Medicine and Health Sciences Commons^™

Measures Of Highly Functioning Health Coalitions: Corollaries For An Effective Public Health System, Priscilla A. Barnes, Paul C. Erwin, Ramal Moonesinghe

Frontiers in Public Health Services and Systems Research

In Tennessee, health coalitions provide guidance in conducting community assessments, health improvement plans and policies and delivering of health and human services, which are considered core functions of public health. In fact, it has been postulated that these coalitions may serve as the organizational embodiment of the local public health system (LPHS). This study identifies functional characteristics of 63 Tennessee County Health Councils (CHCs), advisory councils to local and regional governmental public health agencies on broad issues of health, that contribute to its ability to operate as the primary advising entity of the LPHS. Exploratory factor analysis was conducted on …

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

Pheochromocytoma In A Twelve-Year-Old Girl With Sdhb-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome, Daryl Graham, Megan Gooch, Zhan Ye, Edward Richer, Aftab S. Chishti, Elizabeth Reilly, John D’Orazio

Pediatrics Faculty Publications

A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child's pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency.

Thoracoabdominal Aortic Aneurysm Repair: Current Endovascular Perspectives, Nathan Orr, David Minion, Joseph L. Bobadilla

Surgery Faculty Publications

Thoracoabdominal aneurysms account for roughly 3% of identified aneurysms annually in the United States. Advancements in endovascular techniques and devices have broadened their application to these complex surgical problems. This paper will focus on the current state of endovascular thoracoabdominal aneurysm repair, including specific considerations in patient selection, operative planning, and perioperative complications. Both total endovascular and hybrid options will be considered.

Lipid Extraction From Scenedesmus Sp. Microalgae For Biodiesel Production Using Hot Compressed Hexane, Hee-Yong Shin, Jae-Hun Ryu, Seong-Youl Bae, Czarena L. Crofcheck, Mark Crocker

Center for Applied Energy Research Faculty and Staff Publications

Lipid extraction from Scenedesmus sp. microalgae using hot compressed hexane (HCH) was investigated. Extraction performance was evaluated near the critical point of hexane and was compared with that of hexane extraction performed at room temperature and pressure, and the Bligh and Dyer extraction method. Experimental data showed that HCH significantly improves the lipid yield and rate of lipid extraction compared to the use of hexane at ambient conditions. High yields of biodiesel-convertible lipid fractions were rapidly achieved at the critical point of hexane, at a level comparable to that of the Bligh and Dyer method.

Generation And Behavior Characterization Of Camkiiβ Knockout Mice, Adam D. Bachstetter, Scott J. Webster, Tao Tu, Danielle S. Goulding, Jacques Haiech, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and …

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …

Acute Demyelinating Polyneuropathy After Lung Transplantation: Guillain-Barré Syndrome Or Tacrolimus Toxicity?, Nirmal S. Sharma, Keith M. Wille, Charles W. Hoopes, Enrique Diaz-Guzman

Surgery Faculty Publications

Guillain-Barré syndrome (GBS) has been described after solid organ and bone marrow transplantation mostly due to viral infections and possibly calcineurin inhibitors. Incidence after bone marrow transplant is 0.3-0.7%, though incidence in other transplants is not well known. We present the first description of tacrolimus associated GBS in lung transplant recipients in the English language literature. The pathophysiology of tacrolimus-induced polyneuropathy is not known, but some have hypothesized that tacrolimus induces an inflammatory phenomenon by differential effects on T cell subsets. Diagnosis of association may be challenging and requires high index of suspicion. The optimal treatment of GBS-associated with tacrolimus …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Kentucky Round 1: State-Level Field Network Study Of The Implementation Of The Affordable Care Act, Julia Costich, Glen P. Mays

Health Management and Policy Reports

No abstract provided.

In Vivo Processing Of Ceria Nanoparticles Inside Liver: Impact On Free-Radical Scavenging Activity And Oxidative Stress, Uschi M. Graham, Michael T. Tseng, Jacek B. Jasinski, Robert A. Yokel, Jason M. Unrine, Burtron H. Davis, Alan K. Dozier, Sarita S. Hardas, Rukhsana Sultana, Eric A. Grulke, D. Allan Butterfield

Pharmaceutical Sciences Faculty Publications

The cytotoxicity of ceria ultimately lies in its electronic structure, which is defined by the crystal structure, composition, and size. Despite previous studies focused on ceria uptake, distribution, biopersistance, and cellular effects, little is known about its chemical and structural stability and solubility once sequestered inside the liver. Mechanisms will be presented that elucidate the in vivo transformation in the liver. In vivo processed ceria reveals a particle-size effect towards the formation of ultrafines, which represent a second generation of ceria. A measurable change in the valence reduction of the second-generation ceria can be linked to an increased free-radical scavenging …

Reduction In Overall Occurrences Of Ischemic Events With Vorapaxar: Results From Tracer, Harvey D. White, Zhen Huang, Pierluigi Tricoci, Frans Van De Werf, Lars Wallentin, Yuliya Lokhnygina, David J. Moliterno, Philip E. Aylward, Kenneth W. Mahaffey, Paul W. Armstrong

Internal Medicine Faculty Publications

BACKGROUND: Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.

METHODS AND RESULTS: TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar …

Alcohol Promotes Mammary Tumor Growth Through Activation Of Vegf-Dependent Tumor Angiogenesis, Yanmin Lu, Fang Ni, Mei Xu, Jinlian Yang, Ji Chen, Zhuo Chen, Xinyi Wang, Jia Luo, Siying Wang

Internal Medicine Faculty Publications

Alcohol consumption has been recognized as a risk factor for breast cancer. Experimental studies demonstrate that alcohol exposure promotes the progression of existing mammary tumors. However, the mechanisms underlying this effect remain unclear. In the present study, the role of vascular endothelial growth factor (VEGF) in alcohol promotion of breast cancer development was investigated using a mouse xenograft model of mammary tumors and a three-dimensional (3D) tumor/endothelial cell co-culture system. For the mouse xenograft model, mouse E0771 breast cancer cells were implanted into the mammary fat pad of C57BL6 mice. These mice were exposed to alcohol in their drinking water. …

Novel Synergistic Protective Efficacy Of Atovaquone And Diclazuril On Fetal-Maternal Toxoplasmosis, Helieh S. Oz

Internal Medicine Faculty Publications

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis.

METHODS: Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied.

RESULTS: Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were …

Cardioprotection By Controlling Hyperamylinemia In A "Humanized" Diabetic Rat Model, Sanda Despa, Savita Sharma, Todd R. Harris, Hua Dong, Ning Li, Nipavan Chiamvimonvat, Heinrich Taegtmeyer, Kenneth B. Margulies, Bruce D. Hammock, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart.

METHODS AND RESULTS: By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP …

Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu

Markey Cancer Center Faculty Publications

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC …

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion In The Rat, Michael T. Tseng, Qiang Fu, Khoua Lor, G. Rafael Fernandez-Botran, Zhong-Bin Deng, Uschi M. Graham, D. Allan Butterfield, Eric A. Grulke, Robert A. Yokel

Chemistry Faculty Publications

Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3⁺ lymphocyte proliferation that intermingled with nanoceria-containing …

Method For Treating Hair Growth Disorders, Such As Female Pattern Alopecia, And Compositions Useful Therefore, Elaine L. Jacobson, Myron K. Jacobson, Hyuntae Kim, Donna L. Coyle, William R. Coyle

Pharmacology and Nutritional Sciences Faculty Patents

The invention relates to formulations useful in treating hair disorders, improving the health of hair, increasing hair growth, and in increasing the niacin content of hair follicles. Nicotinic acid alkyl esters having a straight chain alkyl group of from 1 to 22 methylene units, preferably from 6 to 16 methylene units, and most preferably from 8 to 14 methyl units, may be used, alone or in combinations for treating these conditions.

Transition From An M1 To A Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition In App/Ps1 Transgenic Mice, Erica M. Weekman, Tiffany L. Sudduth, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Holly M. Brothers, Kaitlyn Braun, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer's disease, yet the impact of these phenotypes on amyloid-beta (Aβ) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Aβ, but long-term studies have not been performed that track the neuroinflammatory phenotype.

METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFNγ or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNγ protein levels and …

Correspondence: Protocol-Based Care For Early Septic Shock, Hans-Joachim Priebe, Angel Coz-Yataco, Stephen Trzeciak, Antonio J. Dajer, Derek C. Angus, Donald M. Yealy, John A. Kellum, Craig M. Lilly

Internal Medicine Faculty Publications

No abstract provided.

Maternal And Congenital Toxoplasmosis, Currently Available And Novel Therapies In Horizon, Helieh S. Oz

Internal Medicine Faculty Publications

Over one billion people worldwide are predicted to harbor Toxoplasma infection frequently with unknown lifelong health consequences. Toxoplasmosis is an important cause of foodborne, inflammatory illnesses, as well as congenital abnormalities. Ubiquitous Toxoplasma has a unique tropism for central nervous system with a mind-bugging effect and is transmitted sexually through semen. Currently available therapies are ineffective for persistent chronic disease and congenital toxoplasmosis or have severe side effects which may result in life-threatening complications. There is an urgent need for safe and effective therapies to eliminate or treat this cosmopolitan infectious and inflammatory disease. This investigation discusses pathogenesis of maternal …

Newborn Care: What We Can Learn From The Kangaroo Mother, Donald E. Greydanus, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA …

Axial-Centrifugal Flow Catheter Pump For Cavopulmonary Assistance, Dongfang Wang, Joseph B. Zwischenberger

Surgery Faculty Patents

An axial-centrifugal flow catheter pump for cavopulmonary assistance is provided, incorporating a rotor providing both an axial fluid flow and a centrifugal fluid flow. The rotor includes a first terminal impeller configured to provide a centrifugal and axial fluid flow in a first direction, a second terminal impeller configured to provide a centrifugal and axial fluid flow in a second direction opposite to the first direction, and a central impeller configured to provide a predominantly centrifugal fluid flow. The first and second terminal impellers each include blade arrangements configured to provide a centrifugal and axial fluid flow directed toward the …

Method Of Using Ccr3 Binding Agents To Detect Choroidal Neovascularization, Jayakrishna Ambati, Mark E. Kleinman

Ophthalmology and Visual Science Faculty Patents

The results presented herein demonstrate the specific expression of CCR3 in CNV endothelial cells in humans with AMD, and despite the expression of its ligands, eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. The genetic or pharmacological targeting of CCR3 or eotaxins as disclosed herein inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing …

Healthcare For Persons With Intellectual And Developmental Disability In The Community, David A. Ervin, Brian Hennen, Joav Merrick, Mohammed Morad

Pediatrics Faculty Publications

INTRODUCTION: While there has been impressive progress in creating and improving community healthcare delivery systems that support people with intellectual and developmental disabilities (IDD), there is much more that can and should be done.

METHODS: This paper offers a review of healthcare delivery concepts on which new models are being developed, while also establishing an historical context. We review the need for creating fully integrated models of healthcare, and at the same time offer practical considerations that range from specific healthcare delivery system components to the need to expand our approach to training healthcare providers. The models and delivery systems, …

Biomarkers Of Acute Myocardial Infarction In The Elderly: Troponin And Beyond, Martin G. Rains, Charles A. Laney, Alison L. Bailey, Charles L. Campbell

Gill Heart & Vascular Institute Faculty Publications

In the broadest context, biological markers, or biomarkers, are molecules that characterize a biological system or process. In the setting of cardiovascular disease, a number of biomarkers have become an integral part of diagnostic and risk stratification strategies. In this review, we will discuss classic and emerging biomarkers of cardiovascular disease and the role of these biomarkers in the diagnosis and prognosis of elderly patients presenting with acute myocardial infarction.

Pioglitazone Treatment Reduces Adipose Tissue Inflammation Through Reduction Of Mast Cell And Macrophage Number And By Improving Vascularity, Michael Spencer, Lin Yang, Akosua Adu, Brian S. Finlin, Beibei Zhu, Lindsey R. Shipp, Neda Rasouli, Charlotte A. Peterson, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context and Objective: Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.

Design, Setting and Participants: Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.

Results: Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased …

Sox11 Is Required To Maintain Proper Levels Of Hedgehog Signaling During Vertebrate Ocular Morphogenesis, Lakshmi Pillai-Kastoori, Wen Wen, Stephen G. Wilson, Erin Strachan, Adriana Lo-Castro, Marco Fichera, Sebastiano A. Musumeci, Ordan J. Lehmann, Ann C. Morris

Biology Faculty Publications

Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the …