263 research outputs found

    Transcript of The Dory Derby Accident

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    This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

    Nutrient composition of selected traditional United States Northern Plains Native American plant foods

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    Ten wild plants (cattail broad leaf shoots, chokecherries, beaked hazelnuts, lambsquarters, plains prickly pear, prairie turnips, stinging nettles, wild plums, raspberries, and rose hips) from three Native American reservations in North Dakota were analyzed to expand composition information of traditional foraged plants. Proximates, dietary fiber (DF), vitamins, minerals, carotenoids, and folate vitamers were assayed using standard methods and reference materials. Per serving, all were rich in Mn (100–2808 mg). Several provided \u3e10% DRI of Fe (cattail shoots, steamed lambsquarters, and prairie turnips), Ca (steamed lambsquarters, prickly pear, and prairie turnips), Mg (cattail shoots, lambsquarters, prickly pear, and prairie turnips), vitamins B6 (chokecherries, steamed lambsquarters, broiled prickly pear, and prairie turnips), C (raw prickly pear, plums, raspberries, rose hips (426 mg/100 g), and K (cattail shoots, chokecherries, lambsquarters, plums, rose hips, and stinging nettles). DF was \u3e10 g/serving in chokecherries, prairie turnips, plums and raspberries. Rose hips, plums, lambsquarters, and stinging nettles were carotenoid-rich (total, 3.2–11.7 mg/100 g; b-carotene, 1.2–2.4 mg/100 g; lutein/zeaxan- thin, 0.9–6.2 mg/100 g) and lycopene (rose hips only, 6.8 mg/100 g). Folate (primarily 5-methylte- trahydrofolate) was highest in raw lambsquarters (97.5 mg/100 g) and notable in cattail shoots, raw prairie turnips, and blanched stinging nettles (10.8, 11.5, and 24.0 mg/100 g, respectively). Results, provided to collaborating tribes and available in the National Nutrient Database of the United States Department of Agriculture (USDA) (www.ars.usda.gov/nutrientdata), support reintroduction or increased consumption of foraged plants

    Serological Biomarkers of Intestinal Collagen Turnover Identify Early Response to Infliximab Therapy in Patients with Crohn’s Disease

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    BACKGROUND: Crohn’s disease (CD) is characterized by excessive protease activity and extracellular matrix (ECM) remodeling. To date, 30–50% of patients experience non-response to anti-TNF-α treatment. This study aimed to assess whether serological biomarkers of ECM turnover could monitor or predict response to infliximab (IFX) induction therapy in patients with and without a surgical history. METHODS: Serum biomarkers of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen degradation, type III (PRO-C3) and VI (PRO-C6) collagen formation, basement membrane turnover (PRO-C4), and T-cell activity (C4G), were measured at baseline and week 14, in 63 patients with CD undergoing IFX induction therapy. Patients were stratified according to surgical history. RESULTS: C4M was elevated at baseline in responders with a surgical history (n = 10) and associated with response at baseline (P < 0.05). Additionally, C6Ma3, PRO-C3, and PRO-C6 were elevated at week 14 in responders compared with non-responders (n = 8) and could differentiate between the two groups (P < 0.05). Two biomarker ratios (C4M/C4G and PRO-C4/C4G) were elevated at week 14 in non-responders (n = 5) without a surgical history compared with responders (n = 40) and could differentiate between the response groups (P < 0.05). CONCLUSION: Baseline levels of a serological biomarker for type IV collagen degradation associated with response to IFX induction therapy, and biomarkers of type III and VI collagen formation may be used to monitor response at the end of induction therapy in patients with a surgical history. Biomarker ratios of type IV collagen turnover demonstrated promising results in monitoring treatment response in patients without a surgical history

    Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn’s Disease

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    Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4ÎČ7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders (p < 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p < 0.05). All biomarkers were associated with response to VEDO (all p < 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy

    Biomarkers of neutrophil activity and extracellular matrix turnover predict long-term response to vedolizumab in patients with Crohn's disease

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    Background Crohn‘s disease (CD) is a form of inflammatory bowel disease characterized by high infiltration of immune cells into the intestinal tissue, resulting in increased proteolytic mediated extracellular matrix (ECM) remodeling. Disease management has improved with the use of biologics such as vedolizumab (VEDO). However, considering the high rate of primary non-response to VEDO, there is an unmet need for predictive serum biomarkers capable of determining response to treatment prior to its initiation. This study investigated whether biomarkers of neutrophil activity, mucosal damage, and ECM remodeling could serve as non-invasive tools for predicting long-term response to VEDO in patients with CD. Methods Serum biomarkers of human neutrophil elastase (HNE)-derived fragment of calprotectin (CPa9-HNE [serum calprotectin]) and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n=32) before VEDO therapy initiation. The ratio C4M/C4G (myeloid/lymphoid mediated degradation) was computed. Long-term response was defined as the continuation of treatment beyond one year after the start of therapy. Baseline biomarker levels were compared between responders and non-responders using Mann-Whitney U-tests, and area under the curve (AUC) values were generated using receiver operating characteristics (ROC) statistics. Biomarker levels were divided into tertiles and chi-square tests were used to investigate the relationship between tertiles and response proportions. Results Biomarkers CPa9-HNE, C1M, C3M, C4M, PRO-C3, C3M/PRO-C3, and C4M/C4G were significantly increased at baseline in non-responders compared with responders (all P<0.05). All markers were able to predict response to VEDO at baseline (AUC [95% CI]: CPa9-HNE 0.81 [0.66–0.96]; C1M 0.85 [0.75–0.98]; C3M 0.79 [0.62–0.95]; C4M 0.77 [0.6–0.93]; C3M/PRO-C3 0.78 [0.6–0.95]; C4M/C4G 0.74 [0.56–0.92] all P<0.05). Proportions of long-term VEDO users were highest in the first tertiles for all the markers (73–91%) and decreased in a concentration-dependent manner across the second and third tertiles, indicating that patients with the lowest concentrations of these markers less frequently discontinued treatment at one year after initiation (Figure 1). Conclusion Baseline levels of serum biomarkers for neutrophil activity (CPa9-HNE [serum calprotectin]) and mucosal damage (C1M, C3M, C4M, C4G, PRO-C4, and PRO-C3) could predict long-term response to VEDO in patients with CD. Therefore, these biomarkers could aid in early decision making concerning treatment with vedolizumab in patients with CD

    Type I collagen degradation fragments (C1M) and human neutrophil elastase-derived fragments of calprotectin (CPa9-HNE) reflect biochemical and endoscopic disease activity in patients with Inflammatory Bowel Disease

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    Background Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by intestinal inflammation and increased extracellular matrix (ECM) remodeling, which are key pathophysiological mechanisms in patients with IBD and highly related to mucosal damage. Alterations in intestinal ECM turnover as well as macrophage and neutrophil activity may be reflected by secreted products that are released into the systemic circulation. In this study, we aimed to investigate associations between serum biomarkers of neutrophil activity (serum calprotectin) and collagen degradation (mucosal damage), and disease activity in patients with IBD. Methods Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C6), matrix metalloproteinase (MMP)-mediated collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) and intestinal inflammation (VICM [macrophage activity], human neutrophil elastase-derived fragment of calprotectin (CPa9-HNE [serum calprotectin, neutrophil activity]) were measured using Protein FingerPrint assay (PFA) technology in 100 patients with IBD (CD: n=44; UC: n=56). Biochemical disease activity was assessed using C-reactive protein (CRP) levels and available faecal calprotectin (FCal) levels. Endoscopic disease activity was determined using the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Results C1M strongly associated with elevated CRP levels (defined as >5mg/L, P<0.001) in patients with IBD and significantly associated with faecal calprotectin levels in patients with UC (Spearman’s ρ=0.75, P<0.001). In patients with CD, C1M reasonably discriminated between patients with mild and moderate-to-severe endoscopic disease activity (AUC=0.73, P=0.01), whereas this discrimination was more subtle in patients with UC (AUC=0.68, P=0.08). CPa9-HNE levels were significantly increased in patients with elevated CRP levels (P=0.002 for both CD and UC) and associated best with faecal calprotectin levels in patients with CD compared with UC (CD: ρ=0.43, P=0.06; UC: ρ=0.20, P=0.45). Finally, CPa9-HNE levels were able to discriminate between mild and moderate-to-severe endoscopic disease activity in patients with CD (AUC=0.75, P<0.01). Conclusion C1M and CPa9-HNE levels associate with biochemical (CRP, FCal) and endoscopic disease activity in patients IBD, where C1M demonstrated higher accuracy in UC and CPa9-HNE appeared to be more useful in CD in this cohort. Therefore, C1M and CPa9-HNE could serve as surrogate biomarkers for the assessment of disease activity in patients with UC and CD, respectively. Our results should be validated in additional prospective, larger patient cohorts to corroborate these findings
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