Light Increases Astaxanthin Absorbance in Acetone Solution through Isomerization Reactions.

Astaxanthin quantitative analysis is prone to high variability between laboratories. This study aimed to assess the effect of light on the spectrometric and high-performance liquid chromatography (HPLC) measurements of astaxanthin. The experiment was performed on four Haematococcus pluvialis-derived astaxanthin-rich oleoresin samples with different carotenoid matrices that were analyzed by UV/Vis spectrometry and HPLC according to the United States Pharmacopoeia (USP) monograph. Each sample was dissolved in acetone in three types of flasks: amber glass wrapped with aluminium foil, uncovered amber glass, and transparent glass. Thus, the acetone solutions were either in light-proof flasks or exposed to ambient light. The measurements were taken within four hours (spectrometry) or three hours (HPLC) from the moment of oleoresin dissolution in acetone to investigate the dynamics of changes in the recorded values. The results confirm the logarithmic growth of astaxanthin absorbance by 8-11% (UV/Vis) and 7-17% (HPLC) after 3 h of light exposure. The changes were different in the samples with different carotenoid matrices; for instance, light had the least effect on the USP reference standard sample. The increase in absorbance was accompanied with the change of isomeric distribution, namely a reduction of 13Z and an increase of All-E and 9Z astaxanthin. The greater HPLC values' elevation was related not only to the increase of astaxanthin absorbance, but also to light-dependent degradation of internal standard apocarotenal. The findings confirm a poor robustness of the conventional analytical procedure for astaxanthin quantitation and a necessity for method revision and harmonization to improve its reproducibility.

Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries.

BACKGROUND & AIMS: Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. METHODS: We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. RESULTS: Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women. CONCLUSIONS: In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.

Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis.

Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-activating protein 15; rs4662344-T: P=1.9 × 10-18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10-10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10-11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

[Quality of Life after colectomy due to ulcerative colitis].

INTRODUCTION: A significant proportion of patients with ulcerative colitis (UC) undergo colectomy. The aim was to assess the quality of life (QOL) of these patients. MATERIAL AND METHODS: All patients with UC who underwent colectomy at The National University Hospital of Iceland or Akureyri Hospital 1995-2009 were included. 106 patients received three questionnaires. SF-36v2 and EORTC are standardised QOL-questionnaires. The third contained functional questions designed by the researchers. RESULTS: Eighty-three patients replied (78%), 45 men (54%) and 38 women (46%). Average age at operation was 45 years (10-91 years). Forty-four (53%) had ileostomy, 28 (34%) ileal pouch-anal anastomosis (IPAA) and 11 (13%) ileorectal anastomosis. Among patients who had the rectum removed 37% described changes in urinary habits and 46% in sexual life after surgery. Among patients with IPAA 75% admitted to faecal incontinence but this was mild according to Wexner's scale in 83% of the cases. According to SF-36v2 there was no significant difference in the QOL of colectomy patients compared to the general population. Patients generally felt good about their health, body image and weight and had mild symptoms according to EORTC QLQ-CR29. CONCLUSIONS: Urinary habits and sexual life were commonly affected after rectal removal. Faecal incontinence among IPAA-patients was much more common than expected. There was not much difference in quality of life compared to the general population. The results of the study are important for patient education and may aid them in their decision making since removing the colon or having a stoma does not seem to affect quality of life. Key words: Quality of life, ulcerative colitis, ileostomy, colectomy. Correspondence: Elsa B. Valsdottir, elsava@landspitali.is.

Population-Based Colonoscopy Screening for Colorectal Cancer: A Randomized Clinical Trial.

IMPORTANCE: Although some countries have implemented widespread colonoscopy screening, most European countries have not introduced it because of uncertainty regarding participation rates, procedure-related pain and discomfort, endoscopist performance, and effectiveness. To our knowledge, no randomized trials on colonoscopy screening currently exist. OBJECTIVE: To investigate participation rate, adenoma yield, performance, and adverse events of population-based colonoscopy screening in several European countries. DESIGN, SETTING, AND POPULATION: A population-based randomized clinical trial was conducted among 94 959 men and women aged 55 to 64 years of average risk for colon cancer in Poland, Norway, the Netherlands, and Sweden from June 8, 2009, to June 23, 2014. INTERVENTIONS: Colonoscopy screening or no screening. MAIN OUTCOMES AND MEASURES: Participation in colonoscopy screening, cancer and adenoma yield, and participant experience. Study outcomes were compared by country and endoscopist. RESULTS: Of 31 420 eligible participants randomized to the colonoscopy group, 12 574 (40.0%) underwent screening. Participation rates were 60.7% in Norway (5354 of 8816), 39.8% in Sweden (486 of 1222), 33.0% in Poland (6004 of 18 188), and 22.9% in the Netherlands (730 of 3194) (P < .001). The cecum intubation rate was 97.2% (12 217 of 12 574), with 9726 participants (77.4%) not receiving sedation. Of the 12 574 participants undergoing colonoscopy screening, we observed 1 perforation (0.01%), 2 postpolypectomy serosal burns (0.02%), and 18 cases of bleeding owing to polypectomy (0.14%). Sixty-two individuals (0.5%) were diagnosed with colorectal cancer and 3861 (30.7%) had adenomas, of which 1304 (10.4%) were high-risk adenomas. Detection rates were similar in the proximal and distal colon. Performance differed significantly between endoscopists; recommended benchmarks for cecal intubation (95%) and adenoma detection (25%) were not met by 6 (17.1%) and 10 of 35 endoscopists (28.6%), respectively. Moderate or severe abdominal pain after colonoscopy was reported by 601 of 3611 participants (16.7%) examined with standard air insufflation vs 214 of 5144 participants (4.2%) examined with carbon dioxide (CO2) insufflation (P < .001). CONCLUSIONS AND RELEVANCE: Colonoscopy screening entails high detection rates in the proximal and distal colon. Participation rates and endoscopist performance vary significantly. Postprocedure abdominal pain is common with standard air insufflation and can be significantly reduced by using CO2. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00883792.

A Global Analysis of CYP51 Diversity and Azole Sensitivity in Rhynchosporium commune.

CYP51 encodes the target site of the azole class of fungicides widely used in plant protection. Some ascomycete pathogens carry two CYP51 paralogs called CYP51A and CYP51B. A recent analysis of CYP51 sequences in 14 European isolates of the barley scald pathogen Rhynchosporium commune revealed three CYP51 paralogs, CYP51A, CYP51B, and a pseudogene called CYP51A-p. The same analysis showed that CYP51A exhibits a presence/absence polymorphism, with lower sensitivity to azole fungicides associated with the presence of a functional CYP51A. We analyzed a global collection of nearly 400 R. commune isolates to determine if these findings could be extended beyond Europe. Our results strongly support the hypothesis that CYP51A played a key role in the emergence of azole resistance globally and provide new evidence that the CYP51A gene in R. commune has further evolved, presumably in response to azole exposure. We also present evidence for recent long-distance movement of evolved CYP51A alleles, highlighting the risk associated with movement of fungicide resistance alleles among international trading partners.

Incidence of inflammatory bowel disease in Iceland 1995 - 2009. A nationwide population-based study.

OBJECTIVE: We analyzed the incidence of inflammatory bowel disease (IBD) in Iceland for the period 1995-2009. MATERIAL AND METHODS: New cases of ulcerative colitis (UC) and Crohn's disease (CD) were retrieved by thorough review of all small and large intestinal pathology reports with any type of inflammation from all the pathology departments in Iceland for the period 1995-2009. All suspicious new cases of IBD were then scrutinized retrospectively by examination of their clinical records. RESULTS: A total of 1175 cases of IBD were diagnosed, 884 UC, 279 CD and 12 IBD unclassified. The crude annual incidence of UC was 20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5-year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5-year period and 6.6 the last 5-year period. CONCLUSIONS: This study shows statistically significant increase in the incidence of UC during the study period. The incidence of CD has however remained stable.

The influence of genetic drift and selection on quantitative traits in a plant pathogenic fungus.

Genetic drift and selection are ubiquitous evolutionary forces acting to shape genetic variation in populations. While their relative importance has been well studied in plants and animals, less is known about their relative importance in fungal pathogens. Because agro-ecosystems are more homogeneous environments than natural ecosystems, stabilizing selection may play a stronger role than genetic drift or diversifying selection in shaping genetic variation among populations of fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a QST/FST analysis using agricultural populations of the barley pathogen Rhynchosporium commune. Population divergence for eight quantitative traits (QST) was compared with divergence at eight neutral microsatellite loci (FST) for 126 pathogen strains originating from nine globally distributed field populations to infer the effects of genetic drift and types of selection acting on each trait. Our analyses indicated that five of the eight traits had QST values significantly lower than FST, consistent with stabilizing selection, whereas one trait, growth under heat stress (22°C), showed evidence of diversifying selection and local adaptation (QST>FST). Estimates of heritability were high for all traits (means ranging between 0.55-0.84), and average heritability across traits was negatively correlated with microsatellite gene diversity. Some trait pairs were genetically correlated and there was significant evidence for a trade-off between spore size and spore number, and between melanization and growth under benign temperature. Our findings indicate that many ecologically and agriculturally important traits are under stabilizing selection in R. commune and that high within-population genetic variation is maintained for these traits.

The risk of colorectal cancer after an attack of uncomplicated diverticulitis.

OBJECTIVE: According to clinical guidelines, a colonoscopy is recommended after an attack of diverticulitis in order to exclude colorectal cancer (CRC). This is based on studies prior to the use of computerized tomography (CT) for confirmation of the diagnosis. We aimed to investigate the findings of a subsequent colonoscopy after an attack of uncomplicated diverticulitis. MATERIAL AND METHODS: The study cohort consisted of all patients with the diagnosis of uncomplicated diverticulitis, who underwent a subsequent colonoscopy 6-8 weeks later during a 6-years period in the National University Hospital of Iceland. The diagnosis of diverticulitis was based on clinical symptoms verified with a CT of the abdomen. Relevant clinical information was obtained from medical records and from the Icelandic Cancer Registry. RESULTS: A total of 282 patients had uncomplicated diverticulitis and 199 patients underwent endoscopy. Two patients had CRC (0.7%), diagnosed with diverticulitis but did not recover clinically. All other patients recovered clinically. Colonic polyps were found in 33 of 195 (17%) cases. In 19/33 (58%) cases the histology demonstrated hyperplastic polyps, and in 13/33 (39%) adenoma with mild dysplasia. Only 1/33 (3%) of the colonic polyps were >1 cm in size. CONCLUSIONS: Among patients experiencing an attack of uncomplicated diverticulitis the frequency of CRC was equal to what might be expected compared to the average risk in the population. In these patients a routine colonoscopy in the absence of other clinical signs of CRC seems hardly necessary, if the clinical course is uneventful and the patient recovers.

Local adaptation and evolutionary potential along a temperature gradient in the fungal pathogen Rhynchosporium commune.

To predict the response of plant pathogens to climate warming, data are needed on current thermal adaptation, the pathogen's evolutionary potential, and the link between them. We conducted a common garden experiment using isolates of the fungal pathogen Rhynchosporium commune from nine barley populations representing climatically diverse locations. Clonal replicates of 126 genetically distinct isolates were assessed for their growth rate at 12°C, 18°C, and 22°C. Populations originating from climates with higher monthly temperature variation had higher growth rate at all three temperatures compared with populations from climates with less temperature fluctuation. Population differentiation in growth rate (Q ST) was significantly higher at 22°C than population differentiation for neutral microsatellite loci (G ST), consistent with local adaptation for growth at higher temperatures. At 18°C, we found evidence for stabilizing selection for growth rate as Q ST was significantly lower than G ST. Heritability of growth rate under the three temperatures was substantial in all populations (0.58-0.76). Genetic variation was lower in populations with higher growth rate at the three temperatures and evolvability increased under heat stress in seven of nine populations. Our findings imply that the distribution of this pathogen is unlikely to be genetically limited under climate warming, due to its high genetic variation and plasticity for thermal tolerance.

Genetics of gene expression and its effect on disease.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

[Screening for colorectal cancer. Collaboration among politicians and scientists is necessary]. / Skimun fyrir krabbameini í ristli og endathornarmi. Samvinna milli stjórnmálamanna og vísindamanna er nauethsynleg.

Colorectal cancer is one of the most common cancers in the western world. It is especially common in the Nordic countries. In many of the European countries and in the United States colonoscopy is recommended as a screening procedure for CRC. However, there are no randomized studies of the effects of the method on incidence, mortality, possible complications or negative effects on the population. Public pressure to have screening for CRC with colonoscopy will probably increase heavily in the next years to come. We fear that colonoscopy will be introduced as a screening method without proper scientific support. Therefore we want to argue for a common Nordic randomized study on population screening with colonoscopy.

Familial risk of colon and rectal cancer in Iceland: evidence for different etiologic factors?

The aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs.

Clinical and functional results after elective colonic resection in 75 consecutive patients with diverticular disease.

BACKGROUND: Functional results after elective colonic resection in patients with diverticular disease have seldom been studied. METHODS: Seventy-five consecutive patients were reviewed and sent a questionnaire about abdominal symptoms and functional results. Possible associations between patients' characteristics and postoperative complications or functional outcome were analyzed. RESULTS: Major complications including anastomotic leakage, bleeding, and bowel obstruction occurred in 10 patients (13%). Six patients (8%) had recurrent diverticulitis. No significant associations were found between clinical characteristics and postoperative complications or recurrent disease. Fifty patients classified their final result as excellent or good. Functional symptoms or symptoms suggestive of irritable bowel syndrome before the operation predicted a less successful result (P <0.05). CONCLUSIONS: Elective surgery in patients with diverticular disease was hampered by postoperative complications but resulted in most cases in good functional outcome and a low rate of recurrent disease. Those with functional bowel symptoms before surgery had significantly worse results.