PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis.

Lipid homeostasis and inflammation are key determinants in atherogenesis, exemplified by the requirement of lipid-laden, foam cell macrophages for atherosclerotic lesion formation. Although the nuclear receptor PPARdelta has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic target in vascular disease is unclear. We show here that orally active PPARdelta agonists significantly reduce atherosclerosis in apoE(-/-) mice. Metabolic and gene expression studies reveal that PPARdelta attenuates lesion progression through its HDL-raising effect and anti-inflammatory activity within the vessel wall, where it suppresses chemoattractant signaling by down-regulation of chemokines. Activation of PPARdelta also induces the expression of regulator of G protein signaling (RGS) genes, which are implicated in blocking the signal transduction of chemokine receptors. Consistent with this, PPARdelta ligands repress monocyte transmigration and macrophage inflammatory responses elicited by atherogenic cytokines. These results reveal that PPARdelta antagonizes multiple proinflammatory pathways and suggest PPARdelta-selective drugs as candidate therapeutics for atherosclerosis.

Dip Pen Nanolithography (DPN): process and instrument performance with NanoInk's NSCRIPTOR system.

Precision nanoscale deposition is a fundamental requirement for much of current nanoscience research and promises to facilitate exciting industrial applications. Tailoring chemical composition and surface structure on the sub-100 nm scale benefits researchers in topics ranging from catalysis, to biological recognition in nanoscale systems, to electronic connectivity on the nanoscale. Precision nanoscale deposition engenders applications such as additive photomask repair and nanodevice fabrication. Dip Pen Nanolithography (DPN) is a scanning-probe-based direct-write technique for generating surface-patterned chemical functionality and discrete structures on the sub-100 nm scale. In this publication we explore the effects of changing tip radius and surface roughness. We find that blunter tips lead to higher minimum line widths and that higher rms surface roughness leads to higher minimum line widths; line edge roughness also increases with substrate roughness and surface feature size. Also, we characterize the performance of the Nscriptor DPN instrument and demonstrate the placement of pattern features with precision better than 10 nm, and size control better than 15% for sub-100 nm features.

International Society of Sports Nutrition position stand: energy drinks.

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the safety and efficacy of the use of energy drinks (ED) or energy shots (ES). The ISSN has concluded the following. 1. Although ED and ES contain a number of nutrients that are purported to affect mental and/or physical performance, the primary ergogenic nutrients in most ED and ES appear to be carbohydrate and/or caffeine. 2. The ergogenic value of caffeine on mental and physical performance has been well-established but the potential additive benefits of other nutrients contained in ED and ES remains to be determined. 3. Consuming ED 10-60 minutes before exercise can improve mental focus, alertness, anaerobic performance, and/or endurance performance. 4. Many ED and ES contain numerous ingredients; these products in particular merit further study to demonstrate their safety and potential effects on physical and mental performance. 5. There is some limited evidence that consumption of low-calorie ED during training and/or weight loss trials may provide ergogenic benefit and/or promote a small amount of additional fat loss. However, ingestion of higher calorie ED may promote weight gain if the energy intake from consumption of ED is not carefully considered as part of the total daily energy intake. 6. Athletes should consider the impact of ingesting high glycemic load carbohydrates on metabolic health, blood glucose and insulin levels, as well as the effects of caffeine and other stimulants on motor skill performance. 7. Children and adolescents should only consider use of ED or ES with parental approval after consideration of the amount of carbohydrate, caffeine, and other nutrients contained in the ED or ES and a thorough understanding of the potential side effects. 8. Indiscriminant use of ED or ES, especially if more than one serving per day is consumed, may lead to adverse events and harmful side effects. 9. Diabetics and individuals with pre-existing cardiovascular, metabolic, hepatorenal, and neurologic disease who are taking medications that may be affected by high glycemic load foods, caffeine, and/or other stimulants should avoid use of ED and/or ES unless approved by their physician.

The implementation of therapeutic hypothermia in the emergency department: a multi-institution case review.

BACKGROUND: The use of therapeutic hypothermia (TH) is a burgeoning treatment modality for post-cardiac arrest patients. OBJECTIVES: We performed a retrospective chart review of patients who underwent post-cardiac arrest TH at eight different institutions across the United States. Our objectives were to assess how TH is currently being implemented in emergency departments and to examine the feasibility of conducting TH research using multi-institution prospective data. METHODS: A total of 94 cases were identified in a 3-year period and submitted for review by participating institutions of the Peri-Resuscitation Consortium. Of those, seven charts were excluded for missing data. Two independent reviewers performed the data abstraction. Results were subsequently compared, and discrepancies were resolved by a third reviewer. We assessed patient demographics, initial presenting rhythm, time until TH initiation, duration of TH, cooling methods and temperature reached, survival to hospital discharge, and neurological status on discharged. RESULTS: The majority of cases had initial cardiac rhythms of asystole or pulseless electrical activity (55.2%), followed by ventricular tachycardia or fibrillation (34.5%). The inciting cardiac rhythm was unknown in 10.3% of cases. Time to initiation of TH ranged from 0 to 783 minutes with a mean time of 99 minutes (SD=132). Length of TH ranged from 25 to 2,171 minutes with a mean time of 1,191 minutes (SD=536). The average minimum temperature achieved was 32.5°C, with a range from 27.6°C to 36.7°C (SD=1.5°C). Of the 87 charts reviewed, 29 (33.3%) of the patients survived to hospital discharge. CONCLUSION: The implementation of TH across the country is extremely varied with no universally accepted treatment. While our study is limited by sample size, it illustrates some compelling trends. A large, prospective, multicenter trial or registry is necessary to elucidate further the optimal parameters for TH and its benefit in various population subsets.

Self-leveling two-dimensional probe arrays for Dip Pen Nanolithography.

Scanning probe lithography (SPL) has witnessed a dramatic transformation with the advent of two-dimensional (2D) probe arrays. Although early work with single probes was justifiably assessed as being too slow to practically apply in a nanomanufacturing context, we have recently demonstrated throughputs up to 3x10(7) microm(2)/h--in some cases exceeding e-beam lithography--using centimeter square arrays of 55,000 tips tailored for Dip Pen Nanolithography (DPN). Parallelizing DPN has been critical because there exists a need for a lithographic process that is not only high throughput, but also high resolution (DPN has shown line widths down to 14 nm) with massive multiplexing capabilities. Although previous methods required non-trivial user manipulation to bring the 2D array level to the substrate, we now demonstrate a self-leveling fixture for NanoInk's 2D nano PrintArray. When mounted on NanoInk's NLP 2000, the 55,000 tip array can achieve a planarity of <0.1 degrees with respect to the substrate in a matter of seconds, with no user manipulation required. Additional fine-leveling routines (<2 min of user interaction) can improve this planarity to <0.002 degrees with respect to the substrate-a Z-difference of less than 600 nm across 1 cm(2) of surface area. We herein show highly homogeneous etch-resist nanostructure results patterned from a self-leveled array of DPN pens, with feature size standard deviation of <6% across a centimeter square sample. We illustrate the mechanisms and methods of the self-leveling fixture, and detail the advantages thereof. Finally, we emphasize that this methodology brings us closer to the goal of true nanomanufacturing by automating the leveling process, reducing setup time by at least a factor of 10, enhancing the ease of the overall printing process, and ultimately ensuring a more level device with subsequently homogeneous nanostructures.

Non-traumatic splenic rupture in a patient with Kasabach-Merritt syndrome.

This report presents a case illustrating the complications of Kasabach-Merritt syndrome in a 22-year-old man. The patient presented with acute abdominal pain and profound anaemia; a CT scan revealed intraperitoneal bleeding from spontaneous splenic rupture. The patient underwent initial emergency laparotomy and splenectomy, with a subsequent further laparotomy to control haemorrhage. Blood products requirements were extensive: 28 units red blood cells, 14 units fresh frozen plasma, 10 units platelets, 10 units cryoprecipitate and 2× Novo VII. He was then transferred to a nearby tertiary care unit for further management to control his coagulaopathy and he made a full recovery after 4 weeks.

Structural genomics of the severe acute respiratory syndrome coronavirus: nuclear magnetic resonance structure of the protein nsP7.

Here, we report the three-dimensional structure of severe acute respiratory syndrome coronavirus (SARS-CoV) nsP7, a component of the SARS-CoV replicase polyprotein. The coronavirus replicase carries out regulatory tasks involved in the maintenance, transcription, and replication of the coronavirus genome. nsP7 was found to assume a compact architecture in solution, which is comprised primarily of helical secondary structures. Three helices (alpha2 to alpha4) form a flat up-down-up antiparallel alpha-helix sheet. The N-terminal segment of residues 1 to 22, containing two turns of alpha-helix and one turn of 3(10)-helix, is packed across the surface of alpha2 and alpha3 in the helix sheet, with the alpha-helical region oriented at a 60 degrees angle relative to alpha2 and alpha3. The surface charge distribution is pronouncedly asymmetrical, with the flat surface of the helical sheet showing a large negatively charged region adjacent to a large hydrophobic patch and the opposite side containing a positively charged groove that extends along the helix alpha1. Each of these three areas is thus implicated as a potential site for protein-protein interactions.

Prevalence of comorbid conditions and prescription medication use among patients with gout and hyperuricemia in a managed care setting.

BACKGROUND: : Comorbid disorders and multiple prescription drug use are common among patients with gout and/or hyperuricemia and may influence the clinical course and outcome of gout. OBJECTIVE: : We wanted to document the conditions and associated medications in a large group of patients with gout in a managed care setting. METHODS: : This study was a 2-year, retrospective, administrative claims analysis examining comorbid conditions and medication use among managed care enrollees with gout/hyperuricemia across the United States. RESULTS: : Of the 9482 study subjects (82.1% men, mean age 52 years), 57.9% had hypertension, 45.3% had a lipid disorder, 32.5% had both conditions, and 19.9% had diabetes mellitus. During the 24-month follow-up period, subjects had 5 +/- 3.14 (mean +/- standard deviation) different comorbid conditions and filled prescriptions for of 11.0 +/- 7.90 different medications. The most commonly filled prescriptions included antihypertensive drugs, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), and nonsteroidal antiinflammatory drugs (NSAIDs). CONCLUSIONS: : The study indicates a high prevalence of both comorbid conditions and multiple medication use among managed care enrollees with gout and/or hyperuricemia. Heightened awareness of these associated disorders is important because they may warrant treatment of their own accord and often some modification of gout management. Drugs, particularly diuretics and prophylactic aspirin, could potentially contribute to the development of hyperuricemia and gout.