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Louisville, KY, United States

The University of Louisville is a public university in Louisville, Kentucky, a member of the Kentucky state university system. When founded in 1798, it was the first city-owned public university in the United States and one of the first universities chartered west of the Allegheny Mountains. The university is mandated by the Kentucky General Assembly to be a "Preeminent Metropolitan Research University". U of L enrolls students from 118 of 120 Kentucky counties, all 50 U.S. states, and 116 countries around the world.Researchers from the University of Louisville Health science Center participated in the development of a highly effective vaccine against cervical cancer in 2006, the first fully self-contained artificial heart transplant surgery, the first successful hand transplantation, and the development of the Pap smear test. The University Hospital is also credited with the first civilian ambulance, the nation's first accident services, now known as an emergency room , and one of the first blood banks in the US.Between 1999 and 2006 U of L was one of the fastest growing medical research institutions according to National Institutes of Health rankings. As of 2006, the melanoma clinic ranked third in among public universities in NIH funding, the neurology research program fourth, and the spinal cord research program 10th.U of L is also known for its athletics programs, several of which are among the most successful in the country. Since 2005 the Cardinals have made appearances in the men's basketball Final Four in 2005, 2012, and 2013 , football Bowl Championship Series Orange Bowl in 2007 and Sugar Bowl in 2013 , the College Baseball World Series 2007, 2013, and 2014, the women's basketball Final Four in 2009 and 2013 , and the men's soccer national championship game in 2010. U of L's women's volleyball program has three-peated as champions of the Big East Tournament , and its women's track and field program has won Outdoor Big East titles in 2008, 2009 and 2010 and an Indoor Big East title in 2011. Wikipedia.

Background and Purpose-: The traditional time window for acute ischemic stroke intra-arterial therapy (IAT) is <6 hours, which is based on pharmacological thrombolysis without penumbral imaging. This study was conducted to determine the safety of patient selection for IAT based on perfusion mismatch rather than time. Methods-: A cohort of consecutive patients treated with IAT was identified by database review. Patients were selected for IAT based on the presence of perfusion mismatch using CT perfusion or MRI regardless of stroke duration. Thrombolytics were minimized after 6 hours in favor of mechanical embolectomy or angioplasty±stenting. Outcomes (National Institutes of Health Stroke Scale, modified Rankin Scale) were assessed by independent examiners. A multivariate analysis was performed to compare those treated <6 hours (early) with those treated >6 hours (late). Results-: Fifty-five patients (mean National Institutes of Health Stroke Scale=19.7±5.7) were treated, 34 early and 21 late, with mean time-to-intervention of 3.4±1.6 hours and 18.6±16.0 hours, respectively. Thrombolysis In Myocardial Ischemia 2 or 3 recanalization was achieved in 82.8% early and 85.7% late patients (P=1.0). Intracerebral hemorrhage occurred in 25.5% overall, but symptomatic intracerebral hemorrhage occurred in 8.8% of the early and 9.5% of the late patients (P=1.0). Thirty-day mortality was similar (29.4% versus 23.8%, P=0.650). At 3 months, 41.2% and 42.9%, respectively, achieved a modified Rankin Scale ≤2 (P=0.902). Only presenting National Institutes of Health Stroke Scale was a predictor of modified Rankin Scale ≤2 (OR 0.794[95% CI 0.68 to 0.92], P=0.009) and death (adjusted OR 1.29[95% CI 1.04 to 1.59], P=0.019). Conclusions-: In appropriately selected patients, IAT for acute ischemic stroke can be performed safely regardless of stroke duration. The concept of an acute ischemic stroke treatment window for IAT should be re-evaluated with a clinical trial selecting patients with perfusion mismatch. © 2010 American Heart Association, Inc. Source

Birks E.J.,University of Louisville
Circulation Research | Year: 2013

Heart failure is associated with remodeling that consists of adverse cellular, structural, and functional changes in the myocardium. Until recently, this was thought to be unidirectional, progressive, and irreversible. However, irreversibility has been shown to be incorrect because complete or partial reversal can occur that can be marked after myocardial unloading with a left ventricular assist device (LVAD). Patients with chronic advanced heart failure can show near-normalization of nearly all structural abnormalities of the myocardium or reverse remodeling after LVAD support. However, reverse remodeling does not always equate with clinical recovery. The molecular changes occurring after LVAD support are reviewed, both those demonstrated with LVAD unloading alone in patients bridged to transplantation and those occurring in the myocardium of patients who have recovered enough myocardial function to have the device removed. Reverse remodeling may be attributable to a reversal of the pathological mechanisms that occur in remodeling or the generation of new pathways. A reduction in cell size occurs after LVAD unloading, which does not necessarily correlate with improved cardiac function. However, some of the changes in both the cardiac myocyte and the matrix after LVAD support are specific to myocardial recovery. In the myocyte, increases in the cytoskeletal proteins and improvements in the Ca handling pathway seem to be specifically associated with myocardial recovery. Changes in the matrix are complex, but excessive scarring appears to limit the ability for recovery, and the degree of fibrosis in the myocardium at the time of implantation may predict the ability to recover. © 2013 American Heart Association, Inc. Source

Thorp J.H.,University of Louisville
Canadian Journal of Fisheries and Aquatic Sciences | Year: 2015

Anthropogenic reductions in braiding, meandering, and snag abundance have diminished habitat heterogeneity of regulated rivers, factors directly influencing island formation, retentive capacity of the ecosystem, and com¬munity diversity. Habitat heterogeneity associated with riverine islands should, therefore, be of paramount impor¬tance to the ecosystem and may require special management protection. To understand the influence of these alluvial formations on riverine benthos, macroinvertebrate assemblages were sampled near three islands in the Ohio River above Louisville, Kentucky, USA. Benthos was collected along six bank-to-bank transects located 1 km above and below islands and near the head, middle, and foot of islands. Islands have significant positive effects on invertebrate density and diversity that appear related to changes in physical habitat characteristics. Current velocity and substrate particle size are diminished in narrow channels between islands and shore, and areal extent of the littoral zone is enhanced within an otherwise deepwater region. Shallow water and slower currents promote growth of submerged vascular plants and macrophytic algae. Because of a relatively low exploi¬tation by humans, islands probably enhance snag formation and input of organic matter, both factors having positive effects on macrofauna. Creation of selected riverine preserves near islands as a management tactic is recommended. Les réductions d'origine anthropique de la réticulation, de la formation de méandres et de la fréquence des crochês ont diminué l'hétérogénéité de I'habitat dans les cours d'eau aménagés, facteurs qui ont une influence directe sur la formation des lies, la capacité de rétention de l'écosystème et la diversité de la communauté. Lhétérogénéité de I'habitat associée aux Ties fluviales devrait done avoir une importance primordiale pour léco- système et peut exiger un régime spécial de protection. Pour comprendre l'influence de ces formations alluviales sur le benthos de la zone proche des berges, on a échantillonné des assemblages de macroinvertébrés près de trois iles se trouvant dans le fleuve Ohio en amont de Louisville (Kentucky), aux États-Unis. Le benthos a été recueilli le long de six transects de rive à rive situés à un 1 km au-dessus et au-dessous des iles et près de la tète, du milieu et de la queue des Ties. Les iles ontdeseffets positifs notables sur la densité et la diversité des invertébrés, effets qui semblent liés à des modifications dans les caractéristiques physiques de I'habitat. La vitesse du courant et la granulométrie du substrát diminuent dans les chenaux étroits entre les iles et la berge, et la superficie de la zone littorale augmente dans une région d'eau profonde par ailleurs. la faible profondeur de l'eau et le ralentis- sement des courants favorisent la croissance des plantes vasculaires immergées et des algues macrophytes. Du fait qu'elles sont soumises à une exploitation relativement faible par les humains, les iles favorisent probablement la formation de croches et l'apport de matières organiques, deux facteurs qui ont des effets positifs sur la macro- faune. 11 est recommandé comme méthode de gestion de créer des réserves protégeant des zones Iittorales choisies près des iles. © 2015, National Research Council of Canada. All rights reserved. Source

Taylor D.D.,University of Louisville
Seminars in immunopathology | Year: 2011

Cancer cells, both in vivo and in vitro, have been demonstrated to release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and nucleic acids. While only recently have the roles of these vesicular components in intercellular communication become elucidated, significant evidence has demonstrated that tumor exosomes can exert a broad array of detrimental effects on the immune system-ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells and T regulatory cells. Immunosuppressive exosomes of tumor origin can be found within neoplastic lesions and in biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and genetic intercellular exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. By understanding the nature of these tumor-derived exosomes/microvesicles and their roles in mediating cancer progression and modulating the host immune response will significantly impact therapeutic approaches targeting exosomes. Source

We identified multiple single nucleotide variants (SNVs) in the TP53 3' untranslated region (3'UTR) in tumor specimens from 244 patients with diffuse large B-cell lymphoma (DLBCL). Patients carrying a wild-type TP53 coding sequence (CDS) and 1 or more 3'UTR SNVs had a better 5-year survival rate than patients carrying a wild-type CDS and the reference 3'UTR, yet there is no statistically significance difference in overall survival (OS). In contrast, 3'UTR variation predicted poorer OS for patients with a mutant TP53 CDS. We then sequenced TP53 3'UTR in 247 additional DLBCL patients as a validation set. Altogether, we identified 187 novel SNVs; 36 occurred at least twice. Most of the newly identified 3'UTR SNVs were located at sites that are complementary to seed sequences of microRNAs (miRNAs) that are predicted or experimentally known to target TP53. Three SNVs disrupt the seed match between miR-125b and the TP53 3'UTR, thereby impeding suppression of p53 by this miRNA. In addition, a germline SNV (rs78378222) located in the TP53 polyadenylation signal resulted in downregulation of both p53 messenger RNA and protein levels and reduction of cellular apoptosis. This study is the first to demonstrate the prognostic value of the TP53 3'UTR in cancer. Source

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