University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Evaluating two-step PCA of ERP data with Geomin, Infomax, Oblimin, Promax, and Varimax rotations.

Abstract: Principal components analysis (PCA) can facilitate analysis of event-related potential (ERP) components Geomin, Oblimin, Varimax, Promax, and Infomax (independent components analysis) were compared using a simulated data set Kappa settings for Oblimin and Promax were also systematically compared Finally, the rotations were also analyzed in a two-step PCA procedure, including a contrast between spatiotemporal and temporospatial procedures Promax was found to give the best overall results for temporal PCA, and Infomax was found to give the best overall results for spatial PCA The current practice of kappa values of 3 or 4 for Promax and 0 for Oblimin was supported Source analysis was meaningfully improved by temporal Promax PCA over the conventional windowed difference wave approach (from a median 329 mm error to 67 mm) It was also found that temporospatial PCA produced modestly improved results over spatiotemporal PCA

Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning

Abstract: More than 10 years after its discovery, the function of cyclooxygenase-2 (COX-2) in the cardiovascular system remains largely an enigma. Many scholars have assumed that the allegedly detrimental effects of COX-2 in other systems (e.g. proinflammatory actions and tumorigenesis) signify a detrimental role of this protein in cardiovascular homeostasis as well. This view, however, is ill-founded. Recent studies have demonstrated that ischemic preconditioning (PC) upregulates the expression and activity of COX-2 in the heart, and that this increase in COX-2 activity mediates the protective effects of the late phase of PC against both myocardial stunning and myocardial infarction. An obligatory role of COX-2 has been observed in the setting of late PC induced not only by ischemia but also by delta-opioid agonists and physical exercise, supporting the view that the recruitment of this protein is a central mechanism whereby the heart protects itself from ischemia. The beneficial actions of COX-2 appear to be mediated by the synthesis of PGE(2) and/or PGI(2). Since inhibition of iNOS in preconditioned myocardium blocks COX-2 activity whereas inhibition of COX-2 does not affect iNOS activity, COX-2 appears to be downstream of iNOS in the protective pathway of late PC. The results of these studies challenge the widely accepted paradigm that views COX-2 activity as detrimental. The discovery that COX-2 plays an indispensable role in the anti-stunning and anti-infarct effects of late PC demonstrates that the recruitment of this protein is a fundamental mechanism whereby the heart adapts to stress, thereby revealing a novel, hitherto unappreciated cardioprotective function of COX-2. From a practical standpoint, the recognition that COX-2 is an obligatory co-mediator (together with iNOS) of the protection afforded by late PC has implications for the clinical use of COX-2 selective inhibitors as well as nonselective COX inhibitors. For example, the possibility that inhibition of COX-2 activity may augment myocardial cell death by obliterating the innate defensive response of the heart against ischemia/reperfusion injury needs to be considered and is the object of much current debate. Furthermore, the concept that the COX-2 byproducts, PGE(2) and/or PGI(2), play a necessary role in late PC provides a basis for novel therapeutic strategies designed to enhance the biosynthesis of these cytoprotective prostanoids in the ischemic myocardium. From a conceptual standpoint, the COX-2 hypothesis of late PC expands our understanding of the function of this enzyme in the cardiovascular system and impels a critical reassessment of current thinking regarding the biologic significance of COX-2.

Exosomes: Mediators of Neurodegeneration, Neuroprotection and Therapeutics

Abstract: Exosomes have emerged as prominent mediators of neurodegenerative diseases where they have been shown to carry disease particles such as beta amyloid and prions from their cells of origin to other cells. Their simple structure and ability to cross the blood-brain barrier allow great opportunity to design a "makeup" with drugs and genetic elements, such as siRNA or miRNA, and use them as delivery vehicles for neurotherapeutics. Their role in neuroprotection is evident by the fact that they are involved in the regeneration of peripheral nerves and repair of neuronal injuries. This review is focused on the role of exosomes in mediating neurodegeneration and neuroprotection.

Oral bacteria and cancer.

Abstract: Over a number of years, epidemiological studies established several well-defined risk factors for cancer, including age, heredity, diet, tobacco use, chronic viral infections, and inflammation. Paradoxically, the success of these studies left little room for incorporation of any new factors or causative agents, and, consequently, the idea that a bacterial infection could contribute to cancer was generally disregarded. However, landmark studies in the early 1990s established Helicobacter pylori as a causative agent of gastric cancers, resulting in a paradigm shift regarding the relationship between microbial agents and cancers [1]. Indeed, in 1994, H. pylori became the first bacterial species to be officially recognized by the World Health Organization as a definite cause of cancer in humans. Since then, there has been a growing body of evidence supporting an association between specific microorganisms, including those in the oral cavity, and various types of cancers. The oral cavity is inhabited by complex multispecies communities that usually exist in a balanced immunoinflammatory state with the host [2]. Certain species, such as Porphyromonas gingivalis, can disrupt this equilibrium, resulting in a dysbiotic host– microbiota interaction. Subsequently, other community constituents, such as Fusobacterium nucleatum, can become opportunistically pathogenic, and the combined effect of a dysbiotic microbial community along with a dysregulated immune response ultimately causes periodontal disease [2]. These well-studied periodontal organisms have now emerged as the focal point for the developing association between oral bacteria and cancer. Perhaps the most likely carcinogenic link with oral bacteria is with oral squamous cell carcinoma (OSCC), one of the most common cancers worldwide. OSCC surfaces have been reported to harbor significantly higher levels of Porphyromonas and Fusobacterium compared with contiguous healthy mucosa [3]. Moreover, immunohistochemistry with P. gingivalis antibodies revealed higher levels of detection and intensity of staining in gingival carcinomas compared with healthy gingival tissue, although only a small number of cases were examined [4]. A striking association has also been demonstrated between P. gingivalis infection and pancreatic cancer. In a prospective cohort study of over 400 cases and controls, a .2-fold increase in risk of pancreatic cancer was observed among those with high levels of antibodies to P. gingivalis, after adjusting for known risk factors [5]. Similarly, in the extensive National Health and Nutrition Examination Survey III, orodigestive cancer mortality was found to be related to the levels of P. gingivalis antibodies, independent of periodontal disease [6]. Several recent studies have shown a strong association between F. nucleatum and colorectal cancer (CRC) [7–10]. F. nucleatum was found to be one of the more abundant species within and around CRC neoplasms, and levels of F. nucleatum correlated with the presence of lymph node metastases.