STRESS EFFECTS ON ALCOHOL CONSUMPTION: AGE OF ONSET AND GENES IN HEAVY DRINKERS
E Mary
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 1U01AA020890-01 from National Institute On Alcohol Abuse And Alcoholism
Abstract: INIA researchers and others have posited that stress and alcohol exposure trigger allostatic processes which injure limbic and hypothalamic stress pathways and set the stage for increased drinking. This theory is supported by epidemiological findings in the US population that number of life stressors is positively correlated with amount of alcohol consumption and that these effects are strongest in persons with an early onset of alcohol use. Recent studies suggest important modifying effects of the serotonin transporter promoter polymorphism and stress in predicting total alcohol intake, age of onset of drinking, and duration of drinking. Genetic variation in the corticotropin-releasing hormone (CRH) receptor 1 also has been associated with stress-induced heavy alcohol consumption in animals and human adolescents; the role of CRH has been a major focus of INIA. We hypothesize that, in the human laboratory, a social stress procedure will increase alcohol motivated responding and alcohol consumption, and that this relationship will be modified by age of drinking onset and the genes under investigation. To test our hypotheses, non-treatment seeking, heavy alcohol drinkers with and without an alcohol use disorder will be admitted to the clinical research unit for alcohol detoxification. Four days after the start of abstinence, subjects will undergo in random order, the Trier Social Stress Test (TSST) or a time-matched neutral condition; Cortisol will be measured during these procedures. Immediately after the TSST or neutral condition, access to alcohol will be provided using an operant self-administration paradigm in which the response demands progressively increase with each alcohol drink that is earned; earned alcohol is delivered at the conclusion of the session. We also will study subjects using an alcohol sensitivity procedure that establishes a dose-effect function for alcohol on subjective, physiological and behavioral measures within a single session. Study findings will have scientific and clinical importance in establishing potential mechanisms for genetic and environmental influences on the relationship between stress and alcohol in heavy drinkers. Study findings will have scientific and clinical importance in establishing potential mechanisms for genetic and environmental influences on the relationship between stress and alcohol in heavy drinkers
Keywords: Abstinence; Adolescent; Age; Age of Onset; alcohol abstinence; alcohol availability; Alcohol consumption; alcohol craving; Alcohol dependence; alcohol exposure; alcohol reward; alcohol sensitivity; alcohol use disorder; Alcoholic beverage heavy drinker; Alcohols; Alleles; allostasis; allostatic load; Animals; Applications Grants; Autonomic nervous system; behavior measurement; Chronic stress; Clinical; Clinical Research; Consumption; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; cytokine; Dose; drinking; drinking onset; Drug Addiction; Drug Metabolic Detoxication; early alcohol use; early onset; Epidemiology; Exposure to; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Glucocorticoids; Heart Rate; Heavy Drinking; Homeostasis; Hormones; Human; Hydrocortisone; Hypothalamic structure; Immune; Inflammatory; injured; Investigation; Laboratories; Life; Mammals; Measures; Mediator of activation protein; Mental Depression; Minor; Neurosecretory Systems; novel; Nucleic Acid Regulatory Sequences; Organism; Pathway interactions; Peptides; Persons; Physiological; Population; pre-clinical; Prevention strategy; Procedures; Process; Promotor (Genetics); Research Personnel; response; Role; Schedule; Self Administration; Series; serotonin transporter; social stress; Staging; Stimulus; Stress; stressor; Study Subject; Testing; theories; Time; treatment strategy; Trier Social Stress Test; Variation (Genetics)
Relevance: Study findings will have scientific and clinical importance in establishing potential mechanisms for genetic and environmental influences on the relationship between stress and alcohol in heavy drinkers
Project start date: 2012-02-15
Project end date: 2017-01-31
Budget start date: 15-FEB-2012
Budget end date: 31-JAN-2013
1U01AA020890-01 (2012): $318559
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to E Mary
LONGITUDINAL STUDY OF VOCABULARY GROWTH AND PHONOLOGICAL DEVELOPMENT
E Mary, Professor
University Of Wisconsin Madisoncity: Madison country: United States (us)
Grant 2R01DC002932-10A2 from National Institute On Deafness And Other Communication Disorders
Abstract: While there is a large body of literature suggesting that early word learning is critical for the later development of oral and written language, the processes by which problems in word learning interact with deficits in other aspects of linguistic knowledge are not well understood, nor is it clear whether deficits in vocabulary size impact later language development equally depending on their source. A better understanding of these interactions are critical because small vocabularies in early childhood place children at significant risk for delays in acquiring both spoken and written language. This study proposes to begin to fill in some of these gaps in our understanding by examining the relationships among components of phonological knowledge (including the ability to perceive speech sounds in challenging listening tasks, the ability to robustly differentiate among speech sounds in production, and the ability to make inferences about how sounds function in the language being acquired) and lexical acquisition in children with a wide range of vocabulary sizes, where size varies for different reasons across groups. The proposed research is a longitudinal study from 30 to 60 months of age of approximately 200 children with a wide variety of initial vocabulary sizes resulting from a range of advantages or deficits in the types of phonological knowledge that support word learning. The specific research question addressed is what are the developmental relationships among vocabulary growth and three types of phonological knowledge (speech production knowledge, speech perception knowledge, and higher-level categorical knowledge) for children with normal hearing from middle-SES and low-SES families, and for children with cochlear implants (CIs)? The study will include three groups of children one, children from low-SES families, who have smaller vocabularies than peers from middle-SES families because of more limited linguistic input (among other factors); two, children with cochlear implants, who have smaller vocabularies than peers with normal hearing because of their perceptual limitations; and three, children from middle-SES families with a wide range of vocabulary sizes, including a sizeable number of late talkers (i.e., children who have small expressive vocabularies at age 2, in spite of normal sensory functioning, normal cognitive development, and age-appropriate receptive vocabularies). The study also includes a statistical modeling component to determine optimal interventions for children with small-sized vocabularies. Structural equation modeling, based on data from this rich longitudinal sample, will allow us to test what interventions might be most effective to increase vocabulary for these different groups of children. Ultimately, the knowledge obtained from this study will enable us to develop efficacious and targeted early interventions for young children with atypically small vocabularies. Small vocabularies in early childhood place children at significant risk for delays in acquiring both spoken and written language. However, the processes by which problems in word learning interact with deficits in other aspects of linguistic knowledge are not well understood. This study will examine the relationships among components of phonological development and lexical acquisition in children with a wide range of vocabulary sizes for different reasons. Ultimately, this knowledge will enable us to develop efficacious and targeted early interventions for children with smaller vocabularies in early childhood
Keywords: Address; Age; Age-Months; aged; Area; Auditory; Awareness; base; Child; clinical Diagnosis; Cochlear Implants; Cognitive; Complex; Cross-Sectional Studies; Data; Development; Disease; early childhood; Early treatment; Equation; Exclusion; Exercise; Family; Funding; Growth; Hearing; hearing impairment; Hearing problem; Household; improved; Intervention; Intervention Studies; kindergarten; Knowledge; knowledge base; Language; Language Development; Language Disorders; language processing; Learning; lexical; Linguistics; Literature; longitudinal design; Longitudinal Studies; low socioeconomic status; Measures; Modeling; Oral; Pattern; peer; phonology; Plant Roots; Process; Production; public health relevance; Relative (related person); Research; Risk; Sampling; Sensory; Series; Socioeconomic Status; sound; Source; specific language impairment; Speech; Speech Perception; Speech Sound; Statistical Models; Study models; Testing; Time; Vocabulary; Work; Writing
Relevance: Small vocabularies in early childhood place children at significant risk for delays in acquiring both spoken and written language. However, the processes by which problems in word learning interact with deficits in other aspects of linguistic knowledge are not well understood. This study will examine the relationships among components of phonological development and lexical acquisition in children with a wide range of vocabulary sizes for different reasons. Ultimately, this knowledge will enable us to develop efficacious and targeted early interventions for children with smaller vocabularies in early childhood
Project start date: 1998-01-15
Project end date: 2016-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-10-067
2R01DC002932-10A2 (2011): $620000
NICOTINE DEPENDENCE, WITHDRAWAL AND REPLACEMENT THERAPY ASSESSED BY PET IMAGING
E Mary, Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 1R01DA026823-01A2 from National Institute On Drug Abuse
Abstract: While smoking prevalence has declined for both men and women over the last two decades, rates among women have shown a much shallower decrease and, in recent years, prevalence of cigarette initiation has been higher for girls than boys. Smoking among women of child-bearing age has significant negative health consequences for mother and child, increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a quit attempt and more likely to relapse if they do quit. Nicotine replacement therapy (NRT), still the most widely used smoking treatment intervention in the United States, is less effective for women compared with men, and women report less craving reduction on NRT. The endogenous opioid system is involved in smoking initiation, nicotine craving and reward as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic features of the endogenous mu-opioid system may in part explain gender differences in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT responses in women, this proposal will examine NRT effects on mu opioid receptor binding potential (MOR BP) in female compared to male smokers during active versus placebo NRT. Specifically, nicotine dependent women and men in active smoking status will undergo PET imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference group, demographically-matched women and men who have never smoked will undergo two scans as well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained repeatedly across the protocol. The proposed research will provide significant new, gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy. The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to explain the differences in the prevalence of smoking in men and women, sex-specific differences in nicotine craving and withdrawal as well as the poorer therapeutic response to NRT. This work may pave the way to the design of improved pharmacotherapies that can more effectively target the endogenous opioid system in the treatment of nicotine dependence
Keywords: base; behavior measurement; Biological; boys; carfentanil; Child; Cigarette; clinically relevant; craving; design; Endogenous Opiates; Female; Female of child bearing age; fetal; Gender; girls; Health; high risk; Hour; Image; improved; Infant; Intervention; male; Measurement; Measures; men; Morbidity - disease rate; Mortality Vital Statistics; Mothers; Nicotine; nicotine craving; Nicotine Dependence; nicotine replacement; Nicotine Withdrawal; Non-smoker; Opioid; Opioid Receptor Binding; Pharmacotherapy; Phenotype; Placebos; Population; Positron-Emission Tomography; Prevalence; Protocols documentation; Randomized; Receptors, Opioid, mu; Relapse; Relative (related person); Replacement Therapy; Reporting; Research; response; Rewards; Role; Scanning; Severities; sex; Sex Characteristics; Smoke; Smoker; Smoking; smoking prevalence; Smoking Status; System; Therapeutic; therapeutic effectiveness; treatment response; United States; Withdrawal; Withdrawal Symptom; Woman; Work
Relevance: The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to explain the differences in the prevalence of smoking in men and women, sex-specific differences in nicotine craving and withdrawal as well as the poorer therapeutic response to NRT. This work may pave the way to the design of improved pharmacotherapies that can more effectively target the endogenous opioid system in the treatment of nicotine dependence
Project start date: 2011-09-30
Project end date: 2016-05-31
Budget start date: 30-SEP-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-10-067
1R01DA026823-01A2 (2011): $534859
TGF-BETA SIGNALING IN THE KIDNEY
E Mary, Associate Professor
Brigham And Women´s Hospitalcity: Boston country: United States (us)
Grant 2R01DK057661-11A1 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Transforming growth factor-beta 1 (TGF-ss1) is a pleiotropic cytokine which controls multiple cellular functions including cell proliferation, differentiation, apoptosis, and extracellular matrix (ECM) synthesis. TGF-ss1 is a potent inducer of ECM protein synthesis and accumulation, and plays a key role in the pathogenesis of progressive diseases as a central mediator of fibrogenesis in a variety of tissues, including the kidney. TGF-ss1 actions are mediated via TGF-ss type I (TssRI) and type II (TssRII) receptors to activate intracellular pathways. Many central questions remain relating to how the distinct receptors mediate TGF-ss1 signals in a cell-specific and context-specific manner to elicit multiple cellular responses. The overall objective of our research is to understand the cellular and molecular mechanisms of renal injury and fibrosis. The major goals are to investigate the mechanisms of TGF-ss1 signaling pathways and their regulation and functional role in injury responses in the kidney. Our hypothesis is that autophagy represents an adaptive stress response to protect against renal injury by inhibiting apoptosis and promoting renal cell survival, and that TGF-ss1 exerts cytoprotective effects via regulating autophagy. Furthermore, we hypothesize that TGF-ss1 signaling via TAK1- MKK3-p38 is the critical mediator of tissue injury response in which TGF-ss1 regulates autophagy proteins which in turn prevents apoptosis and excessive ECM accumulation. This proposal will focus on examining the mechanism and functional role of TGF-ss1 signaling via TAK1 in renal cells, and the regulation of autophagy and its physiological functional role in an experimental model of renal fibrosis. The Specific Aims are Specific Aim 1 To determine the mechanism and functional role of TGF-ss1 signaling via TAK1 in renal cells Specific Aim 2 To determine the regulation and function of autophagy induced by TGF-ss1 in renal cells. Specific Aim 3 To determine the in vivo physiological functional role of autophagy in an experimental model of renal fibrosis. We will employ state-of-the art approaches including a variety of dominant negative mutants of the signal transducing molecules, the MAPKs, focusing on the TAK1-MKK3 signaling axis, gene silencing by the use short interfering RNA (siRNA), and genetically altered mice, the null mice for the various TAK1, MKK3, Caveolin-1, and the autophagy genes, LC3 and Beclin 1. Relevance Although the central role of TGF-ss1 in the development of renal fibrosis is well documented, general strategies to indiscriminately inhibit TGF-ss1 actions altogether may prove to be imprudent. The studies in this proposal will yield important and novel information in furthering our understanding of the molecular mechanisms of TGF-ss1 signal transduction, that we may be able to selectively block the pathway that signals the deleterious effects of TGF-ss1. Our research centers on understanding the mechanisms of TGF-ss1 actions. By careful dissection of the complex TGF-ss signal transduction pathways, our goal is to be able to selectively block the pathway that signals the deleterious effects of TGF-ss1, and provide a novel therapeutic approach to prevent development of progressive renal fibrosis and ensuing kidney failure in chronic kidney disease
Keywords: Address; Apoptosis; Autophagocytosis; base; Binding (Molecular Function); Binding Proteins; Biological; biological adaptation to stress; caveolin 1; Cell Nucleus; Cell physiology; Cell Proliferation; Cell surface; Cell Survival; Cells; Chronic Kidney Failure; Collagen Type I; Complex; cytokine; Cytoplasmic Protein; Cytoprotection; Data; Development; Dissection; Dominant-Negative Mutation; Down-Regulation; End stage renal failure; Epithelial Cells; Excision; Exhibits; Experimental Models; Extracellular Matrix; Extracellular Matrix Proteins; fibrogenesis; Fibrosis; Gene Silencing; Genes; Goals; Growth Factor; Homeostasis; human MAPK14 protein; human TGFB1 protein; In Vitro; in vivo; in vivo Model; Injury; Kidney; kidney cell; Kidney Failure; Knockout Mice; Lead; MAPK14 gene; Mediating; Mediator of activation protein; mesangial cell; Mitogen-Activated Protein Kinase Kinases; Modeling; Molecular; Mus; novel; novel therapeutic intervention; Nuclear Proteins; Organelles; Pathogenesis; Pathway interactions; Phosphotransferases; Physiological; Play; prevent; Process; Progressive Disease; Protein Biosynthesis; Proteins; receptor; Receptor Signaling; Recycling; Regulation; Research; response; response to injury; RNA; Role; Scheme; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Testing; Therapeutic Intervention; tissue regeneration; Tissues; Transforming Growth Factor beta; Tubular formation; Ureteral obstruction; Wound Healing
Relevance: Our research centers on understanding the mechanisms of TGF-ss1 actions. By careful dissection of the complex TGF-ss signal transduction pathways, our goal is to be able to selectively block the pathway that signals the deleterious effects of TGF-ss1, and provide a novel therapeutic approach to prevent development of progressive renal fibrosis and ensuing kidney failure in chronic kidney disease
Project start date: 2000-06-01
Project end date: 2015-05-31
Budget start date: 5-AUG-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-10-067
2R01DK057661-11A1 (2011): $445454
PORTION CONTROL LIFESTYLE CHANGE TO DECREASE OBESITY IN PERSONS WITH DISABILITIES
E Mary, Research Scientist
Temple Universitycity: Philadelphia country: United States (us)
Grant 1R21HD068010-01A1 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: This study will pilot the use of portion control plates and other visual cues for healthy nutrition and decreased caloric intake to reduce obesity and overweight in persons with developmental disabilities (DD) who live in community group homes with care provider staff. People with DD are at particular risk for obesity, because they often (but not always) have intellectual disabilities including attention, cognitive and memory deficits, making skills like pre-planning and self-monitoring difficult. In addition, tasty energy-dense foods are often seen as highly rewarding "treats" for special occasions or desired behaviors and are consumed in large quantities. Finally, they have limited financial and informational resources with which to cope with health and nutrition needs. This proposal results from the collaboration of a community agency, United Cerebral Palsy of Central Pennsylvania, and an academic center, Temple University, funded through NIH´s "Partners in Research" program to develop feasible projects to improve health promotion in persons with DD. Community members identified as a priority the need for effective, simple-to-implement incremental steps to improve weight control that could be sustained over the long term through positive changes in residents´ everyday routines. The study arms are one set of homes will receive materials including standardized plates and bowls with illustrations of portion servings for different food groups and other visual cues along with an orientation session on using the plates; another set of homes will receive the visual cues and orientation plus a series of onsite educational and problem-solving sessions on the importance of healthy weight, portion control and good nutrition; a third set of homes will serve as an assessment-only control. Specific aims are to 1) calculate effect sizes for change in residents´ BMI to enable a full-scale RCT; 2) determine quantitative changes in mediating variables, including 7 care providers´ and residents´ knowledge about good nutrition and portion control; 7 care providers´ and residents´ perceptions of acceptability and feasibility; and 7 food purchases based on food shopping receipts; and 3) analyze qualitative data from separate focus groups of care providers and residents to enrich understanding of their perceptions of the acceptability of the interventions, their feasibility, the fidelity with which the visual cues were displayed and used, usefulness of the educational sessions, and barriers and facilitators regarding future implementation. Group homes present a "best case" scenario because more control is possible in this setting, in which agency staff can be provided guidelines as part of their continuing education, than in family or independent living situations of persons with disabilities. If the intervention is successful in this setting, it can be modified and piloted for persons with disabilities in other living situations. This pilot project breaks new ground in the search for ways to decrease risk of obesity-related disease in community-living persons with developmental disabilities, an under-served group with higher obesity prevalence than the general population. We will explore the effectiveness of two interventions to decrease meal portion size and increase choice of low energy-dense foods, based on salient cues for behavior change and hands-on presentation of principles of basic good nutrition and their application. If successful, this pilot will lead to a full-scale RCT to improve the health of persons with developmental disabilities
Keywords: arm; Attention; base; Behavior; behavior change; Calories; Caring; Cerebral Palsy; Clinical Trials; Cognitive deficits; Collaborations; Communities; community living; Continuing Education; Control Groups; coping; Cues; Data; design; Development; Developmental Disabilities; disability; Disabled Persons; Educational aspects; Effectiveness; Energy Intake; Enrollment; Environment; evidence base; Family; Fatty acid glycerol esters; Focus Groups; Food; fruits and vegetables; Funding; Future; General Population; Goals; Grant; Group Homes; Guidelines; Health; Health Promotion; Home environment; improved; Independent Living; Intellectual functioning disability; Intervention; Knowledge; Lead; Life; Life Style; Mediating; member; Memory impairment; Menu Planning; Monitor; nutrition; Obesity; Obesity associated disease; obesity management; obesity risk; Occupations; Outcome; Overweight; Pennsylvania; Perception; Persons; Pilot Projects; portion control; posters; Preparation; Prevalence; primary outcome; Problem Solving; programs; Provider; public health relevance; Recipe; Relative (related person); Research; Research Personnel; Resources; Rewards; Risk; Sample Size; Series; Services; skills; Treatment Efficacy; Universities; Visual; Weight; weight loss intervention; Weight maintenance regimen
Relevance: This pilot project breaks new ground in the search for ways to decrease risk of obesity-related disease in community-living persons with developmental disabilities, an under-served group with higher obesity prevalence than the general population. We will explore the effectiveness of two interventions to decrease meal portion size and increase choice of low energy-dense foods, based on salient cues for behavior change and hands-on presentation of principles of basic good nutrition and their application. If successful, this pilot will lead to a full-scale RCT to improve the health of persons with developmental disabilities
Project start date: 2011-04-14
Project end date: 2013-03-31
Budget start date: 14-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-10-069
1R21HD068010-01A1 (2011): $221316
ENVIROMENTAL HEALTH DISPARITIES RESEARCH CORE
E Mary
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 3P60MD003421-03S1 from National Institute On Minority Health And Health Disparities
Abstract: This revision application will integrate a new Environmental Health Disparities Research Core (EH Core) into the existing community-academic research infrastructure of the Weill Cornell Center of Excellence in Health Disparities Research and Community Engagement (CEDREC). The EH Core will create an innovative collaborative infrastructure that will position CEDREC for the next generation of research that will intervene on environmental as well as clinical and psychosocial factors, while simultaneously beginning to train a cadre of academic and community researchers to address environmental contributions to health disparities. The EH Core will add a unique perspective to ongoing CEDREC research, facilitate dialogue between community-based organizations, local residents, and elected officials, and inform researchers, community members and policymakers through lectures, community forums, webinars, and didactic education. The primary aim of the EH Core is to provide CEDREC with the capacity to collaboratively examine environmental factors that drive health disparities and develop innovative and transdisciplinary solutions. CEDREC is comprised of 4 cores 1) Research Core-provides methodological and biostatistical support to 3 ongoing clinical trials; 2) Training Core-provides rigorous training in research methodology to junior investigators; 3) Community Engagement Core-informs the development of new research and community-driven educational activities; and 4) Administrative Core-coordinates all programmatic initiatives. The Environmental Core will leverage these resources to create a vehicle for community and academic partners to jointly develop new research efforts to address environmental factors that drive health disparities. Drs. Boutin-Foster (Pl of CEDREC) and Charison (Co-PI) have recruited Dr. Beverly Watkins to serve as Director of the Environmental Core, who brings a track record of over 12 years experience in environmental health, environmental justice, community capacity building, and community-based participatory research
Keywords: Address; Area; base; Behavioral; career; Clinical; clinical epidemiology; Clinical Trials; Collaborations; Committee Members; Communities; community based participatory research; Community Health; Development; Educational Activities; Educational aspects; Educational process of instructing; Environmental Health; environmental justice; Environmental Risk Factor; Epidemiologist; experience; Fostering; Funding; Health; health disparity; Health Services Research; Informatics; innovation; lectures; Manuscripts; Measures; meetings; member; Mission; Neighborhoods; next generation; Peer Review; Perception; Plant Roots; Poaceae; Policies; Policy Research; Positioning Attribute; programs; Psychosocial Factor; Recruitment Activity; Research; Research Infrastructure; Research Methodology; Research Personnel; Resources; Scientist; Series; Solutions; Surveys; Testing; Training; Work; Yang
Relevance: The mission of the Core is to advance and accelerate the development of transdisciplinary environmental health disparities research and strengthen community capacity to address environmental health issues through research and policy
Project start date: 2009-07-25
Project end date: 2013-05-31
Budget start date: 22-SEP-2011
Budget end date: 31-MAY-2012
3P60MD003421-03S1 (2011): $580758
COMPREHENSIVE CTR OF EXCELLENCE IN DISPARITIES RES & COMMUN ENGAGEMENT (CEDREC)
E Mary
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 5P60MD003421-03 from National Institute On Minority Health And Health Disparities
Abstract: This application will establish a Comprehensive Center of Excellence in Disparities Research and Community Engagement (CEDREC) as a consortium between Weill Cornell Medical College, Hunter College School of Nursing -City University of New York, Lincoln Medical and Mental Health Center and the Center for Healthful Behavior Change at New York University School of Medicine. The Director Dr. Carla Boutin-Foster and Co-Director Dr. Mary Charlson will establish 4 cores 1)The Research Core will advance health disparities research by leveraging Weill Cornell´s and New York University´s expertise in translational behavioral science research ; 2)The Research Training Core will increase the number of well-trained minority investigators by developing a Health Disparities Research program that provides health disparities research training for minority nursing students at Hunter and junior faculty at Lincoln; 3) The Community Engagement Core will strengthen the capacity for research in Central Harlem and the South Bronx and establish an active Community Advisory Board that will participate in designing new community-based projects; and 4)The Administrative Core will coordinate these scientific initiatives and establish an interdisciplinary Executive Committee and External Advisory Board that will ensure the growth and sustainability of CEDREC. Two studies that build upon our completed NHLBI funded projects are proposed. The first entitled "Trial Using Motivational Interviewing and Positive Affect and Self-affirmation in Hypertension (TRIUMPH)", is a randomized controlled trial designed to improve blood pressure control in hypertensive black patients. TRIUMPH is framed on Social Cognitive Theory and applies positive affect induction, self-affirmation induction, and motivational interviewing as behavioral strategies. The second, "Multibehavior Intervention to Increase Screening and Enhance Risk Reduction in Black Men (MISTER-B)", is a novel, randomized community-based trial, conducted in barbershops that targets hypertensive black men over age 50 who have not had colorectal cancer screening. MISTER-B will apply two strategies to improve the rates of blood pressure control and colorectal cancer screening therapeutic lifestyle counseling using motivational interviewing and peer counseling using trained patient navigators from the community. CEDREC is unique because it 1) targets hard to reach populations, black men, 2) utilizes non-traditional venues and 3) translates basic behavioral science theories to understanding and developing solutions to pressing public health issues
Project start date: 2009-07-25
Project end date: 2014-05-31
Budget start date: 10-JUN-2011
Budget end date: 31-MAY-2012
5P60MD003421-03 (2011): $1622985
SYMPTOM MANAGEMENT, PATIENT-CAREGIVER COMMUNICATION, AND OUTCOMES IN ICU
E Mary
University Of Pittsburgh At Pittsburghcity: Pittsburgh country: United States (us)
Grant 5K24NR010244-03 from National Institute Of Nursing Research
Abstract: This application for a Midcareer Investigator Award in Patient-Oriented Research (K24) requests PI salary and research funds to support Dr. Happ´s research to improve care and communication with nonspeaking ICU patients and extend her research mentorship opportunities through two new research projects that explore Symptom Management, Patient-Caregiver Communication, and Clinical Outcomes. Using an adaptation of the Revised Symptom Management Model (Dodd et al., 2001) and building on data from an existing R01 clinical trial, Project 1 will examine relationships between nurse-patient communication performance (difficulty, quality, successfulness), symptom management (symptom experience and treatment), and clinical outcome variables (ventilator-free days, length of ICU stay, hospital LOS). Project 2 will describe (1) families´ perceptions of patient communication difficulty during critical illness, (2) families´ involvement with assisted communication strategies, and (3) patient-family communication performance when ICU patients receive an assistive communication device and/or speech language pathologist (AAC- SLP) consultation intervention. In addition to advancing Dr. Happ´s skill in symptom and outcome measurement in critical illness, this award will help develop an intervention to improve family caregivers´ communication with ICU patients who are unable to speak. Testing associations between communication performance and symptom management will provide a theoretical structure for future biobehavioral research in critical illness. Investigator development will include consultation and training experiences with multi-site investigators and experts in symptom measurement with nonspeaking ICU patients well as attendance at the NIH Summer Institute in Clinical Trials Research. The Midcareer Investigator Award will provide protected time and additional opportunities to mentor undergraduate, graduate students and interdisciplinary junior faculty in theory building research, observational research techniques, and intervention development and testing. This award will also facilitate the interdisciplinary team building necessary to conduct a multi-site RCT. The proposed work is relevant to NINR´s strategic mission in several ways (1) improve recognition and management of symptoms by caregivers and health care providers; (2) develop interventions to improve the quality of caregiving, specifically nurse and family bedside caregiving in the ICU
Keywords: Address; Award; base; biobehavior; biobehavioral; Care Givers; care giving; Caregivers; caregiving; Caring; Clinical; clinical data repository; clinical data warehouse; clinical investigation; Clinical Treatment; Clinical Trials; Clinical Trials, Unspecified; Communication; Communication Aids for Disabled; Communication Aids for Handicapped; communication device; communication disorder aid; Consultations; Critical Illness; Critically Ill; Data; Data Banks; Data Bases; data repository; Data Set; Databank, Electronic; Databanks; Database, Electronic; Databases; Dataset; day length; design; designing; Development; experience; Faculty; Family; Family Care Giver; Family Caregiver; Family Nursing; Family-Centered Nursing; Funding; Future; graduate student; health care personnel; Health Care Providers; health care worker; Health Personnel; health provider; healthcare personnel; Healthcare Providers; Healthcare worker; hospital days; hospital length of stay; hospital stay; Hour; improved; Institutes; Intervention; intervention development; Intervention Strategies; interventional strategy; Investigators; K24 Mechanism; K24 Program; Language; Length; Length of Stay; Measurement; Measures; medical personnel; Mentors; Mentorship; Midcareer Investigator Award in Patient-Oriented Research; Midcareer Investigator Award in Patient-Oriented Research (K24); Mission; Modeling; National Institutes of Health; National Institutes of Health (U.S.); NIH; Number of Days in Hospital; Nurses; Outcome; Outcomes Research; Pathologist; Patient Self-Report; Patients; Perception; Performance; Personnel, Nursing; R01 Mechanism; R01 Program; relational database; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Research Technics; Researchers; RPG; Salaries; Sampling; Self-Report; Site; skills; Speech; Structure; success; Survey Instrument; Surveys; symptom management; Symptoms; Techniques, Research; Testing; theories; therapy development; Time; Training; treatment as usual; treatment development; treatment provider; trial regimen; trial treatment; United States National Institutes of Health; Ventilator; Wages; Work
Project start date: 2007-04-01
Project end date: 2011-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2011
PFA/PA: PA-04-107
5K24NR010244-03 (2009): $112743
COLUMBIA U CTR FOR CAREER DEV. IN REPRODUCTIVE SCIENCES
E Mary, Professor And Chairman, Obstetrics And G
Columbia University Health Sciencescity: New York country: United States (us)
Grant 5K12HD001275-10 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The purpose of the Columbia Center for Career Development in Reproductive Sciences (CCCDRS) is to continue to maintain an overall programmatic environment and mindset within the Department of Obstetrics; and Gynecology aimed at the recruitment, training, career development and retention of new clinician scientists. This program will aim to strengthen the Department´s commitment to develop a highly competent interacting cadre of junior faculty in Obstetrics and Gynecology dedicated to studies in Women´s Health. The CCCDRS builds on the faculty of our Center for Reproductive Sciences (CRS) which has an active faculty, structure and training process centered on both basic and clinical investigation, as well as on faculty from other departments in the College of Physicians and Surgeons within the Columbia University Institution. Through CRS and other internationally reputed Columbia faculty with whom the Department and CRS interact, we have assembled a rich research environment for our clinician scientists. In this continuing proposal, we have selected 22 mentors. These mentors have been selected with great care and according to the following criteria 1) First-rate funded research, laboratory set-up and environment; 2) Research interests that are of relevance to reproductive biology and women´s health and/or deal in techniques of crucial importance to studies in human reproduction; 3) Track record in research training, including M.D.´s; 4) Interaction with the faculty in CRS and in the Obstetrics and Gynecology department. Specific research topics are selected by the clinician scientists, with the advice of the PI and the program director and may cover any area deemed relevant to women´s health-related topics, such as perinatology and development, reproductive endocrinology and infertility, reproductive oncology and relevant public health topics. The research program is carefully tailored to each clinician scientist´s requirements. Our foremost priority is to advice and guide the scientist towards the preparation and submission of an RO1 grant, the first step towards a future independent academic career. A sizeable internal pool of clinician scientists´ candidates is currently available and an external pool will be recruited through advertising and promotion. We presently have I internal and 3 external potential candidates. Substantial institutional support exists for our training program. There is also a firm Departmental financial commitment to our clinician scientists, both during the training and for the critical set-up period following completion of the training program. The department of Obstetrics and Gynecology assumes fiscal responsibility for the CRS and is also and will remain firmly committed to the present program which will foster the training of our future junior faculty. It is envisioned that the success of the CCCDRS will be aligned with the academic accomplishments of the Department as well as the future of our specialty; ultimately, the maturation of this cadre of clinician scientists, our future leaders, will ensure success for progress in academic Obstetrics and Gynecology and in Women´s Health
Keywords: Advertising; Area; Cancer, Oncology; Cannot achieve a pregnancy; career; career development; Caring; clinical investigation; Clinical Trials; Clinical Trials, Unspecified; college; Commit; Development; Difficulty conceiving; Discipline of obstetrics; Ensure; Environment; Faculty; Female Health; Fostering; Funding; Future; Grant; Gynecology; Human; Human, General; infertile; Infertility; Institution; interest; Laboratory Research; Man (Taxonomy); Man, Modern; Medical Specialities; medical specialties; Mentors; Methods and Techniques; Methods, Other; Obstetrics; oncology; Perinatology; Physicians; Preparation; Process; programs; Programs (PT); Programs [Publication Type]; Public Health; public health medicine (field); recruit; Recruitment Activity; Reproduction; reproductive; Reproductive Biology; Reproductive Endocrinology; Research; Research Training; Science; Scientist; Specialties, Medical; Specialty; Structure; success; Surgeon; Techniques; Training; Training Programs; unable to bear children; Universities; Women`s Health
Project start date: 1999-07-23
Project end date: 2011-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2011
PFA/PA: RFA-HD-04-014
5K12HD001275-10 (2009): $388909
PSYCHOLOGY TRAINING ALCOHOL RESEARCH
E Mary, Professor
University Of Washingtoncity: Seattle country: United States (us)
Grant 5T32AA007455-28 from National Institute On Alcohol Abuse And Alcoholism
Abstract: The purpose and objectives of this training grant are to provide training in alcohol research for pre and postdoctoral students in psychology. The training program will provide quality research training in the combined areas of etiology and prevention of alcohol abuse and alcohol dependence. Research training in etiology and prevention of abuse and dependence will be approached from biological, biobehavioral, and psychosocial perspectives. Psychology is in a unique position to provide this combined emphasis in a biopsychosocial approach as the field encompasses a number of specialty areas that bears directly on the study of alcohol. The training faculty participating in the proposed program includes representatives from each of these specialty areas. The principal focus of this training program is alcohol research training in psychology at the University of Washington. Six core and 14 additional faculty, all with primary or adjunct appointments in the Depts. of Psychiatry and/or Psychology, will provide apprenticeship training and research supervision for trainees. Funds are requested to support 3 to 5 postdoctoral and 3 predoctoral trainees each year. Trainees will be required to take part in the Addictive Behaviors Core curriculum, which involves a series of courses and seminars in the field of alcohol and addiction research. Predoctoral trainees are required to complete a core curriculum consistent with departmental requirements for a Ph.D. Required courses include (1) statistics and general methodology, (2) a major area of study in clinical, physiological, developmental, or health psychology, (3) breadth requirements intended to assure broad exposure to other areas of psychology, and (4) out of area coursework relevant to the study of addictive behaviors. Trainees in the course of the program will be expected to (1) acquire research methodologies relevant to the alcohol field with both human and animal subjects and (2) apply such skills and knowledge in the design and execution of both basic and applied research related to the etiology and prevention of alcohol abuse and dependence. For all trainees there is an emphasis on developing the skills necessary for establishing an independent career in the area of alcohol-related research
Keywords: alcohol research; Psychology; Training
Project start date: 1984-07-01
Project end date: 2014-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-06-468
5T32AA007455-28 (2011): $441979
A LUNG CANCER SYMPTOM ASSESSMENT AND MANAGEMENT INTERVENTION
E Mary, Nurse Scientist
Dana-farber Cancer Institutecity: Boston country: United States (us)
Grant 5R01CA125256-04 from National Cancer Institute
Abstract: The proposed study is a two-phase study that seeks to determine the usability of a coordinated symptom assessment and management intervention (SAMI) system in phase I and to evaluate the feasibility of SAMI in Phase II. Over 80% of lung cancer patients experience multiple symptoms at presentation. To date, most studies have addressed the treatment of single symptoms. Because patients with lung cancer experience multiple symptoms, they represent an ideal group to develop and test new approaches to simultaneous management of multiple distressing symptoms. Standardized symptom and health-related quality of life (HRQOL) assessment has been identified as a potentially useful strategy to decrease distressing symptoms and improve HR-QOL. Only 3 studies have been conducted in lung cancer patients and these studies have had methodological issues. The intervention in all of the studies consisted of providing feedback to the health care provider (HCP) about results of the assessment. This study extends previous studies by adding clinical decision support to augment the effect of only providing feedback to HCPs about patient symptoms. During phase I, computer-processable algorithms for managing fatigue, pain, dyspnea, and depression in lung cancer patients will be derived from national clinical practice guidelines by a multidisciplinary team. These algorithms will be implemented on a standards-based clinical decision support system to generate patient-specific care recommendations based on data collected through a computerized symptom assessment tool. A usability evaluation using formative evaluation methods will be conducted with patients and HCPs to develop a final prototype. A pilot study using a group randomized trial (GRT) design will be conducted during phase II to evaluate the feasibility of SAMI regarding completion of the computerized symptom assessment tool and adherence to the algorithms as the primary aim and to evaluate differences in HR-QOL, patient-HCP communication, and clinical management of symptoms within two groups (SAMI and usual care) over time (baseline, 2, 4, and 6 months later) to estimate the effect size of the intervention and to estimate the within- HCP correlation of these measures among patients randomized to SAMI and treated by the same HCP as the secondary aims. We will provide HCPs with a summary of patient-reported symptoms and patient-specific symptom management recommendations based on established clinical guidelines at each clinic visit for six months. Fatigue, pain, dyspnea, and depression were chosen as the target symptoms because they are common in lung cancer patients and national guidelines are available for their management. One-hundred eighty patients will be recruited from two clinical sites; one with a racial and socioeconomic diverse population. The intervention, if feasible, will be tested in a larger GRT in the future. Symptom management interventions are important for patients with lung cancer because over 80% of patients have disease-related symptoms as well as high degrees of psychological distress. This two-part study seeks to determine the usability of a computerized symptom assessment and management system and then to pilot test the effect of the intervention in improving patient-provider communication, clinical management of symptoms, and health-related quality of life in patients receiving treatment for lung cancer
Keywords: Address; Adherence (attribute); Adjuvant Therapy; Adult; Algorithms; base; burden of illness; Cancer Etiology; Cancer Patient; cancer therapy; Caring; Cessation of life; Clinic Visits; Clinical; Clinical Decision Support Systems; Clinical Management; clinical practice; Clinical Practice Guideline; clinical research site; Clinical Trials Design; Communication; computerized; Computers; Data; design; Diagnosis; Disease; Distress; Dyspnea; Evaluation; experience; Fatigue; Feasibility Studies; Feedback; Future; Grant; Guidelines; Health; health care delivery; Health Personnel; health related quality of life; Health Services; improved; Information Technology; innovation; Interdisciplinary Study; Internet; Intervention; intervention effect; Malignant neoplasm of lung; Malignant Neoplasms; Measures; men; Mental Depression; Methodology; Methods; multidisciplinary; National Cancer Institute; NIH Program Announcements; Non-Small-Cell Lung Carcinoma; novel strategies; Outcome; Outcome Study; Output; Pain; Patients; Phase; phase 1 study; phase 2 study; Pilot Projects; Policies; Population; Population Heterogeneity; primary outcome; prototype; Provider; psychological distress; Quality-of-Life Assessment; Questionnaires; Randomized; randomized trial; Recommendation; Recruitment Activity; Reporting; Research; secondary outcome; service intervention; socioeconomics; Staging; symptom management; Symptoms; System; Technology; Testing; Time; tool; treatment as usual; usability; Woman
Project start date: 2008-06-18
Project end date: 2012-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PA-07-295
5R01CA125256-04 (2011): $393503
Sponsored Links Excellgen http://Excellgen.com
MODULATORS OF NITRIC OXIDE SYNTHASE ACTIVITY IN SICKLE CELL DISEASE
E Mary, Professor
Albert Einstein Col Of Med Yeshiva Univcity: Bronx country: United States (us)
Grant 5R01HL092183-02 from National Heart, Lung, And Blood Institute
Abstract: The primary features of sickle cell disease are events resulting in low flow, poor perfusion and blood and tissue hypoxia that are both pre-disposing to and the consequence of vaso-occlusion. We will test the overall hypothesis that BH4 (tetra-hydrobiopterin, an essential co-factor of nitric oxide synthase (NOS)) levels are decreased in sickle cell disease and in sickle transgenic mice and treatment protective of tissue BH4 levels can have greater efficacy than arginine supplementation alone to interrupt the cycle of polymerization, vaso-occlusion and inflammation that is the origin of pathology in sickle cell disease. Depletion of either arginine or BH4 results in loss of NOS NO generating capacity and production shifts to superoxide, resulting in a vicious cycle in which BH4 is oxidized and more superoxide is generated. We have demonstrated that BH4 is depleted in sickle transgenic mice due in part to oxidative stress. NOS is up regulated by hypoxia via a HIF-sensitive, hypoxia-response element. We further speculate that failure to simultaneously up regulate BH4 will increase oxidative stress. Phosphorylation at serine 1177 and threonine 495 modulate NOS activity. We have demonstrated that the percent phosphorylation at serine 1177 is reduced in mild sickle transgenic mice when they are exposed to hypoxia. We speculate that simultaneous reduction of BH4 and serine phosphorylation will severely impact NOS activity. Hemolysis is thought to be a major factor in reduction of NO bioavailability, both through reaction of cell free hemoglobin with NO and through release of argininase that depletes arginine, the substrate of NOS. We have demonstrated that arginine supplementation reduces hemolysis and oxidative stress in sickle transgenic mice, in part, via inhibition of the Gardos channel. Inhibition of the Gardos channel prevents red cell dehydration and inhibits polymer formation and hemolysis that further reduces NO bioavailability. However, arginine supplementation does not completely correct the vasculopathy observed in sickle transgenic mice. We hypothesize that some of the benefit of arginine supplementation may be due to preservation of BH4. To further test this hypothesis, we are breeding mice that over-express GTP cyclohydrolase I (GTPCH) is the rate-limiting enzyme in BH4 synthesis into our sickle transgenic strains. These observations may be applicable to patient interventions
Keywords: Acute; Adult; Affect; Amino Acids; Animals; Antioxidants; Arginine; arginine treatment; base; Benchmarking; Biological Availability; Biological Preservation; biomarker; Biopterin; Blood Vessels; Breeding; Cells; Childhood; Citrulline; Clinic; Clinical Trials; Collaborations; Dehydration; Diabetes Mellitus; Dose; drinking water; Enzymes; Erythrocytes; Event; experience; Failure (biologic function); Folate; Functional disorder; GTP Cyclohydrolase I; Hemoglobin; Hemolysis; Human; Hypoxia; improved; Individual; Inflammation; inhibitor/antagonist; Intervention; Laboratories; Lead; Mediating; Metabolism; Modeling; mouse model; Multienzyme Complexes; Mus; Nitric Oxide; Nitric Oxide Synthase; Ornithine; Oxidative Stress; Oxygen; Pathology; Pathway interactions; Patients; perfusion (blood); Peroxonitrite; Phosphorylation; Plasma; Play; polymerization; Polymers; Preparation; prevent; Production; Protocols documentation; PTGS2 gene; Pulmonary Hypertension; Rattus; Reaction; research study; response; Response Elements; restoration; Role; sepiapterin; Series; Serine; Severities; Sickle Cell; Sickle Cell Anemia; sickling; Superoxides; Supplementation; Testing; tetrahydrobiopterin; Threonine; Tissue Extracts; Tissues; Transgenic Mice; Transgenic Organisms; vascular bed; Vascular Diseases
Relevance: Nitric oxide (NO) that is made by nitric oxide synthase is thought to play a central role in sickle cell disease (SCD). Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide synthase and it may be destroyed by oxidative stress in the course of SCD. Based on our previous observations of the beneficial effects of arginine, the substrate of nitric oxide synthase, we propose to study the role of BH4 and protocols that alter the percent BH4 in our sickle transgenic mouse models
Project start date: 2009-09-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2012
PFA/PA: PA-07-070
5R01HL092183-02 (2010): $415000
LEADERSHIP/ ADMINISTRATIVE CORE
E Mary, Professor Of Medicine
Yale Universitycity: New Haven country: United States (us)
Abstract: The overarching objective of the Leadership/Administrative Core (LAC) is toadvance the field of multifactorial geriatric health condition research. The LAC, under the PI, is ultimately responsible for all scientific, fiscal, ethical, and other activities of the Yale OAIC. The four levels of the LAC include 1) Administrative Core (Director, Co-director, Administrator, and Co-administrator; 2) Core Leaders / Executive Committee; 3) Internal Advisory Panel; and 4) External Advisory Panel. The LAC has gained much experience, knowledge, and understanding of OAIC operations over its 15 years of operation, including the past 5 years under the new P30 format. Decisions are made in a collaborative manner. Efficient and effective methods for communicating and making decisions have been developed. We will build on the existing strong collaborative relatinships and expertise as we enter our next cycle. Specific activities and responsibilities of the LAC for the next 5 years include overseeing OAIC activities to ensure focus on multifactorial geriatric health conditions; overseeing access to core resouces; overseeing selection of awardees; coordinating and facilitating collaborative activities among resource cores; monitoring progress of cores and projects; identifying and facilitating collaborations with other centers and core resources at Yale and with other OAlCs and institutions; encouraging and facilitating translational research; monitoring university, government and fiscal matters; ensuring the preparation of necessary progress reports; and convening the External Advisory Panel
Keywords: Administrator; American; Area; Benchmarking; Collaborations; Communication; Counseling; Decision Making; Elderly; Ensure; Ethics; experience; Funding; Government; Health; Institution; Knowledge; Leadership; Link; meetings; member; Methods; Monitor; operation; Preparation; Progress Reports; ranpirnase; Research; Research Personnel; Resources; Structure; success; TimeLine; Translational Research; Universities; Writing
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
5P30AG021342-09_9005 (2011): $169518
REDUCING OBESITY RISK IN CHILDREN WITH DEVELOPMENTAL DISABILITIES
E Mary, Research Scientist
Temple Universitycity: Philadelphia country: United States (us)
Grant 5U13HD063168-02 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The overall purpose of this project is to establish a regional academic-community partner network to identify community-based research priorities and develop a long-term collaborative agenda to reduce obesity risk and promote long-term health in school-age children with developmental disabilities (DD) such as autism and intellectual disabilities. The proposal is organized around the central theme that community support is essential in identifying, understanding, and targeting risk factors for obesity that may contribute to poorer health outcomes for children with DD. Through this partnership, we will heighten the community´s awareness of state and local health disparities problems, and disseminate to the community relevant health promotion information based on current research findings and initiatives. While children with some DD, e.g. cerebral palsy, tend towards low weight, children with other DD diagnoses are at risk for overweight and obesity, and all are at risk for poor fitness levels and nutrition that are risk factors for obesity. In turn, the network will provide a vehicle through which the community will inform the partners of its research priorities. Through this initiative, the community´s views will culminate in development of a community-based participatory research (CBPR) agenda for developing research projects on obesity in children with DD. Specific aims include building a strong working relationship and a set of research goals focused on community priorities in addressing and reducing health disparities; providing health education about the problems related to childhood obesity in a manner that is sensitive to the community´s perceptions; reaching out to the community to identify members, areas of interest in addressing disparities in obesity; and implementing a Memorandum of Understanding between Temple University and one or more community organizations in the network for the purpose of developing a CBPR agenda on health disparities in obesity for this population. In the longer term, we anticipate that the network will build on this experience to form the core of an ongoing group of community members who continue to promote and implement an agenda for health and wellness projects for this under-served population. The two principal investigators are PIs on a recently-funded .Partners in Research. NIH Roadmap project to bridge the gap on research design between the community and the academy using CBPR principles. Through these grants, these two organizations are sharing information and perceptions of health promotion research for adults with DD. The current proposal will build on the existing funding by extending the principles we are piloting in the funded initiative to a regional network addressing a very important group whose needs are just beginning to be recognized, that is, school age children with DD. The purpose of this proposal is to establish a community-based participatory research network spearheaded by local organizations in south central Pennsylvania to decrease the risk of obesity and improve health and wellness of school-age children with developmental disabilities (DD) such as autism and intellectual disabilities. The effort will lead to a self-sustaining collaborative network dedicated to the goal of promoting good health through everyday living for this greatly under-served population. People with many DD have higher rates of obesity and lower fitness than those in the general population, and children with DD are at elevated risk
Keywords: 0-11 years old; 21+ years old; Academy; Address; adiposity; Adult; adult human (21+); Area; Autism; Autism, Early Infantile; Autism, Infantile; Autistic Disorder; Awareness; Awarenesses; base; Care, Health; Cerebral Palsy; Characteristics; Child; Child Development Disorders; Child Youth; children; Children (0-21); Chronic Disease; chronic disease/disorder; chronic disorder; Chronic Illness; Collaborations; Communities; community based participatory research; community organizations; Consultations; corpulence; corpulency; corpulentia; Development; Developmental Disabilities; Diagnosis; Doctor of Philosophy; Educational workshop; experience; Family Health; Family health status; fitness; Funding; Funding Opportunities; General Population; General Public; Goals; Grant; Health; health disparities; health disparity; Health education; Health Instruction; health literacy; Health Promotion; Health Training; Health Tutoring; Healthcare; heavy metal lead; heavy metal Pb; Human, Adult; Human, Child; improved; Institution; Intellectual disability; Intellectual functioning disability; Intellectual limitation; interest; Investigators; Kanner`s Syndrome; Knowledge; Lead; Letters; Life; meetings; member; Method LOINC Axis 6; Methodology; National Institutes of Health; National Institutes of Health (U.S.); NIH; nutrition; Nutrition; Nutritional Science; obese; obese people; obese person; obese population; Obesity; obesity in children; obesity risk; Outcome; outreach; Over weight; Overweight; Pb element; peer; Pennsylvania; Perception; Persons; Ph.D.; PhD; Population; Prevalence; Principal Investigator; public health relevance; R01 Mechanism; R01 Program; Research; Research Design; Research Grants; Research Personnel; Research Priority; Research Project Grants; Research Projects; Research Projects, R-Series; Researchers; Risk; Risk Factors; RPG; Salutogenesis; school age; school health; School-Age Population; Science of nutrition; Series; social stigma; stigma; Stigmata; study design; Study Type; under served population; underserved people; Underserved Population; United States National Institutes of Health; Universities; Weight; Work; Workshop; youngster
Relevance: The purpose of this proposal is to establish a community-based participatory research network spearheaded by local organizations in south central Pennsylvania to decrease the risk of obesity and improve health and wellness of school-age children with developmental disabilities (DD) such as autism and intellectual disabilities. The effort will lead to a self-sustaining collaborative network dedicated to the goal of promoting good health through everyday living for this greatly under-served population. People with many DD have higher rates of obesity and lower fitness than those in the general population, and children with DD are at elevated risk
Project start date: 2010-01-22
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PAR-09-092
5U13HD063168-02 (2011): $29999
E Mary, Investigator
Joslin Diabetes Centercity: Boston country: United States (us)
Abstract: The objective of the Joslin Genomics Core Facility is to provide support to Joslin and a certain number of external investigators for analysis of gene expression, by providing equipment, expertise, and services in nucleic acid analysis that would be too specialized or costly for individual laboratories to perform independently. Core services include both high-density oligonucleotide array analysis, using the Affymetrix platform, and real-time quantitative fluorescent PCR analysis. The core also provides preliminary genomic analysis, software support, and technical advice regarding experimental design and sample preparation
Keywords: Computer software; Core Facility; density; Diabetes Mellitus; Endocrinology; Equipment; Experimental Designs; Gene Expression; Genomics; Individual; Laboratories; Nucleic Acids; Oligonucleotide Microarrays; Preparation; Research; Research Personnel; Sampling; Services; Time
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
5P30DK036836-25_9015 (2011): $184930
ROLE OF CHROMATIN STRUCTURE IN REGULATING GENE SILENCING
E Mary, Associate Professor
Texas A&m University Systemcity: College Station country: United States (us)
Grant 5R01GM070930-05 from National Institute Of General Medical Sciences
Abstract: The long-term objective of this project is to learn more about how chromatin structure regulates transcriptional gene silencing in eukaryotes. The basic mechanisms used to generate inactive or silent chromatin are largely conserved in eukaryotic organisms ranging from yeast to humans. Our studies focus on understanding the roles of chromatin-associated factors, such as histones, histone-modifying enzymes, and silencing proteins, in regulating the silencing of RNA polymerase II-transcribed genes located in the ribosomal DNA locus (rDNA) of the budding yeast Saccharomyces cerevisiae. The experiments in this proposal will use a combination of genetic, molecular, and biochemical approaches to address how histones and silencing factors affect gene silencing and chromatin structure in the rDNA. First, studies to characterize the histone H3 methyltransferase complex, COMPASS, will be performed. Gene silencing is one of the only cases in S. cerevisiae, where H3 methylation has a clear effect on gene expression. The proposed experiments will investigate the role of COMPASS proteins in rDNA silencing, determine how rDNA chromatin is altered by methylation of histone H3, and address the possibility that methylated histone H3 recruits silencing factors to the rDNA. Mutagenesis studies focusing on the catalytic subunit of COMPASS coupled with in vivo and in vitro assays for COMPASS function will advance the molecular characterization of this evolutionarily conserved catalytic domain. Second, the histone composition of rDNA chromatin will be analyzed using molecular and genetic approaches. These studies will not only shed light on how histones and silencing factors function in gene silencing in S. cerevisiae, they will provide information about how related proteins function in humans. Furthermore, gene silencing is critical for normal growth and development. When the processes that regulate gene silencing are disrupted in mammalian cells, inappropriate gene expression and excessive recombination can lead to diseases, including cancer and leukemia. Our studies investigating the mechanisms that cells use to control gene silencing will provide insight into how changes in regulatory pathways can lead to malignancy and will contribute to the identification of targets for future therapeutics
Keywords: Address; Affect; Biochemical; Blood (Leukemia); Cancers; Catalytic Core; Catalytic Domain; Catalytic Region; Catalytic Site; Catalytic Subunit; Cell Cycle; Cell Division Cycle; Cells; Characteristics; Chromatin; Chromatin Structure; Complex; Coupled; Data; Defect; Disease; disease/disorder; Disorder; DNA Recombination; DNA recombination (naturally occurring); DNA, Ribosomal; DNA-Dependent RNA Polymerase II; Endomycetales; Enzymes; Eukaryota; Eukaryote; Eukaryotic Cell; eukaryotida; experiment; experimental research; experimental study; Future; Gene Expression; Gene Inactivation; gene product; Gene Silencing; Gene Transcription; Genes; Genetic Recombination; Genetic Transcription; Genetics-Mutagenesis; Genome; Goals; Growth and Development; Growth and Development function; heavy metal lead; heavy metal Pb; Histone H2A; Histone H3; histone H3 methyltransferase; histone methylase; histone methyltransferase; Histones; History; Human; Human, General; in vitro Assay; in vivo; insight; L-Lysine; Lead; Learning; leukemia; Leukemias, General; Light; living system; Lysine; malignancy; Malignant Neoplasms; Malignant Tumor; Mammalian Cell; Man (Taxonomy); Man, Modern; member; Methylation; Molecular; Molecular Biology, Mutagenesis; Molecular Genetic; Molecular Genetics; Mutagenesis; mutant; neoplasm/cancer; Numbers; Organism; Pb element; Photoradiation; Play; Process; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); protein function; Protein Methylation; Proteins; Range; rDNA; Recombination; Recombination, Genetic; Recording of previous events; recruit; Recruitment Activity; Regulatory Pathway; research study; Ribosomal DNA; RNA Expression; RNA Polymerase B; RNA Polymerase II; Role; S cerevisiae; Saccharomyces cerevisiae; Saccharomycetales; social role; Structure; Therapeutic; Transcription; Transcription Regulation; Transcription, Genetic; Transcriptional Control; Transcriptional Regulation; Yeast, Baker`s; Yeast, Brewer`s; Yeast, Budding; Yeasts
Project start date: 2004-05-01
Project end date: 2011-04-30
Budget start date: 1-MAY-2008
Budget end date: 30-APR-2011
5R01GM070930-05 (2008): $248329
BIOSTATISTICS AND DATA COORDINATING CORE (BDCC)
E Mary, Assistant Professor
University Of Pennsylvaniacity: Philadelphia country: United States (us)
Abstract: The goals of Core C (Biostatistics and Data Management) are to provide expert biostatistical guidance in the design, conduct and analysis of research projects comprising the P01, and to provide a reliable and accurate data management system for projects involving clinical data. The aims of Core C are to provide biostatistical support to P01 projects at every stage of the research Prior to the initiation of studies, Core staff will consult with investigators to help them select efficient designs and sample sizes that will give adequate power to address study objectives. For clinical studies, they will work with investigators to help set up effective patient recruitment strategies and design case report forms that collect all required information in an unambiguous way. As studies proceed, Core staff will assist in reviewing project databases and monitoring the quantity and quality of data collected, and will suggest modifications to the design or analysis plan as appropriate. When studies are finished, the Core will conduct correct and efficient data analyses, prepare any necessary graphs and tables, assist investigators with the preparation of presentations and manuscripts, and consult on the design of subsequent research. The work of Core C will interface with that of the Physics core providing data management activities during clinical projects, and with the Animal core as laboratory studies are planned and executed. The Core C staff members have extensive experience supporting cancer research, with strong backgrounds in basic science, translational research and clinical trials in addition to being themselves researchers in statistical methods. With their many years of experience with the PDT group, they look forward to further collaborative opportunities for both applying existing methods and adapting or developing new methods as needed
Budget start date: 1-FEB-2011
Budget end date: 31-JAN-2012
5P01CA087971-09_9003 (2011): $169890
SCALE: SMALL CHANGES AND LASTING EFFECTS
E Mary, Professor Of Medicine
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 5U01HL097843-03 from National Heart, Lung, And Blood Institute
Abstract: The goal of the Cornell Center for Behavioral Intervention Development is to translate basic behavioral and social science discoveries into effective behavioral interventions that reduce obesity in Black and Latino communities. To achieve this goal, we have brought together an accomplished interdisciplinary team of scientists who have expertise in conducting translational research in communities of color. Primary aim Among overweight or obese Black or Latino adults who live in Harlem or the South Bronx, the objectives are 1) to establish an infrastructure for translating basic and social science discoveries to develop effective behavioral interventions targeted at preventing and treating obesity; and 2) to further develop and refine mindful eating interventions in order to achieve a >7% within-patient reduction in weight through small sustained changes in eating behavior coupled with sustained increases in lifestyle physical activity. Phase I Defining the intervention We will further develop and refine our mindful eating intervention through focus groups in three different settings individual, family and faith-based. Then small pilot tests of the mindful eating intervention with and without a positive affect/self affirmation intervention will be done. Phase II Characterizing the intervention effects In three parallel ´proof of concept´ randomized trials, the refined mindful eating intervention will be compared in each setting to a education intervention. In these trials, the mindful eating intervention will be coupled with a positive affect/self affirmation intervention which our recently completed randomized trial has shown to significantly increase physical activity in overweight/obese patients. At 12 months, the primary outcome will be % change in weight. Phase III Assessing feasibility and refining the intervention The phase II proof of concept trials will be analyzed and the intervention will be refined. A formative study of those who fared the best and the worst in each of the settings will be done. A large scale trial will be planned to test the effectiveness of the optimized intervention. Long term objective The Center will identify which mindful eating intervention in which setting (individual, family or faith-based) coupled with positive affect/self affirmation to increase lifestyle physical activity have the potential to be more effective in creating sustainable eating and physical activity behavior change and weight loss in a scalable way in Black and Latino communities
Keywords: Adult; Affect; base; Basic Science; behavior change; Behavior Therapy; Behavioral; behavioral/social science; Body Weight Changes; Body Weight decreased; Buffers; Characteristics; Chronic; Clinic; clinical epidemiology; Clinical Research; Collaborations; Color; Communities; Cor pulmonale; Coupled; design; Diabetes Mellitus; Eating; Eating Behavior; Educational Intervention; Effectiveness; Effectiveness of Interventions; Epidemic; Evaluation; experience; faith-based intervention; Family; Fatty acid glycerol esters; field study; Focus Groups; General Population; Goals; Health; Health behavior; health disparity; Hospitals; hypertensive heart disease; Individual; Informatics; innovation; Intake; Intervention; intervention effect; Laboratory Study; Latino; Life; Life Style; Measures; Mediating; Medical center; Medical Sociology; Medicine; Morbidity - disease rate; motivated behavior; New York City; nutrition; Obesity; Outcome; Overweight; Participant; Patient Education; Patients; Phase; Physical activity; prevent; Primary Health Care; primary outcome; Psychology; public health medicine (field); Qualitative Research; randomized trial; Renaissance; Research Infrastructure; Sampling; Scientist; secondary outcome; Self Efficacy; Social Network; Social Sciences; statistics; Stress; success; Testing; theories; therapy design; therapy development; Translating; Translational Research; Treatment Efficacy; Weight; weight maintenance; Woman; Work
Project start date: 2009-09-25
Project end date: 2014-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: RFA-HL-08-013
5U01HL097843-03 (2011): $1284077
3U01HL097843-03S1 (2011): $58722
AUTOREGULATION AND SYSTEMIC BLOOD PRESSURE: A NEW VIEW OF NORMAL TENSION GLAUCOMA
E Mary, Professor Of Medicine
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 5R21EY018150-02 from National Eye Institute
Abstract: The dominant hypothesis about normal tension glaucoma is that progressive visual field loss in normal tension glaucoma is a result of elevated intra-ocular pressures. We will explore an alternative hypothesis that visual field loss in normal tension glaucoma is primarily related to systemic hypotension, specifically nocturnal hypotension, not to intra-ocular pressures. Further, we hypothesize that the visual field defects in normal tension glaucoma occur because systemic hypotension exceeds the lower limit of autoregulation resulting in ischemia and field loss. Thus, as normal tension glaucoma progresses, progressive ischemic damage and visual field loss is a result of periodic and insidious nocturnal hypotensive episodes. Among 85 patients with normal tension glaucoma; that is, patients who have visual field deficits with intra-ocular pressures <21 mm Hg, the principal objective of this study is to determine whether systemic blood pressures >20 mm Hg below the patient´s usual systemic pressure predicts longitudinal within-patient visual field loss over 12 months of follow-up. Nocturnal hypotension will be defined as mean arterial pressure that falls more than 20 mm Hg below the patients´ usual mean arterial pressure. The baseline evaluation will include basic demographic and clinical characteristics. Patients will then have their blood pressures monitored with an ambulatory recording device over the course of 48 hours and will have scanning laser tomography (Heidelberg retinal tomography), optical coherence tomography, and stereo photographs of the optic disc. At 6 and 12 months of follow up intervals, participants will also have ophthalmologic exams, visual field testing (Humphrey 24-2), scanning laser tomography (Heidelberg retinal tomography), optical coherence tomography and repeat 48 hour ambulatory blood pressure. Intra ocular pressures, medications and interval events will also be documented. Visual field loss will be assessed by longitudinal within patient changes in confocal laser scanning tomography (Heidelberg Retinal tomography), optical coherence tomography, stereo photographs and visual fields (Humphrey 24-2) performed at 6 and 12 months. The ophthalmologists adjudicating the outcomes will be blinded to the patient´s ambulatory blood pressure status, as will the technicians measuring blood pressure be blinded to the ophthalmologic measures. The data analysis requires many different multivariate techniques (principal component, spectral and wavelet analysis) to first define measures of outcome (for blood pressure and visual fields), as well as a (multivariate Bayesian) hierarchical analysis to model the longitudinal nature of the data. The effects of glaucoma can be potentially devastating, and include blindness. Of the three million Americans currently suffering from glaucoma, one sixth of patients with glaucoma have normal tension glaucoma. Among patients with normal tension glaucoma, this study will assess the role of hypotension and systemic autoregulation in progression of visual field abnormalities. This study hopes to contribute a further understanding of the relation of hypotension and intraocular pressures to the development of this disease
Keywords: Active Follow-up; adjudicate; Ambulatory Blood Pressure Monitoring; American; Analysis, Data; Anti-Hypertensive Agents; Anti-Hypertensive Drugs; Anti-Hypertensives; Antihypertensive Agents; Antihypertensive Drugs; Antihypertensives; Autoregulation; Blinded; Blindness; Blood Pressure; Blood Pressure Monitors; Blood Pressure, Low; Characteristics; Clinical; Cohort Studies; Concurrent Studies; Cranial Nerve II Injuries; Data Analyses; Development; Devices; Disease; Disease Progression; disease/disorder; Disorder; Doppler OCT; drug/agent; Drugs; Electromagnetic, Laser; enroll; Enrollment; Evaluation; Event; falls; follow-up; Glaucoma; glaucomatous; Homeostasis; Hour; Hypotension; Hypotensive Agent; Hypotensive Drugs; Hypotensives; Individual; Intraocular Pressure; Ischemia; Lasers; long-term study; Longitudinal Studies; Measurement; Measures; Medication; Methods and Techniques; Methods, Other; Modeling; Monitor; Nature; OCT Tomography; Ocular Tension; Ophthalmologist; Optic Disk; Optic Nerve Head; Optic Nerve Injuries; Optic Nerve Trauma; Optic Neuropathy, Traumatic; Optic Papilla; Optical Coherence Tomography; Outcome; Outcome Measure; Participant; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; Photography; Physiologic Intraocular Pressure; Physiological Homeostasis; Pilot Projects; pilot study; Pressure; pressure; Pressure- physical agent; prospective; Protocol; Protocols documentation; Radiation, Laser; Retinal; Risk; Role; Scanning; Scotoma; Second Cranial Nerve Injuries; Second Cranial Nerve Trauma; social role; Sphygmomanometers, Continuous; Techniques; Testing; tomography; Tomography, Optical Coherence; Vascular Hypotensive Disorder; visual field defect; Visual Field Disorder; Visual field scotoma; Visual Fields
Project start date: 2008-08-01
Project end date: 2011-07-31
Budget start date: 1-AUG-2009
Budget end date: 31-JUL-2011
PFA/PA: PA-06-181
5R21EY018150-02 (2009): $253500
SOCIAL NORMS & SKILLS-TRAINING: MOTIVATING CAMPUS CHANGE
E Mary, Professor
University Of Washingtoncity: Seattle country: United States (us)
Grant 5R01AA012547-10 from National Institute On Alcohol Abuse And Alcoholism
Abstract: The current application is a competing continuation of #R01 AA12547. The broad, long-term objective of this program of research is to reduce college student alcohol use and negative consequences. The current application builds on our prior research, through evaluating conditions under which the influence of personalized normative feedback may be enhanced. Questions to be addressed include the impact of relevance of the normative reference group, magnitude of the normative discrepancy, and comparative influence of descriptive, injunctive, or combined normative feedback on drinking behavior. The specific aims are 1) Document the gender-, ethnicity-, and residence-specific descriptive and injunctivenorms for alcohol use on campus, their relation to drinking behavior, and the degree of discrepancy between actual and perceived norms for these specific reference groups. These data will establish the norms and dimensions of normative salience utilized to address aims 2-4; 2) Compare the efficacy of descriptive norms feedbackregardingspecific referencegroups relative to each other and versusa generic (typical college student) referencegroup, as well as in comparison to comprehensivemotivational feedback (WebBASICS) and two controlgroups (repeated assessment and minimal assessment). This will be accomplished through a randomized trial using a 2 (gender-specific versus non-specific) by 2 (ethnicity- specific versus non-specific) by 2 (residence-specific versus non-specific) + 3 (repeated assessment (non-drinking feedback control);WebBASICS (full feedback comparison,); minimal assessment control) longitudinal design; 3) Evaluate proposed moderators of intervention efficacy, including a) the discrepancy between perceived and actual norms, b) the discrepancy between actual norms and drinking behavior, and c) identification with/importance of reference groups (gender, ethnicity, and residence-type); and 4) Contrast the efficacy of injunctive, descriptive, and combined normative feedback to repeated assessment (non-drinking feedback control), webBASICS (full feedback comparison), and minimal assessment in reducing alcohol use and consequences in this population. This research will provide theoretical and practical advances in the study of normative feedback interventions to combat the serious public health problem of college drinking
Keywords: 21+ years old; Active Follow-up; Address; Adult; adult human (21+); Alcohol abuse; alcohol consequences; Alcohol consumption; Alcohol Drinking; alcohol ingestion; alcohol intake; alcohol misuse; alcohol problem; alcohol product use; alcohol use; alcoholic beverage consumption; alcoholic drink intake; Alcohols; Asians; at-risk drinking; Attention; base; Behavior; Caucasian; Caucasian Race; Caucasians; Caucasoid; Caucasoid Race; Chemical Class, Alcohol; college drinking; college student; combat; comparative; comparative efficacy; Consumption; Control Groups; Data; Development; Dimensions; drinking; drinking behavior; Drugs, Nonproprietary; ethanol abuse; ethanol consumption; ethanol drinking; ethanol ingestion; ethanol intake; ethanol misuse; ethanol product use; ethanol use; Ethnic Origin; Ethnicity; Ethnicity aspects; EtOH drinking; etoh use; Evaluation; Feedback; follow-up; Frequencies (time pattern); Frequency; Gender; generic; Generic Drugs; Greek; Group Identifications; hazardous alcohol use; high risk; high risk drinking; Human, Adult; inclusion criteria; indexing; Individual; Influentials; Internet; Intervention; intervention effect; Intervention Strategies; Intervention Trial; interventional strategy; Investigators; Judgment; Literature; longitudinal design; Marketing; Measures; meetings; member; men; men`s; National Institute on Alcohol Abuse and Alcoholism; Nature; NIAAA; normative feedback; Occidental; On-Line Systems; online computer; Online Systems; oriental; Outcome; Participant; Perception; personalized normative feedback; Population; problem drinking; programs; Programs (PT); Programs [Publication Type]; Public Health; public health medicine (field); randomisation; randomization; Randomized; randomized trial; randomly assigned; recruit; Recruitment Activity; reduced alcohol use; Relative; Relative (related person); Research; Research Design; Research Personnel; Researchers; residence; Resistance; resistant; Risk; risky drinking; screening; Screening procedure; screenings; sex; skills training; social; Specificity; student drinker; Students; study design; Study Type; SUBGP; Subgroup; Testing; therapeutic efficacy; therapeutically effective; Treatment Efficacy; University drinking; university student; Variant; Variation; web; web based; white race; Woman; world wide web; WWW
Project start date: 1999-09-27
Project end date: 2011-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
5R01AA012547-10 (2011): $440458
Sponsored Links Excellgen http://Excellgen.com
RCT OF WEB VS. IN-PERSON SUD AND COMORBIDITY TREATMENT
E Mary, Professor
University Of Washingtoncity: Seattle country: United States (us)
Grant 5R01DA025051-02 from National Institute On Drug Abuse
Abstract: The broad, long-term objective of the current research is to reduce the prevalence of disordered gambling and co-morbid substance use disorders and related harm in the population, through development of efficacious and cost-effective indicated prevention/early intervention techniques. While many individuals gamble as an occasional form of entertainment, a significant subset of the population experiences substantive harm related to their gambling. Gambling has been described as a behavioral addiction, with considerable neurobiological and symptom similarity to substance use disorders (SUD). Further, disordered gambling is associated with very high rates of alcohol and drug (AOD) use and SUD co-morbidity. Gambling has been conceptualized as a continuum, from no gambling and non-problem gambling, to at-risk gambling, to diagnosable pathological gambling. Disordered gambling (at-risk and pathological) is estimated to affect 3-5% of the U. S. adult population, with higher rates often reported in young adult (college aged) populations. Disordered gambling has been associated with a host of serious consequences for the gambler and society, including financial, legal, social, familial, and work/educational difficulties as well as elevated rates of anxiety, depression, and suicidal ideation and behavior. These findings have lead to an increasing recognition of disordered gambling as a significant public health problem. The current research builds on our prior work on development of indicated prevention approaches for disordered gambling (R21 MH067026). Our findings indicate a brief, personalized feedback intervention (PFI) utilizing graphic feedback and motivational enhancement strategies is efficacious in reducing gambling and related consequences in a vulnerable population (college students) at risk for or already evidencing pathological gambling. Based on these encouraging findings, we propose to evaluate the longer-term efficacy of this approach, and determine relative efficacy of web- and in-person implementation of PFI interventions, for at-risk gamblers with co-morbid SUDs. Specific aims are 1) Evaluate relative efficacy of in-person vs. web-based PFIs in comparison to assessment only, in reducing gambling behavior, AOD use, and related consequences of at-risk college student gamblers with SUDs. Participants (N=375) screened as at- risk gamblers with SUD will be randomly assigned to one of 3 conditions a) in-person motivational PFI; b) web-based PFI; or c) repeated assessment comparison group, assessed at post-intervention, 3-, 6-, 12-, and 24-month follow-up. 2) Evaluate choice of intervention, gambling motives, and substance use as moderators of efficacy. 3) Evaluate mediators of intervention efficacy, including perceived descriptive gambling norms, readiness to change, illusions of control, and depth of processing of information. Disordered gambling has been associated with a host of serious consequences for the gambler and society, including financial, legal, social, familial, and work/educational difficulties as well as elevated rates of substance use disorders, anxiety, depression, and suicidal ideation and behavior. These findings have lead to an increasing recognition of disordered gambling as a significant public health problem. Development of efficacious indicated prevention for disordered gamblers with co-morbid substance use disorders would result in important public health benefit
Keywords: 21+ years old; Active Follow-up; addiction; Adult; adult human (21+); adult youth; Affect; Affective Psychosis, Bipolar; aged; alcohol behavior; Alcohol consumption; Alcohol Drinking; alcohol induced behavior; alcohol ingestion; alcohol intake; Alcohol or Other Drugs use; alcohol product use; alcohol related behavior; alcohol use; alcoholic beverage consumption; alcoholic drink intake; Alcohols; American Psychiatric Association; Anorexia; Anxiety; AOD use; Approaches to prevention; base; Behavior; Behavioral; bipolar affective disorder; Bipolar Disorder; Borderline Personality Disorder; BPD; Bulimia; Bulimias; Chemical Class, Alcohol; college; college student; Comorbidity; comparison group; coping; cost effective; dementia praecox; Depression; Development; Disease; disease/disorder; Disorder; Drug usage; drug use; Early treatment; ethanol behavior; ethanol consumption; ethanol drinking; ethanol induced behavior; ethanol ingestion; ethanol intake; ethanol product use; ethanol related behavior; ethanol use; EtOH drinking; etoh use; Event; experience; Feedback; Feeling suicidal; follow-up; Gambling; Gamblings; Health Benefit; heavy metal lead; heavy metal Pb; High Prevalence; Human, Adult; Illusions; indicated prevention; indicated preventive interventions; indicated preventive measure; Individual; information processing; Internet; Intervention; Intervention Strategies; interventional strategy; Lead; Legal; manic depressive disorder; manic depressive illness; Marijuana Smoking; Measures; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Mental Depression; Methods and Techniques; Methods, Other; Nervosa, Bulimia; neurobiological; Neurobiology; On-Line Systems; online computer; Online Systems; Outcome; Participant; Pathological Gambling; Pathological Gamblings; Pb element; Persons; Population; post intervention; Preparedness; Prevalence; Prevention approach; prevention directed at individuals; Process; programs; Programs (PT); Programs [Publication Type]; Psychosis, Manic-Depressive; Public Health; public health medicine (field); public health relevance; randomisation; randomization; Randomized; randomly assigned; Readiness; Relative; Relative (related person); Reporting; Research; Risk; Schizophrenia; schizophrenic; Schizophrenic Disorders; secondary outcome; social; Social Conformity; Societies; Students; substance use; Substance Use Disorder; suicidal behavior; suicidal ideation; suicidal thinking; Suicidal thoughts; suicide behavior; suicide ideation; Symptoms; Techniques; therapeutic efficacy; therapeutically effective; thoughts about suicide; Treatment Efficacy; university student; Vulnerable Populations; web; web based; Work; world wide web; WWW; young adult
Relevance: Narrative Disordered gambling has been associated with a host of serious consequences for the gambler and society, including financial, legal, social, familial, and work/educational difficulties as well as elevated rates of substance use disorders, anxiety, depression, and suicidal ideation and behavior. These findings have lead to an increasing recognition of disordered gambling as a significant public health problem. Development of efficacious indicated prevention for disordered gamblers with co-morbid substance use disorders would result in important public health benefit
Project start date: 2010-02-01
Project end date: 2015-01-31
Budget start date: 1-FEB-2011
Budget end date: 31-JAN-2012
PFA/PA: PA-07-070
5R01DA025051-02 (2011): $402840
BIOSTATISTICS AND BIOINFORMATICS CORE
E Mary, Assistant Professor
Childrens Hospital Of Philadelphiacity: Philadelphia country: United States (us)
Abstract: The Biostatistics and Bioinformatics Core, now in its 20th year of continuous funding, received an ´outstanding´ rating in 2005. The existing Core supports IDDRC researchers in experimental design and biostatistical analysis of data from traditional sources, as well as studies that use genomic and functional genomic data. Support for bioinformatics is increasingly important for our users. The proposed Core retains our existing strengths in biostatistics and statistical genetics while strengthening support for bioinformatics. During the current funding cycle, Dr. Avital Cnaan, the Core Director, relocated to Children´s National Medical Center while Dr. David Shera, a biostatistician, took a position with the pharmaceutical industry. Dr. Mary Putt became Director in 2006, continuing a productive history with the IDDRC that began as Associate Director in 1999. Dr. Marcella Devoto, a statistical geneticist, and Dr. Peter Yang, a biostatistician, were recruited to join the Core. The proposed renewal adds Dr. Peter White as co-director. Dr. White, who is nationally known for his work in genomics and bioinformatics, directs the Center for Biomedical Informatics (CBMi) at CHOP. With the tremendous growth of genomics in both basic science and clinical research at Children´s Hospital of Philadelphia and the University of Pennsylvania, our new efforts for this renewal focus on strengthening support for genomic and functional genomics studies, particularly bioinformatics
Keywords: Address; Area; Basic Science; Bioinformatics; biomedical informatics; Biometry; Child; Clinical Research; Complement; Data; Data Analyses; Development; disability; Drug Industry; Experimental Designs; functional genomics; Funding; Genetic; genetic analysis; Genomics; Growth; Medical center; Mental Retardation and Developmental Disabilities Research Centers; Methods; Pediatric Hospitals; Pennsylvania; Philadelphia; Positioning Attribute; programs; Recording of previous events; Recruitment Activity; Research; Research Personnel; Source; Universities; Work; Yang
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5P30HD026979-22_8149 (2011): $194235
STREPTOCOCCUS PNEUMONIAE OCULAR PATHOGENESIS AND THERAPY
E Mary, Associate Professor
University Of Mississippi Medical Centercity: Jackson country: United States (us)
Grant 5R01EY016195-05 from National Eye Institute
Abstract: Streptococcus pneumoniae is a major cause of bacterial keratitis. Pneumococcal keratitis causes damage that can result in irreversible corneal scarring. The corneal damage seen in pneumococcal keratitis has been attributed mainly to bacterial virulence factors that stimulate an intense host response. Important to pneumococcal keratitis is the production of pneumolysin, a virulence factor capable of cell lysis as well as the activation of complement. In non-ocular infections, the production of pneumolysin is not sufficient to achieve virulence; the organism must also produce a polysaccharide capsule. The role of the capsule in keratitis or other ocular infections has not been established and preliminary data from this laboratory suggests that the capsule may not contribute to ocular virulence. This point is significant because vaccination of patients has been suggested as a means to prevent pneumococcal ocular infections. The research proposed is designed to develop means to limit the damage associated with pneumococcal keratitis. This research consists of using new therapies directed toward the virulence factors responsible for protecting the organism and stimulating the damaging inflammatory response. The immediate aims are to 1) determine if the capsule is a virulence factor in keratitis, a study that could show that the cornea, unlike vascularized body sites, is susceptible to infection by unencapsulated strains; 2) determine if the inhibition of pneumolysin by topical application of a molecule that inhibits its binding to cells will provide protection against inflammation to the infected cornea, a possibility that is supported by preliminary studies; and 3) determine if antibody to pneumolysin can be used actively or passively to limit or prevent the ability of this molecule to induce inflammation with tissue damaging effects. From a public health perspective, bacteria including pneumococcus are becoming increasingly resistant to antibiotics. The development of alternative and novel therapies for bacterial eye infections will help to prevent scarring and loss of the eye
Keywords: Alternative Therapies; Antibiotic Agents; Antibiotic Drugs; Antibiotic Resistance; antibiotic resistant; Antibiotic Therapy; Antibiotic Treatment; Antibiotics; Antibodies; Antisera; Award; Bacteria; Bacterial Eye Infections; base; Binding; Binding (Molecular Function); Blood Neutrophil; Blood Polymorphonuclear Neutrophil; Blood Segmented Neutrophil; Body Tissues; CAPS; capsule (pharmacologic); Capsules; Cells; Cholest-5-en-3-ol (3beta)-; Cholesterol; Cicatrix; cicatrix corneal; Clinical; Complement Activation; complement pathway regulation; Conjunctivitis; Cornea; corneal; corneal epithelial; corneal epithelium; corneal scar; Cytolysis; D. pneumoniae; D.pneumoniae; Data; design; designing; Development; Diplococcus pneumoniae; direct application; Disease; disease/disorder; Disorder; Drug Administration, Topical; effective therapy; Endophthalmitis; Epithelial Cells; Epithelium, Anterior Corneal; Epithelium, Corneal; Eye; Eye Infections; Eye Infections, Bacterial; Eyeball; Glycans; Goals; Group Meetings; heavy metal lead; heavy metal Pb; Heterophil Granulocyte; host response; Human; Human, General; Immune; Immune response; Immune Sera; Immunoglobulin Isotypes; Immunology; Immunology (Including BRMP); Immunology (NCI Program); immunoresponse; In Vitro; Infection; Inflammation; Inflammatory Response; INFLM; intervention development; Investigators; Keratitis; Killings; Knowledge; Laboratories; Lead; living system; Lysis; Mammals, Rabbits; Man (Taxonomy); Man, Modern; Marrow Neutrophil; Mediating; meetings; Meningitis; Microbiology; Miscellaneous Antibiotic; Modeling; Molecular Interaction; Morbidity; Morbidity - disease rate; mutant; neutrophil; Neutrophilic Granulocyte; Neutrophilic Leukocyte; novel; Ocular Infections; Ocular Infections, Bacterial; Ophthalmia; Ophthalmology; Organism; Oryctolagus cuniculus; Otitis Media; Parents; pathogen; Pathogenesis; Pathogenicity Factors; Patients; Pb element; Phenotype; plY protein, Streptococcus pneumoniae; pneumococcal disease; Pneumococcal Infections; Pneumococcus; pneumococcus infection; pneumolysin; Pneumonia; Pneumonitis; Polymorph; Polymorphonuclear Cell; Polymorphonuclear Leukocytes; Polymorphonuclear Neutrophils; Polysaccharides; prevent; preventing; Prevention; Production; programs; Programs (PT); Programs [Publication Type]; Public Health; public health medicine (field); Publishing; Pulmonary Inflammation; Rabbit, Domestic; Rabbits; Reagent; Research; Research Personnel; Researchers; Resistance; Resistance to antibiotics; Resistance, Antibiotic; resistant; Resistant to antibiotics; Role; S. pneumoniae; Scars; Science of Microbiology; Sight; Site; social role; Streptococcus pneumoniae; Streptococcus pneumoniae Infections; Streptococcus pneumoniae plY protein; Structure of corneal epithelium; success; Symptoms; Testing; therapy development; Tissues; topical administration; Topical application; topical drug application; topically applied; treatment development; treatment of bacterial diseases; treatment of bacterial infectious disease; Vaccination; Vaccines; Virulence; Virulence Factors; Vision; vision science; Work
Project start date: 2007-03-01
Project end date: 2012-02-29
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
5R01EY016195-05 (2011): $225423
GENDER EFFECTS ON AMPHETAMINE-INDUCED DOPAMINE RELEASE AND SUBJECTIVE RESPONSES
E Mary, Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 5R01DA021779-03 from National Institute On Drug Abuse
Abstract: Sex differences in drug effects is an area of emerging importance for understanding the neurological bases, etiology, epidemiology, toxicity, prevention and treatment of drug use. There is now solid evidence of gender differences in the serotonin neurotransmitter system that may account for differences in rates of depression and anxiety in men and women and therapeutic responses to SSRIs. Of even greater relevance to the proposed study, gender differences have been confirmed in the dynamics of tobacco smoking and cessation in humans. These differences have been attributed to acute and chronic effects of ovarian steroid hormones on nicotinic receptors, although findings have not been conclusive. Using positron emission technology (PET), we recently have reported robust sex differences in dopamine release (DAR) to amphetamine administration in healthy, age-matched men and women; this is the first demonstration of gender-based DAR differences in human subjects. This research has high significance from both a basic science and clinical intervention perspective. Using PET, the proposed study will examine possible mechanisms for gender-based differences in DAR following amphetamine administration in healthy, age-matched men and women. Female subjects will be scanned during both the luteal and follicular phases of their menstrual cycle. Subjects will complete measures of subjective effects of amphetamine. In addition, we will obtain a sex hormone/neurosteroid profile on male and female subjects and determine the relationship to DAR. If our hypotheses of the roles of sex hormones/neurosteroids in DAR are supported, these findings will be important in understanding the etiology, epidemiology, neurotoxicity, prevention and treatment of stimulant use disorders. Further, the scientific and clinical importance of the results extends beyond addiction to include other disorders involving dopamine in the striatum, including schizophrenia, Parkinson´s disease, Huntington´s disease and obsessive-compulsive disorder. Our laboratory has recently found that healthy, young adult men release more dopamine, a brain chemical that influences the rewarding and euphoric effects of stimulant drugs, and report greater "high" and "drug liking" following amphetamine administration compared with age-matched women. The proposed research will study these sex differences, whether the effects of amphetamine change in women during the menstrual cycle, and the role of sex hormones (estrogen, progesterone and testosterone) in modifying drug effects on dopamine. Findings will have considerable public health significance in furthering our understanding of normal sex differences in brain function and hormonal mechanisms for these effects, thus paving the way to better understand these factors in substance abuse and other neuropsychiatric disorders
Keywords: (17Beta)-17-hydroxyandrost-4-en-3-one; 17-beta-Hydroxy-4-Androsten-3-one; 3, 4-Dihydroxyphenethylamine; 3-(2-Aminoethyl)-1H-indol-5-ol; 4-(2-Aminoethyl)-1, 2-benzenediol; 5-HT; 5-Hydroxytryptamine; 5HT; abuse of substances; Accounting; Acute; addiction; adult youth; Affective Disorders; Age; Amphetamines; Androst-4-en-17beta-ol-3-one; Anxiety; Area; base; Basic Research; Basic Science; Benzamide, 3, 5-dichloro-N-((1-ethyl-2-pyrrolidinyl)-methyl)-2-hydroxy-6-methoxy-; Benzeneethanamine, N, alpha-dimethyl-, (S)-; Brain; Cannabinoids; Causality; Chemicals; Chronic; Clinical; Corpus Luteum Hormone; Corpus Striatum; Corpus striatum structure; Crystal Meth; Delta4-androsten-17beta-ol-3-one; Delta4-pregnene-3, 20-dione; dementia praecox; Deoxyephedrine; Depression; Desoxyephedrine; Disease; disease causation; disease etiology; disease/disorder; disease/disorder etiology; Disorder; disorder etiology; Dopamine; Drug usage; drug use; drug/agent; Drugs; Encephalon; Encephalons; Enteramine; Epidemiology; Estrogenic Agents; Estrogenic Compounds; Estrogens; Etiology; Female; Follicular Phase; Gender; gender difference; Gonadal Steroid Hormones; gonadal steroids; Health; High Prevalence; Hippophaine; Hormonal; Household; Human; human subject; Human, General; Huntington Chorea; Huntington Disease; Huntington`s; Huntington`s Disease; Huntington`s Disease Pathway; Huntingtons Disease; Hydroxytyramine; Idiopathic Parkinson Disease; Intervention; Intervention Strategies; interventional strategy; Investigation; Laboratories; Lewy Body Parkinson Disease; Life; Luteal Phase; male; Man (Taxonomy); Man, Modern; Measures; Medical Imaging, Positron Emission Tomography; Medication; men; men`s; Menstrual cycle; Menstrual Cycle, Follicular Phase; Menstrual Cycle, Luteal Phase; Menstrual cycle, proliferative phase; Menstrual Cycle, Secretory Phase; Menstrual Proliferative Phase; Menstrual Secretory Phase; Mental Depression; mesolimbic system; Methamphetamine; Methylamphetamine; Mood Disorders; Moods; N-Methylamphetamine; Nerve Transmitter Substances; Nervous System, Brain; neuroimaging; Neurologic; Neurological; neuron toxicity; neuronal toxicity; neuropsychiatric; neuropsychiatry; neurosteroids; neurotoxicity; Neurotransmitters; Nicotinic Acetylcholine Receptors; Nicotinic Receptors; Obsessive-Compulsive Disorder; Obsessive-Compulsive Neurosis; Opioid; Ovarian Steroid Hormone; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson`s; Parkinson`s disease; Parkinsons disease; Personality; PET; PET imaging; PET Scan; PETSCAN; PETT; Pharmaceutic Preparations; Pharmaceutical Preparations; Positron; Positron Emission Tomography Scan; Positron-Emission Tomography; Postovulatory Phase; Pregn-4-ene-3, 20-dione; Pregnenedione; Preovulatory Phase; Prevention; Primary Parkinsonism; Procedures; Progesterone; Progressive Chorea, Hereditary, Chronic (Huntington); proliferative phase Menstrual cycle; Proton Magnetic Resonance Spectroscopic Imaging; psychologic; psychological; Public Health; public health medicine (field); Raclopride; Rad.-PET; Reporting; Research; response; Rewards; Role; Saline; Saline Solution; Scanning; Schizophrenia; schizophrenic; Schizophrenic Disorders; Serotonin; Sex Characteristics; Sex Differences; Sex Hormones; sex steroid; Sex Steroid Hormones; sexual dimorphism (noncellular); social role; Solid; Stress; stressor; striatal; Striate Body; Striatum; substance abuse; Substance abuse problem; Survey Instrument; Surveys; System; System, LOINC Axis 4; Technology; Testosterone; Therapeutic; Therapeutic Estrogen; Therapeutic Progesterone; Therapeutic Testosterone; Tobacco Cessation; Tobacco smoking; Tobacco Use Cessation; Toxic effect; Toxicities; Trans-Testosterone; Woman; young adult
Relevance: Our laboratory has recently found that healthy, young adult men release more dopamine, a brain chemical that influences the rewarding and euphoric effects of stimulant drugs, and report greater "high" and "drug liking" following amphetamine administration compared with age-matched women. The proposed research will study these sex differences, whether the effects of amphetamine change in women during the menstrual cycle, and the role of sex hormones (estrogen, progesterone and testosterone) in modifying drug effects on dopamine. Findings will have considerable public health significance in furthering our understanding of normal sex differences in brain function and hormonal mechanisms for these effects, thus paving the way to better understand these factors in substance abuse and other neuropsychiatric disorders
Project start date: 2009-03-15
Project end date: 2014-01-31
Budget start date: 1-FEB-2011
Budget end date: 31-JAN-2012
PFA/PA: PA-07-329
5R01DA021779-03 (2011): $494799
ALCOHOL USE TRAJECTORIES AND PREVENTION: A US-SWEDEN COMPARISON
E Mary, Professor
University Of Washingtoncity: Seattle country: United States (us)
Grant 5R01AA018276-02 from National Institute On Alcohol Abuse And Alcoholism
Abstract: Research suggests late adolescence and emerging adulthood (EA; roughly encompassing ages 18-25) are associated with increased risk for development of substance misuse, abuse, and dependence. Despite increased risk overall during this period, there is considerable variability in drinking trajectories during young adulthood (Schulenberg et al., 1996; Tucker et al., 2005). Much of the research on alcohol use and prevention during EA has focused on students who matriculate into college during this period (Larimer & Cronce, 2002), with relatively little research focused on etiology and prevention of alcohol use among individuals who do not immediately matriculate to college (White et al., 2005). Further, little research has compared trajectories of alcohol use and consequences in international samples, including the individual, social, and environmental/cultural factors influencing trajectories and transitions in alcohol use patterns. Finally, almost no research has systematically evaluated efficacy of preventive interventions offered prior to the transition from high school as a means of altering trajectories during EA. The current research is designed to address these gaps, through a longitudinal study of a cohort of high school students in both the US and Sweden, and the evaluation of web-based interventions offered to a random subset (n=400 per country) at the end of high school as a means of reducing or preventing excessive alcohol consumption and related consequences. Specific aims of the current application are 1) Evaluate intrapersonal, peer, parental, environmental, and cultural predictors of alcohol use trajectories upon the transition from high school in US and Swedish populations, guided by the Theory of Triadic Influence; 2) Evaluate the efficacy of a web-based interactive feedback and skills intervention in reducing alcohol use and negative consequences over a four- year follow-up period; 3) Evaluate moderators of intervention efficacy, including individual-level and cultural factors; and 4) Evaluate mediators of intervention efficacy. Aims will be achieved through a longitudinal follow-up survey of 2400 teens across 2 sites the King Country region of Washington State and the Skane region of Sweden. Teens will be recruited during their senior year in high school and assessed twice per year for 4 years. RELEVANCE (See instructions); Alcohol misuse during emerging adulthood is an international public health problem. This research evaluates trajectories and prevention of alcohol use, using the framework of the Theory of Triadic Influence to evaluate transitions into and out of heavy drinking across emerging adulthood. The international comparison allows for disentangling of effects of development from other factors including matriculation into college and attaining legal drinking age, and impacts of distal cultural factors which vary between the US and Sweden
Keywords: Address; Adolescence; Advertisements; Age; alcohol consequences; Alcohol consumption; alcohol exposure; alcohol misuse; Alcohols; base; Behavioral; cohort; college; Country; County; Dependence; design; deter alcohol use; Development; Distal; drinking; drinking behavior; emerging adulthood; Etiology; Evaluation; Event; Exhibits; Expectancy; experience; Family history of; Feedback; follow-up; Frequencies (time pattern); Friends; Goals; Growth; Haemophilus influenzae type b bacteria; Heavy Drinking; high school; Individual; Instruction; International; Intervention; legal drinking age; Life; Longitudinal Studies; Mediating; Mediator of activation protein; Modeling; non-drug; Online Systems; parental monitoring; Parents; Participant; Pattern; peer; Perception; Pharmaceutical Preparations; Population; prevent; Prevention; Preventive Intervention; Principal Investigator; public health medicine (field); Readiness; Recruitment Activity; reduced alcohol use; Relative (related person); Research; Risk; risk perception; Sampling; Self Efficacy; sex; Site; skills; social; Students; Subgroup; Surveys; Sweden; Teenagers; theories; Time; Treatment Efficacy; Washington; young adult
Project start date: 2010-05-05
Project end date: 2015-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PAR-08-004
5R01AA018276-02 (2011): $505222
COMPLEMENTARY AND INTEGRATIVE MEDICINE TRAINING PROGRAM
E Mary, Professor Of Medicine
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 5T32AT001161-05 from National Center For Complementary & Alternative Medicine
Abstract: Our objective is to prepare post-residency physicians with knowledge and skills to conduct scientifically rigorous research in complementary and integrative medicine. The program will focus on complementary approaches that may be useful in the prevention and treatment of chronic illnesses and integrated with conventional medicine. The program will emphasize two areas evaluation of natural products (botanical, herbal and other bio-organic extracts); and psychobiological medicine (meditation, social support, guided imagery, spirituality, yoga, tai chi, and aerobic exercise). The two-year program will emphasize conceptual, methodological and practical foundations to conduct methodologically rigorous research in complementary and integrative medicine. The fellows will enroll in the Master´s Program in Clinical Epidemiology and Health Services Research with 20 required courses. In addition, they will enroll in nine courses focusing on CAM modalities and taught by CAM practitioners. Each fellow will complete all courses and use their resultant knowledge and skills to design and conduct their own research project under highly structured mentorship. This program is research intensive and the research projects are at the core of each fellow´s work. The CAM practitioners will form a collaborative research network to provide the foundation for fellows´ projects in different disciplines. The program is built on the strengths of our multidisciplinary faculty, who have collaborated for fifteen years, with expertise in clinical epidemiology, health services research, behavioral science, biostatistics, health economics and medical informatics. We have now developed a partnership with CAM practitioner experts in mind-body medicine including meditation, guided imagery, yoga, tai chi, qigong, and practitioner experts in acupuncture and traditional Chinese Medicine. This program will prepare new investigators to contribute new knowledge that distinguishes effective CAM treatments from ineffective or potentially harmful ones. It will prepare fellows to become independent investigators who can successfully compete for peer-reviewed funding. A key element of the program is to foster the development of minority scholars in the field of complementary and integrative medicine research. The overall goal of our post-doctoral program is to develop physician-scientist experts in research methodology, who will go on to conduct their own CAM research
Keywords: integrative healing; Integrative Medicine; Training Programs
Project start date: 2004-06-15
Project end date: 2011-06-30
Budget start date: 1-JUL-2008
Budget end date: 30-JUN-2011
PFA/PA: PA-02-109
5T32AT001161-05 (2008): $117752
MECHANISMS OF NON-ALCOHOLIC STEATOHEPATITIS
E Mary, Assistant Professor
Northwestern Universitycity: Chicago country: United States (us)
Grant 5K08DK066032-05 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Non-alcoholic steatohepatitis (NASH) is a major public health problem that can lead to hepatocellular carcinoma and cirrhosis requiring liver transplantation. NASH is an increasingly common condition that is rising in prevalence in parallel with associated conditions such as obesity and type II diabetes. There are no approved treatments for NASH and the mechanisms of disease progression remain largely unknown. Endoplasmic reticulum (ER) stress is an adaptive cellular response to a variety of stressors including excess intrahepatic triglyceride. In experimental models, excessive ER stress promotes apoptosis, further lipid accumulation and activation of pro-inflammatory pathways such as NF-KB thought to be important in the pathogenesis of NASH. Feeding mice a methionine-choline deficient (MCD) diet induces steatohepatosis that resembles human NASH and liver injury is exacerbated in db/db mice fed this diet. The mechanisms by which the MCD diet leads to lipid accumulation and liver injury are incompletely understood. Thus, Specific Aim #1 will define mechanisms of lipid accumulation and liver injury in the db/db mouse fed this diet. Preliminary data from our laboratory illustrate the presence of robust ER stress signaling in both MCD fed db/db mice and human NASH liver biopsy samples. We hypothesize that in this experimental model, ER stress stimulates pathways important to progressive liver injury. Therefore, Specific Aim #2 will show that ER stress is a prominent feature of MCD diet induced steatohepatitis by examining key elements of the PERK and IRE-1 ER stress pathways, and then demonstrate improvement in steatohepatitis through attenuation of ER stress using tauroursodeoxycholic acid (TUDCA). Specific Aim #3 will confirm these findings in hepatocytes exposed to MCD medium and we will determine if c-Jun N-terminal kinase (JNK) mediated NF-KB activation is IRE-1 dependent in this model system. NASH is an important field of research and both my mentor and institution fully support this research proposal. They have made protecting time a priority during the term of my current grant and will continue to do so should I be selected for funding. If awarded a K08, I will apply for an R01 in the last year of the award. Non-alcoholic steatohepatitis (NASH) is a major public health problem and a growing indication for liver transplantation. The experiments outlined in this grant proposal will explore the role of endoplasmic reticulum stress in the development of liver injury in a mouse model of NASH. We hope that insight gained from this work will identify factors responsible for the development of NASH that will guide future experiments and ultimately therapy in human NASH
Keywords: Acids; Animal Model; Apoptosis; Applications Grants; attenuation; Award; biological adaptation to stress; Biological Models; Biopsy Specimen; Choline; choline deficient diet; Cirrhosis; Clinical; Data; db/db mouse; Development; Diabetes Mellitus; diabetic; Diet; Disease; Disease Progression; Elements; Endoplasmic Reticulum; endoplasmic reticulum stress; Eugenia; Evolution; Excision; Experimental Models; Fatty Liver; feeding; Fibrosis; Funding; Future; Grant; Hepatic; Hepatocyte; Human; Hyperglycemia; In Vitro; in vivo; Inflammation; Inflammatory; Injury; insight; Institution; Insulin; Insulin Resistance; intrahepatic; Laboratories; Lead; Lipids; Liver; liver biopsy; liver transplantation; Mediating; Mentors; Methionine; Modeling; mouse model; Mus; N-terminal; Necrosis; non-diabetic; Non-Insulin-Dependent Diabetes Mellitus; nonalcoholic steatohepatitis; Obesity; Pathogenesis; Pathologic; Pathway interactions; Phase; Phosphotransferases; Prevalence; Primary carcinoma of the liver cells; Process; public health medicine (field); Research; Research Personnel; Research Proposals; research study; response; Role; Signal Transduction; Steatohepatitis; stress-activated protein kinase 1; stressor; tauroursodeoxycholic acid; Testing; Time; Tissues; Triglycerides; Work
Project start date: 2007-09-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-06-512
5K08DK066032-05 (2011): $126144
CLONING AND CHARACTERIZATION OF CANNABINOID RECEPTORS
E Mary, Associate Professor
Virginia Commonwealth Universitycity: Richmond country: United States (us)
Abstract: Marijuana is currently the most widely abused illegal drug. However, the functional significance of the cannabinoid receptor system in health and disease includes the use of cannabinoids as analgesics, antiemetics in cancer patients, anticonvulsants for epilepsy and as antiglaucoma agents as well as immunomodulatory agents. To date, two cannabinoid receptor subtypes, CBt and CB2, have been identified by cDNA cloning, yet the complex pharmacological properties of anandamide as well as exogenous cannabinoids are not fully defined by these two subtypes. Anandamide produces the full range of behavioral effects (antinociception, catalepsy and impaired locomotor activity) in CBi receptor knockout mice. In addition, anandamide-stimulated GTPyS activity can be elicited in brain membranes from these mice. Finally, radioligand binding studies indicate the existence of additional binding sites in brain and spinal cord. The goal of this project is to identify and characterize additional subtypes of the cannabinoid receptors in order to elucidate their role in vivo. The first specific aim is to characterize candidate orphan GPCRs for cannabinoid receptor activity. GPR55 has recently been identified as a candidate cannabinoid receptor, and we have evidence that GPR35 has cannabinoid receptor activity. GPR18 is a receptor for Narachinoylglycine, an endocannabinoid. GPR119 is a receptor for oleoylethanolamide and palmitoylethanolamide. We propose to characterize these candidate cannabinoid receptors by expression in heterologous cell lines, allowing the detailed characterization of ligand selectivity and signaling. The second specific aim will identify additional orphan GPCRs with cannabinoid receptor activity using an expression cloning strategy. In specific aim 3, we will investigate the functional role of novel cannabinoid receptors. The experiments in this aim are designed to utilize our collaborations with other Center Grant Investigators in order to understand the functional roles of the candidate cannabinoid receptors. These studies will facilitate the design of new therapeutic strategies involving the cannabinoid system. Furthermore, insight into the molecular mechanisms of activation of cannabinoid receptors may lead to a better understanding of marijuana abuse in humans
Keywords: Absence of pain sensation; Adenylate Cyclase; Agonist; Analgesics; anandamide; Anticonvulsants; Antiemetics; Behavioral; Binding (Molecular Function); Binding Sites; Biochemical; Brain; Calcium; Cancer Patient; cannabinoid receptor; Cannabinoids; Catalepsy; Cell Line; Cloning; Collaborations; Complementary DNA; Complex; Coupled; Data; design; Disease; Drug abuse; Endocannabinoids; Epilepsy; expression cloning; Functional disorder; G Protein-Coupled Receptor Genes; Goals; Grant; GTP-Binding Proteins; Guanosine Triphosphate; Health; Human; In Situ Hybridization; in vivo; insight; Knock-out; Knockout Mice; Lead; Libraries; Ligands; Marihuana; Marijuana Abuse; Mediating; Membrane; Messenger RNA; Methods; Mitogen-Activated Protein Kinases; Molecular; Motor Activity; Mus; novel; novel therapeutics; oleoylethanolamide; Oocytes; Opioid; Orphan; palmidrol; Pharmaceutical Preparations; Play; Property; protein activation; radioligand; receptor; receptor expression; Regulation; Research; Research Personnel; research study; response; Role; Scientist; Screening procedure; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Spinal; Spinal Cord; System; Testing; Tissues; tool; Xenopus oocyte
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5P50DA005274-23_0020 (2011): $192581
5P50DA005274-22_0020 (2010): $191612
THERAPEUTIC COMPETITION AMONG DISEASES IN ELDERS: FREQUENCY AND OUTCOMES
E Mary, Professor Of Medicine
Yale Universitycity: New Haven country: United States (us)
Grant 1R03AG035146-01A1 from National Institute On Aging
Abstract: In this pilot study, we begin to examine the prevalence and health effects of co-occurring chronic diseases for which there is potential therapeutic competition (i.e. the treatment of one disease worsens another disease or interferes with treatment response). We focus on therapeutic competition, one of several clinical dilemmas arising from multi-morbidity, because of the inherent potential to inflict harm. The Primary Aims are to determine 1) the prevalence among older adults of the co- occurrence of selected chronic diseases for which there is potential therapeutic competition; and 2) whether there are differences in treatments received, and adhered to, by older adults with, vs. without, selected co-occurring conditions for which there is potential therapeutic competition. The exploratory aim is to determine whether health and disease-specific outcomes differ among older adults with a selected disease according to the treatment received for co-occurring diseases with potential therapeutic competition. The selected diseases for which we will evaluate the frequency and consequences of co-occurring diseases with potential therapeutic competition include diabetes, heart failure, COPD, and osteoporosis. For this pilot study, we focus on medications as the source of therapeutic competition. The co-occurring diseases with potential therapeutic competition with the selected diseases are chosen based on 1) evidence; 2) biology of the diseases and treatments; and 3) disease specialty guidelines. Participants are members of 2 nationally representative longitudinal cohorts of older adults, both sampled from throughout the U.S. The Medical Expenditure Panel Study (MEPS) has over 11,000 and the Medicare Current Beneficiary Study (MCBS) over 18,000 participants age 65+ years. Both MEPS and MCBS include a wealth of longitudinal data on chronic diseases, disease treatments including medications, health outcomes, and disease-specific outcomes for the selected diseases. Results of this pilot study will heighten awareness and understanding of this important but understudied area and lay the methodological groundwork for future studies. The clinical dilemmas arising from the growing numbers of older adults with multi-morbidity mandate careful scrutiny to ensure that our diagnostic, preventive, and therapeutic armamentaria are deployed as safely and effectively as possible. Therapeutic competition (i.e. the treatment of one disease worsens another disease or interferes with response to treatment) is one of several clinical dilemmas arising from the co-occurrence of two or more diseases. Results of this pilot study will heighten awareness and understanding of this important but understudied area and lay the methodological groundwork for future studies. The clinical dilemmas arising from growing numbers of older adults with multiple chronic diseases mandate careful scrutiny to ensure that our diagnostic, preventive, and therapeutic armamentaria are deployed as safely and effectively as possible
Keywords: Accounting; Address; Adherence (attribute); Affect; Age; Area; Awareness; base; beneficiary; Biology; Chronic Disease; Chronic Obstructive Airway Disease; Clinical; clinical decision-making; cohort; Comorbidity; Data; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; disease characteristic; Disease Outcome; Elderly; Ensure; Expenditure; Frequencies (time pattern); Future; Guidelines; Health; Heart failure; Knowledge; Medical; medical specialties; Medicare; member; Morbidity - disease rate; Osteoporosis; Outcome; outcome forecast; Participant; Persons; Pharmaceutical Preparations; Pilot Projects; Prevalence; Preventive; Research; response; Sampling; Source; Therapeutic; treatment effect; treatment response
Relevance: Therapeutic competition (i.e. the treatment of one disease worsens another disease or interferes with response to treatment) is one of several clinical dilemmas arising from the co-occurrence of two or more diseases. Results of this pilot study will heighten awareness and understanding of this important but understudied area and lay the methodological groundwork for future studies. The clinical dilemmas arising from growing numbers of older adults with multiple chronic diseases mandate careful scrutiny to ensure that our diagnostic, preventive, and therapeutic armamentaria are deployed as safely and effectively as possible
Project start date: 2011-09-30
Project end date: 2013-08-31
Budget start date: 30-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-09-163
1R03AG035146-01A1 (2011): $67889
Sponsored Links Excellgen http://Excellgen.com
PROMOTING BREAST CANCER SCREENING IN NON-ADHERENT WOMEN
E Mary, Associate Professor Of Medicine
Univ Of Massachusetts Med Sch Worcestercity: Worcester country: United States (us)
Grant 5R01CA132935-03 from National Cancer Institute
Abstract: In the U.S. about 23 million women aged 50-74 are overdue for recommended biennial screening mammography. Repeated annual screening is considered optimal by some experts and even more women would be overdue by this standard. The reduction in breast cancer mortality expected from screening mammography requires repeated mammogram use, so women who do not have a mammogram every 1-2 years are at risk for developing advanced stage or incurable breast cancers. NHIS 2005 data show a significant drop in mammograms gotten in the prior 24 months. Between 2000 and 2005, rates dropped for women aged 50-64 from 78.6 to 71.8% and for those >65, from 68 to 63.8%. Those most affected had higher incomes, private insurance and a usual source of care. Despite strong evidence that mail and telephone outreach to women can increase mammography rates, few health care delivery organizations have adopted comprehensive outreach programs, especially ones including a telephone component. Reasons for this include 1) uncertainty about the optimum outreach strategy and long-term effectiveness; 2) absence of feasible, replicable models for use in large organizations; and 3) cost and cost-effectiveness data to guide the decisions on implementation. To address these concerns this study aims to identify the most effective and cost effective of the outreach strategies that studies have been shown to be effective or promising. We propose to randomize all women age 51-84 enrolled in a large group model HMO (n=23,000) to 1 of 3 intervention arms. We will continue to enroll new HMO members and to deliver the interventions over a 4-year period to assess long-term outcomes. The interventions are 1) a reminder letter only (RL) (usual care for this HMO); 2) a reminder letter followed by a reminder phone call to nonresponders (RL-RC) that includes an opportunity to schedule a mammogram; and 3) a reminder letter followed by an enhanced, tailored telephone counseling (ETTC) to nonresponders (RL-ETTC) that includes motivational interviewing, barrier-specific counseling, and an opportunity to schedule a mammogram. Our aims are to 1) compare the effectiveness of the 3 interventions in increasing adherence to screening mammography guidelines (mammogram every 1-2 years) each year for 4 years; 2) Identify ways to improve the efficiency and sequencing of the interventions by identifying patient factors and intervention mechanisms associated with increased intervention effectiveness; and 3) to determine the incremental cost per unit increase in on-time mammography utilization of the 2 telephone counseling arms compared to the mailed reminder only intervention. We hypothesize that ETTC intervention will be associated with a higher prevalence of mammography within 24 months than the brief telephone reminder intervention, and both telephone interventions will be more effective than the mailed reminder alone for each for the 4 intervention years and that the effectiveness of the intensive telephone intervention will increase each year due to the cumulative effect of the education and motivation it provides. Research has shown that mailing reminders and calling women who are due for a screening mammogram can increase the chances that these women will get a mammogram. Research is needed to identify the most effective and cost-effective type of telephone intervention before widespread adoption of reminder and counseling systems can occur. We propose to compare a low intensity and a high intensity reminder/counseling protocol to a mailed reminder alone in a large closed panel HMO. The HMO is committed to incorporating the most study´s successful interventions
Keywords: Address; Adherence; Adherence (attribute); Adopted; Adoption; Affect; Age; aged; arm; base; Behavioral; Booklets; Breast; Breast Cancer Detection; Breast cancer screening; Brochures; Cancer of Breast; Care, Health; Caring; Censuses; Commit; Community Health Planning; compare effectiveness; computer-based representation; computerized; cost; cost effective; cost effectiveness; Counseling; Data; Decision Making; Delivery of Health Care; doubt; Drops; Economic Income; Economical Income; Education; Educational aspects; effect of intervention; Effectiveness; Effectiveness of Interventions; Effects, Longterm; enroll; Enrollment; Evaluation; frame-based representation; Guidelines; Health; health care delivery; health care organization; health care service organization; Health Planning; Health Sciences, Allied and Health Services Delivery; Healthcare; Healthcare Delivery; High Prevalence; improved; Income; information organization; Insurance; Intervention; Intervention Strategies; interventional strategy; knowledge representation; Letters; Long-Term Effects; Mails; malignant breast neoplasm; Malignant neoplasm of breast; Malignant Tumor of the Breast; mammary cancer detection; Mammogram; Mammography; Managed Care; member; MMG; Modeling; Mortality; Mortality Vital Statistics; Motivation; motivational enhancement therapy; motivational interview; Outcome; outreach; outreach program; Pamphlets; Patients; Phone; Plannings, Community Health; Population; programs; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; randomisation; randomization; Randomized; randomly assigned; Research; response; Risk; Role; SCHED; Schedule; screening; Screening procedure; screenings; social role; Source; Staging; SUBGP; Subgroup; successful intervention; System; System, LOINC Axis 4; Telephone; Testing; Time; treatment as usual; Triage; Uncertainty; Woman
Relevance: 7. Research has shown that mailing reminders and calling women who are due for a screening mammogram can increase the chances that these women will get a mammogram. Research is needed to identify the most effective and cost-effective type of telephone intervention before widespread adoption of reminder and counseling systems can occur. We propose to compare a low intensity and a high intensity reminder/counseling protocol to a mailed reminder alone in a large closed panel HMO. The HMO is committed to incorporating the most study´s successful interventions
Project start date: 2009-03-27
Project end date: 2014-01-31
Budget start date: 1-FEB-2011
Budget end date: 31-JAN-2012
PFA/PA: PA-07-070
5R01CA132935-03 (2011): $634649
SUBUNIT INTERACTIONS AND FUNCTIONS IN ALLOSTERIC ENZYMES: GLUTATHIONE SYNTHETASE
E Mary, Assistant Professor
Texas Woman´s Universitycity: Denton country: United States (us)
Grant 1R15GM086833-01 from National Institute Of General Medical Sciences
Abstract: In the present research application, experimental, bioinformatics and computational techniques are utilized to probe important amino acid interactions at the dimer interface of human glutathione synthetase (hGS) in light of the negative cooperativity of hGS. The mechanism whereby the two active sites of hGS communicate across the dimer interface, despite their ca. 50 E separation will be investigated. The hypothesis that amino acids with strong interactions across the dimer interface play a critical role in hGS negative cooperativity will be tested. Aim 1 The most important residues that facilitate the subunitsubunit communication as well as the types of interactions will be identified using computational modeling techniques on the dimeric hGS enzyme. Mutation of the amino acids identified as the most significant vis-
Keywords: Human glutathione synthetase (hGS) is an important enzyme because of its role in the synthesis of the physiologically important antioxidant glutathione, and because hGS serves as a model for other protein families. Long-term our research will impact the understanding of allosteric, multimeric and/or ATP- using proteins and also the burgeoning interest in understanding and controlling protein:protein interactions
Relevance: -vis subunit:subunit communication will be tested using in silico (molecular dynamics) and in vitro site-directed mutagenesis; it is anticipated that mutagenesis of these residues will impact both hGS negative cooperativity and overall enzyme activity. The hypothesis that a loop, specifically the A- loop, of hGS is the conduit by which the subunit active sites communicate, thus leading to negative cooperativity, will be tested. Aim 2: Amino acids in hGS that are in contact with both important dimer interface residues and substrate binding residues will be identified with modeling. To assess whether these residues are involved in negative cooperativity, these amino acids will be mutated in silico and in vitro to understand at an atomic level how such mutations affect the active site geometry of hGS, activity, and negative cooperativity. Human glutathione synthetase is an important enzyme because of the physiological functions of glutathione and also because it serves as a paradigm for other protein families and for allostery. Human glutathione synthetase (hGS) is an important enzyme because of its role in the synthesis of the physiologically important antioxidant glutathione, and because hGS serves as a model for other protein families. Long-term our research will impact the understanding of allosteric, multimeric and/or ATP- using proteins and also the burgeoning interest in understanding and controlling protein:protein interactions
Project start date: 2009-01-01
Project end date: 2011-12-31
Budget start date: 1-JAN-2009
Budget end date: 31-DEC-2011
PFA/PA: MATERNAL FETAL UNITS NETWORK: STANFORD UNIVERSITY AND SANTA CLARA VALLEY
E Mary, Professor
Stanford Universitycity: Stanford country: United States (us)
Grant 1U10HD068268-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: In response to the NICHD RFA-HD-10-008, the Division of Maternal Fetal Medicine at Stanford University submits this application to participate in the ongoing Maternal Fetal Medicine Units Network. This application represents collaboration between two institutions Stanford University and Santa Clara Valley Medical Center (SCVMC). The MFM Division at Stanford has a long history of performing prospective clinical trials, many accomplished with SCVMC under the umbrella of the Stanford-Santa Clara Valley Research Collaboration. The MFM Division at Stanford resides in Lucile Packard Children´s Hospital (LPCH), and the Divisions of Maternal-Fetal Medicine and Neonatal and Developmental Medicine have a long history of close collaboration, as well. In 1997, this relationship culminated in the establishment of The Charles B. and Ann L. Johnson Center for Pregnancy and Newborn Services, a fully integrated clinical service line for perinatal services as well as neonatalogy and developmental medicine. Stanford has been a member of the Neonatal Research Network (NRN) since 1991, and our joint participation in these Networks would be of tremendous benefit to the execution of clinical protocols. Stanford University is world-renowned for creative research endeavors, and would contribute unique strengths in imaging, genetics, placental function and analysis, genomics and proteomics, pharmacogenomics, infectious disease, and simulation to expand the productivity and diversity of projects available to the MFMU Network. In summary, we bring to the MFMU a large, uniquely diverse patient population, a productive and proven research team, and access to the exceptional programs and expertise available at Stanford University. The experience and expertise of Stanford University´s MFM Division dovetails with the MFMU Network´s goals of rigorous evaluation of treatment and management strategies used in the care of pregnant women. The faculty includes an experienced team of board-certified perinatologists with experience and interest in participating in rigorous research protocols. The experience and diversity of these centers will add great value to the MFMU Network
Keywords: Caring; Child; Child health care; Clinical; Clinical Protocols; Clinical Services; Clinical Trials; Collaborations; Communicable Diseases; design; Development; Discipline of obstetrics; Evaluation; experience; Faculty; fetal; fetal medicine; Genetic; Genomics; Goals; Human Development; Image; Institutes; Institution; interest; Joints; Low Birth Weight Infant; Medical; Medical center; Medicine; member; National Institute of Child Health and Human Development; Neonatal; Newborn Infant; patient population; Patients; Pediatric Hospitals; Perinatal; Pharmacogenomics; Pregnancy; Pregnant Women; premature; Prevention; Principal Investigator; Productivity; programs; prospective; Proteomics; Protocols documentation; public health relevance; Recording of previous events; Research; response; Services; simulation; Universities
Project start date: 2011-04-07
Project end date: 2016-03-30
Budget start date: 7-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: RFA-HD-10-008
1U10HD068268-01 (2011): $320000
EFFECT OF TREATING ONE DISEASE ON OTHER DISEASES AND HEALTH OUTCOMES IN ELDERS
E Mary, Professor Of Medicine
Yale Universitycity: New Haven country: United States (us)
Grant 1R01AG038528-01 from National Institute On Aging
Abstract: In older adults with multi-morbidity, treatments targeting one disease may exacerbate co-occurring diseases or adversely affect overall health. Despite the potential for harm for the increasing numbers of individuals with multiple co-existing health conditions, this area has received little research attention. We explore the capability of using national population-based cohorts and novel analytical techniques to determine the harms and benefits of different treatment strategies across multiple disease-specific and health outcomes, particularly in situations in which the treatment of one condition may worsen another. We will use this innovative approach to investigate anti-hypertensive medication intensity in older adults with two commonly co-occurring conditions, namely hypertension and high fall/fracture risk. Modest, but conflicting, evidence suggests that anti-hypertensive medications may increase risk of falls, injuries, and other health outcomes in those at risk. Once we have tested the method with this important clinical question, we will extend to other sets of conditions and medications. This project builds on our ongoing work on tradeoffs among competing health conditions and mapping disease-specific outcomes onto overall, universal health outcomes. Specific aims are to test the hypotheses that, among comparable persons older adults with co- occurring hypertension and high fall/fracture risk, greater anti-hypertensive intensity is associated with fewer CV events and lower mortality but more frequent serious fall injuries, worse symptoms, lower activity level, and greater disability than lower anti-hypertensive intensity. In secondary analyses, we will explore these aims in relevant subgroups defined by age, gender, race, and co-morbidity burden. We will also determine if blood pressure levels and changes confound the effects of anti-hypertensive medication intensity on the outcomes. Two national, population-based cohorts, the Medicare Current Beneficiary Survey and the Medical Expenditure Panel Survey will be studied (study sample 35,000-40,000). Both have a wealth of longitudinal participant-reported, medication, and claims/health care utilization data. This depth and breadth of data allows us to use innovative analytical techniques to assess the effect of treatments on disease-specific and universal health outcomes (e.g. disability, symptom burden, functional limitations, and death), accounting for propensity to receive the treatment and for other confounders. We propose a new paradigm for quantifying the harm and benefit of treatments in complex older persons with multiple conditions. If treatments such as anti-hypertensives cause benefit as well as harm across a range of outcome domains, then this information must be uncovered and must inform clinical decision-making. Our ultimate goal is to develop a method for determining the optimal treatments for older adults with multiple conditions that maximizes benefit and minimizes harm within the outcome domain(s) of highest priority for each patient. Among persons with multiple chronic conditions, treatments for one condition may exacerbate co-occurring conditions or adversely affect overall health outcomes. We are exploring whether greater antihypertensive medication intensity in older adults with co-occurring hypertension and fall/fracture risk benefits cardiovascular outcomes but worsens fall injury outcomes, symptoms, disability, or activity levels. Study results can help determine the net benefit or harm of commonly recommended treatments among the growing number of older adults with multiple health conditions
Keywords: Accounting; Address; Affect; Age; Antihypertensive Agents; Area; Attention; base; beneficiary; Benefits and Risks; Blood Pressure; Cardiovascular system; Cessation of life; Chronic; Clinic; Clinical; clinical decision-making; cohort; Comorbidity; comparative effectiveness; Complement; Complex; Conflict (Psychology); Data; design; disability; Disease; disorder risk; effectiveness research; Elderly; Event; Expenditure; fall risk; falls; Fracture; Gender; Goals; Health; health care service utilization; Hypertension; Individual; Injury; innovation; Intervention; Investigation; Maps; Medical; Medical Records; Medicare; Methods; Morbidity - disease rate; Mortality Vital Statistics; Motivation; multiple chronic conditions; novel; novel strategies; Outcome; Outcome Study; Participant; Patients; Persons; Pharmaceutical Preparations; population based; Prevalence; prevent; Race; Randomized Controlled Trials; Reporting; Research; Risk; Sampling Studies; Subgroup; Surveys; Symptoms; Techniques; Testing; treatment effect; treatment strategy; Work
Relevance: Among persons with multiple chronic conditions, treatments for one condition may exacerbate co-occurring conditions or adversely affect overall health outcomes. We are exploring whether greater antihypertensive medication intensity in older adults with co-occurring hypertension and fall/fracture risk benefits cardiovascular outcomes but worsens fall injury outcomes, symptoms, disability, or activity levels. Study results can help determine the net benefit or harm of commonly recommended treatments among the growing number of older adults with multiple health conditions
Project start date: 2011-09-01
Project end date: 2013-02-28
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-09-265
1R01AG038528-01 (2011): $305425
A CULTURAL HISTORY OF ARISTOTLE´S MASTERPIECE
E Mary, Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 5G13LM010198-02 from National Library Of Medicine
Abstract: I propose to write the first history of Anglo-America´s most enduring popular medical book, Aristotle´s Masterpiece. First published in London in 1684, the book became an instant success, and was still for sale in the early twentieth century. My analysis focuses upon readership to understand how and why the book appealed over such a long time span in both England and America. I argue that the book was both canonical, widely known to provide advice about sex and reproduction, but also flexible, tweaked by printers and publishers to adapt to changing markets. The Masterpiece in its various forms offers a rare window into plebian sexual cultures as well as rich evidence of ordinary people´s interactions with the printed book. More generally, the project builds a model for investigating such vernacular knowledge, the basis of most health care until recently. Drawing upon the methods of cultural history, I argue that we need to understand how knowledge was circulated, consumed, and reproduced in changing contexts
Keywords: Adolescence; Americas; Birth; Blood Circulation; Books; boys; Caring; Childbirth; England; flexibility; Goals; Healthcare; History of Medicine; Knowledge; knowledge base; Learning; Literature; London; Marketing; Mattresses; Medical; Medicine; meetings; Methods; Midwifery; Modeling; Monsters; Morphologic artifacts; Mothers; Newborn Infant; Patients; Physicians; pleasure; Pregnancy; Printing; Production; Published Comment; Publishing; Reader; Reading; Recording of previous events; Reproduction; Research; response; Sales; Scholarship; sex; Sexuality; Side; success; Text; Time; Work; Writing
Relevance: I propose to write a cultural history of Anglo-America´s most enduring popular medical book, Aristotle´s Masterpiece. An analysis of this work illuminates the histories of popular medicine, plebian sexuality, and ordinary people´s interactions with print culture
Project start date: 2010-05-31
Project end date: 2012-05-30
Budget start date: 31-MAY-2011
Budget end date: 30-MAY-2012
PFA/PA: PAR-09-030
5G13LM010198-02 (2011): $48693
1G13LM010198-01 (2010): $46784
E Mary, Associate Professor
Baylor College Of Medicinecity: Houston country: United States (us)
Grant 5R21EY020632-02 from National Eye Institute
Abstract: During the formation of the lens, a transient vessel network, the hyaloid network, forms to nourish the lens as it develops. However, during late fetal development in humans and early postnatal development in mice, hyaloid vessels undergo regression to enable a transparent path of vision through the lens. Abnormal regression or growth of the hyaloid vasculature results in several diseases, including persistent hyperplastic tunica vasculosa lentis (PHTVL), persistent hyperplastic primary vitreous (PHPV), persistent fetal vasculature (PFV) and persistent prepupillary membrane (PPM). In this study, we will use fluorescent reporter mice labeling key cell types involved in vessel regression, live confocal imaging and FACS sorting and expression analysis to define cellular events leading to the onset of vessel regression. The abnormal growth and regression of blood vessels in the eye is the leading cause of blindness in children, adults and the elderly (Campochiaro, 2000). This study will use vital imaging to characterize how vessels regress in the newborn eye using mouse models in which individual cell types in the hyaloid vasculature are labeled with fluorescent protein reporters. Live imaging and FACS sorting will be used to define novel events in that initiate vessel regression
Keywords: Adult; Animals; Anterior; Apoptosis; Binding (Molecular Function); Blindness; Blood capillaries; Blood Cells; Blood Vessel Tissue; Blood Vessels; capillary; Cell Death; Cell membrane; cell type; Cells; Cellular Stress; Cessation of life; Child; Cornea; Data; Development; Disease; Elderly; Endothelial Cells; Event; Eye; fetal; Fetal development of the mammalian embryo or fetus; Functional disorder; Future; Growth; Homeostasis; Human; Hyperplasia; Image; in vivo; Individual; Label; lens; Life; light microscopy; macrophage; Mediating; Membrane; Motion; mouse model; mRNA Expression; Mus; Newborn Infant; novel; particle; Pattern; Phase; postnatal; Process; Proteins; public health relevance; Reporter; research study; Signal Transduction; Smooth muscle (tissue); Smooth Muscle Actin Staining Method; Smooth Muscle Myocytes; Sorting - Cell Movement; Supporting Cell; System; Testing; TimeLine; Tissues; Transgenic Organisms; Tunica Vasculosa; vessel regression; Vision
Relevance: The abnormal growth and regression of blood vessels in the eye is the leading cause of blindness in children, adults and the elderly (Campochiaro, 2000). This study will use vital imaging to characterize how vessels regress in the newborn eye using mouse models in which individual cell types in the hyaloid vasculature are labeled with fluorescent protein reporters. Live imaging and FACS sorting will be used to define novel events in that initiate vessel regression
Project start date: 2010-05-01
Project end date: 2012-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PA-09-164
5R21EY020632-02 (2011): $184200
PAMOIC ACID ANALOGUES AS POTENT GPR35 AGOINSTS INDUCING ANTINOCICEPTION
E Mary, Associate Professor
Temple Universitycity: Philadelphia country: United States (us)
Grant 5R21DA029432-02 from National Institute On Drug Abuse
Abstract: Drug addiction continues to remain a major public health concern in the United States. Addictive behavior results from changes in central nervous system signaling pathways that are modified after exposure to drugs of abuse. In particular, compounds such as cannabinoids and opiates that influence mood and pain perception are commonly associated with addictive behaviors. Many receptors regulating addiction are pharmacologically and biochemically well characterized, but some orphan receptors like GPR35 with homology to known receptors of abuse remain almost totally uncharacterized. The identification of small molecules capable of selectively inhibiting or activating orphans will provide enabling tools for elucidating novel molecular pathways underlying addictive behaviors. This proposal seeks to provide new compounds for characterizing the orphan G protein-coupled receptor GPR35. We have identified pamoic acid analogs as potent GPR35 agonists using in vitro assays and have found that pamoic acid induces antinociception. We propose a strategy to identify predominantly commercially available small molecules towards the objective of identifying a useful molecular probe for GPR35. Optimizing these novel compounds will allow the characterization of GPR35 biology in vitro and in animal models of pain. Our results suggest unexpected biological functions of pamoic acid and potential application for new drug development. This proposal will provide tools for delineating the pharmacology of GPR35, potentially provide compounds for targeted therapeutics of pathways underlying pain, and clarify our understanding of GPR35 biology in vitro and in animal models of pain
Keywords: Acids; addiction; Addictive Behavior; Affinity; Agonist; analog; Animal Model; beta-arrestin; Biological; Biological Process; Biology; Biosensor; Cannabinoids; Chemicals; Drug Addiction; drug development; Drug Formulations; drug of abuse; established cell line; Exposure to; Human; human GPRC5C protein; Hydroxyzine; Imipramine; In Vitro; in vitro Assay; Ligands; Molecular; Molecular Probes; Moods; Neuraxis; novel; Opiates; Orphan; Pain; Pathway interactions; Perception; Pharmacology; programs; Proteins; Psychotropic Drugs; public health medicine (field); public health relevance; Pyrantel; receptor; Research; Signal Pathway; small molecule; therapeutic target; tool; United States
Relevance: This proposal will provide tools for delineating the pharmacology of GPR35, potentially provide compounds for targeted therapeutics of pathways underlying pain, and clarify our understanding of GPR35 biology in vitro and in animal models of pain
Project start date: 2009-09-30
Project end date: 2012-02-28
Budget start date: 1-SEP-2010
Budget end date: 28-FEB-2012
PFA/PA: RFA-NS-09-003
5R21DA029432-02 (2010): $202046
CIRCADIAN CLOCK SUPPRESSION IN CANCER-RELATED FATIGUE
E Mary, Tippit Professor In The Life S
Smith Collegecity: Northampton country: United States (us)
Grant 5R21CA125215-02 from National Cancer Institute
Abstract: Circadian or daily rhythms modulate physiological responses. Robust daily rhythms are predictive of improved prognosis for cancer patients, independent of performance status measures. Disruption of circadian rhythms is associated with poor sleep quality and negative mood, fatigue, and reduced quality of life. The ability to care for a patient at home is often lost when the patient no longer sleeps during the night. The mechanism by which tumors suppress circadian rhythms and impair quality of life is unknown. We hypothesize that cytokine release induced by tumors may act directly in the neural system driving circadian rhythms and this action may induce fatigue and circadian rhythm disruption. Previous studies have shown that central administration of the cytokines TGF-1 and neuregulin-1 and systemic administration of IFN-1 can disrupt behavioral rhythms in hamsters and mice. As an animal model of tumor-induced disruption, we will determine if peripheral administration of TGF-1 and neuregulin-1 can similarly disrupt locomotor activity rhythms in mice. We will determine if cytokines can suppress the rhythms expressed by isolated suprachiasmatic nucleus (SCN), immune system organs, thymus and spleen, and other tissues (lung and mammary gland). Further experiments will assess if erlotinib or gefitinib, blockers of epidermal growth factor receptor (EGFR) tyrosine kinase activation used for chemotherapy, can improve circadian rhythm regularity and amplitude following disruption by TGF-1. These experiments are designed to mimic clinical data showing such effects in patients. We will determine with animals the optimal timing for administration of erlotinib or gefitinib to maximize the potential benefit to the circadian system. This research will increase our understanding of the biological mechanism by which tumor growth can impact the circadian system. We will describe effects of circadian clock output suppression on immune system function and on rhythms endogenous to select organs. Our studies will clarify if such effects could be mediated by cytokines, if action is peripheral or central, and if clinical reports of improved quality of life following administration of specific cytokine receptor blockers might be attributable to improved circadian regularity. This research will apply directly to clinical use of EGFR blockers, by investigating a rationale for optimal timing of these compounds. Cancer patients often suffer from disrupted circadian rhythms resulting in poor sleep quality, negative mood, fatigue and reduced quality of life. Tumors induce cytokine release, which may be responsible for circadian disruption and subsequent fatigue. By blocking the action of cytokines with specific compounds, we hope to clarify the downstream effects of cytokines on the immune and circadian systems. Clinical reports of improved quality of life after administration of cytokine blockers might be attributable to improved circadian rhythms
Keywords: 4-(3Chloro-4-flurophenylamine)-7-methoxy-6(3-(4morpholinyl)quinazoline; 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-4-morpholin] propoxy]; Acetylcholine Receptor Inducing Activity; Animal Model; Animal Models and Related Studies; Animals; ATP[{..}]protein-tyrosine O-phosphotransferase; Automobile Driving; Back; Behavioral; Biological; body system, allergic/immunologic; Breast Cancer Cell Differentiation Factor P45; c-erbB-1; c-erbB-1 Protein; Cancer Patient; Cancers; Caring; chemotherapy; circadian; circadian behavioral rhythms; circadian clock; circadian pacemaker; circadian process; Circadian Rhythms; Clinical; Clinical Data; Cricetinae; cytokine; Cytokine Receptors; daily biorhythm; design; designing; Diurnal Rhythm; diurnal variation; Dorsum; driving; Drivings, Automobile; EGFR; EPH- and ELK-Related Tyrosine Kinase; EPH-and ELK-Related Kinase; EPHA8; EphA8 Protein; Ephrin Type-A Receptor 8; Ephrin Type-A Receptor 8 Precursor; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Kinase; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; ERBB Protein; erbB-1; erbB-1 Proto-Oncogene Protein; ERBB1; erbBl; Erlotinib; experiment; experimental research; experimental study; Fatigue; feeding; Forecast of outcome; Gefitinib; Hamsters; HEK3; HER1; Home; Home environment; hydroxyaryl protein kinase; IFN; Immune; Immune system; improved; Individual; Interferons; Iressa; Lack of Energy; Link; Locomotor Activity; Lung Parenchyma; Lung Tissue; malignancy; Malignant Neoplasms; Malignant Tumor; Mammals, Hamsters; Mammals, Mice; Mammals, Rodents; mammary; Mammary gland; Mammary Glands, Human; Measures; Mediating; Mice; model organism; Motor Activity; Murine; Mus; N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamide; NDF Protein; negative mood; neoplasm/cancer; Nervous; neural; Neuregulin 1; NRG1; NRG1 Gene Product; NRG1 Protein; Nyctohemeral Rhythm; Organ; organ system, allergic/immunologic; outcome forecast; Output; Patient Care; Patient Care Delivery; Patients; Performance Status; Peripheral; Physiologic; Physiological; Prognosis; Protein Tyrosine Kinase; Protein Tyrosine Kinase EEK; proto-oncogene protein c-erbB-1; PTK; QOL; Quality of life; Receptor, EGF; Receptor, TGF-alpha; Receptor, Urogastrone; Receptors, Epidermal Growth Factor-Urogastrone; relating to nervous system; Reporting; Research; research study; response; Reticuloendothelial System, Spleen; Reticuloendothelial System, Thymus; Rodent; Rodentia; Rodentias; Sensory And Motor Neuron-Derived Factor; Sleep; Spleen; Stimulus; stressor; Structure of parenchyma of lung; Structure of suprachiasmatic nucleus; suprachiasmatic nucleus; Suprachiasmatic Nucleus; System; System, LOINC Axis 4; Tarceva; Testing; Thymus; Thymus Gland; Thymus Proper; Time; Transforming Growth Factor alpha Receptor; tumor; tumor growth; Twenty-Four Hour Rhythm; Tyrosine Kinase; Tyrosine-Protein Kinase Receptor EEK; Tyrosine-Specific Protein Kinase; tyrosyl protein kinase; Tyrosylprotein Kinase
Project start date: 2008-03-25
Project end date: 2011-02-28
Budget start date: 1-MAR-2009
Budget end date: 28-FEB-2011
PFA/PA: PA-06-533
5R21CA125215-02 (2009): $140535
BAYLOR COLLEGE OF MEDICINE ADOLESCENT MEDICINE TRIALS UNIT
E Mary
Baylor College Of Medicinecity: Houston country: United States (us)
Grant 1U01HD068046-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Baylor College of Medicine (BCM) is applying for an Adolescent Medicine Trials Unit (ATU) in response to NIH RFA-HD-10-015 Adolescent Medicine Trials Network for HIV/AIDS Interventions. The BCM Trials Unit plans to contribute to the ATN´s research agenda by providing an experienced research team to plan, enroll, analyze and publish results of research trials including behavioral research studies, community needs assessments, and therapeutic trials while meeting clinical and behavioral needs of HIV-infected youth. The BCM ATU will have three resources of patients 1) Teen Clinics for HIV-infected youth at Texas Children´s Hospital (TCH) lead by Drs Paul and Schwarzwald, Sections of Allergy and Immunology, and Retrovirology respectively, Department of Pediatrics, BCM; 2) Thomas Street Clinic (TSC) HIV-infected youth clinic lead by Dr Schwarzwald; and 3) Project Medical Home Clinics which provide adolescent care in medically underserved areas of Houston lead by Dr Desiree Evans, Department of Pediatrics, BCM. BCM will have 225 HIV-infected adolescents and over 1000 at-risk adolescents who are 12-24 years of age available to approach for enrollment into intervention trials aimed at the prevention of HIV, primary prevention In at-risk and secondary and tertiary prevention in the HIV-infected, pre-adolescents, adolescents, and young adults. BCM proposes unique studies involving innovative use of technology for secondary prevention of HIV transmission and adherence to HIV medication regimens among youth, a study of the pharmacokinetics to evaluate interactions of antidepressants when used with antiretroviral medications in HIV-infected youth, and a study that evaluates linkage to care for youth identified as HIV-infected through a large, youth oriented community testing event sponsored by the city health department and a community based AIDS organization. BCM ATU has the clinical, behavioral and research capacities and linkages to community to participate in multiple trials aimed at prevention of HIV in youth and trials aimed at improvements in management and psychosocial functioning of HIV-infected youth. RELEVANCE Youth in Houston and surrounding counties have one of the fastest growing rates of HIV-infection in the United States. Baylor College of Medicine (BCM)´s application to become an Adolescent Medicine Trials Unit is relevant to public health in that BCM plans to implement trials designed to promote primary prevention in HIV at-risk and secondary and tertiary prevention in HIV-infected youth
Keywords: Acquired Immunodeficiency Syndrome; Adherence (attribute); Adolescent; Adolescent Medicine; Adolescent Medicine Trials Network; Age-Years; AIDS prevention; AIDS/HIV problem; Anti-Retroviral Agents; Antidepressive Agents; antiretroviral therapy; Area; base; Behavioral; Behavioral Research; Caring; Cities; Clinic; Clinic Visits; Clinical; clinical research site; Clinical Trials Design; Collaborations; college; Communities; community organizations; County; design; Drug Kinetics; Enrollment; Event; experience; Health; HIV; HIV Infections; Home environment; Hypersensitivity; Immunology; improved; innovation; interactive multimedia; Intervention; Intervention Trial; Lead; Medical; Medically Underserved Area; Medicine; meetings; Needs Assessment; Online Systems; outreach; Patients; pediatric department; Pediatric Hospitals; Pharmaceutical Preparations; Primary Prevention; Principal Investigator; programs; psychosocial; public health medicine (field); Publishing; Regimen; Request for Applications; Research; Research Personnel; research study; Resources; response; Retrovirology; Risk; Risk Reduction; Safe Sex; Secondary Prevention; sexually active; skills training; Structure; Technology; Teenagers; tertiary prevention; Testing; Texas; theories; Therapeutic; therapy adherence; Therapy Clinical Trials; transmission process; United States; young adult; Youth
Project start date: 2011-04-07
Project end date: 2016-02-29
Budget start date: 7-APR-2011
Budget end date: 29-FEB-2012
PFA/PA: RFA-HD-10-015
1U01HD068046-01 (2011): $348782
Sponsored Links Excellgen http://Excellgen.com
TGF-BETA SIGNALING IN THE KIDNEY
E Mary, Associate Professor
Brigham And Women´s Hospitalcity: Boston country: United States (us)
Grant 5R01DK057661-10 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Background Transforming growth factor-beta 1 (TGF-B1) is a pleiotropic cytokine which controls multiple cellular functions including cell proliferation, differentiation, apoptosis, and extracellular matrix (ECM) synthesis. TGF-B1 is a potent inducer of ECM protein synthesis and accumulation, and plays a key role in the pathogenesis of progressive diseases as a central mediator of fibrogenesis in a variety of tissues, including the kidney. However, the precise mechanisms responsible for the pathogenesis of renal fibrosis and progression to end-stage renal failure remain incompletely understood. Our previous studies have focused on the p38 mitogen-activated protein kinase (MAPK), a major stress signal transducing pathway that is rapidly activated by TGF-B1 in renal cells. We have identified MKK3 as the immediate upstream MAPK kinase required for activation of p38 MAPK and stimulation of pro-a1(l) collagen by TGF-B1 in murine mesangial cells and tubular epithelial cells. Our hypothesis is that the MKK3-p38 alpha and p38 delta MAPK signal transduction pathway is the critical mediator of tissue injury response in which TGF-B1 signals ECM synthesis and accumulation leading to progressive renal fibrosis. This proposal will focus on examining the cellular and molecular mechanism of TGF-B1 signaling, and we will further investigate the upstream activators of MKK3-p38 MAPK signaling pathway for TGF-B1, and examine their functional role in injury responses in renal tubular epithelial cells in vitro. In vivo correlates will be sought in an experimental model of renal fibrosis. We will employ state-of-the art approaches including a variety of dominant negative mutants of TGF-B receptors, the MAPKs and specific p38 isoforms, gene silencing by the use of RNAi (RNA interference) induced by short interfering RNA (siRNA), and genetically altered mice, the null mice for the various MAPKs, particularly the MKK3. Relevance Although the central role of TGF-B1 in the development of renal fibrosis is well documented, general strategies to indiscriminately inhibit TGF-B1 actions altogether may prove to be imprudent. The studies in this proposal will yield important and novel information in furthering our understanding of the molecular mechanisms of TGF-B1 signal transduction, that we may be able to selectively block the pathway that signals the deleterious effects of TGF-B1
Keywords: Address; Apoptosis; Arts; base; Cell physiology; Cell Proliferation; Cells; Collagen; cytokine; Data; Development; Dominant-Negative Mutation; End stage renal failure; Epithelial Cells; Experimental Models; Extracellular Matrix; Extracellular Matrix Proteins; fibrogenesis; Fibrosis; Gene Silencing; Goals; human MAPK13 protein; human MAPK14 protein; human RIPK1 protein; human TGFB1 protein; human TGFBR2 protein; In Vitro; in vivo; Kidney; kidney cell; Knockout Mice; MAP Kinase Kinase Kinase; MAP3K7 gene; MAPK11 gene; MAPK14 gene; Mediating; Mediator of activation protein; mesangial cell; Mitogen-Activated Protein Kinase Kinases; Molecular; mouse model; Mus; novel; Pathogenesis; Pathway interactions; Physiological; Play; Process; Progressive Disease; Protein Biosynthesis; Protein Isoforms; Proteins; receptor; Receptor Signaling; Regulation; response; response to injury; RNA; RNA Interference; Role; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Molecule; Staging; Stress; Testing; Tissues; Transforming Growth Factor beta; Tubular formation
Project start date: 2000-06-01
Project end date: 2011-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2011
5R01DK057661-10 (2009): $338502
7R01DK057661-09 (2008): $338072
5R01DK057661-08 (2007): $293807
2R01DK057661-07A1 (2006): $302635
1/4 ALCOHOL RESEARCH CONSORTIUM IN HIV-ADMINISTRATIVE CORE (ARCH-AC)
E Mary, Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 1U24AA020801-01 from National Institute On Alcohol Abuse And Alcoholism
Abstract: Alcohol Research Consortium in HIV (ARCH) is comprised of two U24 and two UOI applications, and will address critical questions regarding the clinical epidemiology of hazardous alcohol use/abuse/dependence in HIV infection (Epidemiology Research Arm), and evaluate the comparative effectiveness of evidence- based alcohol reduction strategies in real world HIV clinic settings (Intervention Research Arm). This research builds upon the unique strengths of a well-established HIV clinical cohort, the CFAR Network of Integrated Clinical Systems (CNICS), comprised of 8 clinics and over 20,000 HIV-infected individuals across the United States. This dynamic cohort provides an ideal scientific platform for long-term study of HIV and alcohol through the collection of comprehensive clinical data and specimens as well as uniformly-collected patient reported outcomes as a part of the Patient Reported Outcomes Measurement Information System initiative. An Epidemlology/Biostatistics Core will be led by experts in epidemiology and biostatistics with specific focus on HIV research. It will provide critical support for the scientific agenda of the U01 applications and focus on development of innovative analytic strategies that will maximize new clinical and scientific knowledge. The U24 at the heart of ARCH is the Administrative Core (AC), the focus of this application. ARCH-AC will provide the critical infrastructure to coordinate and facilitate the consortium´s scientific goals. Structure will include an executive committee; a steering committee; key scientific working groups to conceptualize and implement study aims; and a community advisory board. ARCH-AC is co-led by national experts in alcohol use disorders and HIV, who have over 40 years of combined scientific experience in conducting epidemiologic and clinical research in HIV/AIDS. The AC provides the critical infrastructure to 1) conceptualize, facilitate and oversee the implementation of the scientific epidemiologic and interventional aims; 2) promote communication and collaboration among ARCH components and investigators; 3) manage and optimize access to ARCH resources, particularly the data repositories, epidemiologic/ biostatistics support and the investigational expertise; and 4) provide the support for dissemination of ARCH findings. The Alcohol Research Consortium in HIV combines an unparalleled breadth and depth of investigator expertise with a comprehensive and diverse multisite US HIV cohort to create a world-class consortium that will accelerate advancement of new knowledge of the epidemiology of alcohol use and HIV, and evaluate the comparative effectiveness of evidenced-based psychosocial and pharmacological alcohol treatments
Keywords: Address; Adherence (attribute); AIDS/HIV problem; Alcohol abuse; alcohol abuse therapy; alcohol availability; Alcohol consumption; alcohol effect; Alcohol or Other Drugs use; alcohol research; alcohol use disorder; Alcohols; Anxiety; arm; Biometry; Biostatistics Core; burden of illness; Caring; Clinic; Clinical; Clinical Data; clinical epidemiology; Clinical Research; cohort; Collaborations; Collection; Committee Members; Communication; Communities; comparative effectiveness; cost effectiveness; Data; Data Collection; Databases; Dependence; design; Development; Disease; Drug usage; Effectiveness; Epidemiologic Studies; Epidemiology; evidence base; experience; Funding Agency; Gender; Goals; health care service utilization; Heart; Heavy Drinking; HIV; HIV Infections; Illicit Drugs; Individual; Information Dissemination; Information Systems; innovation; Intervention; Intervention Studies; Knowledge; Longitudinal Studies; Measurement; Mental Depression; National Institute on Alcohol Abuse and Alcoholism; Outcome; Patient Outcomes Assessments; Patients; Persons; Pharmacotherapy; point of care; Population Heterogeneity; Principal Investigator; psychosocial; Publications; Quality of life; Research; Research Infrastructure; Research Personnel; Resources; Risk Behaviors; Specimen; Structure; System; transmission process; United States; working group
Relevance: The Alcohol Research Consortium in HIV combines an unparalleled breadth and depth of investigator expertise with a comprehensive and diverse multisite US HIV cohort to create a world-class consortium that will accelerate advancement of new knowledge of the epidemiology of alcohol use and HIV, and evaluate the comparative effectiveness of evidenced-based psychosocial and pharmacological alcohol treatments
Project start date: 2011-09-15
Project end date: 2016-08-31
Budget start date: 15-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: RFA-AA-11-003
1U24AA020801-01 (2011): $404055
ONDANSETRON PHARMACOTHERAPY FOR HAZARDOUS DRINKING, HIV+, AFRICAN-AMERICAN WOMEN
E Mary, Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 5R01AA018896-03 from National Institute On Alcohol Abuse And Alcoholism
Abstract: African American (AA) women comprise only 12% of US females, and yet account for 66% of new HIV infections in women. The rate of AIDS diagnosis for black women (45.5/100,000 women) is approximately 23 times the rate for white women. In fact, HIV/AIDS-related conditions are now the leading cause of death from AA women aged 25-34. Heavy/hazardous alcohol use impacts HIV/AIDS disease progression and treatment, particularly in women. HIV-infected, hazardous drinking women are less likely to be prescribed antiretroviral therapy and to achieve effective viral load reductions, and they have increased mortality compared to nonhazardous drinking, HIV-infected women and even hazardous drinking, HIV-infected men. Clearly this population is an important target for effective alcohol treatments. The proposed placebo controlled, randomized clinical trial will investigate the efficacy of ondansetron pharmacotherapy for the treatment of hazardous alcohol use and alcohol abuse/dependence among HIV-infected, AA women. Ondansetron, a 5-HT3 antagonist, has been selected because of evidence of effectiveness in persons who want to reduce their drinking but are not abstinent at the start of medication; evidence of moderate to strong effects in early onset drinkers, a characteristic that is overrepresented in our clinic patients; and a mild side-effects profile, making it an ideal drug for patients who are often receiving multiple other medications with significant side-effects. HIV-infected, hazardous drinking, AA women will be randomized to placebo, low dose (0.2 mg bid) and moderate dose (0.8 mg bid) ondansetron. Subjects will be classified by age-of-onset for alcohol problems and genotyped for a functional polymorphism of the serotonin transporter gene. Outcomes will include alcohol use and related symptoms, medication safety and side-effects, HIV biomarkers and treatment compliance, HIV risk behaviors, and quality of life. This study will provide important new scientific and clinical information on ondansetron for alcohol pharmacotherapy in HIV-infected, African American women. African American women comprise only 12% of US females, and yet account for 66% of new HIV infections in women. Hazardous alcohol use negatively affects HIV/AIDS disease progression and treatment, particularly in women. The proposed randomized clinical trial will investigate a novel pharmacotherapy for hazardous drinking, HIV infected, African American women, using the 5-HT3 antagonist ondansetron. This study will provide important new safety and efficacy results on drinking and HIV outcomes
Keywords: Accounting; Adherence (attribute); Adverse effects; Affect; African American; Age of Onset; aged; AIDS diagnosis; AIDS/HIV problem; Alcohol abuse; alcohol abuse therapy; Alcohol consumption; alcohol effect; alcohol related problem; alcohol services; alcohol use disorder; Alcohols; Ambulatory Care Facilities; antiretroviral therapy; Appointment; base; biomarker; Caring; Cause of Death; CD4 Lymphocyte Count; Characteristics; Clinic; Clinical; Compliance behavior; Dependence; Disease Marker; Disease Progression; Dose; drinking; early onset; early-onset alcoholic; Effectiveness; Female; Frequencies (time pattern); Genes; Genetic Polymorphism; Genotype; hazardous drinking; Health; HIV; HIV Infections; Hospitals; Immune system; improved; Intervention; medication compliance; Medication Management; men; Mortality Vital Statistics; Nausea; novel; Ondansetron; Outcome; Outcome Measure; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Population; public health relevance; Quality of life; Randomized; Randomized Clinical Trials; Recruitment Activity; reduced alcohol use; Risk; Risk Behaviors; Risk Reduction Behavior; Safety; Serotonin; serotonin transporter; statistics; Symptoms; Time; uptake; Viral Load result; Woman
Relevance: African American women comprise only 12% of US females, and yet account for 66% of new HIV infections in women. Hazardous alcohol use negatively affects HIV/AIDS disease progression and treatment, particularly in women. The proposed randomized clinical trial will investigate a novel pharmacotherapy for hazardous drinking, HIV- infected, African American women, using the 5-HT3 antagonist ondansetron. This study will provide important new safety and efficacy results on drinking and HIV outcomes
Project start date: 2009-09-30
Project end date: 2014-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: RFA-AA-09-007
5R01AA018896-03 (2011): $509225
ALLELIC CHOICE IN RETT SYNDROME
E Mary, Director Of Cellular Therapies
Winifred Masterson Burke Med Res Instcity: White Plains country: United States (us)
Grant 5R01MH090267-02 from National Institute Of Mental Health
Abstract: A major quest in health care today is elucidating the mechanism for Autism Spectrum Disorders (ASD), one of the leading causes of autistic behavior occurring in 1150 births. Rett Syndrome (RTT) is a developmental disorder of the brain that occurs in females and is responsible for mental retardation and autistic behavior. RTT falls under the umbrella of ASD. Mutations in the X-linked MeCP2 protein situated on the X chromosome are the cause of this genetic disorder. Phenotypic variation ranging from mild to severe manifestations is observed in RTT. A major determinant of this clinical variability is the pattern of X-chromosome inactivation (XCI), a crucial epigenetic process that occurs early in development to balance the gene dose between XX females and XY males. Female cells undergo a chromosomal-wide silencing of one X chromosome at random to equalize the dose. Favorable XCI that silences the X chromosome with the mutant MeCP2 gene will lessen the severity of symptoms in girls with RTT. Insight into how XCI is regulated will provide understanding in the pathogenesis of RTT the may offer hope in the amelioration of severe phenotypes. These studies have profound impact on allelic expression diseases such as genomic imprinted gene disorders, such as Angelman
Keywords: Accounting; Affect; Alleles; Angelman Syndrome; arm; autism spectrum disorder; autistic behaviour; Autistic Disorder; Binding (Molecular Function); Biological; Birth; Brain; cell body (neuron); cell type; Cells; Chromatin; chromatin modification; Clinical; Communication; Complex; Data; Development; developmental disease/disorder; Disease; DNA; DNA Methylation; Dose; embryonic stem cell; Ensure; Epigenetic Process; epigenomics; Equilibrium; Event; falls; Female; Functional RNA; Gene Activation; Gene Dosage; Gene Expression; Gene Silencing; Genes; Genetic Medicine; Genomic Imprinting; girls; Goals; Grant; Healthcare; Hereditary Disease; Histones; Human; Inherited; insight; Knowledge; Laboratory Study; Link; male; Mediating; Mental Retardation; Methyl-CpG-Binding Protein 2; Modeling; Molecular; Mus; mutant; Mutate; Mutation; Neurodevelopmental Disorder; Pathogenesis; Pathology; Pattern; Phenotype; Play; Pluripotent Stem Cells; Prader-Willi Syndrome; Process; Promotor (Genetics); Proteins; public health relevance; Regulation; Rett Syndrome; Role; Severities; Site; stem cell differentiation; Symptoms; System; Testing; Tissue-Specific Gene Expression; Touch sensation; Transcriptional Regulation; Undifferentiated; Variant; Wild Type Mouse; X Chromosome; X Inactivation; X-Linked Mental Retardation
Project start date: 2010-08-01
Project end date: 2015-02-28
Budget start date: 1-MAY-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-07-070
5R01MH090267-02 (2011): $354983
MOLECULAR CHARACTERIZATION OF GPR35 AND GPR55, PUTATIVE CANNABINOID RECEPTORS
E Mary, Associate Professor
Temple Universitycity: Philadelphia country: United States (us)
Grant 5R01DA023204-05 from National Institute On Drug Abuse
Abstract: A large number of physiological processes are controlled by the endogenous cannabinoids. Most of these effects have been attributed to action at either the cannabinoid CB1 or CB2 receptors. Yet there are effects that clearly are not CB1- or CB2-mediated which may not be receptor mediated, but there is also sufficient evidence to suggest the involvement of the vanilloid receptor (TRPV1) in cannabinoid effects and at least two other cannabinoid receptor subtypes defined only pharmacologically until now. Very recently, two orphan G-protein coupled receptors (GPCRs), GPR35 and GPR55, have been suggested to be cannabinoid receptors, with a fairly wide range of cannabinoid ligands reported to display affinity/efficacy at each. We have cloned and expressed both GPR35 and GPR55 and our preliminary studies confirm that they are activated by multiple cannabinoid compounds. In work proposed here, we plan to characterize these two GPCRs through ligand binding and functional studies. Recently developed computer models of GPR35 and GPR55 in their inactive and activated states will be used to guide mutation studies of each receptor. These models are informed by our extensive modeling and mutation experience with the cannabinoid CB1 and CB2 receptors. The goal of mutation studies will be not only to identify residues involved in ligand recognition, but also those residues important for receptor activation. In GPR35 and GPR55 ligand recognition studies, the involvement of specific amino acids with specific ligand functional groups will be tested using carefully chosen compounds. Results of mutation studies in vitro will be used to refine computer receptor models, such that at any given time, these models reflect the current state of knowledge in the field. Because work thus far on GPR35 and GPR55 has not identified a high affinity antagonist for either receptor and because such antagonists would be very valuable tools for studying these two receptors, another goal of the proposed work will be to design antagonists for each receptor sub-type. These compounds will be designed at UNCG (Reggio), synthesized at Research Triangle Institute (Seltzman), and evaluated at CPMCRI (Abood). High affinity antagonists that emerge from this work will be radiolabeled and made available to the scientific community. Determining the distribution of GPR35 and signal transduction pathways of GPR35 and GPR55 will help define their physiological and pathophysiological roles
Keywords: Adenylate Cyclase; Affinity; Agonist; Amino Acids; base; Binding (Molecular Function); Calcium; cannabinoid receptor; Cannabinoids; capsaicin receptor; Cells; Charge; Communities; Computer Simulation; Computers; Data; design; dioleoylphosphatidylcholine; Docking; Drug abuse; Drug or chemical Tissue Distribution; Drug Receptors; Endocannabinoids; experience; functional group; G-Protein-Coupled Receptors; Generations; Goals; GTP-Binding Proteins; Herb; human GPRC5C protein; immunocytochemistry; In Vitro; in vivo; Indoles; Institutes; interest; Knowledge; Ligand Binding; Ligands; Literature; Marihuana; Mediating; Memory; Messenger RNA; Microglia; Mitogen-Activated Protein Kinases; Modeling; Molecular; Molecular Conformation; molecular dynamics; molecular modeling; Molecular Models; Molecular Profiling; Mus; mutant; Mutate; Mutation; Nature; Neurons; novel; Organ; Pathway interactions; Peripheral; Peripheral Nervous System; Phosphotransferases; Physiological; Physiological Processes; programs; Property; protein activation; Proteins; Pyrazoles; Radiolabeled; radiotracer; receptor; Receptor Activation; receptor binding; receptor expression; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Regulation; Reporting; Research; Research Personnel; research study; Reverse Transcriptase Polymerase Chain Reaction; Role; Scheme; second messenger; Second Messenger Systems; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Simulate; Site; Site-Directed Mutagenesis; SR 141716A; Structure; Techniques; Testing; Time; tool; Transmembrane Domain; TRPV1 gene; Western Blotting; Work
Project start date: 2008-07-15
Project end date: 2012-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
5R01DA023204-05 (2011): $308851
5R01DA023204-04 (2010): $317724
ASSEMBLY , TARGETING, AND REGULATION OF DYNEIN MOTORS
E Mary, Professor
University Of Minnesota Twin Citiescity: Minneapolis country: United States (us)
Grant 5R37GM055667-15 from National Institute Of General Medical Sciences
Keywords: Antibodies; base; Biochemical; Biological Assay; Cell Shape; Cells; Chlamydomonas; Chromosomes; Chronic; Cilia; Co-Immunoprecipitations; comparative; Complex; Defect; Development; Diagnostic; digital imaging; Dynein ATPase; Electron Microscopy; Epitopes; Family; Flagella; Genes; genetic analysis; Goals; human disease; In Vitro; Infertility; insight; Instruction; Intracellular Transport; Link; Location; Lung diseases; Microtubules; Mitosis; Motor; mutant; Mutation; nervous system development; nexin; novel; Organelles; Phosphorylation Site; Play; Polycystic Kidney Diseases; Positioning Attribute; Procedures; Property; Proteins; Proteomics; Regulation; Research; Resolution; RNA Interference; Role; Slide; Speed (motion); Therapeutic
Project start date: 1997-04-01
Project end date: 2015-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5R37GM055667-15 (2011): $433857
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