Cardiovascular outcome trials in obesity: A review.

Obesity is a global epidemic associated with over 200 health complications and a significant risk of developing cardiovascular disease (CVD), partly by increasing classical risk factors such as lipid and glucose levels and blood pressure. Weight loss through lifestyle interventions, pharmacotherapy and/or bariatric surgery improves CV risk factors. Cardiovascular outcome trials (CVOTs) of anti-obesity medications aim to evaluate the CV safety and benefits of pharmacotherapy. Many CVOTs in obesity have either failed to demonstrate a CV benefit or have been terminated prematurely because of safety issues, prompting regulatory agencies to define new requirements (based on those for CVOTs in type 2 diabetes [T2D]). CVOTs of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in T2D have demonstrated that some GLP-1RAs reduce CV risk and may help inform future CVOTs in obesity, given the approval of liraglutide 3.0 mg for obesity. In this review, the evidence for the link between obesity and CVD is considered in the context of studies showing that weight loss improves markers of CV risk and risk of adverse CV events. The review also examines the CVOTs in obesity that have been conducted to date and those under way, such as the SELECT trial with subcutaneous semaglutide of 2.4 mg

The 1α,25(OH)2D3 Analogs ZK159222 and ZK191784 Show Anti-Inflammatory Properties in Macrophage-Induced Preadipocytes via Modulating the NF-κB and MAPK Signaling.

Purpose:Key research findings suggest that attenuating metaflammation in adipose tissue might be a strategic step to prevent the metabolic syndrome and its associated disease outcomes. The anti-inflammatory effects of 1α,25(OH)2D3 have been confirmed in our previous studies, but adverse effects induced at high concentrations restrict its potential clinical translation. Two synthetic 1α,25(OH)2D3 analogs ZK159222 and ZK191784 have manifested promising tissue-specific immunomodulatory actions, but limited data are available on adipose tissue. Hence, in this study, we investigated whether ZK159222 and ZK191784 act on preadipocytes or macrophages to attenuate metaflammatory responses via modulating inflammatory and metabolic signaling in macrophage-induced preadipocytes. Methods:Preadipocyte-specific effects of ZK159222 and ZK191784 on macrophage-induced preadipocytes were tested by pre-incubating and incubating preadipocytes with the analogs and MacCM. Separately, macrophage-specific effects of both analogs on macrophage-induced preadipocytes were tested by incubating preadipocytes with analog-MacCM or MacCM. The effects of 1α,25(OH)2D3 were also examined and set as the positive control. Metaflammatory responses were determined as the concentrations and gene expression of major pro-inflammatory cytokines including IL-1β, IL-6, IL-8, MCP-1 and RANTES, measured using ELISA and qPCR. Inflammatory and metabolic signaling including NF-κB and MAPK were probed using Western blotting. Results:ZK159222 and ZK191784 act on preadipocytes and macrophages to decrease the secretion and gene expression of the major pro-inflammatory cytokines in macrophage-induced preadipocytes. The anti-inflammatory effects were at least as potent as 1α,25(OH)2D3, and no preadipocyte apoptosis was induced at high concentrations. In addition, mostly at high concentrations, both analogs moderately decreased the phosphorylation of relA, p44/42 and p38 MAPK in macrophage-induced preadipocytes. Conclusion:ZK159222 and ZK191784 act on macrophages and preadipocytes to attenuate metaflammatory responses in macrophage-induced preadipocytes, by decreasing phosphorylation of relA/NF-κB, p44/42 and p38 MAPK

Effect of the Negative Ion Band on Athletic Performance

Negative Ion bands have been suggested to increase various areas of athletic performance. At this time, the authors are not aware of any studies on these bands. Purpose: To determine if a True Power Energy Band (True Power LLC, Melrose, MA) had an effect on various measures of performance. Methods: Forty-one subjects (age = 29.3±7.1 yrs, ht = 171.5±9.7 cm, wt = 85.4±23.2 kg) had their height and weight measured and were then randomized to wear the True Power band (TB) or a silver bracelet placebo band (PB) (Hobby Lobby). After 5 days, subjects were assessed on reaction time using a color response test and a response test in which the subject clicked a highlighted dot as it appeared in a 5x5 table (www.intelligencetest.com/reflex/index). The subjects then performed a standard balance test (stork test) without shoes, two flexibility tests (V-sit-and-reach & trunk rotation), and two strength tests (hand grip using a dynamometer & push-ups to exhaustion). The tests were conducted in this order with as much rest between trials as needed. One week later, this same procedure was followed but with the opposing band. Repeated measures ANOVA was used to determine if differences exist between the bands, with Alpha set at .05. Results: There were no significant differences in the tests of color (TB = 0.43±0.14, PB = 0.41±0.11 sec), dots (TB = 16.9±3.0, PB = 17.0±2.6 score), stork (TB = 4.4±3.4, PB = 4.7±4.1 sec), V-sit-and-reach (TB = 15.2±16.8, PB = 15.5±17.3 cm), trunk rotation (TB = 35.8±15.0, PB = 37.3±14.0 cm), hand grip (TB = 42.4±12.1, PB = 42.8±11.0 kg), and push-ups (TB = 23.4±10.5, PB = 25.8±11.7 total), p \u3e .05 for all tests. Conclusion: There seems to be no effect of Negative Ion bands on tests of reaction time, balance, flexibility, or muscular strength. The claims of performance in these types of bands have yet to be validated

Evolving proteins at Darwin's bicentenary

A report of the Biochemical Society/Wellcome Trust meeting 'Protein Evolution - Sequences, Structures and Systems', Hinxton, UK, 26-27 January 2009

Immersive Visualization for Enhanced Computational Fluid Dynamics Analysis

Modern biomedical computer simulations produce spatiotemporal results that are often viewed at a single point in time on standard 2D displays. An immersive visualization environment (IVE) with 3D stereoscopic capability can mitigate some shortcomings of 2D displays via improved depth cues and active movement to further appreciate the spatial localization of imaging data with temporal computational fluid dynamics (CFD) results. We present a semi-automatic workflow for the import, processing, rendering, and stereoscopic visualization of high resolution, patient-specific imaging data, and CFD results in an IVE. Versatility of the workflow is highlighted with current clinical sequelae known to be influenced by adverse hemodynamics to illustrate potential clinical utility

Calculating fertilizer value of supplemental feed for cattle on pasture (2006)

Most cattle maintained on pasture receive supplemental feed during some portion of the year. Supplements are commonly fed to grazing cattle when pasture forage quality and quantity are below animal requirements

Transverse momentum distributions inside the nucleon from lattice QCD

We study transverse momentum dependent parton distribution functions (TMDs) with non-local operators in lattice QCD, using MILC/LHPC lattices. Results obtained with a simplified operator geometry show visible dipole deformations of spin-dependent quark momentum densities.United States. Dept. of Energy (grant DE-FG02-94ER40818