Search

Sunday Oluwafemi Oyeyemi,1 Tonje Braaten,1 Edoardo Botteri,2,3 Paula Berstad,2 Kristin Benjaminsen Borch11Department of Community Medicine, Uit-the Arctic University of Norway, Tromsø, Norway; 2Department of Bowel Cancer Screening, Cancer Registry of Norway, Oslo, Norway; 3Norwegian National Advisory Unit for Women’s Health, Women’s Clinic, Oslo University Hospital, Oslo, NorwayPurpose: Norway has experienced an unexplained, steep increase in colorectal cancer (CRC) incidence in the last half-century, with large differences across its counties. We aimed to determine whether geographical distribution of lifestyle-related CRC risk factors can explain these geographical differences in CRC incidence in Norwegian women.Methods: We followed a nationally representative cohort of 96,898 women with self-reported information on lifestyle-related CRC risk factors at baseline and at follow-up 6–8 years later in the Norwegian Women and Cancer Study. We categorized Norwegian counties into four county groups according to CRC incidence and used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk factors. We used the Karlson, Holm, and Breen (KHB) method of mediation analysis to investigate the extent to which the risk factors accounted for the observed differences in CRC incidence between counties.Results: During an average of 15.5 years of follow-up, 1875 CRC cases were diagnosed. Height (HR=1.12; 95% CI 1.08, 1.17 per 5 cm increase); being a former smoker who smoked ≥10 years (HR=1.34; 95% CI 1.15, 1.57); or being a current smoker who has smoked for ≥10 years (HR=1.28; 95% CI 1.12, 1.46) relative to never smokers was associated with increased CRC risk. Duration of education >12 years (HR=0.78; 95% CI 0.69, 0.87) vs ≤12 years, and intake of vegetables and fruits >300 g (HR=0.90; 95% CI 0.80, 0.99) vs ≤300 g per day were associated with reduced CRC risk. However, these risk factors did not account for the differences in CRC risk between geographical areas of low and high CRC incidence. This was further confirmed by the KHB method using baseline and follow-up measurements (b=0.02, 95% CI −0.02, 0.06, p=0.26).Conclusion: Lifestyle-related CRC risk factors did not explain the geographical variations in CRC incidence among Norwegian women. Possible residual explanations may lie in heritable factors.Keywords: lifestyle, diet, risk factors, colorectal cancer, women, NOWAC study

Abstract Background The Norwegian colorectal cancer (CRC) screening program started in May 2022. Inequalities in CRC screening participation are a challenge, and we expect that certain groups, such as immigrants, are at risk of non-participation. Prior to the start of the national screening program, a pilot study showed lower participation rates in CRC screening among immigrants from Pakistan. These immigrants are a populous group with a long history in Norway and yet have a relatively low participation rate also in other cancer screening programs. The purpose of this study was to identify and explore perspectives and factors influencing CRC screening participation among immigrants from Pakistan in Norway. Materials and methods In this study we used a qualitative study design and conducted 12 individual interviews with Pakistani immigrants aged between 50 and 65 years. The participants varied in terms of gender, age, education, work, residence time in Norway and familiarity with the Norwegian language and culture. We performed thematic analysis with health literacy as a theoretical framework to understand Pakistani immigrants’ perspectives on CRC screening. Results We identified four main themes: Health-related knowledge, the health care system, screening, and social factors. Within these themes we identified several factors that affect Pakistani immigrants’ accessibility to CRC screening. These factors included knowledge of the causes and development of cancer, sources of health-related information, the general practitioner’s role, understanding of screening and the intention behind it, language skills and religious beliefs. Conclusion There are many factors influencing Pakistani immigrants’ decision of participation in CRC screening. The roles of the general practitioner and adult children are particularly important. Key elements to improve accessibility to CRC screening and enable informed participation for Pakistani immigrants are measures that improve personal and organizational health literacy.

Abstract Stool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identify, annotate and characterize more than 18000 DNA viruses, using shotgun metagenome sequencing. Only six percent of them are assigned to a known taxonomic family, with Microviridae being the most prevalent viral family. Linking individual profiles to comprehensive lifestyle and demographic data shows 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibit strong and consistent associations with both diversity and relative abundance of individual viruses, as well as with enrichment for auxiliary metabolic genes. We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.

Abstract Background While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. Methods Adherence to the seven‐point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self‐administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen‐detected lesions. Results Of 1486 screening participants, 548 were free from adenomas, 524 had non‐advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. Conclusions Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen‐detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.

Hydrogen from natural gas reforming can be produced efficiently with a high CO2 capture rate. This can be achieved through oxygen-blown autothermal reforming as the core technology, combined with pressure-swing adsorption for hydrogen purification and refrigeration-based tail gas separation for CO2 capture and recirculation of residual hydrogen, carbon monoxide, and methane. The low-temperature tail gas separation section is presented in detail. The main objective of the paper is to study and quantify the exergy efficiency of this separation process in detail. To achieve this, a detailed exergy analysis is conducted. The irreversibilities in 42 different process components are quantified. In order to provide transparent verification of the consistency of exergy calculations, the total irreversibility rate is calculated by two independent approaches: Through the bottom-up approach, all individual irreversibilities are added to obtain the total irreversibility rate. Through the top-down approach, the total irreversibility rate is calculated solely by the exergy flows crossing the control volume boundaries. The consistency is verified as the comparison of results obtained by the two methods shows a relative deviation of 4·10−7. The exergy efficiency of the CO2 capture process is calculated, based on two different definitions. Both methods give a baseline exergy efficiency of 58.38%, which indicates a high degree of exergy utilisation in the process.

IntroductionOrganized cancer screening programs should be equally accessible for all groups in society. We assessed differences in participation in colorectal cancer (CRC) screening among different immigrant groups.MethodsBetween 2012 and 2019, 140,000 individuals aged 50 to 74 years were randomly invited to sigmoidoscopy or repeated faecal immunochemical test (FIT) in a CRC screening trial. In this study, we included 46,919 individuals invited to sigmoidoscopy and 70,018 invited to the first round of FIT between 2012 and 2017. We examined difference in participation between non-immigrants and immigrants, and within different immigrant groups by geographic area of origin, using logistic regression models, adjusted for several sociodemographic factors and health factors.ResultsIn total, we included 106,695 non-immigrants and 10,242 immigrants. The participation rate for FIT was 60% among non-immigrants, 58% among immigrants from Western countries and 37% among immigrants from non-Western countries. The participation rate for sigmoidoscopy was 53% among non-immigrants, 48% among immigrants from Western countries and 23% among immigrants from non-Western countries. Compared to non-immigrants, multivariate adjusted odds ratio for non-participation in FIT screening was 1.13 (95% confidence interval 1.04–1.23) and 1.82 (1.69–1.96) for immigrants from Western and non-Western countries. The corresponding numbers in sigmoidoscopy screening were 1.34 (1.21–1.48) and 2.83 (2.55–3.14). The lowest participation was observed in immigrants from Eastern Europe, Northern Africa and Western Asia, and South-Central Asia.ConclusionParticipation in CRC screening in Norway was particularly low among non-Western immigrants, which could put them at increased risk for late stage diagnosis of CRC. Participation was lower in sigmoidoscopy screening than in FIT screening, especially among immigrants from non-Western countries.

Summary: Background: Effective risk stratification tools for post-polypectomy colorectal cancer (PPCRC) are lacking. We aimed to develop an effective risk stratification tool for the prediction of PPCRC in three large population-based cohorts and to validate the tool in a clinical cohort. Methods: Leveraging the integrated endoscopic, histopathologic and epidemiologic data in three U.S population-based cohorts of health professional (the Nurses' Health Study (NHS) I, II and Health Professionals Follow-up Study (HPFS)), we developed a risk score to predict incident PPCRC among 26,741 patients with a polypectomy between 1986 and 2017. We validated the PPCRC score in the Mass General Brigham (MGB) Colonoscopy Cohort (Boston, Massachusetts, U.S) of 76,603 patients with a polypectomy between 2007 and 2018. In all four cohorts, we collected detailed data on patients’ demographics, endoscopic history, polyp features, and lifestyle factors at polypectomy. The outcome, incidence of PPCRC, was assessed by biennial follow-up questionnaires in the NHS/HPFS cohorts, and through linkage to the Massachusetts Cancer Registry in the MGB cohort. In all four cohorts, individuals who were diagnosed with CRC or died before baseline or within six months after baseline were excluded. We used Cox regression to calculate the hazard ratio (HR), 95% confidence interval (CI) and assessed the discrimination using C-statistics and reclassification using the Net Reclassification Improvement (NRI). Findings: During a median follow-up of 12.8 years (interquartile range (IQR): 9.3, 16.7) and 5.1 years (IQR: 2.7, 7.8) in the NHS/HPFS and MGB cohorts, we documented 220 and 241 PPCRC cases, respectively. We identified a PPCRC risk score based on 11 predictors. In the validation cohort, the PPCRC risk score showed a strong association with PPCRC risk (HR for high vs. low, 3.55, 95% CI, 2.59–4.88) and demonstrated a C-statistic (95% CI) of 0.75 (0.70–0.79), and was discriminatory even within the low- and high-risk polyp groups (C-statistic, 0.73 and 0.71, respectively) defined by the current colonoscopy surveillance recommendations, leading to a NRI of 45% (95% CI, 36–54%) for patients with PPCRC. Interpretation: We developed and validated a risk stratification model for PPCRC that may be useful to guide tailored colonoscopy surveillance. Further work is needed to determine the optimal surveillance interval and test the added value of other predictors of PPCRC beyond those included in the current study, along with implementation studies. Funding: US National Institutes of Health, the American Cancer Society, the South-Eastern Norway Regional Health Authority, the Deutsche Forschungsgemeinschaft.

Abstract Background The Norwegian colorectal cancer (CRC) screening programme started in May 2022. Inequities in uptake of CRC screening is a concern, and we expect that immigrants are at risk of non-uptake. Immigrants from Poland are the most populous immigrant group in Norway. The purpose of this study was to identify and explore factors that may facilitate Polish immigrants’ access to the Norwegian CRC screening programme. Material and methods This study was based on qualitative interviews with ten Polish immigrants in Norway. The participants represented a convenience sample that varied in terms of gender, education, employment, time in Norway, place of residence, Norwegian language skills and ties to the Norwegian-Polish community. We performed thematic content analysis to understand CRC screening from the perspective of Polish immigrants, using transnationalism and Levesque’s conceptualization of accessibility as theoretical frameworks. Results We grouped our findings into three themes; “understanding of CRC development and the need to access health care”, “binationalism” and “improving accessibility through information”. Within these themes, various factors influenced the participants’ accessibility to CRC screening, namely knowledge about the screening and about causes, development and prevention of the disease, language, choice of screening country, trust in health personnel’s competence, information needs, methods and sources, as well as participants’ perception of the faecal immunochemical test screening user manual. These factors were further influenced by communication between the Polish community in Norway and Poland, as well as travel between the countries. Conclusion We identified several factors that can be targeted with an aim to increase Polish immigrants’ access to the Norwegian CRC screening programme. Effective measures could include increasing cultural competence among health care providers and providing information in Polish through Polish-speaking health care professionals, general practitioners and internet portals used by the Polish-speaking community. Focusing on accessibility in a transnational setting, our findings may be of interest for policy makers and service providers planning preventive health measures for immigrants.

A generic exergy targeting tool for gas separation processes is developed, which is applicable to any defined boundary conditions for incoming feed gas as well as delivered separation products. Whereas targeting tools in the literature so far are mostly simplified and limited to post-combustion related cases and isothermal and isobaric conditions, the present approach is based on a rigorous exergy methodology, which enables exergy targeting for a broad spectrum of boundary conditions.Understanding the causes behind thermodynamic losses throughout the process is a prerequisite for improving energy efficiency. In this respect, exergy analysis provides a powerful tool, which enables the identification and quantification of irreversibilities and thereby exergy losses. The methodology is used to show that common separation processes can be attributed with negative minimum separation work, since a corresponding reversible separation process would yield an exergy output in addition to providing the specified product streams.CO2 capture involves considerable energy demand caused by the various processing steps. The exergy balance of a CO2 capture process can in turn be applied to determine the exergy efficiency for each sub-process as well as for the overall process. Exergy efficiency criteria can be formulated in different ways, and in the present work it will be evaluated primarily against the minimum theoretical exergy requirement, that is, the performance theoretically achievable for a reversible process.Through a quantitative example based on published literature on CO2 separation from syngas, it is shown that a process may still require a substantial amount of exergy input despite having a negative minimum separation work, which in turn results in a negative exergy efficiency. A relation between sub-system exergy efficiency and overall system exergy efficiency is derived on a general basis. For the numerical example of CO2 capture from syngas, the derived relation shows consistency and is able to reproduce the total process efficiency also when one of the sub-processes, CO2 separation, has a negative exergy efficiency. Exergy efficiency results are finally compared with corresponding results based on a well-established rational exergy efficiency.Despite different values and even signs for the separation sub-process efficiency, it is still shown that there are no contradictions between the two efficiency criteria when used consistently, since they give identical total exergy efficiency when applied to the control volume of the combined CO2 separation and compression process, and since identical results are obtained also when expressing the total exergy efficiency as a linear combination of the two sub-process efficiencies, one of which has a negative sign.

BackgroundThe microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples.MethodsFrom the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance.ResultsDiversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis.ConclusionUsing a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.

Abstract Background Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening. Method We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations). Results Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p

Antibody Drug Conjugates (ADCs) are emerging in the field of precision cancer medicine. Here, the authors suggest using endocytosis as a predictive biomarker for response

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550 .

Measurement(s) Gastrointestinal Tract • gastrointestinal system disease Technology Type(s) Capsule Endoscope • visual assessment of in vivo video recording Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment alimentary part of gastrointestinal system Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14178905

Abstract Background Intraarticular corticosteroids (IACs) have been used to treat temporomandibular joint (TMJ) arthritis. However, prospective clinical studies with magnetic resonance imaging (MRI) scoring are lacking. The aim of this study was to examine efficacy and safety of a single IAC in the TMJ in adolescents with juvenile idiopathic arthritis (JIA) in a clinical setting. Methods In this Norwegian prospective multicenter pilot study 15 patients with JIA (mostly persistent oligoarthritis or RF negative polyarthritis categories) and a clinically and MRI-verified diagnosis of TMJ arthritis were treated with IACs and followed for 2 years. Demographics, systemic medication, general disease activity and outcome measures were recorded including a pain-index score and maximal incisal opening (MIO). Inflammation and bone damage scores were assessed, using two recently published MRI scoring systems with masked radiological evaluation. Results Among the 15 patients, 13 received a single IAC (5 bilateral), and 2 repeated IACs once unilaterally. Thus, the total number of IACs was 22. Median age was 15 years and the majority had an age not thought of as critical regarding mandibular growth retardation due to steroid injection. During the 2-year observation period systemic medication with disease modifying antirheumatic drugs (DMARDs) including biologics was initiated or adjusted in 10/15 (67%) patients. At the 2-months study visit after injection we observed a minimal improvement in MIO from median 44 (1st, 3rd quartiles; 36, 48) mm to 45 (43, 47) mm, p = 0.045 and decreased MRI mean additive inflammatory score from 4.4 ± 1.8 standard deviations (SD) to 3.4 ± 2.0, p = 0.040. From baseline to the 2-months follow-up pain improved in 6/11 patients but pain scores were not significantly improved. MRI-assessed damage increased in two patients with repeated IACs, and decreased in 3 patients but most of the patients were stable over the 2-year follow-up. Intra-rater repeatability of the MRI scoring system domains varied from poor to excellent. Conclusions In this pilot study of predominately single IACs to the TMJ in combination with systemic treatment we observed improvement in MRI-assessed inflammation, mostly stable condylar bone conditions and minimal clinical improvement in adolescents with JIA and TMJ arthritis. No severe side effects were seen.

BackgroundDespite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged.MethodsTo detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours.ResultsNine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas.ConclusionsBedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.

Sandwich panels have proven to be excellent energy absorbents. Such panels may be used as a protective structure in, for example, façades subjected to explosions. In this study, the dynamic response of sandwich structures subjected to blast loading has been investigated both experimentally and numerically, utilizing a shock tube facility. Sandwich panels made of aluminium skins and a core of extruded polystyrene (XPS) with different densities were subjected to various blast load intensities. Low-velocity impact tests on XPS samples were also conducted for validation and calibration of a viscoplastic extension of the Deshpande-Fleck crushable foam model. The experimental results revealed a significant increase in blast load mitigation for sandwich panels compared to skins without a foam core, and that the back-skin deformation and the core compression correlated with the foam density. Numerical models of the shock tube tests were created using LS-DYNA, incorporating the new viscoplastic formulation of the foam material. The numerical models were able to capture the trends observed in the experimental tests, and good quantitative agreement between the experimental and predicted responses was in general obtained. One aim of this study is to provide high-precision experimental data, combined with a validated numerical modelling strategy, that can be used in simulation-based optimisation of sandwich panels exposed to blast loading.

Ragna Lind,1 Arnold Berstad,2 Jan Hatlebakk,1,3 Jørgen Valeur21Department of Medicine, Haukeland University Hospital, Bergen, 2Unger-Vetlesen Institute, Department of Medicine, Lovisenberg Diakonale Hospital, Oslo, 3Department of Clinical Medicine, University of Bergen, Bergen, NorwayBackground: Patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome (IBS) suffer from several health complaints, including fatigue. The aim of the present study was to validate a Norwegian translation of the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients with self-reported food hypersensitivity and IBS, as compared with healthy controls.Methods: Thirty-eight patients with unexplained self-reported food hypersensitivity and IBS, who participated in the validation of the FIS completed the following additional questionnaires: the Short Form of Nepean Dyspepsia Index for assessment of quality of life, the Subjective Health Complaint Inventory, and questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied in 43 patients with unexplained self-reported food hypersensitivity, 70% diagnosed with IBS, and 42 healthy controls.Results: Cronbach's α for the FIS was 0.98, indicating excellent agreement between individual items. Scores on the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r = 0.50, P = 0.001), indicating good convergent validity, and were higher in patients (median 85.0, interquartile range 36.8–105.3) than in controls (median 14.0, interquartile range 3.0–29.0, P ≤0.0001).Conclusion: The Norwegian translation of the FIS performed excellently in patients with unexplained self-reported food hypersensitivity and IBS, with patients reporting significantly more impact of chronic fatigue than healthy controls.Keywords: irritable bowel syndrome, fatigue, food hypersensitivity, quality of life

Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs) were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38

Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD) was the incentive of this pilot study.Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease) with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone 12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif®, Berna) was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period.Results: Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed.Conclusion: Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

As an alternative to baseline technology a low-temperature syngas separation process has been proposed for pre-combustion CO2 capture from coal-derived syngas for an IGCC plant. Through systematic process synthesis – sequencing of separators and location of compressors and expanders, followed by Pinch Analysis and energy targeting – a process design has been proposed and the net power consumption has been estimated. From a targeted power consumption of 21.9 MW the figure for the proposed design is increased to 22.9 MW mainly due to increased load for auxiliary refrigeration at low temperature. The power consumption of the proposed design represents further improvement from earlier designs that have already been shown to have higher energy efficiency than baseline technology.

CO2 capture and storage has a potential of reducing CO2 emissions from large point sources such as fossil fuel power plants. CO2 capture is associated with substantial capital expenditures, operational expenditures dominated by high energy use and potential operational restrictions on the underlying industrial processes. The main focus of significant research efforts worldwide is thus to reduce investment costs and improve efficiency of capture technologies. The systematic methodologies developed in our group at SINTEF/NTNU for design of energy efficient fossil fuel power plants with CO2 capture are presented and show the importance of utilizing process synthesis in the design of such plants. These methods range from targeting minimum capture work for different CO2 capture processes, optimization methods for process design of pre- and post-combustion capture processes, developing surrogate models for optimization.

Natural gas combined cycles (NGCC) with post-combustion CO2 capture is expected to be an important part of the solution in the future low-emission energy scenario. An overview of the literature shows that until recently there has been no effort to develop systematic methods to integrate the different units in the process. The CO2 capture process cannot be optimized without considering its integration into the power plant and the adaptation of existing process units to the new requirements defined by the CO2 capture process. With this in mind, a systematic energy integration methodology is presented in this work that evaluates the energy targets prior to design. The Sequential Framework for heat exchanger network synthesis is modified to develop the heat exchanger networks including the heat recovery steam generator. Process and component considerations when integrating steam extraction from the bottoming cycle are also discussed. Application of the methodology results in an improvement in efficiency of the overall process by 0.4 % points.

Abstract preview not available - see full-text PDF article.

Background Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD) was the incentive of this pilot study. Methods Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn's disease) with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone < 12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif ®, Berna) was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period. Results Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed. Conclusion Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

Background Intestinal microbiota seems to play an essential role in the development of inflammatory bowel diseases (IBD). We hypothesised that an oral vaccine based on live Salmonella typhi would be well tolerated and could even attenuate dextran sulfate sodium (DSS) induced colitis in rats, an animal model of IBD. Methods Nine male Wistar rats was used for an initial tolerance study, in which we used 3 dose-levels of Salmonella Ty21a, 0.5 × 10 9 , 1 × 10 9 , and 2 × 10 9 CFU, each dose being tested in 3 rats. Four treatment groups consisting of 8 male Wistar rats per group: 1) control group given standard food and water, 2) control group given four daily administrations of Salmonella Ty21a 1 × 10 9 CFU, 3) water with 5% DSS the last 7 days, 4) four daily administrations of Salmonella Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with the drinking water from day 15 to 22. The animals were sacrificed and colonic tissue removed for analysis 22 days after gavage of the first vaccine dose. Results The animals in the tolerance study got no signs of disease. In the treatment study, all animals receiving DSS had histologic indications of colitis, particularly in the distal part of the colon. Administration of Salmonella Ty21a had no significant effect on crypt and inflammation scores (p > 0.05). Conclusion Gastric administration of live vaccine strain Salmonella Ty21a was well tolerated, but did not provide any significant protection against development of DSS induced colitis in rats.

BackgroundThe oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation.MethodsFifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis.ResultsThere were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) < 0.1.ConclusionsIn this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation.

Capture conditions for CO2 vary substantially between industrial point sources. Depending on CO2 fraction and pressure level, different capture technologies will be required for cost- and energy-efficient decarbonisation. For decarbonisation of shifted synthesis gas from coal gasification, several studies have identified low-temperature CO2 capture by condensation and phase separation as an energy- and cost-efficient option. In the present work, a process design is proposed for low-temperature CO2 capture from an Integrated Gasification Combined Cycle (IGCC) power plant. Steady-state simulations were carried out and the performance of the overall process, as well as major process components, were investigated. For the baseline capture unit layout, delivering high-pressure CO2 at 150 bar, the net specific power requirement was estimated to 273 kJe/kgCO2, and an 85% CO2 capture ratio was obtained. The impact of 12 different process parameters was studied in a sensitivity analysis, the results of which show that compressor and expander efficiencies, as well as synthesis gas separation temperature, have the highest impact on power requirements. Modifying the process to producing cold liquid CO2 for ship transport resulted in 16% increase in net power requirements and is well suited for capturing CO2 for ship transport.

For vessel-based transport of liquid CO2 in carbon capture and storage chains, transport at 8 bar(a) enable significant cost reductions compared to transport at higher pressures for most transport distances and volumes. Transport at even lower pressures could further reduce the costs. There are, however, concerns related to dry ice formation and potential clogging in parts of the chain that could lead to operational issues when operating close to the triple point pressure of CO2. In this paper, results from an experimental campaign to de-risk and gain operational experience from the low-pressure CO2 liquefaction process are described. Six experiments using pure CO2 or CO2/N2 mixtures are presented. In four of the experiments, the liquid product pressure was continuously lowered until dry ice was detected and eventually clogged the system. In the final two experiments, the liquefaction process was run in steady-state at low liquefaction pressures for five hours to ensure that there is no undetected dry ice in the process that could lead to accumulation and operational issues over time. These experiments demonstrate that pure CO2 can be safely liquefied at 5.8 bar(a) and a CO2/N2 mixture can be liquefied at 6.5 bar(a) without issues related to dry ice formation.

Ragnhild Undseth,1 Greta Jakobsdottir,2 Margareta Nyman,2 Arnold Berstad,3 Jørgen Valeur3 1Department of Radiology, Lovisenberg Diaconal Hospital, Oslo, Norway; 2Food for Health Science Centre, Lund University, Lund, Sweden; 3Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway Background: Ingestion of low-digestible carbohydrates triggers symptoms in patients with irritable bowel syndrome (IBS). These carbohydrates become substrates for microbial fermentation in the colon, yielding short-chain fatty acids (SCFAs) that are readily absorbed. Aiming to compare colonic fermentation in patients with IBS and healthy controls, we analyzed the concentrations of SCFA in serum at fasting and 90 minutes following ingestion of an unabsorbable, but fermentable carbohydrate, lactulose. Methods: Patients with IBS according to Rome III criteria (n=22) and healthy controls (n=20) ingested 10 g lactulose dissolved in water. Symptoms were graded by questionnaires and SCFA were analyzed using hollow fiber-supported liquid membrane extraction coupled with gas chromatography. Results: Lactulose induced more symptoms in patients with IBS than in healthy controls (P=0.0001). Fasting serum levels of SCFA did not differ between patients with IBS and controls. However, the postprandial levels of total SCFA (P=0.0002), acetic acid (P=0.005), propionic acid (P=0.0001), and butyric acid (P=0.01) were significantly lower in patients with IBS compared with healthy controls. There was no correlation between the levels of serum SCFA and symptom severity. Conclusion: Low-serum levels of SCFA after lactulose ingestion may indicate impaired colonic fermentation in patients with IBS. Conceivably, this disturbance is related to symptom generation, but the mechanism is not clear. Keywords: fermentation, FODMAP, irritable bowel syndrome, microbiota, short-chain fatty acids

Advances in recombinant DNA technology have opened up new possibilities of exploiting toxic proteins for therapeutic purposes. Bringing forth these protein toxins from the bench to the bedside strongly depends on the availability of production methods that are reproducible, scalable and comply with good manufacturing practice (GMP). The type I ribosome-inhibiting protein, gelonin, has great potential as an anticancer drug, but is sequestrated in endosomes and lysosomes. This can be overcome by combination with photochemical internalization (PCI), a method for endosomal drug release. The combination of gelonin-based drugs and PCI represents a tumor-targeted therapy with high precision and efficiency. The aim of this study was to produce recombinant gelonin (rGel) at high purity and quantity using an automated liquid chromatography system. The expression and purification process was documented as highly efficient (4.4 mg gelonin per litre induced culture) and reproducible with minimal loss of target protein (~50% overall yield compared to after initial immobilized metal affinity chromatography (IMAC)). The endotoxin level of 0.05–0.09 EU/mg was compatible with current standards for parenteral drug administration. The automated system provided a consistent output with minimal human intervention and close monitoring of each purification step enabled optimization of both yield and purity of the product. rGel was shown to have equivalent biological activity and cytotoxicity, both with and without PCI-mediated delivery, as rGelref produced without an automated system. This study presents a highly refined and automated manufacturing procedure for recombinant gelonin at a quantity and quality sufficient for preclinical evaluation. The methods established in this report are in compliance with high quality standards and compose a solid platform for preclinical development of gelonin-based drugs.

Lysosomal accumulation of sunitinib has been suggested as an underlying mechanism of resistance. Here, we investigated if photochemical internalization (PCI), a technology for cytosolic release of drugs entrapped in endosomes and lysosomes, would activate lysosomal sequestered sunitinib. By super-resolution fluorescence microscopy, sunitinib was found to accumulate in the membrane of endo/lysosomal compartments together with the photosensitizer disulfonated tetraphenylchlorin (TPCS2a). Furthermore, the treatment effect was potentiated by PCI in the human HT-29 and the mouse CT26.WT colon cancer cell lines. The cytotoxic outcome of sunitinib-PCI was, however, highly dependent on the treatment protocol. Thus, neoadjuvant PCI inhibited lysosomal accumulation of sunitinib. PCI also inhibited lysosomal sequestering of sunitinib in HT29/SR cells with acquired sunitinib resistance, but did not reverse the resistance. The mechanism of acquired sunitinib resistance in HT29/SR cells was therefore not related to lysosomal sequestering. Sunitinib-PCI was further evaluated on HT-29 xenografts in athymic mice, but was found to induce only a minor effect on tumor growth delay. In immunocompetent mice sunitinib-PCI enhanced areas of treatment-induced necrosis compared to the monotherapy groups. However, the tumor growth was not delayed, and decreased infiltration of CD3-positive T cells was indicated as a possible mechanism behind the failed overall response.

A technical evaluation of CO2 capture technologies when retrofitted to a cement plant is performed. The investigated technologies are the oxyfuel process, the chilled ammonia process, membrane-assisted CO2 liquefaction, and the calcium looping process with tail-end and integrated configurations. For comparison, absorption with monoethanolamine (MEA) is used as reference technology. The focus of the evaluation is on emission abatement, energy performance, and retrofitability. All the investigated technologies perform better than the reference both in terms of emission abatement and energy consumption. The equivalent CO2 avoided are 73⁻90%, while it is 64% for MEA, considering the average EU-28 electricity mix. The specific primary energy consumption for CO2 avoided is 1.63⁻4.07 MJ/kg CO2, compared to 7.08 MJ/kg CO2 for MEA. The calcium looping technologies have the highest emission abatement potential, while the oxyfuel process has the best energy performance. When it comes to retrofitability, the post-combustion technologies show significant advantages compared to the oxyfuel and to the integrated calcium looping technologies. Furthermore, the performance of the individual technologies shows strong dependencies on site-specific and plant-specific factors. Therefore, rather than identifying one single best technology, it is emphasized that CO2 capture in the cement industry should be performed with a portfolio of capture technologies, where the preferred choice for each specific plant depends on local factors.

This paper presents an assessment of the cost performance of CO2 capture technologies when retrofitted to a cement plant: MEA-based absorption, oxyfuel, chilled ammonia-based absorption (Chilled Ammonia Process), membrane-assisted CO2 liquefaction, and calcium looping. While the technical basis for this study is presented in Part 1 of this paper series, this work presents a comprehensive techno-economic analysis of these CO2 capture technologies based on a capital and operating costs evaluation for retrofit in a cement plant. The cost of the cement plant product, clinker, is shown to increase with 49 to 92% compared to the cost of clinker without capture. The cost of CO2 avoided is between 42 €/tCO2 (for the oxyfuel-based capture process) and 84 €/tCO2 (for the membrane-based assisted liquefaction capture process), while the reference MEA-based absorption capture technology has a cost of 80 €/tCO2. Notably, the cost figures depend strongly on factors such as steam source, electricity mix, electricity price, fuel price and plant-specific characteristics. Hence, this confirms the conclusion of the technical evaluation in Part 1 that for final selection of CO2 capture technology at a specific plant, a plant-specific techno-economic evaluation should be performed, also considering more practical considerations.

Kine Gregersen1,2, Jørgen Valeur1,3, Kristine Lillestøl1,3, Livar Frøyland2, Pedro Araujo2, Gülen Arslan Lied1,3, Arnold Berstad1,31Institute of Medicine, University of Bergen, 2National Institute of Nutrition and Seafood Research; 3Department of Medicine, Section for Gastroenterology, Haukeland University Hospital, Bergen, NorwayBackground: Food hypersensitivity is commonly suspected, but seldom verified. Patients with subjective food hypersensitivity suffer from both intestinal and extraintestinal health complaints. Abnormalities of the enterochromaffin cells may play a role in the pathogenesis. The aim of this study was to investigate enterochromaffin cell function in patients with subjective food hypersensitivity by measuring serum chromogranin A (CgA) and 5-hydroxytryptamine (5-HT, serotonin) in gut lavage fluid.Methods: Sixty-nine patients with subjective food hypersensitivity were examined. Twenty-three patients with inflammatory bowel disease and 35 healthy volunteers were included as comparison groups. CgA was measured in serum by enzyme-linked immunosorbent assay. Gut lavage fluid was obtained by administering 2 L of polyethylene glycol solution intraduodenally. The first clear fluid passed per rectum was collected and 5-HT was analyzed by liquid chromatography tandem mass spectrometry.Results: Serum levels of CgA were significantly lower in patients with subjective food hypersensitivity than in healthy controls (P = 0.04). No differences were found in 5-HT levels in gut lavage fluid between patients with subjective food hypersensitivity and the control groups. There was no correlation between serum CgA and gut lavage 5-HT.Conclusion: Decreased blood levels of CgA suggest neuroendocrine alterations in patients with subjective food hypersensitivity. However, 5-HT levels in gut lavage fluid were normal.Keywords: food hypersensitivity, chromogranin A, serotonin, gut lavage fluid, liquid chromatography

Background: Intestinal microbiota seems to play an essential role in the development of inflammatory bowel diseases (IBD). We hypothesised that an oral vaccine based on live Salmonella typhi would be well tolerated and could even attenuate dextran sulfate sodium (DSS) induced colitis in rats, an animal model of IBD.Methods: Nine male Wistar rats was used for an initial tolerance study, in which we used 3 dose-levels of Salmonella Ty21a, 0.5 × 109, 1 × 109, and 2 × 109CFU, each dose being tested in 3 rats. Four treatment groups consisting of 8 male Wistar rats per group: 1) control group given standard food and water, 2) control group given four daily administrations of Salmonella Ty21a 1 × 109 CFU, 3) water with 5% DSS the last 7 days, 4) four daily administrations of Salmonella Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with the drinking water from day 15 to 22. The animals were sacrificed and colonic tissue removed for analysis 22 days after gavage of the first vaccine dose.Results: The animals in the tolerance study got no signs of disease. In the treatment study, all animals receiving DSS had histologic indications of colitis, particularly in the distal part of the colon. Administration of Salmonella Ty21a had no significant effect on crypt and inflammation scores (p > 0.05).Conclusion: Gastric administration of live vaccine strain Salmonella Ty21a was well tolerated, but did not provide any significant protection against development of DSS induced colitis in rats.

Abstract non disponibile

Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD) was the incentive of this pilot study. Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease) with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone 12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif®, Berna) was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period. Results: Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed. Conclusion: Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

Background Food hypersensitivity is a prevalent condition with poorly characterized underlying mechanisms. In the present pilot study we investigated effects of seal oil and soy oil on meal-induced symptoms and gastric accommodation in patients with subjective food hypersensitivity (FH). Single dose experiment : On three consecutive days, 10 mL of seal oil, soy oil, or saline were randomly administered into the duodenum of 10 patients with subjective FH and 10 healthy volunteers through a nasoduodenal feeding tube 10-20 minutes before the ingestion of a test meal. Short-term treatment study : 24 patients with subjective FH were randomly allocated to 10 days’ treatment with either 10 mL of seal or soy oil, self-administrated through an indwelling nasoduodenal feeding tube, 3 times daily. In both experiments meal-induced abdominal symptoms and gastric accommodation were measured by visual analogue scales and external ultrasound respectively. Results Symptoms and gastric accommodation were not significantly influenced by single doses of seal or soy oil. When given daily for 10 days, seal oil, but not soy oil, reduced total symptom scores significantly ( P = 0.03). The symptomatic improvement was not associated with improvements in gastric accommodation. Conclusion Daily administration of seal oil may benefit patients with subjective FH. The beneficial effect of seal oil in patients with subjective FH can not be ascribed to improved gastric accommodation.

Abstract non disponibile

Abstract Background We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model. Methods Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR. Results Ovalbumin-specific serum IgE correlated with jejunal MMCP-1+ cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-γ and TGF-β1 remained unchanged. Conclusion In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-γ mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1+ cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.

Abstract Background A high dietary intake of n-6 compared to n-3 fatty acids (FAs) may promote the production of pro-inflammatory eicosanoids and cytokines. In two recent studies, short-term (10-day) duodenal administration of n-3 polyunsaturated fatty acid rich seal oil ameliorated joint pain in patients with inflammatory bowel disease (IBD). Using unpublished data from these two studies we here investigated whether normalisation of the n-6 to n-3 FA ratio in blood and tissues by seal oil administration was associated with improved health related quality of life (HRQOL) as assessed by the generic short-form 36 (SF-36) questionnaire. Results In the first pilot study, baseline n-6 to n-3 FA ratio in rectal mucosal biopsies from 10 patients with IBD (9 of those had joint pain) was significantly increased compared with that in 10 control patients without IBD or joint pain. Following seal oil administration, the n-6 to n-3 FA ratio of the IBD-patients was significantly lowered to the level seen in untreated controls. In the subsequent, randomized controlled study (n = 19), seal oil administration reduced the n-6 to n-3 FA ratio in blood similarly and also the SF-36 assessed bodily pain, while n-6 FA rich soy oil administration had no such effect. Conclusion In these two separate studies, short-term duodenal administration of seal oil normalised the n-6 to n-3 FA ratio in rectal mucosa and improved the bodily pain dimension of HRQOL of patients with IBD-related joint pain. The possibility of a causal relationship between n-6 to n-3 FA ratio in rectal mucosa and bodily pain in IBD-patients warrants further investigations.