Stable isotope food-web analysis and mercury biomagnification in polar bears ( Ursus maritimus )

Mercury (Hg) biomagnification occurs in many ecosystems, resulting in a greater potential for toxicological effects in higher-level trophic feeders. However, Hg transport pathways through different food-web channels are not well known, particularly in high-latitude systems affected by the atmospheric Hg deposition associated with snow and ice. Here, we report on stable carbon and nitrogen isotope ratios, and Hg concentrations, determined for 26, late 19th and early 20th century, polar bear ( Ursus maritimus ) hair specimens, collected from catalogued museum collections. These data elucidate relationships between the high-latitude marine food-web structure and Hg concentrations in polar bears. The carbon isotope compositions of polar bear hairs suggest that polar bears derive nutrition from coupled food-web channels, based in pelagic and sympagic primary producers, whereas the nitrogen isotope compositions indicate that polar bears occupy > fourth-level trophic positions. Our results show a positive correlation between polar bear hair Hg concentrations and δ 15 N. Interpretation of the stable isotope data in combination with Hg concentrations tentatively suggests that polar bears participating in predominantly pelagic food webs exhibit higher mercury concentrations than polar bears participating in predominantly sympagic food webs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73930/1/j.1751-8369.2009.00114.x.pd

Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

Background: Patients with longstanding ulcerative colitis (UC) undergo regular dysplasia surveillance because of increased colorectal cancer risk. Previous studies demonstrated that autofluorescence imaging (AFI) and chromoendoscopy (CE) increased dysplasia detection. The aim of this study was to determine whether AFI should be further studied as an alternative method for dysplasia surveillance in patients with longstanding UC. Methods: In this prospective international, randomised trial, 210 patients undergoing colonoscopy surveillance for longstanding UC were randomised between 1 August 2013 and 10 March 2017 for inspection with either AFI or CE (105:105). Randomisation was minimised for a previous history of dysplasia and a previous history of primary sclerosing cholangitis. The main outcome was the relative dysplasia detection rate calculated by the ratio of AFI versus CE. This relative dysplasia detection rate was determined for the proportion of UC patients in which at least one dysplastic lesion was detected and for the mean number of dysplastic lesions per patient. The relative dysplasia detection rate needed to be above 0·67 for both outcomes to support performing a subsequent large non-inferiority trial, using an 80% confidence interval. Analysis was performed per protocol. The trial is registered at Netherlands Trial Register (NTR4062). Findings: AFI detected dysplasia in 13 (12·4%) patients, compared to 20 patients (19·1%) with CE. The relative dysplasia detection rate of CE versus AFI for the proportion of UC patients with at least one dysplastic lesion was 0·65 (80% CI; 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 for AFI compared to 0·37 for CE (relative dysplasia detection rate 0·36, 80% CI; 0·21-0·61). Two patients experienced an adverse event (intraprocedural mild bleeding = 1, abdominal pain = 1) in the AFI-arm and three patients (intraprocedural mild bleeding = 2, perforation = 1) in the CE-arm. Interpretation: In this randomised study comparing AFI with CE for dysplasia surveillance in patients with longstanding UC, AFI did not meet criteria for proceeding to a large non-inferiority trial. Therefore, current AFI technology should not be further investigated as an alternative dysplasia surveillance method. Funding: Olympus Europe and Olympus Keymed, Oxford and Nottingham NIHR biomedical research centres

Management of acute hypercortisolism

An occasional patient with Cushing's syndrome may require urgent management primarily because the chronic ravages of hypercortisolism have caused the patient to be in a precarious metabolic condition. The side effects of prolonged excess corticosteroids increase the risk of operations in such patients and must be considered in overall management. Among the many effects of hypercortisolism to be considered are hypertension, diabetes, ocular hypertension, myopathies, dermatologic changes including skin infection, pancreatitis, osteoporosis, pathological fractures, peptic ulcers, renal calculi, coagulopathies, hypokalemia, poor wound healing, and increased susceptibility to infection. The most effective way to avert these complications is by earlier diagnosis and definitive treatment of Cushing's syndrome. The present report includes a review of the etiology and diagnosis of Cushing's syndrome and the management of problems associated with hypercortisolism . Il est possible qu'un malade atteint de maladie de Cushing ait besoin d'être traité sans attente en raisons de troubles métaboliques sévères dus aux effets nocifs de l'hypercortisolisme chronique qui augmentent les risques opératoires et doivent être pris en considération avant tout traitement. Il en est ainsi de l'hypertension, du diabète, de l'hypertension intra-oculaire, des lésions dermiques comprenant l'infection cutanée, la pancréatite, l'ostéoporose, les fractures pathologiques, l'ulcère peptique, les calculs rénaux, les coagulopathies, l'hypokaliémie, la lenteur du processus de cicatrisation et l'augmentation de la suceptibilité à l'infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41309/1/268_2005_Article_BF01655367.pd

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

Background The association of fitness with cancer risk is not clear. Methods We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. Results After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. Discussion Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

OP026 Zero diagnostic yield of dysplasia in polyp adjacent biopsies for patients with inflammatory bowel disease

IntroductionPatients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging it is now possible to characterise colonic lesions with higher levels of confidence than previously. We reviewed the diagnostic yield of polyp-adjacent biopsies in IBD. Materials and MethodsA systematic search of our histopathology database revealed cases where polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes. ResultsThree hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. Median polyp size was 4mm (range 1-45) and the predominant morphology was Paris 0-Is (n=98, 32%). Histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), which was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%). ConclusionThe diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high definition technology and chromoendoscopy it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia