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In response to elevated temperatures, plants alter the activities of enzymes that affect lipid composition. While it has long been known that plant leaf membrane lipids become less unsaturated in response to heat, other changes, including polygalactosylation of galactolipids, head group acylation of galactolipids, increases in phosphatidic acid and triacylglycerols, and formation of sterol glucosides and acyl sterol glucosides, have been observed more recently. In this work, by measuring lipid levels with mass spectrometry, we confirm the previously observed changes in Arabidopsis thaliana leaf lipids under three heat stress regimens. Additionally, in response to heat, increased oxidation of the fatty acyl chains of leaf galactolipids, sulfoquinovosyldiacylglycerols, and phosphatidylglycerols, and incorporation of oxidized acyl chains into acylated monogalactosyldiacylglycerols are shown. We also observed increased levels of digalactosylmonoacylglycerols and monogalactosylmonoacylglycerols. The hypothesis that a defect in sterol glycosylation would adversely affect regrowth of plants after a severe heat stress regimen was tested, but differences between wild-type and sterol glycosylation-defective plants were not detected.

BACKGROUND:Inflammatory bowel diseases (IBD) cause a wide variety of gastrointestinal symptoms including abdominal pain, diarrhea, and rectal bleeding. It is well known that the type and level of symptoms that patients experience varies widely. In previously presented work, our group performed a series of focus groups to understand the impact of different symptoms on patients. We identified that symptoms that cause disability, anxiety, and those that are out of the patient's control are perceived to be the most burdensome. The 4 gastrointestinal symptoms that patients described as most burdensome were abdominal pain, rectal bleeding, urgency and incontinence, and stool frequency. Additionally, we observed that the relative burden of different symptoms varied. Therefore, the aim of the current study is to quantify the relative importance of 4 common IBD symptoms and their severity for IBD patients.METHODS:To quantify the relative importance of different symptoms and severity levels, a choice-based conjoint (CBC) analysis survey was developed. In the survey, patients are asked to complete 16 CBC questions, in which they choose one out of 2 scenarios with different levels of severity for 4 different symptoms. Abdominal pain, rectal bleeding, stool frequency, and urgency/incontinence are the 4 symptoms included in the survey. Severity levels are based on the levels used in common disease activity measures. Clinical information including the type of IBD and disease duration is obtained from the chart. A Hierarchical Bayes analysis is used to quantify the relative importance of different severity levels for each of the symptoms. Patients 18 years or older with a confirmed IBD diagnosis are eligible to participate. Patients with a stoma are excluded.RESULTS:Thus far, 100 eligible patients have completed the survey (46% male, mean age 39 [SD 15]). Two patients were excluded after finalizing the survey as they did not fulfill eligibility criteria (stoma and unconfirmed IBD diagnosis). Four eligible patients started but did not finish the survey. Of the included patients, 55% were diagnosed with CD, 39% with UC, and 6% with IBDU, with an average disease duration of 9 years (SD 7). Conjoint analysis revealed that urgency/incontinence was the most important symptom for patients: 1.5× more important than abdominal pain, 2.2× more important than rectal bleeding, and 3.5× more important than stool frequency. As expected, higher symptom levels were perceived to be more important than lower symptom levels. In particular, urgency leading to incontinence was a major factor driving patients decisions to select one scenario over another.CONCLUSION(S):In this study, we quantified the relative importance of 4 common symptoms and severity levels that IBD patients experience. We found large differences in the observed importance of different symptoms for IBD patients. Urgency/incontinence was shown to be particularly bothersome, while stool frequency by itself was not perceived to be very burdensome. These results will be used to develop a score to quantify symptom-burden in IBD patients.

Inflammatory bowel disease (IBD) has classically been associated with malnutrition and weight loss, although this has become less common with advances in treatment and greater proportions of patients attaining clinical remission. However, micronutrient deficiencies are still relatively common, particularly in CD patients with active small bowel disease and/or multiple resections. This is an updated literature review of the prevalence of major micronutrient deficiencies in IBD patients, focusing on those associated with important extraintestinal complications, including anemia (iron, folate, vitamin B12) bone disease (calcium, vitamin D, and possibly vitamin K), hypercoagulability (folate, vitamins B6, and B12), wound healing (zinc, vitamins A and C), and colorectal cancer risk (folate and possibly vitamin D and calcium).

Tumor necrosis factor alpha-induced protein 3 ( ) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single nucleotide polymorphism (SNPs) within the exonic regions of the gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort. Genomic DNA was obtained from 721 participants and sequencing of all exons and an intergenic point mutation (rs6920220) was performed. functional assessment was performed by transfecting mutated constructs into knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student's t-test for continuous variables and Chi-squared test for categorical variables. Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of which encodes the protein's deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ test, P=0.014 to P<0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24-13.18]), and rs2230926:T>G was more prevalent among African Americans (OR [95% CI] 3.65 [1.58-8.43]). assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of to abrogate NF-κB activation by 2-fold (P<0.01) and 1.7-fold (P<0.01), respectively. This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

The evolving understanding of the role of the microbiome and environmental factors in the pathogenesis of inflammatory bowel disease makes diet an interesting and potentially powerful tool in the treatment of disease. However, at this time, evidence is limited but anecdotal reports of success abound. There is a bewildering array of new diets being tried by patients in an attempt to control diseases. This review attempts to summarize the most common diets for the treating physician.

BackgroundWomen with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP.MethodsCRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed.Results19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0–0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants.ConclusionWhen quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-­free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding.Trial registration numberNCT02154425; Results.

Malnutrition is common in inflammatory bowel disease (IBD). Identifying patients who are malnourished or at risk for malnutrition may lead to early intervention and improve patient outcomes. To date, little is known about the role of nutritional assessment and management in IBD care. We aimed to evaluate knowledge, attitudes, and beliefs regarding nutrition in IBD among patients and providers.MethodsSurveys were mailed electronically to patients and providers identified through their membership in the Crohn's & Colitis Foundation of America. In addition, patient and provider focus groups were conducted to explore nutrition-related themes. These surveys and focus groups were designed to evaluate knowledge and perceived importance of nutrition, patient–provider interactions regarding nutrition and use of nutritional resources.ResultsThere were 223 provider respondents (65.5% gastroenterologists, 15.2% nurses, and 6.7% dietitians). Forty-one percent of the gastroenterologists rated their knowledge of nutrition in IBD as “very good” compared with 87% of dietitians and 16% of nurses (P < 0.001). Thirty-three percent of the gastroenterologists reported not routinely screening their IBD patients for malnutrition. The patient survey had 567 respondents with 27% rating their knowledge of nutrition in IBD as “very good.” In the focus groups, a lack of adequate IBD nutritional resources was evident along with a desire for improved access to nutrition specialists.ConclusionsSignificant gaps in knowledge relating to nutrition in IBD seem to exist. Targeted educational initiatives and improved access to nutritional experts are warranted. In addition, a standardized process for the assessment of malnutrition among patients with IBD should be developed.

INTRODUCTION:Gastrointestinal bleeding secondary to duodenal varices is an uncommon finding, and is typically seen in patients with portal hypertension due to cirrhosis. We report a case of a patient without evidence of liver disease who developed significant bleeding from isolated duodenal varices caused by mesenteric venous obstruction from a carcinoid mass.CASE DESCRIPTION/METHODS:A 71-year-old male with a history of a metastatic mesenteric carcinoid tumor presented with recurrent gastrointestinal bleeding. He was initially diagnosed with carcinoid of the mesentery several years prior, for which he underwent resection followed by Y40 ablation of liver metastases. He had been admitted multiple times at a local hospital for recurrent gastrointestinal bleeding, for which he had undergone extensive endoscopic evaluation. He was then transferred to our facility for a higher level of care. A double balloon push enteroscopy and endoscopic ultrasound were performed with findings of a large cluster of bleeding duodenal varices in the third portion of the duodenum not amenable to endoscopic intervention. CT abdomen and pelvis with contrast and CT angiography of the abdomen showed an irregular 3 cm calcified mass at the root of the mesentery. Additionally, several branches of the superior mesenteric artery and vein (SMA and SMV) were noted to be occluded near the mass. Interventional radiology (IR) performed an IR-guided transhepatic portogram revealing obstruction of the SMV at the level of the mesenteric mass. There appeared to be a large colic branch communicating with an abnormal cluster of varices near the third portion of the duodenum. Two overlapping covered stents were placed at the large colic branch into the SMV, decompressing the varices. The patient was started on plavix, propranolol, and octreotide depot and safely discharged home without further bleeding.DISCUSSION:Duodenal varices are an uncommon but potentially serious complication of portal hypertension, and are most often seen as a sequelae of liver disease. The development of duodenal varices as a result of venous obstruction secondary to a desmoplastic reaction induced by a carcinoid tumor has seldom been reported in the literature. This case illustrates a noteworthy example of bleeding ectopic varices in a patient without liver disease, a rare cause of obscure gastrointestinal bleeding.