Rethinking daily aspirin for primary prevention

An updated meta-analysis of newer RCTs seems to settle the matter as to whether to use aspirin in individuals with no known history of atherosclerotic CVD. PRACTICE CHANGER: Do not routinely use aspirin for primary prevention of cardiovascular disease (CVD). There is no identifiable mortality benefit for those without established CVD--regardless of risk factors. And aspirin therapy increases the risk of major bleeding. STRENGTH OF RECOMMENDATION: Based on a meta-analysis of 11 randomized trials involving 157,248 patients who received aspirin for primary prevention

Monotherapy for nonvalvular A-fib with stable CAD?

A meta-analysis found oral anticoagulant (OAC) monotherapy provided efficacy comparable to OAC plus single antiplatelet therapy--with lower bleeding risk.Thomas P. Garigan, MD, MA; John S. Earwood, MD; Michal Poplawski, MD (Department of Soldier and Family Medicine, Eisenhower Army Medical Center, Fort Gordon, GA)Includes bibliographical reference

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

Reversal of diabetic nephropathy by a ketogenic diet.

Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined

Nephropathy-related gene expression in the diabetic Akita mice is reversed by the ketogenic diet.

<p>(A) Kidney gene expression changes associated with the Akita mutation and not in the db/db diabetics that are reversed by the ketogenic diet. The pattern of reversal is particularly evident in the clusterograms form the entire (B) Oxidative Stress and Antioxidant Defense PCR Array and (C) Stress & Toxicity PCR array from SABiosciences. The clusterograms (heat maps) represent relative expression levels for all samples and all genes included on the real-time PCR arrays. Data for each gene in (A) was normalized to a panel of housekeeping transcripts and expressed as fold change compared to the WT-Chow group (except for nephrin, podocin, and zo-1 – see <i>Research Design and </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018604#s2" target="_blank"><i>Methods</i></a>). Data are means ± SE (n = 4–5 for all groups). *p<0.05 (ANOVA) vs. WT-Chow group (or vs. diabetic-Chow groups as indicated by the horizontal brackets).</p

List of genes whose expression is described in the manuscript.

<p>List of genes whose expression is described in the manuscript.</p

Improvement in glomerular histopathology in diabetic <i>db/db</i> mice fed the ketogenic diet.

<p>Morphometric study demonstrating the mean values of glomerular deposition of PAS positive material(A) (% of total glomerular area) in <i>db/db</i> using light microscopy in fixed kidney stained with periodic-acid-Schiff stain as described in <i>Research Design and </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018604#s2" target="_blank"><i>Methods</i></a>. Images of representative glomerular histology from WT-Chow (B), WT-Keto (C), <i>db/db</i>-Chow (D), <i>db/db</i>-Keto (E). *p<0.05 (ANOVA) vs. Control groups (or vs. db/db-Chow group - horizontal bracket).</p

Kidney expression of duox1 and sod1 is affected by the ketogenic diet in <i>db/db</i> diabetic mice.

<p>(A) Ketogenic diet induces Sod1 expression and normalizes Duox1 expression in the <i>db/db</i> mice. The transcripts that show consistent patterns across <i>db/db</i> data sets are depicted in the clusterograms from the (B) Oxidative Stress and Antioxidant Defense PCR Array and (C) Stress & Toxicity PCR array from SABiosciences. The clusterograms (heat maps) represent relative expression levels for all samples and selected genes included on the real-time PCR arrays. Data for each gene in (A) was normalized to a panel of housekeeping transcripts and expressed as fold change compared to the WT-Chow group. Data are means ± SE (n = 4 for all groups). *p<0.05 (ANOVA) vs. WT-Chow group (or vs. diabetic-Chow groups as indicated by the horizontal bracket).</p

Physiological characteristics.

<p>†p<0.05 compared to respective Wt-Chow groups.</p