Inclusion of fish or fish oil in weight-loss diets for young adults: effects on blood lipids.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To assess the effects of fish (lean or oily) and fish oil consumption on blood lipid concentration during weight loss. DESIGN: Randomized, controlled 8-week trial of energy-restricted diet varying in fish and fish oil content. Subjects, 324 men and women, aged 20-40 years, body mass index 27.5-32.5 kg m(-2), from Iceland, Spain and Ireland, were randomized to one of four groups: (1) control (sunflower oil capsules, no seafood), (2) cod diet (3 x 150 g week(-1)), (3) salmon diet (3 x 150 g week(-1)), (4) fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the diets was similar between the groups and the capsule groups were single-blinded. MEASUREMENTS: Total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol, triacylglycerol (TG) and anthropometrics were measured at baseline and end point. RESULTS: The difference in logTG lowering between the control group and the cod diet, salmon diet and fish oil from baseline to end point was -0.036 (95% CI -0.079 to 0.006), -0.060 (-0.101 to -0.018) and -0.037 (-0.079 to 0.006), respectively. Reduction in TC was about 0.2 mmol l(-1) greater in the fish groups (cod and salmon) than in the control group, but only of borderline significance when adjusting for weight loss. HDL tended to decrease less in the diet groups consuming a significant amount of n-3 fatty acids (salmon and fish oil). CONCLUSION: Weight-loss diet including oily fish resulted in greater TG reduction than did a diet without fish or fish oil. Controlled trials using whole fish as a test meal are encouraged to be able to elucidate the role of different constituents of fish for human health

Brief Report: The Value of a Patient Global Assessment of Disease Activity in Granulomatosis With Polyangiitis (Wegener's)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102695/1/art38248.pd

Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress

10.1172/JCI63051Journal of Clinical Investigation12282793-2806JCIN

Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia

Antiapoptotic BCL2 family members have been implicated in the pathogenesis of acute myelogenous leukemia (AML), but the functional significance and relative importance of individual proteins (e.g., BCL2, BCL-XL, and myeloid cell leukemia 1 [MCL1]) remain poorly understood. Here, we examined the expression of BCL2, BCL-XL, and MCL1 in primary human hematopoietic subsets and leukemic blasts from AML patients and found that MCL1 transcripts were consistently expressed at high levels in all samples tested. Consistent with this, Mcl1 protein was also highly expressed in myeloid leukemic blasts in a mouse Myc-induced model of AML. We used this model to test the hypothesis that Mcl1 facilitates AML development by allowing myeloid progenitor cells to evade Myc-induced cell death. Indeed, activation of Myc for 7 days in vivo substantially increased myeloid lineage cell numbers, whereas hematopoietic stem, progenitor, and B-lineage cells were depleted. Furthermore, Mcl1 haploinsufficiency abrogated AML development. In addition, deletion of a single allele of Mcl1 from fully transformed AML cells substantially prolonged the survival of transplanted mice. Conversely, the rapid lethality of disease was restored by coexpression of Bcl2 and Myc in Mcl1-haploinsufficient cells. Together, these data demonstrate a critical and dose-dependent role for Mcl1 in AML pathogenesis in mice and suggest that MCL1 may be a promising therapeutic target in patients with de novo AML

How Do Bone Marrow Lesions Cause Osteoarthritis Pain? a Structural and Functional Tissue-Based Study

Background/Purpose: Susceptibility to ankylosing spondylitis (AS) is primarily genetic; thus far 113 susceptibility variants for AS have been identified. However, most of the AS associated SNPs do not directly affect protein-coding genes. Studies of disease- and trait-associated SNPs suggest they may act by affecting gene regulatory regions in specific cell types or tissues. Therefore, identifying the AS relevant cell types is crucial for further mechanistic studies. Methods: We applied several bioinformatics methods to utilize epigenetic, gene and protein expression information to identify the primary relevant cell types through which genetic variants associated with AS operate. In total, there are 113 AS associated loci; 39 of them show genome-wide significance in AS-only analyses, whereas the remainder are genome-wide significant in analyses leveraging pleiotrophy with other related diseases (Crohn’s disease (CD), psoriasis, primary sclerosing cholangitis (PSC) and ulcerative colitis (UC))1. Results: AS-associated SNPs are disproportionately found in regions bearing epigenetic marks indicating transcriptional activity found in immune cell types including monocytes, CD4+ and CD8+ T cells, NK cells, regulatory T cells, and B cells. Gene expression studies showed enrichment of AS associated loci in genes specifically expressed in monocytes and NK cells while protein expression study shows protein products of AS associated loci were significantly enriched in CD8+ T cells. Epigenetic analyses also showed evidence that AS-associated signals operate in gut cell types including in mucosa from the small intestine, sigmoid colon and rectum. These findings particularly relate to pleiotropic loci also associated with IBD, psoriasis, and PSC. Conclusion: These findings highlight the role of key immune cell types in the mechanism by which genetic associations with AS drive the disease, as well as providing further evidence for the involvement of the gut in the pathogenesis of AS. 1Ellinghaus D. at al, Nature Genetics 201

High effectiveness of self-help programs after drug addiction therapy

BACKGROUND: The self-help groups Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) are very well established. AA and NA employ a 12-step program and are found in most large cities around the world. Although many have argued that these organizations are valuable, substantial scepticism remains as to whether they are actually effective. Few treatment facilities give clear recommendations to facilitate participation, and the use of these groups has been disputed. The purpose of this study was to examine whether the use of self-help groups after addiction treatment is associated with higher rates of abstinence. METHODS: One hundred and fourteen patients, 59 with alcohol dependency and 55 with multiple drug dependency, who started in self-help groups after addiction treatment, were examined two years later using a questionnaire. Return rate was 66%. Six (5%) of the patients were dead. RESULTS: Intention-to-treat-analysis showed that 38% still participated in self-help programs two years after treatment. Among the regular participants, 81% had been abstinent over the previous 6 months, compared with only 26% of the non-participants. Logistic regression analysis showed OR = 12.6, 95% CI (4.1–38.3), p < 0.001, for participation and abstinence. CONCLUSION: The study has several methodological problems; in particular, correlation does not necessarily indicate causality. These problems are discussed and we conclude that the probability of a positive effect is sufficient to recommend participation in self-help groups as a supplement to drug addiction treatment. PREVIOUS PUBLICATION: This article is based on a study originally published in Norwegian: Kristensen O, Vederhus JK: Self-help programs in drug addiction therapy. Tidsskr Nor Laegeforen 2005, 125:2798–2801

SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy