Agronomic and Metabolomic Side-Effects of a Divergent Selection for Indol-3-Ylmethylglucosinolate Content in Kale (Brassica oleracea var. acephala).

Brassica oleracea var. acephala (kale) is a cruciferous vegetable widely cultivated for its leaves and flower buds in Europe and a food of global interest as a "superfood". Brassica crops accumulate phytochemicals called glucosinolates (GSLs) which play an important role in plant defense against biotic stresses. Studies carried out to date suggest that GSLs may have a role in the adaptation of plants to different environments, but direct evidence is lacking. We grew two kale populations divergently selected for high and low indol-3-ylmethylGSL (IM) content (H-IM and L-IM, respectively) in different environments and analyzed agronomic parameters, GSL profiles and metabolomic profile. We found a significant increase in fresh and dry foliar weight in H-IM kale populations compared to L-IM in addition to a greater accumulation of total GSLs, indole GSLs and, specifically, IM and 1-methoxyindol-3-ylmethylGSL (1MeOIM). Metabolomic analysis revealed a significant different concentration of 44 metabolites in H-IM kale populations compared to L-IM. According to tentative peak identification from MS interpretation, 80% were phenolics, including flavonoids (kaempferol, quercetin and anthocyanin derivates, including acyl flavonoids), chlorogenic acids (esters of hydroxycinnamic acids and quinic acid), hydroxycinnamic acids (ferulic acid and p-coumaric acid) and coumarins. H-IM kale populations could be more tolerant to diverse environmental conditions, possibly due to GSLs and the associated metabolites with predicted antioxidant potential.

Phaeochromocytomas overexpress insulin transcript and produce insulin.

INTRODUCTION: Phaeochromocytomas are tumours originating in the medulla of the adrenal gland. They produce catecholamines, and some tumours also produce ectopic hormones. Two types of glucose imbalances occur in phaeochromocytoma patients, hyperglycaemia and hypoglycaemic attacks. Therefore, we tested whether insulin transcript (INS), insulin, and a hybrid read-through transcript between exons from insulin and insulin-like growth factor 2 (INS-IGF2) were expressed in phaeochromocytomas. METHODS: We measured the expression of insulin using immunohistochemistry. The expression of INS-IGF2 was determined by qRT-PCR in formalin-fixed and paraffin-embedded tissue from 20 phaeochromocytomas. The expression of INS and INS-IGF2 transcriptswas also analysed in 182 phaeochromocytomas and paragangliomas using publicly available datasets in The Cancer Genome Atlas (TCGA) Database. RESULTS: Of 20 phaeochromocytomas, 16 stained positive for insulin. The distribution of positive cells was mostly scattered, with some focal expression indicating clonal expansion. Nineteen tumours expressed high levels of INS and INS-IGF2 transcripts. The expression of the two transcripts corresponded closely. In the TCGA dataset, phaeochromocytoma expresses higher levels of INS and INS-IGF2 transcripts compared to the normal non-tumour adrenal glands. Thus, the expression of INS and INS-IGF2 seems to be a general phenomenon in phaeochromocytoma. CONCLUSION: Most phaeochromocytomas contain cells that overexpress INS and INS-IGF2 transcripts. Most tumours also display heterogeneous expression of polypeptides immunoreactive to monoclonal anti-insulin antibodies. Clinically this may relate to both hyperglycaemia and hypoglycaemic attacks seen in patients with phaeochromocytoma as well as autocrine tumour growth.

Effects of supplemental LED light quality and reduced growth temperature on swede (Brassica napus L. ssp. rapifera Metzg.) root vegetable development and contents of glucosinolates and sugars.

BACKGROUND: Low growth temperatures and the special light qualities of midnight sun in northern Scandinavia, have both been shown to improve eating quality of swede root bulbs. To study the combined effect of these factors on root development and sensory-related compounds, plants were grown in phytotron under different 24 h supplemental light-emitting diode (LED) light colours, at constant 15 °C, or reduced end-of-season temperature at 9 °C. RESULTS: Far-red LED (740 nm) light induced longer leaves and produced more roundly shaped bulbs, than the other light quality treatments. At constant 15 °C, supplemental light of far-red LED also produced a stronger purple crown skin colour than the other LED treatments. This difference between light quality treatments disappeared at 9 °C, as all bulb crowns developed a purple colour. There were no significant effects of LED-supplements on sugar concentrations, while the reduced temperature on average did increase concentrations of d-fructose and d-glucose. Total glucosinolate concentrations were not different among treatments, although the most abundant glucosinolate, progoitrin, on average was present in highest concentration under LEDs containing far-red light, and in lower concentration at 9 °C compared to 15 °C. CONCLUSION: The light quality of 24 h photoperiods in combination with temperature appears primarily important for growth and morphological traits in swede root bulbs. Influence of light quality and low temperature on appearance and sensory-related compounds may be utilized in marketing of root vegetables with special quality related to growth conditions of high latitude origin. © 2020 Society of Chemical Industry.

The Potential for Decision Support Tools to Improve the Management of Root-Feeding Fly Pests of Vegetables in Western Europe.

Several important vegetable crops grown outdoors in temperate climates in Europe can be damaged by the root-feeding larvae of Diptera (Delia radicum, Delia floralis, Chamaepsila rosae, Delia platura, Delia florilega, Delia antiqua). Knowledge of pest insect phenology is a key component of any Integrated Pest Management (IPM) strategy, and this review considers the methods used to monitor and forecast the occurrence of root-feeding flies as a basis for decision-making by growers and the ways that such information can be applied. It has highlighted some current management approaches where such information is very useful for decision support, for example, the management of C. rosae with insecticidal sprays and the management of all of these pests using crop covers. There are other approaches, particularly those that need to be applied at sowing or transplanting, where knowledge of pest phenology and abundance is less necessary. Going forward, it is likely that the number of insecticidal control options available to European vegetable growers will diminish and they will need to move from a strategy which often involves using a single 'silver bullet' to a combination of approaches/tools with partial effects (applied within an IPM framework). For the less-effective, combined methods, accurate information about pest phenology and abundance and reliable decision support are likely to be extremely important.

Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities.

BACKGROUND AND AIMS: Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). APPROACH AND RESULTS: We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 patients with PSC-BTC from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations, and copy number variations, along with histomorphological and immunohistochemical characterization. Regardless of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, such as TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g., HER2/ERBB2). We found a high frequency of nontypical/nonductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%). CONCLUSIONS: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC shows a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.

Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men: A Randomized Trial.

Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear. Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912). Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC. Intervention: Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy. Measurements: Age-adjusted CRC incidence and mortality stratified by sex. Results: Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, -0.19 percentage point [95% CI, -0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, -0.78 percentage point [CI, -1.08 to -0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, -0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, -0.33 percentage point [CI, -0.49 to -0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014). Limitation: Follow-up through national registries. Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women. Primary Funding Source: Norwegian government and Norwegian Cancer Society.

Influence of high latitude light conditions on sensory quality and contents of health and sensory-related compounds in swede roots (Brassica napus L. ssp. rapifera Metzg.).

BACKGROUND: Vegetable growers in Arctic areas must increasingly rely on market strategies based on regional origin and product quality. Swede roots (rutabaga) were grown in a phytotron to investigate the effect of high latitude light conditions on sensory quality and some health and sensory-related compounds. Experimental treatments included modifications of 24 h natural day length (69° 39' N) by moving plants at daily intervals to dark chambers with either no light, fluorescent growth light and/or low intensity photoperiod extension. RESULTS: Shortening the photosynthetic light period to 12 h produced smaller roots than 15.7 h and 18 h, with highest scores for bitter and sulfur taste, and lowest scores for sweetness, acidic taste and fibrousness. The photoperiod in combination with the photosynthetic light period also had an influence on glucosinolate (GLS) contents, with lowest concentrations in 24 h natural light and highest in 12 h natural light. Concentrations of vitamin C, glucose, fructose and sucrose were not significantly influenced by any of the treatments. CONCLUSION: High latitude light conditions, with long photosynthetic light periods and 24 h photoperiod, can enhance sweet/less bitter taste and reduce GLS contents in swede roots, compared to growth under short day conditions. This influence of light conditions on eating quality may benefit marketing of regional products from high latitudes. © 2017 Society of Chemical Industry.

Temperature and light conditions at different latitudes affect sensory quality of broccoli florets (Brassica oleracea L. var. italica).

BACKGROUND: Broccoli (Brassica oleracea L. var. italica) is a popular vegetable grown at a wide range of latitudes. Plants were grown in 2009-2011 in pots with standardized soil, irrigation and nutrient supply under natural temperature and light conditions at four locations (42-70° N). A descriptive sensory analysis of broccoli florets was performed by a trained panel to examine any differences along the latitudinal gradient for 30 attributes within appearance, odour, taste/flavour and texture. RESULTS: Average results over three summer seasons in Germany, southern Norway and northern Norway showed that the northernmost location with low temperatures and long days had highest scores for bud coarseness and uniform colour, while broccoli from the German location, with high temperatures and shorter days, had highest intensity of colour hue, whiteness, bitter taste, cabbage flavour, stale flavour and watery flavour. Results from two autumn seasons at the fourth location (42° N, Spain), with low temperatures and short days, tended toward results from the two northernmost locations, with an exception for most texture attributes. CONCLUSION: Results clearly demonstrate that temperature and light conditions related to latitude and season affect the sensory quality of broccoli florets. Results may be used in marketing special quality regional or seasonal products. © 2016 Society of Chemical Industry.

Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease.

BACKGROUND & AIMS: Recruitment of gut-derived memory T-cells to the liver is believed to drive hepatic inflammation in primary sclerosing cholangitis (PSC). However, whether gut-infiltrating and liver-infiltrating T-cells share T cell receptors (TCRs) and antigenic specificities is unknown. We used paired gut and liver samples from PSC patients with concurrent inflammatory bowel disease (PSC-IBD), and normal tissue samples from colon cancer controls, to assess potential T cell clonotype overlap between the two compartments. METHODS: High-throughput sequencing of TCRß repertoires was applied on matched colon, liver and blood samples from patients with PSC-IBD (n=10), and on paired tumor-adjacent normal gut and liver tissue samples from colon cancer patients (n=10). RESULTS: An average of 9.7% (range: 4.7-19.9%) memory T cell clonotypes overlapped in paired PSC-IBD affected gut and liver samples, after excluding clonotypes present at similar frequencies in blood. Shared clonotypes constituted on average 16.0% (range: 8.7-32.6%) and 15.0% (range: 5.9-26.3%) of the liver and gut memory T-cells, respectively. A significantly higher overlap was observed between paired PSC-IBD affected samples (8.7%, p=0.0007) compared to paired normal gut and liver samples (3.6%), after downsampling to equal number of reads. CONCLUSION: Memory T-cells of common clonal origin were detected in paired gut and liver samples of patients with PSC-IBD. Our data indicate that this is related to PSC-IBD pathogenesis, suggesting that memory T-cells driven by shared antigens are present in the gut and liver of PSC-IBD patients. Our findings support efforts to therapeutically target memory T cell recruitment in PSC-IBD. LAY SUMMARY: Primary sclerosing cholangitis (PSC) is a devastating liver disease strongly associated with inflammatory bowel disease (IBD). The cause of PSC is unknown, but it has been suggested that the immune reactions in the gut and the liver are connected. Our data demonstrate for the first time that a proportion of the T-cells in the gut and the liver react to similar triggers, and that this proportion is particularly high in patients with PSC and IBD.

Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study.

Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers.

A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.

OBJECTIVES: The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation. METHODS: In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed. RESULTS: The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests). CONCLUSIONS: In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.

Growth temperature affects sensory quality and contents of glucosinolates, vitamin C and sugars in swede roots (Brassica napus L. ssp. rapifera Metzg.).

Swede is a root vegetable grown under a range of growth conditions that may influence the product quality. The objective of this controlled climate study was to find the effect of growth temperature on sensory quality and the contents of glucosinolates, vitamin C and soluble sugars. High temperature (21 °C) enhanced the intensities of sensory attributes like pungent odour, bitterness, astringency and fibrousness, while low temperature (9 °C) was associated with acidic odour, sweet taste, crispiness and juiciness. Ten glucosinolates were quantified, with progoitrin as the dominant component followed by glucoberteroin, both with highest content at 21 °C. Vitamin C also had its highest content at 21 °C, while the total sugar content was lowest at this temperature. In conclusion, the study demonstrated clear effects of growth temperature on sensory quality and some chemical properties of swede and indicated a good eating quality of swedes grown at low temperatures.

Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma - A population-based cohort study.

BACKGROUND: Multimodality treatment (MMT) improves survival for patients with pancreatic ductal adenocarcinoma (PDAC). The surgery-first (SF) strategy is the most universally accepted approach. MATERIAL AND METHODS: Population-based retrospective cohort study of all cases of resectable PDAC from 2006 to 2012. Patients were planned for adjuvant chemotherapy (AC) with the Nordic 5-fluorouracil/leucovorin regimen. Reasons for and rates of failure to complete AC, postoperative major complications (PMC), and overall survival (OS) were analysed. RESULTS: Of 203 patients, 85 (41.9%) completed AC, 41 (20.2%) failed to complete AC, and 77 (37.9%) never initiated AC. Primary reasons for not initiating or completing AC were early disease progression (34.7%), postoperative complications/poor performance status (32.2%), and age > 75 years (24.6%). Median OS in the whole cohort was 17.0 months, and 20.0 months in patients who initiated AC. Median OS in patients who completed AC was higher than in patients who did not (25.0 months vs. 12.0 months, p < 0.001). PMC (n = 41) were associated with decreased initiation rate (p < 0.001) and completion rate (p = 0.007) of AC, and decreased median OS (11.0 months vs. 19.0 months, p = 0.028). Among patients with R1 resection, PMC again were associated with worse median OS (8.0 months vs. 16.0 months, p = 0.028). Multivariate analysis demonstrated that completion of MMT and tumour grade (G1/G2) were related to mortality rate (p < 0.001). Mortality risk for patients who completed AC was reduced also when adjusting for competing risk (SHR 0.426, p < 0.001). CONCLUSIONS: MMT completion is strongly associated with reduced mortality risk in patients with resectable PDAC undergoing the SF approach. Early disease progression and PMC/poor performance status preclude MMT completion in more than one third of the patients. These reasons for failure to complete MMT underscore the need for strategies to improve patient selection and reduce surgical morbidity in patients with resectable PDAC.

Impact of pre-harvest light spectral properties on health- and sensory-related compounds in broccoli florets.

BACKGROUND: Plants grown at different latitudes experience differences in light spectral composition. Broccoli (Brassica oleracea L. var italica) plants were grown in climate-controlled chambers under supplemental wavelengths (red, far-red, red + far-red or blue) from light-emitting diodes (LEDs). The light treatments were combined with two cold climate temperatures (12 and 15 °C) during broccoli head formation to investigate the effects on morphology and content of health- and sensory-related compounds: glucosinolates, flavonols, ascorbic acid and soluble sugars. RESULTS: Supplemental far-red and red + far-red light led to elongated plants and the lowest total glucosinolate content in broccoli florets. The content of quercetin was highest with supplemental red light. Vitamin C was not significantly affected by the light treatments, but 12 °C gave a higher content than 15 °C. CONCLUSION: The effects of supplemental red and far-red light suggest an involvement of phytochromes in the regulation of glucosinolates and flavonols. A shift in red:far-red ratio could cause changes in their content besides altering the morphology. The sugar and vitamin C content appears to be unaffected by these light conditions. Supplemental blue light had little effect on plant morphology and content of the health- and sensory related compounds.

High Diagnostic Accuracy of Nitrite Test Paired with Urine Sediment can Reduce Unnecessary Antibiotic Therapy.

BACKGROUND: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy. AIMS: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy. METHODS: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI. RESULTS: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was ≥4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT ≥4h and six patients at ≤3h or overall. CONCLUSION: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance. TRIAL REGISTRATION: The Swedish Medical Product Agency 1995 03 01:151:01783/94.

The biliary epithelium presents antigens to and activates natural killer T cells.

UNLABELLED: Cholangiocytes express antigen-presenting molecules, but it has been unclear whether they can present antigens. Natural killer T (NKT) cells respond to lipid antigens presented by the major histocompatibility complex class I-like molecule CD1d and are abundant in the liver. We investigated whether cholangiocytes express CD1d and present lipid antigens to NKT cells and how CD1d expression varies in healthy and diseased bile ducts. Murine and human cholangiocyte cell lines as well as human primary cholangiocytes expressed CD1d as determined by flow cytometry and western blotting. Murine cholangiocyte cell lines were able to present both exogenous and endogenous lipid antigens to invariant and noninvariant NKT cell hybridomas and primary NKT cells in a CD1d-dependent manner. A human cholangiocyte cell line, cholangiocarcinoma cell lines, and human primary cholangiocytes also presented exogenous CD1d-restricted antigens to invariant NKT cell clones. CD1d expression was down-regulated in the biliary epithelium of patients with late primary sclerosing cholangitis, primary biliary cirrhosis, and alcoholic cirrhosis compared to healthy controls. CONCLUSIONS: Cholangiocytes express CD1d and present antigens to NKT cells and CD1d expression is down-regulated in diseased biliary epithelium, findings which show that the biliary epithelium can activate an important lymphocyte subset of the liver. This is a potentially important immune pathway in the biliary system, which may be capable of regulating inflammation in the context of biliary disease.

Effects of temperature and photoperiod on sensory quality and contents of glucosinolates, flavonols and vitamin C in broccoli florets.

Broccoli is grown around the world at a wide range of photoperiods and temperatures, which may influence both sensory quality and phytochemical contents. Florets produced in phytotron and at two semi-field sites (70 °N and 58 °N) were examined for effects of contrasting temperatures and photoperiods on sensory quality and contents of glucosinolates, flavonols and vitamin C. Growth conditions associated with high northern latitudes of low temperature and long photoperiods, produced bigger floral buds, and florets with sweeter taste and less colour hue than more southern conditions. The contents of vitamin C did not vary, while the response of individual glucosinolates varied with temperature and day length, and contents of quercetin and kaempferol were lower in phytotron than under semi-field conditions. Thus, our results show that contrasting temperatures and photoperiods influence the sensory quality of broccoli florets, while contents of different bioactive phytochemicals are not influenced in a unidirectional pattern.

Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93-6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.

Long-term risk of colorectal cancer in individuals with serrated polyps.

OBJECTIVE: Although serrated polyps may be precursors of colorectal cancer (CRC), prospective data on the long-term CRC risk in individuals with serrated polyps are lacking. DESIGN: In a population-based randomised trial, 12,955 individuals aged 50-64 years were screened with flexible sigmoidoscopy, while 78 220 individuals comprised the control arm. We used Cox models to estimate HRs with 95% CIs for CRC among individuals with ≥1 large serrated polyp (≥10 mm in diameter), compared with individuals with adenomas at screening, and to population controls, and multivariate logistic regression to assess polyp risk factors for CRC. RESULTS: A total of 103 individuals had large serrated polyps, of which 81 were included in the analyses. Non-advanced adenomas were found in 1488 individuals, advanced adenomas in 701. Median follow-up was 10.9 years. Compared with the control arm, the HR for CRC was 2.5 (95% CI 0.8 to 7.8) in individuals with large serrated polyps, 2.0 (95% CI 1.3 to 2.9) in individuals with advanced adenomas and 0.6 (95% CI 0.4 to 1.1) in individuals with non-advanced adenomas. A large serrated polyp was an independent risk factor for CRC, adjusted for histology, size and multiplicity of concomitant adenomas (OR 3.3; 95% CI 1.3 to 8.6). Twenty-three large serrated polyps found at screening were left in situ for a median of 11.0 years. None developed into a malignant tumour. CONCLUSIONS: Individuals with large serrated polyps have an increased risk of CRC, comparable with individuals with advanced adenomas. However, this risk may not be related to malignant growth of the serrated polyp. TRIAL REGISTRATION NUMBER: The Norwegian Colorectal Cancer Screening trial is registered at clinicaltrials.gov (NCT00119912).

Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial.

IMPORTANCE: Colorectal cancer is a major health burden. Screening is recommended in many countries. OBJECTIVE: To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry. INTERVENTIONS: Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp ≥10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention. MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality. RESULTS: A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups. CONCLUSIONS AND RELEVANCE: In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00119912.