect of cannabinoid compounds on murine colitis, and two clinical studies were identified. 24 compounds were assessed across 71 endpoints. Cannabidiol, a phytocannabinoid, was the most investigated drug. Macroscopic colitis severity (disease activity index - DAI) and myeloperoxidase activity (MPO) were assessed throughout publications and were meta-analysed using random effects models. Cannabinoids reduced DAI in comparison with vehicle; SMD -1.36, 95% CI -1.62 to-1.09, I²=61%). FAAH inhibitor URB597 had the largest effect size (SMD-4.43, 95% CI-6.32,-2.55), followed by the synthetic drug AM1241 (SMD–3.11, 95% CI -5.01, -1.22) and the endocannabinoid anandamide (SMD-3.03, 95% CI -4.89,-1.17, I² not assessed). Cannabinoids reduced MPO in rodents compared to vehicle; SMD -1.26, 95% CI-1.54 to -0.97, I²=48.1%. Cannabigerol had the largest effect size (SMD -6.20, 95%CI-9.90, -2.50), followed by the synthetic CB₁ agonist ACEA(SMD -3.15, 95%CI-4.75, -1.55) and synthetic CB₁/₂ agonist WIN55,212-2(SMD-1.74, 95%CI-2.81, -0.67, I²=57%). We found no evidence of reporting bias. No significant difference was found between the prophylactic and therapeutic use of cannabinoid drugs. Conclusions: There is abundant pre-clinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted

    Leveraging Automated Image Analysis Tools to Transform Our Capacity to Assess Status and Trends of Coral Reefs

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    Digital photography is widely used by coral reef monitoring programs to assess benthic status and trends. In addition to creating a permanent archive, photographic surveys can be rapidly conducted, which is important in environments where bottom-time is frequently limiting. However, substantial effort is required to manually analyze benthic images; which is expensive and leads to lags before data are available. Using previously analyzed imagery from NOAA’s Pacific Reef Assessment and Monitoring Program, we assessed the capacity of a trained and widely used machine-learning image analysis tool – CoralNet coralnet.ucsd.edu – to generate fully-automated benthic cover estimates for the main Hawaiian Islands (MHI) and American Samoa. CoralNet was able to generate estimates of site-level coral cover for both regions that were highly comparable to those generated by human analysts (Pearson’s r > 0.97, and with bias of 1% or less). CoralNet was generally effective at estimating cover of common coral genera (Pearson’s r > 0.92 and with bias of 2% or less in 6 of 7 cases), but performance was mixed for other groups including algal categories, although generally better for American Samoa than MHI. CoralNet performance was improved by simplifying the classification scheme from genus to functional group and by training within habitat types, i.e., separately for coral-rich, pavement, boulder, or “other” habitats. The close match between human-generated and CoralNet-generated estimates of coral cover pooled to the scale of island and year demonstrates that CoralNet is capable of generating data suitable for assessing spatial and temporal patterns. The imagery we used was gathered from sites randomly located in <30 m hard-bottom at multiple islands and habitat-types per region, suggesting our results are likely to be widely applicable. As image acquisition is relatively straightforward, the capacity of fully-automated image analysis tools to minimize the need for resource intensive human analysts opens possibilities for enormous increases in the quantity and consistency of coral reef benthic data that could become available to researchers and managers

    Multiple Translocation of the AVR-Pita Effector Gene among Chromosomes of the Rice Blast Fungus Magnaporthe oryzae and Related Species

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    Magnaporthe oryzae is the causal agent of rice blast disease, a devastating problem worldwide. This fungus has caused breakdown of resistance conferred by newly developed commercial cultivars. To address how the rice blast fungus adapts itself to new resistance genes so quickly, we examined chromosomal locations of AVR-Pita, a subtelomeric gene family corresponding to the Pita resistance gene, in various isolates of M. oryzae (including wheat and millet pathogens) and its related species. We found that AVR-Pita (AVR-Pita1 and AVR-Pita2) is highly variable in its genome location, occurring in chromosomes 1, 3, 4, 5, 6, 7, and supernumerary chromosomes, particularly in rice-infecting isolates. When expressed in M. oryzae, most of the AVR-Pita homologs could elicit Pita-mediated resistance, even those from non-rice isolates. AVR-Pita was flanked by a retrotransposon, which presumably contributed to its multiple translocation across the genome. On the other hand, family member AVR-Pita3, which lacks avirulence activity, was stably located on chromosome 7 in a vast majority of isolates. These results suggest that the diversification in genome location of AVR-Pita in the rice isolates is a consequence of recognition by Pita in rice. We propose a model that the multiple translocation of AVR-Pita may be associated with its frequent loss and recovery mediated by its transfer among individuals in asexual populations. This model implies that the high mobility of AVR-Pita is a key mechanism accounting for the rapid adaptation toward Pita. Dynamic adaptation of some fungal plant pathogens may be achieved by deletion and recovery of avirulence genes using a population as a unit of adaptation

    Postoperative outcomes in oesophagectomy with trainee involvement

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    BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

    Potential for non-combustible nicotine products to reduce socioeconomic inequalities in smoking: a systematic review and synthesis of best available evidence

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    While some experts have emphasised the potential for e-cigarettes to facilitate cessation among smokers with low socioeconomic status (SES), there is limited evidence of their likely equity impact. We assessed the potential for electronic cigarettes and other non-combustible nicotine-containing products (NCNPs) to reduce inequalities in smoking by systematically reviewing evidence on their use by SES in countries at stage IV of the cigarette epidemic

    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    Population biology of Sclerotium cepivorum

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    grantor: University of TorontoPopulation samples of 'Sclerotium cepivorum', the causal agent of white rot of 'Allium', were genotyped and grouped on the basis of mycelial compatibility and DNA sequence polymorphisms for a set of six genomic regions. 'S. cepivorum' was found to have a clonal population structure within three onion growing localities, two in Canada and one in New Zealand, as would be expected based on its asexual mode of reproduction. On the basis of incongruent gene genealogies and the presence of all expected allele combinations (Hudson's four gamete test) some evidence for recombination was detected when isolates from all three localities, plus others, were considered. Within each of the three localities sampled, however, recombination was absent or infrequent. I conclude that some recombination has likely occurred in the past, prior to colonization of these sites. The occurrence of the same genotypes in a number of geographically distinct sites indicates that 'S. cepivorum' was probably introduced to these areas. The alternative explanation, that each of these repeatedly sampled genotypes evolved multiple times, independently, in a number of locations, is unlikely. The strikingly low genotypic diversity present within each of the areas sampled may have been due to a bottleneck associated with introduction of the pathogen.M.Sc

    Increasing Student Understanding of Microscope Optics by Building and Testing the Limits of Simple, Hand-Made Model Microscopes

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    The ability to effectively use a microscope to observe microorganisms is a crucial skill required for many disciplines within biology, especially general microbiology and cell biology. A basic understanding of the optical properties of light microscopes is required for students to use microscopes effectively, but this subject can also be a challenge to make personally interesting to students. To explore basic optical principles of magnification and resolving power in a more engaging and hands-on fashion, students constructed handmade lenses and microscopes based on Antony van Leeuwenhoek’s design using simple materials—paper, staples, glass, and adhesive putty. Students determined the power of their lenses using a green laser pointer to magnify a copper grid of known size, which also allowed students to examine variables affecting the power and resolution of a lens such as diameter, working distance, and wavelength of light. To assess the effectiveness of the laboratory’s learning objectives, four sections of a general microbiology course were given a brief pre-activity assessment quiz to determine their background knowledge on the subject. One week after the laboratory activity, students were given the same quiz (unannounced) under similar conditions. Students showed significant gains in their understanding of microscope optics
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