Patients with IBD have a markedly increased risk of acute mesenteric ischemia. Subgroup analysis reveals that women over the age of 40 years with IBD are at increased risk of myocardial infarction, whereas those below the age of 40 years exhibit a two-fold higher risk for stroke. In contrast, men with IBD did not share these same risks for arterial thrombotic events.

Trypanosoma brucei protein arginine methyltransferase 7 (TbPRMT7) exclusively generates monomethylarginine (MMA), which directs biological consequences distinct from that of symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). However, determinants controlling the strict monomethylation activity are unknown. We present the crystal structure of the TbPRMT7 active core in complex with S-adenosyl-L-homocysteine (AdoHcy) and a histone H4 peptide substrate. In the active site, residues E172, E181, and Q329 hydrogen bond the guanidino group of the target arginine and align the terminal guanidino nitrogen in a position suitable for nucleophilic attack on the methyl group of S-adenosyl-L-methionine (AdoMet). Structural comparisons and isothermal titration calorimetry data suggest that the TbPRMT7 active site is narrower than those of protein arginine dimethyltransferases, making it unsuitable to bind MMA in a manner that would support a second turnover, thus abolishing the production of SDMA and ADMA. Our results present the structural interpretations for the monomethylation activity of TbPRMT7.

Background Few data exist regarding the impact of socioeconomic factors on results of current TKA in young patients. Predictors of TKA outcomes have focused primarily on surgical technique, implant details, and individual patient clinical factors. The relative importance of these factors compared to patient socioeconomic status is not known. Questions/purposes We determined whether (1) socioeconomic factors, (2) demographic factors, or (3) implant factors were associated with satisfaction and functional outcomes after TKA in young patients. MethodsWe surveyed 661 patients (average age, 54 years; range, 18-60 years; 61% female) 1 to 4 years after undergoing modern primary TKA for noninflammatory arthritis at five orthopaedic centers. Data were collected by an independent third party with expertise in collecting healthcare data for state and federal agencies. We examined specific questions regarding satisfaction, pain, and function after TKA and socioeconomic (household income, education, employment) and demographic (sex, minority status) factors. Multivariable analysis was conducted to examine the relative importance of these factors for each outcome of interest. One of the authors certifies that he (RLB) has or may receive payments or benefits, during the study period, an amount of more than USD 1,000,001 from Smith & Nephew, Inc, and an amount of more than USD 1,000,001 from Stryker Orthopaedics. One of the authors certifies that he (AVL) has or may receive payments or benefits, during the study period, an amount of more than USD 1,000,001 from Biomet Inc, and an amount of USD 10,000 to 100,000 from Innomed, Inc (Savannah, GA, USA). One of the authors certifies that he (KRB) has or may receive payments or benefits, during the study period, an amount of more than USD 1,000,001 from Biomet Inc.One of the authors certifies that he (JP) has or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000 from Smith & Nephew, Inc, an amount of USD 10,000 to 100,000 from 3 M, an amount of USD 10,000 to 100,000 from Cadence Pharmaceuticals, Inc (San Diego, CA, USA), an amount of USD 10,000 to 100,000 from CeramTec (Laurens, SC, USA), an amount of USD 10,000 to 100,000 from Pfizer (New York, NY, USA), an amount of USD 10,000 to 100,000 from Salient Surgical (Minneapolis, MN, USA), an amount of USD 10,000 to 100,000 from TissueGene (Rockville, MD, USA), and an amount of USD 10,000 to 100,000 from Zimmer Inc. One of the authors certifies that he (CDV) has or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000 from Biomet Inc, an amount of USD 10,000 to 100,000 from Smith & Nephew, Inc, an amount of less than USD 10,000 from ConvaTec (Skillman, NJ, USA), and an amount of less than USD 10,000 from CD Diagnostics (Wynnewood, PA, USA). One of the authors certifies that he (WGH) has or may receive payments or benefits, during the study period, an amount of USD 100,001 to 1,000,000 from DePuy, a Johnson and Johnson company, and an amount of USD 1...

No abstract

Neohesperidosides are disaccharides that are present in some flavonoids and impart a bitter taste, which can significantly affect the commercial value of citrus fruits. In this study, we identified three flavonoid-7- O - di -glucosyltransferase ( dGlcT ) genes closely related to 1,2-rhamnosyltransferase ( 1,2RhaT ) in citrus genomes. However, only 1,2RhaT was directly linked to the accumulation of neohesperidoside, as demonstrated by association analysis of 50 accessions and co-segregation analysis of an F 1 population derived from Citrus reticulata × Poncirus trifoliata . In transgenic tobacco BY2 cells, over-expression of CitdGlcT s resulted in flavonoid-7- O -glucosides being catalysed into bitterless flavonoid-7- O - di -glucosides, whereas over-expression of Cit1,2RhaT converted the same substrate into bitter-tasting flavonoid-7- O -neohesperidoside. Unlike 1,2RhaT , during citrus fruit development the dGlcT s showed an opposite expression pattern to CHS and CHI , two genes encoding rate-limiting enzymes of flavonoid biosynthesis. An uncoupled availability of dGlcTs and substrates might result in trace accumulation of flavonoid-7- O - di -glucosides in the fruit of C. maxima (pummelo). Past human selection of the deletion and functional mutation of 1,2RhaT has led step-by-step to the evolution of the flavor-related metabolic network in citrus. Our research provides the basis for potentially improving the taste in citrus fruit through manipulation of the network by knocking-out 1,2RhaT or by enhancing the expression of dGlcT using genetic transformation.

No abstract

Both a family history of inflammatory bowel disease and smoking at the time of the initial ileocolic resection are associated with an increased risk of a second ileocolic resection. Postoperative prescription of immunomodulators is associated with a reduced risk of surgical recurrence. This study supports the concept that both genetic and environmental factors influence the risk of surgical recurrence of ileal Crohn's disease.

We examined United States Renal Data System registry records for Medicare-insured kidney transplant recipients in 2000–2011 to study the clinical and cost impacts of urinary tract infections (UTI), pneumonia, and sepsis in the first year post-transplant among a contemporary, national cohort. Infections were identified by billing diagnostic codes. Among 60,702 recipients, 45% experienced at least one study infection in the first year post-transplant, including UTI in 32%, pneumonia in 13%, and sepsis in 12%. Older recipient age, female sex, diabetic kidney failure, non-standard criteria organs, sirolimus-based immunosuppression and steroids at discharge were associated with increased risk of first-year infections. By time-varying, multivariate Cox regression, all study infections predicted increased first-year mortality, ranging from 41% (aHR 1.41, 95%CI 1.25–1.56) for UTI alone, 6-to-12-fold risk for pneumonia or sepsis alone, to 34-fold risk (aHR 34.38, 95%CI 30.35–38.95) for those with all three infections. Infections also significantly increased first-year costs, from $17,691 (standard error (SE) $591) marginal cost increase for UTI alone, to approximately $40,000–$50,000 (SE $1054–1238) for pneumonia or sepsis alone, to $134,773 (SE $1876) for those with UTI, pneumonia and sepsis. Clinical and economic impacts persisted in years 2–3 post-transplant. Early infections reflect important targets for management protocols to improve post-transplant outcomes and reduce costs of care.