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Thymidylate Synthase Genotype-Directed Chemotherapy For Patients With Gastric And Gastroesophageal Junction Cancers, Laura W. Goff, Nilay Thakkar, Liping Du, Emily Chan, Benjamin R. Tan, Dana B. Cardin, Howard L. Mcleod, Jordan D. Berlin, Barbara Zehnbauer, Chloe Fournier, Joel Picus, Andrea Wang-Gillam, Wooin Lee, A. Craig Lockhart Sep 2014

Thymidylate Synthase Genotype-Directed Chemotherapy For Patients With Gastric And Gastroesophageal Junction Cancers, Laura W. Goff, Nilay Thakkar, Liping Du, Emily Chan, Benjamin R. Tan, Dana B. Cardin, Howard L. Mcleod, Jordan D. Berlin, Barbara Zehnbauer, Chloe Fournier, Joel Picus, Andrea Wang-Gillam, Wooin Lee, A. Craig Lockhart

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.

METHODS: In this phase II study (NCT00515216 registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/NCT00515216), patients with "good risk" TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%).

RESULTS: The ORR in genotype-selected patients was 39.1% (9 partial responses out …


A Dietary-Wide Association Study (Dwas) Of Environmental Metal Exposure In Us Children And Adults, Matthew A. Davis, Diane Gilbert-Diamond, Margaret R. Karagas, Zhigang Li, Jason H. Moore, Scott M. Williams, H. Robert Frost Sep 2014

A Dietary-Wide Association Study (Dwas) Of Environmental Metal Exposure In Us Children And Adults, Matthew A. Davis, Diane Gilbert-Diamond, Margaret R. Karagas, Zhigang Li, Jason H. Moore, Scott M. Williams, H. Robert Frost

Dartmouth Scholarship

Background: A growing body of evidence suggests that exposure to toxic metals occurs through diet but few studies have comprehensively examined dietary sources of exposure in US populations.

Purpose: Our goal was to perform a novel dietary-wide association study (DWAS) to identify specific dietary sources of lead, cadmium, mercury, and arsenic exposure in US children and adults.

Methods: We combined data from the National Health and Nutrition Examination Survey with data from the US Department of Agriculture’s Food Intakes Converted to Retail Commodities Database to examine associations between 49 different foods and environmental metal exposure. Using blood and urinary biomarkers …


Predictors Of Healthcare Professionals’ Attitudes Towards Family Involvement In Safety-Relevant Behaviours: A Cross-Sectional Factorial Survey Study, Rachel Davis, M Savvopoulou, R Shergill, S Shergill, D Schwappach Sep 2014

Predictors Of Healthcare Professionals’ Attitudes Towards Family Involvement In Safety-Relevant Behaviours: A Cross-Sectional Factorial Survey Study, Rachel Davis, M Savvopoulou, R Shergill, S Shergill, D Schwappach

Faculty Publications

OBJECTIVES: To investigate predictors of healthcare professionals' (HCPs) attitudes towards family involvement in safety-relevant behaviours. DESIGN: A cross-sectional fractional factorial survey that assessed HCPs' attitudes towards family involvement in two error scenarios relating to hand hygiene and medication safety. Each survey comprised two randomised vignettes that described the potential error, how the family member communicated with the HCP about the error and how the HCP responded to the family member's question. SETTING: 5 teaching hospitals in London, the Midlands and York. HCPs were approached on a range of medical and surgical wards. PARTICIPANTS: 160 HCPs (73 doctors; 87 nurses) aged …


Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez Sep 2014

Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus …


Randomised Clinical Trial: Polyethylene Glycol 3350 With Sports Drink Vs. Polyethylene Glycol With Electrolyte Solution As Purgatives For Colonoscopy--The Incidence Of Hyponatraemia., Rebecca Matro, Constantine Daskalakis, Dan Negoianu, Leo Katz, Cassandra Henry, Michael Share, David Kastenberg Sep 2014

Randomised Clinical Trial: Polyethylene Glycol 3350 With Sports Drink Vs. Polyethylene Glycol With Electrolyte Solution As Purgatives For Colonoscopy--The Incidence Of Hyponatraemia., Rebecca Matro, Constantine Daskalakis, Dan Negoianu, Leo Katz, Cassandra Henry, Michael Share, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic purgative commonly used for colonoscopy, though little safety data are available.

AIM: To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes compared with PEG-electrolyte solution (PEG-ELS).

METHODS: We performed a single center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG-SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline and immediately before and after colonoscopy. The primary endpoint was development of hyponatraemia (Na/L) the day of colonoscopy. Changes in electrolyte levels were computed as the difference between the lowest value on the day of colonoscopy …


A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich Sep 2014

A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich

Department of Pediatrics Faculty Papers

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis.

STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured.

RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean …


Factors Associated With Neurodevelopment For Children With Single Ventricle Lesions., Caren S. Goldberg, Minmin Lu, Lynn A. Sleeper, William T. Mahle, J William Gaynor, Ismee A. Williams, Kathleen A. Mussatto, Richard G. Ohye, Eric M. Graham, Deborah U. Frank, Jeffrey P. Jacobs, Catherine Krawczeski, Linda Lambert, Alan Lewis, Victoria L. Pemberton, Renee Sananes, Erica Sood, Stephanie B. Wechsler, David C. Bellinger, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali Sep 2014

Factors Associated With Neurodevelopment For Children With Single Ventricle Lesions., Caren S. Goldberg, Minmin Lu, Lynn A. Sleeper, William T. Mahle, J William Gaynor, Ismee A. Williams, Kathleen A. Mussatto, Richard G. Ohye, Eric M. Graham, Deborah U. Frank, Jeffrey P. Jacobs, Catherine Krawczeski, Linda Lambert, Alan Lewis, Victoria L. Pemberton, Renee Sananes, Erica Sood, Stephanie B. Wechsler, David C. Bellinger, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors.

STUDY DESIGN: All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The …


An Intronic Picalm Polymorphism, Rs588076, Is Associated With Allelic Expression Of A Picalm Isoform, Ishita Parikh, Christopher Medway, Steven Younkin, David Fardo, Steven Estus Aug 2014

An Intronic Picalm Polymorphism, Rs588076, Is Associated With Allelic Expression Of A Picalm Isoform, Ishita Parikh, Christopher Medway, Steven Younkin, David Fardo, Steven Estus

Physiology Faculty Publications

BACKGROUND: Although genome wide studies have associated single nucleotide polymorphisms (SNP)s near PICALM with Alzheimer's disease (AD), the mechanism underlying this association is unclear. PICALM is involved in clathrin-mediated endocytosis and modulates Aß clearance in vitro. Comparing allelic expression provides the means to detect cis-acting regulatory polymorphisms. Thus, we evaluated whether PICALM showed allele expression imbalance (AEI) and whether this imbalance was associated with the AD-associated polymorphism, rs3851179.

RESULTS: We measured PICALM allelic expression in 42 human brain samples by using next-generation sequencing. Overall, PICALM demonstrated equal allelic expression with no detectable influence by rs3851179. A single sample demonstrated …


The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels Aug 2014

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …


Modelling The Impact Of Improving Screening And Treatment Of Chronic Hepatitis C Virus Infection On Future Hepatocellular Carcinoma Rates And Liver-Related Mortality., Matthew E. Cramp, William M. Rosenberg, Steven D. Ryder, Sarah Blach, Julie Parkes Aug 2014

Modelling The Impact Of Improving Screening And Treatment Of Chronic Hepatitis C Virus Infection On Future Hepatocellular Carcinoma Rates And Liver-Related Mortality., Matthew E. Cramp, William M. Rosenberg, Steven D. Ryder, Sarah Blach, Julie Parkes

Peninsula Medical School

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated …


Diagnosis-Specific Readmission Risk Prediction Using Electronic Health Data: A Retrospective Cohort Study, Courtney Hebert, Chaitanya Shivade, Randi Foraker, Jared Wasserman, Caryn Roth, Hagop Mekhjan, Stanley Lemeshow, Peter Embi Aug 2014

Diagnosis-Specific Readmission Risk Prediction Using Electronic Health Data: A Retrospective Cohort Study, Courtney Hebert, Chaitanya Shivade, Randi Foraker, Jared Wasserman, Caryn Roth, Hagop Mekhjan, Stanley Lemeshow, Peter Embi

Dartmouth Scholarship

Background: Readmissions after hospital discharge are a common occurrence and are costly for both hospitals and patients. Previous attempts to create universal risk prediction models for readmission have not met with success. In this study we leveraged a comprehensive electronic health record to create readmission-risk models that were institution- and patient- specific in an attempt to improve our ability to predict readmission. Methods: This is a retrospective cohort study performed at a large midwestern tertiary care medical center. All patients with a primary discharge diagnosis of congestive heart failure, acute myocardial infarction or pneumonia over a two-year time period were …


Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis Aug 2014

Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis

College of Science & Mathematics Departmental Research

OBJECTIVES: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group.

PARTICIPANTS: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation.

OUTCOME MEASURES: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods. Self-reported negative affect was also assessed before and after …


Obesity And Mortality: Are The Risks Declining? Evidence From Multiple Prospective Studies In The United States., Tapan S. Mehta, Kevin R. Fontaine, Scott W. Keith, Sripal S. Bangalore, Gustavo De Los Campos, Alfred Bartolucci, Nicholas M. Pajewski, David B. Allison Aug 2014

Obesity And Mortality: Are The Risks Declining? Evidence From Multiple Prospective Studies In The United States., Tapan S. Mehta, Kevin R. Fontaine, Scott W. Keith, Sripal S. Bangalore, Gustavo De Los Campos, Alfred Bartolucci, Nicholas M. Pajewski, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

We evaluated whether the obesity-associated years of life lost (YLL) have decreased over calendar time. We implemented a meta-analysis including only studies with two or more serial body mass index (BMI) assessments at different calendar years. For each BMI category (normal weight: BMI 18.5 to <25 >[reference]; overweight: BMI 25 to60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and increased by 0.63 years for grade 2-3 obesity (P = 0.63). Among women aged ≤60, YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P < 0.001) for grade 2-3 obesity. In women aged >60, YLL for grade 1 obesity decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2-3 obesity. Grade 1 obesity's association with decreased longevity has reduced for older Caucasian men. For Caucasian women, there is evidence of a decline in the obesity YLL association across all ages.


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 Aug 2014

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 …


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 Aug 2014

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 …


Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer Aug 2014

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …


Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham Aug 2014

Vaccines To Combat River Blindness: Expression, Selection And Formulation Of Vaccines Against Infection With Onchocerca Volvulus In A Mouse Model., Jessica A. Hess, Bin Zhan, Sandra Bonne-Annee, Jessica M. Deckman, Maria Elena Bottazzi, Peter J. Hotez, Thomas R R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation …


Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon Aug 2014

Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy. Our objective was to determine any associations between risk factors for sleep-related deaths at different ages.

METHODS: A cross-sectional study of sleep-related infant deaths from 24 states during 2004-2012 contained in the National Center for the Review and Prevention of Child Deaths Case Reporting System, a database of death reports from state child death review teams. The main exposure was age, divided into younger (0-3 months) and older …


Making A Decision About Trial Participation: The Feasibility Of Measuring Deliberation During The Informed Consent Process For Clinical Trials, Katie Gillies, Glyn Elwyn, Jonathan Cook Jul 2014

Making A Decision About Trial Participation: The Feasibility Of Measuring Deliberation During The Informed Consent Process For Clinical Trials, Katie Gillies, Glyn Elwyn, Jonathan Cook

Dartmouth Scholarship

Background:

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of ‘informed-ness’ is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making.

Methods:

Potential trial participants who were approached regarding participation in …


Visual Speech Perception In Foveal And Extrafoveal Vision: Further Implications For Divisions In Hemispheric Projections, Timothy R. Jordan, Mercedes Sheen, Lily Abedipour, Kevin B. Paterson Jul 2014

Visual Speech Perception In Foveal And Extrafoveal Vision: Further Implications For Divisions In Hemispheric Projections, Timothy R. Jordan, Mercedes Sheen, Lily Abedipour, Kevin B. Paterson

All Works

When observing a talking face, it has often been argued that visual speech to the left and right of fixation may produce differences in performance due to divided projections to the two cerebral hemispheres. However, while it seems likely that such a division in hemispheric projections exists for areas away from fixation, the nature and existence of a functional division in visual speech perception at the foveal midline remains to be determined. We investigated this issue by presenting visual speech in matched hemiface displays to the left and right of a central fixation point, either exactly abutting the foveal midline …


Redox Proteomic Identification Of Hne-Bound Mitochondrial Proteins In Cardiac Tissues Reveals A Systemic Effect On Energy Metabolism After Doxorubicin Treatment, Y. Zhao, Sumitra Miriyala, L. Miao, Mihail I. Mitov, David M. Schnell, Sanjit Kumar Dhar, J. Cai, J. B. Klein, Rukhsana Sultana, D. Allan Butterfield, Mary Vore, I. Batinic-Haberle, Subbarao Bondada, Daret K. St. Clair Jul 2014

Redox Proteomic Identification Of Hne-Bound Mitochondrial Proteins In Cardiac Tissues Reveals A Systemic Effect On Energy Metabolism After Doxorubicin Treatment, Y. Zhao, Sumitra Miriyala, L. Miao, Mihail I. Mitov, David M. Schnell, Sanjit Kumar Dhar, J. Cai, J. B. Klein, Rukhsana Sultana, D. Allan Butterfield, Mary Vore, I. Batinic-Haberle, Subbarao Bondada, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria after DOX treatment. A redox proteomics method involving two-dimensional electrophoresis followed by mass spectrometry and investigation of protein databases identified several HNE-modified mitochondrial proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the …


The Evolving Approach To Ethical Issues In Living Donor Kidney Transplantation: A Review Based On Illustrative Case Vignettes, K. K. Venkat, Anne Eshelman Jul 2014

The Evolving Approach To Ethical Issues In Living Donor Kidney Transplantation: A Review Based On Illustrative Case Vignettes, K. K. Venkat, Anne Eshelman

Nephrology Articles

Living donor kidney transplantation which involves performing a major surgical procedure on a healthy person solely to benefit another person has always involved dealing with difficult ethical issues. Beneficence, non-maleficence, donor autonomy, altruistic donor motivation, coercion-free donation, fully informed consent and avoidance of medical paternalism have been the dominant ethical principles governing this field ever since the first successful living donor kidney transplant in 1954. The increasing reliance on living donors due to the rapidly growing disparity between the number of patients awaiting transplantation and the availability of deceased donor kidneys has brought with it a variety of new ethical …


Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman Jul 2014

Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman

Department of Urology Faculty Papers

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.

METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.

RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% …


Erectile Dysfunction As A Motivational Tool For Health Behavior Change In Men With Diabetes, Camille W. Allred, Donna Freeborn Jun 2014

Erectile Dysfunction As A Motivational Tool For Health Behavior Change In Men With Diabetes, Camille W. Allred, Donna Freeborn

Student Works

The purpose of this literature review is to outline a health promotion plan for healthcare providers and diabetes educators, using erectile dysfunction (ED) as a motivational tool to change health behaviors for men with diabetes. Because the most severe complications might not manifest themselves until later in life, patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) are less likely to make the dramatic behavioral changes necessary to control their diabetes at the time of diagnosis. Twenty-eight articles obtained from CINAHL and Medline databases were examined. Eleven of those articles were selected for analysis based …


Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio Jun 2014

Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio

Open Access Publications

The Wallenda (Wnd)/dual leucine zipper kinase (DLK)-Jnk pathway is an evolutionarily conserved MAPK signaling pathway that functions during neuronal development and following axonal injury. Improper pathway activation causes defects in axonal guidance and synaptic growth, whereas loss-of-function mutations in pathway components impairs axonal regeneration and degeneration after injury. Regulation of this pathway is in part through the E3 ubiquitin ligase Highwire (Hiw), which targets Wnd/DLK for degradation to limit MAPK signaling. To explore mechanisms controlling Wnd/DLK signaling, we performed a large-scale genetic screen in Drosophila to identify negative regulators of the pathway. Here we describe the identification and characterization of …


Non Melanoma Skin Cancer And Subsequent Cancer Risk, Judy R. Rees, M. Scot Zens, Jiang Gui, Maria O. Celaya, Bruce L. Riddle, Margaret R. Karagas Jun 2014

Non Melanoma Skin Cancer And Subsequent Cancer Risk, Judy R. Rees, M. Scot Zens, Jiang Gui, Maria O. Celaya, Bruce L. Riddle, Margaret R. Karagas

Dartmouth Scholarship

Introduction:

Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.

Purpose:

The aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer.

Methods:

Participants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. …


Pattern Of Mutation Rates In The Germline Of Drosophila Melanogaster Males From A Large-Scale Mutation Screening Experiment, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Shi-Meng Ai, Shu-Qun Liu, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu Jun 2014

Pattern Of Mutation Rates In The Germline Of Drosophila Melanogaster Males From A Large-Scale Mutation Screening Experiment, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Shi-Meng Ai, Shu-Qun Liu, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu

Faculty, Staff and Student Publications

The sperm or eggs of sexual organisms go through a series of cell divisions from the fertilized egg; mutations can occur at each division. Mutations in the lineage of cells leading to the sperm or eggs are of particular importance because many such mutations may be shared by somatic tissues and also may be inherited, thus having a lasting consequence. For decades, little has been known about the pattern of the mutation rates along the germline development. Recently it was shown from a small portion of data that resulted from a large-scale mutation screening experiment that the rates of recessive …


Treatment Preferences Among Problem Drinkers In Primary Care., Daniel Z Lieberman, Anne Cioletti, Suena H Massey, Rochelle S Collantes, Brad B Moore Jun 2014

Treatment Preferences Among Problem Drinkers In Primary Care., Daniel Z Lieberman, Anne Cioletti, Suena H Massey, Rochelle S Collantes, Brad B Moore

Psychiatry and Behavioral Sciences Faculty Publications

OBJECTIVE: Alcohol misuse is common among primary care patients, yet many do not receive treatment because doctors believe problem drinkers are "in denial," or are unwilling to change their drinking habits. The real problem, however, may be that patients are being offered treatment modalities that do not meet their needs. This study was designed to measure the acceptability of various treatment options among drinkers who were currently not receiving treatment.

METHOD: Patients in a primary care clinic were given a self-report questionnaire that included: (1) the Alcohol Use Disorders Questionnaire, (2) a measure of readiness to change drinking behavior, and …


Resistant Starch Type 4-Enriched Diet Lowered Blood Cholesterols And Improved Body Composition In A Double Blind Controlled Cross-Over Intervention, Sailendra N Nichenametla, Lee A. Weidauer, Howard Wey, Tianna Beare, Bonny Specker, Moul Dey Jun 2014

Resistant Starch Type 4-Enriched Diet Lowered Blood Cholesterols And Improved Body Composition In A Double Blind Controlled Cross-Over Intervention, Sailendra N Nichenametla, Lee A. Weidauer, Howard Wey, Tianna Beare, Bonny Specker, Moul Dey

Health and Nutritional Sciences Faculty Publications

A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in the United States. Effects of resistant starch type 4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of RS4-enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double blind (participants-investigators), placebo-controlled, cluster cross-over intervention (n = 86, age≥18, 2-12 week interventions, 2-week washout) in the United States, individuals were classified as having MetS (With-MetS) or not (No-MetS) following International Diabetes Federation (IDF)-criteria. RS4 …


Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio Jun 2014

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …