Background Vitamin D has been linked to disease activity among patients with inflammatory bowel diseases (IBD). Prior investigation has also suggested that vitamin D levels may affect duration of therapy with anti-tumor necrosis factor-α (anti-TNF-α) medications among patients with IBD. Aims This study aimed to evaluate the relationship between vitamin D levels and odds of reaching remission while on an anti-TNF-α medication. Methods 521 IBD patients enrolled in the Brigham and Women’s IBD Center database were eligible for inclusion. Patients treated with anti-TNF-α therapy who had vitamin D levels drawn within 6 months prior or 2 weeks after initiation of anti-TNF-α medication and who had reported remission status at 3 months were included. A logistic regression model adjusting for age, gender, IBD diagnosis, anti-TNF-α medication (infliximab versus adalimumab) and first or subsequent anti-TNF-α medication was used to identify the effect of vitamin D level on initial response to anti-TNF-α therapy. Results 173 patients were included in the final analysis. On logistic regression, patients with normal vitamin D levels at the time of anti-TNF-α medication initiation had a 2.64 increased odds of remission at 3 months compared to patients with low vitamin D levels when controlling for age, gender, diagnosis, type of anti-TNF-α medication and first or subsequent anti-TNF-α medication (OR 2.64, 95% CI 1.31–5.32, p 0.0067). Conclusion These findings suggest that vitamin D levels may influence initial response to anti-TNF-α medication and that low vitamin D levels may predispose patients to decreased odds of remission.
Background Care of patients with inflammatory bowel disease (IBD) poses a significant burden to the health-care system. Repeat hospitalization in subgroups of IBD patients seems to be a large part of this issue; however, there are limited data examining the characteristics of these patients. The aim of this study was to characterize admission patterns in patients with IBD at a tertiary-care center and to identify preventable risk factors of 90-day readmission after an index IBD admission. Methods Retrospective analysis was performed extracting data from an electronic medical record over a 2-year period. Results Three hundred fifty-six patients were admitted at least once during the 2-year study period for an unplanned IBD-related reason. Of these, 48.9% were admitted once, 38.2% were admitted 2 to 4 times, and 12.9% were admitted 5 or more times during the study period. Patients with any admission within 90 days before index were excluded; n = 33. One hundred two patients had experienced a readmission by 90 days after index admission. Numerous demographic and medical factors were examined for association with readmission. The final Cox model included 3 variables: depression (HR = 1.99, 1.33–3.00), chronic pain (HR = 1.88, 1.14–3.10), and steroid use in the previous 6 months (HR = 1.33, 0.92–2.04). Conclusions Our findings suggest that patients with depression and chronic pain are at greatest risk for a readmission within 90 days after an initial IBD admission. Disease activity, represented by steroid use in the previous 6 months, was not related to readmission. Addressing these problems in the outpatient setting may reduce future hospitalizations.
Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.
Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.
An interview study was conducted to explore volunteers' experiences of creativity in citizen cyberscience. Participants were recruited from 4 projects: GeoTag-X, Virtual Atom Smasher, Synthetic Biology, and Extreme Citizen Science. Ninety-six interviews were conducted in total: 86 with volunteers (citizen scientists) and 10 with professional scientists. The resulting thematic analysis revealed that volunteers are involved in a range of creative activities, such as discussing ideas, suggesting improvements, gamification, artwork, creative writing, and outreach activities. We conclude that the majority of creative products are community-related. Creativity in citizen cyberscience is a collective process: volunteers create within a project and a community, both for themselves and for others.
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