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Detecting Structure In Glass Patterns: An Interocular Transfer Study, Dawn Vreven, Jarrod Berge Dec 2012

Detecting Structure In Glass Patterns: An Interocular Transfer Study, Dawn Vreven, Jarrod Berge

Dawn L Vreven

Glass patterns are visual stimuli used here to study how local orientation signals are spatially integrated into global pattern perception. We measured a form aftereffect from adaptation to both static and dynamic Glass patterns and calculated the amount of interocular transfer to determine the binocularity of the detectors responsible for the perception of global structure. Both static and dynamic adaptation produced significant form aftereffects and showed a very high degree of interocular transfer, suggesting that Glass-pattern perception involves cortical processing beyond primary visual cortex. Surprisingly, dynamic adaptation produced significantly greater interocular transfer than static adaptation. Our results suggest a functional …


Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown Dec 2012

Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown

Dr Robert Brown

Genetic variants in UBQLN1 gene have been linked to neurodegeneration and mutations in UBQLN2 have recently been identified as a rare cause of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To test if genetic variants in UBQLN1 are involved in ALS. METHODS: 102 and 94 unrelated patients with familial and sporadic forms of ALS were screened for UBQLN1 gene mutations. Single nucleotide variants were further screened in a larger set of sporadic ALS (SALS) patients and unrelated control subjects using high-throughput Taqman genotyping; variants were further assessed for novelty using the 1000Genomes and NHLBI databases. In vitro studies tested the effect of …


Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman Dec 2012

Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman

Dr Robert Brown

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …


Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown Dec 2012

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …


Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown Dec 2012

Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown

Dr Robert Brown

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a …


Enhancing Patient Adherence: Outcomes Of Medication Alliance Training On Therapeutic Alliance, Insight, Adherence, And Psychopathology With Mental Health Patients, Mitchell Byrne, Frank Deane Nov 2012

Enhancing Patient Adherence: Outcomes Of Medication Alliance Training On Therapeutic Alliance, Insight, Adherence, And Psychopathology With Mental Health Patients, Mitchell Byrne, Frank Deane

Mitchell K Byrne

The results of interventions to enhance patient adherence to medication have been inconsistent. This research investigated the utility of an enhanced adherence training programme to ascertain its effectiveness and the possible mechanisms of that effect. Forty-six clinicians were trained in 'medication alliance', and data were collected from 51 patients matched to the clinician. Data on clinician changes in skills, knowledge, and attitudes, in relation to enhancing patient adherence and patient changes in adherence, insight, and psychopathology were collected at baseline and at 6 and 12 months. The quality of the therapeutic relationship between the clinician and the patient was also …


Nurse's Beliefs And Knowledge About Medications Are Associated With Their Difficulties Using Patient Treatment Adherence Strategies, Mitchell Byrne, Frank Deane, Tim Coombs Nov 2012

Nurse's Beliefs And Knowledge About Medications Are Associated With Their Difficulties Using Patient Treatment Adherence Strategies, Mitchell Byrne, Frank Deane, Tim Coombs

Mitchell K Byrne

Background: The attitudes and beliefs of patients toward their treatment have been found to be an important factor in treatment outcome, particularly as it relates to treatment adherence. There are also suggestions that knowledge, attitudes and beliefs held by nurses about treatments may also be important influences on treatment outcome but there has been little research relating these to specific clinical behaviour. Aims: This study explored the knowledge and beliefs of nurses toward neuroleptic medications in the treatment of severe mental ill health with the view to identifying specific nurse training needs. Method: A convenience sample of 64 nurses was …


Can Volunteer Counsellors Help Prevent Psychological Trauma? A Preliminary Communication On Volunteers Skills Using The 'Orienting Approach' To Trauma, Mitchell Byrne, Frank Deane, Andrew Phipps Nov 2012

Can Volunteer Counsellors Help Prevent Psychological Trauma? A Preliminary Communication On Volunteers Skills Using The 'Orienting Approach' To Trauma, Mitchell Byrne, Frank Deane, Andrew Phipps

Mitchell K Byrne

The capacity of 73 volunteer telephone counsellors to administer a brief and early intervention for secondary trauma was assessed. The counsellors participated in a 1-day training programme in the ‘Orienting Approach’ to Trauma Counselling (Phipps & Byrne, 2003). Volunteer counsellors showed significant improvements in both knowledge and skills from pre- to post-training. The potential benefits of this intervention to the community and professional health services are discussed.


Enhancing Medication Adherence: Clinician Outcomes From The Medication Alliance Training Program, Mitchell Byrne, Frank Deane, William Lambert, Timothy Coombs Nov 2012

Enhancing Medication Adherence: Clinician Outcomes From The Medication Alliance Training Program, Mitchell Byrne, Frank Deane, William Lambert, Timothy Coombs

Mitchell K Byrne

OBJECTIVE: Patient nonadherence to psychiatric medication is a key cause of relapse but clinicians do not appear to possess specific adherence skills. We sought to demonstrate that a brief training program on medication adherence strategies could improve the adherence skills, attitudes and knowledge of mental health clinicians. METHODS: Twenty-three Tasmanian mental health workers were provided a 3 day training workshop on strategies to enhance patient adherence to medications (Medication Alliance). Pre- and post-training measures were taken of clinician knowledge about adherence strategies, ability to identify predictors of nonadherence, attitudes toward working with nonadherent patients, and optimism about treatment outcomes for …


Mental Health Clinicians' Beliefs About Medicines, Attitudes, And Expectations Of Improved Medication Adherence In Patients, Mitchell Byrne, Peter Caputi, Frank Deane Nov 2012

Mental Health Clinicians' Beliefs About Medicines, Attitudes, And Expectations Of Improved Medication Adherence In Patients, Mitchell Byrne, Peter Caputi, Frank Deane

Mitchell K Byrne

Nonadherence to antipsychotic medications remains a major factor in poor clinical outcomes. This study sought to identify clinician beliefs about patients who do not adhere to treatment, the clinicians' own beliefs about medicines, and the impact of beliefs on efforts to enhance patient adherence. In total, 292 clinicians responded to an anonymous questionnaire that included questions about their beliefs and their efforts to enhance adherence. Results indicated that clinicians' beliefs about their own adequacy to enhance adherence significantly predicted actual efforts to enhance adherence. Both pessimism about outcomes and empathy for the patient predicted outcome expectancy. It was concluded that …


Eight Is Enough?: The Ethics Of The California Octuplets Case, Scott Paeth Oct 2012

Eight Is Enough?: The Ethics Of The California Octuplets Case, Scott Paeth

Scott R. Paeth

The recent California octuplets case raises a number of important issues that need to be addressed in the context of the increasingly widespread practice of in vitro fertilization. This paper explores some of those issues as looked at from the perspective of protestant theological ethics and public theology, examining the moral responsibilities of the various participants in the process, both before and after the octuplets’ birth, including the mother, her doctors, the health care bureaucracy, the wider society, and the media. Each of these participants failed in significant respects to consider the ethical implications of the births in this complicated …


Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …


Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak Oct 2012

Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak

Gyongyi Szabo

Inflammation is a common element in the pathogenesis of most chronic liver diseases that lead to fibrosis and cirrhosis. Inflammation is characterized by activation of innate immune cells and production of pro-inflammatory cytokines IL-1alpha, IL-1beta, and TNFalpha. Inflammasomes are intracellular multiprotein complexes expressed in both parenchymal and non-parenchymal cells of the liver that in response to cellular danger signals activate caspase-1, and release IL-1beta and IL-18. The importance of inflammasome activation in various forms of liver diseases in relation to liver damage, steatosis, inflammation and fibrosis is discussed in this review. Elsevier B.V. All rights reserved.


Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo Oct 2012

Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …


Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo Oct 2012

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …


An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano Oct 2012

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …


Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer Oct 2012

Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer

Gyongyi Szabo

The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of …


Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo Oct 2012

Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo

Gyongyi Szabo

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFNalpha induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNalpha production. Depletion of pDCs from PBMCs attenuated IFNalpha release and purified pDCs produced high levels of IFNalpha after co-culture with FL replicons or JFH-1 …


Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc Oct 2012

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …


Circulating Micrornas In Exosomes Indicate Hepatocyte Injury And Inflammation In Alcoholic, Drug-Induced, And Inflammatory Liver Diseases, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Ivan Levin, Jeanine Ward, Hawau Alao, Karen Kodys, Gyongyi Szabo Oct 2012

Circulating Micrornas In Exosomes Indicate Hepatocyte Injury And Inflammation In Alcoholic, Drug-Induced, And Inflammatory Liver Diseases, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Ivan Levin, Jeanine Ward, Hawau Alao, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

MicroRNAs are fine tuners of diverse biological responses and are expressed in various cell types of the liver. Here we hypothesized that circulating microRNAs (miRNAs) may serve as biomarkers of liver damage and inflammation. We studied miRNA-122, which is abundant in hepatocytes, and miR-155, -146a, and -125b, which regulate inflammation in immune cells in mouse models of alcoholic liver disease (ALD), drug (acetaminophen, APAP)-induced liver injury (DILI), and Toll-like receptor (TLR) 9+4 ligand-induced inflammatory cell-mediated liver damage. We found that serum/plasma miR-122 correlated with alanine aminotransferase (ALT) increases in the liver damage caused by alcohol, APAP, and TLR9 (CpG)+4 (LPS) …


Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …


Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman Oct 2012

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …


Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela Higgins, Anna Doubeni, Karon Phillips, Adeyinka Laiyemo, Becky Briesacher, Jennifer Tjia, Chyke Doubeni Oct 2012

Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela Higgins, Anna Doubeni, Karon Phillips, Adeyinka Laiyemo, Becky Briesacher, Jennifer Tjia, Chyke Doubeni

Chyke A. Doubeni

BACKGROUND: The benefit of screening for decreasing the risk of death from colorectal cancer (CRC) has been shown, yet many patients in primary care are still not undergoing screening according to guidelines. There are known variations in delivery of preventive health care services among primary care physicians. This study compared self-reported CRC screening rates and patient awareness of the need for CRC screening of patients receiving care from family medicine (FPs) vs. internal medicine (internists) physicians. METHODS: Nationally representative sample of non-institutionalized beneficiaries who received medical care from FPs or internists in 2006 (using Medicare Current Beneficiary Survey). The main …


First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris Sep 2012

First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris

Celia A. Schiffer

APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions …


Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte Sep 2012

Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte

Christian Mueller

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 x 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of …


A Link Between Chronic Sleep Restriction And Obesity: Methodological Considerations, Christopher Magee, Donald Iverson, Xu-Feng Huang, Peter Caputi Sep 2012

A Link Between Chronic Sleep Restriction And Obesity: Methodological Considerations, Christopher Magee, Donald Iverson, Xu-Feng Huang, Peter Caputi

Xu-Feng Huang

Emerging evidence suggests that chronicsleeprestriction contributes to obesity. Targeting short sleep duration may therefore offer a novel and effective method of preventing and treating obesity. However, this area of research is only in its infancy, and a complete understanding of how chronicsleeprestriction and obesity are linked is currently lacking. The aim of this paper is to briefly review epidemiological evidence for an association between chronicsleeprestriction and obesity in adults, and outline the key methodological limitations of these studies. Particular attention is paid to the methods used to measure sleep and obesity, as well as the need to control for potential …


Dietary Fat And Carbohydrate Composition: Metabolic Disease, Marc Brown, Len Storlien, Xu-Feng Huang, Linda Tapsell, Paul Else, Janine Higgins, Ian Brown Sep 2012

Dietary Fat And Carbohydrate Composition: Metabolic Disease, Marc Brown, Len Storlien, Xu-Feng Huang, Linda Tapsell, Paul Else, Janine Higgins, Ian Brown

Xu-Feng Huang

No abstract provided.


Effects Of Diets High In Whey, Soy, Red Meat And Milk Protein On Body Weight Maintenance In Diet-Induced Obesity In Mice, Xu-Feng Huang, Y Liu, Gita Rahardjo, Peter Mclennan, Linda Tapsell, William Buttemer Sep 2012

Effects Of Diets High In Whey, Soy, Red Meat And Milk Protein On Body Weight Maintenance In Diet-Induced Obesity In Mice, Xu-Feng Huang, Y Liu, Gita Rahardjo, Peter Mclennan, Linda Tapsell, William Buttemer

Xu-Feng Huang

This study examined the effects of different food sources of protein on energy intake, body weight maintenance, and on the responses of plasma leptin, insulin and adiponectin in chronic high-fat diet-induced obese mice. Obesity was induced in 47 mice with a high-fat diet for 20 weeks. They were divided into five diet groups to test the effects of a higher protein proportion (30% energy), achieved at the expense of carbohydrate. For the next eight weeks, four of the groups were fed diets of chow formulated with whey, soy, red meat or milk while the control group continued on their high-fat …


Relationships Between Clinical Data And Baseline Eating Behaviours In A Sample Of Overweight Volunteers For A Dietary Intervention Trial, Lynette Mackey De Paiva, Lynda Gillen, Linda Tapsell, Marijka Batterham, Xu-Feng Huang, Rachel Cavanagh, Meredith Kennedy Sep 2012

Relationships Between Clinical Data And Baseline Eating Behaviours In A Sample Of Overweight Volunteers For A Dietary Intervention Trial, Lynette Mackey De Paiva, Lynda Gillen, Linda Tapsell, Marijka Batterham, Xu-Feng Huang, Rachel Cavanagh, Meredith Kennedy

Xu-Feng Huang

No abstract provided.


Dietary And Clinical Risk Profiles Of A Sample Of Healthy Overweight Adults Provide Targets For Dietary Advice In An Intervention Trial, Lynda Gillen, Linda Tapsell, Marijka Batterham, Xu-Feng Huang, Rachel Cavanagh, Meredith Kennedy Sep 2012

Dietary And Clinical Risk Profiles Of A Sample Of Healthy Overweight Adults Provide Targets For Dietary Advice In An Intervention Trial, Lynda Gillen, Linda Tapsell, Marijka Batterham, Xu-Feng Huang, Rachel Cavanagh, Meredith Kennedy

Xu-Feng Huang

No abstract provided.