Embracing Biological and Methodological Variance in a New Approach to Pre-Clinical Stroke Testing

Abstract High-profile failures in stroke clinical trials have discouraged clinical translation of neuroprotectants. While there are several plausible explanations for these failures, we believe that the fundamental problem is the way clinical and pre-clinical studies are designed and analyzed for heterogeneous disorders such as stroke due to innate biological and methodological variability that current methods cannot capture. Recent efforts to address pre-clinical rigor and design, while important, are unable to account for variability present even in genetically homogenous rodents. Indeed, efforts to minimize variability may lessen the clinical relevance of pre-clinical models. We propose a new approach that recognizes the important role of baseline stroke severity and other factors in influencing outcome. Analogous to clinical trials, we propose reporting baseline factors that influence outcome and then adapting for the pre-clinical setting a method developed for clinical trial analysis where the influence of baseline factors is mathematically modeled and the variance quantified. A new therapy’s effectiveness is then evaluated relative to the pooled outcome variance at its own baseline conditions. In this way, an objective threshold for robustness can be established that must be overcome to suggest its effectiveness when expanded to broader populations outside of the controlled environment of the PI’s laboratory. The method is model neutral and subsumes...
Source: Translational Stroke Research - Category: Neurology Source Type: research

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The National Institutes of Health (NIH) would receive $34.4 billion in FY 2020, roughly $4.7 billion or 13 percent below the levels enacted by Congress for FY 2019, according to the President’s Budget released on March 11. The budget for NIH includes $492 million in funding made available through the 21st Century Cures Act and $150 million in mandatory funding. The leading biomedical research agency in the world would receive budget cuts across the board. All NIH centers are slated for budget reductions: National Cancer Institute: -8.7 percent National Heart, Lung, and Blood Institute: -14 percent National Inst...
Source: Public Policy Reports - Category: Biology Authors: Source Type: news
Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal of the occlusion being the only therapeutic option. Reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain barrier. Its mechanism, however, is unknown. Here, we identified type 5 NADPH oxidase (NOX5), a calcium-activated, ROS-forming enzyme, as the missing link. Using a humanized knockin (KI) mouse model and in vitro organotypic cultures, we found that reoxygenation or calcium overload increased brain ROS levels in a NOX5-dependent manner. In vivo, postischemic ROS formation, in...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: Available online 18 March 2019Source: Brain StimulationAuthor(s): Brigitte C. Kaufmann, Manuela Pastore-Wapp, Maria Lübeck, Monica Koenig, Stephan Bohlhalter, Tim Vanbellingen, Dario Cazzoli, Thomas Nyffeler
Source: Brain Stimulation - Category: Neurology Source Type: research
CONCLUSION: Coarctation of the aorta is, therefore, a cardiac malformation of significant importance due to its incidence and its significant mortality risk. In this sense, the early diagnosis stands out as an essential piece for better prognosis of the patient.RESUMO INTRODU ÇÃO: A coarctação da aorta é uma cardiopatia congênita caracterizada por um estreitamento que ocorre na artéria aorta. Essa constrição pode ocorrer em qualquer local ao longo de toda a sua extensão, entretanto, é mais comum entre a origem da artéria subclávia esq...
Source: Revista da Associacao Medica Brasileira - Category: General Medicine Source Type: research
The study suggests that the prescription fish oil pill, not to be confused with over-the-counter supplements, reduces the lifetime risk of dying from heart disease; having a non-fatal heart attack or stroke; or needing heart surgery or hospitalization for a heart complication.
Source: WebMD Health - Category: Consumer Health News Source Type: news
Raised blood pressure with age, hypertension, is a major downstream consequence of low-level biochemical damage and cellular dysfunction, converting it into high-level structural damage in the body and brain. Hypertension is an important proximate contributing cause of ultimately fatal age-related conditions of the cardiovascular system, kidneys, brain, and lungs, among others. Pressure damage in delicate tissues degrades function in many organs, particularly in the central nervous system where there is little to no regeneration capable of reversing that damage. More subtly, hypertension also causes heart muscles to enlarg...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
New guidelines say aspirin should rarely be used to prevent cardiovascular disease.
Source: Health News - UPI.com - Category: Consumer Health News Source Type: news
People who consumed at least two sugar-sweetened drinks per day were about one-third more likely to die of heart disease or stroke, versus those who rarely had these drinks.
Source: WebMD Health - Category: Consumer Health News Source Type: news
Abstract Assay technologies capable of detecting biomarker concentrations in unprocessed whole blood samples are fundamental for applications in medical diagnostics. SERS nano-tags integrated magnetic-separation biosensor (MSB) was realized for the first time for immunoassay in whole blood. The reliability and sensitivity of this method rely, in a large extent, on the quality and properties of the SERS nano-tags. The constructed silicacoated Ag SERS nano-tags as labels were used in a rapid and specific MSB immune sensor to detect Matrix Metalloproteinases 9 (MMP-9) in unprocessed blood samples. With fast screening...
Source: Talanta - Category: Chemistry Authors: Tags: Talanta Source Type: research
Abstract Hypertension increases the risk of heart disease and stroke, is commonly known as a silent killer disease and considered as one of the key risk factor for premature death and disability over the world. Herein, we report for the first time a sensitive, costless and reproducible voltammetric method for individual determination of five antihypertensive drugs namely, propranolol (PRO), timolol (TIM), amlodipine (AML), amiloride (AMI) and triamterene (TRI) using differential pulse voltammetry at bare/unmodified screen-printed carbon electrodes (SPEs) in presence of sodium dodecyl sulfate (SDS). Each drug exhib...
Source: Talanta - Category: Chemistry Authors: Tags: Talanta Source Type: research
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