A comprehensive characterization of MPS-STR stutter artefacts.

Interpretation of DNA evidence involving mixtures is challenging when alleles from minor contributors coincide with stutters from major contributors. To accommodate this, it is important to have a good understanding of stutter sequence formation trends. Here, multiple stutter types were characterized based on massively parallel sequencing (MPS) data from 387 single source samples, using the Verogen ForenSeq™ DNA Signature Prep kit. A beta regression model was used to investigate the relationship between the stutter proportion and candidate explanatory variables. In the final model, stutter proportions were explained by the length of the parental uninterrupted stretch (PTUS), which is comparable to block length of the missing motif (BLMM). Also, different stutter types (n+1, n-1, n+2, n-2, n0) were analyzed separately per locus. The fitted stutter models were then integrated into an extended probabilistic genotyping model based on EuroForMix (MPSproto). An illustrative minor/major mock mixture example is discussed. Evaluation of multiple types of stutters on a per locus basis improved the probabilistic genotyping result compared to the conventional EuroForMix model, using the LUS+ nomenclature.

Effect of sprouting on the proteome of chickpea flour and on its digestibility by ex vivo gastro-duodenal digestion complemented with jejunal brush border membrane enzymes.

The demand for sustainably produced proteins is increasing with the world population and is prompting a dietary shift toward plant sourced proteins. Vegetable proteins have lower digestibility and biological value compared to animal derived counterparts. We explored sprouting of chickpea seeds as a strategy for improving digestibility. Protein evolution associated with by the sprouting process was assessed by proteomics. The sprouting induced breakdown of seed storage proteins and doubled the release of free alpha-amino nitrogen in sprouted chickpea flour. During sprouting, several enzymes involved in plant development were newly expressed. An ex vivo model of gastroduodenal and jejunal digestion was applied to assess the bioaccessibility of the protein digests. Proteins from chickpea sprouts showed a greater susceptibility to digestion with a 10% increase in alpha amino nitrogen. Peptides with potential immunoreactivity or bioactivity were catalogued in both digested chickpea sprouts and seeds using an in-silico approach. Peptides belonging to the non-specific transfer proteins, which are allergens in pulses, and peptides belonging to an IgE-binding hemagglutinin protein could only be identified in the digested chickpea sprouts. The observation collected paved the way to immune-based evaluations to assess the effect of germination on the allergenic potential.

Determination of shedder status: A comparison of two methods involving cell counting in fingerprints and the DNA analysis of handheld tubes.

The shedder status of an individual may be important to consider in the context of DNA transfer, persistence and recovery and in Bayesian networks where a person's shedder status may have an impact on the outcome. In this study we compared two methods to determine shedder status: the handheld tube (HH) method and a fluorescent cell count (CC) method. A poor association was observed between the numbers of detected cells in a fingerprint using the CC method and the strength of the DNA result with the HH method. The 20 participants were classified into low (25%), medium (50%) and high (25%) shedders based on the HH method. While the low and high shedders showed a good consistency between the replicates, the medium shedders varied more and have to be considered more carefully as they may act as either a high or a low shedder in an event of DNA transfer.

An LR framework incorporating sensitivity analysis to model multiple direct and secondary transfer events on skin surface.

Bayesian logistic regression is used to model the probability of DNA recovery following direct and secondary transfer and persistence over a 24 h period between deposition and sample collection. Sub-source level likelihood ratios provided the raw data for activity-level analysis. Probabilities of secondary transfer are typically low, and there are challenges with small data-sets with low numbers of positive observations. However, the persistence of DNA over time can be modelled by a single logistic regression for both direct and secondary transfer, except that the time since deposition must be compensated by an offset value for the latter. This simplifies the analysis. Probabilities are used to inform an activity-level Bayesian Network that takes account of alternative propositions e.g. time of assault and time of social activities. The model is extended in order to take account of multiple contacts between person of interest and 'victim'. Variables taken into account include probabilities of direct and secondary transfer, along with background DNA from unknown individuals. The logistic regression analysis is Bayesian - for each analysis, 4000 separate simulations were carried out. Quantile assignments enable calculation of a plausible range of probabilities and sensitivity analysis is used to describe the corresponding variation of LRs that occur when modelled by the Bayesian network. It is noted that there is need for consistent experimental design, and analysis, to facilitate inter-laboratory comparisons. Appropriate recommendations are made. The open-source program written in R-code ALTRaP (Activity Level, Transfer, Recovery and Persistence) enables analysis of complex multiple transfer propositions that are commonplace in cases-work e.g. between those who cohabit. A number of case examples are provided. ALTRaP can be used to replicate the results and can easily be modified to incorporate different sets of data and variables.

Ancestral Wheat Types Release Fewer Celiac Disease Related T Cell Epitopes than Common Wheat upon Ex Vivo Human Gastrointestinal Digestion.

Celiac disease (CeD) is an autoimmune enteropathy triggered by immunogenic gluten peptides released during the gastrointestinal digestion of wheat. Our aim was to identify T cell epitope-containing peptides after ex vivo digestion of ancestral (einkorn, spelt and emmer) and common (hexaploid) wheat (Fram, Bastian, Børsum and Mirakel) using human gastrointestinal juices. Wheat porridge was digested using a static ex vivo model. Peptides released after 240 min of digestion were analyzed by liquid chromatography coupled to high-resolution mass spectrometry (HPLC-ESI MS/MS). Ex vivo digestion released fewer T cell epitope-containing peptides from the ancestral wheat varieties (einkorn (n = 38), spelt (n = 45) and emmer (n = 68)) compared to the common wheat varieties (Fram (n = 72), Børsum (n = 99), Bastian (n = 155) and Mirakel (n = 144)). Neither the immunodominant 33mer and 25mer α-gliadin peptides, nor the 26mer γ-gliadin peptide, were found in any of the digested wheat types. In conclusion, human digestive juice was able to digest the 33mer and 25mer α-gliadin, and the 26mer γ-gliadin derived peptides, while their fragments still contained naive T cell reactive epitopes. Although ancestral wheat released fewer immunogenic peptides after human digestion ex vivo, they are still highly toxic to celiac patients. More general use of these ancient wheat variants may, nevertheless, reduce CeD incidence.

Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-Grade Dysplasia in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. METHODS: We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. RESULTS: Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied. CONCLUSIONS: In an analysis of stool samples from 3 independent studies of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance.

Fecal Calprotectin Responses Following Induction Therapy With Vedolizumab in Moderate to Severe Ulcerative Colitis: A Post Hoc Analysis of GEMINI 1.

BACKGROUND: In patients with ulcerative colitis (UC), fecal calprotectin (FC) concentrations correlate with endoscopic inflammation evidence. This study investigated the effect of vedolizumab induction on FC concentrations and whether FC concentrations could be a reliable surrogate measure of disease status. METHODS: Data from the placebo-controlled, phase 3 trial GEMINI 1 were used to evaluate week-6 relationships between outcomes (including clinical remission, mucosal healing [MH], and endoscopic remission) and both absolute FC concentration values and relative FC concentration changes from baseline (%FC0-6). Sensitivity and specificity were calculated by cross-tabulation; the value of week-6 FC concentration as surrogate biomarker was measured with Youden J statistic computed for various cut points. RESULTS: GEMINI 1 induction phase enrolled 895 patients. Fecal calprotectin concentration decreases were deeper in patients with clinical remission, MH, and/or endoscopic remission than in patients without. The best week-6 indicator of clinical or endoscopic remission in this data set was absolute FC concentration ≤150 µg/g. The surrogate biomarker values (based on areas under the curve) for the best-performing cut points (FC0-6 reduction >90%, FC ≤150 µg/g) were fair (range, 0.70-0.77, total population). More patients met the ≤150 µg/g cut point with vedolizumab than with placebo. Baseline FC concentrations were not correlated with clinical outcomes. CONCLUSIONS: Fecal calprotectin concentration reductions were greater with vedolizumab induction than with placebo. Week-6 FC concentrations had only fair surrogate biomarker value for endoscopic status. Our data suggest that, while FC may reflect inflammatory burden, FC concentration after vedolizumab induction may not be a robust biomarker of mucosal inflammation.

Real-life chromoendoscopy for dysplasia surveillance in ulcerative colitis.

AIM: To evaluate the use of chromoendoscopy for surveillance of ulcerative colitis in a real-life community hospital setting. METHODS: Patients with extensive ulcerative colitis, having disease duration of more than 8 years and who presented between the years of 1999 to 2013, were offered enrolment in this single cohort prospective study. All participants underwent standard bowel preparation with sodium phosphate and chromoendoscopy. Two expert endoscopists, novice to chromoendoscopy, evaluated each segment of the colon with standard-definition colonoscopes after spray application of 0.4% indigo carmine. All observed lesions were recorded and evaluated before being removed and/or biopsied. In addition, nontargeted biopsies were taken from each segment of the colon. The dysplasia detection rate and dysplasia detection yield were ascertained. RESULTS: A total of 21 neoplastic lesions (2 carcinomas, 4 of high-grade dysplasia and 15 of low-grade dysplasia) and 27 nondysplastic lesions were detected in 16 of the total 67 patients (70% male; median disease duration: 17 years; median age at diagnosis: 25 years; 92% aminosalicylate-treated). The dysplasia detection rate was 10.5% (7/67 patients). The dysplasia detection yield was 20.8% (10/48) for targeted biopsies and 3.5% (11/318) for nontargeted biopsies. The sensitivity and specificity for the macroscopic evaluation of neoplasia using chromoendoscopy were 48% [95% confidence interval (CI): 26%-70%] and 96% (95%CI: 93%-98%), respectively. The positive predictive and negative predictive values were 42% (95%CI: 27%-59%) and 97% (95%CI: 95%-98%), respectively. A total of 19/21 dysplastic lesions were detected in mucosa with histologic inflammation. CONCLUSION: Chromoendoscopy seems to be of value for dysplasia surveillance of ulcerative colitis in a community hospital setting. The yield of non-targeted biopsies is negligible.

Multi-target stool DNA test in the surveillance of inflammatory bowel disease: a cross-sectional cohort study.

BACKGROUND AND AIM: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD. MATERIAL AND METHODS: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and ß-actin by a laboratory blinded to clinical data. RESULTS: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16-100%) for CRC and 33% (95% CI 13-61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81-91%) and 93% (95% CI 88-96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93-99%) and was 28 (95% CI 22-34%) to detect any colorectal neoplasia (CRN). CONCLUSION: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.

Exploring Gut Microbiota Composition as an Indicator of Clinical Response to Dietary FODMAP Restriction in Patients with Irritable Bowel Syndrome.

BACKGROUND: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may relieve symptoms of irritable bowel syndrome (IBS). However, nutritional counseling is resource-demanding and not all patients will benefit. AIMS: To explore whether gut microbial composition may identify symptom response to a low-FODMAP diet in patients with IBS. METHODS: Patients were recruited consecutively to participate in a 4-week FODMAP-restricted diet. Response to diet was defined as ≥ 50% decrease in IBS symptom severity scores (IBS-SSS) compared to baseline. Fecal microbiota were analyzed by a commercially available method (the GA-map™ Dysbiosis Test), assessing 54 bacterial markers targeting more than 300 bacteria at different taxonomic levels. RESULTS: Sixty-one patients (54 F; 7 M) were included: 32 (29 F; 3 M) classified as responders and 29 (25 F; 4 M) as non-responders. Ten of the 54 bacterial markers differed significantly between responders and non-responders. Based on median values (used as cutoff) of responders for these 10 bacterial markers, we constructed a Response Index (RI): Each patient was given a point when the value for each selected bacterial marker differed from the cutoff. These points were summed up, giving an RI from 0 to 10. Patients with RI > 3 were 5 times more likely to respond (OR = 5.05, 95% CI [1.58; 16.10]), and the probability to respond was 83.4%, 95% CI [61.2-94%]. CONCLUSIONS: Gut microbial composition, assessed by using a new RI, may constitute a tool to identify patients that are likely to respond to dietary FODMAP restriction.

Persistent symptoms in patients with Crohn's disease in remission: An exploratory study on the role of diet.

OBJECTIVES: Patients with Crohn's disease (CD) often report food hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical remission. We aimed to identify the most frequent symptoms and dietary triggers in such patients, and also explored whether a strict elimination diet may reduce their GI symptoms. METHODS: We assessed GI symptoms and dietary triggers in 16 patients with CD in clinical remission. Of these, 12 patients subsequently participated in a dietary intervention trial: two weeks on a habitual diet including wheat and dairy products followed by two weeks of a strict elimination diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating, abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using visual analog scales throughout the four weeks intervention period. MAIN RESULTS: The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces, and diarrhea. Dairy and wheat products were reported as the most frequent dietary symptom triggers. All symptoms improved (p < .05) during the elimination diet period, especially in patients with small intestinal affection. CONCLUSION: Our exploratory study suggests that dietary interventions such as an elimination diet may reduce GI symptoms in patients with CD in remission.

Fecal Calprotectin: A Reliable Predictor of Mucosal Healing after Treatment for Active Ulcerative Colitis.

OBJECTIVES: Mucosal healing has become the new goal of treatment in ulcerative colitis. Fecal calprotectin has been demonstrated to differentiate between mucosal inflammation and mucosal healing. With this project, we investigated whether a reduction in f-calprotectin to <250 µg/g after medical treatment for active ulcerative colitis could predict mucosal healing. MATERIAL AND METHODS: After a baseline colonoscopy, 20 patients with active ulcerative colitis were followed with consecutive fecal calprotectin monthly until two measurements of fecal calprotectin < 250 µg/g or a maximum follow-up of 12 months. A flexible sigmoidoscopy was then performed and Mayo endoscopic subscore was used to evaluate degree of inflammation. Simple Clinical Colitis Activity Index was used for evaluation of clinical disease activity. RESULTS: A total of 16 patients achieved fecal calprotectin < 250 µg/g during follow-up, and all 16 patients had endoscopic mucosal healing (Mayo endoscopic subscore of ≤1) on the second endoscopy. The remaining four patients had persistently high f-calprotectin levels before the second endoscopy with Mayo endoscopic subscore corresponding to endoscopic mucosal healing in three out of four patients. CONCLUSIONS: Fecal calprotectin <250 µg/g after medical treatment for active ulcerative colitis is a reliable marker of endoscopic mucosal healing.

Usability of a home-based test for the measurement of fecal calprotectin in asymptomatic IBD patients.

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. METHODS: IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. RESULTS: Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. CONCLUSION: The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA.

Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.

BACKGROUND/AIMS: Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may relieve symptoms in patients with irritable bowel syndrome (IBS). We investigated whether this diet alters microbial fermentation, a process that may be involved in IBS symptom generation. METHODS: Patients with IBS were included consecutively to participate in a 4-week FODMAP restricted diet. IBS symptoms were evaluated by using the IBS severity scoring system (IBS-SSS). Short-chain fatty acids (SCFAs) were analyzed in fecal samples before and after the dietary intervention, both at baseline and after in vitro fermentation for 24 h. RESULTS: Sixty-three patients completed the study. Following the dietary intervention, IBS-SSS scores improved significantly (p < 0.0001). Total SCFA levels were reduced in fecal samples analyzed both at baseline (p = 0.005) and after in vitro fermentation for 24 h (p = 0.013). Following diet, baseline levels of acetic (p = 0.003) and n-butyric acids (p = 0.009) decreased, whereas 24 h levels of i-butyric (p = 0.003) and i-valeric acids (p = 0.003) increased. Fecal SCFA levels and IBS symptom scores were not correlated. CONCLUSION: Dietary FODMAP restriction markedly modulated fecal fermentation in patients with IBS. Saccharolytic fermentation decreased, while proteolytic fermentation increased, apparently independent of symptoms.

Clinical importance of faecal calprotectin variability in inflammatory bowel disease: intra-individual variability and standardisation of sampling procedure.

OBJECTIVE: Faecal (f-) calprotectin is a biomarker of intestinal inflammation. Previous studies have described intra-individual day-to-day variability of this biomarker in patients with inflammatory bowel disease (IBD) and morning samples have been suggested for standardisation purposes. With this project, we investigated if day-to-day variability differed from diurnal variability. Additionally, we evaluated a new extraction method for f-calprotectin analysis. METHODS: Fifty patients provided three faeces samples from morning - evening - morning on two consecutive days. Nineteen patients provided two faeces samples from the same bowel movement, one conventional spot sample, and one sample with a device for patient-administered sampling and extraction. RESULTS: The two morning samples differentiated between mucosal inflammation and mucosal healing with same level of agreement as the two samples from the same day (kappa 0.76), using an f-calprotectin cut-off level of 259 µg/g. Although large intra-individual variation in f-calprotectin values, there were no significant day-to-day (p = 0.096) or diurnal variation (p = 0.78). Used by laboratory technicians, the new extraction device correlated significantly with the conventional extraction method (p < 0.001), Spearman's rank correlation coefficient 0.95. Of the 19 patients testing patient administered extraction, two patients provided samples leading to considerably higher f-calprotectin levels than conventional sampling procedure. CONCLUSIONS: The reliability of f-calprotectin morning samples is equal to the reliability of samples from different bowel movements on the same day. The new extraction method is reliable when used by laboratory technicians, but larger studies are recommended to evaluate patient administered extraction.

Prediction of endoscopic disease activity in ulcerative colitis by two different assays for fecal calprotectin.

BACKGROUND AND AIMS: As mucosal healing is the goal of treatment in inflammatory bowel disease, defining a fecal [f-] calprotectin cut-off level for mucosal healing is crucial. Previous studies have presented different cut-off levels. The aim of this study was to investigate the ability of two f-calprotectin assays to differentiate mucosal healing from inflammation in ulcerative colitis. METHODS: Sixty-two patients with ulcerative colitis underwent colonoscopy for classification of mucosal inflammation [Mayo endoscopic subscore]. The patients also submitted a fecal sample for f-calprotectin analysis using two different assays, Calpro ELISA and Buhlmann ELISA. RESULTS: The two assays correlated significantly, with a Spearman rank correlation coefficient of 0.86. Both assays showed significantly different f-calprotectin levels in patients with a Mayo endoscopic subscore of 0 [mucosal healing] and 1­3 [inflamed mucosa] [p <0.001]. Using ROC curve analyses, we selected the best cut-off levels for both assays with responding sensitivity and specificity [presented with 95% confidence intervals]; Calpro ELISA cut-off 61 µg/g, sensitivity 84.1% [75.0­93.2%], specificity 83.3 % [74.0­92.6%], and Buhlmann ELISA cut-off 96 µg/g, sensitivity 90.9 % [83.7­98.1%], specificity 83.3 % [74.0­92.6%]. Defining mucosal healing as a Mayo endoscopic subscore ≤1, cut-off levels increased: Calpro ELISA cut-off 110 µg/g, sensitivity 80.0%[70­90%], specificity 66.6 % [54.9­78.3%]; and Buhlmann ELISA cut-off 259 µg/g, sensitivity 83.3 %[74­92.6%], specificity 71.9 % [60.7­83.1%]. CONCLUSIONS: The study demonstrates the need for assay specific cut-off levels in clinical practice,as the f-calprotectin cut-off level for endoscopic disease activity differed in these two assays.

INSPIRE study: does stress management improve the course of inflammatory bowel disease and disease-specific quality of life in distressed patients with ulcerative colitis or Crohn's disease? A randomized controlled trial.

BACKGROUND: The use of stress management psychotherapy is hypothesized to produce greater improvement in disease course and disease-specific quality of life (IBDQ) compared to usual medical care alone in patients with ulcerative colitis (UC) or Crohn's disease (CD) showing high levels of stress (based on the Perceived Stress Questionnaire [PSQ]). METHODS: Fifty-eight patients with UC and 56 patients with CD who had experienced continuous disease activity or had relapsed over the previous 18 months, with an activity index for UC or CD ≥ 4, a PSQ ≥ 60, and without serious psychiatric disorders or other serious medical conditions were randomized to receive either treatment as usual (TAU) or TAU plus stress management psychotherapy. Psychotherapy consisted of three group sessions (psychoeducation, problem-solving, relaxation) and 6-9 individual sessions based on cognitive behavior therapy-related methods with 1-3 booster sessions at 6 and 12 months follow-up. Gastroenterologists blinded to intervention group assessed disease activity and course at baseline and at 3, 6, 12, and 18 months. Patients completed the IBDQ at baseline, 6, 12, and 18 months. RESULTS: The intervention did not improve disease or reduce relapse; however, it increased the IBDQ score (P = 0.009, mean differences 16.3 [SD 6.1]). On analysis of UC and CD separately, improvement of IBDQ was only found in the UC group. CONCLUSIONS: Stress management psychotherapy does not appear to improve disease course or reduce relapse in patients with IBD. It might improve quality of life, particularly in patients with UC.

[Measurement of calprotectin in faeces]. / Måling av kalprotektin i feces.

BACKGROUND: Calprotectin is a calcium-binding protein found in neutrophils. Increased levels are found in stools after mucosal damage due to inflammation, which causes influx of neutrophils into the gut lumen. MATERIAL AND METHOD: This article is based on a review of the most pertinent publications found on Medline and our clinical experience from more than 10 years of using the test. RESULTS: Calprotectin is primarily a marker of intestinal inflammation. The test is therefore a useful tool for investigation of abdominal discomfort. At diagnosis all patients with inflammatory bowel disease will have clearly elevated values of faecal calprotectin. On the other hand, in patients with irritable bowel syndrome the levels are normal. Normalization of faecal calprotectin seems to be a strong indicator of mucosal healing. INTERPRETATION: Correct use of the test can therefore contribute to reducing the number of unnecessary colonoscopies, which is especially important in children. Faecal calprotectin is a simple test and an objective parameter of inflammatory disease activity which is useful for assessment of disease course and monitoring of response to medical treatment in patients with inflammatory bowel disease.

Technology insight: calprotectin, lactoferrin and nitric oxide as novel markers of inflammatory bowel disease.

Distinguishing patients with inflammatory bowel disease from those with irritable bowel syndrome can be difficult. A simple and reliable test that detects intestinal inflammation would therefore be very useful in the clinic. If such a test parameter correlated with the intensity of the inflammatory reaction it could also be used to monitor disease activity. Calprotectin, lactoferrin and nitric oxide are produced and released locally in much greater quantities in the inflamed gut than in the noninflamed gut. These compounds can be readily measured in fecal samples (calprotectin and lactoferrin) or directly in the intestinal lumen (nitric oxide gas). Here, we discuss what is known about these markers, how they could be used in clinical practice and how they can complement existing techniques used for the diagnosis and monitoring of inflammatory bowel disease.

Mapping of a milk production quantitative trait locus to a 420-kb region on bovine chromosome 6.

A QTL affecting milk production traits was previously mapped to an interval of 7.5 cM on chromosome 6 in Norwegian dairy cattle. This article aimed to refine this position by increasing the map density in the region by a set of single-nucleotide polymorphisms and analyzing the data with a combined linkage and linkage disequilibrium approach. Through a series of single- and multitrait and single- and multipoint analyses, the QTL was positioned to an interval surrounded by the genes ABCG2 and LAP3. As no recombinations were detected in this interval, physical mapping was required for further refining. By using radiation hybrid mapping as well as BAC clones, the bovine and human comparative maps in the region are resolved, and the QTL is mapped within a distance of 420 kb.