Prospective study of psychological morbidity and illness perceptions in young people with inflammatory bowel disease

Background and Aims: Psychological morbidity is increased in young people with inflammatory bowel disease (IBD). Illness perceptions may be an important factor. This study aimed to describe the prevalence and severity of psychological morbidity and examine relationships between baseline illness perceptions and anxiety, depression and health-related quality of life (HRQoL) at baseline and 12-months later in 16-21-years olds with IBD. Methods: IBD patients (n = 121) completed measures of anxiety, depression, HRQoL, and illness perceptions (IPQ-R) at baseline and follow-up (n = 100, 83%). Results: mong the 121 patients at baseline (median age 19.3 years, 40% female, 62% Crohn's disease, 73% in clinical remission), 55% reported elevated symptoms of anxiety/depression and 83% low HRQoL. Negative illness perceptions at baseline were significantly correlated with greater anxiety, depression and lower HRQoL at baseline and follow-up. In regression analysis at baseline, IPQ-R domain of greater perception of a cyclical nature of IBD was an independent predictor of anxiety, whilst a greater perceived emotional impact of IBD was an independent predictor of anxiety, depression and HRQoL. Female gender and clinical relapse were also independent predictors of lower HRQoL. After controlling for baseline measures, clinical risk factors and illness perceptions did not explain additional variance in psychological morbidity at follow-up. Conclusion: A high prevalence of psychological morbidity, stable over one year, was demonstrated in young people with IBD. Having negative illness perceptions, being female and active disease predicted those at greatest risk of psychological morbidity. Illness perceptions may be an appropriate target for psychological interventions

Decorin reduces intraocular pressure and retinal ganglion cell loss in rodents through fibrolysis of the scarred trabecular meshwork

Purpose. To investigate whether Decorin, a matrikine that regulates extracellular matrix (ECM) deposition, can reverse established trabecular meshwork (TM) fibrosis, lower IOP, and reduce progressive retinal ganglion cell (RGC) death in a novel rodent model of TM fibrosis. Methods. Adult rats had intracameral (IC) injections of human recombinant (hr) TGF-β over 30 days (30d; to induce TM fibrosis, raise IOP, and initiate RGC death by 17d) or PBS (controls) and visually evoked potentials (VEP) were measured at 30d to evaluate resultant visual pathway dysfunction. In some animals TGF-β injections were stopped at 17d when TM fibrosis and IOP were consistently raised and either hrDecorin or PBS IC injections were administered between 21d and 30d. Intraocular pressure was measured biweekly and eyes were processed for immunohistochemical analysis of ECM deposition to assess TM fibrosis and levels of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) to assess fibrolysis. The effect of hrDecorin treatment on RGC survival was also assessed. Results. Transforming growth factor–β injections caused sustained increases in ECM deposition in the TM and raised IOP by 17d, responses that were associated with 42% RGC loss and a significant decrease in VEP amplitude measured at 30d. Decorin treatment from 17d reduced TGF-β–induced TM fibrosis, increased levels of MMP2 and MMP9 and lowered TIMP2 levels, and lowered IOP, preventing progressive RGC loss. Conclusions. Human recombinant Decorin reversed established TM fibrosis and lowered IOP, thereby rescuing RGC from progressive death. These data provide evidence for the candidacy of hrDecorin as a treatment for open-angle glaucoma

Reverse-Engineering a Transcriptional Enhancer: A Case Study in Drosophila

Abstract Enhancers, or cis-regulatory elements, are the principal determinants of spatiotemporal patterning of gene expression. For reasons of clinical and research utility, it is desirable to build customized enhancers that drive novel gene expression patterns, but currently, we largely rely on “found” genomic elements. Synthetic enhancers, assembled from transcription factor binding sites taken from natural signal-regulated enhancers, generally fail to behave like their wild-type counterparts when placed in transgenic animals, suggesting that important aspects of enhancer function are still unexplored. As a step toward the creation of a truly synthetic regulatory element, we have undertaken an extensive structure–function study of an enhancer of the Drosophila decapentaplegic (dpp) gene that drives expression in the developing visceral mesoderm (VM). Although considerable past efforts have been made to dissect the dppVM enhancer, transgenic experiments presented here indicate that its activity cannot be explained by the known regulators alone. dppVM contains multiple, previously uncharacterized, regulatory sites, some of which exhibit functional redundancy. The results presented here suggest that even the best-studied enhancers must be further dissected before they can be fully understood, and before faithful synthetic elements based on them can be created. Implications for developmental genetics, mathematical modeling, and therapeutic applications are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63213/1/ten.tea.2008.0074.pd

The Ricci flow on noncommutative two-tori

In this paper we construct a version of Ricci flow for noncommutative 2-tori, based on a spectral formulation in terms of the eigenvalues and eigenfunction of the Laplacian and recent results on the Gauss-Bonnet theorem for noncommutative tori.Comment: 18 pages, LaTe

Evidence against or for topological defects in the BOOMERanG data ?

The recently released BOOMERanG data was taken as ``contradicting topological defect predictions''. We show that such a statement is partly misleading. Indeed, the presence of a series of acoustic peaks is perfectly compatible with a non-negligible topological defects contribution. In such a mixed perturbation model (inflation and topological defects) for the source of primordial fluctuations, the natural prediction is a slightly lower amplitude for the Doppler peaks, a feature shared by many other purely inflationary models. Thus, for the moment, it seems difficult to rule out these models with the current data.Comment: 4 pages, 1 figure. Some changes following extraordinarily slow referee Reports and new data. Main results unchanged (sorry

Search for Exotic Mesons in pi- P Interactions at 18 GeV/c

The recent search for non $q \bar{q}$ mesons in $\pi^{-}p$ interactions at Brookhaven National Laboratory is summarized. Many final states such as $\eta \pi$, $\eta' \pi^{-}$, $a_{0} \pi$, $f_{1} \pi$, $a_{2} \pi$, $b_{1} \pi$, which are favored decay modes of exotics, are under investigation.Comment: 9 pages, PostScript, Presented at the International School of Nuclear Physics, Erice, Sicily, Italy, September 199

How are management fashions institutionalized? The role of institutional work

We explore how transitory management fashions become institutionalized. Based on the concepts of institutional entrepreneurship and institutional work, we postulate that fashionable management practices acquire permanence when they are anchored within fieldwide institutions. The building of such institutions requires various types of institutional work, including political work, technical work and cultural work. Based on a review of the empirical literature on various management fashions, we identify the actors engaging in these different types of works, and their skills. Our results suggest that the institutionalization effect is stronger if more types of institutional work are deployed and if the skill sets of the involved actors vary. We also argue that institutional construction in the case of management fashions is likely to take the form of decentralized `partaking' rather than being led by a single dominant institutional entrepreneur. We conclude with implications for the study of management fashions and the role of agency in institutionalization

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults

Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology. Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean ± SD age: 73 ± 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilution-multiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small-and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology. Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower highdensity lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile (higher LDL cholesterol and triglycerides). Conclusion: Choline and its metabolites have differential associations with cardiometabolic risk factors and subtypes of vascular disease, thereby suggesting differing roles in the pathogenesis of cardiovascular and cerebral large-vessel disease compared with that of small-vessel disease