Protein Adducts of Iso[4]levuglandin E2, a Product of the Isoprostane Pathway, in Oxidized Low Density Lipoprotein

Levuglandin (LG) E2, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H2, avidly binds to proteins. That LGE2-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE2-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now iso[4]LGE2-protein epitopes produced by radical-induced oxidation of arachidonic acid in the presence of protein were detected with an enzyme-linked immunosorbent assay. Iso[4]LGE2-protein epitopes are also generated during free radical-induced oxidation of LDL. All of the LGE2isomers generated upon oxidation of LDL are efficiently sequestered by covalent adduction with LDL-based amino groups. The potent electrophilic reactivity of iso-LGs can be anticipated to have biological consequences beyond their obvious potential as markers for specific arachidonate-derived protein modifications that may be of value for the quantitative assessment of oxidative injury

Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy

The Crabby Creek Initiative: Building and Sustaining An Interdisciplinary Community Partnership

In this article, we identify the steps and strategies that emerged through an interdisciplinary, community-based participatory research (CBPR) project—the Crabby Creek Initiative. The Initiative was undertaken jointly by Cabrini College faculty in biology and psychology, the Valley Creek Restoration Partnership (VCRP), the Stroud Water Research Center, (SWRC) and local residents of this eastern Pennsylvania region. The paper examines the phases the partners have gone through and the strategies used as the building blocks of partnerships in the process of collaboration: trust, mutual design, shared implementation, joint ownership, and dissemination of knowledge, the building blocks of sustainable partnerships. Ultimately, the lessons learned have the potential to galvanize practitioners to engage not only in citizen science, but also more broadly in the practice of applied and engaged democracy

Enabling long-term oceanographic research : changing data practices, information management strategies and informatics

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 2132-2142, doi:10.1016/j.dsr2.2008.05.009.Interdisciplinary global ocean science requires new ways of thinking about data and data management. With new data policies and growing technological capabilities, datasets of increasing variety and complexity are being made available digitally and data management is coming to be recognized as an integral part of scientific research. To meet the changing expectations of scientists collecting data and of data reuse by others, collaborative strategies involving diverse teams of information professionals are developing. These changes are stimulating the growth of information infrastructures that support multi-scale sampling, data repositories, and data integration. Two examples of oceanographic projects incorporating data management in partnership with science programs are discussed: the Palmer Station Long-Term Ecological Research program (Palmer LTER) and the United States Joint Global Ocean Flux Study (US JGOFS). Lessons learned from a decade of data management within these communities provide an experience base from which to develop information management strategies – short-term and long-term. Ocean Informatics provides one example of a conceptual framework for managing the complexities inherent to sharing oceanographic data. Elements are introduced that address the economies-of-scale and the complexities-of-scale pertinent to a broader vision of information management and scientific research.Support is provided by NSF OPP-0217282, OCE-0405069, HSD-0433369 and Scripps Institution of Oceanography (K.S.Baker) and by NSF OCE-8814310, OCE-0097291, OCE- 0510046 and OCE-0646353 (C.Chandler)

Policy Recommendations for Meeting the Grand Challenge to Achieve Equal Opportunity and Justice

This brief was created forSocial Innovation for America’s Renewal, a policy conference organized by the Center for Social Development in collaboration with the American Academy of Social Work & Social Welfare, which is leading theGrand Challenges for Social Work initiative to champion social progress. The conference site includes links to speeches, presentations, and a full list of the policy briefs

Mars as a "natural laboratory" for studying surface activity on a range of planetary bodies

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Diverse perspectives on interdisciplinarity from Members of the College of the Royal Society of Canada

Various multiple-disciplinary terms and concepts (although most commonly interdisciplinarity, which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity, represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world\u27s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demands thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper-that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues

Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study.

The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization of the model(s) being used. There are numerous models that have been generated to study Alzheimer\u27s disease (AD) and the underlying pathogenesis of the disease. While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model. The Model Organism Development and Evaluation for Late-Onset Alzheimer\u27s Disease (MODEL-AD) consortium was assembled by the National Institute on Aging (NIA) to develop more robust animal models of AD with increased relevance to human disease, standardize the characterization of AD mouse models, improve preclinical testing in animals, and establish clinically relevant AD biomarkers, among other aims toward enhancing the translational value of AD models in clinical drug design and treatment development. Here we have conducted a detailed characterization of the 5XFAD mouse, including transcriptomics, electroencephalogram

Psoriasis and Hypertension Severity: Results from a Case-Control Study

BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients