Differential Expression Gene Explorer (DrEdGE): a tool for generating interactive online visualizations of gene expression datasets.

SUMMARY: Differential Expression Gene Explorer (DrEdGE) is a web-based tool that guides genomicists through easily creating interactive online data visualizations, which colleagues can query according to their own conditions to discover genes, samples or patterns of interest. We demonstrate DrEdGE's features with three example websites generated from publicly available datasets-human neuronal tissue, mouse embryonic tissue and Caenorhabditis elegans whole embryos. DrEdGE increases the utility of large genomics datasets by removing technical obstacles to independent exploration. AVAILABILITY AND IMPLEMENTATION: Freely available at http://dredge.bio.unc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The effect of EDTA-based chelation on patients with diabetes and peripheral artery disease in the Trial to Assess Chelation Therapy (TACT).

OBJECTIVE: Approximately 1 in 7 US adults have diabetes; and over 60% of deaths in patients with diabetes have cardiac disease as a principal or contributing cause. Both coronary and peripheral artery disease (PAD) identify high-risk cohorts among patients with diabetes. We have previously demonstrated improved cardiovascular outcomes with edetate disodium-based chelation in post-MI patients with diabetes, enrolled in the Trial to Assess Chelation Therapy (TACT). In these analyses we further studied the effect size of patients with diabetes and severe disease in 2 vascular beds; coronaries, and lower extremity arteries. We questioned whether greater atherosclerotic burden would attenuate the observed beneficial effect of edetate disodium infusions. RESEARCH DESIGN AND METHODS: The multicenter TACT used a double blind, placebo controlled, 2 × 2 factorial design with 1708 participants, randomly assigned to receive edetate disodium-based chelation, or placebo and high dose oral vitamins or placebo. There were 162 (9.5% of 1708) post-MI patients with a diagnosis of diabetes mellitus and PAD for this post hoc analysis. Patients received up to 40 double-blind intravenous infusions of edetate disodium-based chelation, or placebo. The composite primary endpoint of TACT consisted of death from any cause, myocardial infarction, stroke, coronary revascularization and hospitalization for angina. RESULTS: The median age was 66 years, 15% female, 5% non-Caucasian, and BMI was 31. Insulin was used by 32% of patients. Active infusions significantly reduced the primary endpoint compared with placebo infusions (HR, 0.52; 95% CI, 0.30-0.92; P = 0.0069), with a 30% absolute risk reduction in the primary endpoint. There was a marked reduction in total mortality from 24% to 11%, although of borderline significance (P = 0.052). CONCLUSION: Atherosclerotic disease in multiple vascular beds did not attenuate the beneficial effect of edetate disodium infusions in post MI patients with diabetes. Studies now in progress will prospectively test this post hoc finding.

Concussion management in combat sports: consensus statement from the Association of Ringside Physicians.

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1-7 To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.

A Transcriptional Lineage of the Early C. elegans Embryo.

During embryonic development, cells must establish fates, morphologies, and behaviors in coordination with one another to form a functional body. A prevalent hypothesis for how this coordination is achieved is that each cell's fate and behavior is determined by a defined mixture of RNAs. Only recently has it become possible to measure the full suite of transcripts in a single cell. Here we quantify genome-wide mRNA abundance in each cell of the Caenorhabditis elegans embryo up to the 16-cell stage. We describe spatially dynamic expression, quantify cell-specific differential activation of the zygotic genome, and identify genes that were previously unappreciated as being critical for development. We present an interactive data visualization tool that allows broad access to our dataset. This genome-wide single-cell map of mRNA abundance, alongside the well-studied life history and fate of each cell, describes at a cellular resolution the mRNA landscape that guides development.

Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock.

Vasopressors are gaining renewed interest as treatment adjuncts in hemorrhagic shock. The ideal vasoconstrictor will increase systemic blood pressure without increasing pulmonary vascular resistance (PVR), which hinders pulmonary perfusion and exacerbates hypoxemia. However, the selectivity of pressors for pulmonary versus systemic vasoconstriction during hemorrhage has not been characterized. The purpose of this study was to test the hypothesis that vasopressin (VP) has distinct effects on pulmonary versus systemic hemodynamics, unlike the catecholamine vasopressors norepinephrine (NE) and phenylephrine (PE). Anesthetized and ventilated pigs were assigned to resuscitation with saline only (n = 7) or saline with VP (n = 6), NE (n = 6), or PE (n = 6). Animals were hemorrhaged to a target volume of 30 mL/kg and a mean arterial pressure of 35 mmHg. One hour after the start of hemorrhage, animals were resuscitated with saline up to one shed blood volume, followed by either additional saline or a vasopressor. Hemodynamics and oxygenation were measured hourly for 4 h after the start of hemorrhage. Vasopressin increased systemic vascular resistance (SVR) while sparing the pulmonary vasculature, leading to a 45% decrease in the PVR/SVR ratio compared with treatment with PE. Conversely, NE induced pulmonary hypertension and led to an increased PVR/SVR ratio associated with decreased oxygen saturation. Phenylephrine and crystalloid had no significant effect on the PVR/SVR ratio. Sparing of pulmonary vasoconstriction occurs only with VP, not with administration of crystalloid or catecholamine pressors. The ability of VP to maintain blood oxygenation indicates that VP may prevent hypoxemia in the management of hemorrhagic shock.

Percutaneous temporary aortic valve: a proof-of-concept animal model.

BACKGROUND AND AIM OF THE STUDY: An early prototype of a temporary aortic valve (TAV) catheter system was evaluated for its potential to serve as an integrated device for aortic valve intervention and replacement. The prototype consisted of two essential components: a central catheter for the delivery of aortic valve interventional tools (valve debulking, resection, replacement); and a balloon-inflatable temporary valve for hemodynamic support when the native aortic valve is removed. After valve replacement, the TAV catheter system is designed to be readily withdrawn from the subject. METHODS: Individual aspects of both components of the prototype were examined in experiments with four pigs. The central catheter was used to deliver a self-expanding stent for native aortic valve ablation to create acute severe aortic insufficiency (AI). The balloon-TAV was deployed in the proximal aorta to control the induced AI. Electrocardiographic (ECG), cardiac output (CO), pulmonary wedge pressure (PWP), left ventricular (LV) pressure, and aortic pressure proximal and distal from the TAV were recorded. RESULTS: The central catheter was successful in delivering and deploying the valve ablation stent at the annulus to create massive AI; the LV diastolic pressure was increased from 12.6 +/- 1.1 to 32.4 +/- 2.0 mmHg (p < 0.001) with valve ablation. The deployed TAV in the proximal aorta led to a re-narrowing of the distal pulse pressure with a drop in the LV diastolic pressure to 21.5 +/- 1.5 mmHg (p < 0.001). During TAV support, some PWP lowering and a CO rise occurred, but these did not achieve statistical significance; no significant acute ECG changes were noted. CONCLUSION: In this early prototype, the TAV catheter system demonstrated the potential to serve as an integrated device for both aortic valve modification and replacement.

Treatment of mercury intoxication with dimercaptopropanesulfonate.

Treatment of mercury toxicity is controversial and not well studied. Currently there are several proposed methods of chelation and subsequent removal of mercury from the body, including dimercaptopropanesulfonate, dimercaptosuccinic acid, intravenous vitamin C and edetate. Although many of these methods are not approved by the US Food and Drug Administration, they are being used with modest success. Because of the lack of information regarding treatment outcomes, Medical-Dental Pharmacy performed a retrospective analysis of 28 randomly selected patients for whom we had suppplied dimercaptopropanesulfonate in the last 6 months. Dimercaptopropanesulfonate is used to treat mercury toxicity and as provacation to perform mercury testing. Two of the 28 selected patients who received the prescription decided against treatment. Of the remaining 26 patients, 8 patients were using dimercaptopropanesulfonate for treatment with varying success. Overall, this retrospective study shows that dimercaptopropanesulfonate is a safe and effective agent to use for initial mercury level testing.